Using Stem Cells to Cure Autism, Epilepsy & Schizophrenia | Dr. Sergiu Pașca
Andrew Huberman:
安德鲁·休伯曼：
Welcome to the Huberman Lab podcast, where we discuss science and science-based tools for everyday life.
欢迎来到休伯曼实验室播客，我们在这里讨论科学和基于科学的日常生活工具。
I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine.
我是安德鲁·胡伯曼，斯坦福大学医学院神经生物学和眼科教授。
My guest today is Dr. Sergiu Pasca.
今天我的客人是 Sergiu Pasca 博士。
Dr. Sergiu Pasca is a professor of psychiatry and behavioral sciences and the director of the Stanford Brain Organogenesis Program.
Sergiu Pasca 博士是精神病学和行为科学教授，也是斯坦福大学脑器官发生项目的主任。
During today's episode, we discuss autism, schizophrenia, and human brain development generally, both brain development during pregnancy as well as during childhood and leading all the way up to our third decade of life.
在今天的节目中，我们讨论自闭症、精神分裂症和人类大脑的一般发育，包括怀孕期间和儿童时期的大脑发育，一直到我们生命的第三个十年。
During today's discussion, you will get the most up-to-date information about autism and its treatments.
在今天的讨论中，您将获得有关自闭症及其治疗的最新信息。
You'll learn why the prevalence of autism is rising, the role that genes play in autism, and the novel treatments that Dr. Pasca is developing to treat what is called profound autism, which are the most severe cases of autism.
您将了解到为什么自闭症患病率不断上升、基因在自闭症中发挥的作用，以及帕斯卡博士正在开发的治疗所谓的深度自闭症（自闭症最严重的病例）的新疗法。
Dr. Pasca is one of a small handful of researchers that pioneered the discovery and development of what are called organoids and assembloids, which are essentially human brain circuits derived from stem cells that form in a dish, so that one can study them directly.
帕斯卡博士是少数率先发现和开发类器官和组合体的研究人员之一，这些类器官和组合体本质上是源自培养皿中形成的干细胞的人脑回路，因此人们可以直接研究它们。
And while that might sound artificial, today he explains why those organoids and assembloids are immensely powerful for understanding exactly what is wrong in psychiatric illnesses like profound autism, schizophrenia, and other psychiatric challenges, and for developing cures.
虽然这听起来可能有些人为，但今天他解释了为什么这些类器官和组合体对于准确理解严重自闭症、精神分裂症和其他精神疾病等精神疾病的问题以及开发治疗方法非常有效。
So today, you're going to learn a lot about human brain development and about stem cells, which is going to be important for anyone interested in how the brain wires up, how to treat various diseases of the brain, but also for anyone who is considering stem cell therapies.
所以今天，您将了解很多有关人类大脑发育和干细胞的知识，这对于任何对大脑如何连接、如何治疗各种大脑疾病感兴趣的人以及任何正在考虑干细胞疗法的人来说都很重要。
As you'll soon learn, Sergiu is an extraordinary scientist, but also an extraordinary teacher.
您很快就会了解到，塞尔吉乌是一位杰出的科学家，同时也是一位杰出的教师。
By the end of today's episode, you'll have the latest information on stem cells, organoids, autism, and what is being done to cure autism and other psychiatric conditions.
在今天的节目结束时，您将了解有关干细胞、类器官、自闭症以及治疗自闭症和其他精神疾病的最新信息。
Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford.
在开始之前，我想强调一下，这个播客与我在斯坦福大学的教学和研究角色是分开的。
It is, however, part of my desire and effort to bring zero cost to consumer information about science and science-related tools to the general public.
然而，我的愿望和努力的一部分是向公众提供有关科学和科学相关工具的零成本消费者信息。
In keeping with that theme, today's episode does include sponsors.
为了与这个主题保持一致，今天的节目确实有赞助商。
And now for my discussion with Dr. Sergiu Pasca.
现在我与 Sergiu Pasca 博士进行讨论。
Dr. Sergiu Pasca, welcome.
塞尔吉乌·帕斯卡博士，欢迎光临。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Thank you.
谢谢你。
It's great to be here.
很高兴来到这里。
Andrew Huberman:
安德鲁·休伯曼：
We're old friends.
我们是老朋友了。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Mm-hmm.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
Shared a laboratory space years ago.
几年前共享一个实验室空间。
We'll get back to that a little later.
我们稍后再讨论这个问题。
In the meantime, these days there's a ton of interest and I think misunderstanding about autism.
与此同时，现在人们对自闭症产生了很多兴趣，我认为也存在误解。
As soon as the topic of autism comes up, immediately some people will say, "Why are we trying to cure this thing?
一提到自闭症这个话题，马上有人会说：“我们为什么要治这个东西？
I know autistic children and adults that are delightful people that lead functional lives."
我认识自闭症儿童和成人，他们都是令人愉快的人，过着正常的生活。”
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
"They might be a little bit different or a lot different than other people, but why are we trying to, quote unquote, 'cure autism?'" And then other people will say, "Well, there are people with autism who need constant care, who will never live independently." Tell us about autism, what this spectrum really is, and then we'll talk about what your laboratory is doing to try and literally find cures for the most debilitating forms of autism.
“他们可能与其他人有一点不同或有很大不同，但为什么我们要试图（引用不引用的话）‘治愈自闭症？’”然后其他人会说，“好吧，有些自闭症患者需要持续的护理，他们永远不会独立生活。”告诉我们有关自闭症的信息，这个谱系到底是什么，然后我们将讨论您的实验室正在做什么，以尝试并真正找到治疗最令人衰弱的自闭症形式的方法。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Well, autism is a complex condition.
嗯，自闭症是一种复杂的病症。
It's a spectrum, as you said.
正如你所说，这是一个频谱。
In a way you could say autism and neurodevelopmental disorders.
在某种程度上，你可以说是自闭症和神经发育障碍。
It's behaviorally defined.
这是行为上定义的。
There's no biomarker, so in a way it's a condition that is defined exclusively by observing behavior.
没有生物标志物，所以在某种程度上，这是一种完全通过观察行为来定义的状况。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Which is actually the case for most psychiatric disorders.
大多数精神疾病实际上都是如此。
But it's essentially diagnosed by the presence and absence of certain behaviors in a certain period of time or up to a certain age.
但它本质上是通过在特定时间段或特定年龄内是否存在某些行为来诊断的。
And of course, what triggered, I think, a lot of discussions in recent years is because the number or the prevalence of autism has increased.
当然，我认为近年来引发大量讨论的原因是自闭症的数量或患病率有所增加。
So now it's close to almost 3% of the general population, which of course it's a big number.
所以现在它接近总人口的3%，这当然是一个很大的数字。
Andrew Huberman:
安德鲁·休伯曼：
3%.
3%。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Almost 3%, yes.
几乎 3%，是的。
Andrew Huberman:
安德鲁·休伯曼：
Wow.
哇。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
So it has increased even since I was in medical school.
所以自从我上医学院以来它就一直在增加。
When I was in medical school, actually, it was considered a rare disease.
事实上，当我在医学院的时候，它被认为是一种罕见的疾病。
The reason why I actually studied autism, because it was a very rare disease, and we had very few resources, so we thought studying a rare disease would be easier.
我之所以真正研究自闭症，是因为它是一种非常罕见的疾病，而我们的资源又很少，所以我们认为研究一种罕见的疾病会更容易。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
But now we also know so much more about this condition.
但现在我们对这种情况也了解得更多了。
So we do know, for instance, that there is a strong genetic component to it, which for a while, obviously, we didn't.
例如，我们确实知道它有很强的遗传成分，但显然有一段时间我们不知道。
In fact, in early days, the psychoanalytic perspective dominated, especially in the '50s and '60s.
事实上，在早期，精神分析观点占主导地位，尤其是在 50 年代和 60 年代。
So it was thought that it was resulting from having very cold parents, in particular a cold mother.
所以人们认为这是由于父母非常冷漠，尤其是母亲冷漠造成的。
Andrew Huberman:
安德鲁·休伯曼：
Emotionally cold?
感情冷淡？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah, emotionally cold.
是的，感情冷淡。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
It was the so-called refrigerator mother hypothesis of autism.
这就是所谓的自闭症冰箱母亲假说。
And then in the '70s, some of the first biological studies were done, primarily in twins, that show something quite remarkable, that if you have twins that are identical, genetically identical, and one has autism, then the probability that the other one has autism is very, very high.
然后在 70 年代，一些最早的生物学研究主要是在双胞胎中进行的，这些研究表明了一些非常值得注意的事情，如果你有同卵双胞胎，基因相同，并且其中一个患有自闭症，那么另一个患有自闭症的可能性非常非常高。
Andrew Huberman:
安德鲁·休伯曼：
Even with different mothers.
即使是不同的母亲。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Sure.
当然。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yes.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
But generally, we think that there is a strong heritable component to autism.
但总的来说，我们认为自闭症有很强的遗传因素。
So that was in the late '70s.
那是在 70 年代末。
And really just in the last 10, 15 years, we've learned actually that there are genes associated with autism and certainly with very specific forms of autism.
事实上，就在过去 10、15 年里，我们实际上了解到，有些基因与自闭症有关，当然也与非常特殊的自闭症形式有关。
So that's what we would call generally profound autism today, the conditions that are severe, that are causing an impairment, that are very often associated with other conditions such as intellectual disability, so low IQ, epilepsy.
这就是我们今天所说的普遍的严重自闭症，这种情况很严重，会造成损害，通常与其他疾病有关，例如智力障碍、智商低、癫痫。
So because it is a spectrum, of course, it creates a lot of confusion, and certainly there's no doubt that there are individuals that have autistic traits that are fully functional in the general population.
因此，因为它是一个谱系，所以当然会造成很多混乱，而且毫无疑问，有些人具有自闭症特征，但在普通人群中却完全发挥作用。
But the reality is also that there are kids that have autism who are very impaired and will require actually lifelong care of sorts.
但现实情况是，有些患有自闭症的孩子的健康状况非常差，实际上需要终身护理。
Another way of thinking about autism is that autism is not one disease, and I think no psychiatrist or even biologist who's studying autism would ever consider that this is one single disease.
另一种思考自闭症的方式是自闭症不是一种疾病，我认为研究自闭症的精神病学家甚至生物学家都不会认为这是一种单一的疾病。
The way I look at it sometimes is think about the fever of the 19th century in medicine.
有时我看待这个问题的方式就像是19世纪医学界的热潮。
So you see this very often in movies, right?
所以你经常在电影中看到这种情况，对吗？
They will say, "Oh, he has a fever, high fever.
他们会说：“哦，他发烧了，发高烧。
He's going to die from high fever." Well, that fever could have been a viral infection, a bacterial infection, could have been cancer, metastatic cancer.
他会因高烧而死。”嗯，发烧可能是病毒感染、细菌感染，也可能是癌症、转移性癌症。
Could have been an autoimmune disease.
可能是一种自身免疫性疾病。
The treatments are very different, but in that time, that's all we knew.
治疗方法非常不同，但在那个时候，这就是我们所知道的。
It was we were observing that behavior, in which case, raising of the temperature, but we didn't know the biology.
我们正在观察这种行为，在这种情况下，温度升高，但我们不了解其生物学原理。
Today, we will use very different treatments for those conditions, and some of them, of course, we don't even treat.
今天，我们将对这些病症使用非常不同的治疗方法，当然，其中一些我们甚至不进行治疗。
We just observe.
我们只是观察。
So I think in autism research, as it is the case for many psychiatric conditions, they are defined behaviorally, but there is a disconnect with the biology.
所以我认为在自闭症研究中，就像许多精神疾病的情况一样，它们是从行为上定义的，但与生物学存在脱节。
Very often we don't have biological markers by definition, and so that disconnect, I think, creates a lot of confusion.
很多时候我们并没有定义上的生物标记，因此我认为这种脱节会造成很多混乱。
Andrew Huberman:
安德鲁·休伯曼：
I have a couple of questions.
我有几个问题。
First of all, is the prevalence of autism higher in males?
首先，自闭症的患病率在男性中是否更高？
I've been told yes.
有人告诉我是的。
If it's 3% overall, what's the distribution for males versus females?
如果总体为 3%，那么男性和女性的分布情况如何？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
The ratio varies also based on severity, but generally it's been one to four, so more males than females.
该比例也根据严重程度而有所不同，但通常为一比四，因此男性多于女性。
Andrew Huberman:
安德鲁·休伯曼：
And we just recently had our colleague, Nirao Shah, on the podcast, who basically said the difference between a biological male and female comes down to this SRY gene.
最近，我们的同事 Nirao Shah 在播客上表示，生理上男性和女性之间的差异归结于 SRY 基因。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Not even necessarily on the Y chromosome.
甚至不一定在Y染色体上。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Mm-hmm.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
If a baby has the SRY gene, you're going to get a fully functional male.
如果婴儿具有 SRY 基因，您将得到一个功能齐全的男性。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
If not, you're essentially dealing with a female.
如果不是，那么您本质上是在与女性打交道。
So presumably, something about the SRY gene is conferring a vulnerability to autism.
因此，据推测，SRY 基因的某些因素导致了自闭症的易感性。
I think it's fascinating.
我认为这很有趣。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Well, there are a lot of discussions, of course, like what causes this difference, and some discussions are just in terms of diagnosis that perhaps some of the girls are not getting diagnosed properly.
嗯，当然有很多讨论，比如是什么导致了这种差异，有些讨论只是在诊断方面，也许有些女孩没有得到正确的诊断。
We do know that some of them are very good at what we call masking the symptoms, so learning the social skills, and so covering for that diagnosis.
我们确实知道他们中的一些人非常擅长我们所谓的掩盖症状，因此学习社交技能，并因此掩盖诊断。
But what we do know for sure is that there are differences in how the male and the female brain, especially around birth, can actually take up injury.
但我们确实知道的是，男性和女性的大脑（尤其是在出生前后）实际上承受伤害的方式存在差异。
Andrew Huberman:
安德鲁·休伯曼：
Hmm.
嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
So think, for instance, about premature birth.
例如，想想早产。
One of the best predictors for a premature baby in terms of outcomes, it's actually to be a female.
就结果而言，早产儿的最佳预测因素之一实际上是女性。
Just in general, female preemies will do much better for whatever reasons.
一般来说，无论出于何种原因，女性早产儿都会表现得更好。
The way the nervous system is built, the resilience.
神经系统的构建方式，即恢复力。
We know that the maturation stage is also different for the male and the female.
我们知道，雄性和雌性的成熟阶段也是不同的。
Think about acquisition of certain milestones that happen much faster in girls.
想想女孩获得某些里程碑的速度要快得多。
They generally tend to speak a few months earlier, to walk a few months earlier.
他们通常会提前几个月说话，提前几个月走路。
So just the nervous system is maturing at a different pace and can take injury differently.
因此，只是神经系统以不同的速度成熟，并且受到不同程度的伤害。
So it could be that that is certainly a cause, but at the same time, and as we were talking, since autism is not one single disease, it is very hard to point out to one specific factor that is behind it.
因此，这肯定是一个原因，但与此同时，正如我们所说，由于自闭症不是一种单一的疾病，因此很难指出其背后的一个具体因素。
Andrew Huberman:
安德鲁·休伯曼：
I'd like to take a quick break and acknowledge one of our sponsors, David.
我想稍微休息一下并感谢我们的赞助商之一大卫。
David makes a protein bar unlike any other.
大卫制作的蛋白质棒与众不同。
It has 28 grams of protein, only 150 calories, and zero grams of sugar.
它含有 28 克蛋白质，仅 150 卡路里，零克糖。
That's right, 28 grams of protein and 75% of its calories come from protein.
没错，28克蛋白质，其75%的热量都来自于蛋白质。
This is 50% higher than the next closest protein bar.
这比第二接近的蛋白质棒高出 50%。
David protein bars also taste amazing.
大卫蛋白棒的味道也很棒。
Even the texture is amazing.
就连质感也令人惊叹。
My favorite bar is the chocolate chip cookie dough, but then again, I also like the new chocolate peanut butter flavor and the chocolate brownie flavor.
我最喜欢的巧克力棒是巧克力饼干面团，但话又说回来，我也喜欢新的巧克力花生酱口味和巧克力布朗尼口味。
Basically, I like all the flavors a lot.
基本上，所有的口味我都很喜欢。
They're all incredibly delicious.
它们都非常美味。
In fact, the toughest challenge is knowing which ones to eat on which days and how many times per day.
事实上，最艰巨的挑战是知道哪一天吃哪些食物以及每天吃多少次。
I limit myself to two per day, but I absolutely love them.
我限制自己每天只能吃两个，但我绝对喜欢它们。
With David, I'm able to get 28 grams of protein in the calories of a snack, which makes it easy to hit my protein goals of one gram of protein per pound of body weight per day, and it allows me to do so without ingesting too many calories.
有了 David，我就能在一份零食的卡路里中获得 28 克蛋白质，这让我很容易达到每天每磅体重 1 克蛋白质的蛋白质目标，而且我可以在不摄入太多卡路里的情况下实现这一目标。
I'll eat a David protein bar most afternoons as a snack, and I always keep one with me when I'm out of the house or traveling.
大多数下午我都会吃大卫蛋白棒作为零食，当我出门或旅行时，我总是随身携带一根。
They're incredibly delicious, and given that they have 28 grams of protein, they're really satisfying for having just 150 calories.
它们非常美味，而且含有 28 克蛋白质，仅含 150 卡路里热量就已经很令人满意了。
If you'd like to try David, you can go to davidprotein.com/huberman.
如果您想尝试 David，可以访问 david Protein.com/huberman。
Again, that's davidprotein.com/huberman.
同样，这是 david Protein.com/huberman。
Today's episode is also brought to us by Helix Sleep.
今天的节目也是由 Helix Sleep 为我们带来的。
Helix Sleep makes mattresses and pillows that are customized to your unique sleep needs.
Helix Sleep 生产根据您独特的睡眠需求定制的床垫和枕头。
Now, I've spoken many times before on this and other podcasts about the fact that getting a great night's sleep is the foundation of mental health, physical health, and performance.
现在，我之前已经在这个播客和其他播客中多次谈到这样一个事实：睡个好觉是心理健康、身体健康和表现的基础。
Now, the mattress you sleep on makes a huge difference in the quality of sleep that you get each night.
现在，您所睡的床垫会对您每晚的睡眠质量产生巨大影响。
How soft it is or how firm it is all play into your comfort and need to be tailored to your unique sleep needs.
它的柔软度或硬度都会影响您的舒适度，并且需要根据您独特的睡眠需求进行定制。
If you go to the Helix website, you can take a brief two-minute quiz, and it will ask you questions such as, do you sleep on your back, your side, or your stomach?
如果你访问 Helix 网站，你可以做一个两分钟的简短测验，它会问你一些问题，比如你是仰卧、侧卧还是俯卧？
Do you tend to run hot or cold during the night?
你晚上容易感到热还是冷？
Things of that sort.
诸如此类的事情。
Maybe you know the answers to those questions, maybe you don't.
也许您知道这些问题的答案，也许您不知道。
Either way, Helix will match you to the ideal mattress for you.
无论哪种方式，Helix 都会为您匹配理想的床垫。
For me, that turned out to be the Dusk mattress.
对我来说，那是黄昏床垫。
I started sleeping on a Dusk mattress about three and a half years ago, and it's been far and away the best sleep that I've ever had.
大约三年半前，我开始睡在 Dusk 床垫上，这无疑是我睡过的最好的睡眠。
If you'd like to try Helix Sleep, you can go to helixsleep.com/huberman, take that two-minute sleep quiz, and Helix will match you to a mattress that's customized to you.
如果您想尝试 Helix Sleep，可以访问 helixsleep.com/huberman，参加两分钟的睡眠测验，Helix 将为您匹配适合您的床垫。
Right now, Helix is giving up to 27% off all mattress orders.
目前，Helix 为所有床垫订单提供高达 27% 的折扣。
Again, that's helixsleep.com/huberman to get up to 27% off.
再次强调，helixsleep.com/huberman 提供高达 27% 的折扣。
You mentioned that autism is diagnosed by behavioral measures or the lack of behavioral symptomology, what we call positive and negative symptoms.
您提到自闭症是通过行为测量或缺乏行为症状（我们称之为阳性和阴性症状）来诊断的。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Mm-hmm.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
Which can be confusing language because people think positive means good.
这可能会造成语言混乱，因为人们认为积极意味着好的。
No, positive is the presence, negative is the absence.
不，积极的是存在，消极的是缺席。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I haven't looked at this literature in a while, but the last time I did, it seemed that babies or young children failing to Focus their own gaze on the eyes of other people is one of the major diagnostic criteria.
我已经有一段时间没有看过这些文献了，但上次我看的时候，似乎婴儿或幼儿无法将自己的目光集中在其他人的眼睛上是主要的诊断标准之一。
It seems they look at the face more holistically, or they'll zoom in just on the nose, but they're not really making as much eye contact.
他们似乎更全面地看待脸部，或者他们只会放大鼻子，但他们并没有真正进行那么多的目光接触。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Is that still a diagnostic criteria?
这仍然是诊断标准吗？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
It's not part of the diagnostic criteria.
它不是诊断标准的一部分。
Andrew Huberman:
安德鲁·休伯曼：
Hmm.
嗯。
Interesting.
有趣的。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
But it is one of the features that has been observed.
但这是已观察到的特征之一。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Of course, it also has to do with just in general, joint attention is one of the earlier, so if you just tell a child, "Oh, look here." So if they have that attention, if they engage in that attention, it's one of the features that is associated with autism.
当然，这也与一般情况有关，共同关注是较早的一种，所以如果你只是告诉孩子，“哦，看这里。”因此，如果他们有这种注意力，如果他们投入这种注意力，这就是与自闭症相关的特征之一。
It's not certainly diagnostic.
这不一定是诊断性的。
It's not pathognomonic, so to speak, so it's not specific to the disease in any way.
可以这么说，它不是特异性的，因此它在任何方面都不是特定于该疾病的。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
But there are certainly many deficits, and some of them can actually be compensated later.
但赤字肯定有很多，而且有些其实是可以以后弥补的。
Andrew Huberman:
安德鲁·休伯曼：
Interesting.
有趣。
There were some other things I've heard over the years, for instance, that when children with autism have a fever, that their symptoms improve.
多年来我还听到过一些其他事情，例如，当自闭症儿童发烧时，他们的症状会有所改善。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Is that still the case?
现在还是这样吗？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
So those are mostly anecdotic reports-
所以这些大多是轶事报道——
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
...
...
of patients who would have a very high fever, and then, for instance, they were non-verbal.
例如，病人会发高烧，然后他们就不会说话了。
So many patients with autism, or individuals with autism, will be non-verbal.
许多自闭症患者或自闭症患者不会使用语言。
They have very few words, or they're not able to communicate.
他们的言语很少，或者无法沟通。
And so there are a few reports of parents saying that when they spike the very high fever, they'll start talking in sentences very briefly or engage.
因此，有一些报道称，父母说，当他们发烧时，他们会开始用非常简短的句子说话或参与其中。
And in fact, that is known.
事实上，这是众所周知的。
Kids, in general, when they have a high fever, they tend to be more talkative.
一般来说，孩子在发高烧的时候，往往会比较爱说话。
It activates somehow the nervous system.
它以某种方式激活神经系统。
There have been a lot of hypotheses about this.
对此有很多假设。
Some of them having to do with how the noradrenergic system is activating during fever.
其中一些与发烧期间去甲肾上腺素能系统的激活方式有关。
Others saying that there are some of the cytokines, the immune molecules that are present during fever that are somehow getting into the brain, activating the nervous system.
其他人则说，发烧期间存在的一些细胞因子、免疫分子以某种方式进入大脑，激活神经系统。
And others as simple as, oh, ion channels.
其他的就像离子通道一样简单。
Ion channels will open more when the temperature rises, so something about the circuits functioning differently during that.
当温度升高时，离子通道会打开更多，因此在此期间电路的功能会有所不同。
But it's mostly anecdotic at this point, and it's certainly, again, probably not present in all individuals with autism.
但目前这主要是轶事，而且它肯定不会出现在所有自闭症患者身上。
Also because autism is, again, not one single disease, so we would not expect it to be present in all.
另外，因为自闭症并不是一种单一的疾病，所以我们不会期望它会出现在所有疾病中。
Andrew Huberman:
安德鲁·休伯曼：
A few years ago, there was a lot of excitement about the idea that autism might somehow be related, perhaps even caused by deficits in the microbiome.
几年前，人们对自闭症可能与自闭症有某种关联，甚至可能是由微生物组缺陷引起的想法感到非常兴奋。
There were some mouse experiments of doing-
有一些小鼠实验在做——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
fecal transplants from what we call wild type or healthy mice into mice that had some symptoms that resemble autism, and there were improvements observed, to the point where I think there were some human clinical trials using fecal transplants.
将我们所谓的野生型或健康小鼠的粪便移植到具有一些类似于自闭症症状的小鼠中，并且观察到了改善，以至于我认为已经有一些使用粪便移植的人体临床试验。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Sure.
当然。
Andrew Huberman:
安德鲁·休伯曼：
Whatever became of that?
结果怎么样了？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
I think, again, almost everything has been associated or thought to be causal.
我再次认为，几乎所有事情都具有关联性或被认为是因果关系。
But generally, demonstrating this is very, very difficult.
但一般来说，证明这一点是非常非常困难的。
So we cannot deny that perhaps improving the microbiome will improve the quality of life of some of these individuals, but whether it's really causal, there's no clear evidence for it.
因此，我们不能否认，改善微生物群也许会改善其中一些人的生活质量，但是否真的有因果关系，还没有明确的证据证明。
Think about it, just to give you another example.
想一想，再举一个例子。
Think about sleep.
想想睡眠。
Many patients will report, especially the ones that are profoundly impaired, will have severe sleep disturbances.
许多患者，尤其是那些严重受损的患者，会报告出现严重的睡眠障碍。
I mean, 70, 80% of them, they can have nights where they sleep very little.
我的意思是，其中 70%、80% 的人晚上睡得很少。
Then do that for a week.
然后这样做一周。
So just imagine even just improving the quality of sleep for those patients can do miracle.
因此，想象一下，即使只是改善这些患者的睡眠质量也能创造奇迹。
I mean, all of us, if we don't sleep for three, four days, our social skills, we become socially impaired.
我的意思是，我们所有人，如果我们三四天不睡觉，我们的社交技能就会受到社交障碍。
So I think, of course, correcting a lot of these issues.
所以我认为，当然要纠正很多这样的问题。
So for instance, many patients are picky eaters.
举例来说，许多患者都是挑食的。
They don't like certain textures, so they will never eat, for instance, veggies.
他们不喜欢某些质地，所以他们永远不会吃蔬菜等。
So that creates, in the early days, for instance, we thought that there are dietary disturbances that really at the core.
因此，例如，在早期，我们认为饮食失调才是真正的核心。
Of course, it remains to be seen whether just simply correcting those is going to be just improving or certainly reversing some of these forms.
当然，仅仅纠正这些问题是否会改善或肯定会逆转其中一些形式，还有待观察。
But again, most of the evidence points out towards a very strong genetic component behind it, and in fact, we now have hundreds of genes that we know when they are mutated, they are strongly associated with specific forms of autism.
但同样，大多数证据都指出其背后有非常强大的遗传成分，事实上，我们现在有数百个基因，我们知道当它们发生突变时，它们与特定形式的自闭症密切相关。
Andrew Huberman:
安德鲁·休伯曼：
I'm curious what sorts of proteins those genes are upstream of.
我很好奇这些基因的上游是什么类型的蛋白质。
And I ask because David Ginty at Harvard did these really beautiful experiments where he induced mutations just in the periphery, so outside the brain-
我问这个问题是因为哈佛大学的大卫·金蒂（David Ginty）做了这些非常漂亮的实验，他在外围（即大脑之外）诱导了突变——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
of these mouse models for autism and saw a lot of the same symptomology.
研究人员对这些自闭症小鼠模型进行了研究，发现了许多相同的症状。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Raising the question of whether or not autism originates in the brain or whether or not the deficits in the brain are the byproduct of changes in the body.
提出了自闭症是否起源于大脑，或者大脑缺陷是否是身体变化的副产品的问题。
Yes, microbiome, but perhaps their skin, their hearing, et cetera, are more sensitive, and maybe that's why they-- You could imagine if you were ultrasensitive to an environment, that your brain would eventually wire differently according to-
是的，微生物组，但也许它们的皮肤、听觉等等更敏感，也许这就是为什么它们——你可以想象，如果你对环境超敏感，你的大脑最终会根据——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
and overwhelmed by what was happening-
并对所发生的事情感到不知所措——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
in the sensory landscape.
在感官景观中。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah, absolutely.
是的，绝对是。
And those are really elegant experiments that he's done.
他所做的这些都是非常优雅的实验。
Many of the genes fit in different categories.
许多基因属于不同的类别。
You would have genes that would produce proteins that sit at synapses, which was to be expected.
你的基因会产生位于突触处的蛋白质，这是预料之中的。
Some of them are ion channels.
其中一些是离子通道。
They're proteins that would let ions inside or outside of a neuron.
它们是让离子进入或离开神经元的蛋白质。
There are many of these conditions, so-called channelopathies.
这些病症有很多，即所谓的通道病。
Then there are the ones that are synaptic-related, so synaptopathies.
还有一些与突触相关的，即突触病。
There are a lot of chromatin genes, so like proteins that pack the DNA in cells.
染色质基因有很多，就像细胞中包装 DNA 的蛋白质一样。
Those are chromatinopathies.
这些是染色质病变。
So there are really, again, many, many categories of genes.
所以基因确实有很多很多类别。
And then what is also interesting is that many of these genes are also expressed in the periphery.
同样有趣的是，许多这些基因也在外周表达。
So I think the experiments that you are mentioning are really elegant because it showed that indeed that can perturb the development of the nervous system, even if they're affecting just the periphery.
所以我认为你提到的实验非常优雅，因为它表明这确实会扰乱神经系统的发育，即使它们只影响外围。
Of course, now in patients, they are present also in the central nervous system, so it's always difficult to distinguish.
当然，现在在患者中，它们也存在于中枢神经系统中，所以总是很难区分。
But just missing some of these critical periods or perturbing some of these critical periods of development can have certainly devastating effects later on.
但仅仅错过其中一些关键时期或扰乱其中一些发展关键时期肯定会在以后产生破坏性影响。
Andrew Huberman:
安德鲁·休伯曼：
So if a parent comes into the clinic nowadays with a child that's diagnosed with profound autism, what is the treatment?
那么，如果现在有家长带着被诊断患有严重自闭症的孩子来到诊所，治疗方法是什么？
Let's set aside the potential for epilepsy, which hopefully they would treat as well, or other things that might be secondary.
让我们先把癫痫的可能性放在一边，希望他们也能治疗癫痫，或者其他可能是次要的事情。
But what is the typical treatment?
但典型的治疗方法是什么？
And let's assume infinite resources-
让我们假设无限的资源 -
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
which of course nobody has, most people don't have.
当然没有人拥有，大多数人都没有。
But if one had infinite resources, what would be done?
但如果一个人拥有无限的资源，他会做什么呢？
Would it be behavioral training?
会是行为训练吗？
Would it be something to control the activation state of the brain?
会不会是控制大脑激活状态的东西？
As far as I know, there's no single treatment for autism.
据我所知，自闭症没有单一的治疗方法。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
No, there's no single treatment for autism.
不，自闭症没有单一的治疗方法。
Again, in the context of this not being one single disease.
再说一次，这不是一种单一疾病。
What we can say today is that if a family walks into the clinic with the diagnosis of autism or perhaps they receive it into the clinic, there's still a 20% probability that they'll leave the clinic with a genetic diagnosis, meaning that it will be pointed out to them that this gene is mutated in your child.
今天我们可以说的是，如果一个家庭带着自闭症的诊断走进诊所，或者他们接受了自闭症诊断，他们离开诊所时仍有 20% 的可能性会得到基因诊断，这意味着会向他们指出你的孩子的这个基因发生了突变。
And it may be sometimes a mutation that was present in one of the parents and got transmitted, or maybe it was present in both and somehow the child got two copies that were modified now, or many of the genes are actually mutated de novo, meaning that the mutation was not present in either parents, but something went wrong during development, perhaps early in the sperm cell, in the egg cell, or perhaps in early stages of development, and a new mutation was acquired.
有时，它可能是父母之一中存在的突变并被传播，或者可能是双方都存在，不知何故，孩子现在得到了两个被修改的拷贝，或者许多基因实际上是从头突变的，这意味着父母双方都不存在突变，但在发育过程中出了问题，可能在精子细胞的早期，在卵细胞中，或者可能在发育的早期阶段，并且获得了新的突变。
We acquire a lot of mutations.
我们获得了很多突变。
All of us, we have a lot of new mutations.
我们所有人都有很多新的突变。
About 80 new mutations, 30 of them are protein truncating.
大约 80 个新突变，其中 30 个是蛋白质截短。
So certainly the challenge very often is to, even when you see a gene that is mutated, to know whether that gene is truly causing the disease.
因此，即使您看到一个基因突变，通常面临的挑战仍然是要知道该基因是否真正导致了这种疾病。
So very often the way we know is that we find many patients that have a similar presentation clinically.
我们通常知道，我们发现许多患者在临床上有类似的表现。
Let's say maybe they'll have syndactyly, so they have webbing of the finger, and they have autism, and let's say epilepsy, and they all have a mutation in one single channel.
假设他们可能患有并指症，所以他们有手指蹼，他们患有自闭症，比方说癫痫症，他们都在一个单一的通道中发生了突变。
Let's say in a calcium channel.
比方说在钙通道中。
So that would be Timothy syndrome, a genetic form of autism where the mutation is very clear.
这就是蒂莫西综合症，一种自闭症的遗传形式，其突变非常明显。
Actually, there's one single letter in the genome that is changed and causes a relatively similar presentation in all of these patients.
事实上，基因组中有一个字母发生了变化，导致所有这些患者出现相对相似的表现。
So about 20% of the patients will get a genetic diagnosis.
所以大约20%的患者会得到基因诊断。
Now, sadly, that doesn't do that much today because we don't really have specific therapies for those forms.
可悲的是，现在这种方法并没有多大作用，因为我们并没有针对这些形式的具体疗法。
I think the hope is that perhaps we will have individual treatments, whether they're going to be genetic or otherwise.
我认为我们希望也许我们能够进行个体化治疗，无论它们是遗传的还是其他的。
So being part of that community is generally useful.
因此，成为该社区的一部分通常是有用的。
And then the rest of the patients will essentially fit into this larger category of idiopathic, meaning that we don't really know the precise cause.
然后其余的患者基本上将属于这个更大的特发性类别，这意味着我们并不真正知道确切的原因。
Andrew Huberman:
安德鲁·休伯曼：
I want to talk about Timothy syndrome, and I also want to talk about genetic approaches for fixing genes-
我想谈谈蒂莫西综合症，我也想谈谈修复基因的遗传方法——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
so-called gene therapy.
所谓的基因疗法。
Before we do that, would you be willing to just speculate on why you think there's this fairly dramatic increase in the incidence of autism?
在我们这样做之前，您是否愿意推测一下为什么您认为自闭症发病率如此急剧增加？
People will always say, well, maybe it's better detection, better diagnosis.
人们总是会说，好吧，也许这是更好的检测、更好的诊断。
So I'd like your thoughts on that, and if there are increases that can't be explained with that, I just would like your thoughts.
所以我想听听您对此的想法，如果有无法用此解释的增加，我只是想听听您的想法。
I realize-
我意识到——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Sure
当然可以
Andrew Huberman:
安德鲁·休伯曼：
...
...
we're not talking formal biostatistics here.
我们这里讨论的不是正式的生物统计学。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
No.
不。
Andrew Huberman:
安德鲁·休伯曼：
Just in your experience, you're an MD, you think about autism a lot, you're working on potential cures for autism and other neurologic conditions.
根据您的经验，您是一名医学博士，您经常思考自闭症，您正在研究自闭症和其他神经系统疾病的潜在治疗方法。
How do you think about this increased prevalence issue?
您如何看待这种患病率增加的问题？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Well, certainly the increase is still puzzling.
好吧，当然，这种增长仍然令人费解。
So I think on one hand, there's no doubt that the changes in diagnostic criteria, which have happened over time, we had to just refine what autism really is.
所以我认为，一方面，毫无疑问，随着时间的推移，诊断标准发生了变化，我们必须完善自闭症的真正含义。
That changed, to some extent, the prevalence.
这在某种程度上改变了流行率。
We've also seen a diagnostic migration, so to speak.
可以这么说，我们还看到了诊断迁移。
So some children, for instance, 30 years ago would have been diagnosed with intellectual disability, and today they fit the criteria for autism.
例如，有些孩子在 30 年前会被诊断为智力障碍，但今天他们符合自闭症的标准。
About a third of individuals with autism also have intellectual disability, so there is also a great overlap between the conditions.
大约三分之一的自闭症患者也有智力障碍，因此这些情况之间也存在很大的重叠。
So there's been a move sometimes between the diagnosis over time.
因此，随着时间的推移，诊断之间有时会发生变化。
Of course, there are all kind of discussions about availability of services and to what extent that is also contributing.
当然，关于服务的可用性以及服务的贡献程度有各种各样的讨论。
But we don't truly understand all the reasons behind this increase.
但我们并不真正了解这种增长背后的所有原因。
There's no doubt.
毫无疑问。
We know that it's highly heritable based on genetic studies.
根据遗传学研究，我们知道它具有高度遗传性。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
So we know the heritability is very high, one of the highest for psychiatric disorders that we know of.
所以我们知道遗传力非常高，是我们所知的精神疾病中遗传力最高的之一。
But of course, we don't have the genes for every single form, so it is likely that some of them are very rare.
但当然，我们并没有每种形式的基因，因此其中一些可能非常罕见。
So essentially, just think of it as they're individually rare form, but collectively common.
因此，从本质上讲，只需将其视为单独的罕见形式，但总体上很常见。
So it will take a while until we map all of them.
因此，我们需要一段时间才能绘制出所有这些地图。
And then, of course, there are environmental factors that we do know historically can contribute to this, so there are various exposures to environmental factors.
当然，我们历史上确实知道一些环境因素会导致这种情况，因此环境因素的暴露程度多种多样。
Like in early days, thalidomide, for instance, was one of them that we know increases the risk for autism.
例如，与早期一样，沙利度胺是我们知道会增加自闭症风险的药物之一。
So of course, those are contributing.
当然，这些都是有贡献的。
Andrew Huberman:
安德鲁·休伯曼：
Thalidomide was a drug given to pregnant mothers to try and prevent miscarriage, right?
沙利度胺是一种给孕妇服用的药物，用于防止流产，对吗？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Exactly.
正是如此。
Andrew Huberman:
安德鲁·休伯曼：
It's no longer prescribed.
不再规定了。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
It's no longer prescribed.
不再规定了。
Andrew Huberman:
安德鲁·休伯曼：
Because it caused major birth defects.
因为它导致了严重的出生缺陷。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Defects.
缺陷。
Exactly.
确切地。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
So certainly, it's quite complex because first of all, the definition of the condition is quite difficult.
当然，它相当复杂，因为首先，条件的定义非常困难。
And I think that is in general the challenge with psychiatric disorders.
我认为这通常是精神疾病面临的挑战。
And perhaps one of the reasons we've made such slow progress in understanding these conditions, because, of course, the power of modern medicine is in molecular biology.
也许我们在了解这些疾病方面进展缓慢的原因之一是，当然，现代医学的力量在于分子生物学。
We deploy this remarkable force of an understanding.
我们运用这种非凡的理解力量。
And in order to do that, you need two things.
为了做到这一点，你需要做两件事。
You need, first of all, to have a very clear definition of what that disease is, generally, biologically.
首先，您需要从生物学角度对这种疾病有一个非常清晰的定义。
Think about myocardial infarction, very clearly defined in terms of what it actually means.
想想心肌梗塞，它的实际含义非常明确。
You immediately have biomarkers.
您立即就有了生物标志物。
The patient walks in, you take blood, you can immediately tell, yes, in 20 minutes, you can tell that they have a myocardial infarction based on a biomarker.
病人走进去，你抽血，你可以立即看出，是的，20分钟后，你可以根据生物标志物判断出他们患有心肌梗塞。
And then the other one, which is certainly very important, which to a large extent is the source of all the work that we've done, is the unbearable inaccessibility of the human brain, so to speak.
然后另一个问题，当然非常重要，在很大程度上是我们所做的所有工作的源泉，可以说是人类大脑难以忍受的难以接近。
And to a large extent, the human brain is inaccessible for most of its development.
在很大程度上，人类大脑的大部分发育都是无法进入的。
And so if you look actually across branches of medicine, you can see that there is a very strong correlation between how accessible an organ is and how many cures or therapies we actually have.
因此，如果你真正纵观医学各个分支，你会发现器官的可及性与我们实际拥有的治愈方法或疗法的数量之间存在很强的相关性。
Think even just in cancer.
即使只是癌症。
Think about in cancer, which used to be, of course, an incurable disease a century ago.
想想癌症，一个世纪前，癌症当然是一种不治之症。
Think about leukemias in children.
想想儿童白血病。
They were 90% lethal in the '50s and the '60s.
在 20 世纪 50 年代和 60 年代，它们的致死率高达 90%。
Today, they are maybe 10% lethal.
如今，它们的致死率可能为 10%。
And that is because blood from these patients, it's very easy to collect.
这是因为这些患者的血液很容易收集。
We've been bringing it to the lab, studying it, what goes wrong, and then deploying molecular biology to develop therapeutics.
我们一直把它带到实验室，研究它，找出问题所在，然后利用分子生物学来开发治疗方法。
With the brain, sadly, there's no way of doing it.
遗憾的是，对于大脑来说，没有办法做到这一点。
And so largely, what we've been trying to do is to find a way of shortcutting that process.
很大程度上，我们一直在努力寻找一种缩短这一过程的方法。
But I do believe that the major challenges that we're facing in understanding brain disorders, whether they're neurological or psychiatric, are on one hand, the inaccessibility of the organ of interest, the brain, and on the other hand, our challenges are very often defining some of these conditions with biological markers because they're much more complex.
但我确实相信，我们在理解大脑疾病方面面临的主要挑战，无论是神经疾病还是精神疾病，一方面是无法接近感兴趣的器官，即大脑，另一方面，我们的挑战往往是用生物标记来定义其中一些疾病，因为它们要复杂得多。
Andrew Huberman:
安德鲁·休伯曼：
The degree to which correlation has been leveraged to try and understand neurologic disease is kind of staggering.
利用相关性来尝试和理解神经系统疾病的程度令人震惊。
I'll just share a couple, and I would love your reflections.
我只会分享一些，我会喜欢你的想法。
I remember when I was an undergraduate and in graduate school, there was this prominent theory that a mother who contracted influenza, the flu, toward the end of her second trimester had a much higher probability of having a schizophrenic child.
我记得当我还是一名本科生和研究生时，有一个著名的理论，即在妊娠中期末感染流感的母亲生出精神分裂症孩子的可能性要高得多。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Mm-hmm.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
And there was so much said of that.
关于这一点有很多说法。
And then now we barely hear anything about it at all.
然后现在我们几乎没有听到任何关于它的消息。
Although I think schizophrenia is more prominent toward the poles, where you have harsher winters as opposed to around the equator.
尽管我认为精神分裂症在两极地区更为突出，那里的冬天比赤道附近更严酷。
But someone needs to check me on that because those statistics might have melted away with more careful analysis.
但需要有人来检查我的情况，因为通过更仔细的分析，这些统计数据可能会消失。
I don't know.
我不知道。
The other thing is that you'll nowadays hear a growing interest in populations for which a given disease is very rare.
另一件事是，您现在会听到人们对某种特定疾病非常罕见的人群越来越感兴趣。
So one of the things that's circulating out there now that's related to the vaccine debate, and by the way, I'll myself go on record, I don't think there's any solid evidence that vaccines cause autism.
所以现在流传的一件事与疫苗辩论有关，顺便说一句，我自己要记录下来，我认为没有任何确凿的证据表明疫苗会导致自闭症。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
And there's not.
但没有。
Epidemiologically, there's no evidence.
从流行病学角度来说，没有证据。
Andrew Huberman:
安德鲁·休伯曼：
There's not.
没有。
There's this open question as to whether or not vaccines of all kinds can increase inflammation, and there might be things downstream of inflammation.
有一个悬而未决的问题，即各种疫苗是否会增加炎症，并且炎症的下游可能存在一些东西。
But for the record, right now there are no published papers that have not been retracted that support the vaccine-autism link.
但郑重声明，目前还没有发表的论文支持疫苗与自闭症之间的联系，但这些论文都被撤回了。
I think those papers are being reinvestigated under the new administration, but let's leave that aside for now.
我认为新政府正在对这些文件进行重新调查，但我们现在先把它放在一边。
People will say, well, you have groups like Amish populations, where the incidence of autism is significantly lower.
人们会说，嗯，有像阿米什人这样的群体，那里的自闭症发病率要低得多。
Turns out it does exist.
事实证明它确实存在。
I looked at these data, but it's significantly lower.
我查看了这些数据，但明显较低。
And then people will say, well, it's the absence of food dyes, it's the absence of vaccines, perhaps, et cetera.
然后人们会说，好吧，这是因为缺乏食用色素，可能是因为缺乏疫苗，等等。
But then as a genetic disease, we could say, well, there's a tendency for people in the Amish community to reproduce with other people in the Amish community, so it's a more restricted genetic pool.
但作为一种遗传疾病，我们可以说，阿米什社区的人们倾向于与阿米什社区的其他人一起繁殖，所以这是一个更受限制的基因库。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And so that could explain it as well.
这也可以解释这一点。
And I raise this not to create any additional arguments, there are enough out there-
我提出这个并不是为了制造任何额外的论据，已经有足够的论据了——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
between people, but just because I think the correlative nature of all this is what kind of raises the opportunity for anything that's observed, like a fever, they get better.
人与人之间，但只是因为我认为所有这一切的相关性本质上就是增加了观察到的任何事情的机会，比如发烧，他们就会好起来。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Sure.
当然。
Andrew Huberman:
安德鲁·休伯曼：
But as you said, healthy kids without profound autism also talk more when they have a fever.
但正如你所说，没有严重自闭症的健康孩子在发烧时也会说得更多。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Sure.
当然。
Andrew Huberman:
安德鲁·休伯曼：
And so there's been so much made of autism and the various conditions that could create it.
因此，自闭症以及可能导致自闭症的各种条件已经有很多。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And I think it's been very confusing for the general public.
我认为这对公众来说非常令人困惑。
Even as a trained scientist, it's been very confusing for me.
即使作为一名训练有素的科学家，这对我来说也很困惑。
I feel like every six months or so, every year, we have a new pet hypothesis.
我觉得每年大约每六个月，我们就会有一个新的宠物假设。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But except for these genetic data, nothing really is rock solid.
但除了这些基因数据之外，没有什么是真正坚如磐石的。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Right.
对。
And then, of course, the other issue is also that these conditions are disorders of the human brain.
当然，另一个问题是这些病症是人类大脑的疾病。
So if you think about it, even talking about schizophrenia, hallucinations, or phenomena that are very difficult to study, and of course, we don't know this.
所以如果你想一想，即使是谈论精神分裂症、幻觉或非常难以研究的现象，当然，我们不知道这一点。
We know that schizophrenia is present in almost every population that we know of, even isolated population at 1%.
我们知道，精神分裂症几乎存在于我们所知道的每个人群中，甚至在孤立人群中也有 1%。
And again, it's a little bit easier because it's done in adults.
再说一次，这要容易一些，因为它是在成年人身上进行的。
I think in children, it's much more difficult.
我认为对于儿童来说，这要困难得多。
And in fact, many of the genes that were early on identified for autism were identified in these populations, in the Amish populations, for instance.
事实上，许多早期发现的自闭症基因都是在这些人群中发现的，例如在阿米什人群中。
There is a very classic example of a gene that is associated with severe epilepsy and autism that was identified there for the first time.
有一个非常经典的例子，其中首次发现了与严重癫痫和自闭症相关的基因。
It's present in other places as well.
它也存在于其他地方。
So, yeah, I think, of course, the complexity of the problem is that you also want to make sure that you don't just associate something, you also want to reverse it in a way.
所以，是的，我认为，当然，问题的复杂性在于你还想确保你不只是关联某些东西，你还想以某种方式反转它。
So you would want to do the other experiment where you change it and then it goes away.
所以你会想做另一个实验，你改变它，然后它就消失了。
But you can never do that in the human brain.
但在人脑中你永远无法做到这一点。
We can't just turn things on and off to see whether they're truly causal.
我们不能只是打开或关闭事物来看看它们是否真的有因果关系。
And then, of course, human brain development also takes an incredibly long period of time.
当然，人类大脑的发育也需要非常长的时间。
If anything, it seems that the human nervous system has done everything possible to slow down that process.
如果说有什么不同的话，那就是人类神经系统似乎已尽一切可能减缓这一过程。
We myelinate all the way to the third decade.
我们的髓鞘形成一直到第三个十年。
Neurons are born and migrating through the nervous system into early postnatal years.
神经元出生并通过神经系统迁移到出生后早期。
Andrew Huberman:
安德鲁·休伯曼：
Wait, you're telling me that our neurons continue to get myelinated, which, of course, for those that don't know, is the building of the ensheathment that allows electrical signals to be passed down neurons more efficiently, until we're 30 years old?
等等，你是在告诉我，我们的神经元会继续有髓鞘化，当然，对于那些不知道的人来说，这就是建立鞘膜，让电信号更有效地传递给神经元，直到我们 30 岁？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yes.
是的。
There's evidence that myelination, especially in the frontal areas of the brain, are continuing up to the third decade.
有证据表明，髓鞘形成，尤其是大脑额叶区域的髓鞘形成，一直持续到三十岁。
Andrew Huberman:
安德鲁·休伯曼：
Our unfortunately now deceased former colleague, Ben Barris, he used to shout at people in lab meetings-
不幸的是，我们的前同事本·巴里斯（Ben Barris）现已去世，他曾经在实验室会议上对人们大喊大叫——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
when they'd say something he didn't like.
当他们说一些他不喜欢的话时。
He'd say, "What do you know?
他会说：“你知道什么？
You're not even myelinated yet."
你甚至还没有形成髓鞘。”
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Exactly.
正是如此。
Andrew Huberman:
安德鲁·休伯曼：
So he was right.
所以他是对的。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
He was absolutely right.
他是绝对正确的。
Andrew Huberman:
安德鲁·休伯曼：
Okay, so if you're in a disagreement with somebody younger than 30, and you happen to be older than 30, you can leverage the argument, what do you know?
好吧，如果你与 30 岁以下的人有分歧，而你恰好超过 30 岁，你可以利用争论，你知道什么？
You're not even myelinated yet.
你甚至还没有形成髓鞘。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
Completely myelinated yet.
尚未完全有髓鞘。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
All kidding aside, before we get into the incredible experiments that you're doing and the direction that you're taking to tackle these really hard diseases, I have to ask two questions.
不开玩笑了，在我们讨论你们正在做的令人难以置信的实验以及你们为解决这些真正的顽疾而采取的方向之前，我必须问两个问题。
First, is the incidence of autism also increasing outside of the United States, or is this something unique to the United States and Northern Europe?
首先，自闭症的发病率在美国以外地区是否也在增加，或者这是美国和北欧独有的现象？
I don't know why we always pair those two.
我不知道为什么我们总是把这两个配对。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yes.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I should just be fair to the United States and Australia, or whatever.
我应该公平地对待美国和澳大利亚，或者其他国家。
Or is there something going on in the United States in particular that autism is increasing faster here?
或者是在美国发生了一些事情，特别是自闭症在这里增长得更快？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah, no. The prevalence for autism has been actually reported to be higher in other countries even before this.
是的，不。据报道，其他国家的自闭症患病率实际上在此之前就更高。
Some of the early reports many years ago show that in Korea, for instance, the prevalence was very high.
许多年前的一些早期报告表明，例如在韩国，患病率非常高。
Now that the studies are done, also in Scandinavian countries, it shows that it's probably around the same kind of rate, one in 30 to one in 40.
现在，这些研究也在斯堪的纳维亚国家完成，结果表明，这一比例可能大致相同，即三十分之一到四十分之一。
So somewhere between.
所以介于两者之间。
Andrew Huberman:
安德鲁·休伯曼：
Okay, so it can't be whatever is attached to United States specific conditions.
好吧，所以它不可能是与美国具体条件相关的任何东西。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah, very unlikely.
是的，不太可能。
Andrew Huberman:
安德鲁·休伯曼：
Well, because you hear these arguments.
好吧，因为你听到了这些争论。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Of course.
当然。
Andrew Huberman:
安德鲁·休伯曼：
Oh, it's the glyphosates in the-
哦，这是草甘膦——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
the crops in the United States, and while I don't favor that argument, I do think we need to be cautious about what's in the food supply.
虽然我不赞成这种说法，但我确实认为我们需要对粮食供应保持谨慎。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Absolutely.
绝对的。
Andrew Huberman:
安德鲁·休伯曼：
Those same people often will leverage the argument that, well, in Europe, they're not using these things.
这些人经常会利用这样的论点：在欧洲，他们没有使用这些东西。
Well, if the incidence of autism is the same and rising-
好吧，如果自闭症的发病率相同并且还在上升——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
that sort of does away with at least the clean logic of that.
这至少消除了清晰的逻辑。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
And perhaps another argument which is very important to bring is that we find the same mutations.
也许另一个非常重要的论点是我们发现了相同的突变。
The same mutations, if we're talking, let's say, a mutation, a specific calcium channel, you'll find it in a patient in Denmark, as well as one in Africa or in, let's say, Australia.
同样的突变，如果我们谈论的是一种突变，一种特定的钙通道，你会在丹麦的一名患者以及非洲或澳大利亚的患者身上发现它。
So I think some of these genetic mutations are sort of the same.
所以我认为其中一些基因突变是相同的。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Could we briefly talk about gene therapy and CRISPR?
我们能简单谈谈基因疗法和 CRISPR 吗？
Just briefly.
只是简单地说。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Sure.
当然。
Andrew Huberman:
安德鲁·休伯曼：
Because I think in the context of a discussion about these neurologic diseases for which currently there aren't perfect cures, or even cures in many cases, gene therapy does hold some promise.
因为我认为，在讨论这些神经系统疾病（目前还没有完美的治愈方法，甚至在许多情况下甚至没有治愈方法）的背景下，基因疗法确实有一些希望。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah, absolutely.
是的，绝对是。
Andrew Huberman:
安德鲁·休伯曼：
In simple terms that I and everyone else can understand, could you just explain what CRISPR allows physicians potentially to do?
用我和其他人都能理解的简单术语来说，您能否解释一下 CRISPR 可以让医生做什么？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
In other words, can genes be fixed in adulthood?
换句话说，基因可以在成年后固定吗？
Do they have to be fixed in the embryo?
它们必须固定在胚胎中吗？
Just give your thoughts generally about CRISPR and gene therapy, because I think most people have heard of it.
请概括一下您对 CRISPR 和基因治疗的看法，因为我认为大多数人都听说过。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But I think most people don't have an intuitive sense for how it works.
但我认为大多数人对其工作原理没有直观的认识。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
So gene therapy is a rather broad term, and it covers many ways in which you can correct generally a gene or a genetic defect that we think it's causal.
因此，基因疗法是一个相当广泛的术语，它涵盖了许多方法，您可以通过这些方法来纠正我们认为是因果关系的基因或遗传缺陷。
So on one extreme, for instance, you can envision a gene is broken, has a mutation, so what you want to do is you want to put it back.
例如，在一个极端，你可以想象一个基因被破坏，发生了突变，所以你想做的就是把它恢复原状。
So those were some of the early efforts where you would put it in a virus and deliver it to the patient.
这些是早期的一些努力，你将其放入病毒中并将其传递给患者。
Andrew Huberman:
安德鲁·休伯曼：
An adult.
一个成年人。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
In an adult or in a child, depending on the condition, with the idea is that the gene is not there, or there's not enough of it, so I'm just going to deliver more.
对于成人或儿童，根据具体情况，想法是基因不存在，或者基因不足，所以我只是要提供更多。
That's one extreme.
这是一种极端。
Andrew Huberman:
安德鲁·休伯曼：
Is it injected into the blood, or do you have to go into the specific cell type that's lacking the gene?
它是被注射到血液中，还是必须进入缺乏该基因的特定细胞类型？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Many of the studies were done for blood disorders, of course, because it was easier, so you would inject them.
当然，许多研究都是针对血液疾病进行的，因为它更容易，所以你会注射它们。
Of course, the other possibility is sometimes you don't want to put the gene, you want to put the protein already made.
当然，另一种可能性是有时你不想放基因，你想放已经制成的蛋白质。
And that is the case for many conditions where an enzyme, so a protein that does some interesting chemical reactions that are essential to a cell is missing.
在许多情况下都是这种情况，其中缺少一种酶，即缺少一种对细胞至关重要的有趣化学反应的蛋白质。
So sometimes you just make that enzyme, and then you deliver that.
所以有时你只是制造这种酶，然后再输送它。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
It's not always working, but in some cases, it actually works really well.
它并不总是有效，但在某些情况下，它实际上非常有效。
Now, the other thing that you can do is you can try to correct that defect directly.
现在，您可以做的另一件事是尝试直接纠正该缺陷。
That means you need to operate at the DNA level.
这意味着您需要在 DNA 水平上进行操作。
So somehow you need to get into every single cell that is affected, and correct that.
因此，你需要以某种方式进入每个受影响的细胞，并纠正它。
And that's where CRISPR comes into play, where presumably you could at one point deliver the guides, so the tiny pieces of nucleic acid that tell you where to go on the DNA, and then an enzyme that will do the cutting and then the putting back, or various other versions of this that you would correct.
这就是 CRISPR 发挥作用的地方，大概你可以在某一时刻提供指南，即告诉你 DNA 上哪里的微小核酸片段，然后是一种酶，它将进行切割，然后放回原位，或者你可以纠正的各种其他版本。
Of course, there are challenges with that.
当然，这也存在挑战。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, where do you put it?
是啊，你把它放在哪里？
So for sickle cell anemia, I know they've essentially reversed sickle cell anemia using CRISPR technology.
因此，对于镰状细胞性贫血，我知道他们已经使用 CRISPR 技术基本上逆转了镰状细胞性贫血。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
That's in the blood, right?
那是在血液里的，对吗？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
It's in the blood.
它存在于血液中。
Andrew Huberman:
安德鲁·休伯曼：
It's of the blood.
这是血的。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
But if, for instance, we know about a genetic defect of, let's say, we'll talk more about this soon, but a mutated calcium channel that disrupts heart function and brain function-
但是，例如，如果我们知道一种基因缺陷，比如说，我们很快就会更多地讨论这一点，但是一种突变的钙通道会破坏心脏功能和大脑功能——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
and you come in with CRISPR, you know what gene is mutated.
当你使用 CRISPR 技术时，你就知道什么基因发生了突变。
You have the healthy gene that potentially you can put back.
你拥有可以恢复的健康基因。
Where do you put it?
你把它放在哪里？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
Do you inject it?
你注射吗？
Injecting into the heart is possible.
注射到心脏是可能的。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Into the blood supply, obviously easier.
进入血液供应，显然更加容易。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Getting it directed to the bone marrow, but to the brain is hard.
将其引导至骨髓，但引导至大脑是很困难的。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Well, presumably you could inject into the brain as well, right?
嗯，想必你也可以注射到大脑中，对吧？
There are ways in which you can inject through either surgery or through an injection in the spinal canal, like intrathecally.
您可以通过手术或椎管内注射（例如鞘内注射）的方式进行注射。
So that's certainly one way in which we can do it.
所以这当然是我们可以做到的一种方式。
It is very challenging, though, because of course the brain has a lot of cell types.
但这非常具有挑战性，因为大脑当然有很多细胞类型。
And very often the way you deliver this, like through a virus or through other modalities, there's only so much of that virus that you can actually put inside the nervous system.
通常，通过病毒或其他方式传递病毒的方式，实际上只能将病毒放入神经系统中。
And the efficiency is not yet very high.
而且效率还不是很高。
So another way is to go one level down, so that gene will produce an RNA that will produce a protein.
所以另一种方法是降低一个水平，这样基因就会产生RNA，而RNA又会产生蛋白质。
So perhaps we don't have to correct the DNA everywhere, but perhaps we can correct something that happens downstream.
因此，也许我们不必在所有地方都纠正 DNA，但也许我们可以纠正下游发生的一些事情。
And that's been the strategy that we've been using primarily, just mostly because at this point, and probably in the future, it will be possible.
这就是我们主要使用的策略，主要是因为在这一点上，也许在未来，这是可能的。
Who knows, like in 10 years or maybe even earlier, we'll be able to deliver very effectively some of these genetic therapies using CRISPR.
谁知道，十年后甚至更早，我们将能够使用 CRISPR 非常有效地提供其中一些基因疗法。
Andrew Huberman:
安德鲁·休伯曼：
Because certainly in non-human primate models, things like colorblindness-
因为当然在非人类灵长类动物模型中，色盲之类的事情-
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
have been rescued by introducing a gene through a--
通过引入基因而获救——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
When we talk about viruses, people often will think, "Oh goodness, why would I want to get injected with a virus?" But we should just mention there are things like adenoviruses, which cold viruses are adenoviruses-
当我们谈论病毒时，人们常常会想：“天啊，我为什么要注射病毒呢？”但我们应该提一下，有像腺病毒这样的东西，感冒病毒就是腺病毒——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yes
是的
Andrew Huberman:
安德鲁·休伯曼：
...
...
that can be engineered so that they don't make you sick, but they can carry a cargo, like a gene you want to put into-
可以对其进行改造，这样它们不会让你生病，但它们可以携带货物，比如你想要放入的基因——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
a nervous system or body that lacks that gene.
缺乏该基因的神经系统或身体。
So when we say using viruses to deliver genes, it's of the benevolent type.
所以当我们说用病毒来传递基因时，它是仁慈的类型。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
Or at least benevolent motivation.
或者至少是仁慈的动机。
We think that those adenoviruses can live in our body for a long time-
我们认为那些腺病毒可以在我们体内存活很长时间——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
without causing additional trouble.
不会造成额外的麻烦。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
And they're very often modified to make sure that they don't cause disease.
而且它们经常被修改以确保它们不会引起疾病。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Of course, another limitation of that is that if the gene is really large, it simply won't fit in a virus.
当然，另一个限制是，如果基因真的很大，它根本不适合病毒。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
So for instance, that would be the case if you think about a calcium channel.
举例来说，如果你考虑钙通道，情况就是如此。
A calcium channel is a gigantic gene.
钙通道是一个巨大的基因。
It would be very difficult to fit inside a virus.
要想融入病毒内部是非常困难的。
Then, of course, the other thing is with these viruses, very often, especially with the adenoviruses or AAVs, is that you have one shot, meaning that you have to inject once-
当然，另一件事是这些病毒，特别是腺病毒或 AAV，通常是你只能注射一次，这意味着你必须注射一次——
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
...
...
and hopefully it would work, because next time you may have an immune reaction, right?
希望它会起作用，因为下次你可能会出现免疫反应，对吗？
You'll produce antibodies, and so you won't be able to deliver again.
您会产生抗体，因此您将无法再次分娩。
So again, there are all kinds of challenges that people are working really hard to solve, and I have no doubt that in the next decade we'll see therapies or perhaps even cures for some of these conditions.
再说一次，人们正在努力解决各种各样的挑战，我毫不怀疑，在未来十年中，我们将看到针对其中一些疾病的疗法，甚至治愈方法。
Of course, and I think you were bringing this up, one of the challenges is when we do this.
当然，我认为您提到了这一点，挑战之一是我们何时这样做。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Because especially for disorders of the brain, neurodevelopmental disorders, so autism and other neurodevelopmental disorders, the question is always how early it is too late.
因为特别是对于大脑疾病、神经发育障碍、自闭症和其他神经发育障碍来说，问题始终是多早为时已晚。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
How much damage has been done, and how much can I actually correct?
已经造成了多少损害，我实际上可以纠正多少？
And that's one of the things that we're only now starting to really explore as we're thinking about some of the first clinical trials in this space.
这是我们现在才开始真正探索的事情之一，因为我们正在考虑这个领域的一些首批临床试验。
Andrew Huberman:
安德鲁·休伯曼：
This might shock you a bit, but folks in the quote-unquote biohacking community, not me I know some that have gotten follistatin gene therapy-
这可能会让你有点震惊，但是生物黑客社区的人们，不是我，我知道一些人已经接受了卵泡抑素基因治疗——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Mm
毫米
Andrew Huberman:
安德鲁·休伯曼：
...
...
as a body enhancement thing.
作为增强体质的东西。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Mm.
嗯。
Andrew Huberman:
安德鲁·休伯曼：
So they're leaving the country because you can't do it in the United States, and literally getting an injection of a follistatin gene therapy to have more muscle to improve that.
因此，他们离开这个国家，因为在美国做不到这一点，并且实际上注射了卵泡抑素基因疗法，以拥有更多的肌肉来改善这一点。
I wouldn't do it personally.
我个人不会这样做。
Also, I like working out, so I don't need a follistatin gene therapy.
另外，我喜欢锻炼，所以不需要卵泡抑素基因治疗。
But it's interesting to note that people are doing this, and I'm raising this as a segue into a discussion about stem cells-
但有趣的是，人们正在这样做，我将其作为关于干细胞讨论的延续-
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
because people around the world are getting injected with stem cells.
因为世界各地的人们都在接受干细胞注射。
In the United States, it's-
在美国，是——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
still not allowed by FDA for most things.
FDA 仍然不允许大多数事情。
But I think gene therapy has started.
但我认为基因治疗已经开始了。
It's certainly begun.
肯定已经开始了。
But it's not the sort of thing that your physician offers up early.
但这不是你的医生提前提供的那种东西。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
It's still very experimental for most things.
对于大多数事情来说，它仍然处于实验阶段。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
And then for gene therapies, again, in the context of what you're mentioning, is some of these, again, they are irreversible.
然后对于基因疗法，再次，在你提到的背景下，其中一些是不可逆转的。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
So once you put the gene in, and it goes into a cell, let's say through a lentivirus that will integrate, you can't take it out anymore.
因此，一旦你将基因放入细胞中，比如说通过慢病毒进行整合，你就无法再将其取出。
Right?
正确的？
That would be very difficult.
那将是非常困难的。
It would get inactivated over time, but so that's why we have to be extra careful with some of these therapies and make sure that we don't do more harm, right?
随着时间的推移，它会失活，但这就是为什么我们必须对其中一些疗法格外小心，并确保我们不会造成更多伤害，对吗？
Which I guess is always what we try.
我想这始终是我们尝试的事情。
Andrew Huberman:
安德鲁·休伯曼：
Absolutely.
绝对的。
I'd like to take a quick break and acknowledge our sponsor, AG1.
我想稍微休息一下并感谢我们的赞助商 AG1。
AG1 is a vitamin mineral probiotic drink that also includes prebiotics and adaptogens.
AG1 是一种维生素矿物质益生菌饮料，还包含益生元和适应原。
As many of you know, I've been taking AG1 for more than 13 years now.
你们很多人都知道，我服用 AG1 已经超过 13 年了。
I discovered it way back in 2012, long before I ever had a podcast, and I've been drinking it every day since.
我早在 2012 年就发现了它，那时我还没有播客，从那时起我就每天都喝它。
For the past 13 years, AG1 has been the same original flavor.
13年来，AG1始终如一的原味。
They've updated the formulation, but the flavor has always remained the same.
他们更新了配方，但味道始终保持不变。
And now for the first time, AG1 is available in three new flavors, berry, citrus, and tropical.
现在，AG1 首次推出三种新口味：浆果味、柑橘味和热带味。
All the flavors include the highest quality ingredients in exactly the right doses to together provide support for your gut microbiome, support for your immune health, and support for better energy and more.
所有口味均包含最优质的成分，且剂量恰到好处，共同为您的肠道微生物群提供支持，支持您的免疫健康，并支持更好的能量等等。
So now you can find the flavor of AG1 that you like the most.
现在您可以找到您最喜欢的 AG1 口味了。
While I've always loved the AG1 original flavor, especially when I mix it with water and a little bit of lemon or lime juice, that's how I've been doing it for basically 13 years, now I really enjoy the new berry flavor in particular.
虽然我一直很喜欢 AG1 原味，尤其是当我将它与水和一点柠檬或酸橙汁混合时，这就是我基本上 13 年的做法，现在我真的特别喜欢新的浆果味。
It tastes great, and I don't have to add any lemon or lime juice.
味道很好，而且我不需要添加任何柠檬或酸橙汁。
I just mix it up with water.
我只是将它与水混合。
If you'd like to try AG1 and these new flavors, you can go to drinkag1.com/huberman to claim a special offer.
如果您想尝试 AG1 和这些新口味，可以访问 Drinkag1.com/huberman 申请特别优惠。
Right now, AG1 is giving away an AG1 welcome kit that includes five free travel packs and a free bottle of vitamin D3 K2.
目前，AG1 正在赠送 AG1 欢迎套件，其中包括五个免费旅行包和一瓶免费维生素 D3 K2。
Again, go to drinkag1.com/huberman to claim the special welcome kit of five free travel packs and a free bottle of vitamin D3 K2.
再次访问 Drinkag1.com/huberman 领取特别欢迎套装，其中包括五个免费旅行包和一瓶免费维生素 D3 K2。
Today's episode is also brought to us by BetterHelp.
今天的节目也是由 BetterHelp 为我们带来的。
BetterHelp offers professional therapy with a licensed therapist carried out entirely online.
BetterHelp 提供由持证治疗师完全在线进行的专业治疗。
I personally have been doing therapy for well over 35 years.
我个人从事治疗已经超过 35 年了。
I find it to be an extremely important component to overall health.
我发现它是整体健康极其重要的组成部分。
In fact, I consider doing regular therapy just as important as getting regular exercise, including cardiovascular exercise and resistance training, which of course, I also do every week.
事实上，我认为定期治疗与定期锻炼一样重要，包括心血管锻炼和阻力训练，当然，我每周也会进行这些锻炼。
There are essentially three things that make up great therapy.
伟大的治疗本质上由三件事组成。
First of all, it provides the opportunity to have a really good rapport with somebody that you can really trust and talk to about essentially any issue that you want.
首先，它提供了与您真正信任的人建立良好关系并谈论您想要的任何问题的机会。
Second of all, it can provide support in the form of emotional support or directed guidance, or of course, both.
其次，它可以以情感支持或定向指导的形式提供支持，当然也可以两者兼而有之。
And third, expert therapy should provide you useful insights, insights that can help you improve in your work life, your relationships, and in your relationship with yourself.
第三，专家治疗应该为您提供有用的见解，这些见解可以帮助您改善工作生活、人际关系以及与自己的关系。
With BetterHelp, they make it very easy for you to find an expert therapist who you resonate with, and that can provide those three benefits that come from expert therapy.
通过 BetterHelp，您可以轻松找到与您产生共鸣的专家治疗师，并且可以提供专家治疗带来的三大好处。
Interestingly, in a recent survey, 72% of BetterHelp members reported a reduction in negative symptoms as a result of their BetterHelp therapy sessions.
有趣的是，在最近的一项调查中，72% 的 BetterHelp 会员表示，接受 BetterHelp 治疗后，阴性症状有所减轻。
If you'd like to try BetterHelp, you can go to betterhelp.com/huberman to get 10% off your first month.
如果您想尝试 BetterHelp，可以访问 betterhelp.com/huberman，第一个月可享受 10% 的折扣。
Again, that's betterhelp.com/huberman.
再说一次，这是 betterhelp.com/huberman。
Let's talk about stem cells, organoids, and assembloids, and you'll explain what those are.
我们来谈谈干细胞、类器官和组合体，您将解释它们是什么。
But let's wade into this through the way it happened chronologically.
但让我们按照它发生的时间顺序来深入探讨一下。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Sure.
当然。
Andrew Huberman:
安德鲁·休伯曼：
Most people have heard of stem cells, cells that can become other things.
大多数人都听说过干细胞，即可以变成其他东西的细胞。
When I was a postdoc, any laboratory that worked on human stem cells worked on human embryonic stem cells.
当我还是一名博士后时，任何研究人类干细胞的实验室都研究人类胚胎干细胞。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Mm-hmm.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
Literally, cells that were-
从字面上看，细胞是——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Mm-hmm
嗯嗯
Andrew Huberman:
安德鲁·休伯曼：
...
...
collected from aborted fetuses, and given for medical study.
从流产的胎儿中收集并用于医学研究。
There was an incredible discovery, which you'll tell us about, which basically made that technology obsolete and also allowed scientists to bypass a lot of the ethical considerations.
有一个令人难以置信的发现，您将告诉我们，它基本上使该技术变得过时，并且还允许科学家绕过许多伦理考虑。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Mm-hmm.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
Serious ethical considerations.
严肃的道德考虑。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Mm-hmm.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
Regardless of where you sit on that debate, you're using the tissue from a human embryo to study things.
无论你在这场辩论中站在哪一边，你都在使用人类胚胎的组织来研究事物。
You could say some people will support that, some people won't, but then a new technology comes along-
你可以说有些人会支持，有些人不会，但是新技术出现了——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
and basically makes that technology obsolete, allowing you and others to do the work on stem cells and assembloids and so forth without having to take cells from human embryos, which is spectacular.
基本上使该技术变得过时，允许您和其他人在干细胞和组合体等方面进行工作，而无需从人类胚胎中获取细胞，这是惊人的。
So could you please tell us about that discovery of the stem cell technology that really changed the entire game-
那么，您能告诉我们有关真正改变整个游戏规则的干细胞技术的发现吗？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Mm-hmm
嗯嗯
Andrew Huberman:
安德鲁·休伯曼：
...
...
and did away with this serious ethical battle, let's call it what it was.
并废除了这场严重的道德斗争，我们就这么称呼它吧。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Sure.
当然。
Let's start first with stem cells and what they are because I think it's also important to define them.
让我们首先从干细胞及其是什么开始，因为我认为定义它们也很重要。
So stem cells are cells that have two properties.
因此，干细胞是具有两种特性的细胞。
First of all, they in principle can become other cells, and if they are of the most potent type, they will be totipotent, so they can make everything.
首先，它们原则上可以变成其他细胞，如果它们是最有效的类型，它们将是全能的，因此它们可以制造一切。
If they're pluripotent, they can make almost everything.
如果它们具有多能性，那么它们几乎可以制造一切。
And then of course there are lower levels of potency for the cells.
当然，细胞的效力也会降低。
So we all carry stem cells in us.
所以我们体内都携带干细胞。
Not in the brain, or fewer in the brain for sure, but in the liver and in other organs like in the gut, as we renew the gut every few weeks, that is done primarily through the stem cells.
不是在大脑中，或者肯定是在大脑中更少，而是在肝脏和其他器官（如肠道）中，因为我们每隔几周更新一次肠道，这主要是通过干细胞完成的。
But those are restricted.
但这些都是受到限制的。
They can't make everything.
他们无法制造一切。
They can make mostly that specialized cell type for which they have been sort of primed.
他们可以制造出大部分他们已经做好准备的特殊细胞类型。
Now the earliest of stem cells, like those pluripotent that are very important, those are present at early stages of development of the embryo.
现在，最早的干细胞，如非常重要的多能细胞，存在于胚胎发育的早期阶段。
And of course, that happens post-conception, so the challenge has been that you have to remove them from a fertilized egg, and if life starts at conception, then of course you're interfering.
当然，这是在受孕后发生的，所以挑战是你必须将它们从受精卵中取出，如果生命从受孕时开始，那么你当然会干涉。
So I think a lot of the ethical debates have started because of that.
所以我认为很多道德争论都是因此而开始的。
But in the early days, even if you were to do that, you wouldn't be able to keep those cells.
但在早期，即使你这样做，你也无法保留这些细胞。
It turns out that the cells are very difficult to maintain.
事实证明，这些细胞非常难以维持。
And this brings us actually to the second property of the cells, which is that in principle, they can be maintained forever.
这实际上给我们带来了细胞的第二个特性，那就是原则上它们可以永远维持。
If you provide the right conditions, they will divide and stay the same forever.
如果你提供合适的条件，它们就会分裂并永远保持不变。
Those are the two properties.
这是两个属性。
So you can keep them forever.
这样您就可以永远保留它们。
You can freeze them down, put them in liquid nitrogen, bring them out any time, and they'll start exactly where they left.
你可以将它们冷冻起来，放入液氮中，随时取出，它们就会从原来的位置开始。
And then with the right guidance, they can become other cell types.
然后在正确的指导下，它们可以变成其他细胞类型。
So only around 1998, that was when we could actually maintain some of the cells in a dish.
所以直到 1998 年左右，我们才真正能够在培养皿中保存一些细胞。
So somebody figured out a soup of chemicals that you can add, and the cells will survive.
所以有人想出了一种可以添加化学物质的汤，这样细胞就能存活下来。
Because up to that point, it was not possible.
因为到目前为止，这是不可能的。
So that triggered, of course, the promise of this field, that now we'd be able to take those cells and derive various organs.
当然，这引发了这个领域的希望，即现在我们能够利用这些细胞并衍生出各种器官。
Perhaps transplant them, replace organs.
也许移植它们，更换器官。
Of course, that ended up being much more complicated, and of course, there were all these ethical debates related to the source of those cells and what does it actually mean to use these embryonic stem cells.
当然，这最终变得更加复杂，当然，所有这些伦理争论都与这些细胞的来源以及使用这些胚胎干细胞的实际意义有关。
And yet, we've learned a lot about those cells in early days.
然而，我们在早期已经了解了很多关于这些细胞的知识。
What are the properties of those cells?
这些细胞有什么特性？
And then almost 20 years ago, Shinya Yamanaka, who's a scientist in Japan and at UCSF, came up with an absolutely brilliant idea.
大约 20 年前，日本和加州大学旧金山分校的科学家山中伸弥 (Shinya Yamanaka) 提出了一个绝对绝妙的主意。
We always thought that the development of the human or of any, it's a one-way street.
我们一直认为人类或任何事物的发展都是一条单行道。
Once you go down development, you never come back.
一旦你的发展走下坡路，你就永远不会回来。
So once you start making a stem cell that is more restricted, and then at the end you make, let's say, a liver cell, you can never go back and become that pluripotent stem cell again.
因此，一旦你开始制造受到更多限制的干细胞，最后你制造出肝细胞，你就再也不能回去成为多能干细胞。
And that generally is thought to be useful to protect us from cancer or any other, so we don't have parts of our hands differentiating into something else.
人们普遍认为这有助于保护我们免受癌症或任何其他疾病的侵害，因此我们的手部不会分化成其他东西。
And he thought that maybe you could do that, not in a natural way, in an artificial way, and that, of course, would be very useful.
他认为也许你可以做到这一点，不是以自然的方式，而是以人工的方式，当然，这将非常有用。
So what he did is he went and he looked at the genes that are expressed in pluripotent stem cells at very high levels.
所以他所做的就是去观察多能干细胞中高水平表达的基因。
So very high levels.
所以水平非常高。
And almost as gene therapy, because we were talking about gene therapy, he took the top couple of dozens of these genes and then started adding them inside skin cells.
几乎作为基因疗法，因为我们正在谈论基因疗法，他提取了数十个基因中的前几个，然后开始将它们添加到皮肤细胞内。
So he took skin cells initially from mice and then from human, and then started adding them one by one, two by two, three by three, four by four, five by five, six by six, to see whether any of those cells, once they have this combination of genes that are expressed in pluripotent stem cells, would somehow get confused and think that they're actually a pluripotent stem cell, and then go back in time and actually become a pluripotent stem cells.
因此，他首先从小鼠身上取出皮肤细胞，然后从人类身上取出皮肤细胞，然后开始将它们一一、二二、三三、四四、五五、六六添加起来，看看这些细胞中的任何一个，一旦拥有多能干细胞中表达的基因组合，是否会以某种方式感到困惑，并认为它们实际上是多能干细胞，然后回到过去，实际上成为多能干细胞。
And he showed indeed that a combination of four is enough.
他确实证明了四个人的结合就足够了。
Of course, you can have six.
当然，你可以有六个。
And that ended up being what we today call the Yamanaka factor.
这最终就是我们今天所说的山中因素。
In a way, it was almost like alchemy, where you sort of transform something into something else.
在某种程度上，这几乎就像炼金术，你可以将某种东西转化为另一种东西。
You make out of this metal, you make gold.
你用这种金属制造黄金。
It was pretty much like that.
差不多就是这样。
It was like the essence of alchemy.
这就像炼金术的本质一样。
And it turns out that that discovery was so profound because suddenly you could take a skin cell from anybody and put those genetic factors in, turn those cells into pluripotent stem cells that we'd later on learn they're almost identical to those embryonic stem cells, and now have those cells from any of us and use them for various purposes, perhaps for, let's say, making blood cells in the future or perhaps to model something outside of the body.
事实证明，这一发现意义重大，因为突然之间，你可以从任何人身上取出一个皮肤细胞，放入这些遗传因子，将这些细胞转化为多能干细胞，我们后来了解到它们与那些胚胎干细胞几乎相同，现在从我们任何人那里获得这些细胞，并将它们用于各种目的，也许可以用来在未来制造血细胞，或者也许可以用来模拟体外的东西。
And I was finishing my clinical training around that time, and I remember even seeing that paper.
那时我正在完成临床培训，我什至记得看过那篇论文。
And of course, in my naivete at that time, I thought, "Wow, this is it.
当然，当时我天真地想，“哇，就是这样。
This is going to be the entry point for studying human neuroscience." I was doing experiments at that time studying actually the cortex and recording from animals electrical activity of those neurons, and always thought this disconnect between what I was seeing in the clinic, which were these patients with severe profound autism, and then recordings from the brain and thinking, we're never going to be able to do that.
这将成为研究人类神经科学的切入点。”当时我正在做实验，研究动物的皮层并记录这些神经元的电活动，我一直认为我在诊所看到的情况（这些患有严重自闭症的患者）与大脑和思维的记录之间存在脱节，我们永远无法做到这一点。
How are we going to understand this complex disorder of the brain if we cannot even listen to the activity of those cells live?
如果我们甚至无法实时聆听这些细胞的活动，我们如何才能理解这种复杂的大脑疾病呢？
And then suddenly, seeing that discovery, again naive at that time, thought, well, that could be perhaps the way in which we could make neurons from any patient.
然后突然，看到这个发现，当时又很天真，我想，好吧，这也许就是我们从任何病人身上制造神经元的方法。
And so very soon after I came to Stanford, which I guess where we met, with sort of this idea in mind that we will be able to make neurons from these patients and rebuild maybe some of the cells or some of the circuits of the brain outside of the body without doing any harm, because we're not doing a biopsy of the brain or anything invasive, just essentially creating a replica of some of those cells outside of the body, and then finally study them at will in a dish and do all kind of experiments where you remove things and add things and perhaps one day even develop therapeutics.
就在我来到斯坦福大学后不久，我想我们是在斯坦福大学认识的，心里有这样的想法，我们将能够从这些患者身上制造神经元，并在体外重建大脑的一些细胞或某些电路，而不会造成任何伤害，因为我们不会对大脑进行活组织检查或任何侵入性的东西，只是本质上在体外创建其中一些细胞的复制品，然后最终在培养皿中随意研究它们，并进行各种实验，在这些实验中，你可以去除一些东西，添加一些东西，也许还有一个甚至开发治疗方法。
And here we are 16 years later, since that process really started.
16 年后，这个过程真正开始了。
It took a long time, but now for the first time, we've gotten such a good understanding of some of these conditions, and one of them in particular, that actually a therapeutic is in sight, and we're preparing for the first clinical trial that is really arising exclusively through studies done with these human stem cell models, without actually using any animal models, just essentially creating, recreating cells and circuits outside of the brain of those patients.
虽然花了很长时间，但现在我们第一次对其中一些病症有了如此深入的了解，特别是其中一个，实际上一种治疗方法已经在望，我们正在准备第一个临床试验，该试验实际上完全是通过对这些人类干细胞模型进行的研究而产生的，实际上没有使用任何动物模型，只是在这些患者的大脑之外创建、重建细胞和回路。
Andrew Huberman:
安德鲁·休伯曼：
It's amazing because it allows you to study human cells, which has immense benefit.
这是令人惊奇的，因为它可以让你研究人体细胞，这有巨大的好处。
They're essentially limitless in number-
它们的数量基本上是无限的——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yes
是的
Andrew Huberman:
安德鲁·休伯曼：
...
...
because all you need is one fibroblast-
因为你所需要的只是一个成纤维细胞——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
one skin cell-
一个皮肤细胞——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
or some cell that you can provide these Yamanaka factors to and essentially grow other cells.
或者某些细胞，您可以向其他细胞提供这些山中因子并基本上使其生长。
And we'll talk about what those cells that you create are capable of becoming, not just cells, but circuits-
我们将讨论你创建的那些细胞能够变成什么，不仅仅是细胞，还有电路——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yes
是的
Andrew Huberman:
安德鲁·休伯曼：
...
...
in a few moments.
一会儿。
But I know it's going to be in the back of people's minds, and it's certainly in the back of my mind, this idea that when one has a baby, that you should keep the umbilical cord because the umbilical cord-
但我知道这会在人们的脑海中浮现，而且肯定也在我的脑海中浮现，当一个人有了孩子时，你应该保留脐带，因为脐带 -
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
contains stem cells.
含有干细胞。
Usually, I think the umbilical cord is discarded.
通常，我认为脐带会被丢弃。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Mm-hmm.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
Maybe some people keep it, I don't know.
也许有人保留它，我不知道。
What is the current thinking on stem cells that reside in the umbilical cord?
目前对脐带干细胞的看法如何？
People pay a lot of money to freeze those, and most people don't have a minus 80 freezer-
人们花很多钱来冷冻这些东西，而大多数人没有负80度的冰箱-
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
around, so they pay to do that.
周围，所以他们付费这样做。
What is the potential for umbilical stem cells in the future?
脐带干细胞未来的潜力有多大？
Is it something that parents, I don't want to say should invest in, but if they have the disposable income, that they would be wise to do that?
我不想说父母应该投资，但如果他们有可支配收入，他们这样做会是明智的吗？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
So those cells that are collected from the umbilical cord are stem cells, but they're already quite restricted in what they can make.
因此，从脐带收集的那些细胞是干细胞，但它们的制造能力已经相当有限。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
So their applications are also restricted, mostly to blood disorders.
因此它们的应用也受到限制，主要是针对血液疾病。
So I think it's important to keep in mind that they're not sort like a universal solution to anything that would ever involve pluripotent stem cells in the future or stem cell therapies in the future.
因此，我认为重要的是要记住，它们并不是对未来涉及多能干细胞或未来干细胞疗法的任何事物的通用解决方案。
So again, I think it's important to know that while they have certain applications, and there have been quite clear cases where the availability of those cells were useful in a blood disorder in that child later on, they're certainly not They have these universal uses as maybe sometimes they're being advertised.
因此，我认为重要的是要知道，虽然它们具有某些应用，并且已经有相当明显的案例表明这些细胞的可用性对后来那个孩子的血液疾病有用，但它们肯定不具有这些普遍用途，因为有时它们可能会被广告宣传。
Andrew Huberman:
安德鲁·休伯曼：
When we hear about people typically leaving the US to get quote unquote stem cell injections-
当我们听说人们通常离开美国去接受干细胞注射时——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yes
是的
Andrew Huberman:
安德鲁·休伯曼：
...
...
where are those stem cells coming from?
这些干细胞从哪里来？
Are they coming from those patients?
它们是来自那些病人吗？
And I should mention that there was a clinic down in Florida that was offering stem cell injections into the eye for people with-
我应该提一下，佛罗里达州有一家诊所为患有以下疾病的人提供干细胞注射：
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
macular degeneration, and that clinic was shut down, and all stem cell injections in the United States, to my knowledge all, were shut down because those patients, not only did it fail to rescue their vision, it actually made them go blind very quickly.
黄斑变性，那家诊所被关闭了，据我所知，美国所有的干细胞注射都被关闭了，因为这些患者不仅没能挽救他们的视力，反而让他们很快失明。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
So the FDA shut down commercial stem cell injections.
因此 FDA 关闭了商业干细胞注射。
I think there's still places where they do a kind of workaround.
我认为他们仍然在某些地方采取了某种解决方法。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And it's worth mentioning that PRP, platelet-rich plasma, is FDA-approved.
值得一提的是，PRP（富含血小板的血浆）已获得 FDA 批准。
It does not contain many, if any, stem cells, despite what you might read.
不管你读到了什么，它并不包含很多（如果有的话）干细胞。
But what are your thoughts on when people go down to Colombia, it seems like they go down to Colombia-
但是当人们去哥伦比亚时你有什么想法，看起来他们去了哥伦比亚-
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Oh, yeah
哦，是的
Andrew Huberman:
安德鲁·休伯曼：
...
...
or elsewhere, or Mexico, to get stem cell injections, assuming the conditions are clean?
或其他地方，或墨西哥，假设条件干净，可以进行干细胞注射？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And I say that because I know of at least one patient who was paralyzed from an injection of stem cells into their spinal disc.
我这么说是因为我知道至少有一名患者因向椎间盘注射干细胞而瘫痪。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Mm-hmm.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
Paralyzed, almost died.
瘫痪了，差点死掉。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Fortunately, is doing better now, and it was because it went septic, it got infected.
幸运的是，现在情况好多了，是因为化脓，才被感染的。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Well, that's one of the problems, is very often we don't even know what is being injected.
嗯，这是问题之一，我们常常甚至不知道注入的是什么。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
I think that is a very important aspect.
我认为这是一个非常重要的方面。
We don't know what is in-- Sometimes are the cells from the patient are being collected.
我们不知道里面是什么——有时正在收集患者的细胞。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Sometimes some of these umbilical cells, sometimes we don't even know what cells are being injected.
有时这些脐带细胞，有时我们甚至不知道注射的是什么细胞。
Andrew Huberman:
安德鲁·休伯曼：
Like it could be cells from somebody else or-
就像它可能是其他人的细胞或者-
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
They're incredibly risky procedures.
它们是极其危险的程序。
Of course, they've never really been observed.
当然，它们从未被真正观察过。
There have been very few of any clinical trials trying to really address it in a very systematic way.
很少有临床试验试图以非常系统的方式真正解决这个问题。
And very often that's also because they're not really justified.
很多时候，这也是因为它们并不真正合理。
So in the context of autism, this is very often done, and it's done not just in South America, sometimes there are places in Europe where you can get an injection of some stem cells for autism.
因此，在自闭症的背景下，这种做法很常见，而且不仅在南美洲这样做，有时在欧洲的某些地方，您可以注射一些干细胞来治疗自闭症。
Andrew Huberman:
安德鲁·休伯曼：
Wait, parents are taking their kids to these clinics and getting them injected with stem cells-
等等，父母正在带孩子去这些诊所，给他们注射干细胞——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
They're getting-
他们正在——
Andrew Huberman:
安德鲁·休伯曼：
...
...
that come from some other patient.
来自其他一些病人。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Some cells that are collected either from the patient.
有些细胞是从患者身上收集的。
It depends a little bit on where it's done and how it's actually done.
这在一定程度上取决于它在哪里完成以及它实际上是如何完成的。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
But again, even from a biological point of view, what are those stem cells presumably doing, let's say, in autism?
但同样，即使从生物学的角度来看，这些干细胞可能在自闭症中发挥什么作用？
We don't think that there is a cell type that is missing in the brain, so it's not like those cells can go.
我们不认为大脑中缺少某种细胞类型，所以这些细胞不可能消失。
And I think as I was mentioning before, most of the cells already are restricted in their potential.
我认为正如我之前提到的，大多数细胞的潜力已经受到限制。
They can no longer make any cell types.
他们不能再制造任何细胞类型。
So, the idea that you take these pluripotent stem cells, and you just inject them, let's say, in the knee, and it will miraculously grow cartilage, it's very often not really the case because those cells are not even capable of making cartilage.
因此，如果你采用这些多能干细胞，然后将它们注射到膝盖中，它就会奇迹般地长出软骨，但事实往往并非如此，因为这些细胞甚至无法制造软骨。
So I think there's very often a lack of understanding of what these therapies really are, and then of course, there is sadly a lack of understanding of what is actually being injected.
因此，我认为人们常常对这些疗法的真正含义缺乏了解，当然，令人遗憾的是，人们对实际注射的药物也缺乏了解。
So, for autism, this is unfortunately happening much more often than you would think.
因此，对于自闭症患者来说，不幸的是，这种情况发生的频率比您想象的要高得多。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
So I very often get parents or families that are asking me desperately, "We've exhausted all resources.
因此，我经常听到父母或家人绝望地问我：“我们已经用尽了所有资源。
We don't know what else to do.
我们不知道还能做什么。
We've tried behavioral therapy, we've tried these therapies.
我们尝试过行为疗法，我们尝试过这些疗法。
Nothing works, and everybody's recommended that we should just go now to South America and do this injection.
没有任何效果，每个人都建议我们现在就去南美洲进行注射。
Should we do it or not?" Right.
我们该做还是不做？”正确的。
Then, of course, my answer is always no, because again, there's no reason that that would work.
当然，我的答案始终是否定的，因为同样，没有理由这样做会起作用。
Some parents come back and of course, they report an improvement, which is generally temporary to the extent that we know.
一些家长回来后，当然会报告有所改善，但据我们所知，这通常是暂时的。
Of course, it's never really been studied in a very systematic way.
当然，从来没有真正以非常系统的方式研究过它。
Partly, of course, there is a very strong placebo effect, especially in parents by proxy when you have a child who's very sick.
当然，部分原因是，这有很强的安慰剂效应，尤其是当你的孩子病得很重时，尤其是在代理父母身上。
Those placebo effects are very, very strong.
这些安慰剂效应非常非常强烈。
These parents really want those kids to improve, and so they will see things that are improving.
这些父母真的希望孩子能够进步，所以他们会看到事情正在进步。
Plus, those are still developing kids, so week by week, they may acquire new milestones.
另外，这些孩子仍在发育中，所以一周一周，他们可能会获得新的里程碑。
And then the other thing, which of course could be part of this, is that there is an inflammatory effect very often.
然后另一件事，当然可能是其中的一部分，是经常存在炎症效应。
And so that's almost like the fever in a way, right?
所以这在某种程度上就像发烧一样，对吧？
It would increase perhaps some of the cytokines, will create a fever, perhaps that is associated.
它也许会增加一些细胞因子，会引起发烧，也许这与此有关。
We don't really know, but certainly there are dangers associated with procedures like this that lack the rationale, first of all, and then of course, then they lack any regulatory framework.
我们真的不知道，但肯定存在与此类缺乏合理性的程序相关的危险，首先，当然，然后它们缺乏任何监管框架。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, I think the concern is very real for stem cell injections into all tissues, but when it comes to eyes or brain, and of course eyes are brain-
是的，我认为对于将干细胞注射到所有组织中的担忧是非常真实的，但是当涉及到眼睛或大脑时，当然眼睛就是大脑-
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yes
是的
Andrew Huberman:
安德鲁·休伯曼：
...
...
that's where I just take a big deep breath and hold it and wide-eyed like, "Oh my goodness, no," because we don't get new neurons.
在那里，我深吸一口气，屏住呼吸，睁大眼睛，“哦，天哪，不，”因为我们没有获得新的神经元。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
You lose neurons, they're gone.
你失去了神经元，它们就消失了。
We get a few in the olfactory bulb, in the dentate gyrus of the hippocampus, a few.
我们在嗅球、海马体的齿状回中得到了一些。
But once they're gone, that's it.
但一旦他们走了，就这样了。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
And injecting something into the brain, the probability of tumor growth is incredibly high.
而往大脑里注射某种东西，肿瘤生长的概率就高得令人难以置信。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Absolutely, and especially when it is in the brain where there's not enough space, right?
绝对是的，特别是当它在大脑中没有足够的空间时，对吗？
So we know that anything that grows in the cranial cavity will actually push down vital centers.
所以我们知道，任何在颅腔中生长的东西实际上都会压低生命中心。
So there are certainly risks associated with that.
因此肯定存在与之相关的风险。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
So let's talk about the other approach, which is the one that you've been embarking on.
那么让我们来谈谈另一种方法，这就是您一直在采用的方法。
I'll never forget when we were postdocs.
我永远不会忘记我们还是博士后的时候。
Folks, we were postdocs in the same room.
伙计们，我们是同一个房间的博士后。
It was D222.
是D222。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yes.
是的。
Andrew Huberman:
安德鲁·休伯曼：
We had a lot of pride in that room, where you had benches on opposite sides of the room, and we sort of took over that room as an empty room.
我们对那个房间感到非常自豪，房间的两侧都有长凳，我们几乎把那个房间当作了一个空房间。
You probably couldn't do this anymore, but it was like, "There's an empty room.
你可能不能再这样做了，但就像是，“有一个空房间。
Let's bring some microscopes in there." We just started doing experiments there.
我们把一些显微镜带进去吧。”我们刚刚开始在那里做实验。
And I'll never forget when you started building organoids.
我永远不会忘记你何时开始构建类器官。
You started building nervous systems in a dish and how excited you were.
你开始在培养皿中构建神经系统，你感到多么兴奋。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And it's been remarkable to see your arc from that, and it's not lost on me that you were working extremely hard then- ...
从中看到你的弧线真是太了不起了，我并没有忘记你当时非常努力——......
and continue to, to become really one of the luminaries of this field.
并继续努力，成为该领域真正的杰出人物之一。
Tell us what organoids are, tell us why they're useful, and what they're telling us already about how the brain develops and their therapeutic potential.
告诉我们类器官是什么，告诉我们它们为什么有用，以及它们已经告诉我们关于大脑如何发育及其治疗潜力的信息。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
So let's start from the beginning.
那么让我们从头开始吧。
So around 15, 16 years ago, we were able for the first time to get some of the cells that are now known as induced pluripotent stem cells.
所以大约 15、16 年前，我们第一次能够获得一些现在被称为诱导多能干细胞的细胞。
Andrew Huberman:
安德鲁·休伯曼：
These are the Yamanaka?
这些是山中人？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yes, or iPS cells.
是的，或者 iPS 细胞。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
So induced because they've been induced to become pluripotent in an artificial way.
如此诱导是因为它们以人工方式被诱导变得多能。
But again, they stay like that, so you can share them with anybody else afterwards.
但同样，它们会保持原样，因此您可以在之后与其他人分享它们。
So we got some of those first cells in those early days, and now the question was, how do we make neurons?
所以我们在早期就得到了一些第一批细胞，现在的问题是，我们如何制造神经元？
And what you do is you really leverage everything that is known in developmental biology.
你所做的是真正利用发育生物学中已知的一切。
So we already know that there are certain molecules that are very important for making neurons.
所以我们已经知道某些分子对于制造神经元非常重要。
So all you do is you put those cells in a dish, in a plastic dish, in a Petri dish, and then you start almost like when you cook, you start adding various molecules on top, and you see what happens.
所以你所要做的就是将这些细胞放入培养皿中，塑料皿中，培养皿中，然后你开始就像做饭一样，开始在上面添加各种分子，然后你就会看到会发生什么。
And we knew that it's actually quite easy to make neurons.
我们知道制造神经元实际上很容易。
That was already known.
这已经是众所周知的事情了。
There have been a lot of experiments done the decade before that showed that even if you just remove some of the factors that maintain those cells pluripotent, those pluripotent stem cell will start now to differentiate, and they like to become neural cells.
十年前进行的大量实验表明，即使你只是去除一些维持这些细胞多能性的因素，这些多能干细胞现在也会开始分化，并且它们喜欢成为神经细胞。
Andrew Huberman:
安德鲁·休伯曼：
By default.
默认情况下。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Almost by default.
几乎默认。
So it's actually not that difficult to make neurons.
所以制造神经元实际上并没有那么困难。
So in those early days, you would take those cells, play them nicely, those pluripotent stem cells in a dish, and then remove some of these factors, and then within a few days you will see that they'll change shape, and within a few weeks, some of them will really look like neurons.
所以在早期，你会取出这些细胞，好好地发挥它们，那些在培养皿中的多能干细胞，然后去除其中一些因素，然后几天之内你会看到它们会改变形状，几周之内，其中一些看起来真的像神经元。
And when you look at them, you can even look at proteins that only neurons will have.
当你观察它们时，你甚至可以观察到只有神经元才有的蛋白质。
You can actually get an electrode inside a cell and listen to the electrical activity.
实际上，您可以在细胞内放置一个电极并聆听电活动。
So it was very exciting, as maybe you remember in those days.
所以这非常令人兴奋，也许你还记得那些日子。
This burst in curiosity is always sort of the ATP of the life in the lab, so to speak.
可以说，这种好奇心的爆发始终是实验室生活的 ATP。
Andrew Huberman:
安德鲁·休伯曼：
It is.
是的。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Right?
对吗？
You just want to wake up and want to go see what happened to those cells.
你只想醒来并想去看看那些细胞发生了什么。
And it was clear in those days that we would be able to make those cells, but would we actually see any abnormalities in those cells, I think was the question.
当时很明显我们能够制造这些细胞，但我认为问题是我们真的会看到这些细胞中的任何异常吗？
How would you know if you derive cells from a patient with autism, how would you know that you found anything abnormal?
如果您从自闭症患者身上提取细胞，您怎么知道您发现了任何异常情况？
I think that was the question.
我想这就是问题所在。
We didn't even know what would be abnormal in the brain.
我们甚至不知道大脑中会出现什么异常。
And so that's when we decided actually to focus on something that would be relatively predictable.
因此，那时我们决定真正专注于相对可预测的事情。
And that was this mutation in a calcium channel, which was discovered just a few years before in very few patients that had essentially one single letter in their entire genome changed in a gene that makes a protein known as a calcium channel, sits in excitable cells, meaning cardiac cells and brain cells.
这就是钙通道中的这种突变，几年前在极少数患者中发现了这种突变，这些患者的整个基因组中的一个基因基本上有一个字母发生了变化，该基因产生了一种称为钙通道的蛋白质，位于可兴奋的细胞中，即心肌细胞和脑细胞中。
And every time a cell receives electrical input, this protein opens up and lets calcium go inside the cell.
每当细胞接收到电输入时，这种蛋白质就会打开并让钙进入细胞内。
And that's very important because it couples electrical activity of the network with chemical activity inside the cells.
这非常重要，因为它将网络的电活动与细胞内的化学活动结合起来。
And what we knew about that mutation at that point, that it's pretty much all we knew in those early days, is that it probably allows the channel to stay open slightly longer, just a little bit longer, so more calcium would go inside the cells.
我们当时对这种突变的了解，这几乎是我们早期所知道的，它可能会让通道保持开放的时间稍微长一点，再长一点，这样更多的钙就会进入细胞内。
Of course, there will be no way to know because you can't get a neuron or a cardiac cell from those patients to actually test it.
当然，我们无法知道，因为你无法从这些患者身上获取神经元或心肌细胞来进行实际测试。
So what we did is essentially, we recruited some of these patients, we flew them to Stanford, then we got a tiny skin biopsy, made these iPS cells.
所以我们所做的本质上是，我们招募了一些患者，将他们飞到斯坦福大学，然后我们进行了微小的皮肤活检，制造了这些 iPS 细胞。
This takes months.
这需要几个月的时间。
This takes already four or five months.
这已经需要四五个月的时间了。
And then we took those cells in a dish, started deriving neurons, and after about five, six, seven weeks, then we put them under a microscope, and we started looking at the calcium.
然后我们将这些细胞放入培养皿中，开始衍生神经元，大约五、六、七周后，然后我们将它们放在显微镜下，我们开始观察钙。
You can measure calcium inside cells through a microscope and just literally look at it.
您可以通过显微镜测量细胞内的钙，然后直接观察。
And I'll never forget that day when we did that experiment, was looking down the microscope, and we essentially stimulated the neurons, and you could just see how control cells will go calcium goes inside the cells, and then it goes out.
我永远不会忘记那天我们做那个实验，在显微镜下观察，我们基本上刺激了神经元，你可以看到控制细胞如何让钙进入细胞内部，然后它消失。
And then in patients that had Timothy syndrome, so in Timothy syndrome-derived neurons, you could see how the calcium will go and then it will stay longer.
然后，在患有蒂莫西综合征的患者中，在蒂莫西综合征衍生的神经元中，你可以看到钙将如何流动，然后它会停留更长时间。
It takes longer to go out.
出去的时间要长一些。
So it's the first defect that we saw in patient-derived neurons that were actually not coming from a biopsy.
因此，这是我们在患者来源的神经元中看到的第一个缺陷，这些缺陷实际上并非来自活检。
They were not coming.
他们不会来。
So that was incredibly exciting, as you can imagine.
正如你可以想象的那样，这是非常令人兴奋的。
But it was still relatively simplistic, just a few neurons at a bottom of a dish.
但它仍然相对简单，只有培养皿底部的几个神经元。
And of course, for me, what was particularly frustrating was that we couldn't go very far in development.
当然，对我来说，特别令人沮丧的是我们在开发方面无法走得太远。
So think about the cerebral cortex, the outer layer of the brain that presumably makes us human.
想想大脑皮层，大脑的外层，大概是它使我们成为人类。
It has multiple layers, a large diversity of neurons.
它有多层，神经元种类繁多。
It takes 27 weeks to make all those cells in the cortex, 27 weeks to make all those neurons, and we're not even talking about glial cells, the supporting cells that are coming much later for several years afterwards.
皮质中的所有细胞需要 27 周才能形成，神经元也需要 27 周才能形成，我们甚至还没有讨论神经胶质细胞，这些支持细胞在几年后才会出现。
But just making those cells takes about 27 weeks.
但光是制造这些细胞就需要大约 27 周的时间。
And it turns out, something that we discovered through experiments done in a dish, is that the timing of the development of those cells, it's actually recapitulated in a dish as well.
事实证明，我们通过在培养皿中进行的实验发现，这些细胞的发育时间实际上也在培养皿中得到了重现。
So if you keep the cells in a dish, they'll actually essentially develop at the same pace.
因此，如果将细胞放在培养皿中，它们实际上会以相同的速度发育。
They're not much faster, and it's very difficult to keep neurons in a dish for 27 weeks to get all the neurons.
它们的速度并不快，而且很难将神经元放在培养皿中 27 周才能获得所有神经元。
Essentially, they peel off every time you start to move them to another plate, and at one point they just die.
从本质上讲，每次你开始将它们移到另一个盘子上时，它们都会剥落，并且在某一时刻它们就会死亡。
And so then we thought, how about never letting them just sit down on a surface?
所以我们想，永远不要让它们坐在表面上怎么样？
How about just essentially aggregating them as balls of cells and then letting those float?
把它们聚集成细胞球然后让它们漂浮怎么样？
And in those early days, there was this amazing scientist from Japan, Yoshiki Sasai, who started doing really beautiful experiments where he was already moving some of these studies that he was doing of development in 3D cultures, where he show you can make an optic cup, a part of the eye.
在早期，有一位来自日本的令人惊叹的科学家，Yoshiki Sasai，他开始做非常漂亮的实验，他已经将他正在做的一些研究转移到 3D 文化中，他展示了你可以制作一个视杯，眼睛的一部分。
And so it was clear, it was in the air, this revolution of actually moving cells from 2D flat cultures to 3D self-organizing.
很明显，这场革命正在酝酿之中，即将细胞从 2D 平面培养物转移到 3D 自组织细胞。
And that actually unleashed amazing new properties of the cells.
这实际上释放了细胞惊人的新特性。
So essentially, all we did in those days is I ordered from Germany these plates that were counterintuitively coated, so the cells never stick.
所以本质上，我们当时所做的就是我从德国订购了这些带有反直觉涂层的板，因此细胞永远不会粘连。
Right?
正确的？
Every time we keep cells in a dish, you want them to stick.
每次我们将细胞放在培养皿中时，您都希望它们能够粘附。
That's the major problem.
这是主要问题。
So they were actually coated, so the cells will never stick.
所以它们实际上是有涂层的，所以细胞永远不会粘在一起。
And then there were these balls of cells, they were floating there.
然后就有了这些细胞球，它们漂浮在那里。
And of course, I remember talking in the lab, and everybody was like, "Oh, they're not going to survive.
当然，我记得在实验室里谈话，每个人都说，“哦，他们活不下去了。
It's going to be a couple of weeks and they're going to..." And then a week passed, and two week passed, and then they kept growing and growing.
这将是几周的时间，他们会……”然后一周过去了，两周过去了，然后他们不断成长。
And of course, the enthusiasm of every day to see, are they still alive?
当然，每天看到的热情，他们还活着吗？
Right?
正确的？
And then we discovered that we can keep them for months.
然后我们发现我们可以将它们保存几个月。
And these three-dimensional cultures are now known as organoids, which is perhaps not the most fortunate name because it suggests that it's organ-like, and of course, they're not an entire organ.
这些三维培养物现在被称为类器官，这可能不是最幸运的名字，因为它表明它是类似器官的，当然，它们不是一个完整的器官。
So they're not a representation of the entire brain.
所以它们并不是整个大脑的代表。
But that's the term that we refer these days to anything that is three-dimensional and organizing in some way.
但这是我们现在用来指代任何三维且以某种方式组织的事物的术语。
And so we started keeping these cultures, and then at one point, actually, we discovered that we can pretty much keep them indefinitely.
所以我们开始保留这些文化，然后在某一时刻，实际上，我们发现我们几乎可以无限期地保留它们。
My lab maintained the longest cultures that have ever been reported, literally going for years, for two, three years in a dish.
我的实验室保存了有史以来最长的培养物，实际上可以在培养皿中保存数年、两三年。
And at one point, in those early days when, actually, I was running out of funds in the lab, and I came one day in lab meeting really determined for us to actually cut cost.
有一次，在早期，实际上，我实验室的资金已经用完了，有一天我参加了实验室会议，真正决定我们要真正削减成本。
And so I've told everybody, "Go into your incubators, because we're spending so much money in feeding the cells, and everybody throws out 20% of your cultures." And then people started saying, "So should I throw the ones that are 500 days old?" And somebody else like, "The ones that are 800 days old?" Then I said, "What?
所以我告诉每个人，“进入你们的培养箱，因为我们在培养细胞上花了很多钱，而每个人都扔掉了 20% 的培养物。”然后人们开始说，“那么我应该扔掉 500 天前的那些吗？”还有人喜欢问，“那些已经有 800 天历史的？”然后我说：“什么？
You guys are keeping them for such a long..." "Yeah, they just keep growing.
你们把它们养了这么久……” “是的，它们一直在生长。
They're in the incubator." So then we actually did the first study, and then we had a series of three studies done over the years of trying to ask, how far do they go in development?
他们在孵化器里。”所以我们实际上做了第一项研究，然后我们多年来进行了一系列三项研究，试图问，它们的发展进展如何？
So if you have a clump of human neurons that you've made from pluripotent stem cells, and you keep feeding them in a dish, how far do they go in development?
因此，如果你有一团由多能干细胞制成的人类神经元，并且一直在培养皿中喂养它们，那么它们的发育程度如何？
Do they move much faster?
他们移动得更快吗？
Do they move much slower?
他们移动得慢得多吗？
Are they stuck at one point in development?
他们是否陷入了发展的某一阶段？
And it turns out that they actually keep track of development beautifully.
事实证明，他们实际上很好地跟踪了发展情况。
To such an extent that, for instance, we discover when they reach nine months of keeping them in a dish, so about the time of birth, they literally switch to a postnatal signature- Really?
例如，我们发现当他们将它们放在盘子里九个月时，因此在出生时，他们实际上会切换到出生后的签名 - 真的吗？
...
...
on their own.
靠他们自己。
In a dish?
在一个盘子里？
In a dish.
在一个盘子里。
So there's this classic example in developmental neurobiology.
发育神经生物学中有一个经典的例子。
There's this protein that usually changes around the time of birth.
这种蛋白质通常会在出生前后发生变化。
It's an NMDA receptor.
它是一种 NMDA 受体。
So maybe some people know about NMDA receptors.
也许有些人了解 NMDA 受体。
They're binding glutamate.
它们结合谷氨酸。
They're very important.
它们非常重要。
But they change a lot during development.
但它们在开发过程中发生了很大变化。
They're made out of different units, and the units change.
它们由不同的单位组成，并且单位会发生变化。
And it was very well-known that during early development, so prenatal, before birth, you primarily have 2B subunits.
众所周知，在早期发育过程中，即产前、出生前，主要有 2B 亚基。
And then after birth, they're primarily 2A.
出生后，他们主要是2A。
So if you look in brain development, you just see how essentially 2B goes up and then it goes down, and 2A goes up, and when you look, they meet around birth.
因此，如果你观察大脑发育，你就会发现 2B 本质上是上升然后下降，而 2A 上升，当你观察时，它们会在出生时相遇。
So very often, people thought that it's birth itself that triggers that switch.
很多时候，人们认为是出生本身触发了这种转变。
That canonical, it's called a canonical switch because we all thought that it was so classic.
那个规范，它被称为规范开关，因为我们都认为它是如此经典。
And then you take an organoid that you maintain in the dish for 600 days.
然后你取出一个类器官，并在培养皿中保存 600 天。
And of course, we're not inducing birth.
当然，我们不是引产。
We're not changing media.
我们不会改变媒体。
We're not doing anything special.
我们没有做任何特别的事情。
Yeah, no hormones from mom.
是的，妈妈没有荷尔蒙。
No hormones changes.
激素没有变化。
Yeah.
是的。
We keep exactly the same media, which is certainly a very simplistic kind of soup of chemicals, but we don't change it.
我们保留完全相同的介质，这当然是一种非常简单的化学物质汤，但我们不会改变它。
And then you just look at these two subunits, and you see how 2B goes down and 2A goes up, and they pretty much meet that nine months of keeping them in a dish.
然后你只要看看这两个亚基，你就会看到 2B 是如何下降的，而 2A 是如何上升的，它们几乎满足了将它们放在培养皿中九个月的要求。
It's amazing.
太棒了。
So that tells us that there's some sort of intrinsic clock.
这告诉我们存在某种内在的时钟。
Once you start a development, the cells measure really, really well the time of development.
一旦开始发育，细胞就会非常非常准确地测量发育时间。
That does not mean that all aspects of development are going to now be recapitulated in a dish.
这并不意味着发展的所有方面现在都将在一道菜中重现。
But it tells us that there is this incredible ability of cells, especially in the nervous system, because, of course, those cells will keep for the rest of our lives.
但它告诉我们，细胞有这种令人难以置信的能力，尤其是在神经系统中，因为这些细胞当然会在我们的余生中保留下来。
We're never going to renew neurons.
我们永远不会更新神经元。
It's going to be different for liver cells or gut cell.
肝细胞或肠道细胞的情况会有所不同。
But for neurons, probably in particular, they'll need to keep track of time really, really well.
但对于神经元来说，可能尤其如此，它们需要非常非常好地记录时间。
So that was the first discovery that we've sort of made, which is still stunning today.
这是我们的第一个发现，今天仍然令人惊叹。
We still don't know the mechanism.
我们仍然不知道其中的机制。
We're still working really hard on figuring out exactly how the cells are keeping track of time.
我们仍在努力弄清楚细胞到底是如何记录时间的。
Because as you can imagine, if we understand what that molecular machinery is, we used to call it a clock, we now call it a timer.
因为正如你可以想象的，如果我们了解分子机械是什么，我们过去称之为时钟，现在称之为计时器。
We think it's more of a timer than an actual clock.
我们认为它更像是一个计时器，而不是一个实际的时钟。
But understanding what the molecular biology of that is will allow us actually to play with that clock.
但了解其分子生物学原理将使我们能够真正地玩弄这个时钟。
Right?
正确的？
So if you want to make neurons that are 70 years old neuron from a patient with Parkinson, I don't have to wait 70 years in a dish.
因此，如果你想从帕金森病患者身上制造出 70 岁的神经元，我不必在培养皿中等待 70 年。
Could I make it in a few weeks?
我可以在几周内完成吗？
Or perhaps could I take an aging neuron and somehow rejuvenate it by playing with that timer?
或者也许我可以通过玩弄计时器来让一个老化的神经元恢复活力？
But just to make it clear, we still don't know.
但澄清一下，我们仍然不知道。
We have some clues about what it may be, but I think it's still early days.
我们有一些关于它可能是什么的线索，但我认为现在还为时尚早。
And I think that was one of the first things that these cultures allowed us to do.
我认为这是这些文化允许我们做的第一件事。
Just watch development, human brain development, outside of the human body In a dish and actually witness that some fundamental aspects of brain development are actually recapitulated even outside of the uterus and, of course, of the brain.
只要在培养皿中观察人类身体外部的发育，人类大脑的发育，就会真正见证大脑发育的一些基本方面甚至在子宫之外，当然，在大脑之外也得到了重演。
So that was the first.
这是第一个。
And then, of course, I guess I'm a developmental neurobiologist by training, and I've done a lot of circuit work in early days.
当然，我想我是一名受过训练的发育神经生物学家，而且我在早期做了很多电路工作。
Of course, an obsession of mine was that especially for conditions as complex as autism and schizophrenia, we need to recapitulate some of the circuit properties of the brain.
当然，我的一个痴迷是，特别是对于自闭症和精神分裂症这样复杂的情况，我们需要概括大脑的一些回路特性。
So we now know that probably both for schizophrenia and for autism, it is very unlikely based on the evidence that we have so far, that there are cells really missing from the brain.
所以我们现在知道，根据我们迄今为止掌握的证据，对于精神分裂症和自闭症来说，大脑中真正缺失细胞的可能性很小。
We thought for a while that maybe some cells are missing or maybe other cells are in excess, but now the studies that have been done, especially with single-cell profiling of brains of patients that have already died, showed us that the composition of the brain, of the cortex in particular, it's very similar.
我们一度认为可能有些细胞缺失，或者其他细胞过多，但现在已经完成的研究，特别是对已经死亡的患者大脑的单细胞分析，向我们表明大脑的组成，特别是皮质的组成，非常相似。
So it's unlikely that the cells are missing, but likely the way they're connected with each other is what makes a difference.
因此，细胞不太可能缺失，但很可能是它们相互连接的方式造成了差异。
And of course, in the beginning, we were just making this clump of cells.
当然，一开始我们只是制造这团细胞。
They were all for the cortex, but they were not connected to anything else.
它们都是针对皮质的，但与其他任何东西都没有联系。
So then came the idea of assembloids.
于是就出现了汇编的想法。
Because most of the cells in the brain connect with cells across the nervous system, and in fact, even more interestingly, cells do not reside in the place in which they're born in the nervous system.
因为大脑中的大多数细胞与神经系统中的细胞相连，事实上，更有趣的是，细胞并不位于它们在神经系统中诞生的地方。
We have the largest cell diversity of any other organ, almost 2,000 cell types.
我们拥有所有其他器官中最大的细胞多样性，几乎有 2,000 种细胞类型。
By the end of the first trimester, there are about 600 cell types in the human brain.
到妊娠前三个月结束时，人脑中约有 600 种细胞类型。
Think about the liver, right?
想想肝脏吧？
Maybe a couple of dozens.
也许有几十个。
The brain has to make hundreds of times more.
大脑必须制造数百倍的能量。
So how do you do that?
那么你该怎么做呢？
The only way is to actually make the cell types in different parts of the brain, provide local cues there, and then once the cells have been specified, let them move and find their final position.
唯一的方法是实际在大脑的不同部位制造细胞类型，在那里提供局部线索，然后一旦细胞被指定，就让它们移动并找到最终位置。
So the first assembloid that we've actually made were of a very stereotypical canonical movement of cells in the nervous system, which has to do, again, with the cortex.
因此，我们实际上制作的第一个组合体是神经系统中细胞的非常典型的规范运动，这又与皮质有关。
So the cortex, again, the outer layer of the brain, has both excitatory and inhibitory neurons.
因此，皮质，即大脑的外层，同时具有兴奋性和抑制性神经元。
It turns out that most inhibitory neurons are not born in the cortex, but they're born deep in the brain.
事实证明，大多数抑制性神经元并非诞生于皮质，而是诞生于大脑深处。
So essentially, all we did is we made two brain regions, the ones that have excitatory neurons and the one that has inhibitory neurons, and the plan was to put them together, hoping that at one point, the cells will know what to do.
所以本质上，我们所做的就是制作两个大脑区域，一个具有兴奋性神经元，一个具有抑制性神经元，计划是将它们放在一起，希望在某一时刻，细胞知道该怎么做。
And in fact, that was one of the first projects in my lab, planning that.
事实上，这是我实验室的第一个项目，正在规划这个项目。
I remember giving to one of the students this very difficult task of figuring out how we're going to fuse these two cultures, and they're about three millimeters in size, so you can see them by eye.
我记得给一位学生布置了一项非常艰巨的任务，即弄清楚我们将如何融合这两种文化，它们的大小约为三毫米，所以你可以用肉眼看到它们。
And I thought it's going to be very difficult to put them together.
我认为将它们放在一起会非常困难。
So the student worked for months trying to figure out biological glues, using various electrodes and impaling them and everything else until somebody else came one day and said, "It's very simple.
因此，这名学生花了几个月的时间试图找出生物胶，使用各种电极并刺穿它们和其他东西，直到有一天有人过来说：“这非常简单。
You just put them at the bottom of a tiny Eppendorf tube," which is the tiniest of tubes that you get.
你只需将它们放在一个微小的 Eppendorf 管的底部，”这是你能得到的最小的管子。
You put them there overnight, and the next day, they're completely fused.
你把它们放在那里过夜，第二天，它们就完全融合了。
But they're not just fused because now if you look inside, within a few days, the cells that are supposed to move start to actually point out towards the cortex.
但它们不仅仅是融合，因为现在如果你观察内部，几天之内，应该移动的细胞实际上开始指向皮质。
They literally smell the chemicals from the cortex, and they start to move in this very stereotypical way towards the cortex.
它们确实闻到了来自皮质的化学物质，并且开始以这种非常刻板的方式向皮质移动。
And so that was the first assembloid, made around 2015, and I still remember it was Ben, actually.
这就是第一个组装体，大约在 2015 年制作，我仍然记得实际上是 Ben。
Ben was so excited.
本非常兴奋。
Ben Barres was so excited about seeing the cells.
本·巴雷斯（Ben Barres）看到这些细胞非常兴奋。
He wanted to look at these movies every day.
他想每天看这些电影。
And then he said, I still have this email from him, where he was very preoccupied that he kept saying, "This new preparation is not an organoid.
然后他说，我仍然保留着他发来的这封电子邮件，他在邮件中非常专注，一直说，“这种新制剂不是类器官。
It's not a steroid.
它不是类固醇。
It's something else.
这是另一回事。
You have to find another name."
你必须找到另一个名字。”
Andrew Huberman:
安德鲁·休伯曼：
He loved naming things.
他喜欢给事物命名。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
He loved naming things.
他喜欢给事物命名。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
And he understood the importance of naming things, not just for career reasons, although he understood a lot about how to build a career-
而且他了解命名事物的重要性，不仅仅是出于职业原因，尽管他了解很多关于如何建立职业生涯的知识——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah, perhaps
是的，也许
Andrew Huberman:
安德鲁·休伯曼：
...
...
but because naming Yamanaka factors made sense-
但因为命名山中因素是有道理的-
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
to name it after Yamanaka.
以山中伸之名命名。
He got a Nobel, and is immortalized that way, like stem cells, immortalized.
他获得了诺贝尔奖，并且以这种方式永生，就像干细胞一样永生。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yes.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But I think the naming is essential because otherwise, things can get lost in the technical details.
但我认为命名是必不可少的，因为否则，事情可能会迷失在技术细节中。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yes.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So who came up with the name assembloid?
那么 assembloid 这个名字是谁想出来的呢？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
So he kept insisting that I should find a name.
所以他一直坚持要我找一个名字。
So I made this long list I still have in my notebook.
所以我列了一张长长的清单，至今仍保留在我的笔记本中。
I had a long list of about 20, and I would keep sending Ben one, and Ben was always awake, like 24 hours.
我有一长串大约 20 个的清单，我会不断地给 Ben 发送一个，而 Ben 总是醒着，就像 24 小时一样。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, he didn't sleep much.
是的，他睡得不多。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
He never slept.
他从不睡觉。
Andrew Huberman:
安德鲁·休伯曼：
No.
不。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
So I remember after sending many emails going back and forth, and he was just like, "No, bad name.
所以我记得在来回发送了很多电子邮件之后，他就像，“不，坏名声。
I don't like it." And then at one point, I thought, well, -oid because it's like, and then assemble because we assemble the circuits.
我不喜欢它。”然后在某一时刻，我想，嗯，-oid，因为它就像，然后组装，因为我们组装电路。
So I thought assembloid, and I send this, and he says, "Perfect, I love it."
所以我想到了 assembloid，然后我发送了这个，他说，“完美，我喜欢它。”
Andrew Huberman:
安德鲁·休伯曼：
So you named assembloids.
所以你命名为汇编。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
I named assembloids-
我命名为“Assembloids”——
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
...
...
and Ben sort of blessed it one night at 3:00 a.m.
一天晚上凌晨 3:00，Ben 为它祝福了。
And so that was the first assembloid.
这就是第一个汇编体。
And the first assembloid was for cells migrating.
第一个组装体是用于细胞迁移的。
But then the question was, cells have to find each other and form circuits.
但问题是，细胞必须找到彼此并形成电路。
And so within a couple of years, we started making assembloids that will have axons, so the long projections of neurons finding other partners.
因此，在几年之内，我们开始制造具有轴突的组合体，因此神经元的长投射可以找到其他伙伴。
And you know how-- I forgot who said this.
你知道怎么做的——我忘了这句话是谁说的。
Must have been Rodolfo Llinás or who said that the brain is sort of the next evolutionary step towards movement.
一定是鲁道夫·利纳斯 (Rodolfo Llinás) 或谁说大脑是运动进化的下一个步骤。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
So the nervous system has been this theory that has evolved as a way of moving around.
因此，神经系统这一理论已经演变为一种移动方式。
Andrew Huberman:
安德鲁·休伯曼：
That was Sherrington.
那是谢林顿。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Was it Sherrington?
是谢林顿吗？
Andrew Huberman:
安德鲁·休伯曼：
The final common path is movement.
最后的共同路径是运动。
He was a physiologist.
他是一位生理学家。
He was kind of vague in his statement, but I think-
他的陈述有点含糊，但我认为——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Perhaps that was
也许那是
Andrew Huberman:
安德鲁·休伯曼：
...
...
that it was Sherrington.
那是谢林顿。
And I don't doubt that Rodolfo said something about it, too.
我毫不怀疑鲁道夫也说过类似的话。
I'm not going to try and take anything away from Rodolfo.
我不会试图从鲁道夫那里夺走任何东西。
Anyone that knows who Rodolfo Llinás is, he's not somebody you want to piss off.
任何知道鲁道夫·利纳斯是谁的人，你都不想惹恼他。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Well, we should check it, who actually said it.
好吧，我们应该检查一下，究竟是谁说的。
Andrew Huberman:
安德鲁·休伯曼：
No, give him credit.
不，要相信他。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
But-
但是——
Andrew Huberman:
安德鲁·休伯曼：
I like Rodolfo
我喜欢鲁道夫
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
...
...
but for us, that became the next objective.
但对我们来说，这成为了下一个目标。
Can we actually build a circuit That will have a very clear output.
我们真的可以构建一个具有非常清晰输出的电路吗？
So we would know that we've actually built that circuit.
这样我们就知道我们实际上已经构建了该电路。
So what we did is essentially, we thought about like the simplest circuit for movement, which is like the corticospinal tract.
所以我们所做的本质上是，我们思考最简单的运动回路，就像皮质脊髓束一样。
Okay, so that means that a neuron in deep layers of the cortex sends along axons all the way to the spinal cord, finds a motor neuron, makes a connection, then the motor neuron leaves the spinal cord, goes to the muscle.
好的，这意味着皮层深层的神经元沿着轴突一直发送到脊髓，找到运动神经元，建立连接，然后运动神经元离开脊髓，到达肌肉。
And essentially, you only have these two neurons, right?
本质上，你只有这两个神经元，对吧？
That are connecting with each other, with the muscle, two connections, one between the two of them and one with the muscle.
这是通过肌肉相互连接，两种连接，一种是两者之间的连接，一种是与肌肉的连接。
So the simplest of circuits that you can have.
这是您可以拥有的最简单的电路。
Andrew Huberman:
安德鲁·休伯曼：
Now lets me move my big toe.
现在让我移动我的大脚趾。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Right.
对。
Exactly.
确切地。
Andrew Huberman:
安德鲁·休伯曼：
It's pretty long distance, if you think about it.
如果你仔细想想，这是相当遥远的距离。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
It's a very simple, and of course, like in other species, a little bit more complicated.
它非常简单，当然，就像其他物种一样，有点复杂。
It turns out that in mice, there's an additional neuron there.
事实证明，小鼠体内还有一个额外的神经元。
So there are some changes that happened over evolution.
所以进化过程中发生了一些变化。
But for us and in primates, it's as simple as this.
但对于我们和灵长类动物来说，事情就这么简单。
So what we did was we essentially made an organoid that resembles the cortex and has some of those neurons, and then we made an organoid that resembles the spinal cord and has some motor neurons in it, and then we made a ball of human muscle that you can make from a biopsy.
所以我们所做的是，我们基本上制作了一个类似于皮质并具有一些神经元的类器官，然后我们制作了一个类似于脊髓并其中有一些运动神经元的类器官，然后我们制作了一个可以通过活检制作的人类肌肉球。
You can literally biopsy a muscle, you get the myoblast, you grow them, and you get a nice ball of muscle.
你可以从字面上对肌肉进行活检，得到成肌细胞，培养它们，然后得到一个漂亮的肌肉球。
And then, of course, the challenge was that the reality is that we don't know how those cells find each other.
当然，挑战在于现实是我们不知道这些细胞如何找到彼此。
Like in development, we know some of the molecular cues that they use, but we're far from having a comprehensive understanding of how they find each other.
就像在发育过程中一样，我们知道它们使用的一些分子线索，但我们还远未全面了解它们如何找到彼此。
And I remember we were sitting down in the lab and kind of like thinking, I resisted actually doing this as the first assembloid in the lab for a while because the probability was against us.
我记得我们坐在实验室里，有点想，有一段时间我实际上拒绝作为实验室中的第一个组装体这样做，因为可能性对我们不利。
Like those cells in the cortical organoid that are less than 5%, the motor neurons are less than 10%.
与皮质类器官中少于 5% 的细胞一样，运动神经元也少于 10%。
The probability that they find each other perfectly and in enough numbers to trigger muscle contraction was close to zero.
它们完美地找到彼此并且数量足够多以触发肌肉收缩的概率接近于零。
And yet you do it, you put the three parts together, you let them assemble, and within a few weeks, you can actually now stimulate the cortex with whatever you want to use, with an electrode, with light, and then the muscle starts to contract.
然而你做到了，你把这三个部分放在一起，让它们组装起来，几周之内，你实际上可以用你想要使用的任何东西，用电极，用光刺激皮层，然后肌肉开始收缩。
And in fact, the more you do it, the more reliable the process is.
事实上，你做得越多，这个过程就越可靠。
And then, of course, we went on, so like reverse engineering it, and figure out that indeed the cells have connected in that precise way.
当然，我们继续进行逆向工程，发现细胞确实以这种精确的方式连接起来。
So I think what we started actually to realize was that, of course, a lot of stem cell biology was-- I think a lot of biology was based on chemical and physical factors that we were leveraging, but we've never truly leveraged this next level of law or power in biology, which is self-organization, the ability of a biological system of build it itself.
所以我认为我们实际上开始意识到的是，当然，很多干细胞生物学是——我认为很多生物学是基于我们正在利用的化学和物理因素，但我们从未真正利用过生物学中的下一个层次的法则或力量，即自组织，生物系统构建自身的能力。
If you think about it, the human brain builds itself.
如果你仔细想想，人类的大脑是自我构建的。
Of course, there are instructions, but there's no blueprint.
当然，有说明，但没有蓝图。
There's no plan that the brain constantly looks to make sure that it actually made all the connections properly, right?
大脑并没有不断地寻找计划来确保它确实正确地建立了所有连接，对吗？
Instructions are sort of revealed at every step for the next step.
每一步都会显示下一步的说明。
And it mostly comes from the cells finding each other.
它主要来自于细胞相互寻找。
So I think what we also started to learn from this was that all we need to do is make the parts.
所以我认为我们也开始从中学到的是我们需要做的就是制造零件。
And if we make the parts right, then the parts will come with the instructions, and then the circuits will assemble on their own.
如果我们制作正确的零件，那么零件将附带说明，然后电路将自行组装。
And so that has been really the beginning of it.
这才是真正的开始。
And of course, it became progressively more difficult to build circuits.
当然，构建电路变得越来越困难。
And so of course, if you put two, you may think, "Oh, let's make three." And if you make three, can you make four?
当然，如果你放两个，你可能会想，“哦，我们放三个吧。”如果你做三个，你能做四个吗？
So actually, we just published a few months ago, the first four-part assembloid, that actually now reconstitutes the pathway that processes sensory information in the nervous system.
所以实际上，我们几个月前刚刚发表了第一个由四部分组成的组合体，它现在实际上重建了神经系统中处理感觉信息的途径。
So you think about the cortex, sends out to control movement and has an output, but it receives information from the outside constantly.
所以你想想皮层，发出去控制运动，有输出，但是它不断地接收来自外界的信息。
And that happens through neurons that sit close to the spinal cord, have projections in the skin where they sense tactile vibrations or pain stimuli, send that information to the spinal cord, from the spinal cord they cross, they go up to the thalamus in the middle of the brain, and from the thalamus, they go to the cortex.
这是通过靠近脊髓的神经元发生的，这些神经元在皮肤上有投射，感知触觉振动或疼痛刺激，将信息发送到脊髓，从它们穿过的脊髓，它们到达大脑中部的丘脑，再从丘脑到达皮质。
So this is a four-part pathway.
所以这是一个由四部分组成的途径。
So it took us years, first of all, to make the parts, and then to put them together.
因此，我们首先花了数年时间来制造零件，然后将它们组装在一起。
And then again, the beautiful thing about it is that while we still don't know all the rules of assembly, you can make this four-part, we call it the sensory assembloid or a somatosensory assembloid.
话又说回来，它的美妙之处在于，虽然我们仍然不知道组装的所有规则，但你可以将这个四部分组成，我们称之为感觉组装体或体感组装体。
Because it turns out that the sensory neurons that we can make are mostly sensory neurons that sense pain stimuli.
因为事实证明，我们能够制造的感觉神经元大多是感知疼痛刺激的感觉神经元。
And so you can actually put the four parts together, so the sensory, the spinal cord, the thalamus, and the cortex, and you have to put them in that order.
所以你实际上可以把这四个部分放在一起，所以感觉、脊髓、丘脑和皮质，你必须把它们按这个顺序排列。
If you change the order, the cells will not find each other.
如果更改顺序，单元格将无法找到彼此。
So you just have to create the minimal conditions for them, making the right cell types, putting them in the right order, and then they'll find each other.
因此，你只需为它们创造最低限度的条件，制作正确的细胞类型，将它们按正确的顺序排列，然后它们就会找到彼此。
And within a few weeks-- So it takes hundreds of days to build a circuit like this.
几周之内——所以建造这样的电路需要数百天的时间。
But the beauty of it is that suddenly you look at it, and you just see spontaneous activity that arises in the entire pathway, just starts to flicker all in sync.
但它的美妙之处在于，突然你看它，你就会看到整个路径中出现的自发活动，开始同步闪烁。
Andrew Huberman:
安德鲁·休伯曼：
Can you use this assembloid to study the effects of different pain medications?
您可以使用这个程序集来研究不同止痛药的效果吗？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yes.
是的。
So that is certainly one potential.
所以这肯定是一种潜力。
The other thing that you can do, and the first application that we've had was for genetic forms of pain conditions.
您可以做的另一件事，也是我们的第一个应用是针对遗传形式的疼痛状况。
So we very often think that genetic conditions where you have a very clear cause, so like entry points, like Rosetta Stones for understanding anything.
所以我们经常认为遗传条件有一个非常明确的原因，就像切入点一样，就像了解任何事物的罗塞塔石碑一样。
So there are these interesting mutations in a sodium channel, so another channel.
因此，钠通道和另一个通道中存在这些有趣的突变。
But the sodium channel turns out that if the channel is overactive because of a mutation, you'll have excessive pain.
但事实证明，钠通道如果因突变而过度活跃，你就会感到过度疼痛。
So these patients are highly sensitive.
所以这些患者是高度敏感的。
But then if the channel is essentially unable to function, then these patients have loss of pain.
但如果该通道基本上无法发挥作用，那么这些患者就会失去疼痛。
And that's equally bad.
这同样糟糕。
Many of these patients actually will die because they can't sense pain at all.
许多患者实际上会因为根本感觉不到疼痛而死亡。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, I think people don't realize that in mutations where people can't sense pain, people fail to make the postural adjustments-
是的，我认为人们没有意识到，在人们感觉不到疼痛的突变中，人们无法做出姿势调整——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Exactly
正是如此
Andrew Huberman:
安德鲁·休伯曼：
...
...
that allow you to stay alive, or because they, unfortunately, they can be resting a little bit too much on their right leg.
这可以让你活下去，或者因为他们，不幸的是，他们可能用右腿休息太多了。
We normally think, "Okay, no big deal," but-
我们通常会想，“好吧，没什么大不了的”，但是——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
you're constantly making these postural adjustments.
你不断地进行这些姿势调整。
If you don't do that, you actually can damage-
如果你不这样做，你实际上可能会损坏-
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
The legs that you're pushing down too hard on.
你用力向下推的腿。
Seems like a trivial amount of weight, right, to your own body weight.
对于你自己的体重来说，这似乎是微不足道的重量，对吧。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
But we fail to recognize just how often we're redistributing our-
但我们没有意识到我们重新分配我们的——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
our position.
我们的立场。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
No, no, no. And it's absolutely true.
不，不，不。这绝对是真的。
Like feedback in general is very important, including through this painful stimuli, through all stimuli in general.
一般来说，反馈非常重要，包括通过这种痛苦的刺激，通过所有的刺激。
And it turns out that if you now make essentially a four-part assembloid that carries the mutation that causes excessive pain, now the sensor neurons are excessively active, so they keep bursting with activity throughout.
事实证明，如果你现在基本上制造了一个由四部分组成的组装体，它携带会导致过度疼痛的突变，那么现在传感器神经元就会过度活跃，因此它们始终会保持爆发性的活动。
And then we thought we're going to take it out, and of course, in these patients, they can fire.
然后我们想我们要把它拿出来，当然，在这些病人身上，他们可以开火。
It turns out that it's not true, that they can fire.
事实证明这不是真的，他们可以开火。
For some reason, there are probably other channels that are helping them compensate, but they fail to engage the rest of the pathway in a synchronized way.
由于某种原因，可能有其他渠道正在帮助他们进行补偿，但他们无法以同步的方式参与路径的其余部分。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
So that's why we need the four parts, and I think that's why assembloids generally are going to be very useful because there are emergent properties that are arising from the interactions of the cells at distance in the brain, and likely many disorders, and of course, we're very far from understanding complex disorders such as autism.
这就是为什么我们需要这四个部分，我认为这就是为什么组合体通常会非常有用，因为大脑中远距离细胞的相互作用会产生一些新的特性，可能还有许多疾病，当然，我们距离理解自闭症等复杂疾病还很远。
But certainly, these fault interactions at a distance in the circuits are probably going to be key to understanding the biology of these conditions and hopefully at one point, reversing them.
但可以肯定的是，这些电路中远距离的故障相互作用可能是理解这些条件的生物学原理并希望在某一时刻扭转它们的关键。
Andrew Huberman:
安德鲁·休伯曼：
I'd like to take a quick break and acknowledge one of our sponsors, Function.
我想稍微休息一下并感谢我们的赞助商之一 Function。
Last year, I became a Function member after searching for the most comprehensive approach to lab testing.
去年，在寻找最全面的实验室测试方法后，我成为了 Function 成员。
Function provides over 100 advanced lab tests that give you a key snapshot of your entire bodily health.
Function 提供 100 多项高级实验室测试，为您提供整个身体健康状况的关键快照。
This snapshot offers you with insights on your heart health, hormone health, immune functioning, nutrient levels, and much more.
此快照为您提供有关心脏健康、激素健康、免疫功能、营养水平等方面的见解。
They've also recently added tests for toxins such as BPA exposure from harmful plastics and tests for PFAS or forever chemicals.
他们最近还增加了毒素测试，例如有害塑料中的 BPA 暴露以及 PFAS 或永久化学物质的测试。
Function not only provides testing of over 100 biomarkers key to your physical and mental health, but it also analyzes these results and provides insights from top doctors who are expert in the relevant areas.
Function 不仅提供对您的身心健康至关重要的 100 多种生物标记物的测试，而且还分析这些结果并提供相关领域专家的顶级医生的见解。
For example, in one of my first tests with Function, I learned that I had elevated levels of mercury in my blood.
例如，在我第一次使用 Function 进行测试时，我发现我的血液中汞含量升高。
Function not only helped me detect that, but offered insights into how best to reduce my mercury levels, which included limiting my tuna consumption, I'd been eating a lot of tuna, while also making an effort to eat more leafy greens and supplementing with NAC, N-acetylcysteine, both of which can support glutathione production and detoxification.
功能不仅帮助我发现了这一点，还为我提供了如何最好地降低汞含量的见解，其中包括限制我的金枪鱼摄入量，我一直在吃大量金枪鱼，同时还努力多吃绿叶蔬菜并补充 NAC、N-乙酰半胱氨酸，这两者都可以支持谷胱甘肽的产生和解毒。
And I should say, by taking a second Function test, that approach worked.
我应该说，通过进行第二次功能测试，这种方法奏效了。
Comprehensive blood testing is vitally important.
全面的血液检测至关重要。
There are so many things related to your mental and physical health that can only be detected in a blood test.
有很多与您的心理和身体健康相关的事情只能通过血液检查来检测。
The problem is blood testing has always been very expensive and complicated.
问题是血液检测一直非常昂贵且复杂。
In contrast, I've been super impressed by Function's simplicity and at the level of cost.
相比之下，Function 的简单性和成本水平给我留下了深刻的印象。
It is very affordable.
这是非常实惠的。
As a consequence, I decided to join their scientific advisory board, and I'm thrilled that they're sponsoring the podcast.
因此，我决定加入他们的科学顾问委员会，我很高兴他们赞助了这个播客。
If you'd like to try Function, you can go to functionhealth.com/huberman.
如果您想尝试 Function，可以访问 functionhealth.com/huberman。
Function currently has a wait list of over 250,000 people, but they're offering early access to Huberman podcast listeners.
Function 目前有超过 250,000 人的等待名单，但他们正在为 Huberman 播客听众提供早期访问服务。
Again, that's functionhealth.com/huberman to get early access to Function.
同样，可以通过 functionhealth.com/huberman 提前访问 Function。
So I want to discuss an ethical consideration/concern, but before we do that, I want to take a step back and just have you reflect.
因此，我想讨论道德考虑/担忧，但在我们这样做之前，我想退后一步，让您反思一下。
I will never forget the first time I learned neural development, like sperm meets egg, and then you get cell duplications, and then the embryo figures out what's going to become muscle, what's going to become nervous system, and it's a humbling thing-
我永远不会忘记我第一次学习神经发育的情景，就像精子遇到卵子，然后细胞复制，然后胚胎弄清楚什么会变成肌肉，什么会变成神经系统，这是一件令人谦卑的事情——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
to be able to realize that we understand even a small bit of that.
能够意识到我们甚至了解其中的一小部分。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And very little was known until the sort of early parts of the last century really is where some of the defining tissues and interactions were first discovered, so it was a relatively young science.
直到上世纪早期，人们才真正发现了一些定义性的组织和相互作用，因此人们对它知之甚少，因此它是一门相对年轻的科学。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Mm-hmm.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
Nowadays, I'm even more humbled by it because one only has to see a child that-
如今，我对此更加感到谦卑，因为只要看到一个孩子——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
nine months ago didn't exist, and you really start-- Most people understand how babies are made, and yet it's staggering, and I think what's so staggering about it, what's so miraculous, it's a miracle, is the self-organizing aspect of it.
九个月前还不存在，你真的开始了——大多数人都了解婴儿是如何产生的，但它是令人震惊的，我认为它如此令人震惊，如此神奇，这是一个奇迹，是它的自组织方面。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yes.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And now I'm hearing that these self-organization, the cell's own knowledge about what they should do and when is maintained.
现在我听说这些自组织，细胞自己关于应该做什么和何时做什么的知识得到了维护。
And I also have to just both highlight again and applaud the fact that regardless of where one stood on the embryonic stem cell debate, you're describing assembloids that were made from essentially taking a fibroblast, a skin cell-
我还必须再次强调并赞扬这样一个事实：无论人们在胚胎干细胞争论中的立场如何，你所描述的组合体基本上是由成纤维细胞（一种皮肤细胞）制成的——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Exactly
正是如此
Andrew Huberman:
安德鲁·休伯曼：
...
...
from a patient or from a non-patient, a healthy person that at least doesn't have that mutation, putting them in a dish, reverting them to stemness through the Yamanaka factors, then giving them certain things to drive them towards neuronal fates and then other fates, putting them together, and none of this involves the use of aborted tissues.
来自患者或非患者，至少没有这种突变的健康人，将它们放入培养皿中，通过山中因子将它们恢复为干性，然后给予它们某些东西以驱使它们走向神经元命运，然后是其他命运，将它们放在一起，所有这些都不涉及使用流产的组织。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
No.
不。
Andrew Huberman:
安德鲁·休伯曼：
May I ask you this?
我可以问你这个吗？
If today you could bank your fibroblasts turned into a few neurons-
如果今天你可以把你的成纤维细胞变成一些神经元——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Mm-hmm
嗯嗯
Andrew Huberman:
安德鲁·休伯曼：
...
...
would you do it?
你会这么做吗？
Knowing that those cells could eventually be used to create any tissue, like I hope you live a very, very long life, Sergio.
知道这些细胞最终可以用来制造任何组织，就像我希望你活得非常非常长寿，塞尔吉奥。
But let's say when you're 100, your heart has an issue.
但假设当你100岁时，你的心脏出现了问题。
Humans can do heart transplants-
人类可以进行心脏移植——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
from another human.
来自另一个人。
There are immune rejection issues there.
那里存在免疫排斥问题。
Pig hearts have been transferred into humans.
猪的心脏已被移植到人类身上。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But you could potentially build a heart that is of your cells, no immune rejection.
但你有可能建造一颗由你的细胞组成的心脏，没有免疫排斥。
Why wouldn't you bank your cells?
你为什么不储存你的细胞呢？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
I think you can collect them at any time, in principle.
我认为原则上你可以随时领取。
As long as you can-
只要你能——
Andrew Huberman:
安德鲁·休伯曼：
Okay, so you can get them on your 99th birthday.
好的，您可以在 99 岁生日时收到它们。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
I think you can still get them.
我想你仍然可以获得它们。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
For sure, it could be an argument-
当然，这可能是一个争论——
Andrew Huberman:
安德鲁·休伯曼：
So you have time, folks.
所以你们有时间，伙计们。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Right.
对。
So it could be an argument made that all the cells are going to be aging, so there are going to be some changes happening in those cells that maybe they have some mutated-
所以这可能是一个论点，所有的细胞都会衰老，所以这些细胞会发生一些变化，也许它们有一些突变——
Andrew Huberman:
安德鲁·休伯曼：
Yeah, they'll accumulate mutations.
是的，它们会积累突变。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah, that could be an argument made about it.
是的，这可能是一个争论。
On the other hand, what we're also seeing with some of the cell therapies that are just being developed now more broadly is that they don't have to be necessarily personalized.
另一方面，我们还看到，目前正在更广泛地开发的一些细胞疗法不一定是个性化的。
So they don't have to be made from your own cells.
因此它们不必由您自己的细胞制成。
Because you can use immunosuppression, that's one way in which you can do it.
因为您可以使用免疫抑制，这是您可以做到的一种方法。
So you can transplant the cells from somebody else.
所以你可以移植别人的细胞。
Of course, that poses more challenges if you think about the brain, replacing large parts of the brain, which certainly is like-
当然，如果你考虑一下大脑，替换大脑的大部分，这会带来更多的挑战，这肯定是——
Andrew Huberman:
安德鲁·休伯曼：
Yeah
是啊
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
...
...
far into the future.
遥远的未来。
Andrew Huberman:
安德鲁·休伯曼：
You want to be very careful whose brain you're taking about.
你要非常小心你正在获取谁的大脑。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah, certainly.
是的，当然。
But in general, you can see how in the future we may have off-the-shelf cells that have been made from a generic individual that you transplant with immunosuppression, or cells that have been genetically modified so that they're not rejected by the immune system, so they're compatible with all of us.
但总的来说，你可以看到，未来我们可能会拥有由普通个体制成的现成细胞，通过免疫抑制移植，或者经过基因改造的细胞，这样它们就不会被免疫系统排斥，因此它们与我们所有人都兼容。
Now it's much more likely to become a therapy that is broadly used, I think.
我认为现在它更有可能成为一种广泛使用的疗法。
So that's why I'm not that worried about harvesting my own cells right now.
所以这就是为什么我现在并不担心收获自己的细胞。
Andrew Huberman:
安德鲁·休伯曼：
Where do you sit on this idea that at some point in the not too distant future we will be able to immortalize entire organs within our body?
在不远的将来的某个时刻，我们将能够使我们体内的整个器官永生化，您对此有何看法？
Perhaps not ourselves, but our colleague Michael Snyder, Chair of Genetics at Stanford-
也许不是我们自己，而是我们的同事、斯坦福大学遗传学系主任迈克尔·斯奈德——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Mm-hmm
嗯嗯
Andrew Huberman:
安德鲁·休伯曼：
...
...
told me that he thinks that at least in my lifetime, I'm a little bit younger than he is, I'm almost 50, I forget how old Mike is, almost 70, but he said at least in my lifetime that immortalization of human tissues will be possible.
告诉我，他认为至少在我有生之年，我比他年轻一点，我快50岁了，我忘了迈克多大了，快70岁了，但他说至少在我有生之年，人体组织永生化是可能的。
He doesn't think that's a fantasy.
他不认为那是幻想。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah, I think different people mean different things by immortalizing something.
是的，我认为不同的人通过永垂不朽的事物意味着不同的事情。
We generally think like for in vitro studies or for in a dish study, when you immortalize something, it means that the cell is maintained forever, but it generally involves using a cancer-like factor, giving them cancer properties.
我们通常认为，就像在体外研究或培养皿研究中一样，当你使某些东西永生化时，这意味着细胞会永远保留，但它通常涉及使用类似癌症的因子，赋予它们癌症特性。
The cells that are immortalized, if you think about it, are either the stem cells that we talked about or the cancer cells.
如果你想一想，永生化的细胞要么是我们谈论的干细胞，要么是癌细胞。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
So we always have to be careful about what it means to actually immortalize a cell.
因此，我们必须始终小心细胞永生化的真正含义。
Rejuvenate cells, that's an interesting concept.
使细胞恢复活力，这是一个有趣的概念。
Will we be able to actually rejuvenate our cells even if they're aged?
即使我们的细胞已经老化，我们真的能够使其恢复活力吗？
So a lot of discussions have been happening lately whether you can actually use the Yamanaka factors, not to the extent that you completely reprogram a cell, but that you just use them just a little bit so that you rejuvenate the cells, not fully.
因此，最近发生了很多讨论是否可以真正使用山中因子，不是达到完全重新编程细胞的程度，而是只是稍微使用它们，以便使细胞恢复活力，而不是完全。
But as you can imagine, those are complicated experiments.
但正如你所想象的，这些都是复杂的实验。
They're going to have to be tuned.
他们必须进行调整。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
You need to control very carefully the dial there.
您需要非常小心地控制那里的转盘。
Andrew Huberman:
安德鲁·休伯曼：
Microdosing Yamanaka factors.
微剂量山中因素。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Right.
对。
Because you would actually risk moving into another state.
因为你实际上会冒着搬到另一个州的风险。
But that may be possible at one point.
但这在某一时刻可能是可能的。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
I thought that at one point one of the concerns of using Yamanaka factors and this whole technology therapeutically was that you could set the reversal in age of cells back to stemness, back to stem cells.
我认为，在某一时刻，使用山中因子和整个技术进行治疗的担忧之一是，你可以将细胞年龄逆转回干性，回到干细胞。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But then how do you stop them there?
但你如何阻止他们呢？
And also how do you send them-- Ultimately it's not a stem cell that you want, you want a fully differentiated heart cell or neuron, and you want to stop there.
还有你如何发送它们——最终你想要的不是干细胞，你想要的是完全分化的心脏细胞或神经元，你想就此打住。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
The idea being for anyone trying to reverse their age, how far back are you willing to go?
对于任何想要逆转年龄的人来说，你愿意回到多远的年纪？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Right.
对。
And it's true when you use the Yamanaka factors or a combination of them, because we've discovered afterwards that it's not just those factors that can do that.
当你使用山中因素或它们的组合时，确实如此，因为我们后来发现，不仅仅是这些因素可以做到这一点。
There are combinations of other factors that can do the same.
其他因素的组合也可以起到同样的作用。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
So there are various combinations.
所以有各种不同的组合。
There is a lot of redundancy in that pathway, and if you hit the right combinations in a cell at the right time, you can push it back in time.
该通路中有很多冗余，如果你在正确的时间在单元格中击中正确的组合，你可以将其及时推回。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Now, of course, the challenge is that reprogramming is full in the sense that everything is going to be erased.
当然，现在的挑战是重新编程已经全面，因为一切都将被删除。
If the reprogramming is done properly, theoretically all the methylation, so all these methyl groups that you put across DNA that accumulate with age are going to be removed.
如果重编程正确完成，理论上所有的甲基化，以及随着年龄的增长而积累在 DNA 上的所有甲基都会被去除。
All the signatures are essentially removed, so the cell is truly rejuvenated as in the beginning.
所有特征基本上都被去除，因此细胞真正像开始时一样恢复活力。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
And as you mentioned, perhaps you don't want to do that fully.
正如您所提到的，也许您不想完全做到这一点。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Can you do it in a way that is partial reprogramming, as some people refer to?
你能用一些人提到的部分重新编程的方式来做到这一点吗？
But certainly these are still early days for that, but certainly it's a possibility.
当然，现在还处于早期阶段，但肯定有这种可能性。
Andrew Huberman:
安德鲁·休伯曼：
I think for most people if I said, "Look, scientists are developing engineering eyes that can replace eyes for people that are blind, maybe one eye, maybe both," they'd say, "Great."
我想对于大多数人来说，如果我说：“看，科学家正在开发工程眼睛，可以代替盲人的眼睛，也许是一只眼睛，也许是两只眼睛，”他们会说，“太棒了。”
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
You're curing blindness effectively.
你正在有效地治愈失明。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And people are trying to do this.
人们正在尝试这样做。
Neuralink is doing this.
Neuralink 正在做这个。
Ejieshe Oniski and Dan Palanker at Stanford are trying to do this.
斯坦福大学的 Ejieshe Oniski 和 Dan Palanker 正在尝试这样做。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
If I said there are scientists and companies trying to develop chips so that paralyzed people can walk again, or that people who have locked-in syndrome can speak again-
如果我说有科学家和公司试图开发芯片，让瘫痪的人能够再次行走，或者患有闭锁综合症的人能够再次说话——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Mm-hmm
嗯嗯
Andrew Huberman:
安德鲁·休伯曼：
...
...
through one modality or another, they'd say, "Great." But if I said there are scientists who are building assembloids in a dish so that maybe you don't have two hippocampi, you have three.
通过一种或另一种方式，他们会说：“太棒了。”但如果我说有些科学家正在培养皿中构建组装体，这样也许你就没有两个海马体，那么你就有了三个。
You have a super memory.
你有超强的记忆力。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I think most people would be like, "Whoa, slow down.
我想大多数人都会说：“哇，慢点。
You're playing God.
你在扮演上帝。
That's not okay." And as a parallel example, CRISPR gene therapy, which we talked about earlier-
那不行。”作为一个平行的例子，我们之前谈到的 CRISPR 基因疗法——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
was employed by a Chinese scientist to, I think it was to mutate the HIV receptor.
被一位中国科学家雇佣，我认为是为了突变艾滋病毒受体。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
To modify two individuals.
修改两个人。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Two babies.
两个婴儿。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
So there are at least two babies that we're aware of, and probably more around the world, but not terribly many, for whom CRISPR was used to make a genetic modification.
因此，据我们所知，至少有两个婴儿，而且世界上可能有更多婴儿，但数量不是很多，他们使用 CRISPR 进行了基因改造。
Those babies were carried to term, and it wasn't to fix any particular disease, it was to confer them with something additional.
这些婴儿被怀到足月，并不是为了治愈任何特定的疾病，而是为了赋予他们额外的东西。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
In this case, to prevent presumed transmission of HIV from the mother.
在这种情况下，是为了防止艾滋病毒从母亲那里传播。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Which is not necessarily justified in that case, though.
不过，在这种情况下这不一定是合理的。
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
Did the mother have HIV?
母亲是否患有艾滋病？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
I think the idea was that to avoid maternal transmission to the fetus You would not have that.
我认为这个想法是为了避免母体传播给胎儿，你不会有这样的情况。
But there are other ways in which that can actually be avoided.
但实际上还有其他方法可以避免这种情况。
So in this case, it was not perhaps the best choice of a disease to correct.
因此，在这种情况下，这可能不是纠正疾病的最佳选择。
And I think that's why the scientific community has been quite outraged by both, I guess, the rationale and the way the experiment was done, which was not following certainly-
我认为这就是为什么科学界对实验的基本原理和进行实验的方式感到非常愤怒，而实验的原理和方式并没有遵循-
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Yeah.
是的。
The scientific community, as you said, was very upset about that, which brings us to the question of ethics.
正如你所说，科学界对此感到非常不安，这让我们想到了道德问题。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yes.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So I'm sure being really familiar with this technology, that you've thought about a number of ethical issues that aren't going to occur to me, or perhaps you've heard about things from the general public or from physicians and psychiatrists.
因此，我确信您非常熟悉这项技术，您已经考虑过许多我不会想到的道德问题，或者您可能已经从公众或医生和精神病学家那里听说过一些事情。
What are some of the key ethical issues that come to mind when thinking about how assembloids are going to be implemented as eventually treatments for disease?
在考虑如何将组装体最终用于疾病治疗时，会想到哪些关键的伦理问题？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
So we think a lot about the ethical issues, and we think this as a group at Stanford that's part of my center.
因此，我们对道德问题进行了很多思考，我们认为斯坦福大学的一个小组是我中心的一部分。
We have Hank Greely, who's a professor of law and an ethicist.
我们有汉克·格里利，他是一位法学教授和伦理学家。
But actually, we've engaged many ethicists, sociologists of religions.
但实际上，我们聘请了许多伦理学家、宗教社会学家。
We're actually going to have the first meeting at Asilomar this November on the ethics of neural organoids, assembloids, and their transplantation.
实际上，我们将于今年 11 月在阿西洛玛举行第一次会议，讨论神经类器官、组合体及其移植的伦理问题。
And there are various ways of classifying the ethical issues.
对道德问题进行分类的方法有很多种。
The way I think about it is that on one hand, there are ethical issues that are related to the cells.
我的想法是，一方面，存在与细胞相关的伦理问题。
We are taking cells from a human, and so you expect that you have received proper consent for the use of those cells, whatever that is.
我们正在从人类身上获取细胞，因此您希望您已获得使用这些细胞的适当同意，无论是什么。
On the other hand, if, for instance, you put them into an animal, then there are ethical issues related to that animal.
另一方面，例如，如果你将它们放入动物体内，那么就会存在与该动物相关的伦理问题。
Are you doing any harm?
你有做任何伤害吗？
How do we manage pain in that animal that has been transplanted?
我们如何控制移植动物的疼痛？
And then there are issues that are at the interface between the two.
然后是两者之间的接口问题。
So for instance, are there any emergent properties that are arising at one point, whether they're in a dish or maybe perhaps in an animal?
举例来说，是否有任何在某一时刻出现的突现特性，无论它们是在培养皿中还是在动物中？
How complex can a circuit like this become?
这样的电路可以变得多复杂？
Is there any form of learning, of computation?
是否存在任何形式的学习或计算？
Of course, some people have raised the issue that perhaps there is sentience or awareness, consciousness.
当然，有些人提出了一个问题，也许有感觉或意识、意识。
Are they feeling pain?
他们感到疼痛吗？
So for instance, that has been one critique for one of the recent work that we've done.
例如，这是对我们最近所做的一项工作的批评。
Of course, in that case, we know the emotional component of pain is processed in different brain regions.
当然，在这种情况下，我们知道疼痛的情绪成分是在不同的大脑区域处理的。
We don't have those in a dish, so we know that they're not really feeling pain.
我们的盘子里没有这些，所以我们知道它们并没有真正感到疼痛。
We have the pathway of pain.
我们有痛苦的道路。
But it also speaks to the fact that we need to be very careful about how we communicate this type of research.
但这也说明了一个事实，即我们需要非常小心地交流此类研究。
Even just using terms that are trivializing can actually create a lot of confusion.
即使只是使用一些无关紧要的术语实际上也会造成很多混乱。
And the classic example in our field has been to call these preparations, these organoids or assembloids, to call them mini brains.
我们领域的经典例子就是将这些制剂称为类器官或组合体，称之为迷你大脑。
Right?
正确的？
Then it may seem like as a trivial joke that it can't do anything, any harm.
那么它可能看起来就像一个微不足道的笑话，它不能做任何事情，任何伤害。
But you hear that for the first time, scientists have made mini brains in a dish.
但你还是第一次听说科学家在盘子里制作了迷你大脑。
Right?
正确的？
And what do you think?
你觉得怎么样？
You think, "Oh, it must be a miniature human brain that they're keeping in a dish." Right?
你会想，“哦，他们放在盘子里的一定是微型人脑。”正确的？
Isolated.
孤立。
And of course, that's not true.
当然，事实并非如此。
We have not made the entire nervous system.
我们还没有制造出整个神经系统。
We can make parts of the nervous system.
我们可以制造神经系统的一部分。
We can put them in various combinations, but we've never made an entire brain.
我们可以将它们进行各种组合，但我们从未制造出完整的大脑。
Actually, I don't know of any scientist who has as a goal to try to build the entire nervous system as an exact replica of the brain.
事实上，据我所知，没有哪位科学家的目标是尝试将整个神经系统构建为大脑的精确复制品。
So I think the words matter a lot, and in fact, that has been one of the things that we've done over the years.
所以我认为这句话很重要，事实上，这是我们多年来所做的事情之一。
A few years ago, I thought it would be really important to get most of the scientists in the field together and start thinking about these terms really carefully.
几年前，我认为让该领域的大多数科学家聚集在一起并开始认真思考这些术语非常重要。
And so we got together, created an ad hoc consortium, and through many calls, one-on-one, in various groups, we came up with one paper, which was published in "Nature" a couple of years ago, which really comes as a nomenclature for the field.
因此，我们聚集在一起，创建了一个临时联盟，通过各个小组的多次一对一通话，我们提出了一篇论文，几年前发表在《自然》杂志上，这确实是该领域的术语。
We, as scientists, decided this are the way we classify them.
作为科学家，我们决定这就是我们对它们进行分类的方式。
These are the terms that we all agreed should be used, and not use, for instance, project, let's say, complex terms onto this.
这些是我们都同意应该使用的术语，而不是使用例如项目，比如说，复杂的术语。
We'll never say that an organoid sees just because there is a retina.
我们永远不会因为有视网膜就说类器官能看见东西。
Right?
正确的？
We'll never say that a cortical organoid has intelligence because that's a property of an entire nervous system.
我们永远不会说皮质类器官具有智力，因为这是整个神经系统的特性。
So we think that this is actually quite important, especially in communicating with the public.
所以我们认为这其实是非常重要的，特别是在与公众的沟通方面。
And that consortium turned out to be an actually great exercise of getting everybody together and now thinking, what are some of the common practices that we should all use when we report this experiment?
事实证明，这个联盟实际上是一个很好的练习，让每个人都聚集在一起，现在我们在思考，当我们报告这个实验时，我们应该使用哪些常见的做法？
So we just had a few months ago, another paper that came also as a perspective in "Nature," where we also laid out the framework for the field.
几个月前，我们刚刚发表了另一篇论文，该论文也作为《自然》的一个视角，其中我们也提出了该领域的框架。
I think this also speaks to the fact that we're entering a new era in science, where I think you would say all these labs are working separately, they're competing with each other, and yet we all got together, 25 or so labs, discussed some of these issues, reached some consensus, and I think that moves the field forward.
我认为这也说明了我们正在进入科学的新时代，我想你会说所有这些实验室都在各自工作，相互竞争，但我们都聚集在一起，大约 25 个实验室，讨论了其中一些问题，达成了一些共识，我认为这推动了该领域的发展。
And I think in general, in science, we will need more and more of these collaborative efforts because the science is getting more complex, biology is getting really complex, and there's no one single lab that can solve all of that.
我认为总的来说，在科学领域，我们将需要越来越多的协作努力，因为科学变得越来越复杂，生物学变得非常复杂，并且没有一个实验室可以解决所有这些问题。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, I completely agree.
是的，我完全同意。
I think some years back, collaboration became the norm as opposed to the occasional thing, and I always thought that laboratories should be named after projects, missions-
我想几年前，合作已经成为常态，而不是偶尔发生的事情，我一直认为实验室应该以项目、任务命名——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
as opposed to individuals, but that's a-
与个人相反，但那是-
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
that's another story.
那是另一个故事了。
Well, kudos to you for thinking about these issues so carefully and for gathering people around them in order to come up with nomenclature.
好吧，值得赞扬的是，您如此仔细地思考了这些问题，并聚集了周围的人来提出术语。
Going back to this issue of naming, what things are called is so critical.
回到命名这个问题，东西叫什么是非常关键的。
It's so critical, and we see this in the public health sphere when people talk about gain-of-function research now.
这非常重要，当人们现在谈论功能获得研究时，我们在公共卫生领域看到了这一点。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
It's rarely mentioned that gain-of-function studies are critical for understanding things.
很少有人提到功能获得研究对于理解事物至关重要。
It's not always the case you're mutating a virus.
病毒并不总是会发生变异。
Gain-of-function is a general technology.
功能增益是一项通用技术。
More specificity of language, I think, is going to be immensely beneficial.
我认为，更加具体的语言将会非常有益。
So-
所以——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
appreciate you doing that.
感谢你这样做。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
And these terms change with time.
这些术语会随着时间而变化。
I think it's also important to mention that our understanding evolves.
我认为同样重要的是要提到我们的理解在不断发展。
Science progresses, and sometimes there are things that we thought we understood, and then new techniques come and change that.
科学在进步，有时我们认为我们已经理解了一些事情，然后新技术的出现改变了这一点。
I think it was Sydney Brenner who said that progress in science usually comes from a new technique that will yield new discoveries and that will create new ideas.
我认为悉尼·布伦纳（Sydney Brenner）说过，科学的进步通常来自新技术，它会产生新的发现并创造新的想法。
So you think you understand something, and suddenly you have a new machine that can measure it much better with more precision, or let's say you have this technology when you can now recreate some of the circuits, and suddenly new ideas come out of it, new discoveries, and then we rethink and we adjust.
所以你认为你理解了一些东西，突然间你有了一台新机器，可以更好、更精确地测量它，或者假设你拥有这项技术，现在你可以重新创建一些电路，突然间出现新的想法、新的发现，然后我们重新思考和调整。
And I think that's the beauty of science, that in a way, it's self-correcting as we get a better and better understanding of the world around us.
我认为这就是科学的美妙之处，在某种程度上，随着我们对周围世界的了解越来越深入，它会自我纠正。
Andrew Huberman:
安德鲁·休伯曼：
Also essential for people to hear, because I think whenever science or medicine comes out and tries to correct itself, often the general public, not all, but components of the general public will go up in arms as similar to a teenager realizing that their parents also did some bad stuff when they were younger, and they're like, "See?
对于人们来说，听到这一点也很重要，因为我认为，每当科学或医学出现并试图自我纠正时，通常是公众，而不是全部，但公众的一部分会勃然大怒，就像一个青少年意识到他们的父母在他们年轻时也做过一些坏事一样，他们会说，“看到了吗？
I shouldn't believe anything you say." It turns out science as a whole, I think, is a very well-intentioned endeavor.
我不应该相信你说的任何话。”我认为，事实证明，整个科学是一项善意的努力。
You get your occasional bad apples, but I think that this notion of self-correction, it's fundamental.
你偶尔会遇到坏苹果，但我认为这种自我纠正的概念是基本的。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Just like engineering's gotten better.
就像工程学变得更好一样。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
The phone you use now doesn't look anything like-
你现在使用的手机看起来不太像-
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
in terms of technology or speed of the phone you used 10 years ago, likewise with any technology.
就您 10 年前使用的手机的技术或速度而言，任何技术都是如此。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
That's why it's so important that both when we communicate as scientists to the public, we use terms that are not trivializing.
这就是为什么当我们作为科学家与公众交流时，我们使用的术语并不琐碎，这一点非常重要。
I think very often we're told, "Try to simplify so that the public understand." The public understands much more than we think.
我想我们经常被告知，“尽量简化，以便公众理解。”公众的理解比我们想象的要多得多。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
There are always ways in which you can explain something without trivializing it, without using a new term or some comparison so that they understand that.
总有一些方法可以让你在不轻视某些事情的情况下解释它，而不使用新术语或进行一些比较，以便他们理解。
Because very often, analogies can also be dangerous.
因为很多时候，类比也可能是危险的。
But I always assume, and that has being my mantra, that when you explain even to the general public, that they have zero knowledge and yet infinite intelligence.
但我总是假设，这一直是我的口头禅，当你向公众解释时，他们的知识为零，但智力无限。
I think as the saying goes in science.
我认为正如科学上所说的那样。
So I think there are always ways of explaining science very simply, but also communicating that science changes over time, that there are new understandings that are correcting the science, and we've seen this, of course, in medicine.
所以我认为总有一些方法可以非常简单地解释科学，但也可以传达科学随着时间的推移而变化的信息，有新的理解正在纠正科学，当然，我们已经在医学中看到了这一点。
We've sadly seen it in psychiatry many times by labeling, relabeling, doing treatments that perhaps were not the most fortunate over time.
可悲的是，我们在精神病学中多次看到这种情况，通过贴标签、重新贴标签、进行治疗，但随着时间的推移，这些治疗可能并不是最幸运的。
But I think it's important to tell the public that we're always trying to move towards.
但我认为重要的是告诉公众我们一直在努力朝着这个方向前进。
I think most physicians that I know, most psychiatrists that I know, are really motivated by really trying to make their patient better.
我认为我认识的大多数医生，我认识的大多数精神科医生，都是真正努力让病人变得更好。
Andrew Huberman:
安德鲁·休伯曼：
So let's play a game where if I say, if you take two human cortical neurons-
所以让我们玩一个游戏，如果我说，如果你拿两个人类皮质神经元 -
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Mm-hmm
嗯嗯
Andrew Huberman:
安德鲁·休伯曼：
...
...
or three or five or 10 or 1,000 that were developed from one of my fibroblasts, and you put it into a mouse or a non-human primate, like a macaque monkey, I think you've still got a mouse harboring a few of my neurons or a macaque monkey harboring a few of my neurons.
或者从我的一个成纤维细胞中发育出三、五、十或一千个，然后将其放入小鼠或非人类灵长类动物（例如猕猴）中，我认为您仍然会得到一只含有我的一些神经元的小鼠或一只含有我的一些神经元的猕猴。
At what point does that animal no longer become strictly a mouse or strictly a primate?
什么时候该动物不再成为严格意义上的小鼠或严格意义上的灵长类动物？
And then the parallel example, of course, is let's say I could get some neurons from fibroblasts that were made from you and those were put into my brain.
当然，平行的例子是，假设我可以从由你制成的成纤维细胞中获取一些神经元，然后将它们放入我的大脑中。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
At what point do I become more Serguei-like than Andrew-like?
什么时候我会变得更像塞尔盖而不是像安德鲁？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Sure.
当然。
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So how do you think about those questions?
那么您如何看待这些问题呢？
And while it might seem too early to consider those, we've learned through history that it's never too early to start-
虽然现在考虑这些似乎还为时过早，但我们从历史中了解到，开始永远不会太早——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
It is
它是
Andrew Huberman:
安德鲁·休伯曼：
...
...
thinking about the ethical implications-
思考伦理影响——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
It is
它是
Andrew Huberman:
安德鲁·休伯曼：
...
...
of a technology like this where there's transplantation involved.
像这样涉及移植的技术。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
No, it is absolutely not too early, actually.
不，事实上，现在绝对不算太早。
The right time to think about this is as experiments are actually being planned, not when experiments have been done.
考虑这个问题的正确时机是在实验实际上正在计划中的时候，而不是在实验已经完成的时候。
Andrew Huberman:
安德鲁·休伯曼：
Ah, good point .
啊，说得好。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
And that's what we've been doing.
这就是我们一直在做的事情。
And that's why, actually, all experiments that we do undergo ethical approval at Stanford.
实际上，这就是为什么我们所做的所有实验都经过斯坦福大学的伦理批准。
And I think at most major institutions, and certainly in the United States, you have to first propose what you're going to do, especially with pluripotent stem cells and especially with animals, and a committee will decide whether that is acceptable or not.
我认为在大多数主要机构，当然在美国，你必须首先提出你要做什么，特别是对于多能干细胞，尤其是动物，然后一个委员会将决定这是否可以接受。
Now, of course, there are experiments that perhaps are not necessarily illegal, but when you try to break a new frontier.
当然，现在有些实验也许不一定是非法的，但当你试图突破新领域时。
But I think what it's important to think about this process of transplanting or transplantation, that you take cells and you put them either in another individual or another species, is that what really matters a lot, we've learned now, is the timing, when you actually transplant those cells.
但我认为，考虑这个移植过程，即获取细胞并将它们放入另一个个体或另一个物种中，重要的是，我们现在了解到，真正重要的是真正移植这些细胞的时机。
So it turns out that the brain, the adult brain, is not very permissive to forming new connections.
事实证明，大脑，即成人大脑，不太愿意形成新的连接。
We may form small connections.
我们可能会建立一些小的联系。
There's a lot of plasticity of the connections, but we don't have, let's say in our adult brains, we don't have cells that are moving now across the nervous system.
连接有很多可塑性，但我们没有，比如说在我们成年的大脑中，我们没有现在在神经系统中移动的细胞。
We don't have entire pathways that are being rewired.
我们没有正在重新布线的整个路径。
You're never going to have a cortical neuron that just simply regrows and now connects to spinal cord neurons, which is why injury to the nervous system is so devastating.
你永远不会有一个皮质神经元只是简单地再生并连接到脊髓神经元，这就是为什么神经系统损伤如此具有破坏性。
There's so little recovery because the cells are usually not essentially rejuvenating.
恢复的速度非常慢，因为细胞通常基本上无法恢复活力。
There are no cells that are replenishing them.
没有细胞来补充它们。
And it's not just that there are no cells to actually replace them, it's also that the cells are just not that eager to connect with other cells as they are early in development.
不仅没有细胞可以真正取代它们，而且这些细胞并不像在发育早期那样渴望与其他细胞连接。
And so years ago, we've discovered that while we can keep some of these cultures in a dish for very long periods of time and connect them in ever more complex assembloids, and now there are literally dozens and hundreds of assembloids that people have made, and not just in the nervous system, actually even outside of the nervous system, because now there are cardiac assembloids and endometrial assembloids.
多年前，我们发现，虽然我们可以将其中一些培养物保存在培养皿中很长一段时间，并将它们连接成更加复杂的组合体，但现在人们已经制造了数十个和数百个组合体，不仅在神经系统中，实际上甚至在神经系统之外，因为现在有心脏组合体和子宫内膜组合体。
And so the concept took over, and I'm glad to talk about it.
所以这个概念就开始流行了，我很高兴谈论它。
We're going to have the first conference on assembloids at Cold Spring Harbor this year, which is to bridge across fields and try to understand complex cell-cell interactions.
今年我们将在冷泉港举行第一届组装体会议，该会议旨在跨领域架起桥梁，并尝试了解复杂的细胞与细胞之间的相互作用。
But even with these most complex assembloids, we realize that the cells are still missing cues that are present in vitro.
但即使有了这些最复杂的组合体，我们也意识到细胞仍然缺少体外存在的线索。
So a few years ago We were doing an experiment looking at some of the neurons that we made in a dish.
几年前，我们正在进行一项实验，观察我们在培养皿中制作的一些神经元。
And these neurons in the cortex are very often called pyramidal because they look like a pyramid.
皮层中的这些神经元通常被称为金字塔神经元，因为它们看起来像金字塔。
They really have this beautiful triangular shape.
它们确实有这个美丽的三角形。
And we were looking at the neuron, it looked beautiful, exactly like a pyramidal neuron.
我们正在观察神经元，它看起来很漂亮，就像锥体神经元一样。
And then around that time, we got a piece of tissue that was removed from a child who underwent surgery for epilepsy.
大约在那个时候，我们从一名接受癫痫手术的儿童身上取出了一块组织。
So when you sometimes have to undergo the surgeries, intractable epilepsy is really severe, maybe you talked about this previously, you have to remove some tissue.
所以有时候你要做手术的时候，顽固性癫痫真的很严重，可能你之前也讲过，你必须要切除一些组织。
And when you remove some of that tissue, you also have to remove some healthy tissue.
当你去除一些组织时，你还必须去除一些健康的组织。
And so we got some of that healthy tissue, and of course, we're always eager to understand how the cells that were made in a dish are similar or dissimilar to the ones in the actual brain.
所以我们得到了一些健康的组织，当然，我们总是渴望了解培养皿中产生的细胞与实际大脑中的细胞有何相似或不同。
We still need to benchmark before we use that for a therapy or for anything else.
在将其用于治疗或其他任何用途之前，我们仍然需要进行基准测试。
And we compare one day some of the cells, and we realized, to our amazement, I don't know how we'd never noticed it, or nobody has really made a big deal out of it, but the neurons that we were making in a dish were about 10 times smaller than the ones in the cortex on average.
有一天，我们比较了一些细胞，令我们惊讶的是，我不知道我们怎么从未注意到它，或者没有人真正把它当回事，但我们在培养皿中制造的神经元平均比皮层中的神经元小 10 倍。
Andrew Huberman:
安德鲁·休伯曼：
Hmm.
嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
There are kind of miniature versions of what was happening.
所发生的事情有一些微型版本。
And so it was like, of course, immediately it was like, what is happening in vivo?
所以，当然，马上就好像，体内发生了什么？
Is there something, as they say, in vivo veritas very often, right?
正如他们所说，体内经常有一些东西，对吗？
We know this has been the case for immunology, that many experiments in vitro have not always panned once you actually study them in an actual patient.
我们知道免疫学就是这种情况，一旦你在实际患者身上进行了实际研究，许多体外实验并不总是有效。
So that's when we actually started to also use transplantation, meaning we started thinking, could we actually put some of the cells in an animal and see whether they acquire new properties or they look much more like this?
所以从那时起我们实际上也开始使用移植，这意味着我们开始思考，我们是否真的可以将一些细胞放入动物体内，看看它们是否获得新的特性，或者它们看起来更像这样？
And of course, transplantation has been used for 40 years.
当然，移植术已经使用了 40 年。
Many of these experiments were done before I was born, especially in Sweden, when scientists will actually take various cells and transplant them into animals.
其中许多实验是在我出生之前完成的，尤其是在瑞典，科学家们实际上会采取各种细胞并将它们移植到动物体内。
And so what we started doing is taking actual organoids, cortical organoids, and then transplanting them into a rat, an early-born rat, in the somatosensory cortex, so the part of the brain that receives information from whiskers.
因此，我们开始做的是获取真正的类器官，即皮质类器官，然后将它们移植到老鼠（一只早期出生的老鼠）的体感皮层中，也就是从胡须接收信息的大脑部分。
And we've done that in the first few days after birth.
我们在出生后的最初几天就做到了这一点。
And it turned out that that was key because if you do it later, the cells don't really integrate that well.
事实证明，这是关键，因为如果你稍后再做，细胞就不会真正整合得那么好。
They integrate, but they don't fully integrate.
它们整合了，但并未完全整合。
And if you transplant that organoid into the somatosensory cortex of the rat, and then you wait for a few months, that graft starts to grow.
如果你将该类器官移植到老鼠的体感皮层中，然后等待几个月，移植物就会开始生长。
The cells become vascularized by the rat.
这些细胞在大鼠的作用下变得血管化。
They will even receive microglia.
他们甚至会接收小胶质细胞。
The immune cells of the nervous system of the rat start to populate.
大鼠神经系统的免疫细胞开始繁殖。
And then when you look on an MRI, you now can see that about a third of one hemisphere of the rat is now made up of human cells.
然后当你观察核磁共振成像时，你现在可以看到老鼠半球的大约三分之一现在是由人类细胞组成的。
So you can see really on an MRI from the ventricle to the pia.
所以你可以通过 MRI 看到从心室到软脑膜的真实情况。
Now, you may think that that's like an inert piece of tissue that sits there, but it turns out that it is quite well connected to the host, and that happens because the brain is still eager to connect at that early stage of development, but later on is not.
现在，你可能认为这就像坐在那里的一块惰性组织，但事实证明它与宿主连接得很好，发生这种情况是因为大脑在发育的早期阶段仍然渴望连接，但后来就不再连接了。
And so, for instance, you can do experiments where you can actually record the activity of human neurons and at the same time move the whiskers of the rat.
例如，您可以进行实验，实际上可以记录人类神经元的活动，同时移动老鼠的胡须。
So if you move the whiskers of the rat onto the opposite side, obviously because the pathway is crossed, then human neurons now start to respond to that.
因此，如果你将老鼠的胡须移到另一侧，显然是因为路径交叉了，那么人类神经元现在开始对此做出反应。
And then I think probably the most important consequence of that is that they receive now input.
然后我认为最重要的结果可能是他们现在收到了意见。
They're now in an environment that is much more physiological.
他们现在处于一个更加生理化的环境中。
So when we now looked at the cells, it turned out that they're like six to eightfold larger than when we were making the dish.
因此，当我们现在观察细胞时，发现它们比我们制作培养皿时大六到八倍。
They're not yet identical replica, but they're very, very close.
它们还不是完全相同的复制品，但它们非常非常接近。
And that for us has actually been key and started to actually understand the biology of some of these conditions.
这对我们来说实际上是关键，并开始真正了解其中一些病症的生物学原理。
So, for instance, for Timothy syndrome, there is a very dramatic effect in the size of the neurons.
例如，对于蒂莫西综合征，神经元的大小会产生非常显着的影响。
They're almost twice as smaller than a control neuron.
它们几乎比对照神经元小两倍。
Andrew Huberman:
安德鲁·休伯曼：
In the patient.
在病人身上。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Well, in the patient.
嗯，在病人身上。
Only when you transplant the cells, we can see that defect.
只有当你移植细胞时，我们才能看到那个缺陷。
In a dish, you look at them and they're identical.
在盘子里，你观察它们，它们是相同的。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
And then you transplant them, and some of them grow really large to control, and the patients fail.
然后你移植它们，其中一些变得非常大而无法控制，而患者却失败了。
And that phenotype can only really be seen properly in vivo.
而这种表型只有在体内才能真正正确地看到。
So that has been actually essential also as we've been developing a therapeutic for this condition, and you start thinking like, how do you test a therapeutic?
因此，这实际上也很重要，因为我们一直在开发针对这种情况的治疗方法，并且您开始思考，如何测试治疗方法？
If there's no animal model of the disease, you test everything in a dish.
如果没有这种疾病的动物模型，你就可以测试培养皿中的所有东西。
You do want to have some safety check, first of all, for making sure that there are no adverse effects, but also you want to make sure that it works in an in vivo environment.
首先，您确实需要进行一些安全检查，以确保没有不良影响，而且您还想确保它在体内环境中有效。
And actually, it turns out that this model that we've built was essential because now we could take actually the animal and inject the therapeutic into the nervous system of the animal, but look at the effect on human neurons in an in vivo context.
事实上，事实证明我们建立的这个模型是至关重要的，因为现在我们可以实际拿动物并将治疗药物注射到动物的神经系统中，但在体内观察对人类神经元的影响。
And so I think that's one application for this, but if you do the transplantation at a later stage, like for instance in an adult, that integration will probably not happen.
所以我认为这是一个应用程序，但如果你在稍后阶段进行移植，例如在成人中，那么整合可能不会发生。
Andrew Huberman:
安德鲁·休伯曼：
I see.
我明白了。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
So it's quite dependent on the species.
所以这很大程度上取决于物种。
And there's another thing.
还有一件事。
The farther away the species are, the less likely it is, of course, that the cells will integrate.
当然，物种距离越远，细胞整合的可能性就越小。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
So think about it.
所以想一想。
It takes just a couple of weeks for the rat to make the cortex.
老鼠只需要几周的时间就能形成大脑皮层。
It takes us 20 weeks to make most of the cortical cells.
我们需要 20 周的时间才能制造出大部分皮质细胞。
So the human cells are always behind.
所以人体细胞总是落后的。
The rat is finishing development very quickly.
老鼠很快就完成了发育。
The humans are trying, but they're keeping their pace.
人类正在努力，但他们正在保持自己的步伐。
So the integration between the two species happens at some level, but it's not perfect.
所以这两个物种之间的融合在某种程度上发生了，但并不完美。
And that's actually not our goal.
这实际上不是我们的目标。
Our goal has never really been to have perfect integration.
我们的目标从来都不是真正的完美集成。
All we wanted to do is to have a better system where we can capture aspects of disease that we wouldn't be able to see in another way, or test therapeutics that we wouldn't be able to test in any other way.
我们想要做的就是拥有一个更好的系统，在其中我们可以捕获我们无法通过其他方式看到的疾病的各个方面，或者测试我们无法通过任何其他方式测试的治疗方法。
And so that's where this actually comes in handy, and it's been very useful.
这就是它真正派上用场的地方，而且非常有用。
Andrew Huberman:
安德鲁·休伯曼：
It's so interesting that for most people Again, I'm making a lot of assumptions here, but for most people, the idea of a chip, of an electrode implanted into the brain of a patient or spinal cord of a patient isn't that disturbing to them.
这太有趣了，对于大多数人来说，我在这里做了很多假设，但对于大多数人来说，芯片、植入患者大脑或患者脊髓的电极的想法并不会让他们感到不安。
No one would choose to do that in the absence of a clinical issue.
如果没有临床问题，没有人会选择这样做。
But, well, there are some people who are interested in brain augmentation through the implantation of chips to create super memory or to be able to process more bits of information in whatever capacity.
但是，有些人对通过植入芯片来增强大脑来创造超级记忆或以任何能力处理更多信息感兴趣。
But typically, it's discussed in the therapeutic context.
但通常，它是在治疗背景下讨论的。
But as soon as we hear about, for instance, a pig heart or baboon heart was transplanted into a human, all of a sudden it gets to some really core things about our humanness.
但是，例如，当我们听说猪心脏或狒狒心脏被移植到人类身上时，突然间它就触及了我们人性的一些真正核心的东西。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And then, of course, I can't help but be reminded of all the anecdotes that you hear where, oh, a patient died, had donated their heart to medicine, the heart was transferred, and then the person who received it thought that maybe they had adopted some features of-
然后，当然，我忍不住想起你听到的所有轶事，哦，一个病人死了，把他们的心脏捐献给医学，心脏被转移，然后接受它的人认为也许他们采用了一些特征——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Sure
当然可以
Andrew Huberman:
安德鲁·休伯曼：
...
...
the person's experience, and you can't really do the control experiment.
人的经验，你不能真正做对照实验。
But there's a lot of interesting questions that border on mystical.
但还有很多有趣且近乎神秘的问题。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But given that experience is mapped into the nervous system, it's not inconceivable that you would have memory traces, at least of bodily experiences, built into the organ system.
但考虑到经验被映射到神经系统中，你在器官系统中建立记忆痕迹（至少是身体经验的记忆痕迹）并非不可想象。
Although typically we think of that stuff as in the brain.
尽管我们通常认为这些东西是在大脑中的。
So, as I hear and learn more about these incredible assembloids, I'm very enthusiastic about where this is headed.
因此，当我听到并了解更多有关这些令人难以置信的组合体的信息时，我对它的发展方向非常感兴趣。
I also, of course, think that treatment of disease is the primary entry point.
当然，我也认为治疗疾病是首要切入点。
This is what-
这就是——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yes
是的
Andrew Huberman:
安德鲁·休伯曼：
...
...
as opposed to building superhumans.
而不是建造超人。
Which is, I think, why that CRISPR experiment, mutating the HIV receptor, was also disparaged.
我想，这就是为什么 CRISPR 实验（突变 HIV 受体）也遭到贬低。
There was this idea that maybe the HIV receptor, in the absence of HIV, is performing other roles related to learning and memory.
有人认为，在没有艾滋病毒的情况下，艾滋病毒受体可能正在发挥与学习和记忆相关的其他作用。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
And so there were hints of eugenic-type approaches.
因此，出现了优生型方法的迹象。
And that raises a question for me.
这给我提出了一个问题。
You mentioned that there are many genes that are associated with autism.
您提到有很多基因与自闭症有关。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I think most parents or parents-to-be don't take a test for those genes.
我认为大多数父母或准父母不会对这些基因进行测试。
There are companies like Orchid in the Bay Area now that will do deep sequencing of embryos in IVF.
现在湾区有像 Orchid 这样的公司可以对 IVF 胚胎进行深度测序。
Depending on how much you pay, they'll sequence more.
根据您支付的金额，他们会排序更多。
This was in the news a few weeks or months ago.
这是几周或几个月前的新闻。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And people start thinking, oh, this is like eugenics, right?
人们开始思考，哦，这就像优生学，对吧？
On the other hand, partner selection, who one chooses to have children with, is its own form of genetic selection.
另一方面，伴侣选择，也就是选择与谁生孩子，本身就是一种基因选择。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
They'll say, "Oh, he's very kind.
他们会说：“哦，他非常友善。
She's very kind.
她很友善。
She's very smart." People are basing their decisions, hopefully according to features that they would like to create in the offspring.
她很聪明。”人们正在做出决定，希望是根据他们希望在后代身上创造的特征。
It's not always the case.
情况并非总是如此。
So I think sometimes the boundary between what we call eugenics and mate selection and creating offspring in the purely old-fashioned way, it's blurry.
所以我认为有时我们所谓的优生学和择偶与以纯粹老式方式创造后代之间的界限是模糊的。
It becomes a continuum.
它成为一个连续体。
How far off are we from genetic testing of parents as a kind of obligatory thing-
我们距离父母基因检测成为一种强制性的事情还有多远？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Mm-hmm
嗯嗯
Andrew Huberman:
安德鲁·休伯曼：
...
...
now that we know some of the genes associated with autism?
现在我们知道一些与自闭症相关的基因了吗？
We test parents for things like Tay-Sachs, sickle cell anemia-
我们测试父母是否患有泰萨克斯病、镰状细胞性贫血——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Down syndrome
唐氏综合症
Andrew Huberman:
安德鲁·休伯曼：
...
...
congenital adrenal hyperplasia, things that are almost deterministic.
先天性肾上腺皮质增生症，这几乎是确定性的事情。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yes.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Down syndrome, trisomy.
唐氏综合症、三体症。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Mm-hmm.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
And in some countries, they'll implant embryos that are not, as we say, euploid, the proper assortment of chromosomes.
在一些国家，他们植入的胚胎不是我们所说的整倍体，即染色体的正确分类。
But in the US, typically that's discouraged.
但在美国，这种做法通常是不被鼓励的。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So how do you think about all this?
那么你如何看待这一切呢？
You're not responsible for deciding for everyone, but you're right at the leading edge of what's possible, and you can sniff what's going to be possible.
你不必为每个人做出决定，但你正处于可能性的前沿，并且你可以嗅到什么是可能的。
How much information should a person thinking about having a child have in order to make the best-informed decisions?
考虑要孩子的人应该掌握多少信息才能做出最明智的决定？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
So for some of these conditions, it's more straightforward than for others.
因此，对于其中一些条件，它比其他条件更简单。
As you were saying, some of them are very deterministic.
正如你所说，其中一些是非常确定性的。
So if you have three 21 chromosomes, you're going to have Down syndrome, and that's going to be associated with a very classic presentation.
因此，如果您有 3 条 21 号染色体，您就会患有唐氏综合症，这将与一个非常经典的表现相关。
But for others, it turns out, and I think that's where it's much more complicated than just testing and making a decision, is that what we call in genetics the penetrance of the genetic mutations is variable.
但对于其他人来说，事实证明，我认为这比测试和做出决定要复杂得多，我们在遗传学中所说的基因突变的外显率是可变的。
Meaning that you could have a genetic mutation that in one patient could cause a very severe presentation or phenotype, and another would be very mild.
这意味着您可能有一种基因突变，在一名患者中可能会导致非常严重的表现或表型，而在另一名患者中则可能非常轻微。
It's not the case for Timothy syndrome, where actually it's quite predictable.
蒂莫西综合症的情况并非如此，实际上它是可以预测的。
Most of the patients that we know, we've never identified a patient who is non-affected, and they're very severely affected.
在我们认识的大多数患者中，我们从未发现过未受影响的患者，而且他们受到的影响非常严重。
But there are other conditions that are much more common.
但还有其他更常见的情况。
I think the classic one is a deletion that is happening on chromosome 22, the so-called 22q11.2 deletion syndrome, known by many names, velocardiofacial syndrome, DiGeorge syndrome, known by many names because it's so common.
我认为最经典的是发生在 22 号染色体上的缺失，即所谓的 22q11.2 缺失综合征，有很多名字，腭心面综合征，迪乔治综合征，有很多名字，因为它很常见。
It's actually the most common microdeletion in humans, about one in 3,000 births.
它实际上是人类中最常见的微缺失，大约每 3000 个新生儿中就有一个发生。
Now, the condition is associated with cardiac issues, immune conditions, many of which can actually be addressed medically.
现在，这种情况与心脏问题、免疫问题有关，其中许多问题实际上可以通过医学解决。
But it also comes with a 30% risk for schizophrenia.
但它也有 30% 的患精神分裂症的风险。
Andrew Huberman:
安德鲁·休伯曼：
30%?
30%？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
So you think the general population is 1%, so this is about 30 times higher.
所以你认为一般人口是 1%，所以这个数字大约高出 30 倍。
It also comes with a 30% risk of autism.
它还具有 30% 的自闭症风险。
But you could also not have any of this.
但你也可以没有这些。
There are individuals who are carrying the 22q11.2 deletion, which is a large deletion, by the way.
顺便说一下，有些人携带 22q11.2 缺失，这是一个大的缺失。
There's 60 genes that are gone in the classic deletion, and yet still carry it around and have minimal defect or phenotypes.
有 60 个基因在经典缺失中消失了，但仍然携带着它，并且缺陷或表型最小。
Andrew Huberman:
安德鲁·休伯曼：
Do we test for this 22q?
我们测试这个 22q 吗？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
This is tested generally these days, yes, because it's so common.
是的，现在普遍对此进行了测试，因为它很常见。
But I think that the challenge is this problem of penetrance, and in some patients, and we don't know what the context is.
但我认为挑战在于外显率问题，在某些患者中，我们不知道具体情况是什么。
Each of us has a very complex genetic background.
我们每个人都有非常复杂的遗传背景。
So it could be that the same mutation, two different individuals will have different levels of severity because one of them perhaps compensates much better for whatever reason.
因此，同一个突变，两个不同的个体可能会具有不同的严重程度，因为无论出于何种原因，其中一个人可能会补偿得更好。
There is a lot of stochastic forces in development, and if a cell is much faster at opening the other gene, like the similar gene that is unmutated, and in the other case it wasn't, or maybe there are other environmental factors that are interacting.
发育过程中存在很多随机力量，如果一个细胞打开另一个基因的速度要快得多，比如未突变的相似基因，而在另一种情况下则不然，或者可能还有其他环境因素在相互作用。
But the other possibility is that the genetic background that we have is very different.
但另一种可能性是我们的遗传背景非常不同。
And so we're still in early days of truly understanding what are the effects of the genetic backgrounds in modulating the severity of these conditions.
因此，我们仍处于真正了解遗传背景对调节这些疾病严重程度的影响的早期阶段。
But in itself, it's a very interesting question, why some individuals can have a massive deletion of 60 genes and yet still move around.
但就其本身而言，这是一个非常有趣的问题，为什么有些人可以大量删除 60 个基因，但仍然可以四处走动。
So I think that's going to be a lot of interesting biology to discover behind this.
所以我认为这背后将会有很多有趣的生物学有待发现。
And then, of course, we know that there are differences between animals and humans.
当然，我们知道动物和人类之间存在差异。
That we already know, that very often a mutation that would be very severe in a human has almost no defect in an animal model, partly because that gene maybe plays a different role, or perhaps the genetic background is very different.
我们已经知道，通常在人类中非常严重的突变在动物模型中几乎没有缺陷，部分原因是该基因可能发挥不同的作用，或者遗传背景可能非常不同。
Andrew Huberman:
安德鲁·休伯曼：
Speaking of which, what are some of the other diseases that are being modeled and studied with assembloids?
说到这里，还有哪些其他疾病正在使用组装体进行建模和研究？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
So Timothy syndrome has sort of been the first example, partly because it was some of the first neurons that were derived from iPS cells and from patients with neurodevelopmental disorders in those early days, and also partly because it's the disease that we studied so much on all possible angles.
因此，蒂莫西综合征算是第一个例子，部分原因是它是最早源自 iPS 细胞和早期神经发育障碍患者的神经元，部分原因是我们从所有可能的角度对这种疾病进行了大量研究。
First with 2D neurons, then with 3D organoids, then with assembloids.
首先使用 2D 神经元，然后使用 3D 类器官，然后使用组合体。
Then at one point, and I like to say that a therapy became self-evident, so to speak.
然后在某个时刻，我想说，一种疗法变得不言而喻。
I was not thinking that we would develop a therapy for Timothy syndrome, not in the near future.
我没想到我们会开发一种治疗蒂莫西综合症的疗法，不会在不久的将来。
But at one point, we just accumulated enough biological information that you just look at it and you say, "Oh, this is exactly what we need to do." And it turns out that, and this we did about five years ago, that we understood so well how this channel is processed in the cells and what it causes, that at one point, we realized that all we need to do is generate this tiny piece of nucleic acid that we can get inside the cells.
但在某一时刻，我们刚刚积累了足够的生物信息，你只要看看它就会说，“哦，这正是我们需要做的。”事实证明，我们大约五年前就做到了这一点，我们非常了解这个通道在细胞中是如何处理的以及它会引起什么，以至于在某一时刻，我们意识到我们需要做的就是生成这一小段核酸，我们可以将其进入细胞内部。
It will go in, switch the way the channel is actually processed, and rescue or reverse the phenotypes.
它将进入，切换通道的实际处理方式，并拯救或逆转表型。
And it turns out that every single defect that we've described over the past 15 years in the studies can be rescued by just adding the tiny piece of nucleic acid.
事实证明，我们在过去 15 年的研究中描述的每一个缺陷都可以通过添加一小段核酸来修复。
It's almost like a gene therapy in a way.
在某种程度上，这几乎就像基因疗法。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
It just doesn't involve a virus.
它只是不涉及病毒。
And so this is the first disease, and we're preparing for a clinical trial.
这是第一种疾病，我们正在准备临床试验。
These patients are very rare, so I've been traveling around the world trying to find most patients with Timothy syndrome, even try to understand the complexity of the disease, the severity of the disease.
这些患者非常罕见，所以我一直在世界各地旅行，试图找到大多数蒂莫西综合征患者，甚至试图了解这种疾病的复杂性、病情的严重性。
And so we now have a large cohort of the patients ready, and we're preparing for the first clinical trial.
现在我们已经准备好了一大群患者，我们正在为第一次临床试验做准备。
We already started producing the drug.
我们已经开始生产这种药物。
Andrew Huberman:
安德鲁·休伯曼：
So it's druggable.
所以是可以下药的。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
We think that it's druggable, but this will be the first therapeutic for a psychiatric disease that has been exclusively developed with human stem cell models without anything else.
我们认为它是可以药物化的，但这将是第一个专门用人类干细胞模型开发的精神疾病治疗方法，没有其他任何东西。
And I actually joke about it.
我实际上是开玩笑的。
Probably you knew very well Lubert Stryer.
也许您非常了解 Lubert Stryer。
Andrew Huberman:
安德鲁·休伯曼：
He developed the so-called gene chip, early days of evaluating genes in different cells.
他开发了所谓的基因芯片，早期评估不同细胞中的基因。
He passed away recently.
他最近去世了。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
He passed away recently.
他最近去世了。
Andrew Huberman:
安德鲁·休伯曼：
Sadly.
可悲的是。
He would bring coffee by.
他会带咖啡过来。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
He would bring coffee by.
他会带咖啡过来。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
He had their office across our D222, so he would come at 9:00.
他的办公室就在我们 D222 对面，所以他会在 9:00 来。
Andrew Huberman:
安德鲁·休伯曼：
Anyone who's ever taken biochemistry, the big red biochemistry book, Stryer-
任何学过生物化学的人，这本红色的生物化学大书，斯特赖尔——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
It's Stryer
这是斯特莱尔
Andrew Huberman:
安德鲁·休伯曼：
...
...
that's Lubert.
那是鲁伯特。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
That's what it is.
就是这样。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
He was an amazing communicator.
他是一位出色的沟通者。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
I think above anything, he was just a larger-than-life figure who able to go with you in a conversation from a deep molecular mechanism to what does it actually mean?
我认为最重要的是，他只是一个具有传奇色彩的人物，能够与您从深层分子机制到其实际含义进行对话？
Andrew Huberman:
安德鲁·休伯曼：
Yeah, a very kind person, too.
是啊，也是一个非常善良的人。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
So my last conversation with Lubert, which happened I think a month before he passed away, he came to my office at Stanford.
所以我与鲁伯特的最后一次谈话发生在他去世前一个月，他来到了我在斯坦福大学的办公室。
We would meet every few months.
我们每隔几个月就会见面。
He was just so interested about how this is evolving.
他只是对事情的演变非常感兴趣。
And I remember he was sitting in my office, and then he wanted to know, "Where are you with Timothy syndrome?" The paper was still under revision at Nature.
我记得他坐在我的办公室里，然后他想知道，“你患有蒂莫西综合症吗？”这篇论文仍在《自然》杂志上进行修订。
It was coming in the next few months.
它将在接下来的几个月内到来。
And then he said, "The saddest thing is I'm not going to see this paper published.
然后他说：“最悲伤的是我不会看到这篇论文发表。
I want to see this paper published." And I said, "Why?" And he goes, "Do you know what you've done?" Because he would usually use with that intensity, and I thought, "Oh my God, maybe he realized we've made the mistake somewhere in the paper, or it's going to point out to some flaw." And then he says, "No, you've demystified the psychiatric disease." I said, "What do you mean?" He said, "Well, you think about psychiatric disorders.
我希望看到这篇论文发表。”我说：“为什么？”他说：“你知道你做了什么吗？”因为他通常会如此强烈地使用，我想，“天哪，也许他意识到我们在论文中的某个地方犯了错误，或者它会指出一些缺陷。”然后他说：“不，你已经揭开了精神疾病的神秘面纱。”我说：“你什么意思？”他说：“好吧，你想想精神疾病。
They're so esoteric, so complex, mental processes that are arising, behavioral changes, and yet you went all the way down to a molecular defect, a point mutation, figure out the rest, and now you're on a verge of potentially perhaps not reversing, but at least improving some." So he was so excited about this, and I think I never think enough perhaps about it.
它们是如此深奥、如此复杂，正在出现的心理过程、行为变化，但你一路深入到分子缺陷、点突变，找出其余的部分，现在你正处于可能无法逆转的边缘，但至少有所改善。”所以他对此非常兴奋，我想我可能对此想得还不够。
But he was the last one who sort of reminded about how important it is actually to focus on these genetic disorders of which we know more.
但他是最后一个提醒我们关注这些我们了解更多的遗传性疾病实际上是多么重要的人。
Of course, this is just one form of disease.
当然，这只是疾病的一种形式。
There are so many more afterwards.
后面还有很多。
But our hope is that just by understanding and learning from this, we're going to be able to apply to other disorders.
但我们希望，通过理解并从中学习，我们将能够应用于其他疾病。
So another one that we're studying now, there are forms of epilepsy which are very difficult to study.
我们现在正在研究的另一件事是，有些形式的癫痫症很难研究。
There are intractable forms of epilepsies.
癫痫有多种难治性形式。
Patients who have some of these genetic mutations, whether they're in an ion channel or in molecules that are important for cells to stick with each other, they can cause 60 seizures a day.
患有某些基因突变的患者，无论是在离子通道中还是在对细胞相互粘附很重要的分子中，每天都会引起 60 次癫痫发作。
So they're really devastating conditions that are actually causing impairment just by having those seizures every single day for 10, 15 years.
因此，它们确实是毁灭性的疾病，仅仅通过 10、15 年每天的癫痫发作就会造成损害。
And so those are a really big issue right now.
所以这些现在是一个非常大的问题。
So we've been focusing a lot on trying to build now models for these epileptic seizures.
因此，我们现在一直致力于为这些癫痫发作建立模型。
Either through in vitro studies or after we transplant, and then we study more complex networks in patients.
无论是通过体外研究还是在移植后，我们都会在患者身上研究更复杂的网络。
And then, of course, intellectual disability, so severe intellectual disability, schizophrenia, forms of schizophrenia.
当然，还有智力障碍，严重的智力障碍，精神分裂症，精神分裂症的各种形式。
So we've been studying now for almost 12, 13 years, 22q11 deletion syndrome.
所以我们现在已经研究 22q11 缺失综合征近 12、13 年了。
We think it's so like an entry point.
我们认为这就像一个切入点。
It's the highest genetic risk factor that we know of for schizophrenia, so we think it may give us some windows into how molecular defects arise.
这是我们所知的精神分裂症最高的遗传风险因素，因此我们认为它可能为我们提供一些了解分子缺陷如何产生的窗口。
So I think you can think of most psychiatric and neurological conditions that you can study now, as long as they have a strong biological genetic component.
所以我认为你可以想到现在可以研究的大多数精神和神经疾病，只要它们具有强大的生物遗传成分。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
So I think those that have a social component, those that are triggered by social stress, let's say, right, like forms of anxiety, depression, those are much more challenging to study because, of course, we can mimic that social environment.
因此，我认为那些具有社会成分的因素，那些由社会压力引发的因素，比如焦虑、抑郁的形式，这些因素的研究更具挑战性，因为我们当然可以模仿那种社会环境。
Andrew Huberman:
安德鲁·休伯曼：
Can I make a request?
我可以提出请求吗？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Please.
请。
Andrew Huberman:
安德鲁·休伯曼：
That someone in your lab try to tackle dystonia.
你实验室里的某个人试图解决肌张力障碍。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Mm-hmm.
嗯嗯。
Yes.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I had the experience last year of somebody contacting me.
去年我就有过有人联系我的经历。
I get contacted a lot for requests to help with horribly sad situations, right-
很多人联系我请求帮助解决极其悲伤的情况，对吧-
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
as one does if you're in the neuroscience field.
就像你从事神经科学领域的人所做的那样。
Typically, it's people with visual deficits who've gone blind or are losing their vision.
通常情况下，失明或正在丧失视力的是有视力缺陷的人。
This time it was a mother of a young kid who had a form of dystonia, where he was essentially just going from a, by all accounts, normal-appearing and acting kid to having basically no ability to move or do anything.
这次是一位患有某种肌张力障碍的小孩的母亲，从各方面来看，他基本上只是从一个外表和行为正常的孩子变成了基本上没有移动或做任何事情的能力。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Couldn't go to camp, couldn't go to school, and it was just a very tragic situation.
无法去露营，无法上学，这是一个非常悲惨的情况。
He had a neurosurgery.
他接受了神经外科手术。
I will know soon how he's doing.
我很快就会知道他怎么样了。
But I learned that these dystonias are not super uncommon.
但我了解到这些肌张力障碍并不少见。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I mean, fortunately, they're uncommon enough, but you just have to witness one of these stories.
我的意思是，幸运的是，它们并不常见，但你只需见证其中一个故事即可。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And it turns out there is a genetic basis for these.
事实证明，这些都是有遗传基础的。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yes.
是的。
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So I'm putting in a vote for dystonia.
所以我投票支持肌张力障碍。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
No.
不。
Andrew Huberman:
安德鲁·休伯曼：
For the parent and for the child, it's devastating.
对于父母和孩子来说，这都是毁灭性的。
And we don't hear from these people very often, and there are sociological reasons for that.
我们很少收到这些人的消息，这是有社会学原因的。
Certain diseases are underrepresented in the public sphere.
某些疾病在公共领域的代表性不足。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Autism we hear a lot about, not just because of the prevalence, but because we have a certain affinity to kids, and that explains that.
我们经常听到自闭症，不仅仅是因为自闭症的流行，还因为我们对孩子有一定的亲和力，这就解释了这一点。
A discussion for another time.
下次再讨论。
But these dystonias are very hard to witness in a way that has made them kind of veiled-
但这些肌张力障碍很难以某种方式被目睹，这使得它们有点被掩盖了——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
to the public, but they're very, very detrimental, and it would be amazing-- I know you already have a lot on your plate, but I'm putting in a strong vote for dystonia.
对公众来说，但它们非常非常有害，这将是令人惊奇的——我知道你已经有很多事情要做，但我强烈支持肌张力障碍。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
But we are actually working on dystonias-
但我们实际上正在研究肌张力障碍 -
Andrew Huberman:
安德鲁·休伯曼：
Great
太棒了
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
...
...
because they are devastating conditions, and there are now genetic mutations that cause really severe forms of dyskinesia and dystonia, so really uncontrollable movements in these kids that are really devastating for social functioning and, in general, for development.
因为它们是毁灭性的疾病，而且现在的基因突变会导致非常严重的运动障碍和肌张力障碍，因此这些孩子的运动确实无法控制，这对社会功能和总体发展来说确实是毁灭性的。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
And so we do know a little bit about the biology behind it.
所以我们确实对其背后的生物学了解一点。
We do know that the basal ganglia, this deep structure into the brain, is very important for movement.
我们确实知道基底神经节（大脑的深层结构）对于运动非常重要。
We very often stimulate that brain region for Parkinson's disease or parts of that circuitry, so we know it's very important.
我们经常刺激帕金森病的大脑区域或部分电路，所以我们知道这非常重要。
So we've been trying to rebuild it-
所以我们一直在努力重建它-
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
...
...
in a dish.
在一个盘子里。
So we now can build some of the circuits.
现在我们可以构建一些电路了。
We call them loop assemblies, where essentially you can put a cortex, and we've made the striatum.
我们称它们为循环组件，本质上你可以在其中放置一个皮质，我们已经制作了纹状体。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
And then you put parts of the mesencephalon in the midbrain and the thalamus.
然后将中脑的一部分放入中脑和丘脑中。
Andrew Huberman:
安德鲁·休伯曼：
Awesome.
太棒了。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
And the cells connect in a loop-
细胞连接成一个循环-
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
...
...
and now they have activity.
现在他们有活动了。
So you can now induce mutations at various levels of the circuit and see where is that mutation most important.
因此，您现在可以在电路的各个级别诱导突变，并查看该突变在哪里最重要。
So let's say if you were to develop a gene therapy-
假设你要开发一种基因疗法——
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
...
...
where would you deliver that gene?
你会将该基因传递到哪里？
If you were to choose, if you can't deliver it in the entire brain.
如果你要选择的话，如果你不能将它传递到整个大脑。
So these are really early days, but I think it can be applied.
所以现在还处于早期阶段，但我认为它可以应用。
And I think in general, you were mentioning this before about autism, right, and even the ability of communicating these disorders or how much awareness there is, right?
我想总的来说，你之前提到过关于自闭症，对吧，甚至还有沟通这些疾病的能力或者有多少意识，对吧？
I think when I refer to autism, I generally refer to the severe forms and profound autism.
我想当我提到自闭症时，我通常指的是严重形式和深度自闭症。
Andrew Huberman:
安德鲁·休伯曼：
Yes.
是的。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
And as we discussed earlier, there's certainly a continuum, and there are many individuals that are high-functioning, right?
正如我们之前讨论的，肯定存在一个连续体，并且有很多高功能的个体，对吧？
They have high skills.
他们拥有很高的技能。
They may lack certain social skills, but they have other skills.
他们可能缺乏某些社交技能，但他们有其他技能。
They're different.
他们是不同的。
They're productive in society.
他们在社会上富有生产力。
I am not talking about discovering or developing a therapeutic for any of these individuals.
我并不是在谈论为这些人发现或开发治疗方法。
We are talking about the profound forms of autism, the ones that actually the parents are still struggling to even communicate about, right?
我们谈论的是自闭症的深刻形式，实际上父母们仍然在努力沟通，对吗？
The kids who may never go to school, may never be able to actually live on their own.
那些可能永远不会上学的孩子，可能永远无法真正独立生活。
The same is the case for many of these patients with severe dystonias.
许多患有严重肌张力障碍的患者也有同样的情况。
So I think it's very important because I think in the case of autism, partly because it's being talked about, and again, because it is a spectrum, it's also part of the identity, right, of a part of the population.
所以我认为这非常重要，因为我认为就自闭症而言，部分是因为它正在被谈论，而且，因为它是一个谱系，它也是一部分人口的身份的一部分，对吧。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
And that's absolutely fine.
那绝对没问题。
I think perhaps at one point having different terms-
我认为也许在某一时刻有不同的术语——
Andrew Huberman:
安德鲁·休伯曼：
Yeah, that would be useful
是的，那会有用的
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
...
...
it may be useful because we were talking before about terminology, which is so important.
它可能很有用，因为我们之前讨论过术语，这非常重要。
So perhaps that would be useful at one point to define the border between profound forms of autism and forms of autism that are not really a disease.
因此，也许这在某种程度上有助于定义深刻形式的自闭症和并非真正疾病的自闭症形式之间的界限。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
As well-meaning as the psychiatric community is, it's bound by this DSM whatever number-
尽管精神病学界是善意的，但无论数字多少，它都受到 DSM 的约束——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yes
是的
Andrew Huberman:
安德鲁·休伯曼：
...
...
it happens to be on.
它恰好打开了。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Five.
五。
Andrew Huberman:
安德鲁·休伯曼：
For understandable reasons, but I think better nomenclature-
出于可以理解的原因，但我认为更好的命名法 -
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Absolutely
绝对
Andrew Huberman:
安德鲁·休伯曼：
...
...
would really help.
真的会有帮助。
It has societal implications.
它具有社会影响。
It has to do with how we treat people generally.
这与我们一般对待他人的方式有关。
Actually, just as a quick reflection, years ago, I sat down with Bob Desimone who-
事实上，正如我快速反思的那样，几年前，我与鲍勃·德西蒙 (Bob Desimone) 坐在一起，他——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Mm
毫米
Andrew Huberman:
安德鲁·休伯曼：
...
...
a world-class neuroscientist, as you know, but he was the head of the National Institutes of Mental Health at that time, and he said to me directly, it was over lunch, he said, "Do you know why there's so much more money spent trying to understand autism as opposed to schizophrenia?" At least that was the case at the time, and I think it is still now.
正如你所知，他是一位世界级的神经科学家，但当时他是美国国家心理健康研究所的所长，他直接对我说，午餐时，他说，“你知道为什么花在了解自闭症而不是精神分裂症上的钱多得多吗？”至少当时是这样，我想现在仍然如此。
I said, "No." And he said, "Because the strong genetic link in schizophrenia means that oftentimes the parents are struggling as well.
我说：“不。”他说，“因为精神分裂症的强烈遗传联系意味着父母常常也会陷入困境。
They're not bringing their children in." And with severe-- nowadays it's not politically correct to call them schizophrenics.
他们不会带孩子进来。”如今，称他们为精神分裂症患者在政治上是不正确的。
For people with severe schizophrenia, it's scary to be around.
对于患有严重精神分裂症的人来说，周围是很可怕的。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
It's really scary, whereas with autism, even in the profound cases, these are children, and as a human species, we naturally have this, we want to care for our young.
这真的很可怕，而对于自闭症，即使在最严重的情况下，这些都是孩子，作为人类，我们自然有这个，我们想照顾我们的孩子。
And it just pulls on us.
它只是吸引我们。
And he said, "So there's been this incredible lobby of the government, and therefore pressure on NIH to direct funds towards studying autism far, far less for schizophrenia." It's interesting in light of the homeless problem in California and elsewhere, and the huge-
他说：“政府的游说令人难以置信，因此国家卫生研究院面临着将资金用于研究自闭症的压力，远远少于精神分裂症的研究。”鉴于加州和其他地方的无家可归问题，以及巨大的——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
amount of mental disease and drug addiction.
精神疾病和毒瘾的数量。
I think nowadays there's a kind of a broader understanding of brain diseases as diseases that people suffer from, as opposed to-
我认为现在人们对脑部疾病有了更广泛的理解，将其视为人们患有的疾病，而不是——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
cold mothering or something-
冷漠的母爱什么的——
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
like ridiculous theories like that.
像这样荒谬的理论。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I definitely want to talk a little bit about you.
我确实想谈谈你。
Not getting too personal here, but I've known you for some years, and from the first time I met you, it was clear you were going to work on something important, you were going to figure it out, and your work ethic is something to behold.
这里不想太私人化，但我已经认识你很多年了，从我第一次见到你开始，很明显你将致力于一些重要的事情，你将弄清楚它，你的职业道德是值得关注的。
Without inflating numbers how much time are you spending these days either at the computer working on things related to your science, or in the lab, or thinking about your science?
在不夸大数字的情况下，您这些天花了多少时间在计算机上处理与您的科学相关的事情，或者在实验室里，或者思考您的科学？
Of your waking hours, what percentage?
占你醒着的时间的比例是多少？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Well, I've never seen this as work, so probably all the time.
嗯，我从来不认为这是工作，所以可能一直都是。
I think about this all the time.
我一直在想这个。
Luckily now, of course, I have a lab of incredible scientists, and many of them now have their own labs.
当然，幸运的是，我现在拥有一个由令人难以置信的科学家组成的实验室，其中许多人现在都有自己的实验室。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
And we've been teaching so many people around the world now, more than 350 labs around the world to just implement this technology very systematically through courses that we do at Stanford.
我们现在已经在全世界范围内教了很多人，在全世界有 350 多个实验室，通过我们在斯坦福大学开设的课程非常系统地实施这项技术。
So I feel we've amplified so much that there's always something happening.
所以我觉得我们已经放大了太多，以至于总会有一些事情发生。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
But I've never seen it, honestly, as work.
但老实说，我从未将其视为工作。
I think it's so fun to think about the human brain.
我认为思考人脑非常有趣。
It's certainly fascinating to think about the biology of these conditions, and of course for me, training as a physician, I think seeing firsthand some of the devastating effects of psychiatric disorders, which it was a very strong motivation to actually go into neuroscience.
思考这些病症的生物学确实很有趣，当然，对我来说，作为一名医生接受培训，我认为亲眼目睹精神疾病的一些破坏性影响，这是真正进入神经科学的一个非常强烈的动机。
Andrew Huberman:
安德鲁·休伯曼：
I'll never forget when your first paper was published as a postdoc.
我永远不会忘记你作为博士后发表的第一篇论文是什么时候。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yes.
是的。
Andrew Huberman:
安德鲁·休伯曼：
You brought in a cake for everyone else.
你给其他人带来了蛋糕。
I don't know if you remember that.
我不知道你还记不记得。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
No, I don't.
不，我不。
Andrew Huberman:
安德鲁·休伯曼：
You brought in cake for everyone else.
你给其他人带来了蛋糕。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
I don't remember that.
我不记得了。
Andrew Huberman:
安德鲁·休伯曼：
And I was like, "This is the first time I've ever observed this.
我当时想，“这是我第一次观察到这一点。
This is awesome." At the time, I was eating cake.
这太棒了。”当时我正在吃蛋糕。
I don't eat cake anymore.
我不再吃蛋糕了
With each successive decade, I get stricter and stricter with my eating.
每过十年，我对饮食的要求就越来越严格。
I still enjoy food very much.
我仍然非常享受食物。
But it really speaks to your spirit and your generosity.
但这确实体现了你的精神和慷慨。
I feel so blessed that someday I'll be able to say "I can tell you stories from way back when, D222, when we took over that room without permission." I think we just did it.
我感到非常幸运，有一天我可以说“我可以告诉你很久以前的故事，D222，当时我们未经许可接管了那个房间。”我想我们刚刚做到了。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
I think we just took it, yeah.
我想我们刚刚接受了它，是的。
Andrew Huberman:
安德鲁·休伯曼：
Which is the way to do it.
这是做到这一点的方法。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
It's unincorporated.
它是非法人组织。
Andrew Huberman:
安德鲁·休伯曼：
Well, Ben was the one who always said, "Ask for forgiveness, not permission," within the proper context of doing science.
嗯，本总是在正确的科学背景下说“请求宽恕，而不是许可”。
He was famous for bringing his experiments to talks as a postdoc so he wouldn't lose time on his experiments.
作为博士后，他因将实验带到演讲中而闻名，这样他就不会在实验上浪费时间。
And then I think at one point, there's a story where someone had called him out and said, "Hey, why are you bringing your experiments to seminars?
然后我想有一次，有一个故事，有人把他叫出来说：“嘿，你为什么要把你的实验带到研讨会上？
Everyone else is drinking coffee and doing stuff." And he said, "Because I don't know if your seminar is going to be any good, and I don't want to waste the time on my experiments." He had such an incredible spirit about just ceaseless pursuit of knowledge, which clearly you do as well.
其他人都在喝咖啡，做事。”他说：“因为我不知道你们的研讨会是否有好处，而且我不想把时间浪费在实验上。”他有一种令人难以置信的不断追求知识的精神，显然你也有这种精神。
Sergiu, I am so grateful for you taking time out of your immensely busy schedule to come here and educate us all on this incredible technology that you've developed and that other laboratories are now using.
Sergiu，我非常感谢您从极其繁忙的日程中抽出时间来到这里，向我们所有人介绍您开发的以及其他实验室正在使用的这项令人难以置信的技术。
I realize it's a field, but clearly a field that you've been seminal in launching, and I think for a lot of people, if they were to just hear about organoids in the news or hear, okay, we took these neurons, and we were able to grow them in a dish, and they formed some things that resemble circuits, and we're putting them into mice, they'd say, "This sounds a lot like a parlor trick or something that scientists do to keep themselves busy with our tax dollars." But I just want to thank you because you've beautifully illustrated the linear fashion in which you've gone from human disease to building up technologies, one cell type in a dish, two cell types, circuits in a dish, three synapses, modeling, using drugs and other approaches, genetic therapies, to figure out what actually needs to be fixed, going back into patients, which is super exciting.
我意识到这是一个领域，但显然是你发起的一个具有开创性的领域，我想对于很多人来说，如果他们只是在新闻中听到类器官，或者听到，好吧，我们拿了这些神经元，我们能够将它们培养在培养皿中，它们形成一些类似于电路的东西，然后我们将它们放入老鼠体内，他们会说，“这听起来很像一个客厅把戏，或者是科学家们为了让自己忙于我们的税收而做的事情。”但我只是想感谢你，因为你完美地阐释了从人类疾病到建立技术的线性方式，培养皿中的一种细胞类型，两种细胞类型，培养皿中的电路，三个突触，建模，使用药物和其他方法，基因疗法，找出真正需要修复的东西，回到患者身上，这是超级令人兴奋的。
I'm absolutely convinced this is the way science is going to be done on the brain to cure neurologic and psychiatric diseases.
我绝对相信这就是对大脑进行科学研究以治疗神经系统和精神疾病的方法。
I'm absolutely convinced because animal models, while they have their place, they just can't recapitulate everything we're interested in, and we know that, as you mentioned, from other fields.
我绝对相信，因为动物模型虽然占有一席之地，但它们无法概括我们感兴趣的所有内容，正如您提到的，我们从其他领域知道这一点。
So whatever we have to do to keep you going.
因此，我们必须尽一切努力让您继续前进。
You look younger than the last time I saw you which was a while ago.
你看起来比我不久前上次见到你时还要年轻。
So you told me before we started, you walk a lot.
所以在我们开始之前你告诉我，你走了很多路。
How many steps a day are you doing?
您每天走多少步？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
I do more than 12,000, 15,000, for sure.
我肯定做了超过 12,000、15,000 个。
Andrew Huberman:
安德鲁·休伯曼：
So you're walking to and from work?
那么你是步行上下班吗？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah, and I walk all the time.
是的，而且我一直走路。
I like to walk, especially when I travel.
我喜欢散步，尤其是旅行时。
I visit a lot, Europe and parts of the world, and I love to just walk, and art is the only other thing that I do-
我去过很多地方，欧洲和世界各地，我喜欢散步，艺术是我唯一做的其他事情 -
Andrew Huberman:
安德鲁·休伯曼：
Oh, yeah?
哦，是吗？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
...
...
other than science.
除了科学之外。
Andrew Huberman:
安德鲁·休伯曼：
Really?
真的吗？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
I love art.
我热爱艺术。
Andrew Huberman:
安德鲁·休伯曼：
Do you paint?
你画画吗？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
I used to paint.
我以前画画。
Right now, it's mostly thinking about art and like-
现在，主要是在思考艺术之类的——
Andrew Huberman:
安德鲁·休伯曼：
Okay
好的
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
...
...
I've seen most museums in Europe at this point several times.
我已经多次参观过欧洲的大多数博物馆。
Andrew Huberman:
安德鲁·休伯曼：
Whose art is exciting you now?
现在谁的艺术让你兴奋？
I'm fascinated by it.
我对它着迷。
I love art, but whose art are you intrigued by lately?
我喜欢艺术，但你最近对谁的艺术感兴趣？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Well, my favorites have always been Impressionists, but then I go through phases and so I love all art as an expression, and I think that's sort of like a-- I walk a lot, museums.
嗯，我最喜欢的一直是印象派，但后来我经历了各个阶段，所以我喜欢所有艺术作为一种表达方式，我认为这有点像——我经常散步，博物馆。
I think you could probably trace Where I've done most of the walking, and it's probably done in museums or in California walking at night and so like discussing science with students or others.
我想你可能会追踪到我大部分步行的地方，可能是在博物馆或在加利福尼亚州晚上散步，就像与学生或其他人讨论科学一样。
Andrew Huberman:
安德鲁·休伯曼：
Fantastic.
太棒了。
And none of this biohacking nonsense.
这些生物黑客攻击都不是废话。
You eat one meal a day.
你一天吃一顿饭。
That's how you stay so fit.
这就是你保持健康的方式。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
I generally eat one meal a day, yeah.
我一般一天只吃一顿饭，是的。
Andrew Huberman:
安德鲁·休伯曼：
How long have you been doing that?
你这样做多久了？
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Years, I think.
几年了，我想。
Years.
年。
I think in medical school initially as a necessity because I grew up in Romania, and I went to medical school there, and there wasn't really dedicated time for research.
我认为最初上医学院是必要的，因为我在罗马尼亚长大，我在那里上过医学院，并且没有真正专门的时间进行研究。
So I had no option but to do my experiments either very early in the morning or very late at night.
所以我别无选择，只能在清晨或深夜进行实验。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
So there would be very little time to actually eat, to be honest, at that time.
所以说实话，那个时候真正吃饭的时间很少。
So I felt I was running all the time doing experiments or clinical work.
所以我觉得我一直在跑步做实验或临床工作。
Andrew Huberman:
安德鲁·休伯曼：
Oh, like I said, your vigor seems to be just increasing with time.
哦，就像我说的，你的活力似乎随着时间的推移而增强。
It's really wonderful.
真是太棒了。
Clearly, you've found the career path for you, and it's going to benefit us all.
显然，您已经找到了适合自己的职业道路，这将使我们所有人受益。
It already has.
已经有了。
So please come back and tell us about your progress-
所以请回来告诉我们你的进展-
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Absolutely
绝对
Andrew Huberman:
安德鲁·休伯曼：
...
...
in six months, a year, whenever the time is right, we'll have you back.
六个月后，一年后，只要时机成熟，我们就会让你回来。
And once again, thanks for doing everything you do.
再次感谢您所做的一切。
In this time of hearing so much negative news and thinking science is so hobbled and all this stuff, science needs support, obviously.
在这个听到如此多负面新闻并认为科学如此步履蹒跚的时代，科学显然需要支持。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But what's that saying you see on the internet?
但是您在互联网上看到的说法是什么？
"Not all superheroes wear capes." You're doing God's work, so thank you.
“并非所有超级英雄都穿着斗篷。”你正在做上帝的工作，所以谢谢你。
Dr. Sergiu Pașca:
塞尔吉乌·帕斯卡博士：
Thank you so much.
非常感谢。
Thank you.
谢谢。
Andrew Huberman:
安德鲁·休伯曼：
Thank you for joining me for today's discussion with Dr. Sergiu Pasca.
感谢您参加今天与 Sergiu Pasca 博士的讨论。
To learn more about his work, please see the links in the show note captions.
要了解有关他的作品的更多信息，请参阅演出注释标题中的链接。
If you're learning from and/or enjoying this podcast, please subscribe to our YouTube channel.
如果您正在学习和/或喜欢此播客，请订阅我们的 YouTube 频道。
That's a terrific zero-cost way to support us.
这是支持我们的绝佳零成本方式。
In addition, please follow the podcast by clicking the follow button on both Spotify and Apple.
此外，请通过单击 Spotify 和 Apple 上的关注按钮来关注播客。
And on both Spotify and Apple, you can leave us up to a five-star review, and you can now leave us comments at both Spotify and Apple.
在 Spotify 和 Apple 上，您可以给我们留下五星级的评论，现在您可以在 Spotify 和 Apple 上给我们留下评论。
Please also check out the sponsors mentioned at the beginning and throughout today's episode.
另请查看今天节目开头和整个节目中提到的赞助商。
That's the best way to support this podcast.
这是支持这个播客的最佳方式。
If you have questions for me or comments about the podcast or guests or topics that you'd like me to consider for the Huberman Lab podcast, please put those in the comments section on YouTube.
如果您对我有疑问，或者对播客或嘉宾有意见，或者您希望我为 Huberman Lab 播客考虑的主题，请将这些意见放入 YouTube 的评论部分。
I do read all the comments.
我确实阅读了所有评论。
For those of you that haven't heard, I have a new book coming out.
对于那些还没有听说过的人，我即将出版一本新书。
It's my very first book.
这是我的第一本书。
It's entitled "Protocols: An Operating Manual for the Human Body." This is a book that I've been working on for more than five years, and that's based on more than 30 years of research and experience, and it covers protocols for everything from sleep to exercise to stress control, protocols related to focus and motivation, and of course, I provide the scientific substantiation for the protocols that are included.
它的标题是“协议：人体操作手册”。这是我花了五年多时间编写的一本书，它基于 30 多年的研究和经验，涵盖了从睡眠到运动到压力控制的各个方面的方案，以及与注意力和动机相关的方案，当然，我还为所包含的方案提供了科学依据。
The book is now available by presale at protocolsbook.com.
该书现已在protocolbook.com 上预售。
There you can find links to various vendors.
在那里您可以找到各个供应商的链接。
You can pick the one that you like best.
您可以选择您最喜欢的一个。
Again, the book is called "Protocols: An Operating Manual for the Human Body." And if you're not already following me on social media, I am hubermanlab on all social media platforms.
同样，这本书的名字是“协议：人体操作手册”。如果您还没有在社交媒体上关注我，我是所有社交媒体平台上的 hubermanlab。
So that's Instagram, X, Threads, Facebook, and LinkedIn.
这就是 Instagram、X、Threads、Facebook 和 LinkedIn。
And on all those platforms, I discuss science and science-related tools, some of which overlaps with the content of the Huberman Lab podcast, but much of which is distinct from the information on the Huberman Lab podcast.
在所有这些平台上，我讨论科学和与科学相关的工具，其中一些与胡伯曼实验室播客的内容重叠，但其中大部分与胡伯曼实验室播客上的信息不同。
Again, it's hubermanlab on all social media platforms.
再说一遍，所有社交媒体平台上都是 hubermanlab。
And if you haven't already subscribed to our Neural Network Newsletter, the Neural Network Newsletter is a zero-cost monthly newsletter that includes podcast summaries as well as what we call protocols in the form of one to three-page PDFs that cover everything from how to optimize your sleep, how to optimize dopamine, deliberate cold exposure.
如果您还没有订阅我们的神经网络时事通讯，神经网络时事通讯是一份零成本的月度时事通讯，其中包括播客摘要以及我们所说的一到三页 PDF 形式的协议，涵盖从如何优化睡眠、如何优化多巴胺、故意冷暴露等所有内容。
We have a foundational fitness protocol that covers cardiovascular training and resistance training.
我们有一个基本的健身方案，涵盖心血管训练和阻力训练。
All of that is available completely zero cost.
所有这些都是完全零成本可用的。
You simply go to hubermanlab.com, go to the Menu tab in the top right corner, scroll down to Newsletter, and enter your email.
您只需访问 hubermanlab.com，转到右上角的“菜单”选项卡，向下滚动到新闻通讯，然后输入您的电子邮件即可。
And I should emphasize that we do not share your email with anybody.
我要强调的是，我们不会与任何人分享您的电子邮件。
Thank you once again for joining me for today's discussion with Dr. Sergiu Pasca.
再次感谢您参加今天与 Sergiu Pasca 博士的讨论。
And last but certainly not least, thank you for your interest in science.
最后但并非最不重要的一点是，感谢您对科学的兴趣。
Speaker 3:
演讲者3：
NFL football season is here, which means when you switch to Verizon, it feels like touchdown because you get NFL Sunday Ticket from YouTube on us when you buy an eligible 5G phone on select unlimited plans, which means you can watch every out-of-market game every Sunday afternoon.
NFL 橄榄球赛季即将到来，这意味着当您切换到 Verizon 时，感觉就像触地得分，因为当您购买符合条件的 5G 手机并选择无限制套餐时，您就可以从 YouTube 获得 NFL 周日门票，这意味着您可以在每周日下午观看每场非市场比赛。
And it's all on us.
这一切都在我们身上。
Now, that's the Verizon way to kick off the NFL football season right.
现在，这就是 Verizon 开启 NFL 橄榄球赛季的方式。
Switch and get NFL Sunday Ticket from YouTube on us, only with Verizon.
切换并通过我们从 YouTube 获取 NFL 周日门票，仅限 Verizon。