聚焦 Jeanne Loring 博士：干细胞“教母”与生物伦理视角

The great thing about autologous cells is if they do, those cells do die or there weren't enough cells put in the first place, We can redose them because they're autologous. They come from that same person, there'll be no rejection. So there's some really, I mean, that's another advantage of using autologous cells.

自体细胞的伟大之处在于，如果它们确实死亡或者一开始没有足够的细胞，我们可以重新给它们接种，因为它们是自体的。它们来自同一个人，不会有拒绝。所以真的，我是说，这是使用自体细胞的另一个优点。

This is Biotech Innovators, a podcast designed for those who are curious about how biotech businesses become a reality. In each episode, we highlight the stories of innovators who've overcome the challenges of starting and growing a biotech company. Each story uncovers the tactical steps needed for creating a business that helps make the world healthier, cleaner, and safer.

这是生物技术创新者，这是一个为那些对生物技术企业如何成为现实感到好奇的人设计的播客。在每一集中，我们都会突出讲述创新者的故事，他们克服了创办和发展生物技术公司的挑战。每个故事都揭示了创建一个有助于让世界更健康、更清洁、更安全的企业所需的战术步骤。

Hello and welcome to another episode of Biotech Innovators. I'm your host, Josh Judkins. So today I'm very excited to introduce our guest professor doctor Jean Loring. She is a world renowned stem cell biologist and considered by many to be the godmother of stem cells, which I think is an adorable term. And among her many accomplishments, a call out a couple. She is a cosplayer of Aspen Neuroscience, which we'll talk more about later. She is professor emeritus from Scripps Department of Molecular Medicine and also a research fellow at the San Diego Zoo. And that work in particular is super exciting, can't wait to touch on that. And so with that, Doctor Loring, thank you so much for joining us.

你好，欢迎来到另一集生物技术创新者。我是你的主持人乔什·贾金斯。所以今天我非常兴奋地介绍我们的客座教授Jean Loring博士。她是世界著名的词干细胞生物学家，被许多人认为是词干细胞的教母，我认为这是一个可爱的术语。在她的许多成就中，有一个叫了几个。她是阿斯彭神经科学的扮演者，稍后我们会详细讨论。她是斯克里普斯分子医学系的名誉教授，同时也是圣地亚哥动物园的研究员。这项工作特别令人兴奋，我迫不及待地想触及它。因此，就这样，Loring医生，非常感谢您的加入。

Thank you Josh.

谢谢你，乔希。

It's hard for me to hold back from peppering you with a million questions. So we will try and remain structured here, so don't worry. So let's go back to the beginning. You know, I think so, for example, I think for today, in some respects, the new, the next sort of generation now that's coming out of a school and going into the Bible industry. And, you know, they can go to, you know, company websites and buy a lot of the kits for stem cell culture and differentiation on expansion. And I think it can be easy to take for granted that, oh, yeah, we can do some of these things. So tell us more, I guess about the early days, you know, and before you get too much into the detail of that, if you could tell us a bit about your career trajectory, where you went to school, what you studied, and we'll go from there.

对我来说，用一百万个问题问你，很难抑制住你的心。所以我们会努力保持结构化，所以不要担心。让我们回到开头。你知道，我认为是这样的，例如，我认为今天在某些方面，新的下一代即将走出学校，进入圣经行业。而且，你知道，他们可以去公司网站购买很多用于词干细胞培养和分化的试剂盒。我认为很容易想当然地认为，哦，是的，我们可以做一些这些事情。所以请告诉我们更多，我猜是关于早期的日子，你知道的，在你过于深入细节之前，如果你能告诉我们一些你的职业轨迹，你上过什么学校，你学过什么，我们会从那里开始。

So I started, I was an undergraduate at the University of Washington in Seattle, and that's where I started doing, that's where I got hooked on lab research. They had a, it was a brand new program. I know it's common now, but it was really rare then. And I just, I mean, I started, I think it was more of the social thing than the science itself as the fact that I could hang out with with other people who are scientists and I could talk to people who had more experienced than me, postdocs and graduate students, and all enormously more famous than me. And we could just love these conversations. So I really, really loved it.

所以我开始了，我是西雅图华盛顿州大学的本科生，那就是我开始做的地方，也是我迷上实验室研究的地方。他们有一个，这是一个全新的节目。我知道这现在很常见，但当时真的很少见。我只是，我的意思是，我开始了，我认为这更多是社会问题而不是科学本身，因为我可以和其他科学家一起出去玩，我可以和比我更有经验的人，博士后和研究生交谈。而且都比我更有名。我们可以喜欢这些对话。所以我真的非常喜欢它。

And that's so I went on to graduate school, went to the University of Oregon, which was at that time, had just started its Institute for molecular biology, an institute, of course, is like a small group set aside from all the departments it was. It was remarkable because some of the people who were there, people that some people would have heard of, would George Streisand, who started his the first zebrafish studies there while I was there and Frank Stall who people will remember from the famous measles and stall among others. I mean, it was just like a group of, and they were almost, they were all from the East Coast and they'd all gone to this wild place in Eugene, Oregon, in order to have freedom. And so it was just a delightful atmosphere. It was like it was so hopeful and exciting and I just, I loved it.

就这样，我继续读研究生，去了当时刚刚成立了分子生物学研究所的奥里冈大学，当然，这个研究所就像一个在所有院系之外的小团体。这很了不起，因为在那里的一些人，有些人可能听说过的人，比如乔治·斯特里尚，他在我在那里开始了他的第一次斑马鱼研究，而弗兰克·斯特尔斯，人们会记得他从著名的麻疹和斯特尔斯等等。我的意思是，这就像一群，他们几乎都来自东海岸，他们都去了奥勒冈尤金的这个荒野，以获得自由。所以这只是一个令人愉快的气氛。就好像它是如此充满希望和令人兴奋，我只是，我喜欢它。

That's also where I started working on stem cells for the first time. And the stem cells I was working on were neural crest cells from avian embryos. My favorite were the quail embryo, embryonic stem cells. And I just couldn't possibly have been doing anything else in the future. So I was looking at very, very early development and the quail, it was only like 2.5 days after they started being incubated.

这也是我第一次开始研究词干细胞的地方。我正在研究的词干细胞是从鸟胚胎中提取的神经嵴细胞。我最喜欢的是鹌鹑胚胎，胚胎词干细胞。而且我将来不可能做别的事情。所以我研究了非常早期的发育和鹌鹑，它们开始孵化后才2.5天。

Really adorable, tiny, tiny things with beating hearts and soul mites and neural tube and just starting to form the brain. And in the region of the well, this is going on everywhere. I was just studying sort of the middle part of the embryo, which is an interesting thing when you think about it. I was studying the how neural crest cells, which give rise to, they're not pluripotent, but they give rise to pigment cells that give rise to sympathetic and the parasympathetic and pathetic Anglia. And they do this all by coming off the top of the neural tube and migrating. So there was obviously something was telling them where to go and something that was telling them what to do. I focused on the what to do, and I found that there was a an interest. Well, the goal, the end, the most important discovery I made was that there was a flexible stage in which cells could either become sympathetic neurons making norepinephrine, or they could become pigment cells that make melanin, and you could control that with extracellular cues.

非常可爱，微小，微小的东西，跳动的心脏，灵魂螨和神经管，刚刚开始形成大脑。在井的区域，这种情况到处都在发生。我只是在研究胚胎的中间部分，想想看，这是一件有趣的事情。我正在研究神经嵴细胞是如何产生的，它们不是多能性的，但它们会产生色素细胞，从而产生交感神经、副交感神经和交感神经。他们通过从神经管的顶部迁移来完成这一切。所以显然有一些东西告诉他们去哪里，也有一些东西告诉他们该做什么。我专注于该做什么，我发现有一种兴趣。我的目标、最终和最重要的发现是，存在一个灵活的阶段，在这个阶段中，细胞既可以成为产生去甲肾上腺素的交感神经元，也可以成为产生黑色素的色素细胞，你可以通过细胞外线索来控制这一点。

That is just so cool. My background is in chemical biology, so it's always so fascinating to me to think about those connections and those pathways and something so simple as like a cell that is making a pigment in that same cell so essential for a neurotransmitter so cool one of my friends in grad school once told me that the relationship with your academic advisor, if there is one, is, the most complicated one you'll ever have. So I was wondering if you could comment for listeners on your experience with your advisor in grad school?

那真是太酷了。我的背景是化学生物学，所以对我来说，思考这些连接和路径总是如此迷人，就像一个细胞在同一个细胞中制造出如此重要的色素一样简单。神经递质很酷，我研究生院的一位朋友曾经告诉我，与你的学术导师的关系，如果有的话，是你所见过的最复杂的关系有。所以我想知道你是否可以就你在研究生导师的经历向听众发表评论？

Yeah, so my advisor will remain nameless for obvious reasons, my advisor, the work that was going on the lab was fascinating and the graduate students and the postdocs who were there were fantastic. And in fact, he was really smart too.

是的，因此出于显而易见的原因，我的导师将保持匿名，我的导师，实验室正在进行的工作非常迷人，在那里的研究生和博士后非常出色。事实上，他也非常聪明。

It was when I had done my gotten to the point where I'd done my qualifying exams and was and was essentially given the permission to go on for my PhD was when he said, well, now you can quit and be and get a master's degree. And I just, I was, this is like the worst moment of my life and I couldn't figure out why, but it turned out that he'd never had a female graduate student finish before he'd had them start and then go and become get their master's degrees, but he hadn't had a Phd doctoral student finish. So I don't, I didn't think I could probably talk him into it. So I went to my committee and my committee went to him and told him that they would support me and that they thought I should get a Phd. And so it was a group effort. It was pretty amazing. Ed Herbert was the head of my committee and yeah, he became, he's a famous bio, but they were all really, really kind to me and they and they helped me through even though my thesis advisor did not like me at all.

那是在我完成了资格考试并获得了继续我的博士学位的许可的时候，他说，现在你可以辞职并获得硕士学位了。而我只是，这就像是我一生中最糟糕的时刻，我不明白为什么，但事实证明，在他让女研究生开始攻读硕士学位之前，他从来没有让她们完成学业，但他还没有完成博士研究生的学业。所以我不，我不认为我可以说服他。所以我去了我的委员会，我的委员会去找他，告诉他他们会支持我，他们认为我应该读博士。所以这是一个团体的努力。这相当惊人。艾德·赫伯特是我的委员会主席，是的，他成为了一个著名的生物，但他们都对我非常非常好，他们帮助我度过了难关，尽管我的论文导师一点都不喜欢我。

Gosh, it's so frustrating when, you talk about being so excited and the flame of curiosity, you know, being ignited. You're so passionate about something to then come up against someone who's trying to queue that, you know, really not great. So I'm sorry you experienced that, but I think I think that's not a story for, allyship. And, you know, especially, you know, someone in power stepping in and supporting you. Do you have any like nuggets of like advice that for other either grad students or even people that are already at the bench and working in a company that might be facing similar situations?

天哪，当你谈到如此兴奋和好奇的火焰被点燃时，真是令人沮丧。你对某事充满激情，然后遇到一个试图排队的人，你知道，真的不是很好。所以我很抱歉你经历了这样的事情，但我认为这不是一个关于alyship的故事。而且，你知道，特别是，你知道的，有人在权力介入并支持你。对于其他研究生或者已经在板凳上工作并可能面临类似情况的公司的人，您是否有类似的建议？

Yeah, I would say if you can, I mean, if there is another lab doing something interesting, you should switch and talk to the other students because the students always know, you know, unfortunately, I was there in a time where there just weren't very many women at all, no and faculty at all in my, in my, my department. So there was really nobody to who I could talk to who would understand the peculiarities of being female in this world, which was entirely male, so what I would suggest and what a lot of my students once I became a professor myself, I had a lot of rescues I had a lot of students who came to me because they heard that I would be, I was a supportive of mentor, and I think it was because I was trying to be exactly the opposite of what my mentor had been to me, And so a lot of my best students. I call them rescues, I mean, they were really unhappy somewhere else they came to my lab and they thrived. So I, that's what I would recommend doing is to look for another place to go because you are unlikely. It is really hard to win against somebody in academia who has a higher status than you do.

是的，我会说，如果可以的话，我的意思是，如果有另一个实验室在做一些有趣的事情，你应该换工作和其他学生交谈，因为学生们总是知道，你知道，不幸的是，我在那里的时候根本没有很多女性。在我的部门里，没有任何教员。所以真的没有人可以和我交谈，他们会理解在这个世界上作为女性的特殊性，这完全是男性的，所以我的建议和我的很多学生一旦我自己成为教授，我有很多救援，我有很多学生来找我，因为他们听说我会，我是一个支持导师的人，我认为这是因为我试图成为与我的导师完全相反的人，还有很多我最好的学生。我称他们为救援人员，我的意思是，他们在别的地方真的不开心，他们来到我的实验室，他们茁壮成长。所以，我建议你去找另一个地方，因为这不太可能。在学术界，要战胜一个比你地位更高的人真的很难。

I want to ask a couple more questions about your early work and then we'll go on to the next segment and this is revealing my own gaps of knowledge. So I always assumed that basically we were using ipscs because of the sort of ethical and moral and really controversial aspects of embryonic stem cells. Set me straight.

我想再问几个关于你早期工作的问题，然后我们会进入下一部分，这揭示了我自己的知识差距。所以我一直认为我们使用ipscs基本上是因为胚胎词干细胞的伦理和道德以及真正有争议的方面。让我直。

Yeah, that's easy. So I was, I was, one of the, I had started a company, so I went into biotech, which was a, I really was kind of a necessity when you, when your thesis advisor is not supporting you. And I became sort of academic during my biotech Caron around in 1999.

是的，这很简单。所以我曾经是其中之一，我创办了一家公司，所以我进入了生物技术领域，当你的论文导师不支持你时，我真的很有必要。大约在1999年，我在生物技术领域变得有点学术。

I started a company myself, my first company, it's called Arco Bioscience and the goal of that was to make pluripotent stem cells from human embryos and we accomplished that and in 2001, my cell lines, or my cell preparations, they called them, were approved for funding by the NIH, by George Bush on August, in August 2001. So then I was eligible to get an NIH grant, and I got an NIH grant to do the first embryonic stem cell training course from the NIH and that gave me an entry into academia. There was another one. The problems with the company was that there was a patent, a composition of matter patent on embryonic stem cells that was held by Wisconsin Alumni Research Foundation, and they were restricting the research done on any human embryonic stem cells, and they were charging companies like my tiny 1 $75000 a year to use our own cells. So that was obviously not tenable. And I, so I merged my company with another company, which merged with another company. These are all the early stem cell companies, and eventually the company became via site, which is a company in San Diego that was using embryonic stem cells to treat diabetes. So meanwhile I went into academia at the Burnham Institute is now the Sanford and Institute.

我自己开了一家公司，我的第一家公司叫做Arco Bioscience，目标是从人类胚胎中制造多能词干细胞，我们完成了这一目标。在2001年，我的细胞系或我的细胞制剂被美国国家健康研究所批准资助。乔治布什于2001年8月发布。所以我有资格获得美国国家健康研究院的资助，我获得了美国国家健康研究院的资助，参加了第一个胚胎词干细胞培训课程，这让我进入了学术界。还有一个。该公司的问题是有一项专利，一项由威斯康星州校友研究基金会持有的关于胚胎词干细胞的物质组成的专利，他们限制对任何人类胚胎词干细胞的研究。他们向像我这样的公司收取每年75000美元的费用，以便使用我们自己的电池。所以这显然是站不住脚的。所以我将我的公司与另一家公司合并，后者又与另一家公司合并了。这些都是早期的词干细胞公司，最终成为了通过site，这是一家位于圣地亚哥的公司，使用胚胎词干细胞治疗糖尿病。因此，与此同时，我进入学术界的伯纳姆研究所现在是桑福德研究所。

There are a few extra donor since I started and I started running this course and in 2004, I ran that course for six years and moved it, moved the course to the Scripps Research Institute where I was recruited in 2007. I moved my entire lab over there, and then I got CER funding to run courses for them. And what is San Diego?

自从我开始并开始运行这个课程以来，有一些额外的捐赠者，在2004年，我运行了这个课程六年，并将其转移到了斯克里普斯研究所，我在2007年被招募到那里。我把我的整个实验室搬到了那里，然后我有资金为他们开设课程。圣地亚哥是什么？

I'm not familiar with that one.

我对那个不熟悉。

California Institute for Regenerative Medicine. Yeah, sorry, a very, it's a very West Coast thing, but they had $3 billion for they allegedly for human embryonic stem cell research. So I moved it over to scripts, but I don't know if you want me to tell you anything about challenging the Warf patent. The Wisconsin Pat was going to ask.

加州再生医学研究所。是的，对不起，这是一个非常西海岸的事情，但他们据称有30亿美元用于人类胚胎词干细胞研究。所以我把它移到了脚本中，但我不知道你是否想让我告诉你任何关于挑战Warf专利的事情。威斯康辛州帕塔打算问。

you know, because it was the patent landscape there. And I guess, I guess the challenge even briefly in the then pluripotency. Yeah.

你知道的，因为那里有专利状况。我猜，我猜测挑战甚至短暂地出现在当时的多能性中。是的。

okay. So really quickly, when I moved into academia, I was then free from that obligation to pay any any fees to WHF. And so, and I was, I was upset with fact that I thought, no, there were people all over the world who were, who were being unable to do the research they wanted to do because they had to pay a license fee that I didn't think was relevant. So I challenged that patent, that set of patents that Wf had on embryonic stem cells. And it was really fun. I had, I found a lawyer who worked for free. He had a public foundation to overturn patents that were bad for people.

好的。很快，当我进入学术界时，我就没有义务向WHF支付任何费用。所以，我感到很沮丧，因为我想世界各地都有人无法进行他们想做的研究，因为他们必须支付我认为不相关的许可费。所以我挑战了那项专利，Wf在胚胎词干细胞方面的那组专利。这真的很有趣。我找到了一个免费工作的律师。他有一个公共基金会来推翻那些对人们有害的专利。

I went to all the court hearings, we took it all the way to the Supreme Court and we did not he, we were not heard by the Supreme Court, but we did manage to get Wharf to agree to change their when changed their claims in their patent so that instead of claiming all pluripotent stem cells, they were only claiming embryonic embryo-derived pluripotent stem cells. And that was huge because if they had still had that patent when IPS sales were first arrived at in 2007, then they would have also owned those and they also would have charged for that.

我去了所有的法庭听证会，我们把它带到最高法院，我们没有他，最高法院没有听取我们的意见，但我们确实设法让码头同意在改变他们的专利声明时改变他们的权利，这样他们不是声称所有的多能词干细胞，而是声称胚胎衍生的多能词干细胞。这是很大的，因为如果他们在2007年IPS销售额首次出现时仍然拥有该专利，那么他们也会拥有这些专利，并且也会收取相应的费用。

And for our listeners who don't know about this, pluripotent stem cell means that the cell is pluripotent, meaning it can become, it can divide itself, and it can become a myriad of different kinds of final fully differentiated cell types. For example, you had a early stem cell progenitor, you could then differentiate that into a heart cell, a neuron, etc, and induced means. You take a stem cell and you induce it. Or I guess you can maybe clarify that.

对于我们不了解这一点的听众来说，多能词干细胞意味着细胞是多能的，这意味着它可以成为，它可以自我分裂，它可以成为无数不同种类的最终完全分化的细胞类型。例如，你有一个早期词干细胞祖细胞，你可以将其分化为心脏细胞、神经元等，并进行诱导。你取一个词干细胞并诱导它。或者我想你可以澄清一下。

I'll explain that that I mean, because it was pretty cool. Yeah, so in 2007 there, so there were embryonic stem cells that were polari pot, which is, I mean, I can't imagine anybody at that time. And I still believe this. I can't imagine anybody not wanting to work on pluripotent stem cells because they have such potential. And it just opens up your imagination of what can be done with a in 2007 shinya Yamanaka, who is professor in Kyoto, reported a method for turning a cell or in fact skin cell in that case, but any cell type in the body, into a pluripotent stem cell by inducing them with several transcription factors that essentially reset the entire genome. So they're now pluripotent and they continue to divide forever. So that completely changed the face of everything in this field. It not only got rid of the potentially ethically challenging aspects of working with embryos, but it also meant that we could make pluripotent stem cells that were just like embryonic stem cells from anybody.

我会解释我的意思，因为这很酷。是的，所以在2007年，有胚胎词干细胞是polari锅，我的意思是，我当时无法想象任何人。我仍然相信这一点。我无法想象有人不想研究多能词干细胞，因为它们有这样的潜力。这只是打开了你的想象力，关于2007年京都教授山中伸弥 (shinya Yamanaka) 可以做什么，他报告了一种在这种情况下转化细胞或实际上是皮肤细胞的方法，但身体中的任何细胞类型，通过几种基本上重置整个基因组的转录因子诱导它们进入多能词干细胞。所以它们现在是多能的，并且永远继续分裂。因此，这完全改变了这个领域的一切。它不仅摆脱了处理胚胎潜在的伦理挑战，而且也意味着我们可以从任何人身上制造出像胚胎词干一样的多能词干细胞。

It's called reprogramming. I was not the first one in my lab to be reprogrammed. That was my postdoc. I was the second person in my lab to be reprogrammed, and my cell line is still kicking.

这叫做重新编程。我不是我实验室里第一个被重新编程的人。那是我的博士后。我是我实验室第二个被重新编程的人，我的细胞系仍在发展。

that's awesome. One day we'll all have our own.

太棒了。总有一天，我们都会拥有自己的。

right? I think, I think we should, I mean, I certainly tried to do that. Every almost everybody in my lab had somebody else make their cell line. So I have a whole laboratory in my freezer that's amazing.

对吗？我认为，我认为我们应该，我的意思是，我肯定尝试过这样做。我实验室里几乎每个人都有其他人制造他们的细胞系。所以我在我的冰箱里有一个完整的实验室，真是太棒了。

You could, you could have a your own lab in perpetuity.

你可以永久拥有自己的实验室。

absolutely, they just keep them together in the same box.

当然，他们只是把它们放在同一个盒子里。

So we'll touch on this again in a little bit when we talk about Aspen more specifically. But just to get that, that forward looking comment, what's so special about being able to make any cell type? What's the power there?

所以当我们更具体地谈论阿斯彭时，我们将再次讨论这个问题。但是为了得到那个前瞻性的评论，能够制造任何细胞类型有什么特别之处？那里有什么力量？

Well, the simplest thing you can think of is if you can make a cell type that dies because of a disease, 2 really good examples are type 1 diabetes and Parkinson's disease in type 1 diabetes, the other cells of the pancreas are, are, are killed off. And in Parkinson's disease, there is killing of or dying of dopamine neurons in a particular part of the brain called the substantia nigra. These cells are responsible for movement and fine movement control so that when they get killed off, you can see all the characteristics of Parkinson's disease that the freezing, the shaking of the motor problems. So that was the obvious thing to do. A third thing that was obvious was to treat age related and macular degeneration by replacing the pigmented retina layer. One of the reasons I name all of these is that these are the three areas in which there are now clinical trials going on, so we've gone from pluripotent stem cells to making it, making those cells into cells that are actually medically useful.

你能想到的最简单的事情是，如果你能制造出一种因疾病而死亡的细胞类型，两个非常好的例子是1型糖尿病和1型糖尿病中的帕金森病，胰腺的其他细胞都被杀死了。在帕金森病中，大脑中特定部位黑质的多巴胺神经元被杀死或死亡。这些细胞负责运动和精细运动控制，因此当它们被杀死时，你可以看到帕金森病的所有特征，即运动问题的冻结和摇晃。所以这是显而易见的事情。第三件显而易见的事情是通过替换色素视网膜层来治疗与年龄相关的黄斑变性。我将所有这些命名的原因之一是，这是目前临床试验正在进行的三个领域，因此我们已经从多能词干细胞转变为制造这些细胞，使这些细胞成为实际上具有医学用途的细胞。

And now the next generation of stem cells are, well, one of the many, especially in cancer therapies. Are these induced in K cells or natural killer cells? Really exciting where the field is going?

现在下一代词干细胞是众多细胞中的一种，尤其是在癌症治疗中。这些是在K细胞或自然杀伤细胞中诱导的吗？真正令人兴奋的是，这个领域将走向何方？

Yeah, it's almost endless and maybe we'll get around to some of the other stuff I've been doing with Flory, potent stem cells. But, but I think I think I could come up with a new, maybe not practical, but some whimsical use of fluid potency almost every day.

是的，这几乎是无穷无尽的，也许我们可以看看我一直在研究的一些其他东西，这些东西是关于功能强大的词干细胞的。但是，我想我可以想出一个新的，也许不实用，但几乎每天都有一些异想天开的液体效力使用。

I love it and so will just to keep people hanging, will touch back on some of those, those sort of healthcare related applications in a couple segments. But you alluded to earlier other work that you do. So we got to talk about your work in Cryo Zola because it is so cool. I mean, these are, I mean, humans are changing the face of the planet so quickly that species are struggling to keep up and I think the groundwork and work we've done in stem cells and understanding how we can reprogram stem cells into this, these other, this pluripotent state has opened up the ability to save species from extinction. So tell us about your work with the zoo.

我喜欢它，因此只是为了让人们保持悬挂，将在几个细分市场中涉及一些与医疗保健相关的应用程序。但你之前提到了你所做的其他工作。所以我们得谈谈你在Cryo Zola的工作，因为它太酷了。我的意思是，人类正在迅速改变地球的面貌，物种正在努力跟上，我认为我们在词干细胞和理解如何将词干细胞重新编程到这些方面所做的基础工作和工作。这种多能状态开启了拯救物种免于灭绝的能力。所以告诉我们你在动物园的工作。

So I'm in San Diego and about 30 minutes north of me is the San Diego Zoo, actually, it's the wildlife park and it's changed names a lot of times, but I think most of people are are acquainted with it. It's a very, very large park with lots of wild animals that can and savannahs, and really, it's really a lovely place.

所以我在圣地亚哥，在我以北大约30分钟是圣地亚哥动物园，实际上，这是野生动物园，它的名字经常改变，但我想大多数人都熟悉它。这是一个非常大的公园，有很多野生动物和大草原，真的是一个可爱的地方。

So when I'd moved to Scripps, I was contacted or I'd been in contact with a friend of mine named Oliver Ryan, who happened to be the head of the Institute for Conservation Biology of the Sioux. So I was one to celebrate the movement of my lab from a from the burning to scripts, which was much larger lamp, lots more people. I took them on a safari at the safari park. Cool, best mentor ever. Yeah.

所以当我搬到斯克里普斯时，有人联系我或者我联系了我的一个朋友奥利弗·瑞安，他恰好是苏人保护生物学研究所的负责人。所以我是一个庆祝我的实验室从燃烧到剧本的运动的人，这是一个更大的灯，更多的人。我带他们在野生动物园进行了一次野生动物园之旅。酷，有史以来最好的导师。是的。

I mean, I really do believe in field trips, even if you work in the lab the whole time. So we started talking about this while we were on this truck feeding giraffes. And we realized that we, you know, we learned a lot about the fact that the institute and the zoo had created over a period of, they started in 1975, I think what's called the frozen zoo. What it was was interestingly, mostly it was made up of a lot of things, a lot of cells that were were harvested from animals. But really interestingly, one of the cell types that had been harvested from a lot of animals starting then were fibroblasts from the skin. They were cultured and then there were cryopreserved. So when I got back to my lab, I asked if there was anybody who wanted to try to make IPS cells out of an endangered species. And I got, I mean, I got my 1, my postdoc just stood up and said, absolutely, yeah, something like me.

我的意思是，我真的相信实地考察，即使你一直在实验室工作。所以当我们在这辆卡车上给长颈鹿喂食时，我们开始谈论这个问题。我们意识到，我们学到了很多关于学院和动物园在一段时间内创建的事实，它们始于1975年，我想是所谓的冷冻动物园。有趣的是，它主要由很多东西组成，很多从动物身上采集的细胞。但非常有趣的是，从许多动物身上采集的其中一种细胞类型是来自皮肤的成纤维细胞。它们被培养，然后被冷冻保存。所以当我回到实验室时，我问是否有人想尝试用濒临灭绝的物种制造IPS细胞。我得到了，我的意思是，我得到了我的1，我的博士后只是站起来说，绝对，是的，像我这样的东西。

but me.

但是我。

Yeah, no, yeah, exactly, exactly. So I said, okay, yeah, the rest of you got to work on the stuff, you're ready starting, but she's a new postdoc, so we'll give this to her and she accomplish it. We let all of her, she was the animals, he wanted us to reprogram. One of them was the northern white rhino, which is critically endangered. There were, I believe, 7 or excuse me, 8 of them at that time that was in early, that was 2008 or so and the primate called the Dil, which is not quite as endangered. So in bar, Friedrich Ben Nun, my postdoc, managed to figure out how to reprogram the both of those animals using the transcription factor vector is that were designed for humans, which I think is really remarkable. I mean, we didn't think it would work, it worked and we published that work in 2011 And since then I've continued working with the zoo.

是的，没错，没错。所以我说，好的，是的，你们其他人必须处理这些事情，你们已经准备好开始了，但她是一个新的博士后，所以我们会把这个交给她，她完成它。我们让她所有，她是动物，他希望我们重新编程。其中之一是极度濒危的北方白犀牛。我相信，当时有7只，或者对不起，当时是在2008年初，有8只，灵长类动物被称为稀，它并不那么濒危。所以在酒吧，我的博士后弗里德里希·本·尼恩 (Friedrich Ben Nun) 设法弄清楚如何使用为人类设计的转录因子载体对这两种动物进行重新编程，我认为这真的很了不起。我的意思是，我们不认为它会起作用，它起作用了，我们在2011年发表了这项工作，从那以后我继续与动物园合作。

We trained a person named Marissa corrodi we trained a woman named Marissa corrodi who was employed by the zoo. She spent, I think, almost a year in my lab learning how to work with pluripotent stem cells, including the induced chri potent stem cells from those endangered species. And then she went back and helped build a lab at the institute, at the zoo that is now a pluripotent stem cell lab. And they're reprogramming other species.

我们训练了一个叫玛丽莎·腐蚀迪的人，我们训练了一个在动物园工作的女人，她叫玛丽莎·腐蚀迪。她花了将近一年的时间在我的实验室学习如何与多能词干细胞合作，包括来自那些濒危物种的诱导的词干细胞。然后她回去帮助在研究所建立了一个实验室，在动物园里，现在是一个多能词干细胞实验室。他们正在重新编程其他物种。

And just last year, we published our work on reprogramming nine northern rhinos using human, I mean, different animals. At that time, there are only two of them still alive. So that meant that the cells that we made into IPS cells in the lab are really the only living remnants of those animals. And there was one called Angeli who, who was especially, he died 10 years ago or so, something like that. We got his Elsa reprogrammed them. And then I remember this amazing feeling I had when we turned those cells into cardiac muscle cells and they started beating in a culture dish. It was almost like Angela was back. So anyway, so they now, they're only two alive, they're both female.

就在去年，我们发表了关于使用人类，我的意思是不同的动物，重新编程九只北方犀牛的工作。那时，只有两个人还活着。这意味着我们在实验室中制成IPS细胞的细胞实际上是这些动物唯一的存活残留物。还有一个叫安吉利的人，尤其是他十年前去世了，类似的事情。我们重新编程了他的艾尔莎。然后我记得当我们将这些细胞转化为心肌细胞并开始在培养皿中跳动时的那种惊人的感觉。这几乎就像安杰拉回来了。所以无论如何，现在他们只有两个活着，他们都是女性。

The species is going to be extinct in our lifetimes.

这个物种将在我们的有生之年灭绝。

And with the zoo, we're working on methods to make artificial gametes out of the IPS cells, which is not as strange as it might sound because it's already been done in mice. So that's where the effort is right now to try to do, to try to make embryos in a culture dish, then transfer them to a group of southern white rhinos that are very similar that the zoo has brought in for that purpose. They're going to be surrogate mothers. So there's a whole team at the zoo who's working on how to implant embryos in the southern white rhinos, which is non trivial. It's not like humans at all. They're not larger for 1 I and then, and then.

在动物园里，我们正在研究用IPS细胞制造人工配子的方法，这并不像听起来那么奇怪，因为已经在老鼠身上完成了。所以这就是现在努力的地方，尝试在培养皿中制造胚胎，然后将它们转移到一群南方白犀牛身上，这些犀牛非常相似，是动物园为此目的引进的。他们将成为代孕妈妈。所以动物园有一个完整的团队正在研究如何在南方白犀牛身上植入胚胎，这并不简单。它一点也不像人类。它们对于1 I并不是更大的，然后，然后。

you know what doesn't just walk up to a southern right now?

你知道现在什么不只是走到南方吗？

And but no, no, then like a really trainable, so they, I mean, they're very gentle, they're herbivores. I mean, you hear about people being gored by them. I think that's only when you do something really, really bad. But they are really sweet animals. And I, one of the benefits of working with these people is I would get to go to the zoo and then, and then the northern white rhinos that were kept in a particular area would come up to the fence and I could pet them and scratch on behind the ears. They were just, they were so sweet.

但是，不，不，那么就像一个非常可训练的，所以它们，我的意思是，它们非常温和，它们是食草动物。我的意思是，你听说过人们被他们弄得要命。我认为只有当你做了一些非常糟糕的事情时才会这样。但它们真的是可爱的动物。和这些人一起工作的好处之一是我可以去动物园，然后被关在特定区域的北方白犀牛会来到围栏前，我可以抚摸它们，挠耳朵后面。他们只是，他们是如此甜蜜。

Do they purr?

他们呼噜声吗？

Almost, it felt like it felt like a cat except for that part.

几乎感觉就像一只猫，除了那部分。

That's cool, that's so cool. I guess. Side note, is there any similar kind of work being done to similarly cryopreserve and curry embryos, etcetera like any vulnerable insect populations or is it really just.

这很酷，这太酷了。我想。请注意，是否有类似的工作正在进行，例如冷冻保存和咖喱胚胎等，就像任何脆弱的昆虫种群一样，或者真的只是这样。

you know, higher animals? Yeah, no, that's a really good question. And I know that the zoo has insect cells, but nobody's been able to reprogram insect cells yet. I mean, I think it's really just a matter of pushing the funding to that area and, you know, getting if there's somebody out there who's you crazy about a particular insect, then I would recommend them donating that money to the zoo and asking them to please reprogram that animal or that insect that it is an animal.

你知道高等动物吗？是的，不，这是一个非常好的问题。我知道动物园里有昆虫细胞，但还没有人能够重新编程昆虫细胞。我的意思是，我认为这只是一个将资金推向那个领域的问题，你知道，如果有人对一种特定的昆虫着迷，那么我会建议他们把那笔钱捐给动物园，并请他们重新编程那只动物或那只昆虫，使它成为动物。

But if that's not a lesson in, you know, that's the wonderful thing about science is we are never going to answer all the questions, right? So that's that would be a fabulous thesis.

但是，如果这不是一个教训，你知道，科学的美妙之处在于我们永远不会回答所有的问题，对吧？所以这将是一个神话般的论点。

wouldn't it? Oh yeah, absolutely. Yeah.

不是吗？是的，绝对的。是的。

So getting back to Parkinson's, so I understand, I guess, do you have a personal like familial or a friend connection to Parkinson's, if you don't mind me asking?

所以回到帕金森病，所以我理解，我猜，如果你不介意我问的话，你和帕金森病有个人联系吗？

Such a personal. Yeah, no, no, no. I'll tell you, I have no familial connection at all, my family is pretty much disease free. I'm really lucky, but the, but I did get, I mean, it was very interesting.

如此私人的。是的，不，不。我告诉你，我完全没有家庭关系，我的家人几乎没有疾病。我真的很幸运，但是我确实得到了，我的意思是，这非常有趣。

So I guess that was about 2012, I was approached by some physicians that were had heard that maybe could treat Parkinson's disease by with stem cells and that led to a nonprofit patient run group called Summit for Stem cell and they climb to at the top of Mount Kilimanjaro in Africa to raise $200000. That was a goal. They raised it and I started by Parkinson's program in my lab, the summit for stem cell actually provided over the next few years about $3 million that they raised so there so I have a really close relationship with a lot of people with Parkinson's disease. The leader of that group, the CEO, is Jennifer Rob. And she's pretty astonishing. She never fundraised before, but she's, she's really good at it. So they actually helped me start Aspen Neuroscience. So if you want to do that as a segue.

我猜那是在2012年左右，我接触到了一些医生，他们听说也许可以用词干细胞治疗帕金森病，这导致了一个名为 “词干细胞峰会” 的非营利患者运行小组，他们爬到非洲的乞力马扎罗山顶上筹集了200000美元。这是一个目标。他们提出了它，我在我的实验室中通过帕金森计划开始，词干细胞峰会实际上在未来几年内筹集了约300万美元，所以我与很多帕金森病患者有着非常密切的关系。詹妮弗·林建达 (Rob) 是那个团体首席执行官的领袖。她相当令人惊讶。她以前从未筹款，但她真的很擅长。所以他们实际上帮助我开始了阿斯彭神经科学。所以如果你想把它作为一个segue来做。

yeah, absolutely, because I want to know more about Aspen and the sort of the business parts of it, but also I want to also spend time talking about all the, the magic that you're doing at Aspen.

是的，绝对的，因为我想了解更多关于阿斯彭及其商业部分的信息，但我也想花时间谈论你在阿斯彭所做的一切。

Yeah, no, it is pretty magical. It's actually genomics, it's not magic.

是的，不，这很神奇。这实际上是基因组学，而不是魔法。

Well, it's magic until it's science, right?

直到它成为科学之前，它就是魔法，对吗？

Yeah, so the focus I took when I was working at Scripps was to and also before that was to try to understand everything about the genomics of stem cells and the epigenetics of stem cells because. They're unique cell type, so they've got to have unique qualities. I developed my lab, developed an assay called plurry test, which was the expression profiling themo Fisher actually offers it as a service, yeah? Yeah, it's a way of just all you have to do if you work with thermo is send them a sample viewer a cells and they will put the, they'll look at the gene expression profile and it'll tell you whether it matches the profile that we have in this database we created. So that that went all the way back to 2 and 11 and then so it's actually still available online we added RNA seek to it as as a method we did whole methyne sequencing for the first time on pluripotent stem cells in one of their derivative to see how DNA methylation changed when you got them to differentiate.

是的，所以我在斯克里普斯工作时的重点是，以及之前的工作是试图了解有关词干细胞基因组学和词干细胞表观遗传学的一切。它们是独特的细胞类型，因此它们必须具有独特的品质。我开发了我的实验室，开发了一种叫做plurry测试的检测方法，这是themo Fisher实际上提供的表达分析服务，是吗？是的，如果你使用thermo，这是一种只需向它们发送样本查看器细胞，它们将放置基因表达谱，它会告诉你它是否与我们创建的数据库中的表达谱相匹配。因此，这可以一直追溯到2和11，然后实际上仍然可以在网上获得，我们添加了RNA seek作为一种方法，我们首次在多能词干细胞的一种衍生物中进行了全甲基测序，以了解当您获得它们时DNA甲基化如何变化。区别。

We did genotyping and showed that there were lots of mutations that showed up in these cells reproducibly from different lines from all over the world. We discovered that there was a recurrent P 53 mutation in a lot of cell lines and that if we grew the cells long enough, they pretty much would acquire p 53 mutation. And that's sort of the theory of evolution in your, it's not, it's not a theory. There is evolution, an incubator every time a cell divides, a few nucleotides change, and that doesn't matter as long as those nucleotides are not in a bad place in the genome. But if once you start, you get a mutation is something that protects the cells from stress and maybe makes them divide a little faster, inevitably, eventually that will take over. So that's why people keep finding these things in their cultures, because, you know, it's inevitable, you can't prevent it. Really, all you can do is is monitor it and make sure that you don't keep going. Once your culture is it has these mutations, make sure you .

我们进行了基因分型，并发现这些细胞中出现了大量可重复的突变，这些突变来自世界各地的不同品系。我们发现许多细胞系中都存在经常性的p53突变，如果我们将这些细胞培养足够长的时间，它们几乎会获得p53突变。这就是你们的进化论，不是，不是理论。有进化，每次细胞分裂时，孵化器都会有一些核苷酸发生变化，只要这些核苷酸不是在基因组中的不良位置，这并不重要。但如果一旦开始，你会得到一个突变，它可以保护细胞免受压力，也许会使它们分裂得更快，最终不可避免地会接管。这就是为什么人们在他们的文化中不断发现这些东西，因为你知道，这是不可避免的，你无法阻止它。真的，你所能做的就是监控它并确保你不会继续前进。一旦你的文化出现了这些突变，请确保你。

bank low.

银行低。

Oh my God, yes. Oh yeah, that goes without saying. Yeah, bank them really low passage, bank them whenever you can because you're never, you don't want to go back to 0. I mean, it's just, it's not only does it cost money, but it's really, really depressing. So I'm recommending, I still recommend a whole battery of genomic tests on your pluripotent stem cells just to make sure they remain normal while you're still working on them because they don't screw up your research. It'll also screw up your clinical application.

我的天啊，是的。是的，这是不言而喻的。是的，银行把它们放在很低的通道上，只要你能，就把它们银行起来，因为你永远不想回到0。我的意思是，这不仅要花钱，而且真的非常令人沮丧。所以我建议，我仍然建议对你的多能词干细胞进行一整套的基因组测试，以确保它们在你工作的时候保持正常，因为它们不会搞砸你的研究。它还会影响您的临床应用。

The summit for stem cell actually helped me move my lab at Scripps to start the company Aspen Neuroscience in 2018. And they are, in fact, investors and early investors in the seed round in Aspen Neuroscience. And we just essentially lifted the entire lab, including the equipment, all the people, all the IP, and, you know, with Scripps Health, obviously and permission, we turned it into a company. We just took an off site. It became a company, but it had the same people and then it, then we had a temporary headquarters, and then we got our seed funding in, which was $6.5 million. There are a lot of stories associated with that too, because I, you know, it was not an easy time to raise money and yet there were a lot of enthusiastic investors. The story was very attractive. Aspen, unlike other companies in my lab, unlike other labs, decided that the best therapy to replace cells would be a get therapy.

词干细胞峰会实际上帮助我将我在斯克里普斯的实验室搬到2018年创办了阿斯彭神经科学公司。事实上，他们是阿斯彭神经科学种子轮的投资者和早期投资者。我们基本上只是将整个实验室，包括设备，所有的人，所有的知识产权，而且，你知道，在斯克里普斯健康的许可下，我们将它变成了一家公司。我们刚刚关闭了一个网站。它成为了一家公司，但它有同样的人员，然后我们有一个临时总部，然后我们得到了650万美元的种子资金。也有很多与此相关的故事，因为我，你知道，当时筹集资金并不容易，但却有很多热情的投资者。这个故事非常吸引人。与我实验室的其他公司不同，阿斯彭决定替代细胞的最佳疗法是get疗法。

And so can you clarify for the audience what autologous means?

那么，你能向观众澄清一下自体免疫的含义吗？

Yeah, so you can make IPS cells from any individual and you can turn those cells from ASL type, So we collect IPS cells, we make IPS cells from individuals, turn them into dopamine neurons, and then we plan to transplant them into their brains to restore the cells that have been lost. The advantage is that they don't, you don't need to be immunosuppressed, it's not like an organ transplant, and immunosuppression is really hard on people who are already sick.

是的，所以你可以从任何个体中制造IPS细胞，并将这些细胞转化为ASL类型，所以我们收集IPS细胞，从个体中制造IPS细胞，将它们转化为多巴胺神经元，然后我们计划将它们移植到他们的大脑中，以恢复丢失的细胞。优点是它们不需要，你不需要免疫抑制，这不像器官移植，免疫抑制对已经生病的人来说真的很难。

Yeah, so you're taking the patient's own cells, editing them, and putting them right back into the.

是的，所以你要取出患者自己的细胞，编辑它们，然后将它们放回原处。

we're not even editing them for this. We don't need to edit them if we're looking at people who have genetic forms of Parkinson's disease, it'll make sense to edit them.

我们甚至不会为此编辑它们。如果我们正在观察患有帕金森病遗传形式的人，我们不需要编辑它们，编辑它们会很感知。

But what you're also doing, right?

但你也在做什么，对吧？

Yeah, that's yeah, they are, they're working on what's called a GBA mutation, which is a risk factor for Parkinson's disease to try to be more inclusive of who get who can be transplanted.

是的，他们正在研究所谓的GBA突变，这是帕金森病的风险因素，以尝试更加包容谁可以移植。

So we got the money from the series A Kim kamdar from Domain here in San Diego deserves a lot of credit for being the first VC to believe in us and then the next year we raised $70 million and the next year after that, I guess it took two years the CEO of the company and the business people at the company raised another $145 million. So the company is really well financed and they now have 70 people. They started out with just my core group of like 7 and now they have 70 and they're starting to manufacture the cells for the clinical trial. So it's been an amazingly fast progress.

所以我们从这个系列中得到了钱，一个来自圣地亚哥域名的Kim kamdar值得称赞，因为它是第一个相信我们的风险投资公司，然后第二年我们筹集了7000万美元，之后第二年，我想公司的首席执行官花了两年时间，公司的商界人士又筹集了1.45亿美元。所以公司真的有很好的资金，他们现在有70个人。他们一开始只有我的核心小组，像7个人，现在他们有70个，他们开始制造用于临床试验的细胞。所以这是一个惊人的快速进展。

I mean, I know lots of biotech companies that have just sort of languished for years. I think the key to how well we got was really the way we started, how well it went, because we weren't just taking an idea or taking a patent out of some academic lab and then trying to re reestablish a lab. This was the lab who actually invented the technology that we used for in Aspen. So there was already a culture established. They already knew. They knew how those things had been invented. Almost all of them had been with me for 10 years or so, so they really worked as a team. And I think they sort of seeded the company with the right attitude and they were there to answer all the questions about whatever historical information people needed to know.

我的意思是，我知道很多生物技术公司已经萎靡不振多年。我认为我们得到的关键在于我们开始的方式，它进行得有多好，因为我们不仅仅是从一些学术实验室获取一个想法或专利，然后试图重新建立一个实验室。这个实验室实际上发明了我们在阿斯彭使用的技术。所以已经建立了一种文化。他们已经知道了。他们知道这些东西是怎么发明出来的。几乎他们所有人都跟了我10年左右，所以他们真的是一个团队合作。我认为他们以正确的态度为公司播种，他们在那里回答关于人们需要知道的任何历史信息的所有问题。

Still therapy, right? You're putting a cell as a therapeutic inside someone. You mentioned it sort of willy nilly earlier that you we're putting them in people's brains and you don't just go poking around in there. And I understand from talking to other companies that basically there's pretty routine procedures now to do brain implantation. But can you reveal more about exactly, you know, what's you're doing when you're poking around in there?

仍然是治疗，对吧？你正在将一个细胞作为治疗剂放入某人的体内。你之前有点胡思乱想地提到，我们正在把它们放在人们的大脑里，而你不只是去那里找些东西。我通过与其他公司的交谈了解到，现在基本上有相当常规的程序来进行大脑植入。但是你能透露更多关于你在里面四处走动的时候你在做什么吗？

Yeah, so the because of work that had been done with in the 1980s, actually it was known that if you put the right dopamine neuron cells and they survived into their target, which is in with neurons, they connect with other cell types. And so you stick them straight into what's called the striatum, which is another, you know, sort of downstream connected part of the brain if you put those cells directly into the striatum, they would actually innervate the cells in the striatum and people would recover.

是的，因为在1980年代所做的工作，实际上已经知道，如果你把正确的多巴胺神经元细胞和它们存活到它们的目标中，它们与神经元连接，它们与其他细胞类型。所以你直接将它们插入所谓的纹状体，这是大脑的另一个下游连接部分，如果你将这些细胞直接放入纹状体，它们实际上会支配纹状体中的细胞，人们就会恢复。

There's a lot of problems with fetal cells, reproducibility, quality control, etc., etc., etc.. Essentially, we're doing the same thing, but with IPS cells that are turned under scrupulous call to control are made into dopamine neurons at precisely the right stage so that when you put them into the brain, they will thrive and they'll make connections. So the surgery is really not bad, is not even an overnight stay in the hospital. There's lots of neurosurgeons now that do very precise surgeries. It's a that you drill a small hole in the skull, you have to do that and you insert a cannula, you inject the cells into the right part with under MRI, you put them in the right part of the brain, you know where they are, you pull the catheter out, and then you can just seal up that hole in the brain. There is no pain, there's no, you know, because you don't have pain receptors in your brain and there is and so far in both the fetal studies and the few studies that have been done so far in other parts of the world, it's completely safe. The main concern is you hit a blood vessel when you're and it's a surgical risk rather than a risk of the cells themselves. So, but so far, everybody seems to have been skilled enough so that they can place the cells without doing any damage .

胎儿细胞、再现性、质量控制等方面存在很多问题，等等。本质上，我们正在做同样的事情，但是对于那些在严格的控制要求下转化的IPS细胞，它们在正确的阶段被制成多巴胺神经元，这样当你把它们放入大脑中时，它们就会茁壮成长并建立联系。所以手术真的不错，甚至不在医院过夜。现在有很多神经外科医生进行非常精确的手术。这是你在头骨上钻一个小孔，你必须这样做，然后插入一个套管，将细胞注入右侧的MRI下，将它们放在大脑的右侧部分，你知道它们在哪里，你拔出导管。然后你就可以把那个洞堵在大脑里了。没有疼痛，没有，你知道，因为你的大脑中没有疼痛受体，到目前为止，在胎儿研究和目前为止世界其他地方进行的少数研究中，它是完全安全的。主要担心的是当你撞到血管时，这是一种手术风险，而不是细胞本身的风险。所以，到目前为止，每个人似乎都已经足够熟练，以至于他们可以放置细胞而不会造成任何损害。

and then so if these patients have something, maybe it's environmental or it's biological that caused their dopamine neurons to die in the first place, do we expect them to live in perpetuity in the brain? Or maybe they would have to be redose? Do you understand that just yet?

那么，如果这些患者有某种原因，可能是环境因素或生物因素导致他们的多巴胺神经元死亡，我们是否期望它们在大脑中永久存活？或者他们可能需要重新接种？你现在明白了吗？

Yeah, absolutely two things. So one is that they took a long time to die, So these people started probably having their cells, maybe their their in their 60s. Now when the cells start dying when they were in their 30s. And so it takes a long time for those cells to die off from whatever reason it was. So we expect somebody who will get a transplant in their 60s could easily leave to live to 90 symptom free if it works. But the great thing about autologous cells is if they do, those cells do die or there weren't enough cells put in the first place, we can redose them because they're autologous. They come from that same person, there'll be no rejection. So there's some really, I mean, there's another advantage of using autologous cells.

是的，绝对有两件事。所以其中一个原因是他们花了很长时间才死去，所以这些人可能开始有他们的细胞，也许他们在60多岁的时候。现在，当细胞在30多岁时开始死亡。因此，无论出于何种原因，这些细胞都需要很长时间才能死亡。所以我们预计，如果移植手术有效，那些在60多岁接受移植手术的人可以很容易地活到90岁，没有症状。但是自体细胞的好处是，如果它们死亡，或者一开始没有足够的细胞，我们可以重新给它们，因为它们是自体细胞。它们来自同一个人，不会有拒绝。所以，我的意思是，使用自体细胞还有另一个优点。

Fabulous, I can't wait. So you, I understand you have at least one asset right now at your pre Ind, is that right, at Aspen?

太棒了，我等不及了。所以，我知道你现在至少有一项资产在你的前期投资，对吗，在阿斯彭？

Yes, we have done the pre inj, we're doing what's called the in Ena study, which is could be it could last years, hopefully not that that many years, but that's where you do all the work to show the FDA that your cells are safe and that you know what you're doing, that you can identify them, you know, they're not contaminated with anything. I mean, it's kind of tedious work, but it is, it is has to be done. Luckily we practiced all that while we were still at Scripps and so essentially everything's going on Aspen is a redo of that under more obviously, like more paperwork conditions. That's what I paperwork conditions.

是的，我们已经进行了预注射，我们正在进行所谓的伊纳研究，这可能会持续数年，希望不会那么多年，但这就是你做所有工作的地方，向美国食品药品监督管理局展示你的细胞是安全的，你知道你在做什么。你可以识别它们，你知道，它们没有被任何东西污染。我的意思是，这是一种乏味的工作，但它是必须完成的。幸运的是，我们还在斯克里普斯练习了所有这些，因此阿斯彭上发生的一切基本上都是在更明显的文书工作条件下重做的。这就是我的文书工作条件。

So are you working with like patient advocacy organizations to enroll people in eventual clinical trials?

你是否正在与类似的患者倡导组织合作，让人们参与最终的临床试验？

Yeah, so we have, we have several neurologists who are, I mean, we're not just sending people, people don't go to just any old neurologist is that have to be referred to a small group and we're planning to do the trial here in California because there are plenty of patients here. It's a lot easier to follow them if they're nearby patient advocacy group that is is supporting this and educating people, guess what, summit for stem cell, the same people who funded my research back in 2012 I'm now on their board of directors and I am, although I will not encourage people to go to Aspen, I will certainly educate them, we are educating them, we educating Parkinson's disease patients through CME courses, which are our continuing medical education courses.

是的，所以我们有，我们有几个神经学家，我是说，我们不仅仅是派人去，人们不会去找任何一位老的神经科医生，因为他们必须被转介给一个小组，我们计划在加利福尼亚这里进行试验，因为这里有很多患者。如果他们附近的患者倡导组织支持这一点并教育人们，那么跟随他们会容易得多，你猜怎么着，词干细胞峰会，同样的人在2012年资助了我的研究，我现在是他们的董事会成员，虽然我不会鼓励人们去阿斯彭，但我肯定会教育他们，我们正在教育他们，我们通过CME课程教育帕金森病患者，这是我们的继续医学教育课程。

We run like about once a month and we have somebody who knows a lot about stem cells or Parkinson's disease or some other disease talk to whoever it is that shows up. They're supposed to be for doctors because they actually receive credit for them, medical doctors. But anybody can come. I'm the moderator, so it's always really interesting. I like to ask hard questions, and so it's always a very interesting discussion. I think people really, really like some very cool, so Selma just is sponsoring those. Nice.

我们每个月跑步一次，会有一个对词干细胞、帕金森病或其他疾病非常了解的人与出现的人交谈。他们应该是为医生准备的，因为他们实际上得到了医生的认可。但是任何人都可以来。我是主持人，所以它总是非常有趣。我喜欢问一些难的问题，所以这总是一个非常有趣的讨论。我认为人们真的非常喜欢一些非常酷的东西，所以塞尔玛只是赞助这些东西。不错。

a couple weeks ago I attended by a process international in Boston, and, you know, increasingly, as you witnessed that meeting on the Masa, like more and more we're seeing cell therapy sort of be present at these kinds of conferences. And our booth just happened to be by one of the like event stages on the floor. And they were, they had a session while I was there on diversity, equity, inclusion, just in the field in general. And this session, I heard was specifically about clinical trials and making sure that people of color that traditionally are distrustful of the medical field. And one thing that was cited was like the Tuskegee syphilis situation, right, where.

几周前，我参加了在波士顿举行的国际进程会议，你知道，正如你在Masa上看到的那样，越来越多的人看到细胞疗法出现在这些会议上。而我们的展位恰好在地板上的一个类似活动舞台上。当我在那里的时候，他们有一个关于多样性、公平、包容的会议，只是在一般领域。这次会议，我听到的是专门关于临床试验和确保传统上对医学领域不信任的有色人种。有一件事被引用了，就像塔斯基吉梅毒的情况，对吧，在哪里。

oh, yeah, that that will never go away.

哦，是的，那永远不会消失。

never, you know? And we're dealing with the consequences of this. And I guess, could you comment a bit about like prevalence of Parkinson's in different populations? And presumably this organization you're working with is making sure there's equity and accessing that?

从来没有，你知道吗？我们正在处理其后果。我想，你能就不同人群中帕金森病的患病率发表一点评论吗？大概你合作的这个组织是要确保有股权并获得股权？

Yeah, absolutely. I mean, we obviously educate anybody who shows up, but we had a specific mic. One of my first postdocs was from Nigeria, and she actually went on to get her masters of Public Health, which means I have another. I'm actually adjunct in the Department of Public Health at San Diego State because of that. But she took on education of African Americans and Africans specifically, and she's written some papers about it. In fact, she went on to write another paper for her, she went to get her MBA because she is really, really smart and more .

是的，绝对的。我的意思是，我们显然教育任何出现的人，但我们有一个特定的微米。我的第一批博士后之一来自尼日利亚，她实际上继续获得了公共卫生硕士学位，这意味着我还有另一个。因为这个原因，我实际上是圣迭戈州公共卫生部门的兼职人员。但她承担了非洲裔美国人和非洲人的教育，并写了一些关于它的论文。事实上，她继续为自己写了另一篇论文，她去拿MBA是因为她真的非常聪明而且更聪明。

stamina than I do.

耐力比我高。

Oh yeah, she's got, she's got BS Phd, I think she may have 2 PhDs and an MBA and her master's in public health. Yeah, she's amazing, and she wrote an article, I wrote one with her, and then we had another article really about equity of stem cell therapies in the world and it had authors on it from Africa and other countries in Africa. It was a very diverse authorship. It's not going to be enough, but it at least gives you something to refer to when you're, you know, trying to bring up this subject that it actually is of a concern and it's concerns personally to me.

是的，她有，她有BS博士学位，我想她可能有2个博士学位，一个MBA学位，还有公共卫生硕士学位。是的，她太棒了，她写了一篇文章，我和她一起写了一篇，然后我们又写了一篇关于世界上词干细胞疗法公平性的文章，这篇文章的作者来自非洲和其他非洲国家。这是一个非常多样化的作者。这还不够，但它至少给了你一些参考，当你试图提出这个话题时，它实际上是一个问题，这对我个人来说也是一个问题。

so folks might not know that you're an ethicist, which you are, I think officially the first ethicist I've ever spoken to in any capacity.

所以人们可能不知道你是一位伦理学家，而你是，我认为我正式地以任何身份与之交谈过的第一位伦理学家。

Don't worry. I'm not just .

别担心。我不只是。

an ethicist. So tell us more about what that means to be an ethicist and I guess the kind of work that you do in that space and I think looking forward to the future, I guess if you could comment finally on like the biggest ethical questions that in your view, that are sort of facing us today?

伦理学家。所以告诉我们更多关于成为一名伦理学家意味着什么，我猜你在那个领域做了什么样的工作，我想展望未来，我想如果你能最终评论一下你认为我们今天面临的最大的道德问题？

I can't comment on that last one. I'm sorry, but I started out, I was recruited by the Gates Foundation to be on a research and ethics board, so I was the research part, we actually had professional very good ethicists on the board as well to oversee a project that they were doing in Beijing. So they were funding an embryonic stem cell project in Beijing, in Beijing University, and we had, we had to, we really enjoyed going to Beijing every year to hear about the work and to try to set up these oversight committees in house and after five years we'd come to the point where we had established an in thehouse oversight committee and our work was done. So I wasn't, I was being a research slash ethicist, but I got really, I made friends with these people who were really hardcore ethicists, really found it fascinating.

我不能评论最后一个。我很抱歉，但我一开始是被盖茨基金会招募加入研究和伦理委员会的，所以我是研究部分，实际上我们有专业非常优秀的伦理学家在委员会中监督他们在北京进行的项目。所以他们在资助北京大学的一个胚胎词干细胞项目，我们不得不，我们非常喜欢每年去北京听取工作，并尝试在内部建立这些监督委员会，五年后我们已经建立了内部监督委员会，我们的工作已经完成。所以我不是，我是一个研究斜杠伦理学家，但我真的和这些真正的铁杆伦理学家交了朋友，真的觉得这很迷人。

So I then years later about 12 years ago, I was asked to be on the ethics advisory board for Mer, the original Merck in Germany And I said yes. And I've been doing meeting with them ever since. And that has been because it really is ethics. It's not, it's not research, but knowing the research really helps understand what the ethical choices should be. And I'm so I'm, we are talking about everything, you know, clinical trials, equity patient samples, the stem cells, gene drives, CRISPR, I mean, like it's just everything, everything that the company is interested in, we, they arrange that, but they have us us discuss these things very, very pointedly. And the really remarkable thing about Merck is that they listen to us. They actually, they actually have policies that were based on what we had told them and we revisit those things every once in a while What it also taught me was a lot about the stem cell climate or the perception of stem cells in other countries.

所以几年后，大约12年前，我被邀请加入德国最初的默克公司的道德咨询委员会，我答应了。从那以后，我一直在和他们开会。这是因为它确实是道德。这不是，这不是研究，但了解研究确实有助于理解道德选择应该是什么。我是这样的，我们正在谈论一切，你知道的，临床试验，公平的患者样本，词干细胞，基因驱动，CRISPR，我的意思是，就像一切一样，公司感兴趣的一切，我们，他们安排这些。但是他们让我们非常非常有针对性地讨论这些事情。而默克真正了不起的地方在于他们倾听我们的声音。他们实际上有基于我们告诉他们的政策，我们偶尔会重新审视这些事情，它也教会了我很多关于词干细胞气候或其他国家对词干细胞的看法。

Because Merck is an international company. It's based in Germany. And so I learned a lot about what the German, which is one example of a European country, how that people feel about embryos and how people feel about embryonic pluripotent stem cell therapies. And it's very different from the attitudes that I've encountered in the us.

因为默克是一家国际公司。它的总部设在德国。因此，我学到了很多关于德国 (一个欧洲国家的例子) 人们对胚胎的看法以及人们对胚胎多能词干细胞疗法的看法。这与我在美国遇到的态度非常不同。

So, and I just yesterday got invited to be on the ethics board of a small startup biotech. So I guess I'm in the business now.

所以，我昨天刚被邀请加入一家小型初创生物技术公司的伦理委员会。所以我想我现在正在做生意。

I'm an ethicist, and I just really enjoy it. It really takes me out of my usual, just scientific. I mean, I like being able to talk about a philosophy. A lot of the people on the panel are philosophers. There's some lawyers. And so it gets me out of my comfort zone, I guess, and makes me think a little bit larger than what I would ordinarily do.

我是一位伦理学家，我真的很喜欢它。它真的让我脱离了平常，只是科学。我的意思是，我喜欢能够谈论一种哲学。小组里很多人都是哲学家。这里有一些律师。所以它让我走出了我的舒适区，我想，让我思考比平常稍微大一些。

And so then we always, we see every now and then like these headlines, you know, scientists, you know, clone's a human or scientist says this and, they're almost, they almost read like intentionally provocative, you know?

因此，我们总是时不时地看到这些头条新闻，你知道，科学家，你知道，克隆人或科学家说这个，他们几乎读起来像是故意挑衅，你知道吗？

So what's your .

那么你的是什么？

take on that?

接受这个？

Well, as a scientist, I abhor it. I mean, I would never do anything like that. I would hope that nobody I know in the scientific community would do something like that, but there is a tendency because, and it's driven by Grant getting Grants Ni from the NIH, for example, to try to make your, your work look relevant, translational. That's the word at Anh now, translational. So you really do have to do a thought experiment in which you are telling the NIH or the reviewers that how your work is going to contribute to human health, medical, medical advance. And some people take that too seriously. And so when they publish their papers, they publish them with misleading titles.

作为一名科学家，我讨厌这种情况。我的意思是，我永远不会做那样的事情。我希望我认识的科学界没有人会做这样的事情，但是有一种趋势，因为它是由获得美国国家科学研究所的资助所驱动的，例如，试图让你的工作看起来相关，转化。这就是翻译这个词。所以你真的需要进行一个思想实验，在这个实验中，你要告诉国家卫生与健康委员会或评论者你的工作将如何为人类健康、医学进步做出贡献。有些人太认真了。所以当他们发表论文时，他们会用误导性的标题发表。

A lot of people are aware that I am a edfas the opponent of, of pop up stem cell clinics, clinics that show up in town that say they're going to give you stem cell therapies, but they're giving you something else and they're not. They're not overseen by the FDA. They're not even safe and they certainly don't work. And I hate to see people be cheated out of their money by things like that, but it is a money making making enterprise and so it is not going to go away the FDA is trying to slam it down, but they pop up, you know, they get rid of one and five more show up. So really my role in that is to is to whenever I get a chance, whenever I'm interviewed, including now, but also especially if I'm on television, on regular television or on a in a newspaper article, I take the I make sure that they, the people who are interviewing, understand that the stem cells I'm talking about are not the stem cells are being offered by those clinics. The clinics do not have oversight and those the cells they're getting out of your fat or your bone marrow are not the same as they are not pluripotential cells. They can't make neurons, they can't make heart cells, etcetera. So there I've did it, that I've done my statement.

很多人都知道我是一个反对弹出式词干细胞诊所的人，这些诊所出现在城里，说他们会给你提供词干细胞疗法，但他们给你其他东西，而事实并非如此。他们不受美国食品药品监督管理局的监督。它们甚至不安全，而且肯定不起作用。我讨厌看到人们被这样的事情骗走了他们的钱，但这是一个赚钱的企业，所以它不会消失，美国食品药品监督管理局试图把它砸下来，但它们突然出现了，你知道的。他们摆脱了一个和五个更多的出现。所以我在这方面的角色是，每当我有机会，每当我接受采访时，包括现在，尤其是如果我在电视上，在普通电视上或在报纸文章中，我要确保他们，正在采访的人，我明白我所说的词干细胞并不是那些诊所提供的词干细胞。诊所没有监督，它们从你的脂肪或骨髓中获取的细胞不同于它们不是多能细胞。它们不能制造神经元，不能制造心脏细胞等等。所以我做到了，我做了我的陈述。

thank you. I wish I had that exact statement when my father in law, late father in law, talked about getting joint therapy with these stem cells.

谢谢。我希望当我岳父，即已故的岳父谈论用这些词干细胞进行联合治疗时，我有准确的陈述。

And I was like, yeah, same .

然后我就说，是的，一样。

like we're there yet.

就像我们还在那里。

No, no, I mean, the good thing is it hardly ever hurts people except for their wallets, which, you know, if people are poor, that's a terrible blow to them. If they spend money on something like that, $15000 sometimes for an injection of, you don't know what, it's, they're charlatans. But you know, when people are desperate, that's when the charlatans show up.

不，不，我的意思是，好处是它几乎不会伤害人们，除了他们的钱包，你知道，如果人们很穷，这对他们来说是一个可怕的打击。如果他们在这样的事情上花钱，有时15000美元的注射，你不知道，他们是江湖骗子。但是你知道，当人们绝望时，那就是江湖骗子出现的时候。

Yeah, thanks. I'm so glad you took the time to really clarify that because there's so much misinformation out there that we have to deal with to pivot a bit to something that is extra-curricular. I think a little bit to both of us space. So yeah, have my dove Sony in here. This is the 1 I use when I go to star parties.

是的，谢谢。我很高兴你花时间真正澄清这一点，因为有太多的错误信息，我们必须处理一些额外的事情。我觉得对我们俩都有一点空间。所以，我的鸽子索尼在这里。这是我去参加明星派对时使用的1。

Yeah, I know I have my, I just for everybody in the audience, my telescope is smaller than his telescope .

是的，我知道我有我的，我只是为观众中的每个人，我的望远镜比他的望远镜小。

size doesn't always matter, but in space it does.

大小并不总是重要的，但在太空中确实如此。

It does, actually. It does matter for power and resolution of of your view of space. I am, I am an amateur astronomer just like Josh, not just like Josh, he's better than I am, but I also, you're welcome, but, but I'm also really interested in solar eclipses, so I've seen 14 total solar eclipses, which the term .

确实如此。这对您的空间视角的能力和分辨率确实很重要。我是，我是一个像乔希一样的业余天文学家，不仅仅是像乔希一样，他比我更好，但是我也是，不客气，但是，我也对日食非常感兴趣，所以我已经看过14次日全食，这个术语。

for our audience I to cut you out is Umbro filele.

对于我们的观众，我要把你删掉的是Umbro filele。

Yes I'm an umber file. That's right, I want to be in the darkness of the eclipse sun. I've been in the darkness of the Eclipse sun for a total of 45 minutes because somebody is keeping track, so that that is not huge by Umber files Sanders, but it's sort of mid range and I've been to I've been, I love to travel too, so I've been to Easter Island and Libya and Siberia and you know, Bolivia, all over the world Australia to see these total eclipses. So it actually fulfills two of my real interest travel and eclips was so.

是的，我是一个索引文件。没错，我想待在日食的黑暗中。我已经在日食的黑暗中总共45分钟了，因为有人在跟踪，所以这对桑德斯来说不是很大，但它是中档，我去过，我也喜欢旅行，所以我去过复活节岛、利比亚、西伯利亚，还有玻利维亚，以及世界各地的澳大利亚，去看这些日全食。所以它实际上满足了我的两个真正兴趣旅行和eeclips是如此。

oh, go, go ahead, I was going to ask you, what was the longest totality that you experienced?

哦，去吧，继续，我想问你，你经历的最长的整体是什么？

About five minutes. It really is, it really is. It's a sort of, and I you have to be to I'm not going to try to describe to you the feeling, but I am going to urge everybody who is listening to this, if you can get to see one, do it and then just see how you feel because it's a fundamental emotional and physiology experience, not just the darkness, it's the darkness in the middle of the day.

大约五分钟。它真的是，它真的是。这是一种，你必须要做到，我不会试图向你描述这种感觉，但我要敦促每个正在听的人，如果你能看到一个，做一下，然后看看你的感受，因为这是一种基本的情感和生理体验，不仅仅是黑暗，而是白天的黑暗。

Yeah, it's remarkable. Yeah.

是的，这很了不起。是的。

so anyway, a lot I'm really interested in space, so when the opportunity came to get involved in a project to study stem cells on the International Space Station, I said yes, and I started well, I was still when Aspen was in early days, we actually started Scripps, but then Aspen, we had we and the New York Stem Cell Foundation collaborated to design experiments that would allow us to study something about the nervous system in space, so we designed a system of organoids we're using neural organoids that also have glia in them, microglia, which are the immune system of the brain to have little brain like organoids or little spheres that are only about like half a millimeter across at most they're very, very yeah, they're they're very that's how big they and we so we sent them into space we've had four missions now we put the cells into cryotubes or 1 1 organoid in each cryotube with a mill of medium, which is like putting a guppy in a 50, 50 gallon tank, I mean, they're really swimming in there, so small, they were sent up for 30 days, they came back, they've come back four times now and when you culture them after that, they just go nuts, their neurites grow like crazy, I mean these cells are really healthy, we thought that there would be some effect of like microgravity in going through all this on the health of the cells, no, we do think there is a an effect on the differentiation of the cells which we will be revealed when we publish our paper.

所以无论如何，我对太空非常感兴趣，所以当有机会参与一个研究国际空间站词干细胞的项目时，我说是的，而且我开始得很好，我仍然是阿斯彭早期的时候，我们实际上开始了斯克里普斯，但是阿斯彭，我们和纽约词干细胞基金会合作设计实验，使我们能够研究太空中的神经系统，因此我们设计了一个类器官系统，我们正在使用神经器官，其中也有神经胶质，小胶质细胞，它们是大脑的免疫系统，拥有像类器官或小球一样的大脑，最多只有大约半毫米的直径。它们非常大，我们把它们送进了太空，我们已经有四个任务了，现在我们把细胞放入冷冻管中，或者在每个冷冻管中放入1个类器官，用中型磨坊，这就像把一只孔雀鱼放入50加仑的水箱中，我的意思是。它们真的在那里游泳，太小了，它们被送去30天，它们回来，它们现在已经回来四次了，当你在那之后培养它们时，它们就会发疯，它们的神经元像疯了一样生长，我的意思是这些细胞真的很健康。我们认为在经历所有这些过程时，会像微重力一样对细胞的健康产生一些影响，不，我们认为会对细胞的分化产生影响，我们将在发表论文时揭示这一点。

we'll talk to you when they when you publish a paper.

当你发表论文时，我们会与你交谈。

yeah, and you know, you have to repeat your experiment, so we have essentially three good sets of data out of the four runs and we're analyzing the cells by gene expression analysis, we're doing electrophysiology on them, we're doing protein analysis, anything we can analyze, we're analyzing and then histology and all that stuff to make sure that we have consistent results and that we are basing our conclusions, the on real data, that is reproducible and reproducible experiments in space are nontrivial because you can really only reproduce them about once a year or twice a year because you have to get on a flight. So the last flight, we had was in August of this year, the sales came back in September, this one was a little bit different because this time my own IPS cells were made, were used to make the neurons and the glia for the organoids space.

是的，你知道，你必须重复你的实验，所以我们基本上有四次运行中的三组很好的数据，我们正在通过基因表达分析来分析细胞，我们正在对它们进行电生理学，我们正在进行蛋白质分析，任何我们可以分析的东西。我们正在分析，然后是组织学和所有这些东西，以确保我们有一致的结果，并且我们的结论是基于真实的数据。太空中可重复和可重复的实验并不重要，因为你每年只能复制一次或两次，因为你必须要在飞机上。所以我们最后一次飞行是在今年的八月份，销售在九月回到，这次有点不同，因为这次我自己的IPS细胞被制造出来，用于制造类器官空间的神经元和神经胶质。

So I've been this.

所以我一直是这样的。

Is my way of getting into space as a stem cell researcher and I, you know, as far as I know I'm the first. I'm the first to have my neurons in space.

这是我作为词干细胞研究者进入太空的方式，而我，你知道的，就我所知，我是第一个。我是第一个在太空中拥有神经元的人。

So BC you've done it four times, so were the different kinds of, was there some, what other cell types have you sent up?

那么BC你已经做了四次了，那么你发送了不同类型的细胞吗，还有什么其他类型的细胞？

There are a couple of So four times the first two we discovered all the things that could go wrong, okay? And then the second two we then went ahead and did the experiments the right way and gathering the data turned out be really challenging for our last flight, our third because it was actually our second one which was in 2019 and the sales came back in 2020 just in time for the pandemic. Everything just shut down for a year or so. So the analysis those cells is just now finishing and the so we had some success for the second run, the first run was pretty much a loss, but we learned a lot you have to fail sometimes in order to figure out what doesn't work. And then our 3rd, our 3rd, and our fourth were the result of all that knowledge. And when we put it all together, I think we'll have some a really good story about what happens, what might be happening in people's brains when they're in microgravity and then beyond I'm really interested in what would happen to astronauts brains as opposed to their blood or their bones when they go to the moon, when they go to space. So I'm hoping that somebody asked me to make these organoids out of actual astronauts, asked IPS cells and have them accompany the as the astronauts astronauts on their mission like micro astronauts and have them come back and be able to be analyzed to find out what kinds of stresses or what kinds of effects that trip might have had on their brains. So I hope that happens.

前两次有四次，我们发现了所有可能出错的事情，好吗？然后，第二个我们继续以正确的方式进行实验，收集数据对于我们的最后一次飞行来说是非常具有挑战性的，第三次飞行因为这实际上是我们的第二次飞行，发生在2019年，销售在2020年回来，正好可以应对大流行。一切都关闭了一年左右。所以这些细胞的分析才刚刚完成，所以我们在第二次运行中取得了一些成功，第一次运行几乎是一种损失，但是我们学到了很多东西，有时你必须失败才能找出什么不起作用。然后我们的第三，第三和第四是所有这些知识的结果。当我们把所有的东西放在一起时，我想我们会有一个关于发生什么的非常好的故事。当人们在微重力状态下以及超越重力状态时，他们的大脑可能会发生什么？我非常感兴趣的是，当宇航员去月球时，大脑相对于他们的血液或骨头会发生什么变化。当他们去太空的时候。所以我希望有人让我用真正的宇航员制作这些类器官，让IPS细胞像宇航员一样陪伴在他们的任务中，就像微型宇航员一样，让它们回来并进行分析，以找出这种旅行可能对他们的大脑产生了什么样的压力或什么样的影响。所以我希望这种情况发生。

If you're listening Na, please note.

如果你正在听，请注意。

Yeah. Yeah, I think that would be a terrific experiment and really relevant.

是的。是的，我认为这将是一个非常棒的实验，非常相关。

So we're getting towards the end of our time together, so I want to make sure that we end on a note where those that are trying to translate their discoveries into a new company or they're sort of have an idea. What nuggets of information do you have for them? What wisdom do you want them to know? What what would you tell them, you know, starting out?

所以我们在一起的时间快结束了，所以我想确保我们的结尾是那些试图将他们的发现转化为新公司的人，或者他们有一个想法的人。你对他们有什么信息？你想让他们知道什么智慧？你会告诉他们什么，你知道开始吗？

So make sure that you really love the work you're doing. I mean, I, that seems pretty obvious, but I was and that you would be willing to do it for free because you might end up doing so at some point after you start a company. I think I was actually talking with some old friends at this conference this week and they, you know, they all, they all felt the same way about science. They said they would have been willing to do it for free. And so I think that's an attitude you have to have.

所以请确保你真的热爱你正在做的工作。我的意思是，我，这似乎很明显，但我认为你愿意免费做这件事，因为你可能会在创办公司后的某个时候这样做。我想这周我实际上是在和一些老朋友在这个会议上交谈，他们都知道，他们对科学都有同样的看法。他们说他们愿意免费做这件事。所以我认为这是你必须具备的一种态度。

You also have to be really modest about what it is, you know, because you know nothing about how to start a company and you have maybe you're a senior person and you think you've learned everything in your field. That might be true, but you still don't know anything about running a company. It's a very different environment. You have investors, you need to explain things in a different way to investors, and you know you have to, I think what happens? I've seen this happen with friends of mine who went into companies very early on is you have to expect that what you do now is not going to be the same as what the company is going to be like in five years. It will be different. It will either have crashed and burned or be on its last legs because what you decided to do didn't work or it will be really big and you have to be prepared for both of those things.

你还必须对它是什么非常谦虚，因为你对如何创办公司一无所知，而且你可能是一位资深人士，你认为你已经在你的领域中学到了一切。这可能是真的，但你仍然对经营公司一无所知。这是一个非常不同的环境。你有投资者，你需要以不同的方式向投资者解释事情，你知道你必须这样做，我想会发生什么？我在我的一些朋友中看到过这种情况，他们很早就进入了公司，你必须期望你现在所做的不会和公司五年后的样子一样。会有所不同。它要么已经坠毁并燃烧，要么因为你决定做的事情不起作用而处于最后时刻，要么它会非常大，你必须为这两件事情做好准备。

One thing I learned and I decided on was that I did not want to be a CEO of a company because I did not have that skill set. I wanted to partner with a CEO and have a person that would be who would know the other part of the business. So that and Aspen now has a really good CE CEO and I, he's, he's fantastic, he's, he's excited, he's honest, he's, you know, dependable, all those, all those good things you want. And he's also been a CEO before. So he's, he's gone through that stage and what he doesn't know what he's doing, so now he does know what he's doing. So that's the other thing about transition. So I don't, there are occasional cases in which a postdoc will come out of a lab and start a company and the company will succeed, but those are pretty rare. I think postdocs need to get if they, if they want to start companies, they should go to a company and learn how a company works first.

我学到并决定的一件事是，我不想成为公司的首席执行官，因为我没有那种技能。我想与一家首席执行官合作，并有一个了解业务另一部分的人。所以阿斯彭现在有一个非常好的欧洲合格认证首席执行官，他很棒，他很兴奋，他很诚实，他很可靠，所有那些你想要的好东西。他以前也是个首席执行官。所以他经历过那个阶段，他不知道自己在做什么，所以现在他知道自己在做什么。这就是过渡的另一件事。所以我不知道，偶尔会有博士后走出实验室创办公司，公司会成功的情况，但这种情况非常罕见。我认为如果博士后想要创办公司，他们需要去一家公司学习公司的运作方式。

Really good at really, really, really good advice there. So lightning round, just I'm going to fire off a couple of questions. And first thing that comes to mind, coffee or tea?

非常擅长非常非常好的建议。闪电般地转过来，我只想问几个问题。首先想到的是咖啡还是茶？

Coffee.

咖啡。

yeah, lots of lots of black coffee. Your favorite drink, alcoholic or not.

是的，有很多黑咖啡。你最喜欢的饮料，酒精或非酒精饮料。

mango juice.

芒果汁。

Oh yum yum.

哦，好啊。

I, you know, I stopped drinking because I, you know, it just wasn't doing me any good. I will have a glass of wine once in a while, but not very much, not very often. I like to, I mean, I, whatever.

我，你知道，我戒酒了，因为我，你知道，这对我没有任何好处。我偶尔会喝一杯酒，但不是很多，不是经常。我喜欢，我的意思是，我，随便。

do you have a favorite wine?

你有最喜欢的葡萄酒吗？

Yes, I like champagne because it's c-lebrity it has to be a good champagne though it can't be one of those sweet ones.

是的，我喜欢香槟，因为它是c-lebrity，它必须是一个好的香槟，尽管它不能是那些甜的香槟之一。

I promise when we get together, when you're in Boston and we're at High Rock Tower, which I can see out of my window, I will have a bottle BS, thank you. Are you an extrovert, an introvert?

我保证，当我们聚在一起的时候，当你在波士顿，我们在高高的岩石塔，我可以看到窗外，我会喝一瓶，谢谢。你是一个外向，内向的人吗？

I'm an introvert.

我是个内向的人。

Oh, okay, you would not get that from.

好吧，你不会从中得到这个。

I'm an introvert who can do other things, I love it.

我是一个内向的人，可以做其他事情，我喜欢它。

roller coaster or waiting it out and taking pictures for people while they're on the ride.

过山车或等待，并在人们乘坐时为他们拍照。

I guess it has to be the pictures now because last time I was on a roller coaster, I actually did get sick. Before that, I was a roller coaster.

我想现在肯定是照片了，因为上次我坐过山车的时候，我真的生病了。在那之前，我是过山车。

I'm very motion sick now, it's like you hit 30 and all of a sudden the brain says, nope, are you a morning person or a night out?

我现在非常晕车，就像你到了30岁，大脑突然说，不，你是早上的人还是晚上外出？

I can be both, probably more night than morning. But the pandemic has taught me that if there's a conference call or a phone call with somebody Sweden, then I don't mind waking up at 4 in the morning to do it .

我可以两者兼得，可能比早晨更晚。但大流行教会了我，如果有电话会议或与瑞典某人的电话，那么我不介意在凌晨4点醒来去做。

nice. What was the subject that you did the worst at in school?

不错。你在学校学的最糟糕的科目是什么？

I didn't do badly at anything and .

我做任何事情都不差。

that not a single thing.

这不是一件单一的事情。

There was one class I took in college that I was doing an experiment. And I hate to say this because it sounds really arrogant, but I was truly, truly arrogant when I was in college. There was one sociology course, which was a required course. My friend and I made a bet that we could take the final and never attend class and still get a, So I didn't get AI got AB.

我在大学里上过一门课程，当时我正在做实验。我讨厌这么说，因为这听起来真的很傲慢，但当我在大学的时候，我真的非常傲慢。有一门社会学课程，是必修课。我和我的朋友打了一个赌，我们可以参加决赛，从不上课，但仍然得到一个，所以我没有得到AI得到AB。

still pretty good.

仍然相当不错。

Yeah, but you know, there were things I didn't want to learn. I started out in college as a literature major. I thought I was going to be a writer, but then I found that science was a lot more, it was a lot easier for me. I liked the structure of it, but I think that still say with me. I like, I like the sort of imaginative thought experiment kind of side of science a lot.

是的，但你知道，有些事情我不想学。我在大学的时候主修文学。我本以为我会成为一名作家，但后来我发现科学更重要，对我来说更容易。我喜欢它的结构，但我认为这仍然对我说。我很喜欢科学的那种富有想象力的思想实验。

Well, because being a scientist, you have to write. So would that be, do you see yourself ever writing any, any works of fiction or nonfiction?

因为作为一名科学家，你必须写作。那么，你认为自己会写任何虚构或非小说作品吗？

I think I think I need to, yes, I just not ready to start. I have too much to do right now.

我想我需要，是的，我只是还没准备好开始。我现在有太多的事情要做。

I encourage you, I would read that book Professor Doctor G Lauren, it was really wonderful to get to know you on this project, really an honor and a privilege to be able to have so much time with you and speak with you about your career, your life and your interests. Thank you so very much for spending your time with us today. I know you get, I have a lot of choice in what you do on a Saturday, and I'm glad you spent at least an hour. But with me.

我鼓励你，我会读那本书，教授，了解你的项目真的很棒，能够有这么多时间和你在一起，和你谈论你的职业、生活和兴趣，真的是一种荣幸和荣幸。非常感谢您今天与我们共度时光。我知道你明白，星期六我有很多选择，我很高兴你至少花了一个小时。但是和我一起。

Yeah, you'd be surprised, but thank you because I really enjoy getting to talk about this stuff and you've been very, very kind, thank you. For joining us on Biotech Innovators, this is brought to you by Thermo Sure, the world leader in science. If you enjoyed what you learned in this episode, make sure to follow Biotech Innovators wherever you listen to your favorite podcasts, see you next time.

是的，你会感到惊讶，但谢谢你，因为我真的很喜欢谈论这些事情，而且你非常非常友好，谢谢。关于加入我们的生物技术创新者，这是由世界科学领导者Thermo确保为您带来的。如果你喜欢这一集所学到的内容，一定要关注生物技术创新者，无论你在哪里收听你最喜欢的播客，下次见。