Endgame with Gita Wirjawan - Harvey Lodish: Biotechnology - Humanity's Promising Future

Episode Date: January 27, 2023

Harvey Lodish, a professor at the Massachusetts Institute of Technology (MIT) for almost 50 years, explains the significance of biotechnology in the medical world's future scenario. Prof. Lodish also gives his perspective on creating a supportive and lucrative academic atmosphere and science entrepreneurship—based on his experience mentoring two Nobel Prize Winners and starting eight biotech companies, respectively. Prof. Lodish is the chair of the Board Research Committee: Boston Children's Hospital and the founding member of the Whitehead Institute for Biomedical Research. His expertise includes biomechanics, biomolecular engineering, macromolecular biochemistry, metabolism, genetics, to genomics. Some of his well-known companies are Genzyme Inc., Millennium Pharmaceuticals, and Rubius Therapeutics.  #Endgame #GitaWirjawan #HarveyLodish -----------------  Pre-Order the official Endgame merchandise: https://wa.me/628119182045 SGPP Indonesia Master of Public Policy March 2023 Intake: admissions.sgpp.ac.id [e-mail] https://wa.me/628111522504 Other "Endgame" episode Playlist: https://endgame.id/season2 https://endgame.id/season1 https://endgame.id/thetake

Look, it's all education. Yeah. It's all higher education and the willingness of the governments and the politicians to put the money in there. Right. AI and biology are merging and that will become very important in the future. It's already becoming important. Hi, friends and fellows. Welcome to this special series of conversations involving personalities coming from a number of

campuses, including Stanford University. The purpose of the series is really to unleash thought-provoking ideas that I think would be of tremendous value to you. I want to thank you for your support so far, and welcome to the special series. It's such an honor to have Professor Harvey Lodish, who is a founding member of the Whitehead Institute, and also professor of biology and biomedical engineering at MIT. Ravi, thank you so much for the time. It's a pleasure to be on your show and look forward to talking with you. Thank you.

Thank you. I want to explore a little bit about where and how you grew up. You came from Ohio and of all the great universities that you could have gone, but you chose to go to a small college. Tell us. Right. I was a very good student in high school, and everyone assumed I would go to Harvard. I applied to Harvard. It was the only school I applied to. I got in, I got a nice scholarship, but I had visited Harvard, and I realized it was simply too big, too impersonal. I suppose at the time I was pretty insecure.

And I went to my high school guidance counselor and said, where should I go to study chemistry and mathematics? And she suggested Kenyon College. At the time it was an all-men school. about 400 students. It hasn't grown that much. It's now 1,600 and it's co-ed. But I went there, spent a lot of time with a couple of the professors and realized that I could get exactly the education I wanted. I could organize my own class schedule and take the courses that I wanted.

I double majored in chemistry and mathematics and graduated in three years. years. Two of the courses, there were only two students. And one of the courses I put together, I had to do three semesters of physical chemistry in one. And the physical chemistry professor was on sabbatical. But they had a visitor who had just done a PhD in biophysical chemistry. And I talked with him, and we agreed to have a course. There was a book that had just been published called Biosphysical Chemistry, that neither he, of course, nor I had read, and we agreed that for the course we would read the book together. He would give me lots of problems to solve, and in parallel, I would read the standard textbook on physical chemistry, which I found

slightly boring. Anyway, I learned Biosophysical Chemistry and Physical Chemistry and did it very efficiently on a one-on-one course with a professor. And that's the kind of thing you get in a small liberal arts college. You simply can't get it in a large university. So I'm forever grateful to Kenyon that it was really a privilege to be there and have that kind of education. I can relate to this a lot because I'm sort of a product of a liberal arts education earlier.

And what the world doesn't know is that liberal arts colleges, certainly in the, well, they're almost unique to the United States. That's the first point. Most of them started as church-related institutions to train ministers in the new wilderness that America was expanding into. And yet they produce a large fraction of our leading scientists for exactly the sorts of classes that I just talked about. Yeah. We'll get to that. in a bit, but let's, you know, there's been some great personalities coming out of Canyon College, including yourself, of course, a great actor, a former president. Yeah, Paul Newman.

Yeah. But. You acted went in. I was in a Kenyan movie, a development movie where we're together, although I've never met, I've never met him. But my daughter, Heidi, went there. She met her husband there. Right.

Their daughter, Emma just. graduated from Kenyon and I've taught there. I've taught a seminar class a number of years ago on stem cells and I hope to go back to Kenyon and teach a short course on biotechnology this coming fall. So it's always been a big part of my life. I also served on the board of trustees at Kenyon for almost 20 years. You went on to Rockefeller University. I did. Which is a great university that, unfortunately, Unfortunately, not a lot of people in Asia are aware of. Well, they should be because a lot of the students in Rockefeller are foreign.

Okay. And again, I picked Rockefeller over, well, let me go back. I went to graduate school. I started a graduate school in 1962. Okay. And molecular biology was an emerging field. It was not even an established part of biology. There were only three or four universities in the United States that had substantial,

research in molecular biology. Rockefeller being one, Berkeley and Stanford being the others. In a sense, I was taking a risk by going into a brand new field. But there was something about understanding biology at a molecular level that appealed to me. And Rockefeller was, again, a perfect place for me. The whole graduate class that I entered with was about 20 students. And even to this day, several of them are my best friends. Yeah, many of them are Nobel laureates too.

I have friends there. I remember the story of your encountering David. Well, I'll tell you, I should say, my parents were very, very conservative and were quite upset that I wasn't in medical school, which is where they thought I should be. And it got worse during my first day of Rockefeller because I was shown into my single room, but I was sharing a bathroom with the next room, and the person in the next room was a hippie. I mean, he seemed nice enough, but my mother's parting words were, you know, Harvey, he's not our calling.

You shouldn't have anything to do with him. Now, 13 years later, when that hippie, David Baltimore, won the Nobel Prize in Medicine, And then it was completely different. The message was. All over Cleveland, exactly. You know, my son's best friend just won a Nobel Prize. Okay? And David, to this day, is still one of my best friends.

Right. And this is 60 years ago almost. But that's the atmosphere then. I mean, these were a lot of very bright, very creative, very interesting people who were going into molecular biology. And I was privileged to know and work with many of them. So on my thesis committee were two Nobel laureates, Ed Tatum and Fitzlipman. And then later I was privileged to be a postdoc at the molecular biology laboratory in Cambridge, England.

Probably the world's leading center for molecular biology where I was able to work with Francis. Crick, who had just won the Nobel Prize for the NA structure, and also was Sidney Brenner who was going to win a Nobel Prize. And one or two of my classmates did win a Nobel Prizes from there. And you got an offer to teach at Berkeley, and you somehow— Well, no, no, okay. I was in my last year at Rock—well, I'll tell you. I was in—no, it's because of Ronald Reagan that I'm at MIT.

Okay. So my last year of Rockefeller in 1966, I was invited to give a series of lectures at Berkeley, which turned out to be a job interview. And they offered me a faculty position that I would take up in 1968 after my postdoc. And I actually accepted the job that summer. I had to sign a loyalty oath and explaining to a British barrister what an American loyalty oath. from something else. But I was actually listed on the faculty of the University of California, Berkeley.

But that was 1967. This was the peak of the Vietnam War, the peak of the anti-war movement, the peak of students for Democratic Society, SDS, and so forth. And that fall, Ronald Reagan, got elected governor of California and started putting the screws on Berkeley,

particularly. that the faculty should spend more time with students and not politicking and so forth. And I was very concerned. I was in England. And I resigned. And then God bless him, Salvador Illuria, who was on the faculty at MIT then. And again, a future Nobel laureate recruited me to MIT. Wow.

And I've been here my whole professional career. it's been the most fabulous place in the world to be able to do research. And in particular, I get to work with some of the literally brightest students in the world. Tell us about what you've been doing all this time, you know, the field that you've been working on. Yeah, it's called molecular biology. When I was trained as a graduate student in postdoc, the research was almost entirely, on bacterial cells and viruses that infect bacterial cells. Because experimentally, that's what we knew how to handle.

There was very little, if any, work on what we call eukaryotic cells. Cells are the true nucleus that would include yeast, but more importantly include humans and fruit flies and worms and things of that sort, experimental. And we were just beginning to work on these higher cells. So soon after I arrived at MIT, my laboratory started working on the formation of red cells, and particularly on the protein hemoglobin, which is the major protein in red blood cells.

I mean, to give you an idea, we didn't know how proteins initiated in higher cells. We knew that a methanol T RNA was initiator in back. bacterial cells, but we really had no idea of what amino acid, if any, was the specific initiator in higher cells. And I had a brilliant graduate student, David Hausman, who figured out how to solve the problem. And I think it was three years after I joined the MIT faculty, we published a paper showing that it was methioning. And that really was the last letter of the genetic code.

And then at that time, I had my first sabbatian. medical visitor who was then a young MD from Children's Hospital named David Nathan. So he was a hematologist who I guess he'd heard that molecular biology was going to be the future of academic medicine and came to my lab. And together we studied a disease of hemoglobin synthesis, which you may know is quite common now in Southeast Asia, beta thalcemia. one of the two globin chains is not made in the right amount. And we figured out, this is 1970, so we're talking over 50 years ago.

We designed an experiment to show that it was an insufficient amount of the messenger RNA that made the beta globin. Now, we of course had no cloning or anything like that, but we could establish that the message just wasn't there the small amount of message that was there function normally, but it didn't make a sufficient amount of the beta globin, so you had the disease. So it was the beginning of using molecular biology to understand medicine. And that started, for me, a 50-year involvement with children's hospital. You set pretty much the foundation for molecular biology. Talk a little bit about how the process of writing that molecular cells.

A very liberal biology book. Oh, the textbook. Yeah, which is a precondition for anybody that wants to be in this field. All over the world. Well, it's a graduate-level textbook. Yeah. We use it in undergraduate courses at MIT. That came later.

In the 70s, I taught molecular biology, but it was mostly molecular biology of bacterial cells. Because, again, that is what we knew. And then 77-78, I was in sabbatical in London. And then when I came back, I started teaching with Mary Lou Pardue, a faculty colleague, the first cell biology course at MIT. There had never been a course in cell biology until 1978. And we taught the first one, which was sort of a combined graduate undergraduate class. And I accumulated enough notes that I was I thought it would be useful to have a textbook.

You thought it would be easy, too, to write it. Well, it was a long story. I'll try to shorten it. But basically, I wrote the first two editions with David Baltimore. Right. And Jim Donnell, who is a distinguished professor of Rockefeller. And Jim and David handled the nuclear part, that is, the structure of DNA and how DNA is copied into RNA and all of the sort of molecular aspects. And my part covered the rest of the cell, the cytoplasm, protein synthesis, protein secretion, what we knew back then about how cells move, how they muscle cells contract.

how they interact with other cells, that sort of thing. And yes, I said, you know, I can write, I forget, 10 chapters in six months, which indeed I did. The problem, and I was a good writer. I mean, I went to Kenyon and I really knew how to write, and I wrote well. But as a textbook, it was a disaster. And they finally, they, the publishers, Scientific American Press, that, got me a scientific editor who worked with me chapter by chapter and pointed out, you know, Harvey, you know, in this heading, you said that in this section I'm going to cover A, B, and C.

And there were five pages on A and a page on B, and you never quite got to C, you see. And, you know, I just wasn't conscious of how to put together a textbook. Right. But I learned quickly. Right. And the first two editions, as I said, I did with Jim and David, and then they decided to step back, and we started recruiting a number of other authors. And I have to say writing this book, particularly with my co-authors, has been very enriching experience. Before we were, there are nine editions.

And before each edition, we would meet for a couple of days and just talk. You know, what's new in science? What should we include? What are the hot new things that are solid enough that they belong in a textbook? Right. You see. And what could we exclude? What's old?

Are there techniques that we're covering that people aren't using now and that sort of thing? So those discussions were very, very informed. and figured out who is going to write what chapter. Each chapter has a major author, but each chapter is read by one or two other authors. So it's really a community effect. It's been translated into, you know, a number of languages. It's in 14 languages. My gosh.

When is the Indonesian version going to come out? Well, I'll have to ask Nova. I would love it. The Vietnamese edition came out. Oh, my gosh. They got ahead of us. No, do you know there was a Vietnamese edition? I heard about it.

Yeah, no, again, it was a student of mine, Midler, who is now a professor at National University in Singapore, but she grew up in Hanoi, and she organized the Vietnamese translation of the book. and really found about a dozen Vietnamese who were fluent enough in English and knowledgeable enough about the science to translate it. So it came out. Do I see any of them here?

I had a couple on the desk. Well, this is the English version. That's the English version. The fourth edition? There's one. Oh, no. No, that's Japanese. Anyway.

Well, we got to work on translating to Bahasa or Indonesian. Well, and my understanding, correct me if I'm wrong, is that that would work also in Malaysia. Yeah. You see. Some parts of Thailand, too. Okay, well, you know, what we worked out for the Vietnamese edition, it was published in five small paperback books. Okay. Each one costing about four or five dollars.

Yeah. So the idea was to make it very important. inexpensive and make it accessible to everybody. Right. And nobody made money on it. So I arranged that there were no royalties to the authors, either the authors of the American edition or the Vietnamese edition. The publishers in New York got no revenue from it.

There was an excellent publisher, Trey in Huchman City, that, of course did. earn money on it. It was when back in 2019, I was there for celebrating the publication of the last two volumes. And I was a bit of a celebrity.

You still are? Well, no, I mean, this was... I can't believe I'm the rule. My picture was on a huge bulletin board on a major street in Hoceman City. And the street was filled with about 500 students and there was a band

Oh, man, we got to get a bill for it with your face on it. It was really quite rewarding, and I sat there for about two hours autographing copies of the book. And, I mean, it sounds hokey, but, you know, these were students who were standing in line to get a copy of the book so that they could read it. And this is a science book. This is not a copy book.

Your book is the holy book for anybody that wants to be the book. Well, it's not holy. It's not religious. I mean, it's, well, you know, it's the metaphor of a Bible. It is one of the most used books in graduate courses. And it covers a lot of areas from transcription and DNA replication and everything to do with gene expression and its regulation to stem cells to how the nervous system functions, how the immune system functions. So it's used very broadly. And at a personal level, our daughter used the fourth edition when she was in medical school.

And one of my grandsons just graduated from the University of Virginia and used grandpa's textbook in his salveology course. But he has a different last name than me. Okay. So. Did you offer any tutorial? Well, no, no, Isaac, no. Isaac was very talented. Put it that way.

His name is in the book in the acknowledgement section, but nobody reads it. So his professor had no idea that his grandpa wrote the book. But that's okay. I want to push on this. I think it's important for people to understand a little bit better about the process of education. You've grown up, you've been working with so many Nobel laureates, even to the point where you've actually mentored a couple of two Nobel, Couple of Nobel laureates.

Two of my postdoctoral fellows, Aaron Chaconover and James Rothman, went on to win the Nobel Prizes, yes. And eight of my students who are in the U.S. National Academy of Sciences. I don't know that it's a record, but I'm very proud of their accomplishment. Okay, as a Southeast Asian, I'm sort of vested in what it would take for Southeast Asia to be up there, you know, in terms of being recognized, at that kind of level.

You need to build top-level universities and put in the money to generate the facilities that will attract and retain world-class people. From anywhere around the world? From anywhere around the world, but particularly from Indonesia. Yeah. You know, I'm staring at one of them right now.

You know, one of the most talented undergraduates from Indonesia. Right. Valentino came to MIT. He's now in graduate school at Stanford. He's getting a fabulous education. Now, whether he will go home to Indonesia is an interesting question. And if he does, are there facilities, universities, laboratories, where he could do his research and train Indonesians students,

at this sort of high international level. And it's much deeper than just saying we need a great university. I mean, countries like, well, every country. They have diseases that are common, particularly genetic diseases, that are common or abundant in a particular area, perhaps, in Ireland. There are agricultural issues. that need modern technologies, improving yields of crops, that kind of thing. Biological technologies as part of climate remediation,

where you really want your own talented students to stay there and do research that will benefit the country specifically. Indonesia should be able to make many of its own pharmaceuticals, you see. and innovate some new ones. I mean, for instance, the disease like beta thalassemia is endemic in many parts of Indonesia, as it is throughout Southeast Asia. And we have gene therapies for it that work in the United States, but these are very expensive, very complicated technologies.

And can one develop gene therapies that could be used on a mass level to eliminate the suffering of beta thalcemia? Right. You see, just as an example of the kind of thing that could be done that requires highly trained people with a lot of facilities. So when I'm asked this question, I always look at the universities to start with. And, you know, in parallel to develop the secondary schools that will train the people at a high enough level so that they can, do this work at a high level in the universities. Well, you know, what Valentino is doing, what NOVA is doing,

they're an extension of what you've been doing, right? Oh, yeah. And I think the application of what they're doing will be so tremendous for not just Indonesians, but many people around the world. Oh, absolutely. I mean, they're both working at, you know, the highest level on the type of institutions. I mean, NOVA is now the CEO of a company. that is developing novel treatments for certain autoimmune diseases.

Right, right. And these autoimmune... Which is relevant to a lot of situations in Indonesia. Well, it's relevant to autoimmune diseases are common throughout the world. No ethnic group is spared. Correct. And yet the work right now has to be done in the United States because there aren't facilities.

On the other hand, we're talking about establishing a manufacturing facility. for some of these recombinant proteins in Indonesia. Now, that would be new there, but again, it would be an example of what could be done, but we'd have to train the people inside in the country to run these machines. Do you see biotechnology more as a remedial technology, as opposed to something that could be augmenting

upon a pre-existing condition? Well, right now we see it as long-term therapies, particularly therapies for diseases that are lethal or very, very debilitating. Yeah. I mean, the two that my lab is focused on, and several of my companies focus on, are sickle cell disease, which is endemic in Equatorial Africa. Right.

And then beta-phalcemia, which is, you know, endemic in South Southeast Asia. I mean, these are huge public health problems. And much of the courses that I teach in biotech focus on these, and the gene therapies are spectacular, and they do work, but they're very expensive, and they involve long-term hospitalizations, and they will cost in the millions of dollars,

which may be tenable in the United States. We're not sure, but it's certainly not. tenable in any lower middle income country. Right. I want to talk to you about CRISPR. What's your take on CRISPR? I mean, that's been proven to be good for sickle cell disease. Yeah, CRISPR is a kind of, it's actually not one technique, it's several techniques.

It's basically a way of bringing a protein to a specific piece of the DNA of the genome. And in the original iteration, when it goes to that site of the genome, it cuts the DNA. But modifications of it means it can change one base. It can induce expression of that region of the gene. There are a lot of clever things that CRISPR can do that aren't in the public press. And a lot of groups are trying to develop this into real therapies. The difficulty is getting the CRISPR itself into the right cells.

Once it gets there, it can do great things. But getting it into the cells, cells normally don't like to take up foreign proteins. You say you have to use tricks or they don't like to take up foreign DNA, which could instruct the cell to make the protein. So it's complicated. And yet it is working in several companies. and it will be very useful. But how we're going to pay for it is another issue.

You see this as being transformative in the near foreseeable future? Yes, if a lot of these technical problems can get solved. It will be used in how many diseases for what purpose remains to be seen. Pediatric blindness is another. Yeah, yeah. I think diseases right now, everyone's talking about either lethal or very debilitating diseases. I mean, sickle cell is not generally lethal, but it can be debilitating. And it certainly shortens the half-life, the lifetime of the person. But, you know, we talked earlier. I have a grandson with Gossé disease, and he's being treated quite successfully with enzyme replacement therapy. And we don't know

the long-term risks of gene therapy. I mean, I could make a gene therapy for him in my laboratory. Technically, that's not all that complicated. But would I subject him to this? Right now, the answer is no, because we don't know the long-term effects. Perhaps in 10 years when there's more safety profiles and things like that. These are brand-new technology, as you say. Yeah. Well, you know, you hear stories about genetic editing, right? Yeah, well, this is part of... It sounds a little bit scary because people tend to interpret it as something that it could actually augment humanity, increasing... Well, okay, you have to be careful with what you mean.

We are not gene editing the germ cells. In other words, the only cells that we have that pass on genetic information to our offspring are the sperm in the eggs. And right now these are not being edited and there are prohibitions everywhere so that you don't do that. It can be done technically. That's not the issue. Right. So it's done on what we call the somatic cells, the cells that form our tissues and organs, but are not passed on to our offspring. And my instincts are that rule is going to stay for quite a long time. In most countries.

Hopefully in all countries. Hopefully in all countries. You don't see the geopolitics of things, reshaping. There's no rational... There's no reason you would want to change the DNA of your offspring. There are other ways of preventing passing on bad genes to your offspring. And for the record, there's... no easy way of doing gene therapy on sperm or egg cells anyway.

Okay. But what about conversations that talk about potentially increasing somebody's IQ? That is far in the future, if it will ever happen. There is no single gene that controls IQ. There are certainly mutations that cause intellectuals. intellectual disability and one might want to treat those in a young child. I mean, in fact, for instance, one of my companies is focusing on gene therapy for Drouvet, which is a pediatric epilepsy, but also the children have enormous developmental defects.

Now, it may be that our gene therapy would correct the developmental defects and the children would be able to speak, which they currently cannot do or do so poorly. On the other hand, that trait would not be passed on to the offspring. You see, it would be, again, somatic gene therapy, in this case, to the brain. And their one would argue, sure, if you can take a nonverbal child and get her to talk, that would be huge, you see. So again, we're talking about correcting genetic defects and not trying to improve something.

Yeah, exactly. And, you know, the studies of intelligence have clearly said that there's no easy way of putting a gene in and increasing your intelligence. And for that matter, even measuring intelligence is complicated, and there's a lot of discussion about what that means. So it's not something I can see happening in the near future now. I want to get to the business side of things, right?

You've been exposed to combining signs in business since the 60s and 70s. And you've been a big part of making Boston or Cambridge the way it has turned out in the last few decades. I mean, in 1961, I was working in an organic chemistry. laboratory at Stanford. I was a Kenyan undergraduate, and the head of the lab, Carl Jurassic was a Kenyan graduate, one of the world's great organic chemists. But he had also realized that starting from a particular chemical in a Mexican tree, he could synthesize the molecules that became the basis of the oral contraceptive, the birth control bill. And when I was at Stanford in 61,

I would visit Syntex S.A. his company. Right. Because his graduate students would work part-time there and part-time in the Stanford lab. And I could see what was going on. It never occurred to me that I would be part of this sort of thing. But 20 years later, when cloning was coming along, and there was, for the first time, the ability to isolate the gene for any protein, and manufacture the protein, that the first generation of biotech was born,

which were all recombinant proteins or monoclonal antibodies. So that's when I got involved together with seven colleagues from MIT and founding enzyme, which made the first enzyme replacement. My gosh. It turned out okay. It became so big. Yeah, well. You got acquired by Sennifer, right?

Well, we did, but this was the vision, not of the age scientists, particularly, but of Henry Tamir, who was the businessman who was the president, who realized that one could build a company on recombinant enzyme replacements for rare genetic diseases. As I may have mentioned, my grandson has Gosey, who's been on the enzyme drug for, what, nine or ten years now. Now, it's covered by insurance, but his insurance pays about $200,000 a year for the product. So it's It's not inexpensive. On the other hand, it's allowed them to lead a perfectly normal life. Right.

Tell us the story about how you first discovered money, right? How I discovered money. Your scientific pursuit was actually worth a lot more than you thought when you met up with investment banker. Well, this was at the very beginning when I was talking, this is well before Genzyme, when You met a lady. Well, no, she was our next to her neighbor, Linda. Right.

And we were just talking about the possibilities of biotechnology. And she worked for a small investment bank in downtown Boston and brought me there one day for lunch. I'd never been in this kind of environment. But I was sitting at a lunch table with a group of bankers. And just talking in general about the research in my laboratory. making recombinant proteins and so forth. And at one point, the head of the bank turned to me and said,

you know, Harvey, we like you and we like your research. And we'd like you to start a company and we'll give you $5 million. Now, that was a lot of money and certainly more than I had ever heard of in my life. So I was kind of stunned by it and didn't know what to say. So I said nothing. and the gentleman seeing my unease turned to me and said, well, you know, if money is a problem, I'm sure we can get you $10 million. And this is not a joke. I realized what I was worth. The laboratory that I had built and the research that we were doing had measurable value in the commercial world. And I never followed up on that, but it was that conversation that led me to,

talked to a lot of my faculty colleagues at MIT, many of whom were given similar offers. And eight of us formed, this is pre-genzyme. We formed a professional consulting group called BIA, Bioinformatics Associates, where we did a lot of consulting throughout the world on biotechnology. We actually positioned ourselves as strategic management consultants to advise multinational corporations on the impact of biotech on their core business. And that taught us a lot. I mean, there were five of us spent a whole wonderful week in Paris for the food conglomerate.

I'm not joking. I mean, they took us to the Stella Artaire brewery. It's just amazing. And asked, you know, what impact will biotech have on the beer industry? Because there were notions that you could use the yeast to make recombin in human proteins, which made no sense. Anyway, the simple answer is it has no effect, and they were willing to pay handsomely for it. But this was the group that wound up putting genzyme together.

So, you know, it was a very interactive group. No, we were all from different fields. I was a cell biologist. There were organic chemists. There were biophysical chemists, food process engineers, bioreactor designers, and so forth. And we really work together as a group to put together a enzyme and then to serve as a scientific advisor. What did you learn in terms of having the ability to combine science and entrepreneurship?

And I want to take this a little bit further. The biotech industry has just blossomed. Right. And what you said is key. that is what I've learned and what I try telling governments throughout the world, the key is actually faculty entrepreneurs.

You know, faculty members in whose lab, certain discoveries were made that they realized could be converted into a therapeutic or a diagnostic who then work with the business folk to set up and run a company. And, you know, as you may know, I've started probably a dozen companies,

But when I say start, I will serve on a scientific advisor board. I'm not allowed to actually run the company. And I'd be incompetent to a company. That's not my skill. My skill is evaluating science and figuring out how to make things work better and so forth. The business end, I leave to the business people. How easy is it to replicate faculty entrepreneurship? We teach it all the time.

I mean, I learned here. But, you know, I'm sure there are so many countries out there that want to replicate what Cambridge is not. No, no, no, no. When I joined the Children's Hospital Board of Trustees, I work with a technology licensing office, and they set up really mini courses for faculty. You know, most faculty have no idea what a patent is. We can start there. You see, what exactly is in a patent?

What protection does a patent give you? Does a patent allow you to sell your product? No, it prevents other people from following your invention. Well, that's very different, you see. So, you know, a one or two hour course on what is a patent becomes very important. What is venture capital? How do you fund a company? You see, that's something that is mysterious to faculty outside of a few, even in the United States.

Right. You see. So that's what I try to do when I go to countries like, I mean, wherever I've been recently, Japan, Singapore, France. China. China. India. Well, I was in India, but as a tourist. Although I have been there on that when I was in Calcutta.

I've been all over. I've been to Chile. I've been to other countries. We've got to talk about your visit to Indonesia. You were there quite recently. I've been a couple times to Indonesia. I know. But as a tourist.

What was your take on a country? Which parts of Indonesia that you visit and what turns you off or what turns you on? Well, I like, I should say, when I say, I mean, my wife and I. You and a family. Yeah. And we like going off the beaten track. So one of our first visits, we went to Barogadoor because it's, you know,

Tartit is the largest Buddhist monument in the world. In fact, much of the base is Hindu. Right. But, you know, I'm proud of the fact when I saw the complex, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the. monument, I recognized what it actually was. But anyway... But Buddhism was first in Indonesia before Hinduism came over. No. The foundation is Hindu. Oh, yeah. I mean, the foundation...

You want to go back hundreds of thousands of years. That would have been in India. Yeah, yeah. But the base of the statue, the base of Barobador, the whole... You're right. There's Hindu influence. No, it is not Hindu influence, it is Hindu. Okay, fair enough. It is Hindu, and then the second layer is Buddhist. Anyway, I like this kind of stuff.

Yeah. And so that trip was Barobador, and then we went to Taraja. Hang on, you went to Pramban also. Prabanon, yeah. Yeah. Which would have been Hindu. Prahbanon was Hindu. Yeah.

Well, there were three temples. Correct. And then we went to Taraja. And it was just fascinating. You survived the seven-hour car ride or you stopped over somewhere? We drove from Makasar to Penny and stayed the night and then drove up to Turaja. You know, if you want to visit interesting places, it takes time to get there. But then more recently, my wife and I went back with three of our young grandchildren.

There you go. Flores and Bali. And we spent quite a bit of time in Bali where I officiated at the wedding of Nova, one of my students, on the beach and Denpessar. But then the whole wedding party got on two boats. We flew to Flores Island and got on two boats and visited the Komodo Island and Komodo Dragons. And it was fabulous. So, you know, as a tourist, it's a fabulous place to be. And, you know, the people are very hospitable.

We had, just every place we went, it was just very, very pleasant and interesting. You know, I remember particularly in Turaja, we went for long walks into the villages and so forth. I thought we would just meet people, and they were just the most open, you know, wonderful, hospitable people. I mentioned that because it is a Muslim country. Oh, but it's diverse. It's very, you know, several of our friends were concerned that we were going to a Muslim country. I'm telling you, this is the... They were watching the wrong channels.

They were watching the wrong channels in the United States, and I kept saying, no, this is not what Islam is. And Indonesia was entirely safe. That's a general observation about Indonesia. Here's the fourth most populous country in the world. the third largest democracy in the world. Yeah. But nobody talks about it. Enough.

Well, this is why I was privileged to spend time there. Yeah. And to see it and to meet some of the people, of course. And I've had many Indonesian students here. Well, I mean, there should be more, if not a lot more. I mean, the representation of Indonesia through the Valentinos of the world, the novas of the world, could be more. compared to some other countries of scale.

No, I agree with you. Many countries send more of their top young people abroad. Right. And that certainly would help. But again, I argue that you really want to build the universities in the country. I agree. I agree. That, you know, many countries I visited in Asia and for that matter in South America,

the elite all send their children abroad. Share your thoughts or observations about the Indian universities and the Chinese universities. Yeah, well, again, I've been to probably a dozen in each country. India, I was very sad when I visited universities. The ones I visited really were 20, 30, 40 years out of date. in terms of the facilities. The government just doesn't spend enough money there. And what I learned is at least a few years ago when I checked it,

it was something like 0.7% of the GDP in the country was spent on research, which is far lower than the G20s. And then, on the other hand, I've been to China probably a dozen times in the last 10 years. And when I first visited China in 1995, the universities and the research institutes were really struggling from the aftermath of the cultural revolution. And what I learned is there were only about 10 million university students in the entire country. China, albeit not a democracy, has built dozens, if not more, universities. And several of them are absolutely world class. Correct.

Particularly, Peking University, Qingwa, Fudan. Or you've been teaching too. Pardon? You've taught there. Well, I've lectured there in several, and I have many facts. I mean, for instance, one of my former postdocs, Wu Hong, is the Dean of Biology of Peking University. And she's hired literally dozens of top faculty there.

Right. You know, just to give you a picture, when I went to school. here in the 80s. We had about 16,000 Indonesians all over the U.S. at any given point. Okay. Right now it's less than 9,000. Interesting. So it's dropped. It's dropped. And I would argue that some of the drop is attributable to some rotational behavior to other countries. Yeah, yeah. But you know, that number should have been in the 100,000, at least. You know, you've got 450,000 Chinese in the U.S. You've got probably 150,000 to 200,000

Indians studying at... And Indonesia's at that level of population. It's not a small potato. It's 280 million people. Yeah. You're probably likely to see more Singaporeans at any campus. Which is what? 5 million people?

5.5 million? Yeah. You're probably now likely to see more Vietnamese, you know? Interesting. Yeah. At MIT, you know. Vietnam has a lot smaller population, less than 100 million people. Oh, yeah.

And it's a game of scale, right, for the benefit of all of Southeast Asia? Look, it's all education. Yeah. It's all higher education. And the willingness of the governments and the politicians to put the money in there. Right. The United States, our education system works because it's largely private. Right.

Most, certainly not all, but most of the top universities are private. Right. And they're run by philanthropy, by grants, and a variety of other things. A few of the states like California have extensively supported the universities. Berkeley or the University of Virginia or Wisconsin or many others are absolutely world-class. But not all the states do it. Yeah. Harvey, this has been great, but I want to ask you one last question. This is on a topic of artificial intelligence versus biological intelligence.

Artificial intelligence seems to have grown quite exponentially, right? Oh, it absolutely has. Do you foresee the kind of exponentiality with which works on biotech will be moving? Well, I mean, AI is heavily influencing biology. I mean, the most spectacular recent ones were AI programs that predict the three-dimensional structure of proteins from their amino acid sequences, which is a Google offspring. It was not a Google. And they can predict the, which is something academic scientists could never do, but actually predict

with a great deal of success. the molecular structure of proteins. And that can greatly expedite drug development, because if you have the structure of the protein, you can begin imagining how a small molecule might interact with it and change its properties, inhibitor, or turn it on or whatever, as a drug. So...

The future is pretty bright. And you see biotech not being able to grow as exponentially as... Well, okay, there I can. can't help you. Biotech is growing by leaps and bounds. It has certain. AI is growing by leaps and bounds. AI is influencing biotech in great ways.

Wow. You know, another is in diagnostics that is in radiology, looking at an x-ray and trying to decide if the patient has lung cancer. AI programs can often do that better than the most highly trained radiologists. Okay? Amazing. So, AI and biology are merging, and that will become very important in the future. It's already becoming important.

Okay? I'm glad to hear that. Good. Any final message for all of us in Southeast Asia? Build up your universities. build up your education systems and train people locally in these modern techniques, these new developments in biotech, in AI, and whatnot, to help the country solve whatever problems it has, biological problems, medical problems, agricultural problems, and so forth.

It all hinges on better education systems. Thank you so much, Harvey. Well, thank you for coming to my office and interviewing me. It's swell. Okay. That was Harvey Lodish from the Whitehead Institute. Thank you. This is Endgame.

My gosh, that was... Okay. Thank you so much, my man. Okay. And Dr. Silver. Dr. Dr. Dr. That's me. I'll text you later.

Yeah, no, no, no. I'll just show you. When we were in Vietnam, and he, so he took, this is my granddaughter, and there was another guy on the boat besides the crew whom he introduced as his cousin.

It wasn't his cousin. This is a picture of me, my family.