Endgame with Gita Wirjawan - Walter Gilbert: Tech Feudalism, Bioethics, and Winning the Nobel Prize

Episode Date: August 12, 2024

Join Endgame's first and biggest conference ever! https://www.endgametownhall.com ---------------------- Join Gita Wirjawan for an in-depth conversation with Nobel Laureate Walter Gilbert as he shares his extraordinary journey from his early life in Cambridge to his groundbreaking contributions to science. Explore his shift from chemistry to theoretical physics, the pivotal role of technology in his lab experiments, and the critical discoveries that shaped modern genetics. Delve into his entrepreneurial ventures, the ethics of scientific advancements, and his thoughts on the current state of science and society. #Endgame #GitaWirjawan #WalterGilbert ---------------------- About Luminary: Walter Gilbert is a renowned American biochemist and 1980 Nobel Laureate in Chemistry, known for his pioneering work in DNA sequencing. He also co-founded biotech companies Biogen, Myriad Genetics, and Paratek Pharmaceuticals. Beyond science, Gilbert is also an accomplished artist, working primarily in photography and visual arts, with his works exhibited in galleries worldwide. About the Host: Gita Wirjawan is an Indonesian entrepreneur, educator, and Honorary Professor of Politics and International Relations at the School of Politics and International Relations, University of Nottingham. He is also a visiting scholar at The Shorenstein Asia-Pacific Research Center (APARC) at Stanford University (2022—2024) and a fellow at Harvard Kennedy School's Belfer Center for Science and International Affairs. ---------------------- Earn a Master of Public Policy degree and be Indonesia's future narrator. More info: [e-mail] https://admissions.sgpp.ac.id https://wa.me/628111522504 Visit and subscribe: ‪@SGPPIndonesia‬ | @Endgame_Clips‬

Moles itself is used to. What we do with it, you know, is here part. Humanity is dangerous. Dr. Wally Gilbert. Dr. Wally Gilbert, who won the Nobel Prize in Chemistry in 1980 for discovering one of the first methods for sequencing DNA. You could say that Wally is one of these people who needs no introduction, but I actually think he needs 14 introductions because he's had 14 jobs.

Professor Gilbert is not only the scientist, who's also a successful businessman, and a great artist. So our sequencing method and Fred Sanger's method, both the police just run this 1976 spirit. And by 10 years later, 8 million bases of DNA and incisions around the world. We talked about tech feudalism. It's amazing how few and fewer.

We're controlling more. Whilst we no longer have the virtue of the capitalist system, our GDP, a good chunk of it, is totally fictitious because it's, in fact, money just piding itself on making more profitable money, not actually making anything. What should you take on perspurn? I always defined this as physics envy on the part of the biologists. They began to tear their shirts and say,

we're doing something dangerous. Stop us before we destroy the world. Hi, friends. I want to take this opportunity to thank you for being with us ever since we started Endgame some years ago. The conversations have been invariably elevating, and animating, at least from my personal point of view, it's been a tremendously rewarding experience. And I'm hopeful that you could be further supportive of us by way of clicking on the subscribe

button, watching every episode as much as possible, if not as fully as possible, and also joining us as a member of the Endgame channel. I can only promise you that whatever we're going to be doing going forward, we'll try to make endgame a better experience for all of you. Thank you. Hi, friends. Today we're honored to have Wally Gilbert, who is a Nobel laureate in chemistry. And Wally is a longtime friend of Harvard University.

He's been teaching there. He went there to study. Wally, thank you so much for coming on to our show. As always, I always ask my guest about how they grow up. Talk a little bit about how you grew up. I was actually born up here in Boston, in what was then Richard's house, in the hospital. My mother was a psychologist, and my father was at that time a assistant professor at

Harvard in economics. They had gotten married on the way up to Harvard. She went to Bradpiff and arrived there as a married woman, which was then considered totally scandalous in those days. So I spent my childhood up here in Cambridge and Watertown. I was homeschooled. My mother thought the local schools were terrible since she had a college degree. The rules were that she could really teach at home.

And so she taught my sister myself how to read and we read extensively. I was trying to think of, I went to Washington. My father went to Washington as the Harry Hopkins Brain Trust working for Roosevelt in 1949. And we then went to Washington. I went to school actually in Washington. and so my early schooling years were all down there. I grew up, I mean, even when I was here at the age of eight, I had a chemistry set.

I'm laughing because in those days, and of course all through that period, you could buy chemicals, strong chemicals, male, if you can set of things, a chemistry laboratory at home. I actually blew myself up making hydrogen at one time and still have a scar on my wrist from the broken glasses. My mother is, I'm sitting near the kitchen playing in my laboratory. When you were eight. No, this is probably later. This is when I was in probably high school. It's not what I made this is after.

After I'm in Washington, four years lived, 12, I'm probably 13 and 14. My mother actually is sitting watching me. I'm experimenting, making hydrogen, hydrochloric acid, and zinc. And I light it too early, and a bottle of flask explodes, and I have a nice little scar right here. Get taken and stitched up. And my mother's memory of that episode is that I'm very quiet. is that I'm very quiet as we're going to doctor and finally I say to her,

I know what I did wrong. So I collected minerals. I, as I said, was interested in chemistry. I had my uncle's college chemistry texts left off from his college experience so that I was happily, you know, night to late grade school reading those things. I went to high school in several friends, which is a Quaker private school in Washington, mainly because I had gone to school in Virginia at that time

toward the end of the war. And Virginia didn't teach Latin. was the Washington District Schools taught Latin. And so I couldn't switch into Washington High School since they didn't know any Latin. And luckily, private school permitted me to... They're not knowing Latin, so I never learned any Latin. Took French and German in school. Because my memory of that entire experience in high school,

one of the memories is that I spent most of my time in the Library of Congress, reading about all sorts of things going on, reading about atomic energy, actually, because that's a period from, it's at high school from sort of 45 to 49. So it's right after the war, the atomic bomb has dropped in 80 in 45, and I'm fascinated by the physics of it, and so I read this Mike's report. I was reading, trying to build x-ray machines, reading papers, reading things, as the Library of Congress until the school finally wrote to my mother saying, you know,

he should attend school a little more. And so my memories of growing up, really that collected minerals. I joined the mineral Society at following the age of 13, even being young as a person there, and wandering around being interested in such things. went to Harvard thinking I would be a chemist. This would have been after the war. That was in 1994. My father was in the government during the war.

And then I'm going all the way through. He was the chief economist for the office of price administration during the war. Before when he'd gone down to Washington, he was among other things, he wrote speeches through us, well, and all sorts of things. But he then became a private economists after the war. And then a later point, he began, he ran the Ford Foundation program providing economic advice to the five-year plants in Pakistan. So he went to Pakistan in the 50s.

and I visited him there in 61. So it's a later time, another story. Right. So I'm going to Harvard, I thought I'd be a chemist. It was a chemistry and physics combined major, so I took that. And my interest gradually shifted from, I found the chemistry,

those days, it was a very antique chemistry. So being taught by Louis Feezer, who dominated the organic chemistry field, organic chemistry field but sort of kept it 20 years out of date until he retired and then suddenly came but that was after my time the chemistry renewed and became something different. I became more and more interested in physics and theoretical physics, which is the highly mathematicized side of physics and graduate. Should I go on and sort of time?

Sure. Sure. Graduated from Harvard in 53. And first went to graduate school at Harvard per year and then went to Cambridge. Why Cambridge? Cambridge, England. Why? Why not Harvard?

Why? Well, because... Why not the US? Because in fact, in those days, in fact, people often, people just travel more freely. Got it. My feeling about science, especially then, is totally international. And, you know, the history of American science is, of course, people going to Germany to learn quantum mechanics, the whole previous cycle. The people like Alpenheimer coming back here, you know, then created schools of science in America.

But the relationship, science around the world, then was much more fluid than it is now. I mean, now they're much more barriers. Even though lots of people still come here to study, we put up much more. barriers against people coming. Those days, in terms of the, in terms of the thought, oh, going to York to study science is a perfectly natural thing to do. And people still do it.

I mean, so, but it has become rare. Those days are still perfectly reasonable. It's a perfectly reasonable thing to do. I, well, the graduate student at Cambridge, went there, we call out a research student, went there for two years, came back to the States, still sort of enlisted at Harvard as a graduate student thinking I'd do a Harvard PhD, but I just kind of sit in on courses. They wouldn't be to take more courses, I couldn't stand it,

so I stopped taking courses and wrote my thesis and sent my thesis by mail to Cambridge in those years. you submitted a bound thesis. And it was then examined and it was either accepted or you came back a year later. No correcting of typos or anything like that. It was already a bound document that was going to the library. And I was a student, officially graduate student, here I get called into, or get examined by Vicki Weisskulp and Hans Beda over a student, over in Vicki's office at MIT. And there's sort of been an evening and we have a thesis examination and they passed me and I become a P.m., become a doctorate. I was already married. I was married at the time I got married in that year I graduated Harvard. You got married with somebody you met when you were

eight. That's right. I met my wife back in Washington in 1940. her father was a journalist, Die of Stone, and came to Washington at that time. And he came to borrow $5 from a cousin of my father's and my father and the cousin's family were all living together in a big house in Washington. And so my family met Celia's family, and they became friends. And so I met at the age of eight, she would come over and have overnights with my sister and so it was about six months the other than i have and um i see her in our shirley temple night galile in any case we became friends uh at that point and years later we started going out together and then um it became serious as she graduated uh high school

which is sort of the year after i went up to college and then got married right after I graduated right before she graduated. You're still with her. Yeah, we're still together. So we've been married 70 years at this point. My gosh. I got to ask you later, when you do it. And then?

It's quite wonderful. So I was just thinking I can. I would only, we'll have this, I wrote quick, in theoretical physics, written enough papers so that Harvard made me an assistant professor in theoretical physics. And so in 1950, came back to Harvard in 1956 from Cambridge, I guess at page 27, 58, that's probably 50. I became an assistant professor, first an instructor and then an assistant professor. And so I began teaching quantum theory, quantum field theory, electricity of magnetism, the basic courses for the graduate students, the wonderful experience, strange experience,

suddenly being on the other side of the lecturing to students, about two years before he'd been sitting in, in the class, taking a class, then you suddenly find yourself on the other side, teaching the class. You enjoyed it? Yeah, we've both enjoyed it. And the life, it's hard to be a professor if you don't at some level enjoy what you're doing enough. So one of the major things you do is a professor's you teach. So the scientists, actually very amusing inside us, we give talks,

we almost always do it without notes. And the humanists simply read their talks. Very, very interesting. The scientists simply, we practice our talk before the class, but in fact, it's done much more and lived. I was just trying to think. So, talk about the transition to biology. So here I am writing papers.

writing papers and theoretical physics. Fundamentally, how did you change from being theoretical to being experimental? Would that go back to your early days? Special thanks to the Belfour Center for Signs and International Affairs at Harvard Kennedy School for providing support for this episode. Check out links in a description to know more about research, ideas, and leadership programs for a more peaceful world. As I said, I'd use my hands. There's a period in which I'm supposed to be writing my thesis. My wife is getting nervous. I mean, here it is now fourth year.

We've married several years. We spent two years in Cambridge. We're back in this Cambridge, living in an apartment on an NSF graduate fellowship. In those years, we're living on $2,500 a year. hundred dollars a year, which is the nature. That's a lot of money. Back then, it was a graduate fellowship. There's a moment in which I, we're in England then, I think fellowship.

The renewal hasn't arrived and I turned to sit and I say, oh, I'm sorry, the people are going to have to go home. And she says, it's the wrong day. And then it arrived the next day, I had another year of fellowship. But there I am supposed to be writing my thesis and I'm sitting on the ground of the soldering iron, you know, putting together an amplifier, you know, recorder, making from a fancy kit, making a 15-watt amplifier. It was as you could get a kit and then it can solder and put it together. I was going to say the last paper I wrote in

Tewebrenah for physics, Higgs had to disprove in order to develop a theory of the Higgs boson. And I was proud of that paper, but it turned out to be wrong. Somebody said it to me again years later as Higgs boson became very famous. I was amazed that I thought I remembered it, but there's all sorts of things in it that I Couldn't remember it all and couldn't do it all anymore. Switch to biology. I met Jim Watson at a party in Cambridge. Celio, my wife always claims that he was attracted to her ponytail and started talking to her.

She brought him over to talk to me and we found the conversation and probably spent an hour or so with that party talking. I had already heard about the DNA structure of to having heard Francis Crick talk about it to a club of physicists. And so I do about the general ideas. And we became friends. Celia then fed him, continued. We met in April. He probably fed him almost every other day for a month or so as the last part of the time we were in Cambridge.

Then he came to Harvard as his professor and I came back here. here a graduate student. And Syria actually was his first laboratory technician. And she poured plates and made tea and did various things until she got monobiosis and had to stop. So we were all friends during that period from a, they came back here in 56. Jim's laboratory started working. Most of it didn't sound that interesting. then 1960, around April, he said something very exciting is happening in the laboratory. We're working on the idea of messenger RNA. That's the idea that the DNA that holds the information makes a copy of a gene in the RNA.

That RNA copy goes over to the factories that make proteins called the rhizomes, and there it codes for the string of amino acids that makes them a protein. The idea was in fact that the way you turned a gene on, is to start the gene would make an RNA copy, you'd make several copies with a protein, and then that RNA would be destroyed. So you could then turn on a different gene, make a different protein. The idea was the messenger would be, was an unstable RNA that nobody had seen at that time. At that time, the thinking was basically based on idea of Francis Cricks that DNA made RNA, nucleus with DNA and a lot of RNA in the cytoplasm.

The RNA and cytoplasm must make proteins. So the proteins were made. People had just begun to do radioactive labeling and try to face these patterns. But the RNA, people couldn't understand the nature of the RNA in the cytoplasm. It didn't really, was in these large particles, but didn't really seem to have the characteristics of the information character and so it looked much more inert. We now know that that RNA is the critical enzyme that actually ties the amino acids together as the proteins are being synthesized on the structure, we call a rhizome,

with using the instructions that come with the message RNA. But Jim said something very exciting is going on. I went over and visited his laboratory. He saw he and Francois Groh do an experiment. Jim gave me six papers to read and went home with the papers. That then told me every day was known about the field at that time, so I went back the next day and joined in doing the experiments. And so we physically, Jim, Fraswell and I physically did the experiments together.

The experiments were at the beginning, very, very primitive. Ranswell would be holding a large flask of bacteria and swirling it. I would be holding a little vial of radioactive phosphorus, a 20 billion curates. Jim would be holding a stopwatch. Jim would shall go. I would pour the radioactive material into the flask, and shake the flask vigorously. Jim would shall stop, pour the condoms of flask into a big bucket

full of dry ice and ice and a side to stop everything. Everything would be stopped. They take that radioactive bucket into the cold room. We would then spin down, centrifuge down the bacteria, collect them, scar the radioactive supernatant, grind the bacteria up, make an extract and contain the particles of the bacteria, centrifuge it through a centrifuge tube to separate the molecules by size, collect the little samples, dry down the samples, and then count the samples with the

Geiger counter, which in those days was actually a true Geiger counter, they're sitting under lead bricks, you put a sample under that, take a stopwatch and start it, stopwatch, push a button. The counter would count with electronic tubes. At the end of a minute, stop the watch, read, stop everything, read the number, write it down on your notebook, take out the sample, do the next sample. Things have to be pretty radioactive in order to have enough counts so that the errors if you're doing this way don't really matter. And this is the way we did all the first experiments for several months as we began to do these experiments. During the year before we wrote the papers, the technology transformed over and over again.

People began to make automatic calories. The whole technology of science changed from this, totally crude, do it by hand, to now automatic you could load up and then fancier counters and cuddlation counters that can count distinguish the radioactive decay of one element from another so you can now do double label experiments you can follow not only the radioactive phosphorus in the RNA you could also simultaneously look at a radioactive carbon in the amino acid and so you could label the cells in the variety of things so we continue doing experiments like that for about a year we published in December, published again, in 61.

And then summer 61, I still was doing biology. I was teaching theoretical physics all this time. I had graduate students in theoretical physics. I was doing an experiment. Summer 61, we went to the end of the end of the research. We went to the International Biochemical Congress in Moscow. It's a big Congress in Russia. They opened up enough.

There are 5,000 foreigners that would come into Moscow. But this strain on the nature of that society at that time. Because they had just come out under the Senko sort of vision of, of anti-genetics vision, of biology. This would have been the start of the Cold War. Well, the Cold War is going on. I mean, all during this time. You know, in fact, Russia had been entirely closed.

As I said, it was while striking, they opened up. We went, Jim and I go to Russia. We were still in Leningrad at that time. We visit outside of the laboratories in Leningrad. hear stories about what happened to the Jewish scientists, also a whole range of things. As we go to this, yeah, we actually go to the meeting in Moscow, we went actually to what we're called the Sunday seminars, which were the Jewish dissidents, we went to other jobs because they had asked to go to Israel, And they gathered together every Sunday in somebody's apartment.

I don't remember the details in this point. And we is visiting CITUS, went there, told them what was going on in the Cyborg world they were doing, they were trying to keep up, keep in touch with what was going on around. It's actually at that meeting, Marshall Nirenberg talked about discovery, discovered that Paula you made Polycololian, which is the first coat on that was discovered. And Jim and I are having lunch, having breakfast at the hotel of the Metropoles, gigantic hotel in Moscow, you put us all up in. And we're having breakfast, and somebody comes over, it's Marshall.

We didn't know at all. He comes over to tell us that he's going to talk. And he's about his discovery that Paula, you made Paula Falunali. well of course we were delighted we had been working on messenger RNA we were probably known because of the papers at that time and jim and i go to his 10-minute talk and hear that and jim gets frances to arrange for him to give us symposium talk of the meeting and to me goes up because this was the major news of the meeting in a sense was the breaking the genetic code talking about the genetic code,

talking about I traveled all through Russia at that time down to India, Pakistan, probably back up through Paris and back home. It's been a long trip to.

I spent some period my parents at that time. I said we're in Pakistan. I spent some time there in Pakistan. And in late Lahore, which is where the government was then, we visited up

pinned the area up there the Khyber Pass. Interesting. You know, try to see. We learn things about Pakistan. Your advisor in Cambridge. Well, my advisor to Pakistani, and Islam. How was he? Fine, wonderful. You know, he's a few years older than I was, but not very much older.

He was born in the 20s, you were born in the 30s. That's right. He was probably, he's five years or maybe seven years older than I was. You know, we had a fine time together. He always told me he got the Nobel Prize later for, um, well, you like one year before you got it. Yeah, and he always told me that, um, you know, if I had stayed with him and not going back to Harvard, we'd have done the work together than the Nobel Prize.

You've accelerated by one year. the government night said we never tell um the um i was just trying to think of what i lost my train of thought oh that's right i was just going to my life on science i came back to harbour thinking i'd go back to physics and so i spent the next after that that summer in moscow spent the fall probably doing physics and then decided how i really enjoyed the laboratory work more than they um than the theoretical work. Theoretical work is, in sense, very isolating. You're together with your friends during the day, and then you go home and you work late at night on your ideas, so separately, come back, you had a rack, but you're not actually,

in those days, people work a little different than today, but lots of theory we're still very, you're alone with your thoughts. Laboratory is the sort of constant environment of people, Then you're interacting with people all the time, asking questions, talking about things, doing your own experiments, and in between you, in this bath of people. So I found I enjoyed the experimental work, and I have what we call good hands, so I'm really happy doing it. Jim did not have good hands, tended to draw things, but he had a very clear idea of, how you do experiments. And the really critical aspect of doing experiments is how do you actually prove something to be true?

How do you do enough controls to understand something? How reproducible is what you're seeing. You know, do you just go off the deep end because you see something once that you can never reproduce? Or do you carefully reproduce things and construct? enough substance around it to understand things. So I went back and I started doing, Jim gave me a room, a laboratory, a technician, and I started doing research first and the nature of how proteins are made.

Right, excuse me, and first, that stream of papers in biology about the details of protein synthesis and discovered several things about the that and those papers were enough that I was about to come up for tenure. In those days, the assistant professor was non-tenured was a five-year appointment and the only appointments of both that were tenured so that by the fourth year of your students and professorship university to decide you or send you out. And so I was no longer doing physics, I'm still teaching physics, but I was really in biology. The physics department wasn't going to point.

They began to look for jobs elsewhere, but they managed to find a, my friends at Harvard effective, we managed to find that in some group to bring my name up with tenure. And so I became tenured as an associate professor first in biophysics and continued in biology. the Harvard tenure process at that time was Harvard tenure process at that time involves writing letters other people as it does now but in those years the letter would be there's so-and-so we're interested in making an appointment in biophysics

who would you suggest be no names suggested at all you know we're going to make an appointment in theoretical physics. And they would send that out to who? They'd send it out to a group of experts in the field. At the university. No, out to the world. Oh, my.

Oh, wow. And they would get letters back. And then they'd have what they call an ad hoc committee, sure, which was actually people, some people other departments, the university, and people outside the university. And that group and the president would sit in those days for an entire day, They'd hear testimony from the department members who were proposing the appointment. They'd see all these letters.

They'd have lunch. And then after lunch, the president would go around the room and ask each person what they thought. Committee never doesn't vote. They would just give their opinions. Is this a good appointment? Might it be better? Are there better people? one of the classic moments is one of the presidents

usually saying to the physics department who were proposing somebody spoke to the guy who's talking this guy up and they say suppose he died who would you have said you recommend it so shocking the professor but that was much more of the attitude the attitude we no longer quite do it this way

I mean this is the old it's changed It's changed. Unfortunately, at those days, it had the advantage that the president got a essentially report from across the field, what's going out on the field and how the external world looks at the local department. Respect it, doesn't it respect it, what's really going on. And that actually gets used very often, used to the historic thing. It's actually abolish entire departments. You know, experts in, they say, look, you've got this group of people, but they're out of, they're, they're often in their own world. They're no longer paying attention to what's going on in the world. You get rid of that department, create something different.

It's happened to astronomy here, that time when the ad hoc committee said, look, the future is astrophysics. and have the geography department. So it turns out. By nowadays, this has all gotten much simplified. People do not. There's still an effort to try to get this a good external review, but it is much more focused. The world was, of course, is another element.

As we're actually talking about a long time ago, the world of science historically has doubled every 10 years. You talked about that. You know, so that the number of papers or the number of scientists and the number of people. It's been going up with Factor 10, two every 10 years, since the World Society began. I know that. Hundreds of years ago. So that already means that in, you know, in 50 years, there are 32 times more people in each of these fields of science

and that 32 times more papers. But I began doing the biology. As I said, I could read six papers, and that was a commending of knowledge. I worked across with RISOMs, with messenger RNA, making proteins, how genes, how genes are controlled, these all have become entirely separate fields of science with deep knowledge, but each of them separate, almost separate. One says you should be curious about them, but they're...

And so there's a sense in which, like asking, who would you suggest in physics or who would you suggest biophysics in those days is a much easier question that it would be today. Today, there's so many of them. Today's, this is now, 1950, and we're 70 years later. You know, it's 120 times more people in every field. You know, you could make a reputation then, but now there were hundred people around you with the same reputation. So. But you got it. Well, that was promoted here and continued, continued, set up a leverage, you had the set up a leverage.

Yeah, the set of the laboratory. Well, I actually sort of began, well, set up a sort of, with Jim, we just sort of expand the laboratory. We ran a laboratory together of occasion with the system professors for a number of years. This was actually about 65, a few years. Then by 60, he began to meet Morris in Coltsbyn Harbor.

I ran the laboratory, he went off the Coltswick Harbor. I ran laboratory biology here until about 1980, so in the early 80s. The great discovery of that period, the earlier discovery was, about how genes are controlled, how one gene makes a protein, and that protein goes to DNA and other turns off another gene,

the one that case that we worked out, that protein goes to DNA and turns off a gene. In our bodies, the most common pattern, pattern is that protein goes to the DNA and transonic gene. But we worked out one of the first systems like that. In doing that, you identify the protein, we identified the DNA region that it found to, and then we worked out the sequence of that DNA region, by copying it in the RNA and working out the sequence of RNA with medicines and Fred Sanker had developed.

It took us two years to work out 24 bases of DNA, sort of one base. a month. This is sort of rate of sequencing. This is actually one of the first. This would have been in the 70s already. This is the middle 7th. This is the this is actually the early 7th, about 72. At the time, I had this DNA fragment in my hand. That's the way I isolated this DNA fragment, copy in the RNA, worked out of sequence. We published the sequence and said one of the first long DNA sequence is done. And I tried to develop DNA sequencing methods at that time, but nothing it worked out. And then in the middle 70s, a Russian visitor, Adrian Reza Beko, came, got out

to Russia, got a trip around America. And he came to the laboratory and tried to convince me to do an experiment with a reagent called dimethyl sulfate, which is a way of putting methyl groups on DNA. And he, it's a chemical reagent and multiplies the basis in DNA. And he wanted me to see how the repressor interacted with DNA by asking didn't. You put the repress on DNA. Then it blocked the methylation. I couldn't think of any way of doing that experiment. So he went away, he traveled around America, came back, and we had lunch together again,

kept on arguing, I should do this. And then I thought of a way of doing the experiment that involved breaking the DNA at the point where the methylation had been and looking at the size that the DNA fragment that was released. And I did that experiment. It's one of the last experiments actually with my own hands in myrology. So I did that experiment. And it was the second time I did it was a great success. Quite clear you can see you got a pattern of bands on a gel from radioactive DNA, suffered by size. And the pattern was distinctly discreet.

So you can see, oh, here is a band that corresponds to a guanine. You put the repressor on DNA. It blocks that guanning. You didn't modify it. And the control, you did modify it. But the pattern was then so distinction that I could look at it and say, oh, this is a sequencing method. I'm looking at sturdy faces at positions 32 and 33 along the DNA. and I can see the two adneins there.

Fantastic. For months to find that out. This is just one gel run in an afternoon. So we started to look, my technician, and I started to look for, it's complete this, a sequencing method, let's find a way of breaking the DNA and the C's, the T's. And nine months later, we had a complete sequencing method,

and you could display hundreds of bases. that you can display a pattern on a radioactive DNA that you can get on in film. That film, which was a pattern of bands, the smallest, the largest. You can read the sequence from that pattern. Was this the ureca moment for you? Well, it is a re-game. The renecule moment is probably earlier when you realize it's going to be possible. And when you work it out, it is possible.

You start doing it. We gave the method away. we went to Gordon conference, told people, 76, told people how this work. Wow. Gave the method. Give out bibliographed instructions. People came to the laboratory, learned the method. So everybody began the sequence.

We probably published the official paper about about two years later. Well, hang on. The Nobel that you got in 1980, for a paper you published three years early. Well, it said it would have been 77 then. Well, it depends. The papers, the actual time, you know where the sequence of information is, as it begins in 76.

People begin to use it. There's a time delay before papers get published. But I began doing physics, theoretical physics. The time delay was two years. Between the time we submitted a paper in theoretical physics at the time it appeared. Got it. And then they, all that,

early period of biology, we would send out papers as preprints to maybe 20 or 30 people around the world who would be interested. So the messenger are they papers would be right, we wrote. We then set out the preprints form because in fact they're going to appear months, months later. And all during that period, 60s, 70s, 80s, there's a world of preprints. It becomes organized and then there's a massive duplication of preprints and we get set around that massive form, not just the build communication between the 20 laboratories that have a common interest. You know, this then shifts in the modern world. There is, in fact, and a computer archive in which people deposit papers immediately long before they're published.

Sometimes they never get published. They just send the computer in the archive because they're put there before the referee. This is very, very strong in physics. It's also somewhat strong in biology. Some of the journals fight against it saying we want the paper to be in our case. So in one level there's a rush to publish. Another level is this constant of the friction of the reviewers. You know, so various things can take two years to get published.

So the world is, you know, somebody can spend a year arguing with reviewers rewriting the paper of the reviews for the experiments and the paper never gets published when it doesn't get published natural. But back in those days, as I said, one of the ways is spent reading the news was that tell people at a Gordon conference and hand out a memory graph sheet that told you how to do it. People either data themselves or they'd come visit the laboratory and do it. So our sequencing method and Fred Sanger's method both have released just from this 1976 period and by 10 years later 8 million bases of DNA and sequence around the world about half by each of the methods.

Americans most use our method. The Europeans most used Fred Sanger's method. You won the Nobel with Sanger and... That's right. Nobel... Two other people, right? Yeah, Fred Sanger and Polberg.

Polberg, okay. The Nobel Prize that's your, was given in 1980. It was given for what's called a recalvenant DNA techniques. The two things in current, the spirit. People have begun to realize you could move DNA fragments from one cell to another. And you could take a little DNA circle that existed as a pre-living element in one cell,

cut it open, put a piece of foreign DNA in it, insert into another bacterial cell, and get that circle to replicate inside that bacterial cell. We grow a bacteria that had a piece of foreign DNA. Oh, this gave one, when it had tremendous ability to cut DNA in portions, separated pieces by size, but this actually gave one a way of isolating that piece, piece of DNA, making large copies of it,

making it, growing a bacteria, could make a lot of it. This technology begins to emerge in the early 70s, and 73 actually, so there's no point to which technology is the official start date. But that's all very nice. Prince, we could have a, take a piece of mammalian DNA, it has a gene, put that little gene into this little

plasma, put in the bacteria, growing bacteria that have pieces of an emillion DNA in it. But how would you know what you have? Yeah, so that's the DNA sequencing, Brent Sanghaer of our methods. So the prize that you was given have to, half the money. I mean, prizes are curious in a sense. Each West gets a no more prize, but then the money gets divided. And the amount hasn't gone out for a decade. No, it doesn't go about, it went

up shortly. Really? Back in those days, it was only about a quarter of a million, now it's about a million, maybe a million and a half. So you had to split it three ways. So it was about a quarter of a million. Well, no, we all got half of it because he sued for one half of the prize, he stood in for everybody who had moved DNA fragments around and devised the idea of how to put DNA fragments into another one DNA fragment to another and get it to grow with bacteria. And Fred and I seared half the prize for working out the DNA sequencing methods. I mean, by 1980, he discovered the sequencing meant it clearly as possible to understand genes. As I said, it took us a month to do a month per base, two years to do 24 bases. A gene is, bacterial gene is 1,500 bases.

Could you understand it at that rate? No. But once we had developed a sequencing method, a graduate student for his PhD worked out of the bacterial gene in my laboratory, 1500 bases, working by itself. Because PhD actually corrected the protein sequence because in fact the people doing the protein chemistry had made a mistake. You could get the correct sequence by reading the DNA. Next graduate student to do a thesis on DNA sequence in Tiroplasm. Wow. And 1,500,000, about 4,500,000 bases.

It says PhD goes off and has a career in science. But that's actually, you know, working alone for a year or so, that technology was. You could rapidly, begin to rapidly sequence DNA. And so the prize is given to that realization. They're probably in the order, 76, there are 8 million bases of DNA done. 81, there's probably about a million bases have been sequenced around the world. But you can already see that that gets going faster and faster, 80s by 86.

Around that time, I realized, well, it gets ahead of the story. The sequencing methods is sequencing methods about 76, which was 1980. By the late 70s, we were very interested in the question of can you make, can you understand human genes? Can you make human proteins in bacteria? And we were working on that problem, and we, in fact, trying to make mammalian proteins. We, the first group to make insulin in bacteria.

We made the bacterial strain that made pro-insulin. And that led me actually into the biotechnology, because that interest. Pause right there. How did you find out that you would have won a Nobel? I mean, you know, I've talked to other Nobel. No, that's right. They would have gone on a phone call at two or three in the morning.

Well, that's, this would have been more recent. More recently, they telephoned. This is now back in 1980. Things are still very primitive. No fax machine. At one level, by that time, you've won all sorts of prizes. French Chang and I has shared all sorts of awards together, so that we're obvious candidates for a Nobel Prize by 1980.

But in that year, we did not win the prize in physiology of medicine, which is where I thought of it. That's weird. In chemistry, right? So the night before the prize in chemistry, I'm talking to my friend who's a chemist? say, I say, who do you think is going to win the prize tomorrow? It looks to be strangely, but we talk about other people. You know, we talk about what sort of, what chemists might win. My friend is at that time, a close friend was a organic chemist, Jeremy Knowles.

But in case, I go home, I haven't heard anything in the morning. I go into the laboratory. probably 8 o'clock the morning. The phone rings. I pick up the phone. It's a newspaper reporter. And my thought is, oh, they want me to comment on whoever's won the Nobel Prize. And then the reporter says, no, I've won no, no prox.

So I'm delighted. I have a conversation with the reporter. How would he know? Well, because at noon, the Swedes announce it. I see. And so the newspapers reporters. Okay. And I get a new in a Swedish time, which would have been.

New in Swedish time, which is probably 6 o'clock in the morning, our time. So you see, it's on the local news, probably the 9 o'clock news. Because in fact, I get a cold reporter, as I said, it's about maybe 7.30, 8 o'clock, something like that. I go home to tell my wife, my parents are actually, my father, it has, had a knee operation. It was living with us. My parents were living with us. They go home, tell everybody. By that time, it's on the local news. Go back to the laboratory. We began to celebrate at the laboratory at throw. Actually, a party that night, we had a champagne party for 300 people,

my friend at the chemist's house. And the people in the laboratory, had a laboratory about 30 people in it and they um the postdocs organized organized the party through a lovely big champagne party had people like my doctor my doctor had hey yeah that's right yeah just had a bypass operation that's why it was in the house the doctor did the bypass operation came to came to that no-go party oh we had a gigantic affair and those years the Nobel set a telegram but it sort of arrived about three days later. And so I went off and you collected the price money. Then you ventured, you ventured into entrepreneurship. Well, I took the prize money. I spent the prize money as I said. The prize money

was my cut of the prize money, maybe 60,000. I probably spent most of it, taking my parents and children to the prize ceremony. We flew everybody first class. My father just operated upon. Well done. We all went to Sweden. They were all there with my son and daughter. In 1980, they were 20 and 22.

And my parents were still alive at that point. So we were all in Sweden and that I can't even the hotel anymore, but that's a lovely affair. Well, you figured out the order of the nucleotides, and then you ventured into biotech. That's right. I mean, you set up a behemoth company. It is now a behemoth company. It wasn't restart.

I didn't know that you would have been the founder of that massive company, but that's That all starts, actually starts back in 78. Wow. And two venture capitalists make a, think of making an investment in Genentech. And they get Phil Sharp to come as a advisor and he comes and looks at Genentech. Kigenetic at that time was trying to synthesize human insulin by making synthetic genes to the separate genes to the separate parts.

And they were exploiting the chemistry to make DNA of prolifically. Phil Seizant, he says, oh, you make a small investment, why not? So they get intrigued to venture calculus. One of those, a man named Dan Adams, and they travel around, they talk to Phil Sharp about what is this new science. Phil brings them to me, I talk to them. They travel around Europe and talk to European scientists, and they get the idea, let's set up a company in Europe. There's room in the world, here's this company, in Chantanget who's invested in the company in America,

we'll set up a second company in the world in Europe, there'll be two companies. So they get together with about a dozen European scientists, 10 European, and Bill and myself. And we start meeting in Europe talking about should be set up with such a company. Is there any reason to do it? Should we do it?

Is there? And S&S are groups somewhat skeptical, but intrigued. And after a couple of meetings, they say, well, we like to set up a company. They raised, I was going to say, three quarters of a million dollars, half in kind services, half actually cash, they're going to say about thousand. And we're all meeting in the hotel, and the two venture capitalists go out and decide us all gather in a room. And we all decide we'll do the company.

And besides, like me, is chairman of the scientific group. We put all sorts of restrictions on the company. The scientific board will have a third of the board of directors. We will have control of the expenditure of the laboratory, and we'll control of the stock issuance. And we come out and we tell them, you want to do this. They're sitting there thinking, oh, my God, nobody's going to join us. And the scientific group says, don't we'll do it.

So, in fact, we begin to use that money, we raised that point a little bit to do research in some of the laboratories. So I'm board members. Charles We've spent our time talking about what would be good projects, what would be meaningful projects to do. I start working on cerebrookul and thinking that that might be a useful protein to make human about use therapy and also, I guess, insulin, I've had to continue the insulin project.

The company, of course, just us, the scientists attacked through about that sort of first year. I get more and more involved. I'm chairman of the civic board, which means I'm then involved in all of the effort to raise money. So I get involved, get more and more involved. involved in this. And we do manage to get an investment from

Curing Plough, $8 billion, another million a quarter from international nickel, and we're off-running and we start setting up laboratories in Geneva. I'm thinking, yes, we could be European European country. I'm still ahead of the Simonic Board, I'm also the sort of vice chair of the board, and I find myself doing more and more in this. We lose some of the first venture capitalists. We didn't have to hire people who sort of of run the laboratory in Europe. As we do, we hire Ralph Cothorn. Once the doesn't know, also, but originally the laboratory in Europe, we decide to move forward, you can raise more money, in the several laboratories here. Charles is

successful including interferon. I go to Europe and try to clone human insulin, but doesn't work. It's a wonderful sort of story. It's actually a lovely book called Invisible Frontiers. It's a lovely description of that episode. So we start setting a lot for here. I get the Nobel Prize. what am I going to do for an encore? I look at this company, I think it's going too slowly. It's not like you haven't done too much. I mean, you've done so much already. You know, but that's why, but there, it's now 1981.

And I, it's just, it's just moving too slowly. And so I say to the board directors, we need to move faster. I'll take over the company. They say, no, can't do that. So I say, okay, I'll leave. I say, okay, you can take over the company. So I become CEO. By that time, we already had two people in the company and CEOs.

This would have been back in Cambridge or in Europe? Well, I'm still in Cambridge. We're setting up a laboratory in Cambridge. By that time, we've actually set up a laboratory in an embedded space. We've hired Bob Files, who's going to, well, that laboratory, Ralph Cawthon is willing, laboratory in Europe. The company has maybe, by that time, maybe, you know, I've had a business laboratory in Europe. Right.

I'm flying over to Europe, sort of. Well, actually, about once a month, I get. As I try to go into real timing. Yeah, I don't know that's right, but somewhere of 81. one of probably we had involved. We raised another $10 million to the company. We raised another $20 million soon after that. And but as I said, I thought moving too slowly and saying the board, I should run it.

Then they say fine. So I finally start, I could run it, I come in a new with them as CEO. And within a year, they had both left, put in other people running those laboratory. from Korthland left first, Balfiles stayed on, probably another year of it by 83. He left and I took the company public in 83. I actually did that public offering. You myself, I'm doing, I didn't have sort of business people, presentable business people.

The Europeans are quite presentable to the Americans. So I did the road show for that public offering very much. using in those days, days, everything's, because everything's changed over and over. In those days, when you did a road show, it's actually about a week to two weeks in this country and maybe a week in Europe. And you would go talk to large groups of investors. Right. There being 400, 600 investors sitting around, people who invested in through public companies. And so he traveled around America, giving these talks. and give a talk, answer questions, go on.

The next slide. Travel around Europe, you know, talk to 600 people in London, give a gigantic group. We didn't sell much stock in Europe, but give a gigantic group in Paris, you know, lunch. We're talking about the company, traveling in Switzerland. And we had the, we had the, we had, We actually got out to just the peak of the market, just before the IPO market changed.

And so we was very successful, we raised $50 million. But the company was actually one of the largest IPOs back in 83, for the next 10 years. By now the IPOs are gigantic compared to that. But the company had a valuation of $500 million. Fantastic. So I kept on running the company. We had several hundred, maybe 400 by the time I finished, 400 people we'd grown, well, two large laboratories here and there.

And Salt Price went down, market goes down, Falk price comes down, four hundred directors gets discouraged. So with, you know, it's five, a few years later, 1988, to Republic 83. No, it's probably 80, sometime in 84, early 85 thing. I got fired as CEO. Stop. Leave the board for a while. I went back on the board. I sort of gave them board directors time to pick a new CEO.

I came back here, wrote papers, got reappointed at Harvard. I had to resign entirely from Harvard. because we couldn't have more than two years of leave, and I had two years of leave. I still had a laboratory, we had the first part, still at Harvard. And I kept a laboratory going in the company. So I had postdocs and started doing research on our own themes, not on company. You came back into physics, chemistry or biology? Came back into the, I was originally in what you might call the left wing of biology,

which would have been biochemistry. Right. I came back into the center, which was like a set of developmental. We have a right wing at Harvard, which would have been the museum people, the evolutionary biologists. And Harvard biology and many out themes, one of which is, of course, it's actually created in a conflict between the creationists and the evolutionists. in Agassiz, great name of biology as a creationist, believes the species are always independent.

We're in, at Gray's Gardens, Aza Gray, a botanist at Harvard in that period. He was a friend of Darwin's and wrote back and forth. Darwin, he was early evolution. And that conflict continued in Harvard biology all the time I was there. There were the museum people who tended to be creationists. The species are all different. And the molecular biologists who think everything is related and was true for equally, would be true for elephants.

It turned out not to be quite the case. But they're very closely related. The genes are very, very related. Well, Cambridge has been known as the mecca for entrepreneurship and science. being fertilized or cross-fertilized, particularly in the context of biotech. Why is Cambridge so different? Cambridge is not quite unique in that. We also have California areas.

Yeah, but the California is a non-biotech. We have several themes. We have a very strong university pattern here, both MIT and Harvard and many of the smaller schools. When I think about that problem, I would think about it, it's almost like, There's an entire entrepreneurial streak in America that's much later come to Europe. And it's an oldest streak in America. When we tried to finance fires, originally, we traveled around Europe, talking to companies, trying to get them to invest a little bit in the company.

and of which the simplest response was, I'm a group at Solvay, the Belgian company, who said, we mean take 10% interest? If we like it, we buy it. The whole idea of actually participating or having an entrepreneurial group as opposed to a company group, two things. It was just alien back then. This is back in the late 70s. The Americans, the American pattern at that time was once more entrepreneurial in the sense of being willing to do things, to fail at things, to start and do them again. And there's in a sense in which the scientific culture is very much that. You fail at lots of things. Lots of experiments don't work.

and you have to sort of get up and go on and do something else. And so it's that both experimental culture and the attitude toward failures of something you just get over and go on, you know, that is behind the creation of small companies. The world was a different scale. I mean, by now the venture, venture groups are having very large amounts of money. They want companies to grow very, very fast. There's actually a company that just did a, you'll say, a 500 million,

a round, first round of investment. There have been companies that do almost a billion dollars, first round of investment in ideas. Absurd an amount of money to try to put into things. And most times when you do that scale, things just collapse and do not actually recover. But the period we're talking about in 1980s, yes, the scale of the venture groups, the groups that sort of begin to say can we begin to develop things as companies. and the still the willingness of people to try to explore.

It was still very, very great. Avajun was the first, we soon and how you get started. This then becomes an example here. The next institute begins here. Again, the same sort of impulse, taking off from the fact that we just started a company. Now one gets started. the Cambridge, the first laboratory in Cambridge, who was the first laboratory set up in company laboratory set up in Cambridge.

But the people who went through the company, who then created a group called the bygones, then started to kind of involved starting more and more companies around. So you have this plethora of growth of biotechnology companies around Cambridge. We started by Bayesian coming here and then the spinoffs as Bayesian grew, becoming greater. greater. Yeah, rooting about that question, of course, I think, again, the degree to which the world has changed. You know, this country used to pride itself on being able to make things.

There's a book I Mark Twain, the Connecticut Yankee, King Arthur's Court. This was the sort of the classic view of New England, the Connecticut Yankee was the guy who could build anything. And he goes there, he gets thrown back into King Arthur's Court, and he creates a telephone and telegraph, builds old locomotives, builds the entire world around around him. And as young as a boy, you would read books like that and they were the way things should do things. America's industry and the Second World War was very powerful.

Not by the strength of the industrial system itself, but actually through government intervention. My father was, in fact, in the government at that time, he was actually involved in saying to the people who were running the aircraft industry, no, 5,000 planes a year is not enough. We need 50, You know, the government built the plants that built the Ford and the sort of thing that built the, built the tanks and all this. Because industry left on its own devices, but it waited. In fact, did wait. They sort of said, we've got to finish this round of this year's car releases. Then next year we can make tanks. Actually, if you read back in some of the discussion

what was going on at the time. It's very true. And of course, it's what's going wrong now. This country is, looking at, this country sort of is behaving as though it's going to war. But of course, it's entirely incompetent and can't do that anymore because in fact, there is no central, there is no spirit that says, let's do it, let's really make things. Yeah. Now it's all, it can be a right good price and I'll make something. So, very different attitude. Very different. That's a separate podcast. That's right.

You can talk about that. Someone else is right. No, I want to pick up on CRISPR. What's your take on CRISPR? Well, it depends like me. Lovely discovered. and it's created tremendous power to do things both in research and now moving over into medicine. I mean, I'm not sure what the real meaning of your question is. Well, I mean, will it be net good for humanity? I mean, it's been able to help remedy sickle cell disease.

Well, that's right. But see, there's that sense in which impression is like about recombin DNA. Everybody was then terrified back in 19. In the middle 70s, they began to think, oh dear, this is going to be bad for humanity. There's going to be something. I always defined this as physics envy on the part of the biologists. They wanted, they began to tear their shirts and say, we're doing something dangerous. Stop us before we destroy the world because it's, you know, like the atomic energy. Right.

we're now doing something really important. And that led to discussions here that the Moriana in Cambridge, the CILOMAR meetings full cycle. I didn't go to the CILOMAR because I was writing a grant at that time at Harvard to set up a laboratory to do virus research. Recombinate DNA came in. We actually used that laboratory to the recombin DNA work. In fact, all of the early recombin DNA work.

was done in very secluded, carefully constructed laboratories. I went to England and worked in Portendown, which was a British chair worker place, in order to try to clone make a bacteria that made human insulin. That was considered possibly so dangerous that we had to go work in before laboratories. Our attitude sort of that have shifted away, and we no longer see that is well be dangerous. And your question about Christopher is again,

if it affects a deeper craziness that people often have, it's knowledge dangerous. As a scientist, I always feel that knowledge itself is useful. What we do with it can always be a problem. Humanity is dangerous. Humanity is vicious. People are no damn good as one of the classicists. statements about the world. You look around the world today, you're not convinced of the good behavior of humanity to itself. We're simultaneously going through a world, which is going through a very rapid transition at one level to a better world in which the economic structure of the world has has been increasing all around the world. The birth rate is dropping everywhere.

We're about to, oh, we will go through a peak population shortly, and then the population, world population, is going to begin to drop. Population is dropping in China, it's dropping in Russia, it's dropping in this country. If we didn't have the immigration, it's dropping in Europe, catastrophically. Again, immigration is saving the day

for these countries as young people migrated and begin to help support the countries. So at one level, the world is doing very well, then another level is doing its best to destroy itself. Got off to be too seriously at all of it. We talked about tech feudalism. Yeah, that's right. A lovely book called Techfuton by Bernacus. Yeah, it's amazing how few and fewer we're controlling more and more.

Well, that's right. We both have. That's right. The theme of his book is that we moved it. In certain ways, we've moved into a pattern in which we no longer have the virtues of the capitalist system, which was the ones we were talking about a few minutes ago, the entrepreneurial drive, the creation of novel companies that are doing new things. and building things. It was actually amazing, but I took Vajun public.

The young bankers I dealt with who were then taking me around on this roadshow are constantly pointing out with pride things that their bank has made happen. We funded that building over there. This one here, the bank's money has been used to build things all around the country. So that attitude has disappeared. The bankers today, money is being made solely out of money.

The country today, our GDP, a good chunk of it, is totally fictitious, because it's in fact money just priding itself on making more profit out of money. not actually making anything. And the country, my negative view, of course, the country is stopped being able to make anything. Boeing is a fantastic example. We have an entire hospital system here, Stewart Hospital System, which is wrecked by private equity,

which is a way of attitude. You see actually functioning structure, and you go in and rob it. You buy it and rob it. They get into the ground, pull out every dollar you can, and go on to something else. Rather than rowing it. Intrinsically, you take the world around you as something that's there to be stripped. Any value that there should be stripped out of it, turned into cash.

You know, that's a disaster, because you made up with just piles of cash, we came in by, I think, with them. We have the attitude. that you could buy success in war, by just spending dollars. You know, it's an absurd attitude. You know, there's this tendency for the world to be more and more multipolar. And then by way of multipolarity, there's this growing proliferation of risk that could come from, be it nuclear, climate change, cyber and all that, right? I was trying to think you as a scientist, science can play a big role here in mitigating, you know, the increasing risk.

Not clear. That's a wishful thinking. The, you know, the issues are very much, I was going to say, political nature of the kind. people who want to have a conflict. Science is not, plays a different role. We can find out that scientists were curious about the world. We find out the facts about the world. But we can reveal those facts of people. Though we're warming is a perfect example.

Science has been quite clear for years now that the increase in carbon dioxide in the atmosphere is going to lead to an increase in global temperatures. For years, in fact, there was still a scientific discussion. What's the cause of the increase? Is a human error is some natural process? By now that scientific discussion has gotten fully resolved and it's clearly the human release of carbon dioxide and methane

that's causing the warming. But that doesn't mean we as societies, we do anything about it. We're sort of watching the world burn up around us. Europe is actually, and Greece is actually burning great chunks of Europe. Canada was burning a year ago. Why is politics so messy now? But it's always been messy. It's always, I think it's always been messy.

and we've gone to bad political periods before. Maybe it's with people with too much power. Too much political, too much economic power. I mean, you've always had concentrations of power, possibly always a little bit more balanced. Right. You get to think of how extraordinarily wealthy the exchange have become. We've got to think, oh, maybe too much power there.

You know, in the old days, we would have seen a lot of people going into politics as a crusade to try to make a difference. Well, that's right. We're seeing more and more people go into politics, more for vocation as opposed to a crusade. Well, that's a great, that's right. This country has seen, I think, a fantastic shift of values. And that's what I was thinking, looting to very often when I talk about what it was back 40 years. ago. The country went through a here in the 30s. Great Depression, came out of that and we had

strong unions. We had people who believed in doing good in the world. That was the real issue. We now have a culture that believes in making money. That's not a different thing. No, You're not, there's a sense, you know, the scientists as a group or the large part, the people go into it, go into it to find out about the world. They don't go into it to make money. They go into it because they're curious and they're driven by curiosity and they think, oh, we're fantastic, lucky that society at least supports us well enough that we can live and do our research. And that's the underlying theme. Now different populations are going into science and get caught up by that feeling.

So the group that the people that go in the science now, there are different ethnic groups than they were going in, going in earlier. So that depends again on just the flow of the population. We've caught in a culture, so the advantage of the multi-polar world can be many other cultures. Oh, this country would call a culture that began to value monetary rewards more than any others. And so, you know, people used to graduate Harvard

and go into science as opposed to go into Wall Street. And going to Wall Street becomes more and more attractive. So you think it's more attractive. You don't realize, don't realize what the rewards are. The, I mean, sad, very sad business, but it is the, it is what it is. No, no, I was, yeah. I took companies public in 83,

83, around 95, probably again involved around 2005, in a, and a company public offering. And those structures, those offerings were very, the discussion was very different. The early one that I said, we talked to large numbers of people. Yeah. Next time around, we talked to groups of three to five people in large investment groups. And here we go and give a talk.

20 minutes talk, to answer questions, go on to the next one, 20 minutes talk. No one wanted to ask questions anyone else could hear, because they always thought we have our own secrets. So it's even more extreme. The third go around, 10 years later, by then, the public offering is primarily being subscribed by the inside investors We're already paying seemingly being buying the money and buying the stock.

There's almost nobody there. Except, you know, a sucker over here. So we go buy the stock at a high price. The best owners. And I still were more at a high price. The innocent bystanders. You know, it's like the Trump, Spock.

You realize that there were people raising money into a structure of a company. which has nothing. There's no product. Its purpose is to go find a product after the people invested. And so that group then goes and

finds the Trump structure. We've seen a lot of those. And there it is. Now it's a multi-billion dollar public company that's losing $50 million a year on an income of $3 million. And we have

We have fantastic, I've been involved in, generally companies have been involved in actually made profit and been functional. But we've had, we've had public companies, massive public companies, and never made a profit. That's simply burn investors' money. You know, it's unbelievable. The world has changed. I mean, I'm laughing at one sense, you know, I could come out of a culture in which if you own stock, that's because you got paid dividends. that I was remembering the issue that I once learned from President Schering Prow, who sort of said, well, we decided not to pay dividends. It didn't seem to make any difference.

It turns out there's a lot of companies that don't be different. No, that's right. It turns out not to make any difference. And then there's, then there's even the fancier device, oh, let's buy the stock back, which is what Boeing was doing. The banks love this. And, well, it was actually involved in the, um, Myriad, I was actually on the board, we bought back, shame to say, a billion dollars of stock. Company could have used that billion dollars to do... Restriction development. That's right.

The company does load research and development. But it helped... It helped decrease the share price. Well, only for a while. People make money from the bankers. You know, after something else happens, the share price goes down and that billion dollars has just disappeared. I did have a scene of the bankers' comments who had convinced the board members, it's the best use you could make of money is buying back your stock.

They have charts, I'd try to show you how profitable this is. Of course, the stock price doesn't mean anything to the company. It's actually relevant to the company. It means things that the company can do with stock, but it doesn't actually mean anything. Amazing. Anyway, Wally, you started out being schooled at home. You explored physics, explored chemistry, biology, entrepreneurship.

I want to talk about the last bit, the most important. You've been spending time in a studio taking, working on your photographs and all that. Talk about this. It's beautiful. You don't have to come and see the original. It's about that size. put by feedback um about 20 years ago um use the camera off and on to all my life as a child i had a dark room developed films had they enlarger made prints and then as the color cameras came in

I developed color film. Probably used a made slides, large part of my life, these other cameras. Digital cameras came in and I began to use them. And around 2000, I had a two megapixel camera and was traveling around photographing all things.

And discovered I could make large images. And everybody at that time said, no, no, you could make little postcard sized images. I was making first by 13 by 19, then 2 by 3 foot, then 4 by 6 feet, then even still larger, 8 by 10. Let's go to make large images, and by adding pixels in the computer, you know, an image that your eye would then complete, you see it as an interesting image. And I said, this is an arc form, I should do it. And so I began to, given that people said you can't do this, I might as well do it as an art form.

In those days, people were rejecting photography as an art form very often. So I started originally photographing just fragments of the world. I have some pictures near the rooms from that period. And so I had experimented with it. the photography. The original photography is little fragments the world. And then got a very fancy camera and took pictures of ballet dancers in rehearsal. I did an entire installation in an old factory in Morseau. He was invited the photo, come in photograph by photograph there. They then did an

installation with eight foot by 12 foot hangings and two by thirty two by three foot with pictures of the fragments of the factory. And then over the years, I've explored different things. I spent a year. It's been about few years, actually, just playing the geometric forms that I drew. First, patterns of squares and patterns with triangles, patterns with lines. Oh, then I spent a couple of years just doing black and white photographs.

And these years, last 10 years, last five, for 10 years, I've been, I was just working in very intense color. And so I take photographs, I superimpose them, drive the images to color intensity, and create novel patterns out of the supervision. You selling any of these? I sell a few of them every time. When is your next exhibition? I'm going to show next weekend in my studio.

I showed, had a bit of show on the show on. New York last October, although we're showing New York again about a year from now. Wally, thank you so much. You're welcome. Any final messages? Well, my final, actually, I do have several underlying messages. One is that you can change what you're doing. You don't have to always do the same thing.

People tend to get, feel I've been doing, train to do something, I should do that. They don't realize that the deeper aspect of training is learning how to do anything. And the specific knowledge you do need to do any particular field is actually very shallow and can be almost gotten very easily. The actual working knowledge in any field is not thoroughly deep. But how to work with knowledge. That's really a large part of training. So I've changed what I did. I was trained as a theoretical physicist. I became an experimental biologist. I wanted to know more prize in chemistry. I never really had courses in chemistry in college. I never had a serious course in biology since high school. I became an entrepreneur,

are realizing that the real issue was a turn of mind. They can try to decide to do something, can try to convince other people to do it, and can raise money, raise resources to do it. And the real drive and the entrepreneurship is, let's do it quickly. And it's quite amazing to watch. One of the great problems in small companies,

or a problem in any company, is that time is money. You're burning money, you're burning your investors money. Every day that you don't do something, money's been spent. So the question of how quickly can you move is very, very important. It's really a dominant part of what you do. And if you don't know that, you don't feel that. Your company grows, it can be very large, and they can just go down into nothing.

So that my advice is actually people who realize that thing was. should do other things you should find what they love to do. I try to find, try to find, like Francis Crick used to advise. The way of picking a field is to go into the field that you like to gossip about. The way of asking yourself, what is it that you really find interesting?

They should go do that. Interesting. What will I see you doing next after this? What's your next gig? No idea. Thank you so much. I sponsor a dig in Egypt in archaeology. So could be that. I could go find myself doing that, but we'll see.

Wally, thank you so much for your time. You're being gracious. You're welcome. Good luck to you. Thank you. That was Wally Gilbert, an artist and an Nobel laureate. Thank you. This is Endgame.