How Science Built America

President & CEO, Science History Institute
How Science Built America
From the Founding Fathers to modern breakthroughs, David Cole uncovers how scientific discovery has shaped the nation and why understanding that history matters now more than ever.

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Science and citizen scientists have played a foundational role in American history, serving as the backbone of scientific discovery and innovation for more than 250 years. They have been absolutely fundamental to shaping the United States into a global superpower driving both economic prosperity and cultural transformation. David Cole is the CEO of science his of the science history institute and he will tell you a story of science in our American history that will awaken you to the excitement of science and technology that is uniquely in the United States DNA. Please welcome David Cole, CEO of the Science History Institute. David. Well, we've had uh we've had quite a day, I think. Um

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we've heard this morning and this afternoon from a very distinguished group of historians who've had uh a lot to say about the history of this republic going back 250 years and some of the exciting projects they're working on to chronicle that and to share it with the current generation of Americans. And we've also heard some really extraordinary presentations like the one you just heard on some uh some science and technology that really hold a lot of promise for the future. AI, regenerative medicine, biotech in general has been a theme of the day, helping us think about beyond the semiquincentennial, the 250th, what might the next 250 years look like in in this country. And um today though, I want to tell you a story uh about a moment when uh science, the science we've been hearing so much about shaping our past and our future when science took a pause, when science was in some sense interrupted

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on purpose. But I want to argue in my little short story that the biotechnology industry that has come to shape our lives in such profound ways, the the 1.6 six trillion dollar industry that Moragun talked about earlier actually has its origins in a strange way in this moment when science was interrupted. Why am I excited about this story? Why am I telling it? Well, I work at a place called the Science History Institute in Philadelphia. We are uh historians of the chemical and the life sciences. And our building, which you see here, is located just across the street in Old City, Philadelphia, from our good friends at the American Philosophical Society. You heard all about them just a few minutes ago. And just a block down the street from Independence Hall and the Liberty Bell. So, we're in the historic corridor in Philadelphia. But our job is not to tell stories of try-ornered hats and buckled shoes and

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serious things like the Constitution, the Declaration. We're really focused on, as our motto says, telling the stories behind the science. And we do that in a few ways. Uh we have a Heria Museum, a museum chocked full of interesting artifacts and exhibits and experiences that share with uh young people of all ages, if you would, the history of the chemical and the life sciences, particularly in the 19th and 20th centuries. how these sciences have really changed and shaped our everyday lives in kind of unsuspected ways. And we also run a rare book library, the Omerr Library, which contains more than500 rare books in the history of the chemical and the life sciences going back to the late Middle Ages. We also run what is we believe the largest fellowship program in the history of science in the Americas. So, it's come one all, come one, come all to scholars around the world who come to us to do

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original research in the history of the chemical and life sciences. But we also want to reach the public who can't come to Philadelphia in really important ways. And we produce a magazine, an online magazine, and a podcast series that currently reach more than three million people annually. And we do this in service to this organizational mission. uh we explore the historical roots of scientific phenomena and we reveal the historical context for today's scientific challenges and you've been hearing about some of those scientific challenges and opportunities especially opportunities uh today and many of these we chronicle at our institute and why does this matter why is this relevant this history well I'm a Philadelphiaian and I work in old city Philadelphia And as you know, Philadelphia is identified as being kind of a in many ways an 18th century city, right? That's our vibe. We're the place

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where the Constitution was developed and written, where the Declaration of Independence was agreed. All of these all these firsts happened in Philadelphia. You heard some of those earlier today. But the Philadelphia that I live and work in today, you see it here, has been profoundly transformed by the biotechnology industry. We're no longer just a Siri that a city that celebrates yesterday. We're really a city that looks forward because of the enormous life sciences research and industrial progress that is taking place in Old City and in West Philadelphia, the university committee uh community and really profoundly transforming what had been kind of a sleepy place into an engine for innovation. And that begs a number of questions. Why? Why has this happened? What are the origins of this biotechnology that have transformed a place that was perhaps previously as as stodgy uh as Philadelphia? How did that come about? This is the story I want to talk about today.

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And that story begins with this fellow who I expect most of you have never heard of before. Friedrich Misher. Friedrich Misher, a German Friedrich Misher who uh worked in the mid to late 19th century. He was he was what we would now describe as a cell biologist. Free Misher was also a pretty handy guy with the microscope and he spent a lot of time looking inside the cells in our bodies and he became particularly expert at peering inside the nuclei in our cells to find out what was going on in there. And in 1869 he discovered something interesting in those nuclei. a substance that he couldn't quite put his finger on, but he called it nucleon. Nuclean. And he pondered what could its function be? This nucleon. Today, you know, nucleon as DNA. DNA. He didn't call it that. He called it nuclean. But he in in one stray sentence in one publication, he speculated. He said, you

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know, I wonder if this nuclean has something to do with heredity. And then he let it go. But over the course of the next 70 years, others didn't let that go. And the subject of that that subject nuclean, later to be called DNA, became in fact the subject of a an enormously uh competitive scientific race that took place in the 1940s to discover the structure of what was now understood to be DNA. And that scientific race took place across an ocean. It involved the American Lionus Polling who was pretty sure that he knew what the structure of DNA was going to be and this cast of characters from Britain. Jame well actually an American James Watson working at Cambridge. Francis Crick uh working at Cambridge in obscurity in a laboratory there and then their colleague and sometimes rival

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Rosyn Franklin the much underappreciated Rosyn Franklin who was working at King's College London and who was taking what we now call photographs images of DNA trying to discern what its structure might be because scientists by this point by the late 40s had concluded that DNA was going to be central to our understanding of heredity. That in fact it would be seen as the engine of heredity. But everyone knew that until they could decipher its structure, we were never really going to understand how it worked and we were never going to be able to exploit that knowledge for our benefit. So, some of you probably know this story. uh Rosalyn Franklin takes a series of photographs of DNA using a very innovative camera and a very innovative photographic techniques. And in this series of photographs, she takes one number 51 in the series, you see it just to uh the left of her head there in this image, very murky abstract

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image that has gone on to be called the Mona Lisa of science in the 20th century. the Mona Lisa, arguably arguably the most important scientific image of the 20th century. And she speculates that this says something interesting about the structure of DNA. The photograph, without her knowledge, is passed on to Watson and Crick, who look at this and immediately get a sense that they're on to something profound here. It's suggestive to them that DNA is a double helix. Pauling had thought actually that DNA was a triple helix. one of the few times in his life that Lionus Pauling was wrong about much of anything. But in this instance, they discern that it's a double helix and and in some sense the rest is history, right? That this this catalyzes a search for an understanding of DNA and ways to exploit it for the potential of of improving human health over the next 20, 30, 40 years.

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Incidentally, I should mention that my institution, the Science History Institute, is now in possession of Rosyn Franklin's copy of photo 51. And in beginning in 2027, if you want to see the real thing, if you want to see the Mona Lisa of modern life science, please do come and visit us at the Science History Institute. So, as I said, over the 50s and the 1960s, there is a MAD race, much of it funded in in scientific labs across the US and America, much of it funded by federal uh research monies um to to discern more about the structure and function of DNA and to figure out how to best exploit its potential. And uh in 1969, uh we have the isolation of the first gene. That was a major moment. But it's in 1971 that this story gets really interesting. 1971, a laboratory at

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Stanford, Paul Berg's laboratory, um, starts doing some really interesting work trying to work out the puzzle of how you can create recombinant DNA or RDNA. And the graduate student that you see here, Janet Mertz, all of 23 years old at this time, is able to develop techniques for recombining DNA. She was the first person, in other words, to use what were called restriction enzymes to cut or to splice pieces of DNA from different organisms and then combine them into a single molecule. Right? An astounding achievement. Using this method, she's able to create the first recominant DNA molecule. The next step in her mind uh was to continue work in that lab and clone what was called the SV4 uh 40 virus, a known Anka gene uh so dangerous. And she wanted to clone this virus in E. coli.

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But this work really started to raise alarm bells for a lot of scientists including her boss Paul Berg himself. people started to get concerned all across the country as this work is being published that this is going to lead some to some very um uncharted territory with respect to biosafety. And you know could they was there even possible that they could end up creating an organism that could be dangerous to human health and in some in a sense a mutant or monster organism. And uh and this fear really gripped the scientific community. So much so that Berg made the decision shortly after the 1971 experiments to halt to put a moratorum on this work in his lab and to encourage the his peer scientists around the country to also put a halt on such work because they were very concerned that the next step they were going to pursue the cloning step of cloning and scaling

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the cloning process uh would create potentially really dangerous organisms. and public safety hazards. But while this lab paused, the Berg lab, there was another lab just down the hall at Stanford where actually work preceded a pace. And this is where Herb Buer of the University of California, San Francisco, and Stan Cohen, also of Stanford, were using Janet Mertz's techniques um and were able to demonstrate in 1973 that recombinant DNA could be successfully cloned and replicated at scale in bacteria. So Borer and Coen, Boer and Cohen would go on to receive the first patents for the cloning of recombinant DNA, which is in itself an interesting dimension to the story. It's the first time that scientists working with federal funding are going to pursue a patent with the aim of commercializing their findings, commercializing that

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work. an enormously controversial idea at the time that in some sense alienated Cohen and Ber from many of their scientific colleagues, including those in the Bird lab. But they proceeded thankfully and in November 1973, Ber and Cohen performed the first DNA cloning by inserting DNA from an African clawed frog. There's the handsome fellow right there, into a bacterial plasmid, which was then transferred into E.coli. transferred into E.coli. What this proved was that DNA could be replicated in a foreign host in another organism, enabling the possibility of genetically modified organisms, what we now know as GMOs. This was a bombshell. A bombshell that sent, as David Baltimore, the uh future Nobellist, called it in the early 70s, a bombshell that sent shock waves across

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the scientific community all over the world. Baltimore later said that reccombinant DNA was the most monumental power ever handed to us. The moment you heard you could do this, the imagination went wild. People literally felt that they had the prospect of playing God. And they were both tantalized by the prospect and frightened by it all at the same time. And no one more so than Paul Berg back at Stanford who as we go into 1974 becomes increasingly concerned that people are going to start pursuing recombinant DNA technological research and DNA cloning research perhaps heedless of or not sufficiently chasened by the risks involved. And is he while he was tantalized by the prospects of the research wanted to pursue it he wanted to ensure that it was pursued safely number one that that this work would not create biohazards in

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laboratories all over the country all over the world. Very concerned about that and number two he was concerned that as word started to get out that scientists were pursuing this research the general public and people in government might become very concerned. so concerned that they would want to regulate this technology and Berg and his fellow scientists that they believed one thing. They believed that scientists should really be self-regulating here. Scientists knew the material. Uh they understood the protocols. This work was really best left to the people who had created it. And they were worried that if government got involved and laid on a very heavy regulatory hand that not only would we would we lose the promise of these technologies potentially for many years that there would also create profound misunderstanding and even even unwarranted fears in the minds of the public. So Berg begins to think about and with colleagues begins to think

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about ways that the scientists themselves who are working on these technologies can forestall government regulation convince regulators potential regulators and the public and fellow scientists that work that this work can be uh uh uh prosecuted safely that they can move forward and uh do this work in a deliberate more or less risk-free pace. And so in 1974, uh, Berg and the undersigned that you see in this letter, really prominent scientist, life scientist at the time, Nobellis David Baltimore, you see our friends Stan Cohen and Herb Boyer here, uh, Jim James Watson, he of structure of DNA fame. They all signed a letter to the National Academy of Sciences. A letter that is published simultaneously in the proceedings of the NAS in science and in nature. Right? A letter that no one had ever really seen circulated so widely before. And in it they call for

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discussion about how to um not just put a moratorium on this work permanently but really to get together and figure out which work in our DNA technology and DNA cloning should proceed, what work should hold, what work was absolutely positively should be forbidden and that they wanted to have this conversation soon. This letter has been identified by historians as the first self-denying ordinance in the history of modern scientific research. And following this publication of this letter, these folks met a number of these important scientists gathered together at a place on the Pacific coast called Ayamar. Ayamar, Pacific Grove, California to hold a meeting for 4 days, February 24 through 27, 1975. A meeting that nature, the publication that year called a meeting that future historians of science may record uh a highly

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significant event took place in a California state park. That's putting it mildly. What were they there to grapple with? Really two big issues. The astonishing and seemingly limitless potential of recent breakthrough discoveries in DNA cloning and the worrying biosafety and ethical implications of these discoveries. And the organizers, Singer, Norton Zinder, Sydney Brener, and Paul Berg were laboring under a cultural context with that was not very favorable to the work that they were exploring. Just a few years before, in 1969, Michael Kricton, he of eventual Jurassic Park fame, had come out with his first novel, The Andromeda Strain. Andromeda Strain, which tells a story of an extraterrestrial organism that hijacks a a a US satellite, falls to Earth in New Mexico and spreads across the desert southwest, killing people almost instantly that it touches. And so the

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process prospect has been raised that microorganisms can create massive public health hazards. And between this novel and the movie that engendered, the public gets genuinely a little freaked out. So the moment is not propitious but it's in this climate spurred by this scientific enthusiasm and also these cultural concerns that the Oyllar conference is convened in February 75. It's attended by 140 extraordinary scientists from mainly Europe and the United States. Uh only a few women, mostly men, but 16 journalists showed up to chronicle the whole thing and five lawyers. And on the first day, David Baltimore welcomed the group and he said, 'The focus of discussion must be must be on issues which are unusual for a scientific meeting. It's kind of a first time. What should we know before we do a certain thing? If we come out of here split and unhappy, if they can't come to

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a resolution about how to pursue this research safely, we shall have failed the mission before us. And so the meeting begins and the scientific presentations begin and the quarrels begin among scientists. Marian Dickman who was Paul Berg's assistant said it was the most quarrelome meeting that I ever attended. Several people right up front said that we should declare a moratorum. Morton Zinder, if we had any guts at all, we tell people not to do these experiments until we can see where we're going. And Paul Berg said maybe a little care before we leap would pay off in the long run. An organization called Science for the People advocating for restrictions on science that might harm human health uh stepped in wrote a letter to the organizers of the conference saying we don't believe that the molecular biology community is capable of wisely regulating this development. It's like asking the tobacco industry to limit the manufacturer of cigarettes.

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But then you had others, the very distinguished South African scientist Joshua Letterberg, who said, you know, there's nothing worse than a moratorum to over dramatize a problem. Let the scientists solve it. And Jim Watson himself, who said, compared to almost any other object that starts with the letter D, DNA is very safe indeed. Better to worry about daggers, dynamite, or drunk drivers than to scheme how laboratorymade DNA will lead to our extinction. But remember, the journalists were there. The journalists were there, 16 journalists, and they're chronicling every word. And word is starting to leak out to the public about what's being decided at this meeting, creating anxiety among the participants. And then on the last evening of the conference, they receive a legal presentation from the five lawyers at the conference who said, "By the way, you know, if something bad happens in your labs, you might be institutionally and

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individually liable for what happens. This was new for most of these scientists, this threat." And so on the last evening of the conference, they stayed up all night, future Nobelists, junior scientists. They stayed on all night drafting a conference summary statement about what what recommendations they wanted to offer, what science to pursue, what science to put a hold on, what science never to pursue. And this statement was published and made public. And the next day it immediately makes the New York Times, world biologists tighten rules on genetic engineering work. So the cat's already out of the bag. And shortly the story gets into even publications like Glamour, Cosmopolitan, and the Rolling Stone. And in the Rolling Stone, the the drafter of this article said the conference four intense 12-hour days of deliberation on the ethics of genetic manipulation should survive. It should survive as a landmark and a watershed in

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the evolution of social conscience in the scientific community. people already recognizing when an important moment has just occurred in terms of scientists scrutinizing and regulating their own work. In the aftermath, did people think it was a good idea? Well, Maxine Singer says, "We learned some lessons, many of them negative. It's not certain we act more wisely in the future." James Watson when it was at the other end of the extreme. He said, "The outcome of the Oyomar meeting was nothing more than five sad years of delay in important research. Not completely true. Surely in the years that followed, there was a lot of public debate. As many university laboratories tried to build labs, uh, build projects focused on RDNA and DNA cloning. A lot of communities got up in arms. In Cambridge, Massachusetts, there was a ferocious public debate about whether Harvard should be able to proceed with an RDNA DNA cloning laboratory. And after much back and

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forth, but only some years later was that project allowed to proceed. But this didn't deter these two fellows. Herb Buer, remember our friend from DNA cloning, and a young venture capitalist named Bob Swanson, who in the aftermath of a Syllamar with uh a government more or less convinced that scientists can produce uh this research responsibly, they find a community that was more than ready with open arms to welcome this research, South San Francisco. And in 1976, using our DNA and DNA cloning technology, they found the first biotechnology fullyfledged successful biotechnology organization, Janentech. And in Janentech, in just two short years, is able to produce the first successful product from DNA cloning, humulin, or synthetic insulin, that goes on to save millions of lives. an enormous success story that got the

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attention of the public and led in short order to the creation of other biotech organizations, Amgen, Biogen, Chiron and many others. And by 1980, the government is now convinced enough of the responsible posture of the scientists in talking about and pursuing this technology and the track record of biotech so far to actually lend a hand. And in a bipartisan act in 1980, Burch Bay and Bob Dole create the BA the BY Dole act which allowed universities to own and license patents on technologies that were supported with federal funding. This was a first dramatically enhanced biotech investment. And as the economist said over 20 years ago, more than anything, this policy measure driven by trust in biotechnology engendered really by a syllar and its aftermath uh helped to reverse America's slide into industrial irrelevance.

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So what lessons can we learn for the future from a syllar 1975? Well, as we have today, as we contemplate a world where AI will place an play an increasingly powerful role in the direction of the life sciences and we explore the potential of fields like synthetic biology, maybe it's worth hearkening back to the words of Paul Berg in 1974. I believe that some prudent thought and action beforehand is better than a policy of sticking our heads in the sand. Maybe a little care before we leap would pay off in the long run. Thank you very much.