Short Wave - From Scientific Exile To Gene Editing Pioneer

Episode Date: December 14, 2022

Gene editing was a new idea in the mid-1970s. So when Harvard and MIT planned new research in recombinant DNA, alarm bells went off. "People were worried about a 'Frankengene,'" says Lydia Villa-Komaroff, then a freshly minted PhD. Amidst a political circus, the city of Cambridge, Massachusetts banned research into recombinant DNA, forcing scientists like Villa-Komaroff into exile. But that turned out to be just the prelude to a breakthrough. In this episode, Dr. Villa-Komaroff tells Emily Kwong the story of overcoming the skeptics and coaxing bacteria into producing insulin for humans. See pcm.adswizz.com for information about our collection and use of personal data for sponsorship and to manage your podcast sponsorship preferences.NPR Privacy Policy

You're listening to Shortwave from NPR. Today, I want to start with some time travel to Cambridge, Massachusetts in the 1970s, a tumultuous decade of anti-war protests, desegregation of schools, and major scientific controversy. The controversy began really with some of the scientists, both at MIT and Harvard, who raised objections. Lydia Villarraf is a molecular biologist and a scientist, and a scientist. a really famous one at that. But back then, she was a postdoc working in the brand new field of recombinant DNA, where scientists were learning how to cut and paste genes.

And when the public found out, it sparked some fear among the citizens of Cambridge. The way they would put it was we're mucking around with life. People were worried about a Franken gene that perhaps by moving a piece of DNA from one organism to another, we might cause something that was truly dreadful. The tensions came to a head in 1976 when Cambridge mayor Alfred Volucci called a city council meeting to debate this research unfolding at Harvard and MIT.

I have made references to Frankenstein over the past week and some people think this is all a big joke. The mayor was a wonderful showman, and so he had a high school group come in and seeing this land is your land. There were people with signs. There was protesters outside on both sides, but primarily on the against side. This is a deadly serious matter, sir.

Mayor Volucci asked provocative questions about the DNA research. He raised the specter of playing God. He asked the National Academy of Sciences to investigate whether this research was connected to a recent reported citing of a, quote, hairy nine-foot creature. And he was one of those people who could ask questions without listening to or waiting for answers. It was quite a show. If worse comes to worse, we could have a major disaster on our hands. This meeting led this small city government to take a bold step.

They banned research on recombinant DNA in the city of Cambridge. Therefore, be it resolved that the Cambridge City Council insists, insists that no experimentation involving recombinant DNA should be done within the city of Cambridge for at least two years. I wasn't there because I was in exile in New York. Wait, exile in New York? What do you mean by that? My work at the time required recombinant DNA.

That was banned in Cambridge. And so I went someplace where I could do it, which was New York, Cold Spring Harbor Labor Laboratories. What was going through your mind when all this was going down? Like, what were you telling yourself? What were you thinking at that time? I was thinking why aren't my experiments working. I was living in a dorm at Cold Spring Harbor Labs. I was doing experiments that weren't working. I was basically working around the clock, and I wasn't really thinking about the politics at all.

It was a very sobering and depressing experience. But these frustrations, they actually set the stage for Lydia's later triumph, a landmark achievement in recombinant DNA technology that directly benefits millions of Americans now. Today on the show, Lydia Villacomeroff traces her journey from scientific exile at a lab in Long Island to a pioneer of gene editing. I'm Emily Kwong, and you're listening to Shortwave, the Daily Science podcast from NPR. Lydia Villacomerof found her way to molecular biology through a combination of things, a thirst for learning, a love of life. Star Trek and a noisy house. I came from a big family. We lived in a small house, and so it was crowded. I didn't have a room. I had a wall. And so I think that part of it was,

first of all, I was a curious child. I really wanted to know how things worked. And second of all, I envisioned science for some reason. I don't know where I got this idea, that it would be, you know, big rooms that were very quiet and clean and white, and you could work quietly. alone. That, of course, was a completely wrong thing. You went on to go all the way in science. You got a PhD in cell biology at MIT in 1975. And as a postdoc, got into the world of recombinant DNA, which I remember learning about in biology class in high school, by the way. At the time, though, in the 70s, it was very seldom known, certainly not what it is today. What is recombinant DNA? It was the discovery of a group of enzymes called restriction enzymes that really allowed that next step where you could take DNA from one organism and combined it with another.

Can you say more about these enzymes? Like, where do you even find these enzymes? What they are is they're a defense mechanism for bacteria against bacterial viruses. These enzymes arose in bacteria to do. destroy the incoming DNA of the viruses. But they did it in a very specific way. They didn't just break all the DNA into random pieces. They were very precise in how they cut. They had to recognize a specific sequence. And so the discovery of those enzymes really opened this world up. And it began as a purely, how does this work question? And then someone else said, oh, well, If I broke up bacterial DNA with this enzyme and then I took the same enzyme and broke up, say, mouse DNA and then mixed them together, I would get a combination of both. And that is what recombinant DNA is.

When I learned about restriction enzymes in biology, my mind was blown because I realized basically our bodies have like tiny little surgeons with little scissors that can snip up our DNA at a very precise. precise place. Exactly. So this is what's going on in molecular biology at the time. In 1977, the ban on recombinant DNA was lifted and you were able to move back to Harvard and use this technology for some really significant research, research trying to induce bacteria to make a building block for insulin, a hormone that's really important for regulating blood sugar in our bodies. Can you walk me through, how do you take a human gene and wedge it into bacteria's DNA to make insulin? So in the human and in rats and in all mammals, insulin is made in a piece of the pancreas called the beta cells. And then you can clone that

DNA. And so that's what we were doing with insulin. How did the experiments go? And why do you think it went so well? That was the only time in my life where everything worked all the time. We got it done in six months. Oh, man. Okay. I mean, we were, it was, the whole time was exhilarating because we'd do something and it would work. Do you think this all would have been possible without the ban? Oh, yes. It would have happened faster. Okay. So the ban just slowed you all down. Yeah. But that was okay because it helped, I think, because we got a lot better as scientists about explaining what we were doing and why. Insulin we picked for the project that we did, specifically because, well, most people may not understand how insulin works or anything about the RNA or DNA,

everybody knows somebody with diabetes. I know, too, people. Yes. Yeah. And, you know, my father's mother, I never met because she died of diabetes because there was no insulin available. You ask people in a room how many people know somebody, you know, second graders, they will raise their hand because everybody knows. So that meant that if we could show that we could make insulin, then that would be instantly

recognized as something of use. And so that was pretty cool. You talking about your late grandmother makes me think about my grandfather. My grandfather was diabetic. And I know that one of the reasons I was able to spend time with him as a kid that he lived pretty good life was because of insulin treatment. Yes. So thank you doesn't really quite cover it. It's extremely significant what you all did. Yeah, and we knew it then, and it really did transform our ability to treat certain things. So this was groundbreaking work. It was the first time a mammalian hormone was synthesized by bacteria. It paved the way for insulin treatment to be scaled up, to help people with diabetes. Beyond that, what did this insulin work mean for the fields of biotechnology and genetic engineering? Well, the legacy is, for example, now it really is that diabetics take insulin made by this process.

And in fact, many proteins, people who have diseases where their blood won't clot so they tend to, they can bleed to death. You can replace the enzymes and the proteins in people when they're not there because you can make them in bacteria, yeast, or mammalian cells. And now that's almost routine. So it was enormously impactful. so impactful that molecular biology pretty much disappeared as a field. It has become a tool that is of use in every field of biology and medicine today. Do you think we as a society have moved beyond where we were in the 70s at the Cambridge City Council meeting? No, I think we've regressed. We're in a particularly difficult time right now. There is a significant piece of the population which does not. chooses not to believe things that scientists say. So we had a large population that wouldn't take

the vaccines for a variety of reasons. So I think in many ways we're in a worse spot now than we were then. A really critical lesson for all scientists, especially the young ones, because they're the ones who are taking over now, is communication. We have to get really good at describing our work to people who aren't scientists. And I also think that we need more science from a very early age, because it's just the foundation of pretty much anything we do in society now. It just underlies everything, absolutely every part of our life. Thank you so much for taking the time. Oh, I enjoyed it immensely. Thank you very much for inviting me. Lydia Villacomeroff still lives in the Boston area, where she does consulting work and advocacy

for diversity, equity, and inclusion. She's also one of the founding members of Sochnus, the Society for the Advancement of Chicano's, Hispanics, and Native Americans in science. This episode was produced by Burley McCoy and edited by Gabriel Spitzer. Abbey Levine checked the facts. The audio engineer was Gilly Moon. I'm Emily Kwong. Thanks, as always, for listening to Shortwave,

the daily science podcast from NPR.