EMILY KWONG, HOST:
You're listening to SHORT WAVE from NPR.
Today, I want to start with some time travel to Cambridge, Mass., in the 1970s, a tumultuous decade of anti-war protests, desegregation of schools and major scientific controversy.
LYDIA VILLA-KOMAROFF: The controversy began really with some of the scientists, both at MIT and Harvard, who raised objections.
KWONG: Lydia Villa-Komaroff is a molecular biologist and a really famous one at that. But back then, she was a post-doc 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.
VILLA-KOMAROFF: The way they would put it was, we're mucking around with life. People were worried about a Franken-gene (ph), that perhaps by moving a piece of DNA from one organism to another, we might cause something that was truly dreadful.
KWONG: The tensions came to a head in 1976, when Cambridge Mayor Alfred Vellucci called a city council meeting to debate this research unfolding at Harvard and MIT.
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ALFRED VELLUCCI: I have made references to Frankenstein over the past week, and some people think this is all a big joke.
VILLA-KOMAROFF: The mayor was a wonderful showman. And so he had a high school group come in and sing "This Land is Your Land." There were people with signs. There was protesters outside, on both sides, but primarily on the against side.
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VELLUCCI: This is a deadly serious matter, sir.
KWONG: Mayor Vellucci 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 sighting of a quote, "hairy, nine-foot creature."
VILLA-KOMAROFF: And he was one of those people who could ask questions without listening to or waiting for answers. It was quite a show.
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VELLUCCI: If worse comes to worst, we could have a major disaster on our hands.
KWONG: This meeting led this small city government to take a bold step. They banned research on recombinant DNA in the city of Cambridge.
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VELLUCCI: Therefore, be it resolved that the Cambridge City Council insists that no experimentation involving recombinant DNA should be done within the city of Cambridge for at least two years. And be it further...
VILLA-KOMAROFF: I wasn't there because I was in exile in New York. And...
KWONG: Wait, exile in New York? What do you mean by that?
VILLA-KOMAROFF: 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 Laboratories.
KWONG: 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?
VILLA-KOMAROFF: I was thinking, why aren't my experiments working? I was living in a dorm in - 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.
KWONG: 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 Villa-Komaroff 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 SHORT WAVE, the daily science podcast from NPR.
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KWONG: Lydia Villa-Komaroff found her way to molecular biology through a combination of things - a thirst for learning, a love of "Star Trek" and a noisy house.
VILLA-KOMAROFF: 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.
KWONG: You went on to go all the way in science. You got a Ph.D. in cell biology at MIT in 1975 and, as a post-doc, 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?
VILLA-KOMAROFF: It was the discovery of a group of enzymes called restriction enzymes that really allowed the - that next step, where you could take DNA from one organism and combined it with another.
KWONG: Can you say more about these enzymes? Like, where do you even find these enzymes?
VILLA-KOMAROFF: What they are is they're a defense mechanism for bacteria against bacterial viruses. These enzymes arose in bacteria to 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.
KWONG: When I learned about restriction enzymes in biology, my mind was blown because I realized basically our bodies have, like, tiny little surgeons...
VILLA-KOMAROFF: Yes.
KWONG: ...With little scissors that...
VILLA-KOMAROFF: Yes.
KWONG: ...Can snip up our DNA at a very precise place.
VILLA-KOMAROFF: Exactly.
KWONG: 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 the bacteria's DNA to make insulin?
VILLA-KOMAROFF: 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.
KWONG: How did the experiments go, and why do you think it went so well?
VILLA-KOMAROFF: That was the only time in my life where everything worked all the time. We got it done in six months.
KWONG: Oh, man. OK.
VILLA-KOMAROFF: I mean, we were - it was - the whole time was exhilarating 'cause we'd do something and it would work.
KWONG: Do you think this all would have been possible without the ban?
VILLA-KOMAROFF: Oh, yes. It would have happened faster.
KWONG: OK. So the ban just slowed you all down?
VILLA-KOMAROFF: Yeah. But it - that was OK 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, while most people may not understand how insulin works or anything about the RNA or DNA, everybody knows somebody with diabetes.
KWONG: I know two people.
VILLA-KOMAROFF: Yes.
KWONG: Yeah.
VILLA-KOMAROFF: And, you know, my father's mother, I never met because she died of diabetes 'cause she - 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.
KWONG: 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, you know, a pretty good life, was because of insulin treatment.
VILLA-KOMAROFF: Yes.
KWONG: So thank you doesn't really quite cover it. Just - it's...
VILLA-KOMAROFF: (Laughter) Well...
KWONG: ...Extremely significant what you all did.
VILLA-KOMAROFF: Yeah. And we knew it then. And it really did transform our ability to treat certain things.
KWONG: 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?
VILLA-KOMAROFF: 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 in - of use in every field of biology and medicine today.
KWONG: Do you think we, as a society, have moved beyond where we were in the '70s at the Cambridge City Council meeting?
VILLA-KOMAROFF: 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...
KWONG: Yeah.
VILLA-KOMAROFF: ...Many ways, we're in a worse spot now than we were then. A really critical lesson for all scientists, especially the young ones 'cause 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 just the foundation of pretty much anything we do in society now - it just underlies everything, absolutely every part of our life.
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KWONG: Thank you so much for taking the time.
VILLA-KOMAROFF: Oh, I enjoyed it immensely. Thank you very much for inviting me.
KWONG: Lydia Villa-Komaroff 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 SACNAS, the Society for the Advancement of Chicanos, Hispanics and Native Americans in Science.
This episode was produced by Berly McCoy and edited by Gabriel Spitzer. Abe Levine checked the facts. The audio engineer was Gilly Moon. I'm Emily Kwong. Thanks, as always, for listening to SHORT WAVE, the daily science podcast from NPR.
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