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Theories on the Origins of the Life: An Interview with Astrobiology Chair Nathaniel Comfort

In March, Astrobiology Chair Nathaniel Comfort interviewed four pioneering scientists about their roles in developing key models for the origins of life. The program titled “The Origins of the RNA World,” was part of Comfort’s year-long residency at the Kluge Center working on a book project about the genomic revolution’s impact on origins of life research. Dan Turello asked Comfort, a historian of recent science at Johns Hopkins University, to discuss the history of genetics, its effects on origins of life research, and his time at the Library of Congress thus far.

Nathaniel, you’ve been examining a period of time from the 1970s forward during which scientists, including the four you gathered here at the Library, shifted their attention from DNA to RNA. Why was this transition important?

It’s not so much that researchers shifted their attention away from DNA as that they began to fathom the importance of RNA. In 1961, the genetic code was cracked, and by 1966 molecular biologists had assigned a triplet of DNA bases—drawn from the familiar A’s, C’s, G’s, and T’s—to each of the twenty amino acids that make up the basic set of building blocks for proteins. Genetic information is stored in the DNA, and all the interesting work of the cell is done by proteins, from which enzymes are made—including a class of enzymes called polymerases, which read off the DNA.

About that time, several of these researchers began to think about how such a code could have evolved. DNA encodes the instructions for making proteins, including the polymerase enzymes that copy the DNA and read off the messages. It seemed like a chicken-and-egg problem: you can’t make enzymes without DNA instructions, and you can’t read those instructions without enzymes. Which came first?

Several people, including Francis Crick (of Watson and Crick), suggested that RNA, which, like DNA, can store genetic information, might also be able to act like an enzyme. It was pure speculation at the time, so not a whole lot was done with it. But in the early 1980s, Tom Cech’s group at the University of Colorado discovered a piece of RNA that did act like an enzyme. Then, Sidney Altman’s group at Yale realized that the RNA part of an RNA-protein complex they were studying was catalytic. Soon after that, one of my guests at the event, Walter Gilbert, wrote a now-iconic article in which he suggested that at the dawn of life, before DNA and protein, there could have been a world in which all genes, and all enzymes, were made of RNA: an “RNA world.”

Nathaniel Comfort

Baruch S. Blumberg NASA/Library of Congress Chair in Astrobiology Chair Nathaniel Comfort

How does this theory change our perceptions about the origins of life?

If you mentally walk back down the evolutionary tree, eventually you reach what origin-of-life researchers affectionately call “LUCA”: the last universal common ancestor. What did LUCA look like? It probably looked vaguely like a bacterium (although some think it was more like a vast colony of bacteria). The RNA world hypothesis takes us back to sometime around LUCA, or maybe a bit before.

Other researchers, particularly geochemists, are trying to go the other direction: from rock and seawater forward to LUCA. The RNA world gave us a kind of target to shoot at from either direction. There’s still a big gap between basic biochemistry and life, but researchers are chipping away at that gap. Just a few months ago, researchers at the Rensselaer Polytechnic Institute and NASA’s Jet Propulsion Laboratory reported creating chains of RNA in the lab, in an experimental set-up that mimics a type of hydrothermal vent that may have been the cradle of life. So the RNA world is an important theory that, when combined with laboratory experiments and natural observations, helps researchers home in on the origin of life.

What was it like interacting with the scientists who drove such an important shift?

One of the best parts of my job is getting to hang out with scientific legends. I hadn’t met any of these researchers before our event in March. But we bonded immediately. It was terrific fun.

Having had these four men in a room together, answering my questions, sparking each other’s memories, and arguing about the order of events, is proving really transformative for my work. First, I now understand that the RNA world idea didn’t come out of a vacuum. I’m beginning to grasp the set of problems these scientists and others were wrestling with at the time. Second, it has opened up many new avenues for me to pursue as I try to understand the revolution in research on the origin of life that’s taken place in the last forty years or so. These scientists have stories that aren’t written down—not in their published articles, not in their emails and letters, not anywhere. That’s historian’s gold.

You’ve mentioned that the “RNA World”–a term coined by Nobel Prize winner Walter Gilbert–has opened the door to advances in synthetic biology. Why is this?

Life is a circle. If you follow it back far enough, you come around to the future. Roughly four billion years ago, nature synthesized life out of rock and water and CO2. One important aspect of synthetic biology today is the effort to make life in the lab. So these disparate groups of scientists are working on basically the same problem with different tools. Recently, researchers at the J. Craig Venter Institute announced that they had created a “minimal organism”: the world’s simplest bacterium. It has only about 400 genes. For most of these genes, all they know is that the critter dies without them—they don’t know what the gene’s function is. So synthetic biology and origin-of-life research are in a kind of dance, with each leading the other to new advances in understanding.

Synthetic biology and origin-of-life research are in a kind of dance, with each leading the other to new advances in understanding.

Genetics can be controversial, in part because of its early linkages to eugenics. You wrote about this in your latest book, “The Science of Human Perfection.” Would you give us a snapshot of the issues at play?

I argue that human genetics has always been about two things: human improvement and the relief of suffering. The eugenicists of the early twentieth century were interested in disease genes and modern genomic medicine still contains the residue of eugenics. Although eugenics was a dirty word for decades—and for many people, still is—some scientists and ethicists are now talking about a new eugenics, based on individual choice and the free market rather than state control. These ideas have gained new force with the rise of direct-to-consumer genetics companies such as 23andMe—which lets you spit in a test tube and send it off to them, and they then send you your genetic profile—and with the recent development of so-called gene editing techniques such as CRISPR.

Modern genomics has tremendous promise for all aspects of biomedicine, but it’s like a chainsaw: like any powerful tool, you can do a lot of cool things, but if you misuse it, you can do a lot of damage. My hope is that by putting this work into historical perspective, we can learn from experience, avoid the pitfalls, and help ensure that genomic technologies are used for good.

Modern genomics has tremendous promise for all aspects of biomedicine, but it’s like a chainsaw: like any powerful tool, you can do a lot of cool things, but if you misuse it, you can do a lot of damage. My hope is that by putting this work into historical perspective, we can learn from experience, avoid the pitfalls, and help ensure that genomic technologies are used for good.

Have you found any surprising resources within the Library’s collections? What is in store for the remainder of your residency?

I am stunned at the depth of the collections. My desk is piled high with books on astrobiology and the origin of life. I feel like a kid in a candy store: With a couple of clicks of my trackpad, I can have almost any book in the world!

I have also been exploring the papers of Carl Sagan and his wife Anne Druyan. It’s an enormous collection, full of letters, notebooks, and articles. I discovered that Sagan became interested in the origin of life at least as early as the beginning of his undergraduate days. One of my favorite discoveries isn’t especially revelatory, but it’s fun, because it refers to his famous catch-phrase from the original Cosmos series. I found an outline for a book Sagan was planning, to be called “Profiles in Scientific Courage”—a riff on John F. Kennedy’s “Profiles in Courage.” On the back of the sheet, Sagan wrote, “I. Science; Billions and Billions”!

Nathaniel Comfort is a historian of recent science at Johns Hopkins University and the 2015-2016 Baruch S. Blumberg NASA/Library of Congress Chair in Astrobiology at The John W. Kluge Center. On September 15, 2016, he will host a symposium on the origins of life on Earth, in the lab and elsewhere. Click here to learn more. 

§ Watch:The Origins of the RNA World”, Astrobiology Chair Nathaniel Comfort interviews pioneering scientists Walter Gilbert, W. Ford Doolittle, Ray Gesteland and George E. Fox.

One Comment

  1. Jeanmarie Amend
    September 23, 2016 at 11:44 am

    Neil Shubin? at this question, introduce the precise medicine inference about method, that of the interpretation mathematical, and ask our host scholars about per se the Courant Institute, NYU, a summary and interpretation of findings; about the mathematical as scientific and objective, and definition, what is mathematical, from reading the writing of Mario Livio, e.g., among investigators and most gifted scientists.

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