Christian de Duve, 1974 Nobel laureate for physiology or medicine, talks about going from a cell biologist to a theorist on evolution and the origin of life.
Steve: Welcome to the Scientific American podcast, Science Talk, posted on September, 9th 2011. I'm Steve Mirsky. This week on the podcast:
de Duve: Everything that takes place in this flower, in my brain, and in your heart and so on depends on enzymes and the right kind of catalysts.
Steve: That's the legendary Christian de Duve who will turn 94 in October. He won the Nobel Prize for Physiology or Medicine in 1974 for the discovery of lysosomes and peroxisomes, organelles within the cell. He is perhaps best known for his ideas about the origin of life on Earth, about which he has published widely and for the lay reader. We spoke on June 30th at the Lindau Nobel Laureate's meeting in Lindau, Germany in a restaurant adjacent to the conference hall, which as you will hear, goes from empty to quite busy while de Duve and I talk.
Steve: I'm very interested in how in your own, the development of your own thinking, how your early work on recognizing and characterizing these cellular organelles of the lysosome and the peroxisome led to your later interest in origin of life issues.
de Duve: Well, it's a long story. My life is a long story and what really started it was, that will interest you, something at Rockefeller—you know, I spent part of my time at Rockefeller and part of my time in Belgium—Rockefeller University, where it used to be the Rockefeller Institute for Medical Research; and I was invited to give what is now called the Alfred Mirsky lectures.
Steve: A distant cousin perhaps.
de Duve: A distant cousin. And Alfred Mirsky was a professor at Rockefeller, he was an expert in the cell nucleus, and he created at Rockefeller something which at that time was called the Christmas lectures, and the Christmas lectures had been created first in London in the 18th century by Faraday, and those were lectures that members of the Royal Society would give for the general public; and so he resurrected the Christmas lectures. They were changed to the Alfred Mirsky lectures. And it's a wonderful set of lectures. They were given at Rockefeller at Christmas time by one member of the Rockefeller faculty for an audience that was made of 550—which is the seating capacity of our auditorium—550 young students recruited in all, or selected in all, the schools high schools of the New York area. So, you had what the best audience you could dream of, just truly motivated youngsters. And so Alfred asked me, in 1976, whether I would give those lectures, a set of four lectures. So, I did, and I thought I would take my young listeners for a visit of the cell, and I called the lectures, "A Guided Tour of the Living Cell". They were made able to visit the cell, and I called them cytonauts.
de Duve: Cytonauts. And it was a special gear and using that gear they were able to enter the cell by endocytosis, follow me into the lysosomes, there they had to defend themselves against very nasty enzymes and so on. And we went to all the different parts of the cells, as if on a visit, and I was the guide. And before giving those lectures, I had to do a lot of studying, because I knew nothing about several parts of the cell. I knew the lysosomes and peroxisomes because I had discovered them; I knew the mitochondria because I was interested in them; I knew the membrane system because my friend, George Palade, had worked on that. But, some areas I didn't know about at all, so I had to do some studying. So that's the beginning of my learning experience in life after my early studies. And the youngsters were very pleased with everything, and so it worked out alright and then the lectures were recorded, and William Bayless who was the director of Rockefeller University Press asked me whether I would agree to have them published, and I said, "No way." I said, "I have other things to do than writing books; I have a lab to run, and I'm creating a new institute in Belgium, so I'm not going to." He said, "Okay fine with it." And so a few years later, a young man came from Argentina, and he was interested in—he was a biologist—interested in science journalism. So he heard about the tapes, and he said, "Do you mind if I edit the tapes?" And foolishly I said, "No, I don't mind. And of course, you have to show them to me before you publish anything." So, I got his first chapters, and they were terrible, so I started rewriting the first chapters, and one thing leading to another, I ended up writing two books. So it became a major work, learning first and then to work it all out so that I could explain it. And the Rockefeller people, who of course were interested in publishing it, but they couldn't do it well on their own—it was too expensive—and so they got in touch with Scientific American. Neal Patterson was the chairman of that, the president, created something called Scientific American Library and the first book in the Scientific American Library was Powers of Ten—I think it's probably still in print; the Morrisons have written that—and the second and the third, because there are two volumes, were A Guided Tour of the Living Cell. And so my first book was published by Scientific American Library, and my major effort was really to learn all that I had to learn to write that book. And so when that book ended up I said, "Well now what I want to do, I would like to summarize for my fellow scientists what is needed to make a living cell." What I was concerned with was life, what are the major features that are common to all living organisms that subtly define life. So I looked at the whole problem as a chemist, as a biochemist and as a molecular biologist. So I wrote a new book which was called Blueprint for a Cell. When I finished that book, I came to the conclusion, I need a final chapter on the origin of life, to complete it. It's a subject I had become interested in; so it took another two years to do all the studying and thinking about the origin of life. And so half of the book, the second half of the book, became devoted to the origin of life. And I even proposed some new theories, which have been accepted, so I'm now a member of the origin-of-life crowd.
Steve: You had to propose new theories because there was no origin-of-life research.
de Duve: Yes, there was Stanley Miller who had started writing really quite a bit of…
Steve: That was very rudimentary; it was the discovery that amino acids would be available.
de Duve: It started a lot of work. But they were chemists, organic chemists, and I was a biochemist, and so I brought in a new vista, a vista of the biochemist on the origin of life. Anyway, I came up with a theory. It is my nature. I cannot look at a question and not try to find the answer, even if I don't know it. So anyway, you asked this, it's a long story as I told you. But then from the origin of life, the next step, of course, was the history of life. And the history of life became a big book, and again I went into the whole evolution, which I had not studied before, from the first cells through human beings; so I had to enter the field of advent ofhumankind or some philosophy, what's the meaning of it all and so on. That became book number three, which was called Vital Dust. And then Vital Dust led to further thinking, because in Vital Dust, I had been a little cautious about my philosophical or religious belief, because I was associated with a Catholic university in Belgium—I didn't want their hurt their feelings, since I didn't share their beliefs. But then I said, decided, well I have to, I don't want to die before without saying exactly what I have on my mind. So I wrote another book which in English is called Life Evolving—so in French the title is much better; it's called Listening to Life, A L'écoute du Vivant—and in that book for the first time, I say what I believe about religion, about the meaning of it all and so on. So this now moves from humankind down toward the human brain to actually to philosophy and religion and so on. And so I think I wrote two more books after that. Then I went over those books that I had written for the general public, it occurred to me that in those books, I was making, in fact, a few original proposals from the scientific point of view, but they were sort of hidden because they were hidden in book for the general public. So I just said, "Now, I think my fellow scientists are not going to read Life Evolving or Vital Dust, so I have to write a book they will read." And so I called it Singularities, and that's a very nice little book, in which I go into—again, it's sort of a sequel to to The Blueprint for a Cell—and in it all those things that are really important and are singularities, you know, a single origin of life, single origin of eukaryote, etc., etc., all the singularities in the history of life. And that's a very nice little book, and I think it didn't sell at all but it doesn't matter, but anyway.
Steve: Let me ask you, your name, to most people that I know who are not professional scientists, is most associated with the term RNA world.
de Duve: Yes.
Steve: mRNA world.
de Duve: Yes.
Steve: That the early biological world was an RNA-based world.
de Duve: Well that's the conclusion of my fellow laureate Walter Gilbert, who got the prize for sequencing DNA. And he invented the world, RNA world, and that kind of theory has become extremely popular among all the experts in the field. Leslie Orgel was one, Stanley Miller to some extent, but just then the others and all the people really very much involved in this field had bought this idea of RNA world; I don't buy it.
de Duve: I don't buy it. Because the RNA world was described by Gilbert as a stage in the origin of life in which there was no DNA and no proteins and RNA did it all. RNA was the bearer of genetic information, doing what DNA does today; but in addition, it acted as catalyst for the earlier reactions. Because at that time, a major discovery had been made by Tom Cech and Sidney Altman, and they discovered catalytic RNA, ribozymes, that is RNA molecules that work as a catalyst. And so Walter Gilbert came up with this RNA world idea, in which RNA did it all. And my answer to that was a little article in Nature titled, "Did God Make RNA?"
Steve: So did he?
de Duve: Well, of course not, I mean, I don't know (laughs) I mean, I don't know. But, as a scientist, I have to take as a working hypothesis that this came about naturally and not supernaturally. So whatever happened, I don't know, but I have to base my research and my thinking on the hypothesis that this was a natural process that took place. And so the question that I'm asking is, How did the first RNA molecule? I agree, you see, I agree that RNA came before DNA; there's a lot of evidence supporting that RNA came before DNA. I agree that RNA came before proteins because the whole protein-making machinery is RNA. Ribosomes contain RNA, messenger RNA provides the information, transfer RNAs brings the amino acids; so the protein-making machinery is an RNA machinery, completely. So that RNA machinery must have come before the proteins. But what came before the RNA is what involves me, you see, and the RNA world people don't answer that question. They start with a hypothesis, RNA was there. And so what I've become mostly involved in, in this field, has been to try—I don't have time to do experiments unfortunately; I'm too old for that and I don't have a lab, but I know experiments that I want to make but anyway—so the question today is how did RNA arise? So, the question that I asked in Nature, "Did God Make RNA?" is still valid today because nobody knows.
Steve: You have a hunch?
de Duve: Well, it's not a hunch. I have reasons to believe. which goes against the creed or the belief of most of the chemists that are involved in this kind of work. My belief is that early chemistry,first of all, my belief is that it was chemistry, because the problem is a chemical problem—how do you get a molecule like RNA together? Once you have it, it can reproduce itself, but how do you get it together? So answer number one is it's chemistry. Then answer number two is this chemistry is biochemistry, because you see, that is what Stanley Miller and Leslie Orgel and all the people who work in this field do not accept. They believe that this is a special kind of chemistry they call abiotic chemistry which has nothing to do with biochemistry that created the first RNA molecule. And then with the first RNA molecule, a new chemistry was born, which was biochemistry. And my reason to believe that something like biochemistry had to arise originally is a somewhat complicated argument; but for the new chemistry to arise, the new, the biochemistry is based on enzymes; because all the reactions of biochemistry are reactions that would not take place on their own. Everything that takes place in this flower, in my brain, and in your heart and so on, depends on enzymes, on the right kind of catalysts. And so biochemistry can arise only with the required catalysts. Those catalysts are proteins, so you're getting the egg…
Steve: Chicken-and-egg problem.
de Duve: The chicken-and-egg problem. But to me this new kind of chemistry of enzymes could not arise if the circumstances—I'm taking a Darwinian view on that—if the circumstances had not made it favorable for these molecules to reproduce, so had not made them useful. And so they had to fit in the early chemistry. So the early chemistry served as a screen for the selection of the agents of the later chemistry, and so there is congruence between the two chemistries.
Steve: And the screen has disappeared over the course of evolutionary time.
de Duve: The screen has disappeared or it's left in terms of its descendants, which are the present reactions of biochemistry and the present enzymes and so.
Steve: The reactions but not the entities, necessarily.
de Duve: Right. So my conclusion was that biochemistry had to be prefigured already in the early chemistry, and so I'm looking for an early chemistry that could do something like biochemistry. And to have something like biochemistry, you need the right kind of catalyst; you can't do it without catalysts. So what I need is catalysts.
Steve: Are you thinking of abiotic catalysts though?
de Duve: I'm thinking of catalysts that could have occurred under the primitive conditions and that could mimic what enzymes do, and I'm thinking of peptides—those associations of amino acids. The amino acids were there; Stanley Miller, showed it, they are on meteorites, the amino acids are available and how they got together is not so difficult, it's not a big thermodynamic problem. The Japanese are making peptides in hot springs and so on. And so I think what we’re looking for, that's what I would do if I had a lab—I would look for catalytic peptides.
Steve: Catalytic peptides. You know, it's very interesting. There was a paper just published on a meteorite that had broken into fragments…
de Duve: Yes.
Steve: And was examined fragment by fragment—different chemistries in the different fragments.
de Duve: I see.
Steve: So, that means that chemistry, active chemistry, was occurring within the meteorite.
de Duve: And that appeared where? This paper?
Steve: I can find it for you.
de Duve: I would love to see that because that's really fantastic.
Steve: I just want to thank you so much for your time. I really, more than anything, I just wanted to meet you and have the opportunity to talk to you.
de Duve: Well, Thank you. I hope at least something comes out of it. (laughs)
Steve: If you're interested, the paper I shared with de Duve was published in the journal Science on June 10th by Christopher Herd, et al. It's titled "Origin and Evolution of Prebiotic Organic Matter as Inferred from the Tagish Lake Meteorite." For a quick summary, listen to John Matson's 60-Second Space podcast of June 13th titled, "Fragments of Single Meteorite Showed Different Chemistry." You can find it in the podcast section of our Web site at http://www.ScientificAmerican.com/podcast (music) While you're at the Web site, check out the Web content related to our September single topic issue on cities—chances are you're in a city right now. And follow us on Twitter, where you'll get a tweet each time, a new article hits the Web site. Our Twitter name is @sciam. For Science Talk, I am Steve Mirsky. Thanks for clicking on us.