Ribonucleic Acid (RNA) – Conversations with History

– [Narrator] This
program is a presentation of UCTV for educational
and noncommercial use only. (upbeat electronic music) – Welcome to our
Conversation with History. I’m Harry Kreisler of the Institute of International Studies. Our guest today is Sidney Altman, who is the Sterling Professor
of Molecular, Cellular, and Developmental Biology and
Chemistry at Yale University. He received the Nobel
Prize in Chemistry in 1989 and is the 2010 Hitchcock
Professor at Berkeley. Professor Altman, welcome to the campus. – It’s a pleasure to be here. – Where were you born and raised? – Montreal. – And looking back, how
do you think your parents shaped your thinking about the world? – That’s a difficult question in terms of shaping my
thinking about the world. I think they were very
focused on education as the path to improvement. They were essentially
penniless immigrants to Canada and they felt that education
was the path to the future. In terms of, let’s say,
social interactions, I grew up essentially in
an immigrant community with values that had been talked about in many different contexts. It was a Jewish community and we had all the appropriate
social and cultural values of that community. – And books were very important? Reading? Did they open a world up to you? – Yes, they certainly did, and reading was extremely important to me. As soon as I learned how to read, which was a fairly young age,
I was obsessed with reading. Occasionally, we went to
the local public library to pick up books. My mother and I went. And there was no inhibition to doing that or to acquiring more books. There weren’t too many
books in our house actually. My mother’s father was
a rabbinical scholar and he taught that in a
parochial school in Montreal until, I don’t know, he
was perhaps in his 60s when he stopped doing that. And anything that I
wanted in terms of books, if it was not expensive,
we usually managed to get one way or the other. So that went on for the rest of my life and reading is still my
main hobby, I would say. – And were you reading about science or were there other
things that turned you on to the possibilities of being a scientist? – I wasn’t reading about science. I was reading anything
I could get my hands on. The culture that I was
being brought up in, and I’m not talking
about the Jewish culture, was, of course, a new one for our family, and my parents were
working in that culture, but I had to learn about it, too. There were some aspects
of science involved and I remember reading
at one time a book that, maybe I was five years
old when I was given it, about various famous people and there were a few scientists there and then the prominent one, of
course, was Albert Einstein. And then I think we had
some encyclopedias around. When I was a little older, my brother was three
years older than I was, so perhaps when I was seven or eight, we got a set of the Book of Knowledge, which you may be familiar with, maybe not. And I just read through
it from time to time and maybe picked up some
things about science. In fact, I know I picked up
some things about science, and there were thoughts of my own about what goes on in nature, and I would say it was
when I was perhaps 12 or 13 when I began to read in a
little more focused fashion about science. – And did you have any teachers
before you went to college who really sorta turned you on to science beyond what you had been reading? – Absolutely not. (Harry laughs) – [Harry] Okay. – My teachers were regular,
unremarkable teachers. – And what about events in the world? ‘Cause you must’ve been about seven when– – [Sidney] Six. – Six when the war ended, and talk a little about that, because did that have an effect, even as a young person, what
you could pick up in the papers about what science had
done with the atomic bomb? – Absolutely. There were, let’s say, two
events which were important in terms of increasing
my interest in science, and one of them was the
ending of the war in Japan and the atomic bomb, and I
clearly remember pictures in the Sunday newspaper
that came out very shortly after the bomb was exploded of
a picture of a bomb explosion and it probably was a
picture of what happened at the test site in New Mexico, but there was a lot written about the bomb and the function that scientists played in developing atomic weapons and principally how it related
to Albert Einstein’s work. So I figure that was important and I figured nuclear
physics was important, and I should say the war
was a very important event or series of events in my life because my parents, my father listened to the radio every day, to the news, and I was there and there was
a lot of discussion of the war in our house. And then when I was 12
or 13, I was given a book which was a very good and interesting book and still exists, I believe. It certainly exists in libraries, and I’m not sure if it is
in print or not right now. It was called Explaining
the Atom by Selig Hecht, who was, I later found out,
a professor at Columbia. Maybe it said it on the book, but I didn’t realize it ’til later. And that was explaining what
the properties of an atom were, what the structures were,
what the periodic table was, and to some extent, I think it said something
about the making of the bomb, but it was written for lay people and I found it perfectly understandable and I found it quite exciting, too, especially the description
of the periodic table. – And then what led you as
a Canadian to think about going outside Canada to do
your undergraduate work? – Well, in fact,
virtually everybody I knew did their undergraduate
work at McGill in Montreal, and nobody left home to go to university, nobody that I knew anyway, because to go to the
States cost a lot of money. In fact, I never even thought
of going to the States. But a friend of mine in
high school wanted to study aeronautical engineering, and they didn’t offer it at McGill, and he said, well, I’m
applying to an American school. Why don’t you just keep me
company and apply with me? And the first step in that application was take the SAT exams, which we normally didn’t do in Canada. So we sort of registered
to take the SAT exams and one Saturday afternoon,
we went down to McGill where there was a room reserved for that. Excuse me. And we took the exam. And later I found out that I
got into, as it turned out, MIT and he didn’t, which
was unfortunate for him, and that was the only
school we applied to, and I knew very little about it until we ordered whatever
material they were sending out and I read about it and it sounded like a
pretty exciting place. So in our family, we
reached another crisis when the letter came admitting me, because it was clear I
was going to go to McGill at no cost whatsoever,
and the question is, could we afford to send
me, essentially, to MIT? At that time, MIT didn’t
give any scholarship aid to foreign students, and we were definitely
foreigners in Canada. So for, essentially, the only
time that I can remember, my parents sat down and
had a serious discussion about what should be done, and my father ultimately
agreed that I should go and I should do my best
to win a scholarship. So I went. – And how different was
America from Canada back then? And what was MIT like
as a place for somebody who had led a relatively
sheltered existence in Canada? – Well, I think, first of all, I have to separate the two questions. One is MIT, the other
is Canada and the US. Although I grew up in a certain community, I don’t think I led a sheltered life. It was a different time and
Montreal was a big city. I believe there were over a
million people in the city at that time, or very close to a million. Now it’s much larger. And you could travel everywhere. As a child, you got on
a bus or a streetcar, the streetcars in the
streets at that time, and literally you could
travel all over the city and you told your parents
where you were gonna go and approximately what
time you were gonna be back and that was no problem at all. So I saw a good part of what
was going on in the city and certainly when I was in high school, I did my best to appreciate
what was going on in the city, and especially with respect
to the French culture. Although I was in essentially
an English speaking family growing up, we learned French
at a very early age in school, and I was interested in that. I took part as much as
I could in the culture and in street fights along the way. (Harry laughs) – Which I guess was useful when you became a scientist later. (laughs) – Actually, you’re more than correct. – Stand for what you think is important. – Stand and figure out how to get the advantage in some ways. So it wasn’t as if, I’m
speaking out of turn right now, it wasn’t as if I approached
my scientific career as one long fight of one kind or another, but there were situations
where there were various events that impinged on me that arose my supposed fighting instincts, and we can talk about that later. So that’s one aspect. Now with respect to coming to the States, life was pretty similar
in Canada and that States. However, there were differences
in our education, too. I would say that I learned
things in high school which they paid no attention to, and this had to do with matters outside of the United States. They knew nothing about, essentially, what was going on outside
of the United States. – The students at MI– – Yes, yeah.
– Yeah, yeah. – And they knew things in high school, they went a little further
than I did in high school, and I had to catch up there, but I also was a year younger
than the other students. We only had 11 grades of
school in Quebec at that time. I found MIT to be, almost
from the first day, a very exciting place, and initially, it was
because of the students. Every student I met was very
smart in many different ways and some of them were slightly
crazy in a good sense. One could lead one’s life with a tremendous amount of humor there. So day to day, there was a lot happening and it was very stimulating. And, of course, then
there were the teachers who were quite good, so
that was no problem at all, and as time went on, and one made more
contact with the faculty, it was apparent that
you could learn a lot. – And you majored in physics? But then toward the
end, the last semester, you took a course in
biology and microbiology? – No. In the last semester of your senior year, you knew you were gonna graduate. You had enough credits and all that, and so you could sort of fool around and do whatever you want. There was a new course and it was called, I think, biophysics or something like that. It was taught by Cyrus Levinthal, who had recently come to MIT, and it was a very elementary
survey of modern biology. Up to that point, there was
no real modern biology at MIT. It was sort of a
classical biology subject. – And this would be what year? – That would be the spring of 1960. So this told you something
about DNA and RNA, and process of information
transferent cells, and it was a short course. It wasn’t too deep, but I did learn something
about biology from that. Well, molecular biology, put it that way. – And then, so physics was
an important foundation, but I guess the MIT
education and your background prepared you to sorta look at
new and different pathways. – Well, I can’t say that I
wouldn’t have done that anyway, but MIT certainly enhanced
that considerably, and I think what you
graduated with from MIT was an idea that the
whole world was out there and you could go out and
challenge it in any way. And to some extent, that led to a little bit
of overconfidence, I think, which is probably not appropriate, but it made you do things that
you wouldn’t ordinarily do. – Let’s talk now about being a scientist. You made some references to that earlier. The first question that comes to mind, what do you think are the
skills and the knowledge base that you need to be fluent
and to then make these choices about which direction you wanna go? – Well, I can tell you a little bit about what was important to me, and some of it comes from MIT. I think that one thing you learned at MIT and perhaps one had a reservoir from that that was sort of untapped, was
the feeling that you had to look carefully at everything
happening in the world around you and especially
in whatever science you were doing, and treat it with a certain amount of deliberate, hard judgment. Also, another thing that I
learned was to be careful about taking data. You took data and you
looked at it carefully and you didn’t throw any of it away and it could all be useful. I think, as a graduate
student, I learned more about being very hard-nosed
about looking at the problems you were interested in, and that I took from my PhD supervisor, who insisted on that. – And who was that? I mean, was he influential in pushing you in the direction you finally went? – [Sidney] No. – No? – No, the direction I finally went in resulted from a serendipitous
number of happenings, but the person who I wound
up doing my thesis actually in Colorado, in a small
department of biophysics at the medical school in Denver, and the person who was my
supervisor is Leonard Lerman, and he was a student of
Linus Pauling’s at CalTech. So he was a pretty serious
guy in terms of science. He was, still is, an excellent scientist. I don’t know what you want from me, where I should continue from there. – Well, it’s intriguing the
extent to which you move across these fields, and I’m curious as to, does this suggest that a
basis in all of these sciences become important as the sciences converge? Or is it really up to
the individual to draw on what his background is in
terms of what he’s studied? – I think it’s up to
the individual, really. But, in fact, I went to Columbia in graduate school in physics and I didn’t like it at all. And that became apparent
in my second year, where I quit after the first semester. I had a great time and I
thought I did a good job on my senior thesis at MIT, and I wanted to be an
experimental scientist, and there was just no opportunity
to do that at Columbia, nothing that I was aware of, anyway, and it seemed to me that would
have to wait for three years and take courses in the
meantime and pass exams before I got to that point, and I got a little upset
by that and I quit, probably before they’d kick me out, and I went home and tried to get involved in the world of writing in different ways, and then somebody who had
been one of my professors at Columbia remembered I
could write and called me up and got me a job as a science writer for a new institute in Boulder, Colorado. And he indicated that I could attend the summer institute in physics there, so I went out there, and I had a job. I attended the summer
institute in physics. I took courses in physics. It was all very refreshing, I should say, and by that, I mean the whole atmosphere towards going to school
was completely different from the East. Students seemed relaxed and happy. So I did those things
and during the summer, I met George Gamow at a party. He was a very famous physicist. I don’t know if you know the name. He wrote several books that
were sorta science fiction. They were the Mr. Tompkins books and The Fantastic Voyage, a
movie which was very successful, was essentially plagiarized
from one of Gamow’s books and he was fighting it
in court at that time and he won that battle. Anyway, he was a very
interesting and exciting person. He was a Russian emigre, constantly in fear that
the NKVD was after him, and he was a confirmed alcoholic. I learned partly all of this because I became friendly with his son and daughter-in-law
while I was there. And I met Gamow at a party and I had perhaps knew at some point that he made some contribution to understanding something about DNA, and, in fact, he had
contributed an interesting idea. So we were just talking at the party, and he suggested that if I was
interested in these things, I should contact the department
of biophysics in Denver and just go down to speak
to them, which I did, and on that afternoon,
I met Leonard Lerman and by the time we’d finished talking, we’d more or less decided that
I would become his student. – Which then led you on
the path that you took. – I should say that these
essentially were my decisions. – Right, right. So it was finding in your
environment the things that interested you. – The appropriate environment
for learning something, which I felt I did not have at Columbia, and in this small department,
I felt it was there, and then pursuing something
that seemed was interesting. – Now what about the
character of a scientist? What are the virtues, the qualities? You made reference to that earlier. Let’s talk a little about that,
that make the problem solver that you are strengthened in this process. – Well, I would say that
there a some common properties that one can refer to, which
must exist in most scientists. But aside from that, scientists are just the same, general part of the population as any other
sample of the population is, and it took me a little
while to realize that. I thought science was a
little bit above the rest of the population in terms of its respect for good and evil and honesty. (Harry laughs) And I learned that wasn’t true. But the fact is, what you
just described is real. You have to be a problem solver. You have to have discipline and control and perseverance, and
all with capital letters. – And curiosity, I guess? – Yes, certainly. Some people are guided
more or less by that. – Let’s talk now about the work that won you the Nobel Prize. You were a co-recipient of the prize. What problem were you dealing with and what were you looking
for that led to that work? – Perhaps the most important
part of all of that was accidental. I wasn’t looking for what I found, and so I can dismiss various
schools of philosophy, popular schools of philosophy
just by that statement. I did not have a genuine, logistical path that led me one way or another. I was working on a purification
of a certain enzyme which I discovered because
of other work I had done when I was a postdoc in England, and we were trying to further
the purification along when I went to Yale as
an assistant professor, and our first unexpected finding was that the enzyme had an RNA substrate, excuse me, an RNA subunit
as one of its components, and that in itself was highly unusual and it took a certain amount
of experimental diligence to prove that, mostly supplied by one of my graduate students, Ben Stark. And then it took even more of my care to survive the assaults
of various colleagues in the general community to
try and get it published. – Let’s explain that a little. So you were working with RNA. Is that correct? And help our audience, recall
to them what RNA is, yeah. – Well, I think most
people have some inkling of what DNA is. That is, DNA is the material in your cells which contain genetic information, and DNA generally appears as a double-stranded helical
structure, very long, and there are monomeric
subunits in the structure, and the sequence of the
monomeric subunits indicates what the information is that’s carried. RNA is not a double-stranded structure. It’s a single-stranded molecule that looks very much like DNA, but is chemically
different in certain ways. But it has the same capacity
to carry information. And I was looking at a certain
species of RNA at that time and the enzyme I found was capable of cutting that piece of RNA
in a very specific place. So it was interesting
from the point of view of understanding how this
RNA got used by the cell, the one that’s what we call
a substrate for the enzyme, and, of course, there
was some further interest in understanding this new
enzyme which we found. – And what I would like to clarify is the conventional wisdom at the time was that RNA was only a
carrier of information. That was its function. – Absolutely. – And to go against that notion
was revolutionary in a way. – Well, first of all,
we showed, as I said, that the enzyme, Ribonuclease P, which is what I was working
on, had an RNA subunit. So that, in a sense, was the
first distinction that we drew. So it meant that the
RNA had some function, seemingly had some function
other than information. But that’s all we knew at that time. Then about six years later or
so, six or seven years later, we showed in our lab, one of my postdocs, who was an absolutely brilliant woman, showed that the RNA actually had some catalytic function of its own, and that means that the RNA by itself could carry out this reaction
over and over and over without changing the RNA in any way. So that essentially
defined what a catalyst is. Just as you might define
chemically a catalyst as lead, when you added it to
gasoline in the old days before lead was outlawed, the
lead increased the combustion of gasoline drastically. So in this case, the RNA of
the enzyme was very active in cleaving another piece of RNA. So that was the truly revolutionary move, and that really upset a
notion that had been in place for perhaps 150 years. Well, not 150, maybe 120 years, that was first annunciated by Pasteur when he was the first person
to describe what an enzyme was, to isolate enzymes. – Now going back to your
earlier work as a postdoc, ’cause I read about that experiment and it sounded interesting. You were the first one to
isolate an RNA by tracking it across a gel. That was a very understandable experiment and it seems like it was an important step in what you later wound up showing. – Well, other people had isolated RNA, very stable RNAs that we
knew were inside cells. But I succeeded in isolating
a pure species of a tRNA that was radioactively labeled. I won’t go into the labeling
procedure or why we did it, but we were able to
label the RNA with P32, which is a common radioactive
isotope in use at that time. Still is in various ways. And all you had to do was
put whatever mixture you had on a gel, which is essentially jello, of different composition and nature, and then you could put electrodes
at either end of the gel, positive and negative, and run
an electric field on a gel, and you knew what the charge of RNA was. It has a negative charge. And the RNA would run through the gel and at a certain time, you would turn off the electric field, put a piece of saran wrap over the gel, and on top of that, put a
photographic film in a dark room, and wait a little while,
and develop the film, and you would see a dark band
where the RNA was on the gel. And so we, I should say,
I succeeded in doing that, and some of my colleagues in the lab were quite interested in this. Well, that was circumstantial evidence that we actually had isolated
a single species of RNA. The next stage was to
extract that RNA from the gel and if you put some
perforations in the gel and in the film at the same time, you could put the film on the gel and you could cut out that
dark band from the gel, depending upon where it was on the film, and you could extract the RNA from that. And then you could do what is
called fingerprinting the RNA, which is essentially a technique
invented by Fred Sanger, to characterize the pieces of RNA that you isolated, and fingerprint means that you had a unique identification of that RNA. And so several of my colleagues
were anxiously awaiting this fingerprinting to know
exactly what was going on and I had to avoid them
because I didn’t want them hovering over me when I did this. And I developed the gel and it showed what I hoped it would show, and there were three or four of us who were pretty excited by that. – And before we talk about
that moment of excitement, I wanna emphasize for our audience, so the presumption before was that whatever catalytic
activity RNA was engaged in was the result of a
protein that had carried, and this process, you, over
time, were able to isolate it and demonstrate, no, that it was the RNA that was the catalyst. – Yes, we took this piece of
RNA that I just described, which was a tRNA precursor, and we made crude extract of E. Coli. E. coli is a small bacteria
that grows in your gut, completely harmless unless
it’s in your bloodstream, and you just broke it
open in various ways, and you exposed this
to this tRNA precursor and ran that on a gel. And instead of getting one
band in a certain position, I got two bands because it
had been cut in one place. So the two bands indicated
there was an activity there, which was the enzyme that cut the gel. So then we purified the activity and ultimately as you
purify it, you wanna get it to the point where you
have, in principle, only one or maybe a couple of bands of protein, because that’s what we
thought was responsible for the activity. But when we ultimately purified it, we found one band of
protein and one band of RNA and subsequently we show the
RNA was the actual catalyst. – So then what was your feeling like? What were you feeling when you realized aha, it did this by itself to simplify? – It put in place a
lot of questions we had about the problem we were working on. We had various ideas that we published at one time or another
about what was happening, and this indicated that we
finally understood the problem. It’s as if you were banging
your head against the wall and suddenly, you didn’t
have to bang your head against the wall ’cause you understood it, and so that was very satisfying. And from then on, a series
of experiments was suggested that we just carried out
over the next few years, but they weren’t intellectually
demanding experiments. We knew exactly what had to happen. But that one moment where we understood that the RNA was a catalyst
was the principal excitement in terms of some
confirmation of what we felt. But the fact was, it was
sort of an anticlimax because it was a very difficult process to go through the
previous five or six years when essentially we were pummeled from virtually every direction
about even the statement that RNA was part of the enzyme. And that relaxed somewhat
when other people found other particles that had RNA in them, that weren’t catalytic, but they had RNA in them, and someone else tried to
disprove our experiment by trying it in another bacterium, but, in fact, he showed
that we were right. So I felt no pressure on that. But the final fact that
we showed that the RNA was the catalyst was the,
as I said, anticlimactic. – And presumably during
this number of years where what you were doing
was being questioned, your street smarts from
Canada came into play, as you resisted or continued on your work, despite the criticism. – Yes, I think that’s true. I can’t say it was a happy time. But I was damn sure that
none of the guys out there, and I just edited the
language I was gonna use, none of the guys out there was going to beat me down over this ’cause I knew what I did was correct. And one of my first
postdoctoral mentors, Meselson, who was at Harvard, I met him
at a meeting during this time, and he said, what was new? And I told him what was new, and I said, it’s been very difficult because nobody believes this, and he’s another extremely self-confident, extremely intelligent person, also a student of Linus Pauling’s. He said, well, did you do all the necessary control experiments? Are you sure this has worked? You’ve done it many times? I said, we’ve done everything
possible we could think of. It always gives the same result. We’re sure that it’s the case. He said, well, there’s no problem at all. That’s what nature is telling you. And then he said, and
somebody else will repeat it and then everything will be fine. And I thought afterwards
that it was easy for him to say that because I knew that he was a very self-confident
and self-assured person, and I said, well, maybe I’ll
believe the same at some point. But he was absolutely right. – I read a quote from you. You were talking about
creativity or this process, and you made an interesting point, which I would like for you to restate, which is that not only
did you solve your problem of banging your head against the wall, but also that it solved the
problems of other people who were working in this area. I mean, in other words, that
somehow you opened up doors that then made greater sense
of a number of other problems. – Well, that’s certainly possible and I should say that Tom Cech
at the University of Colorado was working on a
completely separate system, and about a year before
we published our data on the RNA as a catalyst, he came out with a very similar
experiment in his system, so that there was a feeling
now that what we had published was probably true because Cech had a similar, not identical, but a similar kind of result, and one thing I did say was
that it would be obvious that many more different kinds
of RNA would now be found because you just had to
know how to look for them in a certain way. It had been that people
only looked for RNAs that were very stable and
present in large amounts in cells like ribosomal RNA, which is
involved in making protein, and transfer RNA, also
involved in making protein. But if there was concrete evidence that there was RNA inside the cell, although in very small amounts, and you knew how to look for it, people would find it and that would really open
up the field enormously. And, in fact, that is
exactly what happened. – Now the implications of this discovery, let’s talk about two of them. First, this has important implications for the treatment of disease. How does that work? – Okay, that is a
subsequent finding we had, and it may turn out to be useful. What we found is that, usually
when you find an enzyme, you try and find out exactly how it recognizes the
molecules that it acts on. What are the features of the structure that it acts on that are important? And we did that, and we show
that there’s a small portion of these molecules that was
recognized by the enzyme. And then we understood, a brilliant Australian
postdoc did this is my lab, how you could reconstruct
that small segment of RNA, two pieces of RNA, that look just like what
this enzyme recognized, and if the enzyme saw this, it would cut one of the pieces of RNA. The RNA could be any RNA inside the cell, but you have to put
another small piece of RNA that complexed with it in a specific way, and then the enzyme would
see that and cut it. And the enzyme was inside all cells. It’s an essential enzyme. So we did some experiments over the years in which we did put in
pieces of RNA into cells to target other RNAs that were
either dangerous to the cells or essential to the cells, and we found that this always worked. The host Ribonuclease P
always cut the target RNA under these conditions. So you could say under those conditions, I should say, you could
say that in principle, we have a universal therapy,
which is a very large statement unlikely to be entirely true. But in fact, you can design
this particular system to work under any conditions you like, and we’ve shown it’s
true in mammalian cells as well as many bacteria. The problem is getting that
extra piece of RNA inside cells, and we know how to do it pretty well inside bacteria at the moment, and the question is, will
anybody pay attention to this? Will anybody with money want
to invest into starting up a biotechnology company? Excuse me. So that’s where we are. – And then the second
area, which you touched on in your lecture, is that your discovery sort of begins to help us grapple with the problem with the
origin of life, basically, that it’s put a new
factor into the equation to understand that RNA may
have been a key element in creating life. – Yes. I myself did not put that forward. Other people put it forward and Tom Cech certainly
put it forward also, but in 1967, Francis Crick and
Leslie Orgel and Carl Woese published, in separate papers,
that if we’re thinking about the origin of life, it’s a big puzzle because nobody believed
that protein was present at the origin of life, because you can’t transmit
information to proteins. I won’t go into that at the moment. And they each mentioned specifically that there has been no enzymatic function ever shown for RNA, therefore we can forget
about RNA at the moment. But if RNA had some enzymatic functions, it would open up the whole picture. So that because of Cech’s discovery, and essentially my discovery,
this created a big splash in terms of what people thought
about the origin of life, and then there were suggestions made that if you had RNA present
which has information, it could transmit that information, providing another piece of
RNA could replicate the RNA. And if you had RNA that could proceed in terms of carrying
out metabolic functions inside the cell, then you could have a
primitive cell with RNA, and that’s logically correct,
but it makes an assumption that scientists frequently make. That is to say, if you have
one example that works, then you expand that to
have all kinds of examples of that particular feature,
and you can say this will work. See, the idea is if you
had catalytic function that broke pieces of RNA, then, oh, you can say quite readily that RNA can have all kinds
of enzymatic functions or metabolic functions, and
we can go on from there. And that essentially has been
what people have talked about. – Your work really points to the importance of basic research. ‘Cause your discovery, which in a way, you weren’t looking for, I think you’re saying, but you knew where to look as it emerged, really is probably, and is said to be, as revolutionary as the
discovery of DNA itself. – I don’t agree with
that, but that’s okay. – Okay. So I think it’s important for
our audience to understand the importance of basic research. – You’re absolutely right about that. I wouldn’t rate my discovery equal to some of the
other great discoveries, but that’s a separate issue. But you’re absolutely
right about basic research. I believe extremely strongly that individuals carrying
out research without any specific idea about the
utility of this research, that has no bearing on what
you’re trying to find out, or how you’re gonna try and find out it. The real bearing is just
to solve another problem. It’s to add something
to our bank of knowledge as we do what we have to do, and I believe, as I indicated previously, that individuals and perhaps small groups are the best possible
arrangement for this, and not only that, it’s
absolutely essential for our government to
support basic research. There are some aspects of science where large groups are necessary, for example, high energy particle physics, where you have to have large groups to build large accelerators. That’s a separate issue, but the fact is, the
government has to believe that this is something
that is worth doing. Now if you’re an economist,
and excuse me for saying it, as my son is, you can show quite readily that the future wealth
of the country depends to a large extent on basic
research in the sciences and in technology. And what we’re doing
today is a major factor in the future prosperity of this country, and that isn’t gonna happen
in the next few years. It might happen in 10 years
from now or 20 years from now. – [Harry] That is, the payoff from that. – That’s right, the payoff will
be 10 or 20 years from now. Unfortunately, politicians
have a very short lifetime and what they see, but in fact, Congress is
a large body of people, and there are some people who recognize that this payoff is worthwhile. So I would make a strong case
for supporting basic research. – And are you concerned that
now the US is losing sight of that principle? Going back to the start of your career, the victory in World War
II, the role of science, the government really embraced
the idea of basic science, and there was public support for it. – Well, I think that the view
of science and technology has changed somewhat. We’re still investing
very heavily in science, although our leads, in
comparison to other countries, is diminishing to some extent, and I don’t wanna speak for
all of sciences right now. If you press me, I will offer things that may or may not be true. I don’t know. But in the biological sciences,
there’s been a big push on what is called translational research. Translational research is research that can be immediately applied in terms of clinical therapies. Now obviously, we want
to do that ultimately. We want some of what
we’re doing to be relevant to the health sciences in a real fashion, and unfortunately, too
many Congressmen feel that’s most important, but I think it’s a mistake
to characterize our research as translational research,
and not to give money if it’s not translational research. That, in my view, is a very bad idea, and that’s the idea which is prevalent now at the National Institutes of Health, where the statement is being
made if you’re doing something that’s relevant to translational research, the odds of you getting
money are very high. So I think we have to be
careful about how these efforts are managed and focused in different ways. – In your career, you also
served as Dean of Yale College, and I’d like to talk a little about that, ’cause the other piece of this, beyond funding basic research, is training the next generation of
scientists on the one hand, but also graduating undergraduates who are familiar with science
and can be informed citizens. Talk about what you learned
in that period as a dean and what you tried to do. – Well, I was Dean of Yale
College from 1985 to 1989. So it’s some time ago. And maybe the world
has changed since then. But prior to the time I was
dean, I was chair of a committee at Yale College that
reviewed the curriculum, the whole curriculum. One of the things we found out
was that 30% of the students at Yale never took any science
at Yale, zero, nothing. Another perhaps equal
percentage took one course, but very few courses. So that meant that in terms of science, the students were being,
in my view, short-changed. So we reorganized the curriculum, we recommended that the
curriculum be reorganized so that students take a
science course at least. When I became dean, there
was a very intelligent person who served as the associate dean in terms of academic functions. His name was Martin Griffin, and unfortunately he
died three years hence after I became dean, and we decided if we wanted
to do anything about science, we would have to review
again a whole curriculum, and we did that. Ultimately we came up with
a plan that all students, let’s say, students not
studying science or engineering, all students would have to
take at least three courses in science before they graduated, and presumably three courses in one area, so they’d get more than a very rough
familiarity with something. And that passed in the faculty. And, of course, the deal was
that if you were in science and engineering, you had to
take at least three courses in the humanities, at least three courses in the social sciences, et cetera. So it was all balanced very nicely, but, in fact, it then became
the case that all students had to take at least
three courses in science, and you could not use AP
credit from high school or anything else you did in
high school to satisfy that. I don’t know that that’s
still required today, but it might be. – And then one final question,
how would you advise students to prepare for the future, especially if they want to be scientists? – My advice generally is to find something you’re interested in,
science or otherwise, and study it seriously and carefully, and the final two words are work hard. Work hard is extremely important. – Professor Altman, on
that note of encouragement, I wanna thank you for taking your time from your busy schedule
while you’re on the campus to be on our program. I think it was a very
informative discussion. – Thank you. – And thank you very much for joining us for this Conversation with History. (upbeat electronic music)

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