Subotnik,R. 1995  Talent developed: conversations with
	masters of the arts and sciences.  Joshua Lederberg:
	scientific risk taker and innovator.
	J. Educ. Gifted 18(2): 210-226


INTERVIEW WITH JOSHUA LEDERBERG

RS:  This is an interview conducted on April 9th with Joshua
Lederberg at Rockefeller University.  Tell me, or tell our
readers about the nature of your work.

JL:  The center of my professional life is my laboratory which
I've reconstituted during the last two-and-a-half years. It is
focused on looking at the interrelationships of DNA secondary
structure or  conformation, on the vulnerability of DNA to
mutagenesis.  That's saying a lot in a short sentence.  Whereas
most of the attention given to DNA during the last 40 years has
been directed at its primary structure, namely the sequence of
bases which embody the information that it carries, DNA is also
a macro-molecule, a very long and thin one that undergoes all
kinds of contortions of shape and form while preserving its
topology. It is still a string, but a string can be knotted,
raveled, unraveled, kinked, or bent.  That's what we mean by
secondary structure.  Changes in secondary structure are taking
place all the time.  It's part of the regulation of gene
activity. This laboratory is essentially alone in making a
systematic inquiry into how changes in secondary structure
relate to locally differentiated vulnerability of DNA to genetic
damage.

RS:  Are you looking at why a string of genes would organize
itself in a certain shape or do you know why already?

JL:  You can get very complicated interactions between primary
and secondary structures. To simplify matters, for the time
being, I want to hold the first constant. So for a given primary
structure I ask, "How will it change in secondary structure and
what difference will that make?"  We do know that it will change
in secondary structure mostly because of interaction with other
substances in the cell.  If you have histones or other basic
proteins present, the DNA will wrap around those, leading to
differences in secondary structure.  There are enzymes that will
assist in the rewinding or unwinding of the DNA, so you get
changes in the supercoiling. There are proteins that can stick
at two places on a DNA and make it bend, giving it a little loop
that puts stresses on the DNA in the loop. For a given primary
sequence we know we can get a wide manifestation of secondary
structures.  What I'm looking at is how the mechanical stresses
on DNA in different secondary structures cause changes in the
reactivity of the bases.  You end up with changes in the primary
sequence as a consequence of what secondary structure they've
been in, and that's a fairly novel approach.  Nobody else in
genetics is holding primary structure constant.  They are
interested in differences in primary structure, the mutant gene
and the normal gene.  But I want to start out with a given DNA
and ask how it can fold itself in different fashions and then
make it vulnerable to different kinds of genetic damage and
change. I think there's no doubt that DNA which is unravelled is
more vulnerable than DNA which isn't.  To the extent that there
are other predatory molecules lying about in the cell, or even
radiation for that matter, they will have a different likelihood
of causing genetic damage in the unravelled regions as opposed
to those that are tightly wound up.  So, it's a complicated
interaction.

RS:  How come you chose to explore this specific field?

JL:  Well, I've always believed in going after high-stake, high
risk kinds of projects.  It would take a long time to go into
the whole intellectual history of this issue, but since I played
a rather significant role in establishing the existing system of
thinking in the area, I thought it was my job to be the
revisionist in another incarnation.  It also happens to be a
very timely in terms of available technology.  I had what I
thought was an insight into how to preserve the best of the old
and what might be the new.  There have been other more radical
propositions which I view as completely wacky, and I thought I
could see a mechanistic basis on which to find a middle ground
to reconcile scattered observations within the framework of this
construct of the role of secondary structure of DNA.  So it had
all the elements of both excitement and grounding, and I
continue to feel it's a sure thing. We're busy with all the
experimental details, which may take a very long time, but the
basic precepts, I've come to believe are almost tautological.

RS:  How did you develop your sense of what is a good research
question?  Is it something that you were born with or did
someone help you to learn this important skill?

JL:  I've had a lot of intuitions and they've been proven almost
all correct.  The one period that might be argued about was the
ten years of my research life spent in planetary exploration and
issues of looking for life on Mars.  As one of the experimenters
on the Viking mission, I was imbued mainly with the view that
this was a national and human effort and I wanted to be sure it
was done correctly.  I did not have any great confidence about
whether there was life on Mars or not, but I thought with the
enormous investment that was going into that kind of
exploration, that it should be done on a scientifically sound
basis. And I think I did help to do that.  The answers have come
out mostly negative, and one could argue for that reason that it
was a waste of time.  I don't fully accept that reasoning, but I
think there would be less argument on the matter if it had come
out positive.  I still have some engagement with that set of
issues.  But seeing that it was done on the basis of rigorous
science is what I would say was my purpose, and I think I did
play some part in that.
[ I quoted an exception rather than answer your question].

RS:  Tell me more about your question developing skills.

JL:  I start out with an intuition, or with some observed
behavior on my part.  Then I step back and say, "Josh, what are
you really doing? What principles
are you following?"  So there's a certain amount
of revealed structure. Trying to make a more systematic effort
out of it, I would then look much more systematically and make a
scan.
     I have an interjection here about elements of creativity. I
have quoted Lawrence Kubie talking about stresses in a
scientific life. I have found a number of people were at first
startled, then excited when I referred to creativity as having
to do with very dynamic tensions between contradictory aspects
of behavior.  That's not something that you are going to be able
to index except in terms of an individual being able to survive
quite contrary tensions.  There exists a selfishness and
generosity of imagination and rigor. I wish I could do a better
job, and someday I will, about getting a truly orthogonal
classification of those elements.

RS:  You talked about following your intuitions and then saying,
"What are you doing, Josh?"  What is the nature of those
intuitions?  Are these questions that arise when you are reading
something?

JL:  I'd rather call it behaviors than intuitions, although the
behavioral includes what seem to be spontaneous cognitive acts,
but can be a variety of other things.  I'll give you another
example.

I'm often invited to do this or that and I'll sometimes be
tempted - this is the intuitive aspect - to say "Yes."  But
before I do, I'll step back and say, "Look, you're being a
pawn.  Somebody invited you to do something and you agreed to
it.  If you're that interested in following it up, why don't you
take a more aggressive posture and say, if you had complete
freedom of action, what would you do within that framework,
having discovered that you have that interest."  So that's
another revealed behavior.  I don't know whether there's that
much intuition in it, but the unresolved elements of behavior,
particularly in a cognitive domain is what I would call
intuition.  So, this is a heuristic of abstraction in
generalization that I do use all the time when I see a specific
phenomenon either in the outer world or in my own behavior.
There comes a moment when I say, "Look, this is a special case
of some general principle,  Let's discover what the principle is
and what kind of case can be made around that."  So, I'll 
initiate that selection of research topics if I'll have an inkling of an
insight or an idea, then the more systematic way of following it
up will be along the lines I've just given to you.

RS:  Did you get guidance with this heuristic along the way?

JL:  It's hard for me to say.  I don't think that I was ever
told that heuristic.  It may have been revealed to me in various
ways.

The person who would have had the most influence in that regard
was Francis Ryan.  I think I always had a facility for doing
that. It was a way I could keep up with him.  He knew a lot, a
lot more than I did, but I had an ease of jumping to the next
layer of abstraction that I guess I've not seen widely displayed
by anybody else, so I don't think I learned it any place that I
could identify.

RS:  Do you feel that the post docs or the scientists that are
coming to you have this skill highly developed?

JL:  I think they do in varying measures but they are not self-
conscious about it. Part of my job is to get them to another
layer of organized insight, so that they can call on this
resource and not just wait for it to happen spontaneously.

RS:  How do you do that?  By example?

JL:  Mostly.  By example, by doing this in the course of
argument and then every now and then we will talk about
heuristics. We'll ask, "What other heuristics are there?"  A
related one, but not at the same level of abstraction, is that
of relentless combinatorics.  Once you have identified what some
of the variables might be that could be included in experimental
design or influence the outcome of an experiment, the
abstraction would be to say, "Well, these are some of the
variables, what are the others, what are the ones we haven't
talked about yet, do we have some way of exhausting the space of
possible variables. And then what happens if we look at all of
them in any imaginable combination?"  We can't always do that,
so we say, "What rule of reason can I apply that would give me
an efficient and likely successful reduction in the search space
that still involves as wide a set of these components as
possible." We've embodied those heuristics in computer programs
directed at discovery, and the whole DENDRAL project was
essentially a reduction of that mode of thinking into something
that could be programmed.

RS:  That seems more like a brute force approach.

JL:  I'm not sure that we do much more than brute force in our own
heads but that with
some elegance.  I think a lot of "imagination"  is ringing the
changes on the combinatorics. Being able to do it quickly and
efficiently, to do some pruning of areas that are not likely to
be productive.

I don't know my own or anybody else's mental processes well
enough, but it's the only thing I know how to implement on the
computer so I have a way of mechanizing it.
     Back to problem choice. There are elements of taste. Some
experiments just seem like fun, just seem like they are very
easy to do and will answer a question that appears to be
interesting at the time.  That's a fairly powerful motive.  And
every now and then you step back and think about a research
strategy, again generalizing from those instances, scanning for
what's the most revolutionary thing that might be a possible
outcome, reviewing your techniques and resources to see if you
have any chance of getting there. There are a lot of exciting
questions which are unreachable, and a lot of easy things which
are sort of trivial, so trying to find some balance between them
is the strategy. At one stage, about 30 or 40 years ago, I wrote
down what I thought were the major unresolved questions in
biology. One by one, they've all become very nearly resolved.
The details of developmental control have ended up being the
most complex and the most refractory, but bits and pieces of
that are coming together.  So, in a way, by the end of my
lifetime, I may have actually seen the resolution of all the big
questions that I started with in science.

RS:  How did you elicit those ideas?  I mean, did you sit down
one day and say, "What are the big questions in science?"

JL:  Yes.  Every two or three months I go through a kind of
strategic mode and plan how I am going to use my time, not just
on the basis of what's come along so far. Sometimes I imagine
starting again from scratch.  I find that being on an airplane
is sometimes an appropriate setting because I'm limited in the
number of alternative things that I can do, so I just start to
write out systematic strategic inquiries of various kinds.

RS:  What is the process by which you recruit talented people to
work with you?

JL:  The network of personal connection is probably the most
important way, although there have been slightly more systematic
vehicles.  When I set up my lab, I had a very sharply focused
research project in mind.  I knew that it would have very high
appeal to very few people and wanted to find out who they were.
This was one of the times when advertising really did pay off. I
put ads in a number of places -  a couple of the major journals
and The Scientist - mentioning what the program was and said
don't bother to apply unless you can say something meaningful
about the topic in question.  I got about a dozen replies.  If
it had been an undifferentiated ad for a post doc, experience
tells that I would have gotten about 300 responses.  All 12
applications were pertinent, and half of the candidates were of
sufficient quality that I would have felt happy to have taken
almost any of them.  The three more senior people that I have in
my lab right now really were an outcome of that circulation.

RS:  Could you have predicted where they had been trained?

JL:  I wasn't surprised that one of them came out of Frank
Stahl's  lab.  As for the other two, their training was
consistent, but there was nothing that would have highlighted
that.  They were all very skilled, very well trained in their
prior experience.

RS:  What was the nature of your interview.  What were you
looking for when you met them?

JL:  I wanted to know that they had a background of technical
competence.  I needed very experienced people because I was
setting up a lab de novo. They were going to have to be pretty
much on their own that first year, getting only the most general
guidance from me.  My job was to raise the money, set the
general direction of the lab, and see to it that the lab could
get organized. They would have to take on a lot of the detail.
That's quite a daunting task particularly because they would be
taking about a year out of their most productive period of
scientific activity in order to set the lab up. But it would
also give them experience with the sort of autonomy that might
not be available at this early point in their career. So it was
a consciously arrived at contract.  Their independent thinking
was the most important consideration, but it had to be coupled
with proven competence to actually do the lab work. And I got
what I looked for.

RS:  What are the roles of values, peers, mentors, innate
talent, and luck or chance in the development of high level
science talent?

JL:  Well, I haven't thought as much as I should about this in
terms of my own students, and I need to reflect on that more
than I have.  The case I know most about is my own personal
experience, and there the greatest element of luck was my
finding Francis Ryan when I was an undergraduate at Columbia
University.  I, no doubt, would have sought somebody out as a
mentor, but Francis was a very special person.  I know that
nobody else in the Department of Biology at Columbia appealed to
me the way he did and that's already telling you something.
     My insight on how to choose an undergraduate college was
very, very limited. But I had seen and studied a few books.
Lester Sharp had written the Textbook of Cytology, so I thought
Cornell might be a good place to go to.  Sharp would not have
been a particularly appropriate mentor for me, as it turns out.
At Columbia I thought of E.B. Wilson.  But Wilson had written
his masterpiece in 1933 and had long since retired. Even if I
had known that I would have said, "Well, it must still be a
great place for biology."  And that was more or less true,
although not to the degree of my iconic images of it.  I had no
idea that there was going to be Francis Ryan there.  And I had
no idea of what to expect by way of relationships with
professors.  I knew there would be people who knew a lot and to
whom I could ask questions, and they would be sympathetic in
responding. I also knew that they did a lot of research there,
and I hoped that I might somehow connect with it. But otherwise,
it was very, very vague.  I didn't know anyone in the profession
that I could talk to or get any guidance from.
     There was also the question of affordability. My high
     school yearbook says that I was going to go to CCNY [City
College of New York].  That was all that was affordable.  I knew
they had very limited laboratory capability, however, and I had
never heard of anybody from CCNY publishing in the areas that I
was concerned about.  I was very much aware that there would be
severe limitations, but I also knew a lot of smart people that
were going there.  Arthur Kornberg went to CCNY, so people have
managed although they didn't get a lot out of their college
experience, frankly, in terms of training towards graduate
oriented kinds of work.  How much difference that makes in the
long-run, I don't know.  I certainly could not have done
significant research as an undergraduate had I gone to CCNY, so
one element of luck was that I was able to get financial
assistance and go to Columbia.
     I was especially lucky to find Francis.  Above all, he gave
me a sense of discipline.  My mind was a riot of ideas. I needed
to know how to shape those ideas into a specific research
program, how to focus my attention on a few things I wanted to
do. I learned that very directly from him.  I adored him and I
would do anything he suggested or wanted. To have his esteem was
my most important aspiration during that time.  He knew how to
design experiments, he would be quite rigorous in what one
needed to do to put all the elements together, and he used a lot
of Socratic discourse.  He used the dialectical method very
extensively, and rarely would he tell me, "No, you've got to do
it this way."  He allowed me a sense of self discovery, the mark
of a wonderful teacher.

-------------------part 2

RS:  What about peers?  When you were school-age, did you have a
group of peers you could talk to?

JL:  I was very lonely in grade school.  Very lonely.  In high
school, and this is at Stuyvesant High School [specialized
science high school in New York City], there were three or four
kids my own age that I could feel comfortable with about sharing
ideas and experiences, and they could talk back to me and vice
versa. That part was O.K.  None of them was directed in the same
career path that I was, but at least they helped to assuage that
isolation I had when I was younger.  Unfortunately, Stuyvesant
was all boys at that time, and it was difficult to meet any
women that I could relate to on that kind of plane. That was
very unfortunate.  I certainly felt so at the time.
     At Columbia the students were not as rigorously selected as
they were at Stuyvesant, and I didn't have many effective peers
among the other undergraduates.  I did have the lab, however. I
related much more to Francis than I did to any of the other
students.  My peers ended up being the graduate students in that
department. The age disparity required some social adjustment on
my part, but they came to accept me without reservation. I did
meet a Barnard student, a psychology major, I became very fond of.
We didn't work out in the long term for possibly silly reasons; but
I was heartsick when I learned she had died a while ago, 45 years
later.

RS:  How did you deal with your loneliness in elementary
school?

JL:  I think part of my intensity of preoccupation with academic
studies was that I didn't have the distraction of social
interactions.

RS:  Were you harassed at all?

JL: Physically,
I was in danger of some hassle if I ventured a few blocks south of
where I lived, into Harlem, or walked on the wrong streets in peril
of Jew-baiting Irish Catholic kids whom the local priest had taught
about "Christ-killers".  But the kids in those days didn't carry
knives or guns.

At school, No.  In fact, I have no recollection of being harassed.  I
very lately had a reunion with someone who was my classmate in
third, fourth, and fifth grade.  I asked her what she remembered
from that period and she said, "Well, you were a figure of awe.
We really respected you very much.  We knew that you had
problems in your social relations.  We were willing to give you
all kinds of allowances for that because of that admiration."
But Abbey said, "We were kind of baffled, we just didn't know
what to talk to you about."  And she affirmed that most of the
teachers were equally sympathetic, and "equally baffled with
what to do with you."

RS:  Were you in any kind of special class?

JL:  No.  I skipped grades, that was it.

RS:  How many grades?

JL:  Well, I graduated high school in January of 1941 when I was
fifteen-and-a-half.  So it was about two years, I guess.
Columbia wouldn't admit me until I was sixteen so I had a little
hiatus there.  I spent it working in a lab.

RS:  Even at Stuyvesant you only found three people to talk with
at a really high intellectual level?

JL:  No, but there were three with whom I had a very special
affinity.

RS:  How did you find each other?

JL:  We met in class, but I can't recall the date.  All of us
were eventually in uniform, but I was the one who stayed in
training.  One of them was shipped overseas fairly early, stayed
on a little bit after the war and was murdered by his Fraulein
when he decided to go back to The States and didn't want to
bring her with him.   It sounds like soap opera, but
things like that happen to people you know!

RS:  What happened to the other two?

JL:  Jack ended up being an English major.  He spent most of the
war in Iceland as a signal non-com.  He spent two or three years
at the Institute for Living at Hartford. I think he had a
depressive diagnosis.  While he was teaching at the University
or Bridgeport, I had kind of an on and off continued
correspondence with him.  He died quite young of a heart
attack.  And then Bob Mavis  went out to the Pacific, stayed
in the Philippines for a while, came back, got a chemical
engineering degree, and runs an adhesives factory out in New
Jersey somewhere. I have to put it fairly bluntly.  Jack came
closest; but I don't think
I had intellectual peers at Stuyvesant either.

RS:  Did you ever feel that you were abnormal because of the
intellectual distance that existed between you and the world
around you? Or did you experience enough support outside of
school?

JL:  My teachers were wonderfully supportive.  I wasn't harassed
by other kids in school but they didn't know what to do with me and I did
not at early ages have easy social relations with either sex,
especially not girls.
It wasn't until I connected with Francis and the graduate students
(men and women)
at Columbia that I felt there really were peers that
were equal, that had both the confidence and the substance to
put up a good argument, and sometimes show I was wrong and so
on. That was 1941 on.

RS:  You lived in a family and school system, etc. that
valued your being, but couldn't necessarily deal with you at the
same level.

JL:  The important thing was that they knew when to leave me
alone and that was my contract.  In public school that was quite
explicit. When I got bored I would try to show up the teacher
when she didn't do the math just right. It almost brings tears
to my eyes to think of the compassion and understanding which
Mrs. [Sadie] Gold, my teacher, showed me. Mrs. Gold asked me to stay
after class and said, "Josh, we know that you're brilliant, you
ought to know that we know it. But let's make a contract.  I
have a job to do, I've got these other kids who don't have your
gifts and they've got to learn. Let's be partners, and the prize
includes your own development. If you get bored, do your own
work.  I won't bother you, but don't disrupt the class."  The
sense that she was approaching me as an equal was quite
extraordinary.
     So I had all the passive elements of support.  But nobody
took me in charge, gave me a sense of what to do.  I was allowed
to follow my own resources and got lots of reinforcement.  You
know, "You're an unusual person, you have gifts, you ought to do
something with them. We're not sure what to do to help you, but
you're doing just fine on your own."  And that's more or less
the way it worked out.

RS:  Do you think that people who are intellectually developed
far beyond the mainstream should be left to their own devices?
Don't they need teachers too?

JL:  They need guidance. The most efficient way to teach is to
teach people how to learn as much as possible on their own.  I
don't know how far down you can carry this, but most of my
education involved my own reading. I could've used more
guidance, you know, what to read, how to structure what was
going on, even an occasional exam now and then as a way of
pacing what was happening.  If I had met Francis six years
earlier \1/ that would have been enormously helpful without
necessarily taking a lot of his time.  I'm trying to organize
mentorships, including something not as costly or intense as having kids
spending hours and hours working in the lab.  But some form of
organized guidance.

\1/ But he would have been still an undergraduate at Fordham then.
N.B. I just had a great reunion with Elizabeth Ryan (Francis' widow)
perhaps 8 years my senior, and Salome Waelsch, then a research
associate, now still a very active and finally renowned scientist
at age 86.


RS:  What advice do you have about the training of teachers to
work with talented students in science?

JL:  The part that I know most about has to do with their
cognitive depth, their knowledge of the content, and that's
difficult to monitor with science moving as quickly as it does.
Whatever they have learned in school tends to be obsolete pretty
quickly.  So, I think continuing education is probably the major
issue. I know there are programs like the Wilson Center. The
master teacher development design is an excellent concept.  But
I also think that boards of education need to understand that if
you deliver eight hours-a-day of teaching in the classroom, you
don't have time for professional development.  On the other
hand, it's not automatic that if a teacher is relieved of
teaching duties that he or she will spend time on professional
development, so I think you somehow have to find ways of
structuring both access to and taking advantage of continuing
education.  I don't know what there is by ways of books and
publications addressed to teachers in science.  I know there is an
association, but there ought to be a level of awareness and educational
enhancement that's between the graduate textbook level on the one hand,
and the popular books on the other.  I suppose Scientific American
isn't too far different from that.

     I'm speaking now especially in high school. I know my children's
experience with high school science teachers was very mixed, covering
the spectrum from atrocious to mediocre with a few exceptionally
gifted, alert, and knowledgeable people.  But you have to ask what more
you can expect in terms of what the incentives and rewards are for
getting people into science teaching these days.  With very rare
exception, or very particular motivation, really hot shot scientists
are not going to go into teaching.

RS:  How did your children describe their most gifted teachers?

JL:  More in terms of inspiration than content.

RS:  Were they lacking in content?

JL:  No, I'm not saying that. They did have teachers who were at most
three lines in the textbook ahead of them and were unable to explain
things when they raised questions and so forth.  However, the kids take
knowledge of the content for granted, so you're not about to get a lot
of raves about how smart the teacher is.  You get raves about how
effective they are.

RS:  And how was the effectiveness demonstrated?

JL:  They made the subject interesting, they were able to deal with
questions, they managed discourse in the classroom and kept students
involved, and they knew how to relate the subject matter to other
aspects of the world.  The usual.  But the kids in the school were not
in a position to make critical judgements about what a teacher does and
doesn't know.  They only know when it's a flop, so if it isn't, they
sort of take it for granted.

RS:  Reflecting back on your own experience as a professional
scientist, can you talk a bit more about your experience in high
school?

JL:  I was an anomaly. With rare exception, I knew more than they did
about the subjects that I was learning, certainly in the sciences.
There might have been marginal exceptions to that in some fields. If I
ever sensed that a teacher knew more than I did, I repaired the
difference. I would just hit the books and go to work and master it.
That was not true in every subject.  I remember having a thrilling
course in civics. I didn't take any more political science in college or
whatever, but I think it gave me a very solid grounding.  The teacher
was someone who really understood his subject and dealt with it at a
very effective level.  But within the sciences, with all the vaunted
advantages of Stuyvesant, it was not the teacher's knowledge of science
that was critical.\2/  They were sympathetic to science, they were
encouraging about it as a career, but my peers were more important to
me in that respect than my teachers.  But remember, I was a freak, so I
don't judge by my own experience what they ought to be and do in
relation to other students.

2/ Perhaps I take that too much for granted

RS:  Let's tie this into your interest in helping, guiding, young
scientists. What age groups do you think would be most receptive and
most positively affected by this mentoring?

JL:  It's at the high school level that I'm hoping to find some way of
setting up a mentoring system where students who might have an interest
in science can get some well informed grounding about what to do to
achieve that aim or to understand better what their relation to that
aim might be: what to do about their studies, how to allocate their
time between what they have to do in class and their own reading, what
to think of in terms of college aspirations.  I visited the science
teachers at Hunter College High School a few weeks ago, and they
understood their own limitations about how to relate to some of those
professional issues.  You raise an interesting question about what age
groups to deal with.

I don't know whether eleventh or twelfth grade might be late in the
differentiation of students' interests or whether I could do much with
the younger kids.  Fairly casual contacts are not likely to be too
productive.  I don't know how I would come across to an eight year old
I didn't know.

RS:  According to the research that I've read, ninth grade is the point
that differentiates which students are in or out of the science
pipeline.

JL:  If ninth grade is critical than that's what we ought to focus our
attention on.  I think even at a younger age a gray beard like myself
might still be able to have a meaningful contact.  I have a sense that
it just takes longer to cultivate an interest and to get to know them
than it would for the somewhat older student.

RS:  I think gray beard or not, if you approach them with respect, in
the same way that you described your elementary school teacher speaking
to you, the students would respond.  What would be the logistical
nature of your idea?

JL:  One-on-one is what the core of it has to be. But I need a lot of
help on this point.  I only have vague ideas on how it might be
structured, but I thought there could be a clearing office, maybe at
The New York Academy of Sciences that would have lists of volunteers
who would be willing to be available and would then also, mostly
through the schools, identify the teachers who would be interested in
cooperating.  Some teachers will find it threatening to their own
monopoly of relationship.  In fact, I had a warmer reception at Hunter
than I did at Stuyvesant, when I mentioned this idea to a few people,
maybe because Hunter doesn't regard itself as the unique place for
science education.  Perhaps there could be a way in which the
professional scientists would make some group appearance, but then
indicate that the students who are interested, and they might need a
little egging on by their teachers to overcome their bashfulness, might
get some guidance, advice, and instruction. And it's not necessarily
going to be signing up for a lab experience, which is the immediate
presumption as soon as I mention this at all.  That's about as deep as
my thoughts on that have been.  I'm very eager to get your own
impressions about that.  RS:  I would love to assist you with this
project.

JL:  Well, I've been urging Bob Lichter to get hold of you and the
Dreyfus Foundation might be willing to find some support for this.  We
were wondering in what ways a modest amount of money might make a
difference.  Car fare for the kids might be an issue, maybe limited
funds for some books or journals or whatever, for both parties in the
transaction.  Even a few hundred dollars a year for a volunteer.  My
view is that once any of the potential mentors get hooked into it,
they'll do it out of their own pocket.  I mean, it's a pretty modest
amount of money and their time would be worth a lot more than that.  So
that's as far as I've thought that one through.

RS:  Can you give me your views on the value of contests like the
Westinghouse Science Talent Search?

JL:  I think as a way of eliciting interest on the part of the students
who come in with marginal involvement, it's probably all to the good.
I'm not sure it's the best way for a committed student to spend his or
her time.  I can think of more fundamental studies if they are willing
to put their nose to the grindstone.  You can't learn too much by way
of basic mathematics, physics, and chemistry no matter what else you
are going to do, especially if you are going to go into biology.  It
sounds like an anomaly but if you are really interested in biology,
postpone doing biology and make that the last and not the first thing
you do.  Make sure you build your fundamentals as deeply as possible.
Unless we get more students who have had intense mathematical
preparation, we're not going to get the biological breakthroughs.  I
think there are similar things to be said about chemistry and physics.

RS:  The teachers at Hunter College High School are apparently not in
favor of students competing for the Westinghouse Science Talent Search
if it means working at an outside lab. They are concerned about the
students going to labs and not doing their own work. Is that correct?
Do you sympathize with that view?

JL:  To some degree.  There are inappropriate expectations for being
able to do any really creative and original work in the lab.  I'm not
saying that that's always the case, but if you are going to have to
come out with a poster to present in the Talent Search, the implication
is that this is "all mine." Laboratory experience provides the best
learning when it helps to habituate you to most experiments not working
the first time, to then going back to fix it up, getting that kind of
discipline. If it can be done in a supportive way and it isn't too much
of a challenge to the students' self esteem and so on, it is part of
being an apprentice, so that part is good.

RS:  What are the alternatives to working in a lab where you have
access to equipment and expertise?

JL:  I think book studies are the best alternatives, but you may need
both inspiration and guidance to stick to that. To this day,
I'm still torn between
learning what I can from reading the literature as compared to the very
slow and inefficient process of my own personal discovery in the lab  In
half-an-hour I can get the distillation of 10 years of somebody else's
work by reading it.  There's always the need to keep the balance
between the two.

RS:  Unfortunately, you can't do a review of the literature for a
Westinghouse project.

JL:  That is very unfortunate.  For one thing, knowing how to do it is
a very important skill.  It's just as important as knowing how to do
the lab work.  I think reviewing the literature is underemphasized and
that's one of the things I would do in counseling students, is to try
to find something that they are curious enough about to really want to
know all that can be known about it from reading.  The chance that they
will find out the same amount or make a major advance by doing a lab
experiment is very low, and less if they don't have their grounding in
the reading to know what the platform for that research would be.  So
those would be my druthers.  Much more emphasis on the research
libraries as compared to the research laboratory.

-------------- part 3


RS:  How about introducing the concept of research design, like
validity, reliability, etc.

JL:  I think criticizing other experiments is more efficient
than doing it on your own.  I mean, it may be more dramatic when
you've been through it yourself, but there again, it's a
two-stage matter.  I think first there should be a critical
analysis of published experiments, and then one could be in a
better position for self criticism of your own design.  I feel
it's partly a matter of staging.  The junior year of college is
in some ways the more appropriate time to think about organized
research, once you've got four more years of platform and a
background in all the other reading that I'm talking about.
Then the likelihood of being able to do a serious research
project is much greater.  Now it doesn't have to be all or none,
but I certainly would find more ways to put emphasis on the
library.  That may take some heavy mentoring.  For a student to
jump straight into the contemporary literature is asking a lot,
but I think with some counseling and support, a lot can be done
in that direction.

RS:  In earlier days, more students participated in the
Westinghouse Science Talent Search. Currently, students seem to
need more enticements to think of themselves as scientists.  Can
you elaborate on how science seems different today than it was
when you were a novice?

JL:  Well, I have to be fairly humble about pronouncements when
this is a sort of prototypic social science exercise and there
are methodologies to try to answer questions like that.  I don't
know if that's ever been done, and in particular I doubt there
is a baseline to make any comparison generationally. My
reflections are projectionist. I judge what another generation
thinks just from what I see about science in the popular
culture. The cognitive elements have exploded, become highly
differentiated. There's no such thing as "science" anymore in a
certain sense.  There are a lot of different "sciences" and
sub-sub-specialties get to be the dominant elements.  You don't
expect anybody today to be conversant in both cosmology and
molecular biology.  If you are going to be in science, you have
to come up very quickly with a differentiated interest.  To get
to those sub-specialties there's a longer and more daunting
course of training.  I may have been the last of any generation
who could do a significant experiment as an undergraduate in a
new field.  I would ask myself where would there be
opportunities like that today. I'd be inclined to guess that I'd
need another four, five, or six years of specialized training to
be capable of doing anything at the frontiers today.  So string
and sealing wax are less and less effective as scientific
instruments and a larger and larger proportion of the work that
could be done at that level has already been done and
exploited.  Those are the cognitive elements.
     There are also what I'd call ideological and ethical
considerations.  There are many more ambiguities about how
science relates to human affairs. The Bomb has been the crowning
technological achievement of modern science and that's elicited
Frankensteinian images.

RS:  How did the Bomb affect you when you were a very young
man?

JL: Recall I was 20 in 1945. My answer relates to the 1930s.
     I didn't put much credence in the horror stories.  I knew
there were abuses that were possible, but I thought that better
education would relieve people of inflammatory prejudices.  I
thought religion was the major cause of many excesses and that
the scientific revolution would dispel that.  I take a slightly
different view of that today.  I still think there is a lot of
superstition and ignorance behind excess behavior, but I
certainly don't attribute the entire problem to religion.  You
see something like what happened at Waco and you are reminded of
the people who participated in the Holocaust.  I mean, there are
elements of human nature that are easily exploited and where
issues of ignorance and superstition do play a role, I no longer
believe it's a sufficient answer to human ills to eliminate
superstition.  There are value judgements about what to do in
the world that are extrascientific, and you can't derive or
moralize strictly on scientific considerations. I know that the
scientists involved in the Manhattan Project were also the ones
who almost unanimously advised against using it. They had been
involved in the development of the bomb because they thought it
was necessary for defensive purposes.  Science is not
intrinsically evil, it's not intrinsically good either, and if
you don't have people in power who are morally motivated, then the power
of destruction is vastly enhanced as a result of scientific and
technical development.  These are heavy questions and no matter
how you come out, they present a moral load on the whole issue
of going into science which I think is substantially greater
today than it was before 1945.

RS:  How about the lifestyle questions?  That seems to be an
issue for the children of the Eighties.  Unless they can be
convinced that the intellectual pleasures of science surpass the
low income and huge time commitment, lifestyle issues remain
very pressing.

JL:  Well, there's a certain circularity in that.  If you're not
involved in science, you're not going to be interested in it.  I
think most scientists say that the lifestyle they prefer is one
of involvement. The preoccupation and so on are part of the
fun.

RS:  How about the time spent seeking grants?

JL:  That's really coming to a head just now and I think that
probably is a deterrent at this stage.  If you look at students'
career choices at the college level, I think they have been
until very, very recently heading in droves to law and business,
and you read that an MBA is worth $100,000 salary right off the
bat. If you have to be grubbing around for grants for years to
make it in science, I'm sure that that's a deterrent.  On the
other had, that argument can be overdone.  I think any youngster
with real talent doesn't have to worry.  I see thousands of
scientists who are in fairly happy situations with their lives.
They're doing the work they want to do.  In many respects their
income, relative to other occupations, has improved somewhat,
although probably not relative to business. It would be an
interesting to get some facts on this question.
     It's interesting to note that science has been a career
     that in the United States traditionally offered some
mobility. Through science, people have risen very dramatically
in many cases from what their parent's economic status had been.
Jews, in particular, had few good alternatives in earlier times.
Science and medicine seemed like the obvious things to do
because you were going to run into more immediate ceilings in
other professions.  With medicine, you had problems getting into
medical school but once you were there you were pretty secure
after that point.  I think for Jews the more or less complete
disappearance of restrictions on mobility may be one of the
reasons that less of them are going into science than used to be
the case.
     I have a feeling that the moral issues are even more
important than the economic ones.  Your ninth graders I don't
think have heard a lot about grant seeking, but they've heard
plenty about what scientific monsters can do. Why don't we
investigate those points instead of speculating about attitudes
in those cohorts?

RS:  I think that can be part of the preparation for your
guidance program.

JL:  It's a good idea to know what the problem is if you try to
develop remedies.  But if you see how this has been hammered
home over and over again, how science is portrayed in popular
culture, it just tends to reinforce all the negative myths.  The
younger the receiving population, the worse it is.  Until a few
years ago, the Sunday morning cartoons were filled with mad
scientists. The cliche was perfectly obvious.  If someone was a
scientist, they were portrayed as an evil wizard. (Cf. Jurassic
Park).

RS:  What I have found in my conversations with young people
talented in science at the middle school and high school level
is a concern about using animals in research.

JL:  Well, it's certainly an issue.  It's dissuaded my daughter
from going into biology.  She just couldn't bear the thought of
dissection.  She understood why it had to be done, but she
couldn't do it herself.  And I don't know why there's been such
a change in emphasis there.  I think maybe urbanization of
America has a lot to do with it.  You don't find a lot of
compunction about animals out on a farm.  What do you think?

RS:  I think a lot of it is due to the success of the animal
rights and environmental movements in counteracting the cavalier
attitude that many people, including some researchers, have
towards animals.  There are some interesting paradoxes. The same
people who have no problem running over pigeons in the city
might not feel comfortable with dissecting a fetal pig.
Inexplicably, certain animals have higher status than others. I
think the children who have given animal research a lot of
thought and are really serious about their concerns have to
confront this status system and decide how to deal with it.
JL:  It may be an issue of affluence.  If people are hungry
enough they'll eat whatever is around and not give too much
thought to it.  When you can afford to be a vegetarian, then
maybe deeper instincts of animal empathy that have been
suppressed at an earlier time may arise.  I never turned the
question on it's head before.  I think there is a very
interesting issue of ideological history pursuing that
question.  There are certainly very important national
differences.  You will get nowhere in Japan on any question of
animal rights, believe me.

RS:  But in England, on the other hand...

JL:  There's a long history of it.  The Englishman and his
dog...

RS:  And his horse.

JL:  Anyhow, it certainly is a deterrent and I think biology
education is going to have to continue to take account of it.
Some students get into biochemistry through chemistry so they
can avoid the dissection components of their academic
preparation.
     But there are other ideological issues.  When you start out
with a generation like mine that had, in general, much deeper
religious convictions, I think a commitment to science was in
some measure a displacement, a sublimation, if you like, of
that.  Religious issues generally don't seem to count for very
much right now, so I think there is, to that degree,
correspondingly less impetus for science to play a role in
people's lives.

RS:  Today people seem to be more able to live without putting
order in the world around them.

JL:  It's not a question that's presented to children in an a-
religious world, and so there's less motive for what I'd call a
counter-religion.  Some people would say that science deflated
religion and in the process reduced some of the motive to think
about doing science in the first place.

RS:  Do you think that science could be made more attractive to
spiritually oriented kids by focusing on some of the more
aesthetic or the cosmological sides to it?

[ Yes!  Cf Carl Sagan.]
JL:  I think that already happens by way of self selection in
careers, but the fragmentation of science goes against that.  If
you had the feeling that you might have been among the "Giants
of the Twenties" who really changed our world view at a very
fundamental level, you would feel that you were dealing with
some very important eschatological issues.  The expectation of
being able to do that in today's fragmented world is so low.  If
you are going to be a discoverer of a new particle, you'd be one
of a team of 300 people.  So I think that must be a major
demotivating factor.  We're back to the issues of complexity and
fragmentation again.  I feel very fortunate.  I've been able to
keep a perspective about science which is much broader than
almost any of the other people I know, but I do feel like a
dinosaur in that respect.

RS:  David Feldman, a developmental psychologist, has proposed a
"theory of coincidence" as related to prodigies. He believes
that one of the major variables affecting prodigious behavior is
the stage of development of the field in which a prodigy
appears.  This theory speaks very well to what you are saying.
If a field is too highly developed,  it's hard to nurture a
prodigy, because it's not feasible for a child or a young person
to have achieved enough experience or knowledge to make an
impact.  If you can't do really frontier level work until you
are a post-doc, then the field becomes less insightful!

JL:  It's also part of what you have to counsel the youngster
on.  On the one hand, have to have realistic expectations. On
the other hand, you cannot be so dampened by realism that you
destroy the motive to go into it in the first place.

RS:  Do you see any budding areas where a young person could be
one of these "Giants of the Twenties" in biology?

[ See very last paragraph]
JL:  All the ones I know about are very well populated right
now.

I don't know if it's the poverty of my imagination or if it's
really true that the habituation of science has become uniformly
dense.  Most of the domains that are not thoroughly developed
are borderline areas of applications rather than fundamental
theory.  And it's a question I've asked myself many, many times
and others have as well.  The only place that I could expect
some significant breakthrough is in new approaches that are
going on right now in the mathematization of biology.  It would
be something very different from the logical mathematics being
done right now, but until we develop better ways of codifying
our present knowledge, we are caught in this ever increasing
fragmentation difficulty. I have a program in computer science
affiliated with my lab program which is intended to kind of
nibble away at those sorts of issues but it's going to take more
than we are doing to make any significant breakthroughs in that
field.  And it may be unfeasible.  This is what I label as
Leibnitz's dream and I'm not sure how seriously to take the
enterprise.  Leibnitz's dream, the codification of knowledge, is
the area that I see as waiting for a new conceptual
breakthrough, and it's one of the reasons I've been interested
in computer science for a number of years.  We've done some work
that provides steps in that direction, but it doesn't begin to
be the major leap that I'm looking for.

RS:  What might be a reason for people from various fields at
Rockefeller University to come together and apply themselves to
a problem.  Does that ever happen?

JL:  Oh sure.  But usually it's due to a convergence of
technique rather than to a conceptual framework. We have people
who do X-ray crystallography and others who do NMR studies, and
other people who have got the DNA specimens to be looked at.
They'll get together and collaborate on that basis.  We have
people doing clinical work and people doing basic science and
that's a little closer to the intellectual collaboration that
you were talking about.  There are efforts just burgeoning to
try to enhance the opportunity for collaboration by making
geography irrelevant. That's a good deal of what the National
Information Infrastructure is all about.  I've been on some of
the committees looking at collaboratory organization and so
forth.  In biology the Human Genome project has a lot of appeal
to some people because it is so narrowly framed.  There's a lot
of work to do in a well defined arena that parcelling out of
tasks and organization of labor is in some ways more feasible
there.  It may not be a particularly worthy objective, but it's
something that can be done, so that's the main arena in which
there's very organized activity in biology that probably
coordinates what a lot of people are doing.  See, they all speak
a common language and the codification is trivial.  You end up
with the DNA sequence as the common article of interaction.
That's only the beginning of the biological process.

RS:  Theoretical physicists design logical, mathematical ways to
prove theories.  Is there something like that going on in
biology?

JL:  Very little.  I've indulged in a bit of it myself, mostly
with the view of the theoretical framework for my own research.
But every now and then there's an opportunity to do it on a
larger scale.  My main contribution of that kind was in the
elaboration of the theory of immunology.  They call it
"Clonal Selection Theory."  In fact, I had organized how to think about
the problem, but I relied on a false premise, and so walked
right up to an articulation of the theory and then, in effect,
rejected it, but for the wrong reasons.  The false premise is
that there is an infinite number of antibodies.  There are a lot
of antibodies.  You put in any antigen you can think of, you can
get an antibody to it.  There's still a big step between that
and infinity, and when you ask yourself, "What's the minimum
number of antibodies there might be in order to satisfy what we
know empirically, today we would say it is somewhere between 10
and 100,000.  Well, 10 and 100,000 is a small number for the
different cells of the body to be able to elaborate one by one.
Infinity is a large number, and that was the contradiction that
I allowed myself to fall into.  So, I articulated this in 1955,
a theoretical paper which a few people are beginning to
acknowledge was at the root of it.  The history that Tom Brock
has written on bacterial genetics has been very sensitive to
that.  The basic controversy that underlies all of this, and we
are talking in very theoretical terms, is whether the
information for biological products comes entirely from the
information that's in the genes, or do environmental influences
leave their stamp.
     Here is a biological example - enzyme induction.  You have
     a bacterium growing on one medium and you add a new
substrate. It very often happens that after you've added the new
substrate, the bacterium develops the enzymes to attack that
substrate.  The classical example of that is the attack on milk
sugar, or lactose.  The very first problem that I addressed in
applying bacterial genetics to gene physiology was in that
direction. I'd gotten a bunch of mutants incapable of making
this response, and that system, it's called the beta
galactosidase system, has become the core of this kind of
investigation, not only in bacteria, but people even transplant
bacterial genes into mammalian cells so that they use the lac
[sic] system in that setting.
     But the phenomenon was bacteria not making lactase, the
enzyme, until after you put lactose, the substrate, into the
medium. The prevailing view was that the lactose must somehow be
shaping the proteins of the cell so that they will then react
with it.  But there is another possibility.  The alternative
possibility is that all the genetic information for making
lactase is there, the only role of the lactose is to be a signal
to switch on the machinery that will make that particular
enzyme.  So one is the instructive hypothesis, that the lactose
instructs the formation of the lactase structure. The other is
the elective one, that it's just a signal.  The properties of
the mutants that I had developed persuaded me about the second
alternative.  I was in a debate with Jacques Monod in the
50's about that. It was 90% theory and 10% experiment.  The
experiments were not firm enough to draw very definite
conclusions.  Two years later, Jacques completely reversed his
position and became the main exponent of what is called the
Operon Theory, developing beautiful experimental detail in
order to corroborate it, and that was his Nobel Prize.
     In that same discussion, I said, "Let's also think about
antibodies, would they operate that way."  I said, "Maybe, but
probably not, if there's an infinity of antibodies, then there
can't be an infinity of switches to be signals, so possibly they
operate through a different mechanism."  Burnet, a long
time immunologist from Melbourne, two years later had the
insight that there is not an infinity of antibodies, that
selection could play a role. As soon as he told me, I said, "Oh!
Oh! O.K!, that could be put into the clonal selection model."
Burnet published his ideas about clonal selection. His
was a brilliant central insight, totally uninformed about
molecular biology. He just did not understand DNA, protein
synthesis, and the rest of it. Coming back to a theoretical
paper, it's unique in my experience and rare in general
biological experience, that a theoretical paper could have that
much impact. It was an exegetical interpretation of Burnet's
revelation, put in the language of molecular biology and
framed in rigorous detail, with twenty propositions. It's
written in a somewhat self-consciously, Spinozistic style, as I
wanted people to understand that they could pull it apart and
that elements of it might prove to be wrong, but that the
general theoretical structure could still survive. More of them
have proven to be correct than I could have believed, but it was
a clarification that really has had some central importance in
how immunologist think about antibodies today.  Evidence has
come in to bolster every piece of it, so I don't want in any way
to minimize the importance of experiment, but it was a case
where clarification of theoretical issues was absolutely
central.
--------------part 4 (last)

RS:  Why do you think that physics and biology have developed so
differently?

JL:  In biology you're dealing with a much more complex set of entities,
and generalizations are never going to be as rigorous. Even my
theory of antibody formation has a lots of soft edges to it by
comparison with any physical theory. Extend that one step
further to behavioral science and I don't have to tell you the
further problems you have trying to make generalizations on
multitudes of organisms.

RS:  Did your years of service to Rockefeller University as its
President create a gap such that your laboratory research took a
new direction upon your return?

JL:  Serving as President of Rockefeller University was a total
hiatus from my own research.  I found myself in the middle
Seventies in a kind of rut wherein the questions that I wanted
to answer, which meant really a reduction of biology to
chemistry, were becoming feasible but required enormous
technical resources and effort.  I'd gone earlier to Stanford,
in very large measure in order to be more closely associated
with Arthur Kornberg. For various reasons I ended up heading my
own department instead of, as would have been my preference,
being a part of his, and there was no way that I had either the
temperament or the ability to put together the technology that
he had assembled for the isolation and purification of all the
enzymes and substrates and so on.  He had a whole department,
not working for him, but under his general leadership, focused
in an entirely coordinated fashion, particularly with respect to
the reagent materials and skills.  The technology for doing that
was very costly and very difficult.  I saw little merit in
trying to emulate what Arthur was then doing.  It was really
quite frustrating, to not know what my role was going to be.
That was one of the reasons I found taking the detour of
University President more appealing than it would have been at
any other time.  In the mean time, the technology did catch up.
     It could be that the most important thing that I did during
that interval in the Seventies, and boy, this is rather intense
self-deprecation in a way, was encouraging  Kary Mullis to
go on with the discovery and development of PCR.  I don't know
if you know that story at all.

RS:  No, please share it.
JL:  PCR is Polymerase Chain Reaction.
It was written up as "The Science of the Year" by Science
Magazine three or four years ago.

It was called then, very correctly, the democratization of DNA
research.  It provides exactly the technical tool that was
lacking in the Seventies for the kinds of things I wanted to
work on.  It's an easy manipulation of DNA so that you could
clone the DNA molecule in vitro.  You can start out with one DNA
molecule, then make as many copies of it as you want and do it
without having to have a factory full of support, which is what
it had required when I was at Stanford.  Mullis was one of
the workers at the Cetus Corporation  where I was a
consultant, and he was doing this as a kind of a side project.
He has written this up in Scientific American.
I thought it was an extraordinary stroke of insight. It resembled
some of the things that Bodmer, Kornberg, and I had attempted
some years earlier, but we had lacked one essential insight that
he had.  Basically, that was to do this replication of DNA in a
highly selective fashion.  The way he goes about doing this is
he has a prepared primer, a string of DNA 15 or 20 units long,
that can be added to the reaction mix.  It looks for
complementary DNA that has an exactly complementary sequence
that it can bind, to and then he adds the enzyme, the necessary
precursors that will elongate the primer so that it copies the
rest of the template down to the end. Putting in that ingredient
is what made this thing work and made it an extraordinarily
valuable tool.  I told him that this was a very important
finding and he really ought to go ahead with it.  I think that
gave him the encouragement to continue.  It ended up being the
most valuable property to the Cetus Corporation netting them
$350 million when they sold themselves off to Roche. The world
has obviously shared that evaluation of what this technology
means.  It's ended up being exactly the tool that was needed to
let me come back into the field and thousands of others as
well.

RS:  When you went out to Stanford, you had a question, but you
didn't have the technology to address it?

JL:  Yes.  I started my research stimulated by Avery's discovery
about DNA as the transforming molecule.  I began bacterial
genetics in order to provide an experimental vehicle for
following up on that observation.  The immediate question was
how do you do genetics in bacteria which are the right
experimental material to do the chemistry of the gene?  I ended
up doing the biology and getting into the chemistry whenever
possible.  I had a lot of rewards, especially the personal
gratification and so on of that biological research, but always
the deeper question was how do you use this in order to look at
gene chemistry?  In the Seventies, the chemical technology to
pursue this question was out of my grasp at a point when the
questions were very clear.  I'd gone out to Stanford in 1959
with the expectation that I might work more closely than in fact
eventuated with Kornberg, in terms of becoming more of a
biochemist.  There was a lot to do as a geneticist, I don't want
to decry it, but there was nothing startling that came out of
the work that I did in the Sixties.  It was just part of the
mainstream that I'd helped to found. Partly because it was
ordinary work, by my own standards, I was dividing my time with
the space related project and with getting started in artificial
intelligence.  The technology finally matured to the point where
I could use it in a modest lab.  A lab my size could not have
done a thing in this direction if this were the Seventies.  We
can do a lot in the Nineties.  For one thing, we can buy the
reagents, and
don't have to spend enormous time and effort making them
ourselves.

RS:  Please share any last thoughts about whether there is still
room for great talent in biology to be developed?

JL:  Oh, it shouldn't be misunderstood.  You might have no way
to see yourself a Heisenberg, but again, we can come back to the
Human Genome project, a very well articulated set of challenges
that are exciting and important at every level from basic
science on to invaluable biomedical applications that are almost
inexhaustible.

The odd thing about it is that it's innumerable.  I can count
100,000 genes and say that maybe 5000 are being actively worked
on right now. It's the opening up of a frontier with a fairly
well delineated geography. The chief limitation with exploration
these days is funds.  We can see an enormous payoff, it has
indeed attracted quite a few people and there's not enough money
to go around to support it all.  At some level, that will always
be the case, that the margin of opportunity exceeds the GNP, so
just exactly where that will go is hard to say.  So as far as
biology is concerned, that's manifest.  Now, it may seem a
little dull to say I'm going to look at gene number 47,744, but
the fact is once you get into it, every one of them has a lot of
wonders to tell you and that's been the experience of a lot of
very capable and successful young scientists.  What's harder to
get is a synoptic overview of the whole enterprise.