(dramatic trumpet music) - Welcome to a Conversation with History. I'm Harry Kreisler of the Institute of International Studies. Our guest today is
Professor Sir John Gurdon who is a researcher at the Wellcome Trust Cancer Research UK Gurdon
Institute of Cancer and Developmental Biology. And he served as its first
chairman from 1998 to 2001. He is a professor of cell biology in the University of Cambridge and he served as master of
Magdalene College Cambridge from 1995 to 2002. In the spring of 2006, he is visiting the Berkeley Campus as the Hitchcock Lecturer. Professor Gurdon, welcome to Berkeley. - Thank you. - Where were you born and raised? - I was born in the
southern part of England in a small village in the area where they expect people largely to be stockbrokers, though my family was not. - (laughs) And you chose not to be. Looking back, how do
you think your parents shaped your thinking about the world? - Well, they were extremely supportive in the sense I was
accorded private education. Not the state sector and it was actually better education that way
which was rather expensive and they kindly provided that. So when the time came to
aim for a particular career, my father thought the
most appropriate thing would be a career in either the army or in the financial world, and
arranged some introductions. But fortunately for me I was refused entry to the army for the National
Service, a piece of good luck. I was actually a competitive
squash player at the time and rather fit, but the
family doctor decided I was not suitable for the army and diagnosed my slight cold as bronchitis. And that eliminated any
possibility, thank heavens, of entering the army as a career. - So what did your parents think
of your going into science? - Well my mother could always see that I was fascinated by biological things. Even at school I used to grow
thousands of caterpillars to make moths to the intense
annoyance of my tutor. But I had a sort of
fascination for these things. And I think it was really her particularly who enabled me to switch
from my education, which was completely non-scientific, into a scientific direction. - And you were identified early
in your educational career as somebody who was not
qualified for science, correct? - That's correct, yes. I have this rather amazing report, which roughly speaking says
I was the worst student the biology master had ever taught. (Harry laughing) And he goes on to say that
he had heard there was some possibility of me
becoming interested in science, but this would be, to quote him, a total waste of time both
on his part and on mine. And this whole whole idea should
be immediately discouraged. - And at what level in your
education did you get this news? - This was age 15, when I had done one first semester of science and that was the end of it, no more
science from then on. Until later on when I was
able to return to the subject. - And how did this affect you, your self-esteem, so to speak? - Yes, well it was, excuse me,
it was sort of discouraging but curiously enough in retrospect, if you have bad teaching,
which was in fact the case 'cause this was just after the World War, you're better off not being
taught a subject badly and therefore come back to it when you can take it from a different point of view. So in a curious sort of way
I see it as an advantage to have not had to do the
dreary kind of school science that people did have to do at that time. - And I would imagine a key
factor in being a good scientist is being able to stand on
your own feet in a way, and go in new directions. - Yes I think that's right, I was, I had another piece of
curious good fortune in a sense that I was extremely interested in insects and always have been. And I actually applied to do a PhD with the entomology department, but again, luckily for me I was refused
as being a bad student. (Harry laughing) And then took up this embryology in effect with a very sympathetic person. So I moved into that slightly by default, but what a happy situation for me it was, because actually entomology
in those days was a dull subject, there weren't really any scientific questions as there
clearly are in development. - Many of the people I interview
always talk often about doing what you want to
do, really liking it, and it sounds like this was
a ballast for you as you moved through different
periods of your career because you really were drawn
to the subject matter. - That's correct, I always
had a fascination for it, and the interesting, thing
is nowadays this, my career would have been impossible
in the sense that I did classics, Greek, ancient Greek and Latin all my school time and then
had to switch to science, and this involved my poor
parents had to pay an extra year of private tuition to get
into science and in those days they were actually short of
students in Oxford and so I received this curious letter
from the admissions tutor in Oxford that said they would
accept me on two conditions. One was that I came into
residence immediately, in a week's time, and the
second was that I did not study the subject in which I had been examined. (Harry laughs) This is unimaginable at present. - So you were being ordered
not to become a classicist. - Absolutely, they said
I'm not suitable for that. And actually I later met the
person socially, he was a man called Trevor-Roper who
later became Lord Dacre and very involved in in
the last days of Hitler. And he told me privately that
his mind was on greater things and he'd realized he hadn't
filled the places in the college and so he looked down the
list of unsuitable people. - So I guess we can say that
Fortuna is at work here. - Absolutely, a lot of
it, great deal of it. - So what did you do your dissertation on? - My PhD dissertation, that
was indeed on the subject I still work on, which is to
say nuclear transplantation and that was thanks to my
supervisor, a wonderful man who put me onto that as a very novel subject. It was practically rather
a challenge because it, like everything, it didn't
work at all at first, but he was persuasive and
had ideas and it finally did so that was an extraordinary
piece of good luck to be able to work with someone who
was an outstanding mentor. - So you have become a
developmental biologist, and I guess what I'm
curious about how would you characterize the temperament and character required to do this kind of science? You've given us some hints already, perseverance is clearly one. - Yes, I think that's probably
right because as all of us find, most of the things we
try in the lab don't work, at least if they're at
all innovative or novel they usually fail, and the
question is do you keep at it or do you just say I'll
try something else. And I think the, my
feeling is you have to feel convinced it's an important problem. That may be the single most
important thing to decide that if you could do it it
really would be worth doing. And then one keeps at it and
goes at it different angles, and finally some little
unexpected result comes up which gives you a feeling of how you can make progress in that area. But I must say I was fortunate in having a complete fascination
for both biological things and also doing things by hand. I used, when I was
smaller out of amusement I used to make model sailing
ships in the shell of a walnut. Just 'cause, doing micro things with hands has always appealed to me. - So it's a dealing with
frustration experimenting, but of course in your work really working with microscopic entities. - In my case that's, really
does appeal to me a great deal, and perhaps I'm rather bad
at looking after the people in my lab in the sense that
I do an awful lot of my own experiments myself by hand and
they rather have to manage. But I like to hope that
gives them some sort of help, the fact that one can usually
do these things oneself. - Now you told us that
you were a humanist become a scientist, and most people
probably couldn't do that today so what sort of skills do
you need, do you think? I mean chemistry, physics, what? - You mean to be a scientist
or failed classicist? (Harry laughing) - Well, both, but let's
do the scientist, yes. - [Sir John] What sort of science? - Yeah, but maybe the
other is as interesting. - That's something interesting, too. Well, what do you need, I suppose, in a way I suppose you must
have to have this inherent interest in something that
you're trying to study. But one thing that was
very prominent in my mind and in a way answers
both those two questions, I thought if I'd spent my
life as a classics person I would end up at the
end of my career saying I've now achieved the
level that everybody else has achieved for the
last few hundred years. I wouldn't know more about Homer and Thucydides than anybody else. I might reach the same
level, it wouldn't advance anything in human society in my view. Whereas in science you felt
that at the end of a career you could actually see
some genuine progress, both in understanding and
in fact in practical use. So that was very much in
my mind that one wants, I'd like to give my career
to something where I can see at the end of it there's
been a real advance. - And is there a root of
that perception on your part, is that something you got
in your early schooling from the humanities or from your parents? - No, from parents if anybody, maybe it was just sort of innate. Sort of thinking about one's
future, one lives much of one's life by saying what am
I going to do the next year and I often ask my, sometimes
you have very bright students and I sometimes say to them, PhD students, where will you be in 40 years time? Most of them say I can't
tell you, I'll tell you where I will be next year
but I haven't any idea. In some ways it's a good
thing to think what you, how your career might
evolve if things go well. - Talk a little about this synergy between the individual scientist,
his team of collaborators, and the broader scientific community. Because when we start
talking about your work, it really needs to be placed in a tradition and with the work of others. - So maybe the comment to
make is that in my time, and I think there's been a real
change from the possibility of someone working almost as
an individual as opposed to part of a team, and of course
in physics my understanding is you work in enormous teams
with big instrumentation. Things are moving that way, I
think, in biological sciences. But I don't think they're going to be, ever exclude someone who
explores novel ideas. It's rather easy now to get
a grant for a huge piece of equipment and to have
10 people getting out lots, large amounts of data of sequences or something which you analyze. But I'd like to think there is
still and will be for a while an opportunity to do things
on a more individual scale, but not as much as there was. When I started you really
could work as one person in a field and you wouldn't
be worrying every day that you're going to read the results of your work in the paper next day. - So what then was the evolution
of your research up until the 60s when you made a major discovery, which we will talk about in a second. What problems interested
you after your dissertation, and where did they lead you? - Well, after my PhD
dissertation my supervisor, my mentor said you should do
something completely different. And that was right, and
that's why I went to Cal Tech where I in fact worked on
bacteriophage genetics. But interesting, to me I could
never make it work at all. Every experiment I did failed completely. But I learnt an enormous amount by meeting a number of very interesting
people, and the whole idea of how you do science became
much more clear to me. So I went back again to
what I'd been doing before, but in a more informed way. - What became clearer
to you, if I may ask? - How you try to analyze things
at a more molecular level, more detailed level, so I'm the... I'm the extreme opposite of
the systems biology person who says we must look at
everything, I actually can't. I look more and more down into,
focus down on a tiny thing, to understand just one thing, and then try and enlarge afterwards. And I think it became clear
after my year in Cal Tech how people can do, can
make a molecular analysis. So if something happens in
biology, the end result has to be that you understand it
in terms of molecules, individual molecules doing something. And that was, my education
didn't reveal that. For example, when I was a student we spent three days a week learning
about paleontology. We had to learn every
dinosaur bone that as far as I could see everyone
at any one had dug up. But it wasn't really scientific,
it was just a memory test. - So how did your work of
transplanting a specialized cell into an E-nucleated egg,
and then a tadpole emerge, how did that come about and
what were its implications? 'Cause it was truly a revolutionary moment in developmental biology. - Right, so the background there is that the concept of using micro glass needles to move things around had
actually been in operation since around 1900, when
people, someone called Bataillon did some work of that kind. But the real advance took
place when two people in this country called
Briggs and King who were the first to be able to,
within the vertebrates, take the nucleus out of a
cell and put it into an egg. And it worked extraordinarily well. The odd thing is that a few
years later they found that when they started doing
this experiment with somewhat later stages of development, taking the nuclei from later cells, it didn't work really at all. Also my supervisor put me onto this, copied their work at a very early stage. And we were lucky in that it
actually worked differently. And since the the more
advanced the cell was from which you took the
nucleus, you nevertheless ended up getting normal individuals. And that was really the
breakthrough that made all the difference in my career, so
that you ended up with an admittedly small number of
completely normal individuals. When you take the nuclear
site of an intestine cell, put it into an egg, you
actually can end up with normal adult fertile
animals, and that made me take a different view of this
work from Briggs and King, who I greatly respected, and
indeed if I'd had their results I'd have reached the
same conclusion as them. But at first it led to
quite a lot of controversy, I mean here was I just a graduate
student sort of contesting the conclusions of two very
highly respected workers. So naturally enough people didn't believe what I said, and I can see why. - What had they argued,
Briggs and his colleague? - Right, right. Well they quite reasonably
from their experiments had argued that as an
embryo develops into a into a little later embryo in an
organism, and at a very early stage the nucleus of those
cells is no longer able to replace the egg and sperm
that normally occupy the egg. And so the conclusion was
that as development proceeds, the genetic material undergoes
some kind of stable change which precludes it then
substituting for the egg and sperm. That's a very fundamental
question, and it has to do with whether, as we form from an
egg, the genome so-called, the set of genes, remains
constant or it doesn't. So it was it was a question
which had interested scientists for at least fifty years before
that, and this was really the first really good attempt
to answer that question. - And may I ask what the
animals were that you were dealing with, South African frogs, yeah. - Yes, it turns out that I
was, for a odd reason, but there's quite a lot of
history to how it came that a South African frog
turned out to be a favored, one of the most favored
organisms, which ultimately came down to the fact that
someone had more children than they could afford
to educate in England. So they went all around the
world ending up in South Africa and finally ended up in
England when the animal was used for human pregnancy tests. And the spare eggs were
then of use to people doing developmental biology, so I used that. Now Briggs and King
used the American frog, which turned out to be less
good for these experiments. - So this a moment, a
very important moment in the history of science, of
the biological sciences. What was what was that
feeling of creativity like, that wow when this happened? Could you really talk about,
here you are tinkering, and I gather from what I've
read that the really complicated thing here is taking the cell
out and moving it around. So it's a very, somebody who's
worked with delicate items like sailboats and walnuts
you said, is prepped. Talk a little about that. I mean, the difficulty
and then the aha moment. - Yes, so that that was an
early event in my PhD work was to attempt this experiment which got, as I say, completely failed. And the most obvious reason
why it failed was that when you used a micro glass
needle to put into the egg, you could push it in and
it came out the other end but it actually hadn't
entered the cell at all. It had taken the membranes
with it, pushed the whole lot through out the other end and come back. And it turned out to be
impossible to get through this very viscous jelly, so that
was the first major problem. And that was solved largely
by the fact that my mentor had recently got a grant for a new microscope, which had nothing to do with this work, it was for an ultraviolet microscope. And we discovered more by
chance than anything else that it happened to emit
light of a wavelength that dissolved this elastic jelly. As it happens, it also
killed the resident nucleus, so it was a extraordinary piece of good fortune that that worked. And that then, suddenly
things started developing, you found that you
could do the experiment. And that was a key point, if that had went on and continued to fail, I really don't quite know
where one would have gone. - But talk a little about your feelings, about that aha moment when this, I guess what you got was a mature, you got a tadpole, right? - You've got a tadpole,
that's absolutely right. - Right, right.
- That's right. - When previously nothing happened at all, suddenly this thing. So the next you thought,
well this is amazing, could it actually be
right, that's the thing one always thinks, even at my stage. Whenever you get a result you think, could there be an artifact? And there was an obvious
artifact and that would be that the resident female
nucleus in that egg had not been destroyed, and all
you've done by pushing a needle in was to somehow activate that. So we needed a way of proving
that that was a rare result. And then another piece
of, partly good fortune, partly wisdom of my mentor came about. He had a student who is doing
some completely different experiments, and they failed
too, for an odd reason. Instead of him saying
well, do something else, he said there must be reason
why these are failing. So he discovered what turned
out to be a exceedingly important mutation, which
acted as a genetic marker. And so we could put in the
nucleus of one cell which was genetically marked into this
egg, grow the embryo up, and prove that the embryo
carried that genetic marker appropriate to the nucleus you
put in, and not appropriate to the resident nucleus that
you hope to have removed. And that was I think really why it was that the general scientific
public believed our results. They probably wouldn't
have done otherwise. So that was very important. - Now in terms of
science, this was a very, a real turning point in the road that led to the cloning of Dolly many years later. And I wanna help our
audience understand this. So what you had, you won the Copley medal, which recognized your work that
had given decisive evidence that specialized cells are
genetically equivalent, and they differ only in
the genes they express and not the genes that
they contain, explain that. - It's a very precise
and accurate statement. So the idea, just going
back a little is that after, particularly after the
results of Briggs and King, the thought was that the nucleus
or the collection of genes we have would actually change as the egg develops into different cells. So our skin, intestine,
brain, blood and muscle would all have different sets of genes. Because they would lose the
ones that you no longer need. So the, for example the skin
cells don't need brain genes. And indeed it was an idea of
someone in the 1880s called Weissman that that's indeed
how development worked. It was a plausible idea, as
the egg develops it sheds off these genes, and so as the
cell decides to follow a particular pathway, that's
a very neat way of doing it. You get rid of the genes. And so it gets narrowed down to that fate. And the really important thing
about this question and the experiments was that that
turns out not to be the case. So all our cells with
very minor exceptions contain the same set of genes. And I would say that's
fundamental in any kind of cell replacement therapy
which we might envisage. And indeed, obviously if
that had not been true Dolly the sheep could
not have been formed. But it turns out it is that way, and so what we now understand
(coughs) excuse me, is that as cells develop they
contain the same set of genes. The only difference is that
something decided to read the skin genes in skin,
and brain genes in brain. So that's what they meant by
expression in that statement. - Now why did it take so long, because we're talking about
a 30 year interval, really. Your experiment was in what year? - Well the first time we got an adult, a successful adult it was 1958. - [Harry] Oh, really, oh, okay. So why so long? - Yes, very good question
and I've wondered about that, too, and I've
tried to explore that. Now, one reason for that was
that (clears throat) excuse me, when they were doing these
experiments of mammals, and I might have stared that
I had a PhD student in early 1960s who did indeed try
transplanting nuclei in rabbits. And it didn't work or at
least not significantly well. And then that got left aside, now why? And the reason is that
someone called Davel Salto took this up very seriously
and did a lot of experiments, and he found that you
the best you could do was take a nucleus out of a two cell embryo and put it back into a one cell embryo. If you did anything else,
anything further they didn't work. Now it turns out the
explanation is that if you put, transplant a nucleus into a
fertilized egg, an activated egg that's already started, it's
extremely difficult to do and it doesn't like to
receive that nucleus. We had always chosen
to do experiments using un-activated eggs, they're sort
of naive and waiting to go. And for reasons that I'm
only partly clear about, that was not done in
the early mammal work. They felt that a better route would be to, and they had reasons for doing that, to thinking of going
into the fertilized egg, but it essentially doesn't work. And Davel Salto did, it was
very careful experiments published through very good
journalists explaining that that this particular route
he used does not work, and indeed it doesn't. But switching back to
the route that was done with amphibia it actually does work, and that's how Dolly the
sheep came to be successful. So it's not entirely clear
to me why they wouldn't have tried that, I think it was
technically more difficult. But that seems to be the
explanation so you're quite right, it took about forty years
for this essentially similar result, in many respects, to be obtained. - And I gather it was really out of industrial experimentation as opposed to coming out of university
science, is that -- - Dolly the sheep?
- Yes, yeah. - Well I'm not so sure that that's right, I don't really know
whether perhaps that is, never really asked, it
came out of an institute that had a lot of industrial support called the Roslin
Institute, but it wasn't, I don't believe that they
were really being told we we want you to do this work because it's going to be profitable. I don't think there
was a perceived profit, it was more that it was
exploratory work with animals. Hence the sheep, not a mouse. - So what what directions
then did your research take after this, help us
understand that and we'll talk a little about what you were
lecturing about here at Berkeley. - Yes, right, well the, I mean if we, we could say it this way, that
my only results tell me that actually the way development
works, and that was the fundamental question I've
always been interested in, interested how does an egg make an animal? It's an extraordinary process,
I should just emphasize, because this egg has no,
no one tells it what to do. Just one cell and somehow it knows how to make an animal, so how is that? Well, we were satisfied
then that that's not by any loss of genes, the genes are there, so something must read the genes, decide which genes to to
read and which ones not to. That then took me off in
a number of directions, much of which I talked
about yesterday, which is what kind of thing tells
the cell that it must read one gene not another,
and that was how we got into what I call morphogen gradients,
signals that come from another cell and say, I want you now to read that gene not another one. And that then was a large
part of my mid-career, and dealt with the morphogen gradients, community effects, signaling and so on. And then much more recently I've gone right back to the original question of how is a transplanted
nucleus reprogrammed? What I'm going to be talking about today. And I see that as all connected,
it's all the same question. Just going off one direction
and then coming back to the same one, perhaps
another direction, it's all going back to the same question to try and understand
ultimately how this happens. - Yesterday I noticed, and
now that I know you were a classicist, you, I think
the headline on the slide you were showing was cell commitment to future development, so
let's talk a little about that. Because what you were telling
us, and were really four ways that a cell after formation
would would commit to a path of development, what are those four elements? - Yes, well one of the things which you certainly absorb very
well, and which I refer to again today is this surprising
fact that when the cell begins to set out on its
on its career and pathway to become something like skin or muscle, at an amazingly early stage it
refuses to change direction. Even within a matter of
hours, that says I'm going in this direction, I'm not going
to go any other direction. And as long as I'm left as a whole cell, so inside that cell it's
sort of re-instructing itself to keep going in this direction,
won't take another pathway. And the point that I will
make today is that if you then take that cell apart and
take the nucleus away, then it's completely
happy to change direction. So it's a surprising contrast
between a whole cell, which is committed to
a particular pathway, hence commitment, as opposed to the individual parts of
the cell which are not. - Now in this initial process,
I think you identified four elements that said it's on this path. To repeat them, that the
pre-fertilization controlled development, asymmetric cell
division, signaling between cells, and then what you
call a community effect. Summarize that for our
television audience. In other, so what you
have is a set of processes at work that say you're
going this way, fella. - Yes, that's right, that's
exactly right, what you say. And the, in a way surprising
thing is, (clears throat) excuse me, this egg which is, you know, we we eat a chicken's
egg or see frog eggs. But the egg before it's
received a new sperm already has a fair amount
of information in it. In fact it's taken, in many
cases as much as a year to make that egg from us
very specialized cell, and that already is a part
of the whole of our life, is determined before fertilization. So that's point one, and
then the the other thing is I emphasize, but this asymmetric
division is a way of again telling cells to choose one
pathway as opposed to another. And then of overall importance
is this signaling by which a cell receives molecules
telling it in which way to go, of which the community
factors are variant. So it's a progressive process,
and I think that's a logical way of viewing it, with four
steps that are fundamentally responsible for deriving a thing like a heart or brain cell from an egg. - Now, either the humanist in you made the comparison between the phrase... faith hope and charity, and of these the most important is charity. And you turn that around to say space, time, and concentration, and with concentration
being the most important. - That's right. - So these are the factors
that set us on this course. - Yes, I've increasingly
become intrigued with how precisely things work, so
let me give you an example. There's a phrase called
haploinsufficiency syndrome. Now, all that means is that
you and I have one gene inherited from our mother
and one from our father, so we have two genes that
should do the same thing. Sometimes things go wrong, and one of them isn't any good, so we only have one. Now amazingly in a number
of cases, if you have one copy of a gene instead
of two, things go wrong. Now that means that a
factor of two difference makes an enormous difference,
and indeed other experiments are referred to, so factors of
three make a huge difference. So everything in us is
regulated to an extraordinarily precise degree in actually concentration. And that when you go into this in detail, as much of my career has been involved, it turns out that that's
the single most pivotal component in making
things work the way we do, is the concentration of things. So that was why I chose
to emphasize that point. - Talk a little about this reverse process which you're gonna be
talking about this evening. I haven't had the fortune
yet to hear that lecture but what then becomes the
implication for all this work in stem cells of what we
might achieve with that. - Yes well what I will be
saying is that if you take the nucleus genetic material
out of one of these cells that are quite clearly
committed, they know what they're going to do
and nothing will change it. But you take that nucleus
out and put it into the egg, then that essentially rejuvenates
that nucleus in most cases and what I'll show is that you
can take a cell from an adult put it through this process
and it then essentially forgets everything it knew about following that pathway and starts life again. And there are things
called stem cell genes, genes which mark the
fact that it's gone back to the beginning of life again. And so that in a sense
creates a stem cell, because if you go right back
to the beginning of development the ultimate stem cell is an egg, because it can form everything at all. It's totally potent. And you recreate these sort
of universal stem cells by this procedure, so that's
what I refer to my talk as, from egg to adult and back again. Take it right back to the beginning again. And of course if we could make
that work really efficiently, I do believe this would
give the opportunity for cell replacement in humans. - So that one could
use one's own materials to actually make repairs. - That's absolutely correct. - Right.
- Yeah, that's right. - And the key thing which
I haven't said yet is that in terms of replacement,
all of us eventually would welcome some replacement of parts. You really like to have
cells of your own genetic constitution, so you can
receive cells from other people but you may know that if
you do, you have to be subjected to what's
called immunosuppression. It means you can't reject
the cells and of course you also can't reject any
infections that you get. So immuno-suppressed people
are quite disadvantaged. In an ideal world, we would give ourselves rejuvenated cells of our
own genetic constitution. And this, whatever you call
it, cloning or anything like that, that is actually
the only efficient way in which you can hope
to derive rejuvenated embryonic cells from your own adult cells. - Now what are the big
obstacles to achieving this in, within terms of a lack
of information, or what? - Right, so the big obstacle is that it works, but not very well. That's the fact of the matter. And so when you do this, you sometimes get amazing results, like I
mentioned the adult animal derived from an embryo
cell or Dolly the sheep derived from mammary glands, spectacular, and it can work, but the
efficiency with which it works is actually extremely low. And that is the reason why
my own work for example is completely committed
now to trying to understand the mechanism, molecular
mechanism of how it is that you rejuvenate a nucleus, send it back to the beginning again. 'Cause my view is that only
if we really understand that mechanism, can we hope
to make this work efficiently enough to actually be useful
in a therapeutic sense. - I wanna go back to this
earlier career of you as a humanist, which you
turned away from because this is really, this
work is raising a lot of sort of big questions about who we are and where we might go and so on. How do you think about
that, or is it part of the professional list of a scientist not to focus on those questions? - Well I do think about
it, and I shall say a bit about that today, but
my own view in short is that there's completely unjustifiable
concern on these issues, people talk about the ethics of this. And they would say for example that if you transplant the nucleus
of one of your skin cells into a donated egg from
some woman, this will form an early, very early embryo, and it would. And they say that is a
potential human life. I would completely disagree with that on the grounds that it is
not a potential human life in the absence of implantation, a key step in mammalian development. So I see this rather
skeptical where people who are in good health, in high places,
whether they're lawyers or whatever sitting there
and saying, I'm fine, but I don't like you to
do these experiments which might in fact greatly improve
the health of other people. So I find that quite an
unacceptable philosophy. So I would say this early
human embryo is actually not a potential life and
has no significant validity. I don't think it may or may not have a soul, it doesn't matter, The fact is it's not going to,
you're not killing anything that's significant, and if you don't do it you're then not taking advantage
in the way that we could of relieving an awful
lot of human suffering. - So it is that practical
application and the intention here of the
good that might be done that should define the process. Are there things that
we should worry about in this process that
might get out of control, and that is that, what is
your insight on that problem? - Yes, well I, at the end
of my talk today I shall go through five reasons why
people might object to that. And one of the ones which I
find particularly unpersuasive is what I call the thin
end of the wedge argument. So they say you scientists
are doing this kind of thing, that's okay, but they say we
don't know what you'll do next, we'd better stop it quickly
before anything worse happens. It's a very bad argument,
and I shall go through these points, and I don't think any of them have any worthwhile validity, to be honest. - And how do you see the the
commercialization of this, these insights ultimately being achieved? Will the scientific breakthrough lead the market to see the implications, and then it will happen
in a broader scale? - Well that's an interesting
question of whether there will be commercial
gain from this kind. Let's assume the technology,
like most, improves, people find out how to do a
thing and it works better. It's unclear to me how
commercially useful that will be. The end point of my work that
I'm currently engaged in, if it were to go well,
would be to understand what molecules you need
to rejuvenate a nucleus and create a universal stem cell. So now if that was some
special molecule which I could put a patent or patent on,
maybe there'd be money in that but I rather doubt if
it will work that way. So I'm not sure that there is
going to be a huge commercial consequence of this work,
however successful it might be. - What would be your advice to students as they prepare for their future? Your career stands out as
one where rejection paid off once you chose to do
what you wanted to do. - Yes, I'm very troubled that
every now and then one has extremely gifted PhD students,
and I'm lucky enough to have those from time to time,
and almost without exception the recent ones have all given up science and gone into the finance world. I regret that, and I'd
like to say to them, consider yourselves at
the end of your career. You will have probably made
a large amount of money and you'll have an expensive
car and a big house and you can take holidays
wherever you want, but is that really what
you want out of your life, or would you rather say that
what you've been able to do is to make a real difference
to the quality of human life by relieving suffering, in
the way that centuries later they say oh you know, Dr.
Chrysler, you actually did some of this work which was
really helped the whole of human society rather
than, you have actually made enough money to live comfortably. So I would hope that progressively,
people will be prepared to see, look at their life
as a whole and look at the end point, other than in
simply financial terms. And when I was young that
was, the scientific career was regarded, highly regarded
as a good career. and I think it's unfortunately less so now largely because it's very poorly rewarded, at least in Europe, financially. So he will have to suffer. But in the long run that
will probably change. - What, looking down
the road, should we be, the general public be
watching for in terms of milestones, are there
certain questions out there that in this work that you're describing we hope to be getting the answers from? - Now, do you mean what they should be looking towards as a positive effect -- - [Harry] Yeah, yeah, yeah, right. - Not worrying about a negative effect. - Yes, right, worrying about a positive, yes, yeah yeah yeah. - Looking about the positive,
what can they hope for. - In other words in this
realm of questions that you're dealing with, some, a couple
of questions, or one that stands out that needs to be
answered in the next stage to achieve these positive developments? - Well in my opinion the single
most important steps will be to understand how this rejuvenation
process actually works. And we and others are beginning
to pick away at that problem and to give you some feeling for it, we have to know what it
is that removes the marks, as they're called, that make
a a set of genes specialized. So as you have your cells
becoming, say, skin cells, they actually switch off, as we've said, the genes needed for the brain. They're there, but they're
not very easily activatable, and they acquire marks which
for example they're called methylation of DNA is one such thing. And we know actually nothing at the moment about how that is reversed. It is reversed, I have
no idea how it's done so. But if it isn't reversed it won't, the whole process won't work. So you can divide the whole
process into a few steps like that, and I think that's
what we would be watching for to see as people gradually
find a way of reversing these marks, that gets it back
the beginning again, and then of course you
have to start telling it in which direction to go after that. But this reversal process
is undoubtedly complicated, but I'm quite sure it will
be eventually worked out, and those are the steps
which were ultimately, if it really works well, just
to give you a feeling for this I would say eventually we should
be able to take a skin cell and apply these molecules,
which we by then would have found out what they are, to that skin cell to directly switch it back
into an embryonic cell, from which you can derive
heart muscle brain and so on. So that's the ultimate vision
one would have of this. - And then one final
question, where do you think the leadership will be in
in these new directions, do you think the politics
of some countries, unnamed, will affect its future leadership role? Because although in
your mind a lot of these ethical issues are
resolved, they have become political issues in some countries. - So I would doubt whether the
constraints or restrictions which do apply in this country
and even more in some others are really holding up progress
significantly at the moment. It's unrealistic to do
experiments with human eggs, just an inefficient way of doing it. And once you know how a
thing works in a mouse egg or even in a fish or frog egg, the principles usually
turn out to be similar. So if we really knew how
it worked in a mouse, for example, it wouldn't be that difficult to switch over to humans, and
I would assume that by then any public concern will have evaporated. Let me give an example, it was
the in-vitro fertilization, as we call it, was invented
primarily by Bob Edwards in Britain, as it happens,
and the first two years when he did it he got
terrible abuse, bad press, letters of people
threatening his life, etc, For all sorts of, they said
unnatural, we don't like this. But in a couple of years it
turned out to be very useful. And the whole thing's
completely forgotten. So I think what will happen
in the world is people will realize that this is a really
valuable kind of direction to follow, and these
reservations will just evaporate. - Sir John, on that hopeful
note I want to thank you very much for taking the time to be
here today and thank you for delivering the Hitchcock lectures
on the campus, thank you. - Thank you very much for your interesting questions and discussion. - And thank you very much for joining us for this Conversation with History. (dramatic electronic music)
