Jack:
I know youve talked generally about your approach to science, but
there are lots of paths you could have followed; weve already talked
about music. Were there other directions you could have followed?
Andrew: Philosophy.
At one point I was very interested in philosophy and truth and all that
sort of thing, and then I suppose science came along for me. Natural Science.
Lets take an example, lets think about the nineteenth century.
You see, to me Nietzsches ideas of the will to power
pale in comparison to Darwin's Origin of Species, because
if you read them back to back, one guys talking about these platitudes
that are not real what Nietzsche writes about is not what is really
happening in nature. So I pursued the scientific questions I wanted to
ask, and one question turned into another question, and another question,
and another question. Thats how science proceeds. Thats what
science is. So, I've been on the path, all this time.
Jack:
Tell us some of the questions.
Andrew: Do all the
structures in the cell derive only from the genes?
Jack:
Do they?
Andrew: No! That
came from an experiment we did where we took out an organelle [just as
as humans have livers and spleens, cells have substructures that perform
specialised functions]. And the living cell that we removed the organelle
from, just couldn't make a new one. And we did all the controls and we
did all the sham operations to show that the organelle couldnt
regenerate because of something we did experimentally. And other people
have confirmed it. It is known that this mass of protein which
is the subject of this meeting here - or the microtubule organizing center
in the cell is an exquisitely fine structure that goes back a billion
years or so ago. And its structure has been responsible in the way it
interacts with the gene products to make new structures of its own kind.
The information from genes (via polypeptides) to proteins does not just
flow in one direction. In fact it runs both ways. That's one question.
Jack:
Why have you and the other people been concentrating so hard on proteins?
Our lay readers, our less scientific readers would say, I suspect, that
they would go for the gene.
Andrew: Right. The
way Darwin defined it - I think the way you're asking the question
a gene is an hereditary unit. But we don't find hereditary units by themselves.
We find them in an environment. And one hereditary unit influences the
way another one is behaving or expressing itself. When you then play with
numbers and get up into the billions, then you encounter difficulties
of network theory and complexity. So far as we know it right now, it is
not linear you can't say one gene codes for one thing. You're
dealing with a network of potentials.
Jack:
All right, lets come back to that
Andrew: O.K. But
what I mean you went the protein way. And everyone here at this conference
has gone the protein way and not the gene way. I am just making a point
about reductionism. Even within this collection of protein people there
are the kinesin people, and there are others saying no-ho were going
to be the dynein people, and still others are specialists in actin. Its
categorised, divided up
Andrew: Yes. You
do have this balkanization. And, yes, what these people are doing here,
in the worst kind of reductionistic possible way, they are taking these
motors apart, alright, and they are putting them back together in reconstituted
systems. And they are certainly finding pieces of information, that are
extremely useful, and which generate new ideas. And we can then try to
apply them, we can try to fit that information into the big picture. In
the presentations here, the good ones, people are putting possibilities
to us. The individual cells are completely autonomous units at some stages
of development.
That wasn't known before
experimental science was able to take portions of the brain out and put
em in a dish. Now one of the things I have looked at in my time has been
the gene element in information. I was reading all these books in French
philosophy by Monod the Nobel laureate Jacques Monod and others.
And I read a lot of material in which the authors tried to incorporate
physics into the whole mixture.
Eventually what I did was
to go back to the structure of the cell. And within the cell there were
entities I could study, which are important for the creation of new structures
and which are independent of the genome, of the so called heredity units
of Mendel, you know.
Jack:
Genes. Right.
Andrew: And then
I found, you know, that by taking these organelles out, these centrosomes
[ the principal microtubule orgainsing in the cell], and by observing
the inability of the cell to make new ones, the way in which that impinged
on the cell cycle, I could see how what I was doing impinged on cancer.
Again it came from a, a preoccupation with continuity, in this case the
continuity involved when one organelle generated another organelle. Did
you need a template there that did not originate out of nucleic acid?
That was not DNA and was not RNA. And the answer was, yes you did. And
other scientists confirmed it.
Much like the mitochondria,
actually. What is the structural continuity from the outside of the cell
to the nucleus? That led another 7 or 8 years of work. By pulling on the
outsides of the cells could I get things on the far interior to change?
And I found out what I could and what I couldn't. Where there were continuities,
where there weren't continuities. That led to my work with cancer in the,
in the ontogenesis realm, because there's a continuity if you appreciate
it, in between the host and the cancer - if you believe this idea of tumor
ontogenesis.
And so I tested the idea
of tumor ontogenesis by actually putting cancer cells and host cells in
the same dish. And by asking the host cells to interact with the cancer
cells and then supply that cancer with blood, I found a discontinuity.
That was that the cancer cells make their own vessels. They make their
own little cracks and crevices and spheroids and these cause the tumor
to have all these increased abilities to metastasize or profuse.
Jack:
And what's' controversial?
Andrew: The centrosome
work was controversial in a way because although there is a contingent
that believes that what I have achieved is great and who say that Ive
found the cog that measures time and mass increase in cells and have shown
the effects in the cell cycle, most of the world t ignored the work essentially.
People continue to this day to try to find the gene that encodes the centrosome,
or the genes. I mean even 20 years before I started there was a list of
436 known proteins, Mazia published it, and that list shows clearly what
constitutes this barrel that sits in the middle of the cell.
Clearly there is no one
gene that makes a centrosome, even though paper after paper, after paper
you read - I have stacks of them at home [CHUCKLING] and
they all say this gene is fundamental for centrosome replication. Its
a way of thinking: You find the one cause in a haystack of millions of
causes.
Jack:
And?
Andrew: And, I came
up with a new paradigm and the quest to prove a new hypothesis based on
the way architecture works and the tensegrity models of Buckminster
Fuller. I figured out a way to adapt it to living systems. In an unique
way.
It was Donald Ingbers
idea to demonstrate tensegrity in living systems in different ways, and
with my micro-manipulation skills I figured out how to do it. In fact
long before Ingber and I and others were thinking about life and tensegrity,
Fuller himself was making accurate models of viral DNA based on his ideas
of tensegrity. You can see a beautiful picture in his big book Synergetics;
he has a model of the gyre of viral DNA. Its all there. I figured
out how to ask the question of a living cell, because I pay very close
attention to cells I, I stroke them, I poke them. I'm not like most biologists
who, you know, throw chemicals on them. I actually must reach down and
touch them, and poke about and feel how they yank on the apparatus
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