Lewis Wolpert: My ideas on cell division were neglected, but at last I've got the support that I sought for 44 years
Wednesday 09 March 2005
Careers in biology can take strange turns. I was originally trained as a civil engineer in South Africa. I would have liked to have studied science, but could not see it as a career in those days.
Careers in biology can take strange turns. I was originally trained as a civil engineer in South Africa. I would have liked to have studied science, but could not see it as a career in those days. I qualified, worked at a building research institute for two years, and became hooked on research. I then came to London and did a postgraduate course at Imperial College. But I wanted to change topics as engineering was not all that important to me. And then the fateful letter arrived.
A friend in South Africa who knew of my dilemma was getting married in Cape Town, and to get him out of the way during the preparations, they sent him to the public library where he came across, quite by chance, an article in which scientists were measuring the mechanical properties of the cell membrane when the cell divided into two. He told me that that was what I should study.
And I did. I got a scholarship from the Nuffield Foundation, and King's College London accepted me for a PhD, but I did have to pass some exams in Zoology. I was encouraged by the brilliant biologist John Maynard Smith, who had originally trained as an aeronautical engineer.
The problem that I studied was the nature of the forces in the cell when it divided into two. I worked on sea-urchin eggs at marine stations. These eggs are reasonably large, easy to obtain in the summer, and an hour after fertilisation the egg divides into two cells by a constricting furrow developing between them. It can be visualised by thinking of a perfectly round balloon, and putting a string across the middle and pulling it tight so that the balloon is constricted beneath the string and becomes divided into two equal spheres. But what were the forces in the cell that did this, and how did it divide so beautifully into two equal cells?
I measured the mechanical properties of the cell membrane using an apparatus lent to me by the cell-cycle specialist Murdoch Mitchison. With this I could bring a fine glass tube up to the surface of the egg, lower the pressure of water in the tube, and so suck out a bulge from the egg. Again, think of a balloon, putting a tube on its surface, and then sucking on the tube to make it bulge up the tube. The more resistant the membrane was to deformation, the lower the pressure that was required to suck out a bulge a particular distance.
I found, as had already been published, that just prior to division the membrane was much more difficult to deform. I then found that, as the cell divided the constricting furrow region was also resistant to deformation. But away from the furrow, at the polar region the resistance went down. Hence my theory. At the start of division there was an increase in tension in all of the membrane, and so its resistance to deformation went up. Then the tension went down at the poles, it relaxed there, and so the tension in the furrow could constrict the cell into two.
The reason the polar regions relaxed is related to a structure inside the cell associated with the separation of the chromosomes into the two cells. This structure has a spindle that lies across the path of constriction , and at the end of the spindle there are rays going out to the poles, which are known as asters and are made of microtubules. My theory was that the asters caused the poles to relax - the astral relaxation theory.
But there were other models, particularly one which suggested that the asters' rays met in the region of the furrow and their joint positive action caused the furrow region to contract - quite the opposite to my theory. And so my ideas were neglected for many years and I moved on to other problems, though I kept contacting those in the field to try to make them reconsider my ideas. And happily, I have recently heard of results that give me the support I sought for 44 years.
So, do not give up your ideas just because others do not like them.
Lewis Wolpert is Emeritus Professor of Biology as Applied to Medicine at University College London
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