I.M. Gelfand as a Biologist

Sometime in 1962 my friend Alexander Fridenstein called me and told that mathematician I.M. Gelfand will probably telephone me as he starts organizing the seminar on cell biology. I was very skeptical as I knew that at that time many physicists and mathematicians were eager to improve something in biology. I told him that nothing good was produced by these efforts. Nevertheless I agreed of course to discuss this matter with a famous mathematician. Soon Gelfand himself telephoned and we had a long conversation. First of all he assured me that he is not trying to introduce mathematics in biology but to understand better the biology. He invited me to attend his seminars and I agreed. I participated in almost all weekly seminars in University for more than 20 years. This seminar was very unusually organized. The official time was 7pm. The members came usually at that time but I.M was always late. We were angry but later we got used and understood that these delays gave us possibility to speak with one another and to better learn about each other. This was essential as we came from many different institutes in Moscow.

When I.M. came he asked somebody present to give a talk; usually the name of the speaker was agreed before. After 10-20 minutes the speech was usually interrupted by questions by I.M. Very often he asked the audients: did he say anything? Was does it mean? Some volunteers from the audience then tried to summarize in a few words the meaning of the talk. I.M. asked again and when he was at last satisfied he told the speaker: why didn't you make it clear from the beginning? This was harsh experience for most distinguished speakers. Some regarded themselves as offended and left the seminar forever. However for those who survived this atmosphere it proved to be a great school. We learned to think and to speak clearly.

We also learned from various talks and discussions about news in many fields of cell biology as the nucleus of the seminar had scientists of many specialties: molecular biologists (Spirin, Ptitsin, Skulachev), immunologists (Abelev, Gurvich, Brondz), virologists (Agol ), plant biologist (Ivanov), and clinicians (Vorobiev), to name only a few. This style of seminar was essential especially in conditions of the Cold War when we worked in almost complete isolation from Western science. The seminar in Moscow continued to work for more than 20 years and died only when I.M. left for the US.

Now about the scientific work of I.M. in cell biology. Gelfand started to work with my collaborators and me in 1964 and continued almost until his recent death. Most of our work was made using cell cultures. The list of our joint publications contains 48 papers and one monograph on biology of normal and neoplastic cells in culture; this monograph was published in Russian, English and Chinese. All our experiments were made in the laboratory of Moscow Cancer Center and in Moscow University. The University laboratory was organized by Gelfand with the support of the Dean I.G. Petrovsky. In the last years it was also supported by the next Dean V.A. Sadovnichiy. These laboratories attracted many students; many of them later became members of the stuff. I wish to mention especially several students of mathematical faculty (V. Gelfand, L. Margolis and A. Bershadsky), whom I.M. Gelfand persuaded to acquire the second biological specialty. When I.M. moved to Rutgers, he initiated formation of our scientific group there with the great support of the Dean of Biology H. Feder and of E. Bonder. We continued to work there until recently. Several people including myself periodically came to Rutgers from Moscow and worked there for 2-3 month each time.

I will not describe all the data obtained during many years of cooperative work in biology with I.M. I will mention only 3 our results which I consider most significant.

Discovery of microtubular stabilization of cell activity was obtained during the first years of our cooperation with I.M. We then used a technique of wound made in culture by removing mechanically a part of this culture. The cells started to move into the wound and filled it. These cells (so called fibroblasts) extended and attached pseudopodia at the front but not at the lateral borders. This made the movement of cell directional. We used colchicine, which destroys microtubules, to stop multiplication of cells in the wound. Unexpectedly this drug also stopped migration of cells into the wound. We supposed that microtubules destroyed by colchicine are essential for cell movement. However micro-cinematography of culture showed the cells without microtubules were not paralyzed. On the contrary they extended pseudopodia from all parts of their borders, frontal and lateral. The movement of these cells became non-directional; they moved randomly in different directions. For some time we could not understand what this effect means. And then I.M. looking at the movies, coined the new term: stabilization. Microtubules are stabilizing vectoral cell organization essential for directional extension of pseudopodes and cell motility. This concept of microtubular stabilization proved to be essential for further analyses of such processes as migration of cells, extension of processes by neurons, cancer cell invasion and so on. Later our group found that microtubules probably act by orienting contractile actin-myosin bundles of fibrils. This work is still in progress.

Among other results one should notice the demonstration of special ability of the surface of pseudopodia to form adhesions with others cellular and non-cellular surfaces. This "pseudopodial attachment reactions" are the basis of formation of many types of cellular contacts. This is one of the main processes in the formation of tissues.

Our last paper prepared with I.M. (2004) described the detachment of cells from the epithelium monolayers during mitoses. This "mitotic detachment" may be very important component of the mechanism of dissemination of cancer cells.

In general, the work of Gelfand group in cell biology made important contributions to the new rapidly developing branch of biology that may be named "dynamic architecture of normal and neoplastic cells".

At about 90 years of age Gelfand started with A. Kister the work on quite a new topic: the architecture of protein molecules.

A. Kister can better describe the results of this work.

In conclusion I wish to say that Gelfand was an extraordinary man in all fields he touched. Nadezda Mandelstam, the widow of a great Russian poet, once said about him: "One should not know mathematics to understand that Gelfand is a genius".

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