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Torbjörn Caspersson: Some Personal Perspectives

by George Klein and Eva Klein
Department of Tumor Biology, Karolinska Institutet, S-104 01 Stockholm, Sweden

Truly revolutionary changes in biology during the past decades can be traced back to the work of a few pioneers. Most of the pioneers have made one major contribution resulting in a radical change in thinking and methodology. Torbjörn Caspersson has made three.

From the beginning, Caspersson strongly emphasized the need for exact biophysical measurements of biological materials; this remains his trademark. He was the first to recognize the potential of quantitative cytochemical techniques and, almost a half century ago, showed their usefulness by an ingenious combination of microscopy and spectrophotometry. His doctoral dissertation was the first major attempt to apply biochemical studies to individual cells in situ. This is his first outstanding contribution, and it forms the basis for all current techniques and applications of quantitative cell analysis.

His second outstanding contribution developed from the application of the first. He was the first to identify, 20 to 30 years before thc dcvclopment of modern molecular biology, the relationship between RNA and protein synthesis. His measurements of the nucleic acid and protein concentration of various cellular organelles showed that RNA mediates the flow of information from the nucleus in this exchange. In the late 1940s, many of Caspersson’s colleagues still believed that genetic information must be carried by proteins. His arguments for a relationship between nucleic acid and protein synthesis and the role of DNA in chromosomal functions were quickly recognized and accepted.

The third, and most recent, outstanding contribution of Caspersson was the development of the chromosome banding techniques. These techniques, now taken largely for granted but developed only 20 years ago, have totally revolutionized the field of cytogenetics. The ability to identify every chromosome in virtually every species has had far-reaching implications. To mention only one of many examples in our field, it led to the discovery of specific chromosomal translocations in certain tumors. The crucial significance of the translocations lies in one form of oncogene activation.

In 1947, one of us (G.K.) had the good fortune to join Torbjörn Caspersson’s laboratory as a student, shortly after the first postwar Congress of Cell Biology held in Stockholm. The likelihood that cell biology could be transformed into a quantitative science through Caspersson’s work was the main news of the congress. I was one of the first to visit the new Nobel Institute of Cell Research at the Karolinska Institute. I failed to realize that the tall young man fixing some machines in the basement and dressed in the blue overalls of a machinist was Caspersson himself. When I realized my mistake, he had already changed into a suit and left for a major trip to the Western Hemisphere.

On a personal note, having just arrived from a totally feudal country – Hungary – I was amazed and delighted by the friendly and informal atmosphere of his laboratory and by his deeply humane treatment of even the youngest students from the strangest countries. It would have been hard to find a better time to join the lab. The first large postwar influx of guest workers had just begun. The lab buzzed with people from both closely and distantly related disciplines, ranging from plant and insect physiology, through bacteriology and virology, to pathology, hematology, neurobiology, and even psychiatry. Frequently, our group discussions centered around the measurement errors and possible artifacts that could interfere with the measurement of UV-light absorption in various specimens. Caspersson’s uncompromising emphasis on quantitative methodology and adequate instrumentation created the basis for modern quantitative cytochemistry. Both detailed microscopic analysis of single cells and flow cytometry of large cell populations have arisen directly from this approach.

In addition to science, there was another dominating topic in the laboratory. It overshadowed talk on the ways of life in different cultures, or the pleasures and vicissitudes of existence. It was the enigma called Torbjörn Caspersson. What was behind the curtain of impeccable politeness and perfect manners? What was he really interested in? Was it optics, biophysics, or was it biology? What was to be the future direction of the lab? What was dominating in his mind, methodology or application? And what applications, biological, pathological, or clinical? Labs were organized, built, rebuilt, changed, and moved before you could blink an eye. Was the work really important, or was it reaching a point of stagnation? And then suddenly came all of molecular biology. And much later – and just as suddenly – a completely new event: chromosome banding. We never have, nor shall we ever, learn what really is in Torbjörn’s mind. But the result is here, for all of us to see. His many disciples, colleagues, and friends express their best wishes for many productive years to come.