9—
Max Delbrück—
A Caltech Interlude

For an audience of generally reserved physicists, the applause was extraordinary. Max Delbrück had just concluded his third lecture on his path-breaking research with bacteriophage. These studies, over a fifteen year period, had brilliantly transformed a microbiological oddity into a principal means for the advancement of molecular biology, genetics, and biophysics.

The lectures were stirring. The research, the clarity of its conception, the elegance of its execution and interpretation, and the lucidity and sophistication of its presentation caught everyone's imagination and enthusiasm. Biology, a messy and descriptive field to most physicists, could be approached in a quantitative, analytical manner often using mathematical insight to produce clear, unambiguous results.

Frank Spedding, the director of the Ames AEC Laboratory, had made funds available to invite distinguished visiting lecturers. My nomination of Delbrück had been approved, and to my great delight he had accepted the invitation to stop over on his way to some East Coast meetings. We had never met. Delbruck was tall, thin, and crew cut with an energy that belied his forty-five years. In his three days, he met with most of the more prominent research faculty and, I believe, was pleasantly surprised by the activity he found on his first visit to a midwestern "Ag school."

I had become increasingly convinced that my biophysical and biochemical studies on nucleic acids would be much more meaningful if they could be related to a functional biological process. The long-range

goal was to understand what nucleic acids did, how they did it, and how their activity was controlled. The bacteriophage system as developed by Delbrück seemed ideal for my purpose. After his visit in the fall of 1951, we remained in contact. When reformed of my interest, he proposed that I should come to his laboratory at Caltech to learn the current state of bacteriophage biology and associated techniques.

In my third year at Ames, I was not yet eligible for sabbatical leave. However, I could take six months unpaid leave. I sought fellowship support for the six months. After my interview, I was informed by the fellowship board that they would award me a fellowship not for six months, which they thought would provide inadequate training, but for one year! My dilemma was happily resolved when Max was able to offer me a six-month fellowship from Caltech itself. I was to start on 1 January 1953.

We left Ames before Christmas in the midst of a sleet storm, wended our way across the frozen Midwest to Texas and on to Arizona, and spent Christmas in the snow at the Grand Canyon. Finally, we crossed the Mojave and descended through Cajon Pass into southern California. Once again, I had the sudden shock of emerging from bitter winter into warm sunshine and palm trees and fragrant flowers. We were just in time for our first Rose Parade.

Caltech was a revelation. Here were "giants"—scientists of the highest eminence—in almost every field. Lee DuBridge, who had directed the Radiation Laboratory, had assumed the presidency of Caltech in 1946 and had revitalized the institute. He had brought George Beadle, the leading geneticist, to head biology, and along with him Norman Horowitz and Herschel Mitchell. Alfred Sturtevant and Ed Lewis continued Thomas Hunt Morgan's drosophila research. Frits Went and James Bonner led an outstanding program in plant physiology. And Max Delbrück, Renato Dulbecco, and Jean Weigle were preeminent in bacteriophage research.

In chemistry, Linus Pauling was preeminent in the field of molecular structure, aided by Bob Corey. Jerry Vinograd, Walter Schroeder, and Norman Davidson were other leading chemists in the Pauling orbit. Jack Roberts had recently arrived to launch his NMR (nuclear magnetic resonance) program. In physics there were Richard Feynman, Murray Gell-Mann, Carl Anderson, and Charles Lauritsen; in geology Charles Richter and Benno Gutenberg; in astronomy Jesse Greenstein, Horace Babcock, and Martin Schmidt; in engineering Clark Millikan, Hans Liepman, and so on.

In a large university, a "post-doc" in Delbrück's laboratory such as myself might never have even seen these great men. But Caltech is a small, surprisingly democratic institution, and I met all of them and had significant discussions with several. Caltech was clearly a world center for science, one of the leading two or three in the world. In biology, almost everyone of distinction visited and lectured periodically. The newest discoveries were quickly known and discussed in a ferment of ideas. Biology at MIT had been much less dynamic, and the contrast with the near-isolation of Ames was extreme.

Max Delbrück was a profound influence on many students and colleagues, largely through the sheer force of his personality. Bright and rigorously logical, he imposed a quantitative intellectual discipline on the field of bacterial virology, which had been largely qualitative and unfocused. As the founder of a revived bacteriophage research program, Delbrück served as a combination pater familias and Herr Professor for the informal college of phage researchers developing about the country. He had insisted that they exchange cultures and limit the number of different bacteriophages studied so that different laboratories could obtain comparable results. Any new findings were quickly communicated to Delbrück for his comment and evaluation and through him to the community. He had a remarkable status and for a while produced an extraordinary cohesion within the phage fraternity. Of course, in time the field outgrew its founder.

In scientific debate, he could be mercilessly caustic but never mean-spirited. Delbrück had a weekly phage seminar at which ongoing research was discussed, or a visitor lectured. Max was known for his blunt and open criticism, his insistence on clear concepts and logical presentation, and his persistence in exposing ambiguities and uncertainties in a speaker's chain of reasoning. Many a speaker in his seminar or in the general biology seminar was sharply deflated; however, the net effect was to set and enforce a high standard of presentation.

His approach with students was generally "sink or swim"; it was salutary for the more resourceful, devastating for others. At the same time, Max was fond of playing the father-professor role, throwing large and often elaborate parties for the phage group at his house near campus, and taking caravans out for camping trips on the desert. The desert was quite unpopulated in those days and even a large group could be quite isolated in its own valley. These excursions featured long hikes and climbs and explorations of caves. At night, the brilliance of the stars

in the clear air, absent city lights, was startling to one raised in the always slightly hazy Midwest and East. Lying out in the open and watching the heavens revolve enabled me to comprehend how significant and mysterious the nightly stars must have seemed to primitive man.

Max had several "Maxims." For delivering a lecture to an audience of uncertain background knowledge, his advice was to "assume they are totally ignorant and infinitely intelligent." When skeptical of a new result, he would say, "I don't believe a word of it."

Max was convinced that important principles should be explicable in a simple and straightforward manner. If a convoluted and arcane argument was used, he was dubious His comment "what a swindle" indicated his belief that some big step had been overlooked or some error had been made in the complex exposition. He was frequently bemused by the progressivity of evolution—that each evolutionary advance, presumably achieved by selection to cope with a particular environmental circumstance, seemed again and again to bring additional new and unexpected potentials. "Nature provided more than was needed." The T4 bacteriophage he had studied proved to have over 150 genes, many of which would be of significant utility only in quite exceptional circumstances. The evolutionary steps that converted our anthropoid ancestors into Homo sapiens could hardly have been intended to solve problems in X-ray diffraction or quantum mechanics.

Delbrück's own research had mixed success. A physicist by training and inclination, he had little taste for the complexities and variations of chemistry. He sought out problems that could be approached quantitatively, analyzed abstractly, and preferably studied with simple equipment. This bent succeeded admirably in his early studies of bacteriophage, in the quantitative analysis of mutations and the discovery and analysis of bacteriophage genetics, and in his insistence that workers in bacterial virology should focus their efforts on a limited set of viruses.

But this approach was much less successful in his later studies of the biological effects of ultraviolet radiation on bacteriophage—in retrospect, the analysis was hopelessly complicated by the existence of multiple cellular repair mechanisms—and in his prolonged effort over twenty years to establish the mold Phycomyces as a model system for the study of sensory processes. This last was doomed by the inability to develop Phycomyces genetics. At the symposium in celebration of fifty years of biology at Caltech, Max, as chairman of a session, gently chided Dale Kaiser for having spent too many years researching the lambda

bacteriophage, long after the more significant discoveries had been made. Dick Feynman, sitting next to me, leaned over to say that Max should have applied his advice to his own work on Phycomyces .

As a physicist, Max sought to find principles of great generality, as opposed to solutions involving specific chemical interactions. It was his initial hope that the phenomena of genetics—cloaked in obscurity in the 1930s—would prove to rely on principles of physics previously undiscovered. In this, of course, he was grievously disappointed.

Much later, one of the most pleasant activities of my tenure as chairman of biology at Caltech was to organize the celebration for Max after he received the Nobel Prize in 1968. Admired, even exalted, for two decades at the institute, Max was felt by all there to deserve the Nobel Prize for his bacteriophage work. But after he had been passed over for so many years, and biology had moved on, many feared it was not to be. This made for all the more delight when the word came.

Max took the ensuing hoopla with his usual diffidence. I well recall the news conference the next day, with Max attempting to display and explain his current work with Phycomyces, which was completely unrelated to the research for which the prize was awarded. Prominent among the newspeople was a TV reporter who did a nightly interview with a local personality. The evening before, she had interviewed the superintendent for sewers. (Science reporting was at a low ebb in those days.) Actually, while Max was very pleased at the belated recognition, he was a little embarrassed that it had come long after he had left the phage field. He could no longer cogently discuss the current state of the science; bacteriophage research had passed him by. Knowing this, he would deprecatorily call himself "the old windbag" at the inevitable required speeches.

The celebration parts took the form of an elaborate musical skit with various members of the biology division commemorating and commenting in humorous doggerel on the several phases of Max's career. It was a loving "toast and roast" of a deservedly admired and venerated presence who had finally been appropriately honored.

At Caltech, I was primarily a student. I learned phage techniques by working through a lengthy set of prescribed laboratory exercises—I recall Max watching amusedly as I first learned to master sterile technique, that is, the art of holding all the tubes and cotton plugs while transferring liquid from one container to another. I also learned the current state of phage research in the group discussions. But I learned far more of biology and chemistry by attendance at the great variety of seminars

and from conversations with visitors and Caltech faculty and researchers, almost osmotically absorbing the ambience. Those six months introduced me to science at a still higher level of intensity and synergistic interaction.

In 1953, James Watson and Francis Crick propose the double helix structure of DNA, based upon the X-ray diffraction studies of Maurice Wilkins and Rosalind Franklin This structure made explicable in chemical terms many of the previously mysterious properties of genes and opened the way to molecular genetics.