DELBRüCK, MAX LUDWIG HENNING

(b. Berlin, Germany, 4 September 1906;

d. Pasadena, California, 10 March 1981), viral and bacterial genetics, molecular biology.

Delbrück shared the Nobel Prize for Physiology or Medicine in 1969 for his pioneering work in viral and bacterial genetics. He was one of the founders of molecular biology as well as a guiding and exacting spirit in its early development, particularly through the so-called Phage Group.

Early Life . Delbrück was a product of Germany’s academic and intellectual aristocracy. The great German chemist Justus Liebig was among his maternal forebears, and his father was Hans Delbrück, who had served briefly in the Prussian parliament and the Reichstag and was a professor of history at the University of Berlin. The youngest of seven children, Delbrück grew up in the Grunewald suburb of Berlin amid family and friends who included Adolf von Harnack, a cofounder and president of the Kaiser Wilhelm Gesellschaft (Kaiser Wilhelm Society), and Karl Bonhoeffer, his brother-in-law and a professor of psychiatry at the University of Berlin. Delbrück later reflected that in this bustling, politically engaged milieu, he turned to science—his first love was astronomy—as a way of establishing his own identity.

Starting in 1924 Delbrück studied astronomy, physics, and mathematics at several universities; then, in 1926, he enrolled at Göttingen University in Germany, where he remained to pursue doctoral work in theoretical physics. He was caught up in the enthusiasm for the new quantum mechanics and came to know several of the young scientists—including J. Robert Oppenheimer, Pascual Jordan, and Victor Weisskopf— who had come to the university to pursue the new theory. (“I learned at an early age that science is a haven for the timid, the freaks, the misfits,” Delbrück later mused, explaining, “If you were a student in Göttingen in the 1920s and went to the seminar ‘Structure of Matter’ … you could well imagine that you were in a madhouse.… Every one of the persons there was obviously some kind of severe case” (“Homo Scientificus”). He failed in an attempt to write a doctoral thesis on novae because he found the mathematics too difficult. He managed to obtain his doctorate in 1930 with a study that extended to lithium the quantum mechanical theory of the homopolar bond that had recently been developed for hydrogen.

Growing Interest in Biology . In 1929 Delbrück had joined the physics faculty at Bristol University in England, and after gaining his PhD the following year, he received a Rockefeller Foundation postdoctoral fellowship that enabled him to spend the spring and summer of 1931 studying with Niels Bohr in Copenhagen, Denmark, and then the fall and winter with Wolfgang Pauli, in Zürich, Switzerland. While in Copenhagen he was inspired to start learning biology as a result of hearing Bohr propose that living systems might operate under the principle of complementarity, exhibiting features comparable to the duality of light as a wave and a particle. An organism might, for example, be investigated as a collection of molecules or as a behavioral whole, but not as both simultaneously. In mid-1932, after he spent another six months in Bristol, Delbrück’s growing interest in biology was strengthened upon listening to Bohr lecture in Copenhagen on “Licht und Leben” (Light and life), suggesting, in line with his ideas about complementarity, that biological understanding would require concepts that could not be reduced to those of atomic physics. What fascinated Delbrück was precisely that biology might ultimately yield such concepts, some new principle inherent in the human observer’s attempt to comprehend vital nature. He would tell Bohr in 1962 that the question of complementarity in biology had given him his primary motivation for his work.

Delbrück returned to Berlin in 1932 to become an assistant to Lise Meitner at the Institute for Chemistry within the Kaiser Wilhelm Gesellschaft. Part of his research involved the scattering of gamma rays by a Coulomb field. Although inapplicable to the case that stimulated the effort, the results were theoretically sound and were later dubbed “Delbrück scattering” by Hans Bethe, who confirmed them. He also further explored biology by organizing a private discussion group of physicists, biologists, and biochemists. In pursuit of complementarity in biology, he resolved to investigate a simple biological system—something akin to the hydrogen atom in physics—and press its analysis until paradoxes appeared, just as they had emerged in the exploration of atomic physics. The system he was lured to was the gene.

Delbrück collaborated with two members of the discussion group, the Russian geneticist Nicolai TimofeeffRessovsky and the physicist Karl Günter Zimmer, to study the effect of ionizing radiation on genes. In 1935 the three men published “Uber die Natur der Genmutation und der Genstruktur” (The nature of genetic mutations and the structure of the gene), a paper that combined experimental data and—Delbrück’s interpretive contribution— the quantum theoretical idea of atoms residing in “energy wells” to account for both genetic stability and the occurrence of mutations in response to energetic ionizing radiation. Although ultimately proved wrong in several important respects, the paper indicated that genes were not abstract entities but relatively stable macromolecules susceptible to analysis by physical and chemical methods. Published in an obscure journal, the paper, Delbrück later said, got “a funeral first class.” However, the physicist Erwin Schrödinger, the Nobel laureate in physics for his contributions to quantum mechanics, called prominent attention to it in his influential book What is Life?, which was published in 1944 (a German translation Was ist Leben? was published in 1946). Schrödinger contended that he had been inspired to write the book by Delbrück’s paper. The book, a tour de force of how physical reasoning might be applied to biological problems, stimulated a number of young physicists to emulate Delbrück by becoming molecular geneticists.

War Years in America . The merits of his research did not earn Delbrück a regular academic post in Nazi Berlin. Unlike his family, he was doggedly apolitical, alienated from state and society by World War I—in which he had lost his oldest brother—and by the ugly political passions that had bubbled, not always beneath the surface, in Weimar Germany. Even so, in the 1930s he made no secret of the fact that he found the Nazis contemptible, as did members of his family, some of whom opposed them actively. Despite his impeccable German (and nominally Christian) credentials, he was deemed politically unreliable and was unable to obtain a university post. Coveting one greatly, Delbrück went to considerable lengths to prove that he was not Jewish, and he submitted to courses at Nazi indoctrination camps—all to no avail. However, the paper on genetic mutations led to an opportunity to escape the difficulty—a Rockefeller Foundation Fellowship to spend the 1937–1938 academic year in the United States, mainly at the California Institute of Technology (Caltech) in Pasadena, to study genetics with Thomas Hunt Morgan, who in 1933 had been awarded a Nobel Prize for his pioneering work on the genetics of Drosophila(fruit flies).

Delbrück found fruit-fly genetics not to his liking because it was too ridden with elaborate jargon. But he was exhilarated when, by chance, he met the Caltech biochemist Emery Ellis, who was working with bacteriophage, a virus that preys on bacteria. If the phage were permitted to infect bacteria contained on a flat plate, they would multiply in the infected cells, killing them, and the dead cells would reveal themselves as clear areas called “plaques” on a lawn of bacterial growth. In 1935 the biochemist Wendell Stanley succeeded in crystallizing a tobacco virus, which indicated, as Delbrück put it, that a virus is a “living molecule.” In Delbrück’s view, bacteriophage presented a simple system—the hydrogen atom for biology—he had been looking for. With Ellis’s plaque methods, bacteriophage’s actions of infection and reproduction through time could be quantitatively scrutinized and analyzed.

Delbrück promptly embarked on a program of phage research, remaining in the United States for another year via an extension of his Rockefeller fellowship to 1939 and then—amid the outbreak of war in Europe—indefinitely, with an appointment in January 1940 to the faculty of Vanderbilt University in Nashville, Tennessee. Collaborating with Ellis while still at Caltech, he refined the treatment of the one-step growth curve (the spread of infection from a single particle) and devised the so-called single-burst experiment, which permitted a comparison of phage multiplication in individual cells. He also devised mathematical formulas for calculating the rate of adsorption of free phage by bacteria under different experimental conditions and, using Siméon Denis Poisson’s statistics of random sampling, for assessing the proportion of virus particles able to produce plaques. These methods proved to be crucial for the subsequent development of phage research.

In the summer of 1941 Delbrück went to the Cold Spring Harbor Laboratory, on Long Island in New York, to work on bacteriophage with Salvador Luria, whom he had met in 1940. A refugee from Italy, Luria had been eager to collaborate with Delbrück since reading the paper on genetic mutations. In 1942 Luria and Delbrück began to think about whether bacterial resistance to phage originated from the bacteria’s contact with the phage or from spontaneous mutation. Luria had the idea of resolving the issue by comparing the numbers of resistant bacteria in independent cultures, each seeded with only a few sensitive cells. Resistance induced by contact with the phage would yield numbers of resistant cells within the limits expected by random sampling. In contrast, resistance arising from mutation would generate numbers of resistant cells with much larger variation. In sum, a fluctuation greater than that of sampling error in the numbers of resistant bacteria would mean that these variants had arisen before they were exposed to the phage and were therefore mutants.

Delbrück enthusiastically endorsed Luria’s idea with a fully developed mathematical theory of the proposed experiment that enabled calculation of the rate of mutation from the data. Luria’s experiment showed unambiguously that bacterial resistance is the product of spontaneous mutation, not of some Lamarckian adaptation. Delbrück and Luria’s paper “Mutations of bacteria from virus sensitivity to virus resistance,” published in 1943, was a landmark in the history of bacterial and phage genetics. It offered the first solid evidence that bacterial inheritance is governed by genes, an unpopular view at the time among leading microbiologists, and it laid out powerful methods and modes of analysis by which bacterial genetics could be studied efficiently.

The Phage Group . Also in 1943, Delbrück and Luria took into their partnership Alfred Hershey—Luria and Hershey would be Delbrück’s co-recipients of the Nobel Prize—a chemist on the faculty of the Washington University School of Medicine in St. Louis, Missouri. Hershey’s arrival initiated what came to be known as the Phage Group, an informal network of viral and bacterial geneticists. In 1944 Delbrück negotiated a “phage treaty,” a kind of standardization agreement intended to make the results of phage research comparable across different laboratories. According to the agreement, members of the Phage Group would deal mainly with a set of seven phage (T1 through T7) and use the bacterium E. coli as the object of infection.

Delbrück modeled the Phage Group after the network of physicists centered on Niels Bohr that had created quantum physics, later reflecting how it was formed to imitate “the Copenhagen spirit” in physics. He helped

recruit a number of scientists, especially physicists, into postwar molecular biology, both indirectly, by the showcasing Schrödinger gave him in What is Life?, and directly, by organizing in 1945 what became an annual summer phage course at Cold Spring Harbor that continued for twenty-five years. Intended for biologists, biochemists, and physicists, it inculcated the Phage Group’s quantitative and statistical approach to biology, and it drew a steadily increasing number of students, ranging from young postdoctoral fellows to senior physicists, for a total of some four hundred by the end. In 1947 he initiated a series of phage meetings that continued until his incapacity in 1981 and that eventually drew hundreds of scientists. Also in 1947 he returned to the California Institute of Technology as professor of biology, and he made Caltech into a center of the new quantitative molecular biology.

DNA . After the war Delbrück continued to hope that the study of the genetics of microorganisms would expose some deep paradox that would compel the forging of a new principle. Although the evidence had kept accumulating that genetics was chemistry, Delbrück tended not to think biochemically. He and Luria were well aware of the evidence developed by Oswald Avery’s group at the Rockefeller Institute for Medical Research that the genetic material might be DNA. However, they did not credit what Avery and others had learned about the transforming principle in pneumococcus with broad applicability to phage research or even other types of bacteria. They did not see how DNA could carry hereditary information. And, in any case, they did not attach great importance to whether genes were proteins or nucleic acid.

Once James Watson and Francis Crick together pieced out the structure of DNA in 1953, it was clear that the key to the transmission and expression of genetic information inhered not in some new physical laws but in a supple, compact, and beautiful molecule whose functions were explicable in terms of conventional chemistry. This denoument disappointed Delbrück because it did not reveal any profound new principle of nature. He thought the structure of DNA was marvelous, to be sure. But, as he wrote in 1986 in Mind from Matter: “Upon the discovery of the DNA double helix, the mystery of gene replication was revealed as a ludicrously simple trick. In peole who had expected a deep solution to the deep problem of how in the living world like begets like, it raised a feeling similar to the embarrassment one feels when shown a simple solution to a chess problem with which one has struggled in vain for a long time.”

Later Career . In 1950 Delbrück began moving away from phage research, believing that it was well established and could take care of itself. He began turning his attention to problems of sensory perception and its transduction into physiological activity. Looking for a model organism with which to investigate the subject, he first tried the bacterium Rhodospirillum, which swims towards a light source. After a few experiments, however, he decided to switch to Phycomyces, a simple fungus that sprouts large aerial stalks called sporangiophores that exhibit a number of behavioral responses to different stimuli, notably growing toward light, against gravity, into the wind, and away from nearby objects. In 1953 Delbrück began his first experiments with the fungus and in 1956 published a paper, “System analysis for the light growth reactions of Phycomyces,” that proposed a kinetic model of adaptation to light. The model proved to be influential for analyzing other sensory systems and the paper became a classic. Delbrück gradually established a Phycomyces group, recruiting members mainly from physics. Sufficient work had accumulated by 1969 to warrant a review of the field. He had hoped that the work with Phycomyces might reveal paradoxes that would lead to a new principle of nature, but he was no more satisfied in this endeavor than he had been with genetics.

Delbrück felt acutely the terrible losses suffered by friends and relatives who had stayed in Germany. He considered those who had remained and resisted the regime— like his brother-in-law Karl Bonhoeffer, who had survived, and Karl’s brother Dietrich, who was murdered by the Nazis—prisoners of conscience, and he donated his Nobel Prize money to Amnesty International “as a debt to all prisoners of conscience.” From 1961 to 1963 he took leave of absence from Caltech to help establish the Institute for Genetics at the University of Cologne in Germany. He organized four research groups there, including one led by himself, to study the photochemical effects of ultraviolet light on DNA. He also established phage courses on the Cold Spring Harbor model. He maintained connections with the Genetics Institute as honorary professor, returning every year or so to give a series of lectures or a seminar. Later he served as an adviser in natural science on the founding committee of the new University of Konstanz in Germany, founded in 1966.

Otherwise, Delbrück hewed to a largely apolitical life, keeping the house clear of radio, television, and magazines. He held to the belief, as he declared in an autobiographical fragment, that “the pursuit of scientific truth, of poetic truth or of mystic truth, is ultimately far more important and influential in shaping man’s fate than the power game of those with political aspirations who try to change the world directly.” Among the truths he tried to puzzle out in his later years was how mind emerged from matter, which was the subject of a series of lectures that he gave at Caltech in 1972 and of an essay that he presented to the Nobel Conference in 1977. In the end, he could find no explanation for the remarkable fact that the brain, if selected for its survival value, could nevertheless range over disparate abstract subjects such as cosmology, genetics, and number theory.

Delbrück’s insulation from the world was made all the more possible by his American circumstances. He was favored by the increasingly abundant resources of American science, and also by his marriage. His biographers, Ernst Peter Fischer and Carol Lipson, report that his wife “sheltered him, allowing him to concentrate on science,” adding, “Manny ran the house, looked after the car, did the income tax, and later on guided the children” (1998). Yet if politics and public affairs meant little or nothing to Delbrück, neither did material goods or fame. He lived modestly. He was uncomfortable with kudos. When he won the Nobel Prize, he acknowledged the congratulations that poured in from friends by mailing out a handwritten excerpt from a Japanese poem that he had read at the end of the press conference occasioned by the award:

The temple bell echoes the impermanence of all things …

Before long the mighty are cast down

And are as dust before the wind.

While an advocate of cooperation, Delbrück himself sometimes behaved more in the irascible manner of Wolfgang Pauli, who was quantum physics’s uncompromising intellectual conscience, than in the way of the tactful Bohr. Delbrück’s criticism could be devastating. He might comment on a seminar by stalking out after five minutes or, worse, by telling the speaker afterwards that this was “the worst seminar I ever heard.” (He kept a bottle of brandy in his desk for the restoration of the distressed.) Some thought of him as hypercritical and arrogant. Still, he was widely respected for his nagging questioning, his tendency to poke holes in seemingly settled results or new claims. Scientists on both sides of the Atlantic, encountering fresh ideas or data, would commonly wonder, “What will Max think?”

Delbrück was also on the whole an unusually engaging, humorous, and generous colleague, devoting “great effort and intelligence,” Hershey once noted, “to encouraging, appreciating, and steering the work of others, probably often at the expense of his own.” He was playful and unpretentious, never the distinguished professor, always “Max.” He and his wife, the former Mary Adeline Bruce, the daughter of a prosperous mining engineer, familiarly known as “Manny,” whom he married in 1941, were warmly hospitable in their Pasadena home to students, colleagues, and other visitors. Max and Manny often led weekend camping trips to the desert accompanied by an entourage of undergraduates, graduates students, postdoctoral fellows, staff, dogs, and children, including their own four. A camper might awaken in the middle of the night to see Delbrück standing naked, his binoculars balanced on the car, observing the sky.

When Delbrück learned that he had multiple myeloma—the disease that eventually killed him—he gathered his students together for a seminar on the subject and, as the disease progressed, told his son Jonathan that he was embarked on his “last great adventure.” A few months before his death, he suffered a stroke that impaired his vision on one side. He was fascinated by the limitation and made himself available to students for “some tests they cannot do with the monkeys.”

BIBLIOGRAPHY

Unpublished letters and other papers of Delbrück and an oral interview with him are in the Max Delbrück Papers at the archives of the California Institute of Technology in Pasadena. Requests for use of these materials can be made at http://archives.caltech.edu.

WORKS BY DELBRÜCK

“Uber die Natur der Genmutation und der Genstruktur” [The nature of genetic mutations and the structure of the gene]. Nachrichten von der Gesellschaft der Wissenschaften zu Gottingen 6 (1935): 189–245.

With Salvador Luria. “Mutations of bacteria from vrius sensitivity to virus resistance.” Genetics 28, no. 6 (1943): 491–511.

With Werner Reichardt. “System analysis for the light growth reactions of Phycomyces.” In Cellular Mechanisms in Differentiation and Growth, edited by Dorothea Rudnick, 3–44. Princeton, NJ: Princeton University Press, 1956.

“Homo Scientificus According to Beckett.” Lecture at California Institute of Technology. Chemistry and Society Lecture Series, 24 February 1971. Available from http://barnesworld.blogs.com/delbruck1971.pdf.

Mind from Matter? Oxford, U.K.: Blackwell Scientific Publishing, 1986.

OTHER SOURCES

Cairns, John, Gunther S. Stent, and James D. Watson, eds. Phage and the Origins of Molecular Biology. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory of Quantitative Biology, 1966.

Fischer, Ernst Peter, and Carol Lipson. Thinking about Science: Max Delbrück and the Origins of Molecular Biology. New York: Norton, 1988. The most comprehensive treatment of Delbrück, the man and the scientist. Fischer was one of his last graduate students.

Hayes, William. “Max Ludwig Henning Delbrück, September 4, 1906–March 10, 1981.” National Academy of Sciences Biographical Memoirs62 (1993): 67–117. A valuable short treatment of Delbrück.

Judson, Horace Freeland. The Eighth Day of Creation: Makers of the Revolution in Biology. New York: Simon and Schuster, 1979.

Luria, Salvador E. A Slot Machine, a Broken Test Tube. New York: Harper and Row, 1984.

Mullins, Nicholas C. “The Development of a Scientific Specialty: The Phage Group and the Origins of Molecular Biology.” Minerva 10 (1972): 51–82.

Olby, Robert. The Path to the Double Helix. London: Macmillan, 1974.

Schrödinger, Erwin. What is Life? The Physical Aspect of the Living Cell. New York: Macmillan, 1944.

Strasser, Bruno J. La fabrique d’une nouvelle science: La biologie moléculaire à l’âge atomique, 1945–1964[The making of a new science: Molecular biology in the atomic age, 1945–1964]. Florence, Italy: Olschki, 2006.

Daniel J. Kevles