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

Max Delbrück

Max Delbrück (1906-1981) has often been called the founder of molecular biology. In 1969 he shared the Nobel Prize for physiology or medicine for work in the area of molecular genetics.

Max Delbrück has often been called the founder of molecular biology. Although educated as a physicist, Delbrück quickly became interested in bacteriophages, a type of virus that infects bacterial cells. He perfected a method of culturing bacteriophages and found that they could infect a bacterial cell and, within twenty minutes, erupt out of the cell in a hundredfold their original number. Each of these offspring bacteriophages was then ready to infect another bacterial cell. Among his many contributions to the field, Delbrück and another researcher together discovered that bacterial cells could spontaneously mutate to become immune to the bacteriophages. He also found that two different types of bacteriophages could combine to create a new type of bacteriophage. Perhaps as much or more than his discoveries, he forged the field of molecular biology through his involvement in the work of so many other scientists. While he was highly critical and not easily convinced of a new discovery, Delbrück also inspired many scientists to new heights. His work paved the way for an explosion of new findings in the field of molecular biology, including the discoveries that viruses contain the genetic material deoxyribonucleic acid (DNA), along with the eventual unveiling of the structure of DNA itself. In 1969, Delbrück won the Nobel Prize for physiology or medicine, which he shared with Alfred Day Hershey and Salvador Edward Luria, for their work in molecular genetics.

Delbrück was born on September 4, 1906, in Berlin as the youngest of seven children to Hans and Lina Thiersch Delbrück. Many of his relatives were prominent academicians, including his father, who was a professor of history at the University of Berlin and editor of the journal Prussian Yearbook; his maternal great-grandfather, Justus von Liebig, is considered the originator of organic chemistry. Throughout his youth in the middle-class suburb of Grünewald, Delbrück developed his interests in mathematics and astronomy, and carried those interests into college.

In 1924 he enrolled in the University of Tübingen, but switched colleges several times before enrolling at the University of Göttingen, where he obtained his Ph.D. in physics in 1930. Delbrück began writing a dissertation about the origin of a type of star, but abandoned it because of his lack of understanding of both the necessary math and English, the language in which most of the pertinent literature was written. He took up a new topic, and completed his dissertation by explaining the chemical bonding of two lithium atoms, and why this bonding is much weaker than the bond between two hydrogen atoms.

For the next year and a half, through a research grant, he did postgraduate studies in quantum mechanics at the University of Bristol in England. There, he became friends with other researchers, several of whom went on to make major contributions in the fields of physics and chemistry. In the early 1930s, he continued his research as a Rockefeller Foundation postdoctoral fellow under Neils Bohr at the University of Copenhagen, one of the major intellectual centers in the world. Bohr's beliefs had a strong impact on Delbrück. Bohr had developed a theory of complementarity, stating that electromagnetic radiation could be described by either waves or particles, but not both at the same time. He followed that by a now-famous lecture in 1932 called "Light and Life." In it, Bohr suggested that a similar paradox existed in living things: they could be either described as whole organisms or as groups of molecules. Delbrück was hooked. He began to study biology. In 1932, Delbrück returned to Berlin and the Kaiser Wilhelm Institute. He remained at the institute for five years, and continued his shift from physics to biology. From 1932 to 1937, while an assistant to Professor Lise Meitner in Berlin, Delbrück was part of a small group of theoretical physicists which held informal private meetings; he was devoted at first to theoretical physics, but soon turned to biology. In his acceptance speech for the Nobel Prize, Delbrück recalled that "Discussions of (new findings) within our little group strengthened the notion that genes had a kind of stability similar to that of the molecules of chemistry. From the hindsight of our present knowledge," he said, "one might consider this a trivial statement: what else could genes be but molecules? However, in the mid-'30s, this was not a trivial statement."

In 1937, by virtue of his second Rockefeller Foundation fellowship, Delbrück immigrated to the United States, where he began to study biology and genetics and the reproduction of bacteriophages, in particular, at the California Institute of Technology in Pasadena. A year later, he met Emory Ellis, a biologist also working on these viruses, and together they designed experiments to study bacteriophages and the mathematical system to analyze the results.

By 1940, Delbrück had joined the faculty of Vanderbilt University in Tennessee and during the following summers continued his phage research intensively at the Cold Spring Harbor Laboratory on Long Island in New York. Also in 1940 he met Italian physician Salvador Luria, with whom he would eventually share the Nobel Prize. Luria was conducting bacteriophage research at the College of Physicians and Surgeons of Columbia University in New York City. Their collaborative work began, and in 1943 Delbrück and Luria became famous in the scientific community with the publication of their landmark paper, "Mutations of Bacteria from Virus Sensitivity to Virus Resistance." The paper confirmed that phage-resistant bacterial strains developed through natural selection: once infected with a bacteriophage, the bacterium spontaneously changes so that it becomes immune to the invading virus. Their work also outlined the experimental technique, which became a standard analytical tool for measuring mutation rates. The publication of this paper is now regarded as the beginning of bacterial genetics.

Also in 1943, the so-called Phage Group held its first informal meeting, with Delbrück, Luria and microbiologist Alfred Hershey in attendance. At group meetings, members discussed research and ideas involving bacteriophages. The number of members grew along with the excitement over the possibilities presented by this area of research. The meetings were much like those Delbrück had so enjoyed while he was working in Meitner's lab in Berlin. In the following year, the Phage Group drafted guidelines—called the Phage Treaty of 1944—to ensure that results gained from different laboratories could be compared easily and accurately. The treaty urged all bacteriophage investigators to conduct their studies on a specific set of seven bacteriophages that infect Escherichia colistrain B and its mutants. It also spelled out the standard experimental conditions to be used.

While on the faculty at Vanderbilt University, Delbrück organized the first of his summer phage courses at Cold Spring Harbor in 1945, the year he also became a U.S. citizen. The course became an annual event and drew biologists, geneticists and physicists who traveled from laboratories all over the world to learn not only about the experimental and analytical methods of phage research but also about its potential.

In 1946, Delbrück's and Hershey's labs separately discovered that different bacteriophage strains that both invade the same bacterial cell could randomly exchange genetic material to form new and unique viral strains. They called the phenomenon genetic recombination. According to Biographical Memoirs of Fellows of the Royal Society, this finding "led, about 10 years later, to the ultimate genetic analysis of gene structure by Seymour Benzer."

The following year, Delbrück returned to the California Institute of Technology as a professor in the biology department. In 1949, he delivered an address, "A Physicist Looks at Biology," that recalled his scientific journey. "A mature physicist, acquainting himself for the first time with the problems of biology, is puzzled by the circumstance that there are no 'absolute phenomena' in biology. Everything is time bound and space bound. The animal or plant or microorganism he is working with is but a link in an evolutionary chain of changing forms, none of which has any permanent validity. … If it be true that the essence of life is the accumulation of experience through the generations, then one may perhaps suspect that the key problem of biology, from the physicist's point of view, is how living matter manages to record and perpetuate its experiences." He described the cell as a "magic puzzle box full of elaborate and changing molecules (that) carries with it the experiences of a billion years of experimentation by its ancestors."

In the late 1940s and early 1950s, Delbrück expanded his interests to include sensory perception, eventually studying how the fungus Phycomyces uses light and how light affects its growth. As he did with the phage research, Delbrück formed a Phycomyces Group to gather and discuss ideas. Despite his shift, he and his work continued to have an influence in bacteriophage research. In 1952 Hershey, one of the original three members of the Phage Group, and Martha Chase confirmed that genes consist of DNA and demonstrated how phages infect bacteria. The following year molecular biologist Francis Crick and physicist James Watson, once a graduate student of Luria's, determined the three-dimensional, double-helix structure of DNA. While their work was in progress, Watson would frequently write Delbrück to discuss ideas and to tell him about their results, including the first details of the double-helix structure.

Delbrück remained busy throughout the 1950s and 1960s as investigators and students sought his knowledge and advice, despite his reputation for being a tough critic with a brusque manner. Following an investigator's explanation of his research and results, Delbrück would often respond, "I don't believe a word of it," or if it was a more formal presentation, "That was the worst seminar I have ever heard." Once, according to Seymour Benzer in Phageand the Origins of Molecular Biology, Delbrück wrote to Benzer's wife, "Dear Dotty, please tell Seymour to stop writing so many papers. If I gave them the attention his papers used to deserve, they would take all my time. If he must continue, tell him to do what Ernst Mayr asked his mother to do in her long daily letters, namely, underline what is important." Yet, many scientists persisted in bringing their research to Delbrück. In his essay in Phage and the Origins of Molecular Biology, molecular biologist Thomas Anderson recalled Delbrück: "At each phase in our groping toward discovery, Max Delbrück seemed to be present not so much as a guide, perhaps, but as a critic. To the lecturer he was an enquiring, and sometimes merciless, logician. If one persevered, he would be fortunate to have Max as conscience, goad and sage."

Delbrück also had a lighter side. As reported in Thinking About Science, Delbrück remembered pitting his wits against those of his college professors. He would not take notes during the lectures, but would try to follow and understand the professor's mathematical argument. "When the professor made a little mistake, with a plus or minus sign or a factor of 2, I did not point that out directly but waited 10 minutes until he got entangled and then pointed out, to his great relief, how he could disentangle himself—a great game." When Delbrück joined the faculty ranks, he developed a rather unusual tradition with his students and peers. He often invited them along on camping trips with his family, including his wife and eventually their four children. Delbrück married Mary Adeline Bruce in 1941. They had two sons, Jonathan and Tobias, and two daughters, Nicola and Ludina.

In 1961, while still a professor at the California Institute of Technology, Delbrück took a two-year leave of absence to help the University of Cologne in Germany establish its Institute of Genetics. In 1966 back in California, the former Phage Group members celebrated Delbrück's sixtieth birthday with a book in his honor, Phage and the Origins of Molecular Biology. The book is a collection of essays by the group members, many of whom had gone on to make important discoveries in bacterial genetics. The larger scientific community also recognized Delbrück's contributions with a variety of awards. In December of 1969, Delbrück, Luria and Hershey accepted the Nobel Prize in physiology or medicine for their work in molecular biology, particularly the mechanism of replication in viruses and their genetic structure.

Delbrück continued his sensory perception research into the next decade. He retired from the California Institute of Technology in 1977, and died of cancer four years later in Pasadena on March 10, 1981. In Phage and the Origin of Molecular Biology, phage course alumnus N. Visconti recalled a conversation he had with Delbrück. "I remember he once said to me, 'You don't have the inspiration or the talent to be an artist; then what else do you want to do in life besides be a scientist?' For Max Delbrück it was as simple as that."

Further Reading

Biographical Memoirs of Fellows of the Royal Society, Volume 28, Royal Society (London), 1982.

Fischer, Ernst P., and Carol Lipson, editors, Thinking about Science: Max Delbrück and the Origins of Molecular Biology, W. W. Norton, 1988.

Hayes, William, "Max Delbrück and the Birth of Molecular Biology," in Social Research, autumn, 1984, pp. 641-673.

Kay, Lily, "Conceptual Models and Analytical Tools: The Biology of Physicist Max Delbrück," in Journal of the History of Biology, summer, 1985, pp. 207-246.

Physics Today, June, 1981, pp. 71-74. □

DELBRÜCK, Max Ludwig Henning

(b. 4 September 1906 in Berlin, Germany; d. 10 March 1981 in Pasadena, California), geneticist called the father of molecular biology who won the 1969 Nobel Prize in physiology or medicine for his cross-disciplinary approach to the study of viruses.

Delbrück was born to Hans Delbrück, a professor of history at the University of Berlin, and Lina Thiersch Delbrück, a granddaughter of the scientist Justus von Liebig, who is considered the originator of organic chemistry. The youngest of seven children, Delbrück grew up in a very active family and among members of the academic, professional, and merchant classes. As a youngster he developed a strong interest in astronomy, partly as a way to distinguish himself among so many strong personalities in his family and among their friends. However, Max Planck, a boy in the neighborhood who grew up to be a physical chemist of high distinction, became a mentor and a lifelong friend to Delbrück. Their relationship shifted Delbrück's focus from astrophysics to theoretical physics during the latter days of his graduate studies at the University of Göttingen, just after the breakthrough discoveries that opened the field of quantum mechanics. Delbrück received his Ph.D. in 1930.

Delbrück took three postdoctoral years (1929–1932) in England, Switzerland, and Denmark. He began a lifelong association with Wolfgang Pauli and Niels Bohr, and it was Bohr who first influenced Delbrück's final turn toward biology and cross-disciplinary studies in science. Delbrück moved to Berlin in 1932, where he wrote a very influential paper, Über die Natur der Genmutation und der Genstruktur ("On the Nature of Gene Mutation and Gene Structure"), with Nikolai Timoféeff-Ressovsky and K. G. Zimmer on mutagenesis that was published in 1935 and later reprinted in Erwin Schrödinger's essay, What Is Life? (1944). This association and the paper laid the foundation for the rapid development of molecular genetics in the 1940s, 1950s, and 1960s.

In 1937 Delbrück immigrated to the United States with the help of a Rockefeller Foundation fellowship, which provided him with greater freedom to pursue his research interests in biology. He went to the California Institute of Technology because of its strength in fruit fly genetics and ended up working with Emory L. Ellis in phage research. Ellis introduced him to bacteriophages, or phages, viruses that affect bacteria, an area of study that appealed strongly to Delbrück's physics-trained mind. Like the hydrogen atom, the simplest form of matter, the bacteriophage was then considered the simplest form of life. When the fellowship ran out in 1939 and World War II started, Delbrück decided to stay in the United States, accepting an instructorship in the physics department at Vanderbilt University in Nashville, Tennessee. In 1941 Delbrück married Mary Adeline Bruce, and in later years they had four children.

During World War II, around 1941, Delbrück began his association with the Cold Spring Harbor Laboratory of Quantitative Biology on Long Island, New York, and with Salvador E. Luria and other well-known luminaries in the field of biology. This began what became known as the Phage Group, which eventually originated fluctuation theory. At this point, Delbrück and Luria began studying bacteria and viruses to determine their mode of transmission. Much to their surprise, they discovered that viruses and bacteria were capable of transferring their DNA in order to replicate rapidly. Research began into the mechanism of the transfer, and Luria came up with the idea of treating the bacteria as though they were slot machines. Exposure to viruses caused the bacteria to die, but those that survived would spring back with continued growth and take back the territory formerly possessed by the viruses. Thus the scientists could determine whether the survival was based on chance or if the bacteria were mutating in response to the challenge from the viruses. This discovery marked the beginning of phage research and began science's present-day insight into the nature of viruses. Among other discoveries and accomplishments from the Phage Group were the mutual exclusion principle, the fluctuation test, and the phage theory. Delbrück and Luria's students included James Watson, Renato Dulbecco, and other interested physicists and biochemists such as Leo Szilard, the father, with Enrico Fermi, of the nuclear chain reaction, and the atomic scientist Philip Morrison.

Delbrück became a U.S. citizen in 1945, and in the early 1950s his research interests shifted from molecular genetics to sensory physiology and phage research. One of the first grants the National Science Foundation ever awarded was to Delbrück for research. The study was called "Mechanisms Underlying Genetic Recombination in Bacteria." The results of Delbrück's work and teaching contributed to the rise of modern molecular genetics. Initially he began work on sporangiophores of Phycomyces to study stimulus transductions at the molecular level and to determine transducer processes of sense organs in general. In 1962 Delbrück was instrumental in setting up an institute of molecular genetics at the University of Cologne to demonstrate the possibilities behind modern interdisciplinary research within Germany and to promote the field of molecular genetics there. This institute was dedicated on 22 June 1962, with Niels Bohr the primary speaker, one of his last appearances.

Delbrück won the 1969 Nobel Prize in physiology or medicine using a cross-disciplinary approach to the study of viruses by fusing biochemistry, genetics, and physical principles to study replication mechanisms and the genetic structure of viruses. He shared the prize with Alfred Day Hershey and Luria, and a brief biography refers to him as "one of the founding fathers of modern genetics." Also in 1969 both Luria and Delbrück won the Louisa Gross Horowitz Prize for their contributions to the understanding of the genetics of bacteria and bacteriophages.

In 1978 Delbrück was diagnosed with multiple myeloma. Successful treatment prolonged his life for three years, and then a few months before his death in 1981, he also had a mild stroke that affected his vision.

Scientists writing about this era in genetics who worked closely with Delbrück refer often to his happy spirit, quick wit, and generosity of spirit. In 1966 Delbrück's colleagues honored his sixtieth birthday by publishing Phage and the Origins of Molecular Biology, a collection of essays by Phage Group members. It is remarkable to read the list of luminaries that Delbrück brought together at Cold Spring Harbor. He appears to have been a wonderful catalyst and mentor to many. His was a remarkable and intelligent influence on modern gene research, molecular biology, phage theory, and tumor virology. Perhaps his greatest strength was his broad, deep knowledge of several scientific fields and his ability to intermingle biochemistry, genetics, and physical principles in his research and thinking.

For more information, see Ernst P. Fischer and Carol Lipson, eds., Thinking About Science: Max Delbrück and the Origins of Molecular Biology (1988). See also Robert S. Edgar, "Max Delbrück," Annual Review of Genetics 16 (1982): 501–505, and William Hayes, "Max Ludwig Henning Delbrück," National Academy of Sciences. Biographical Memoirs 62 (1993): 67–117. An obituary is in the New York Times (13 Mar. 1981).

Kim Laird

Delbrück, Max

Physicist, Molecular Biologist 1906-1981

Max Delbrück made major contributions to the understanding of replication and viral function. Raised in Berlin in a distinguished family of German intellectuals, Delbrück trained as a physicist with Niels Bohr and other leaders in the field of quantum mechanics. In the early 1930s his interests turned toward biology and the nature of the gene. This was only thirty years after the rediscovery of Mendel's work and twenty years before Watson and Francis Crick discovered the structure of DNA. With two colleagues, he published a theoretical paper on quantum mechanical restrictions on gene structure. These ideas were popularized by the physicist Erwin Schrödinger in the book What is Life?, which inspired many young midcentury scientists to join the quest to understand the gene.

Delbrück moved to the United States in 1937 to pursue genetics and escape the increasingly repressive atmosphere of Nazi Germany. He first went to Columbia University in New York, where he joined Thomas Hunt Morgan's group to study Drosophila. Soon, however, he became interested in bacteriophages . It was in the understanding of this model system that Delbrück made his greatest contribution.

Bacteriophages are among the simplest genetic systems, and thus provided Delbrück with an elegant tool for exploring fundamental processes of reproduction and mutation. Delbrück collaborated with Salvador Luria and Alfred Chase to work out the fundamental mechanisms of viral replication and to explore the genetics of mutation in this system. This loosely allied trio, and the ever-widening circle of scientists with whom they collaborated, became known as "the phage group." This group conducted training courses at Cold Spring Harbor Laboratory in New York, where they introduced many other biologists to this model system, while inculcating in them their own rigorous and quantitative approach. Watson was one of Delbrück's students in the phage course. The phage group began and shaped the field of molecular genetics, and Delbrück is usually considered the father of this discipline. Delbrück, Luria, and Hershey were awarded the Nobel Prize for physiology or medicine in 1969 for their discoveries in phage genetics.

Later in his life, Delbrück turned his attention to the cellular physiology underlying perception, but the model system he chose for this research, a light-sensitive fungus, had too little in common with animals to make the research strongly relevant to animal perception. He died in 1981.

see also Crick, Francis; Morgan, Thomas Hunt; Watson, James; Virus.

Richard Robinson

Bibliography

Fischer, Ernst Peter, and Carol Lipson. Thinking About Science: Max Delbrück and the Origins of Molecular Biology. New York: W. W. Norton, 1988.

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

Schrödinger, Erwin. What is Life? New York: Cambridge University Press, 1992.