Max Delbrück

For more information on Max Delbrück, visit Britannica.com.

German-born American physicist and molecular biologist (1906–1981)

The son of a history professor, Delbrück trained as a physicist first in his native city of Berlin, and then at Tübingen, Bonn, and Göttingen, where he completed his doctorate in 1930. After spending the period from 1931 to 1933 in Copenhagen, Delbrück was appointed to the Kaiser Wilhelm Institute for Chemistry, Berlin. He left Germany for America in 1937, working first at the California Institute of Technology and from 1940 until 1947 at Vanderbilt University, Nashville. Delbrück returned to Cal Tech in 1947 and remained there as professor of biology until his retirement in 1976. He became a naturalized American citizen in 1945.

While at Copenhagen, under the influence of Niels Bohr, Delbrück's interest was diverted from atomic physics to questions about the nature of life. In the late 1930s he began to work with bacteriophages, the viruses discovered by D'Herelle that infect and destroy bacteria. They were relatively simple, reproduced quickly, and were easy to handle; an ideal organism, Delbrück argued, in which to study the mechanisms of replication and development.

In 1939, with E. Ellis, he first demonstrated the phenomenon of ‘one-step growth’. Working with the phage T4 he found that “a virus particle enters a bacterial cell and after a certain period (between 13 and 40 minutes, depending on the virus, on the dot for any particular type), the bacterial cell is lysed and 100 particles are liberated.” How can one particle, Delbrück asked, become 100 in a mere 20 minutes?

Soon after he began to collaborate with Salvador Luria. In 1943 they published a paper, Mutations of Bacteria from Virus Sensitivity to Virus Resistance. How, they asked, do bacteria acquire resistance to lethal phage? Is it induced by contact, or does it arise from a fortunate mutation? Luria and Delbrück realized that the dynamics of bacterial growth would differ in each case. The number of resistant strains found in bacterial colonies exposed to phage should fluctuate more than if the resistance was induced. Delbrück worked out the statistics and Luria performed the experiment; the results clearly revealed that bacteria underwent mutations.

Delbrück went on to show in 1945, in collaboration with W. Bailey, that phage can reproduce sexually. They were working with the two viruses T2 and T4r, both of which could be bred in bacterium B. They found that:


T2 formed small colonies and attacked bacterium A.
T4r formed large colonies and attacked bacterium C.
When both T2 and T4r were bred together in B, the parent types produced two new strains:
Strain 1: formed small colonies and attacked bacterium C.
Strain 2: formed large colonies and attacked bacterium A.

Obviously, Delbrück concluded, “the parents had got together and exchanged something.”

By this time Delbrück had begun to be recognized as the leader of what became known as the phage group. From 1945 onwards he ran an annual summer phage course at Cold Spring Harbour Laboratory, New York, which was attended over the years by most of the leading molecular biologists of the following decade. For Delbrück himself, however, the mid-1950s seemed to be a good time to move on. He turned to the study of sensory mechanisms in the fungus Phycomyces. It grew towards the light, against gravity, and into the wind. How did it sense these stimuli? What range of light did it respond to? These and other questions were tackled by Delbrück and his coworkers in what was soon called the Phycomyces group. His last published paper in 1981 was in this field and proposed that the chemical photoreceptor of Phycomyces was a flavin and not, as had been supposed, a carotene.

For his earlier work with the phage group Delbrück shared the 1969 Nobel Prize for physiology or medicine with Salvador Luria and Alfred Hershey.

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.

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.

—Richard Robinson

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.