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 Phage and 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 on Max Delbrück

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.