Max Delbrück: Pioneer of Molecular Biology. An Interview with Manuel and Ann Varela

Nov 3, 2020 by

Max Delbrück

Michael F. Shaughnesssy

1) Max Delbrück is a name that needs no introduction to scientists in the field of molecular biology—but where was he born, and what do we know about his early childhood?

Professor and Nobel Laureate Max Delbrück is noted for many pioneering studies of phage genetics. He determined how many viruses burst out of a single bacterium’s cell—the so-called burst size. Delbrück also helped to clearly define the chemical nature of the gene and the mechanism of gene replication. Furthermore, he performed one of the 20th century’s most famous experiments, the so-called fluctuation test. On September 4, 1906, Max Delbrück was born in Berlin, Germany. Delbrück was the youngest of seven children. He was raised in a fashionable district of Berlin called Grünewald. Delbrück’s father, Hans, was employed as a history professor at the University of Berlin and was well known. There is a street named after Delbrück there. His mother, Lina, managed the home and garden.

Many of their neighbors held academic positions. Delbrück’s childhood memories were pleasant until the onset of World War I. After that, his memories were mostly of “hunger, cold, and patriotic war games.”

2) Where did Delbrück go to school, and did he have mentors?

In high school, Delbrück wanted to distinguish himself from his family and neighbors, so he decided to pursue a degree in astronomy to satisfy his interest. Naturally, Johannes Kepler was his newfound idol.Delbrück attended a lecture on wave mechanics, in which Albert Einstein was in attendance. As a consequence, Delbrück changed his focus to mirror the current fascination with quantum theory.

Delbrück began his college career at the University of Tübingen but switched colleges many times before enrolling at the University of Göttingen. Delbrück was a graduate student of Max Born and completed his Ph.D. in physics at the University of Göttingen in 1930. Delbrück’s first thesis was about the origin of a star type. Still, he lacked the mathematical skills and command of the English language to complete this thesis. Not being one to give up, Delbrück changed the emphasis of his second thesis to the bonding of two lithium atoms.

Delbrück received a research grant to continue his postgraduate studies at the University of Bristol in England. There he studied quantum mechanics for almost two years. In the early years of 1930, Delbrück was a postdoctoral fellow, sponsored by the Rockefeller Foundation. Niels Bohr was his supervising professor. After attending a lecture given by Niels Bohr entitled “Light and Life,” Delbrück was captivated with biology. Bohr proposed that living organisms were not reducible to atomic physics. Nevertheless, there could be a complementarity relationship between them, such as what was known for light particles versus waves.

Delbrück became a research assistant at the Kaiser Wilhelm Institute for Chemistry in Berlin from 1932 until 1937. His research in the lab of Lise Meitner sparked his interest in bacteriophages. Delbrück was experimenting with the scattering of gamma rays, more specifically, the Coulomb field’s polarization. He published many papers about his findings relating to the scattering of gamma rays. In 1935, Delbrück published a report of which he co-wrote with Nikolay Timofeev-Ressovsky and Karl Zimmer. The collaboration was titled, Über die Natur der Genmutation und der Genstruktur, which translates roughly to “About the Nature of the Gene Mutation and the Gene Structure.” The treatment applied quantum mechanics to model the gene. The authors proposed that the gene was the “ultimate unit of life.”

3) Delbrück spent time at Caltech University—what did he research there?

In 1937, Delbrück received a fellowship from the Rockefeller Foundation in the United States. The molecular biology department’s research program at California Institute of Technology initiated research in the fruit fly’s genetics, Drosophila melanogaster. Delbrück had recently converted from physics to biology because he wanted to apply the complementarity concept that he had learned in physics and apply it to biology. Furthermore, as he once put it, he kept physics’s progress from moving forward because Delbrück had misinterpreted the findings of specific physics-based experiments. He delayed the work of Lise Meitner and Otto Hahn in discovering nuclear fission.

As mentioned above, Delbrück was eager to discern whether a complementarity relationship existed in biology as it had in physics. He reasoned that because the gene, a yet undefined entity, seemed to replicate itself for the next generation, similar to radioactive reproduction, the gene would make a good target in the search for complementarity. The best place in the world for the study of genetics was Caltech, where Thomas Hunt Morgan was using the fruit fly Drosophila melanogaster in his famous “fly room.” In 1937, Caltech would also provide a needed refuge for Delbrück from Nazi Germany. Interestingly, during the 1930s, Delbrück failed two of his Nazi standards tests, perhaps on purpose, which did not endear him to members of the Nazi Party of the day.

In Morgan’s fly lab, Delbrück applied radiation to fruit fly genes to determine the gene’s size. He invoked a mathematical treatment, called target theory, to calculate the probability that the gene structure would be affected by varying radiation doses. Delbrück felt he could determine how stable the gene was when mutated by radiation. Applying physics to gene stability estimation, Delbrück reasoned that the size of a typical fly gene was about nine microns. In modern times, we know this size to be the equivalent to about 60 genes.

The gene stability work of Delbrück produced a physical picture of the gene. Erwin Schrödinger adopted the idea to explain life’s nature in his now-classic book, “What is Life?” which was published in 1945. Delbrück had envisaged the gene like a state of radiation, having various energy states, similar to those of quantum states in atomic physics. The Delbrück-view of the gene was described in the book and read by the likes of James Watson, Francis Crick, and Erwin Chargaff to focus on genes and biology.

His quantum theories of the gene indirectly influenced others to study genetics. Delbrück’s radiation work with fly genes, however, did not necessarily lend itself closer to understanding the gene’s actual nature. Thus, Delbrück switched to the bacteriophages as a model system for studies of the gene. See Figure 28 depicting a phage structure. In 1938, he met Dr. Emory Elllis, who had a bacteriophage laboratory tucked away in the Caltech building basement that housed Morgan’s fly room. The phage work of Ellis was virtually unknown to most geneticists. Upon visiting the basement lab, Delbrück learned that the phages could be studied with simple lab equipment and glassware.

Furthermore, Delbrück realized that he could enumerate the phage quantities by employing the plaque assay method. The lab method used a bacterial culture, phages, culture media, an autoclave, and a simple incubator. The bacteria formed lawns on Petri plates with culture media. When a phage virus infected a bacterium on the bacterial layer, a hole, called a plaque, would be created. One could count the plaques and use the numbers to study the nature of the gene effectively. In 1939, with Emory L. Ellis, Delbrück coauthored “The Growth of Bacteriophage,” a paper describing how viruses reproduce in one step. The phage work of Delbrück and Ellis would result in a landmark breakthrough in genetics. The discovery was called the one-step growth curve for phage viruses.

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Figure 28. The structure of a typical bacteriophage.

The one-step viral growth experiment was elegant in its implementation. Ellis and Delbrück first added phages to a bacteria culture, permitting the phages to attach to their bacterial hosts. Then, just before the attached phages could enter the bacteria, Delbrück and Ellis diluted the phage-bacteria mixture to remove unattached viruses, washing them away. This dilution and washing process of phages bound to bacteria ensured that the infection process was synchronized for all cells in the culture. The synchronization permitted Ellis and Delbrück to isolate a single replication cycle in the viral infection. Thus, one step, a single replication step, could be studied experimentally. Ellis and Delbrück then took samples of the phage-bacteria complexes, performed the plaque assay, and graphed the growth data. The results were surprising.

Delbrück and Ellis found a consistent so-called eclipse-period, which showed no new phages in the infected bacteria. The eclipse-period lasted perhaps 10 or 15 minutes. It was characterized by a complete loss of infectious phages from the mixture. The failure was later discovered to be the result of the viral genome’s release from the bacteriophage, which then permitted the genome’s genes to be transcribed in the host. The eclipse period was a highly active process of RNA and later protein production.

Then, a closer examination of the one-step growth data showed that a giant burst of phages was released from the infected bacteria at some point in the infectious process. Finally, the phage numbers would level off, producing a plateau on the graph. From these types of data, Delbrück and Ellis could go on to calculate the “burst size,” that is, the number of phages that would burst out of a single infected bacterium, a single cell. See Figure 29.

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Figure 29. Anatomy and infection cycle of phage T4. 1: Attachment of phage’s fibres to a bacterium, 2: Injection of DNA, 3: Synthesis of phage components, 4: Assembly of new phages, 5: Burst of bacterium and release of infectious phages.

The one-step growth cycle experiment now permitted Delbrück and others to examine other viruses, such as those that infected animal cells. These studies, in turn, allowed investigators to explore poliovirus and cancer-causing virions. Notably, the initial phage work of Delbrück defined for the first time in scientific history the chemical nature of the gene. It was learned that these seemingly discrete packets of information, the gene, was a definitive chemical entity. The gene was composed possibly of nucleic acid—at the time was virtually unclear what genes were. The was inaccurately believed that many genes were proteinaceous. Delbrück’s phage work would ultimately lead to others’ discovery that DNA constituted the gene.

4) Then—he traveled to Vanderbilt—what were some of his accomplishments there?

As the end date of his Rockefeller fellowship approached, Delbrück was fortunate enough to find funding, provided by the Foundation and Vanderbilt, as a faculty member in the physics department at Vanderbilt University in 1940. Delbrück taught his courses and occupied an office in the Physics department; however, his lab was located in the Biology Department. In that biology lab, he continued the work initiated at Caltech. He ultimately won the Nobel Prize in the category of Medicine or Physiology in 1969, along with his fellow researchers, Alfred Hershey and Salvador Luria, for their findings involving the replication mechanism and viruses’ genetic structure.

In 1943, Delbrück was a member of the Phage Group, of which both Luria and Hershey were members. In 1945, Delbrück organized the first of his summer phage courses at Cold Spring Harbor on Long Island, New York. These summer courses ran for twenty-six years. He remained at Vanderbilt until 1947, teaching physics.

Delbrück returned to the California Institute of Technology in 1947 as a biology professor and remained there until he retired in 1977 and became Professor of Biology Emeritus.

5) In 1942—Delbrück and Salvador Luria researched and published on bacterial resistance to virus infection. The issue here was that the viral infection seemed to be mediated or changed by random mutation. Why is this important?

Max Delbrück and Luria would collaborate to perform what is considered by many scientific historians as one of the most meaningful experiments of the 20th century, the co-called fluctuation test. The pioneering investigation arose out of an attempt to rectify two seemingly controversial viewpoints regarding evolution. One view held that hereditary traits were passed to the next generation from an organism that had picked up the quality or acquired it by an environmental deed. One example was proposed by Trofim Lysenko, who was Stalin’s favored geneticist. Lysenko invoked Jean-Baptiste Lamarck to argue that exposure of wheat to the harsh Russian winters produced winter-resistant grain. Lamarck had stated that finches acquired more rigid beaks if exposed to hard seeds or that antelopes achieved longer necks by stretching them to forage in tall trees.

The other view was that in a population of organisms, genetic variation existed among the individuals. Natural selection played a role in an organism’s success in passing along favorable traits, a process referred to as a random mutation. Suppose, by chance, an individual has a specific genetic feature that permits its survival. In that case, it could pass its genetic complement to the next generation. The successful individual had already possessed the beneficial quality from its parents. Random chance favored the natural selection of that trait for propagation into the next generation.

In 1942, Delbrück and Luria came up with a brilliant experimental design to test the Lamarckian view, called physiological adaptation, versus the random mutation hypotheses. The famous experiment came to be known as the fluctuation test. The reasoning behind the experiment was as follows.

If a mutation that confers a favorable trait, like phage resistance, is random and spontaneous, then there would be a significant fluctuation in the numbers of resistant mutants per bacterial culture. The fluctuation in resistant mutant numbers would occur positively and independently of the phage’s presence. If indeed a random mutant selection was correct, it predicted that a bacterium that mutated early on during its culturing would produce many mutant progenies. If a bacterial mutation appeared late in the incubation period, fewer mutant progeny would occur. Furthermore, if no resistant mutants occurred, then no such progeny would appear. In other words, the mutant numbers would fluctuate widely if a random and spontaneous mutation process were correct. Thus, it was the essence of the Darwinian model of natural selection.

On the other hand, if Lamarckian inheritance were responsible, then bacterial resistance to phages would only be acquired if the phage was present. It predicted that culturing bacteria in the presence of phage would result in the production of resistant mutants. Further, different bacteria cultures, each with phage, would generate roughly equal numbers of resistant mutants. The hypothesis also predicted that cultures without phages would have no resistant bacteria.

To distinguish between these two hypotheses, i.e., the induction of mutants via Lamarckian adaptation versus a natural selection of spontaneous mutants in a population, Drs. Delbrück and Luria conducted the fluctuation test. They grew a phage-sensitive bacterial culture in a large glass flask without the phage being present during the growth. Next, Delbrück and Luria dispensed the phage-sensitive bacterial culture into hundreds of individual test tubes, without phage. The new cultures were allowed to grow to saturation. Both the large flask and the hundreds of test tube cultures were grown to saturation.

Then, Delbrück and Luria took many samples from one large flask and conducted the plaque assay. They plated all of the bacteria strains onto many agar Petri dishes containing phage in the top agar medium. Likewise, they took a small volume of bacteria from each of the hundreds of test tube cultures. Similarly, they plated these samples onto Petri dishes with phage in the agar medium. Both sets of Petri plates were incubated overnight and allowed to form plaques on the bacterial lawns. The lack of plaque formation represented a phage-resistant bacterial mutant, whereas the plaque-forming represented phage-sensitive bacteria. The results were clear-cut if not startling. The data would forever change the face of genetic research and give birth to molecular biology.

Delbrück and Luria saw similar numbers of phage-resistant on plates originating from the large flask. The mutants in the large flask had been distributed throughout the liquid medium. Thus, the numbers of resistant mutants were similar per plate.

In contrast, highly fluctuating numbers of phage-resistant bacteria appeared on the plates. These plates had been inoculated from the hundreds of individual test tube cultures. The fluctuating colony number indicated that the resistant mutants arose at different times during growth. The mutants had appeared spontaneously and randomly during the culturing period.

If the induction hypothesis had been correct, then no mutants would have appeared as there was no phage in the original flask to induce such mutations. Therefore, the famous fluctuation experiment of Delbrück and Luria demonstrated that mutations that confer a beneficial trait, e.g., phage resistance, occurred randomly, not because of induction by the phage’s presence. The Lamarckian hypothesis had been dealt a severe death blow, and few scientists from then on have since given it serious consideration.

6) Mutations—seem to be singularly random events that happen—whether they are helpful or useful. Is this still pretty much the same and the shared wisdom?

Indeed, mutations can be chance or random events in natural circumstances. A mutation is defined as an alteration in the base sequence of a DNA string. These nucleotide base changes in DNA can sometimes affect the coding properties for producing RNA and proteins. Often, mutations can be faithfully propagated during DNA replication when making progeny or daughter DNA for the next generation of organisms. During DNA synthesis, the cellular machinery devoted to copying the parental generation’s DNA for the daughter’s generation can be amazingly accurate.

Under naturally occurring circumstances, DNA mutations appear spontaneously and in a random manner. These random spontaneous mutations are, however, permanent. Mutations that appear in the DNA of a somatic cell stay with those cells until it dies. The mutant cell is, thus, not propagated to subsequent generations of the organism. Suppose mutations occur in the DNA of reproductive cells, such as sperm or eggs of eukaryotes. In that case, during fertilization, the altered nucleotide sequences can go to the next generation. In prokaryotes, however, the modified base sequences will be transmitted to new generations during binary fission.

The base error rate of the DNA replication machinery, while highly accurate, is nevertheless not zero. Furthermore, the range of the random and spontaneous DNA sequence errors varies tremendously. The spontaneous mutation rate ranges between one in a thousand to one in a billion for every living cell division. Thus, a random mutation can occur spontaneously once in a thousand cellular divisions for a given gene. In contrast, a different gene might experience a nucleotide sequence modification once in every billion cell divisions.

The nucleotide base mutation rate can dramatically increase if DNA is exposed to mutagens, producing induced mutations. Mutagens generate the induction of DNA base alterations. That is, mutagens mutate DNA by changing the base sequence. There are two general types of mutagens called physical and chemical. The physical mutagens consist of radiation, such as ultraviolet light or X-ray and gamma-ray radiation. The ultraviolet light mutates DNA to produce thymine dimers. Two neighboring thymine bases on the same DNA strand are connected abnormally by a covalent bond, resulting in an abnormal kink structure in the double helix of DNA. Gamma- and X-rays break DNA molecules. DNA serves a template role for its replication and RNA synthesis. Thus, physical mutagenic agents can disrupt DNA synthesis and impair transcription.

Chemical mutagens can alter the base sequences of DNA, creating mutations. Several classes of chemical mutagens are known. One type is represented by the base-analogs, which vary base-pairing properties. Alkylating chemicals add specific chemical substituents called alkyl groups, like methyl groups (–CH3), to nucleotides, which then exhibit alterations in their base pairings. Likewise, deaminating agents remove amino groups (–NH3) from DNA bases, affecting their base associations. The chemical results of these types of mutagens are base substitutions. A different one replaces the original nucleotide base. These nucleotide substitutions are often referred to as point mutations because a specific point in the DNA double helix has been affected.

Another type of DNA mutation is called a frameshift. Some chemical mutagens are known to distort the double helix structural motif of DNA, which permits the insertion or the deletion of nucleotides into the distorted DNA. The addition or subtraction of bases into DNA can alter its transcriptional and translational reading frames of the genetic code. Typically, frameshift mutations produce premature stop codons in the genetic code of a gene. The result is a shortened protein. The truncated protein is abnormal, and it will be degraded readily. Thus, frameshift mutagens can result in the complete removal of a gene’s end-product, perhaps having severe detrimental consequences upon the organism. Another result of exposure to physical and chemical mutagens can be the generation of tumors, and some tumors can be cancerous. Such agents are known as carcinogens.

7) Delbrück’s Nobel Prize— for what was it granted?

In 1969, Delbrück shared the Nobel Prize in medicine or physiology with Drs. Salvador Luria and Alfred Hershey because of their work dealing with the viral replication mechanism in living cells and viruses’ genetic structure. Hershey’s role in the Nobel’s bestowment stems from his work with Martha Chase. During bacteriophage infection of bacteria. They discovered that the phage’s DNA entered the host. Thus, Chase and Hershey pointed to DNA as the hereditary material in living organisms. Luria and Delbrück would work together to make several significant discoveries, ensuring their role in earning the Nobel. While Luria’s part is somewhat intertwined with that of Delbrück, Luria nevertheless had several other contributions. Luria had also demonstrated that mutations could occur in bacteriophages. He also studied the phenomena of lysogeny in bacteria and transduction by phages of bacteria. Luria’s primary interest with phages was geared towards knowing the nature of the gene.

Delbrück’s main interest, on the other hand, was in understanding the reproductive role of phages in bacteria. In general, it has been reported that Delbrück received the Nobel for two primary reasons. The first discovery was the famous 1943 Luria- Delbrück fluctuation experiment, described in detail above, demonstrating spontaneous mutation drove the evolution of microorganisms. The second great discovery involving Delbrück was made in 1946. He and Luria provided experimental evidence of genetic recombination in mixtures of phages during simultaneous infection of bacteria. In the early 1940s, Luria and Delbrück had studied the relationship between a given phage and a bacterium. It would be the first work they published together. They had become curious about the phage activities that occurred inside of the bacterium. They were well aware that the infecting phage made more of itself while inside the bacterial cell. But Luria and Delbrück were at a complete loss about how the viral replication process occurred inside the bacterium.

They reasoned that studying two types of phages would lend insight into these intracellular viral activities. One phage type was slow in its infectious ability to kill a bacterium by lysis. The other phage type was more rapid in its bacterial lytic activity. They reasoned that by mixing the fast and the slow phages, the infection might result in the fast virus breaking open the bacterium while it made the slow phage. Hence, they had expected an intermediate stage of infection to emerge between the two viruses, the fast and the slow phages. Instead, they were much surprised by the observed results of the famous mixed-infection experiment.

Delbrück and Luria observed that the two phages, the fast and slow viruses, interfered with each other while inside the host cell! They termed this novel phenomenon “mutual exclusion” and “interference.” Such a spectacle had never been observed before in the history of molecular biology. Delbrück had gone back to his physics days to name the new marvel. He had recalled that he had once written about the so-called physics principle of mutual exclusion. He now invoked these physics-based terms to apply them directly to principles observed in biology.

Following up on the newly discovered phage interference process, Delbrück would learn that during mixed infections, the genomes of the different infecting phages inside a bacterium would recombine. He had become a member of the famous Phage Group, a team of pioneering molecular biologists convinced the gene’s nature would be discovered if one studied the bacteriophage. Delbrück also became quite involved with the equally famous Phage Course he had developed each summer at Cold Spring Harbor, New York.

Working with W.T. Bailey, Jr., Delbrück studied an interesting mixed-phage infection using two specific phages. First, they examined a phage called T2, which formed tiny plaques on lawns made by two bacterial strains of Escherichia coli, called A and B. The second phage was called T4r, for rapid lysis of an Escherichia coli called strain C. When phages T2 and T4r were mixed and used to infect Escherichia coli, both the original T2 and T4r parental phages could be shown to emerge from the lysed bacterium. However, additional phage variants emerged!

One of these two new variants was called T2r, and the other was named T4. It had seemed that their properties had been switched. Delbrück reasoned that inside the bacterium, the T2 and T4r parental phages merged their genomes to produce the new T2r and T4 variants. The result would be interpreted as the first scientific evidence for the genetic recombination between two disparate genomes, producing genetically exchanged variants. At first, Delbrück was disappointed. While extremely interesting and ultimately crucial to molecular biology’s birth, the phenomenon of genetic recombination went directly against Delbrück’s notion of mutual exclusion, one of his favorite ideas.

In modern times, the mutual exclusion data can be interpreted as a form of genetic recombination. The two phages could combine different parts to produce a new variant that emerged from the burst cells. Ironically, the phenomenon has been called complementation. Two mutant phages defective in one distinctive viral part cannot infect a cell. But when recombined, the defective sections are complemented by the other phages’ healthy functions, forming an intact and functional phage variant.

8) Max Delbrück has a plaque (Figures 30 and 31) honoring him and his work at Vanderbilt. Can you summarize his main contributions to modern molecular biology?

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Figure 30. A drawing of a plaque in Buttrick Hall, Vanderbilt University memorializing the life of Max Delbruck.

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Figure 31. Bronze Bust, Max Delbrück by Hans Scheib, 2003, Robert-Rössle-Straße 10, Berlin-Buch, Germany.

Max Delbrück is considered among many to be a founding father of molecular biology. His contributions to the field are both legendary and legion. One of Delbrück’s earliest influences has to do with providing a more exact notion of the gene’s nature. In 1935, he had reasoned that the phages either were or contained genes. We know in modern times that phages harbored genes and were collections of proteins that enclosed the genes. Delbrück also reasoned genes were the “ultimate units of life,” which meant that genes were considered targets for alteration, such as that seen in mutagenesis. Along these lines, Delbrück provided an astonishingly convincing set of data in the legendary fluctuation experiment. He established a fundamental molecular basis of evolution, namely, that natural selection encompassed naturally occurring spontaneous mutations drove genetic variation. Some historians of science have traced the birth of molecular biology, if not the birth of bacterial genetics, to February of 1943. On this date, Max Delbrück, T.F. Anderson, and Salvador Luria published their fluctuation studies in a groundbreaking article published by the Journal of Bacteriology.

Other contributions to molecular biology included his quantum mechanical treatment of the gene itself. Delbrück lent an insight into complementarity that he had sought for so many years, as inspired by his mentor Niels Bohr. Similarly, Delbrück studied the gene stability characteristics using his physics background to do so. Though he was somewhat off base with the gene’s quantum nature, he was nevertheless years ahead of his time when he considered gene at the atomic level. It was part of his push to learn about genetics from the standpoint of the “atoms of biology,” a property that Delbrück used to describe phages.

As mentioned above in some detail, Delbrück conducted the 1939 one-step growth experiment. The famous investigation had shed significant new light on the replicative nature of viruses in bacterial host cells. In this vein, Delbrück’s work is often confused with studies of DNA replication. The truth is that his discoveries have relevance to viral replication in the form of reproduction or multiplication, not necessarily with DNA synthesis, which is confusingly also called replication. In the case of Delbrück, we are concerned with bacteriophage replication in terms of its reproduction to produce new phage progeny.

Of course, Delbrück is noted to have discovered a new method for determining the burst size of viruses per infected cell. In modern times, students of virology laboratory courses will often perform the burst size experiment themselves, attesting to an experiment’s contemporary relevance first performed in the early 1950s.

The epic world of molecular biology has its origins in the process of genetic recombination, and Delbrück would prove that his work was a critical factor in its emergence. He was one of the first to grudgingly admit that different phage viruses were exchanging genes inside the confines of a bacterial cell. Although genetic recombination has its relevance in molecular biology and will continue to do so for millennia, Delbrück was reluctant to give up mutual exclusion to do so. His reluctance to new ideas like genetic recombination appears to have stemmed from a personality trait that he often exhibited. He repeatedly announced that he “did not believe a word of it” when new data was presented to him, independent of its nature, the excitement, or the importance of the findings.

9) What have I neglected to ask?

Mary Bruce married Max Delbrück in 1941, and he became a U.S. citizen in 1945. The couple had four children.

Interestingly, when Fritz Lipmann, a Nobel Laureate who shared the honor with Hans Krebs, would study a milk-fermenting bacterium called Lactobacillus delbrueckii to honor one of the Delbrück’s, though it is not clear who. The lactic acid microbehas been used in food microbiology circles to make rye bread and soy sauce. The Lactobacillus delbrueckii is a probiotic ingredient in yogurt, contributing to its aroma and flavor.

Delbrück was noted to have the impression that,

[A] scientist can bring much more change into the world than any politician or military leader, and he can do so by just sitting in his office and thinking.”

Moreover, Max Delbrück loved to do this all the time.

In addition to the 1969 Nobel Prize in Physiology or Medicine, Delbrück was selected to be a Foreign Member of the Royal Society (ForMemRS) in 1967. Delbrück was elected an EMBO Member in 1970. Max Delbrück Prize, formerly known as the biological physics prize, is awarded by the American Physical Society and named in honor of him. The Max Delbrück Center, located in Berlin, Germany, and the national research center for the Helmholtz Association’s molecular medicine, also bear his name. At Caltech, a seminar room, the Delbrück Lounge, is named after him.

In later years, Delbrück would switch his research interests to the fungi. One fungus in particular that caught his eye was called Phycomyces. See Figure 32. He measured the fungal response to light exposure by examining its ability to use light availability to disperse its spores for later reproduction. The fungal work produced astonishing dramatic images of the Phycomyces responding to light and presenting spores for dissemination. He would show that the Phycomyces harbored dedicated photoreceptors to seek the light.

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Figure 32. Phycomyces Kunze.

An exciting finding concerning genetic mutations has to do with sabbatical work he conducted while still amid the fungi-light studies. Because Delbrück could not take his fungal spores with him on sabbatical to Germany, he studied the relationship between “light and life.” The work had to do with the effects of UV light upon the chemistry of DNA. Here, Delbrück studied the photochemistry of thymine dimers. He looked at a phenomenon known as photoreactivation, a process in which UV light exposure converted a lysogen into a lytic type of phage. Delbrück published the hobby-like work in 1963 but quickly returned to studies of light and Phycomyces upon returning to Caltech. The Germany trip had been taken because of an agreement made before his exit from war-torn Europe. He had promised to return from the U.S. to Germany to obtain permission to leave the country in the late 1930s. But as the Second World War went into full swing, he astutely decided not to return during the war.

He continued his work with Phycomyces, generating mutants that altered their visible characteristics on plates. One set of mutants was called “car” because of the inability to grow without added β-carotene. The Phycomyces mutants could not finish the biochemical pathway leading to the biosynthesis of β-carotene, giving the mutants an altered color that differed from the wild type parental fungi. Another breakthrough occurred in the Delbrück laboratory when Dr. Enrique Cerdá-Olmedo, a postdoctoral fellow, helped discover fungal behavioral mutants. These new mutants were called mad, for Max Delbrück, and they altered their behavioral responses to light. They found other fungal mutants with adverse reactions to external environmental factors like gravity or physical barriers. The mutants avoided these factors, producing a so-called avoidance struggle. Delbrück and his laboratory would discover that many of these genetically altered behavioral mutants were defective in specific signal transduction machinery. They could track the mutant fungus movement as it made its way in the dark and in the light. It was to be some of Delbrück’s last scientific work.

Max Delbrück died on March 9, 1981, in Pasadena, California.

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