Salvador Luria, 1912-1991: A Scientist for Our Time

Yves here. KLG was not being ironic in writing his title. Nobel Prize winner Salvador Luria was not simply a highly accomplished scientist but also an honorable man: a dedicated administrator and teacher, and a public intellectual back in the day when serious thinkers wanted to advance ideas, not themselves.

Luria is a model for what a scientist or a serious professional should aspire to be. But lofty aims are out of fashion.

By KLG, who has held research and academic positions in three US medical schools since 1995 and is currently Professor of Biochemistry and Associate Dean. He has performed and directed research on protein structure, function, and evolution; cell adhesion and motility; the mechanism of viral fusion proteins; and assembly of the vertebrate heart. He has served on national review panels of both public and private funding agencies, and his research and that of his students has been funded by the American Heart Association, American Cancer Society, and National Institutes of Health

Although it undoubtedly looks better in retrospect than it was at the time, there really was a Golden Age of Biomedical Science. It began after World War II and extended through the 1980s and into the 1990s. At the clinical end of the spectrum, Sidney Farber and others began to search in earnest for pharmacological cures of cancer while focusing on childhood leukemias, which now are one of the few cancers that can be cured outright (albeit sometimes with serious sequelae). That story has been told in The Emperor of All Maladies (2010) by Siddhartha Mukherjee. 

At the other pole was the rise of modern molecular biology, which has been described for the general reader in The Eighth Day of Creation (1979; still in print at CSHL Press and on sale!) by Horace Freeland Judson. Although there were a few dissidents, such as my first research mentor, who did later come around, and Erwin Chargaff of Chargaff’s Rules, who stated only somewhat tongue-in-cheek that “molecular biology is the practice of biochemistry without a license.”

With all respect to Chargaff and the old-school biochemists who taught me at my beginning: Actually, no. Molecular biology was and is different in focus, emphasis, and design. But it is true that good molecular biologists also pay attention to their biochemistry. The running joke made by biochemists is that if you ask a biochemistry graduate student how much crude protein was used in that experiment, she will say “50 micrograms.” If you ask the molecular biology graduate student he will reply “15 microliters, because that’s what “Maniatis” said to use.” The molecular biologist would then retort that the “what” is just as important as the “how much.” But I digress. Again.

Salvador Luria was one of the founders of modern molecular biology, but his contributions are not nearly as well-known as they should be. The story of his life and work is told succinctly but with justifiable enthusiasm in the biography just published by Rena Selya, Salvador Luria: An Immigrant Biologist in Cold War America. As one who believes that acknowledgments should come at the beginning, when possible, I want to thank the now retired but fondly remembered Naked Capitalism stalwart Jerri-Lynn Scofield for telling me last month that this book had been published by MIT Press in October. Otherwise, I would have missed it!

Salvador Luria was born into a Jewish family in Turin in 1912. He was 10 years old when Benito Mussolini was appointed prime minister by Victor Emmanuel III. His first biological research was conducted as a medical student at the University of Turin in 1930, when he worked in the laboratory of Giuseppe Levi, who was a histologist (histology is the study of cell and tissue structure, generally using microscopy) and anatomist.

Although histology is now largely the clinical science of pathology, in the early 20th century it was at the cutting edge of biology and has since formed a large part of the essential foundation for the molecular, cellular, and systems biology of today. Although Luria did not find the work particularly interesting at the time, Professor Levi taught the young medical student how to do science by thinking well, completing the work, and publishing it. Every young scientist requires this very specific mentorship.And while it is a coincidence that Salvador Luria was joined in the Levi laboratory by Rita Levi-Montalcini and Renato Dulbecco, it is not a coincidence that all three were awarded a Nobel Prize in Physiology or Medicine for their subsequent research on bacteriophage, growth factors, and tumor viruses, respectively.  In the United States as it turned out.

After medical school, Luria completed his obligation to serve as a medical officer in the Italian army.  When his military service ended in 1937, he moved to Rome to pursue a residency in radiology at the University of Rome and where he also worked in the laboratory of Enrico Fermi.  It was then that began to consider a career as a scientist rather than as a physician, which he recalled was a time of “torment, although a delicious one” as he struggled through courses and laboratory experiments.  At the time, the nature of the gene as the unit of inheritance was an unanswered question, and Luria thought to use radiation as a tool to identify small structures, such as the then hypothetical gene, that were not easily studied by other techniques.  But in 1938 with the Manifesto of Race, Mussolini finally made it impossible for a Jew to pursue a professional career in Italy.  

With the blessing of his family, Luria moved to Paris where he joined the laboratory of Eugène Wollman, who was a pioneer in the use of bacterial viruses (bacteriophages) as experimental models in biological research.  When the Nazis invaded France in May 1940, Luria applied for a visa to the United States as an Italian refugee.  He escaped Paris on a bicycle, eventually making his way to Marseilles, where he studied physical chemistry on his own.  He then traveled across Spain to Lisbon, where he was granted a visa.  He arrived in New York in September 1940 with $52.  Eugène Wollman was murdered in Auschwitz in 1943.

At the beginning of his study of what became known as molecular biology/genetics, Luria had made preliminary contact with Max Delbrück, whose papers on radiation genetics had been Luria’s introduction to the subject.  Delbrück was a physicist who became a leader in the development of molecular biology as a discipline, and several other physicists were indispensable in the creation of molecular biology as a discipline (see Footnote #1).  Biologists have subsequently come down at times with a relapsing, remitting form of “physics envy.”  This can be useful but not when combined with “theory envy.” 

As I have previously mentioned in this series, “theory” has had a checkered past in biology, which lacks a Higgs boson.  Biology does have more than three billion years of evolutionary history, however, and physicists were instrumental in the establishment of the Theory of the Gene by asking questions such as: What is the gene?  Is the gene a particle?  How big is the gene?  Is the gene a unitary object that contains the information of inheritance?  What is the nature of mutation?

The key to the success of Luria’s research as part of the Phage Group was picking an experimental model that could answer the questions asked with Yes, No, or Think Again.  All good biologists do this at whatever level they work – molecules, organelles, cells, organisms, ecosystems.  The biology of viral infection of bacteria was a near perfect model to answer questions about the nature and function of the gene. 

Luria and the Phage Group described conditions and mechanisms of viral replication, how mutations affected infection and replication, the co-linearity of the gene sequence and protein sequence, how DNA replicates semi-conservatively using one strand of the double helix and the template for replication of the other strand, and the mechanism by which a bacteriophage such as lambda can infect a bacterial cell and remain dormant in the lysogenic phase (capable of replication and subsequent lysis of the host cell) or immediately replicate within the cell and cause the cell to lyse (lytic phase) and release thousands of mature virus particles that can infect other cells…things that animal and plant viruses do.  

Alfred Hershey and Martha Chase used bacteriophage to prove that DNA is the genetic material.  Experiments in Luria’s laboratory accidentally indicated that bacteria have a defense against viruses.  He called this restriction-modification.  Later, restriction enzymes were recognized as enzymes that cleave viral (and other DNA) at specific sequences.  Every molecular biologist knows that the recognition sequence for EcoRI (pronounced Eco-R-one) from the bacterium Escherichia coli is 5’-GAATTC-3’.  These magic scissors made the practice of DNA manipulation in modern molecular biology possible, long before the polymerase chain reaction was developed.  Gene cloning was facilitated by the development of a variant of phage lambda as the vector that allowed for the creation of libraries containing as many as 300,000 clones that could be identified using probes specific for each [which I did at the Roche Institute of Molecular Biology (RIP) 36 years ago].  Luria was awarded the Nobel Prize in Physiology or Medicine in 1969 along with Alfred Hershey and Max Delbruck “for their discoveries concerning the replication mechanism and the genetic structure of viruses”.  

Salvador Luria’s contribution to molecular biology is quite enough reason to write his biography, but the subtitle of the book is “An Immigrant Biologist in Cold War America.”  The latter is just as important, and Rena Selya provides an excellent account of why.  That Luria was a refugee from Mussolini’s Italy and Hitler’s Europe undoubtedly conditioned him to look at things in the United States as a citizen as he moved through Indiana University, the University of Illinois, and the Massachusetts Institute of Technology (MIT) from 1942 until his death in 1991.

While helping establish virology as an independent discipline at IU in the 1940s – where James Watson, a 19-year-old graduate of the University of Chicago who knew a lot about birds was his first graduate student at IU – yes, that Watson of Watson & Crick – the young Professor Luria was “attracted to (Henry) Wallace’s vision of America as a world leader for peace and democracy, and supported the citizens’ movement that seemed to be a ‘genuine enough new political movement against the social retrenchment of the Truman years and the beginning of the Cold War, with its testing of atom bombs and the growing nature of nuclear war.” 

Luria served as a delegate to the Progressive Party convention in July 1948 and was a poll watcher on election night.  Quite naturally, J. Edgar Hoover took an interest in this Italian immigrant with unsound political views and directed that an FBI File on Salvador Luria begin.  When Luria was invited to speak in 1951 at the meeting of the Society for General Microbiology in Oxford, his passport application was summarily denied as because “Your proposed travel would not be in the interests of the United States.”  Okay, then.  Another in a long line of outrages brought on by fear.

Luria had moved to the University of Illinois in 1950, where in 1955 he raised concerns that the annual meeting of the American Association for the Advancement of Science (AAAS), which publishes the journal Science, was scheduled for Atlanta.  “The City Too Busy to Hate” did have some of that character but nevertheless Jim Crow was alive and well, and the city was segregated in its so-called “separate but equal” bubble that would prevent scientific colleagues from sharing accommodations in the city’s hotels and restaurants.  The protests did not stop the meeting, but they were heard.  Not until 1990 did the AAAS return to the Deep South.  Progress, of a sort.  

While the Luria’s lived in Bloomington, Indiana, Salvador’s wife Zella had earned her PhD in Psychology, but because of ridiculously strict nepotism rules at UI, she could do no more than teach an occasional course in the psychology department.  Thus, when MIT came calling the Luria’s were inclined to answer, and despite the pleas of the Dean at UI for them to stay, go they did. 

While at MIT, Salvador Luria hit his stride, beginning the conversion of MIT into the colossus of modern biology that it is today.  Prior to the 1960s biology was not a discipline.  Rather it was a congeries of separate fields, each with its own way of apprehending the natural world.  The gap between the classroom and the frontiers of research was an abyss.  Botany and Zoology and Microbiology departments remained separate through the 1990s in many institutions; I was offered a position in a Department of Zoology in 2000.  While this made a certain conventional sense, Luria and his colleagues saw through the futility of such division.  

As the Department of Biology flourished, along with that came the MIT Center for Cancer Research.  The key to that success was Luria’s insistence that “cancer research” was likely to be successful only if it was not focused on cancer itself, which is a thousand different diseases, but rather the cell biology and genetics of the cancer cell.  When the American Cancer Society pushed for the War on Cancer as an analog of the Apollo Program, Luria pushed back.  Rightly. 

And this is why, 31 years after his death, Salvador Luria remains a scientist for our time.  Our current President has successfully pushed ARPA-H, a DARPA knock off, using the exact same emotion as in 1970.  It didn’t work then and is unlikely to work now, no matter how many billions are spent on a “moon shot” to cure cancer, Alzheimer’s disease, and a host of other diseases.  Which is not to say that the research support is unwelcome.  Nor should it be. 

But the Apollo Program, fabulously illustrated here, was basically a technical problem of keeping the astronauts alive for the trip whose underlying physics would have been nothing much new to Newton or Kepler.  Biology is not physics.  Directed fundamental biomedical research, along with being an oxymoron, is akin to “Theory” in biology.  The yield has been historically low for the effort expended, whatever the press releases say, and the opportunity costs are unmeasurable but likely to be large.  The MIT Center for Cancer Research was inevitably succeeded by the Koch Institute for Integrative Cancer Research at MIT and before that the Whitehead Institute was established.  Along with the Broad Institute of MIT and Harvard these entities are very rich, very visible, and outwardly productive.  One can only hope they meet expectations.

And expectations are high.  Which brings us back once again to Salvador Luria as the scientist and citizen for our time.  Along with several others, Luria was a leader in the local and national responses to the issues of his day: “If Arthur Schlesinger, Irving Kristol, and John Kenneth Galbraith (not sure I would put JKG in this particular group) represented the elite intellectuals, Luria, (Everett) Mendelsohn, (Hilary) Putnam), and (Noam) Chomsky saw themselves as the public’s intellectuals, who chose to communicate their ideas about national policy directly to the American People.”  Chomsky is still going strong at age 94. 

For example, when Edward “Father of the Hydrogen Bomb” Teller published an article in the Saturday Evening Post about how to prepare for and survive nuclear war, Luria and the others replied in no uncertain terms that Teller’s plan was “a signal example of the combination of factual error and emotionalism which might lead to…catastrophe…not only an illusion, but also a tragic dissipation of all hope for the future.”  Yes, exactly what we should expect from scientists who are also citizens.  We could do with more of this kind of response now, in the Age of Global Pandemic, which is a topic for another time.

Luria published “The Microbiologist and His Times” in 1968.  The title was taken from an essay by Albert Camus “The Artist and His Time” in which Camus raised the issue of the “responsibility (and) recognition of the consequences of one’s activities and the willingness to face up to them.”  Luria asked his fellow biologists to examine their responsibility to science and society, because “it is painfully clear that the findings of science can all too easily be employed, not to enrich the human experience, but to make it more painful.”  He asked that his colleagues consider two issues: Genetic manipulation and eugenics and the application of science to warfare. 

In fairness, Luria also asked “whether MIT was a university with many government research institutions appended to it or a cluster of government research laboratories with a very good educational institution attached to it.”  Unsurprisingly, Luria was early in the fight against the gross oversimplifications of sociobiology, even before E.O. Wilson published Sociobiology: The New Synthesis in 1975.  And he had no use for those who claimed that differences in “intelligence” among different groups were based in anything other than the misuse of Alfred Binet’s insight and socioeconomics.  These were and remain problems that biology has no answer for, other than the trite response that poor environments do not lead to human flourishing.  

In 1972 Salvador Luria was a member of the AAAS Committee for Science in the Service of Life, which produced the statement:

As scientists we cannot remain silent while the richest and most powerful nation of the twentieth century uses the resources of modern science to intervene in the problems of poor and distant lands.  Our Association objective “To increase public understanding and appreciation of the importance and promise of the methods of science in human progress” compels us to refute the view that scientists and engineers are responsible for and endorse, by their actions or by their silent consent, the wanton destruction of man and environment, in this case through warfare.

This was naturally a response to the War in Vietnam, but the lesson held for other issues of that day and ours such as air and water pollution and the abuse of the land as a sink for industrial waste (coal production using “mountaintop removal and oil drilling through fracking come immediately to mind).  What is most remarkable in this statement is that the “Committee members were explicit in their acceptance of special responsibility for speaking out against the war by virtue of their unique position in American culture.  As scientists and citizens they had a double charge to reject the violence done in their names.”

Hmm, by virtue of their unique position in American culture…Where are the scientists like Salvador Luria and his colleagues today?  Are they giving TED Talks on how science, which could be a force for good in this world had it not been corrupted by cupidity brought on by the Late Neoliberal Dispensation, can provide a path to a livable future?  I think not.  They are undoubtedly keeping their heads down while working on their next NIH grant in a world in which 4 out of 5 applications are not funded.  And who can blame them?  No grant money, no job.  Unless and until we return to an era in which undirected basic research returns to prominence and 2 out of 3 research grants are funded, eventually, the outlook is dismal.  But we can do this.  But those relatively few scientists un-enamored by their place in the Professional Managerial Class (PMC) will be required to speak up, as both scientists and citizens.  I remain hopeful we will follow the example of Salvador Luria and do so.

It is fairly obvious that Salvador Luria has a guiding light for me for a long time.  Yes, like all of us he was a mortal with the usual run of human failings.  But from a distant time and space, I feel like his long-time assistant, Nancy Ahlquist, who commented that others told her that “she will either love Salva or hate him, but I never found out what I was supposed to hate.” 

I have not even mentioned that Professor Salvador Luria was a teacher of the first rank, which came to me through his 36 Lectures in Biology (1975) when I was beginning to think as a biologist, thus making a hash of the common but ridiculous saying among my tribe, “Those who can do, those who can’t, teach.”  And as Gunther Stent commented in 1969 after the Nobel announcement that October, “Although it would be difficult to imagine three personalities more unlike than those of Delbruck, Luria, and Hershey, they have one trait in common – total incorruptibility – and it was just this trait…that these three men managed to impose on an entire scientific discipline.”  Several other areas of biology have been as well formed.  For example, Edwin Krebs and Edmond Fischer established reversible protein phosphorylation as the major regulatory mechanism in eukaryotic cells of all types.  For 25 years every biochemist, with few exceptions, who worked on protein phosphorylation did so the integrity and generosity of Fisher and Krebs.  Finally, the photograph on the dust jacket of Salvador Luria: An Immigrant Biologist in Cold War America, with his smile and the peace pin on his left lapel, says it all.  From his time as a medical student in pre-war Turin to his Nobel Prize and beyond, he was a scientist for his time.  And for ours.