Lasker~Koshland
Special Achievement Award in Medical Science

Award Presentation by Stanley Cohen
Recently, I re-read The Microbe Hunters, Paul De Kruif's classic book about scientists and discoveries that provide the foundation for current knowledge about the microbial world. The book recounts medical research from Antonie van Leeuwenhoek, the seventeenth-century inventor of the microscope and the first person to actually see bacteria, to Louis Pasteur, Robert Koch, Paul Ehrlich, Elie Metchnikoff, and others. De Kruif's classic was published in 1926; if updated for this century, Stanley Falkow would surely merit inclusion in the pantheon of great microbe hunters. During a scientific career that has spanned more than five decades, the magnitude and breadth of Falkow's contributions to an understanding of how microbes cause disease and become resistant to the antibiotics used to treat infections have made him a giant among microbial biologists.

Falkow was born in 1934 during the depths of the Great Depression into a Ukranian/Polish immigrant family living in Albany, New York. In a remarkable autobiographical article published earlier this year, he described his childhood in a noisy, colorful neighborhood of tenement row houses filled with a mélange of languages, smells, and customs. Notwithstanding his claim that he was a terrible student, at age 11 Stanley decided that he wanted to be a bacteriologist, and he later began to pursue that goal in earnest. As a young Brown University graduate student carrying out Ph.D. thesis work at Walter Reed Army Medical Center with an older microbiologist named Lou Baron, Falkow found that extrachromosomal pieces of bacterial DNA known as plasmids could transfer themselves even to bacteria that were not closely related. Falkow then helped to prove that differences in composition between the plasmid DNA and the chromosome of the new host enabled the plasmid to be detected biochemically. At that time, the problem of multi-drug antibiotic resistance, which first had been observed in the late 1950s, was becoming the focus of increasing worldwide attention, and the approaches that Stanley pioneered were quickly applied for investigations of the molecular nature of resistance plasmids.

Stanley accepted a faculty position at Georgetown University and during the next decade continued to elucidate the characteristics of resistance plasmids while also beginning studies of bacterial virulence. In 1972, at a U.S.-Japan joint symposium on plasmids in Honolulu, Hawaii, he was present at the Waikiki beach delicatessen discussion—over corned beef and pastrami sandwiches and very cold beer—that resulted in the invention of recombinant DNA by Herb Boyer and me. Stanley's description in an MIT oral history document helped to make that discussion public. Stanley quickly saw the potential of DNA cloning to solve key problems in both plasmid biology and pathogenesis, and he rapidly established methods in his own lab to do this.

Those were particularly heady times for scientists studying plasmids. Stanley's lucid and prescient 1975 monograph on bacterial plasmids captured this excitement in an unparalleled way and quickly became a period classic. This burgeoning field also required a uniform nomenclature. Stanley was among the first to recognize this, and was part of a group of plasmid workers that addressed the nomenclature issue. The group morphed into a Committee whose report at the 1975 Asilomar Conference on Recombinant DNA provided a framework for research guidelines developed during the subsequent years of the biohazard controversy. Working with Stanley on this committee was an experience one does not easily forget; not only was his expertise about microbial disease far greater than the know-how of any of the rest of us, but he was a skillful mediator whose judgment and spirit of compromise brought together disparately thinking scientists.

Later, Stanley's knowledge and wisdom as a member of the first NIH recombinant DNA Advisory Committee were crucial in providing perspective in discussions about governmental regulation of research during the early days of DNA cloning. By virtue of his abilities, knowledge, and integrity, he gained respect among persons of widely differing views and was a voice for scientific reason. Although less visible than his research contributions, Falkow's impact also on the conduct of science has also been enormous through his role as an advisor to the NIH and the Food and Drug Administration, and to companies translating the fruits of scientific discovery into new therapies.

Quite remarkably, increasing his non-lab responsibilities did not in the least slow the pace of Stanley's scientific contributions. In early 1975, he and his collaborators provided some of the earliest molecular information about bacterial transposons. During this period, he also initiated studies of how bacterial pathogens cause disease: microbial pathogenesis.

Stanley's laboratory was the first to clone genes that encode bacterial toxins and the molecules that enable pathogens to adhere to and be taken up by mammalian cells. The concept that pathogenic bacteria interact dynamically with the host to cause disease came largely from such work. The list could go on and on. His decades of seminal contributions toward an understanding of microbial pathogenesis have made him the undisputed father of the field. He is also renowned as a master technologist in developing and applying new approaches that address important scientific questions, and as a philosopher who is well known for his love of knowledge and his sage advice. Stanley Falkow is also an outstanding and generous mentor who has trained and/or influenced in a major way virtually all of the scientists that now populate his field.

It is not possible today for me to describe all or even nearly all of Stanley Falkow's enormous contributions to science, but I've tried to convey some sense of who and what Stanley has been. No description of Stanley's life, whether as a scientist or person, would be complete without mention of his wife, Lucy Tompkins, who has been his closest scientific collaborator and who has brought much love and joy into his life.

The selection of Stanley Falkow for this award speaks directly to the question of what it is that makes a scientist extraordinary. One ingredient is the human qualities that make a person extraordinary, scientist or otherwise—including wit, humility, kindness, and fairness. All who know Stanley know exactly what I mean. Scientific greatness also results from an ability to identify the important questions to address, to creatively design experiments and tools to answer these questions, to correctly interpret results that lead to new concepts, and to provide leadership that inspires awe and respect. During a lifetime of accomplishment, Stanley has epitomized these qualities, and the field of microbiology would not be the same if not for a man and scientist named Stanley Falkow.