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Howard Schachman (1918–2016)

2016; Cell Press; Volume: 166; Issue: 6 Linguagem: Inglês

10.1016/j.cell.2016.08.059

1097-4172

Marc W. Kirschner,

Howard Schachman, renowned physical chemist and protein chemist, professor at the University of California, Berkeley, extraordinary teacher, and a lifetime fighter for civil liberties, died on August 5 in Oakland California at age 97 from complications of pneumonia. Schachman's active career spanned fundamental work on virus structure, the development of the analytical ultracentrifuge and its use to measure size and shape of proteins, and incisive understanding on how enzymes control their activity. He remained an active teacher until this year. In his life he was deeply engaged in postwar American science: its enthusiasm, its unimaginable triumphs, its prejudices, its generosity, and its corruption. Schachman was kind and fair but a fighter when it came to arrogance, dishonesty, and injustice. He had an exceptional sense of humor, and he found science a rich place to practice his satirical art. Howard Kapnek Schachman was born in Philadelphia in 1918 less than a month after the close of World War I. He remarked that he had no plans to be a scientist and even thought about being a rabbi, but in 1935 when he entered the University of Pennsylvania, he was advised to go into engineering, where jobs were available even during the depression. He transferred to MIT in chemical engineering, but when he graduated in 1939, he found that for Jews there were virtually no opportunities in industry. By chance he heard a lecture about research on tobacco mosaic virus undertaken at the Rockefeller Institute, which then had a site outside Princeton, N.J. He applied for and was offered a job as a technician. Benefiting from good mentorship he moved briefly to a PhD program in physical chemistry at Harvard, but within a year Wendell Stanley, at Rockefeller, asked Howard to come back to his lab for a wartime project on flu; Howard managed to convince Princeton University to accept him as a part-time PhD student with Walter Kauzmann. Soon afterward, Howard married Ethel Lazarus, his steady girlfriend from his undergraduate days in Boston, whom he first met when his MIT roommate invited Ethel out for a date. In Princeton, Ethel was employed by the Emergency Committee of Atomic Scientists and acted as a liaison with Albert Einstein. Through this position, she and Howard had a ringside seat at extraordinarily consequential discussions of science policy and government with Oppenheimer, Bohr, and Einstein. Howard and Ethel (who died in 2013) were together for almost 75 years; they were lifetime partners on issues of politics and social justice. Stanley moved to Berkeley to set up the Virus Lab and offered Howard an instructorship. Howard began his new job in 1948 by improving and exploiting ultracentrifugation, which became the most unambiguous method for characterizing the size and shape of proteins and the heterogeneity of DNA. His biochemical, optical, and analytical innovations were important for the development of protein chemistry and led to many discoveries. One project, with Pardee and Stanier, contributed to the discovery of ribosomes. Soon after they arrived, Berkeley was convulsed in conflict. The University had attached an inflammatory corollary to the state loyalty oath, and Howard became one of the leaders in opposing it and refusing to sign it. He persisted until the very end when a threat of firing and his concern for his family caused him to sign under strong protest; the 26 faculty who did not sign were indeed dismissed. The fight ultimately led to the State Supreme Court, which concluded that the new oath was unconstitutional. After the ultracentrifuge period, Howard was looking for a problem on protein function that would be worthy of all the powerful techniques now at his disposal. In 1962, he began a long and fruitful collaboration with John Gerhart, a newly minted assistant professor who had discovered feedback inhibition and cooperativity in the enzyme aspartate transcarbamylase. Gerhart's inspired work had laid bare the enzymatic properties of that molecule, but had not probed its underlying structural and dynamical features. This led to Howard's 40 year love affair with the enzyme. Collaborating with Gerhart, and then on his own, Howard was able to measure the concerted changes in the oligomeric protein, independently from the local changes, by sensitive sedimentation techniques and spectral methods. He reconstructed the molecule in many different ways as hybrids of inactive and active subunits and with specific mutations and elegantly demonstrated intra-allelic complementation. That large body of work, bolstered by the X-ray structure of the molecule done by Bill Lipscomb at Harvard, gave science its most intimate portrait of how allosteric regulation of enzymes takes place. These then are Howard's scientific contributions, worthy of his many awards and elections: the perfection of the ultracentrifuge for dissecting the structure of proteins and nucleic acids and the deep understanding of the allosteric transition, a process fundamental to biochemistry. Howard's political activism never abated. He was concerned about holding universities to their commitment to freedom of speech, about the corrosive effect of close commercial alliances on openness in academia, about the policies of the NIH, and about the uproar over scientific misconduct. He has been perhaps the most persistent and influential scientist to address these issues. In 1964, as Berkeley erupted in mass student protests over the suppression of political speech, Howard led a group of 200 faculty protesting the forced firing of an assistant professor for refusing to answer questions before the House Un-American Affairs Committee. As provocation by the state and the university mushroomed, he played a role in defending students and defusing conflicts, working for solutions that would maintain the function and the freedom of the university. As those risks receded, other concerns about the integrity of science loomed large in Howard's mind. He worried that commercialization was changing the university from a marketplace of ideas to simply a marketplace. The normal process of sharing was now governed by material transfer agreements and technology transfer offices, which Howard believed "impeded the exchange of materials and knowledge." He characterized the massive increase of indirect costs and federal funding of faculty salaries, as "Ponzi economics." He summarized his views in a 2005 paper entitled, "From 'Publish or Perish' to 'Patent and Prosper'." It is still worth reading today. As President of the American Society of Biochemistry and Molecular Biology in 1987-1988, and for more than ten years its Chair of Public Policy, Howard had a clear view of trends in universities and in the NIH. In 1994, Harold Varmus became the new NIH director and asked Howard to serve as a roving ambassador, bridging the widening gap between the NIH and its extramural community. This required him to put aside much of his still vibrant laboratory research, but he ultimately agreed. Varmus remembers fondly that "Howard's reputation, common sense, and wit helped to strengthen and humanize the agency's relationship with the research community." The other policy issue that captured Howard's interest was scientific misconduct. The atmosphere in the 1980s surrounding the ultimately disproven allegations against Iminshi-Kari and others took place in front of Congressional committees and made it to the front pages of newspapers and the cover of Time magazine. And yet, the term scientific misconduct was so vague that everything bad that a scientist might do could be fit into that rubric. Some argued for a broad definition that included "deception and practices that seriously deviate from those that are commonly accepted within the scientific community." Howard argued that this definition would open the door for modern witch hunts. At a key NIH meeting filled mostly with lawyers, Howard argued passionately that scientific misconduct should be limited to falsification, fabrication, and plagiarism. Other crimes could be handled by existing laws. While he lost the initial battle, his view won in the end and science is safer for it. The most endearing features of Howard's nature were his passion for teaching and his sense of humor. He loved to poke fun at pompous scientists, clueless university administrators, insincere congressmen, and despots. He received invitations just because people wanted to hear his elaborately illustrated jokes and the spontaneous one-line zingers. One of his cartoons is reproduced here. I think Howard was born with a special comedic awareness of ordinary circumstances; he was sort of a Jerry Seinfeld of biochemistry. Howard's teaching was undoubtedly his most serious endeavor. In his lifetime he produced three extraordinary courses that influenced generations of scientists. The first was his physical biochemistry course that opened with the work of Einstein, Perrin, Debye, Bragg, and Pauling, then connected their ideas with the most recent papers in biochemistry and molecular biology. For more than 50 years, he would teach the course, revise half the course each year, and consume half his time doing it. The second was his course at the Marine Biological Laboratory, which he taught for 6 years, again widely influential. The final one was a course for graduate students on responsible conduct of science, which Howard taught the same way he taught the other two: up to date; with deep scholarship into history, motivations, and legality; and as a drama replete with a cast of grotesque characters and bumbling investigators. His teaching also included decades of mentoring doctoral students and postdocs, who were deeply affected by him. Through all of his lectures, speeches, protests, and struggles Howard relied upon Ethel as his ultimate critic and editor. Their life together was a partnership of love and mutual respect. They left a wonderful inheritance. Their son Marc, a musician, and their son David, a lawyer and photographer, were devoted to their parents. Howard and Ethel took great pride in their extended families: two daughters-in-law, four grandchildren and four great grandchildren. From Howard, we learned many tangible things but the greatest may be the obligation to defend justice and fairness. If in the future we see things through his eyes, we will not forget the serious purpose of science, and we will not forget the humor of it all.