The Fevers of Reason

by Gerald Weissmann

  In time, after tedious consular visits and visa and passport hang-ups, Jan and Marica arrived in New York on February 4, 1965. Jan had been given a faculty appointment in microbiology at NYU School of Medicine, earned though the promise of his interferon research and the good offices of his brother-in-law Ivan, by then an anesthesiologist at University Hospital.

  In New York, Jan was given an empty lab that previously had been used as animal quarters for the Medical School. He began to write grants, and wait. But soon he was funded, and the lab filled with machines and people. The Vilceks settled into junior faculty digs, and Marica started a new job in the Catalogue and Acquisitions Department of the Metropolitan Museum of Art. Both careers took flight. “And one day, in our third or fourth year in New York, Marica and I made a radical decision. From that day on we would no longer speak to each other in Slovak . . . only in English.”

  Love and Science continues the story of Vilcek’s career as a productive investigator, a tale familiar to any scientist with an “h factor” over 50. It describes the flowering of his interferon work in the springtime of New York immunology. At NYU, Lewis Thomas, Sherwood Lawrence, John David, and Ed Franklin had drawn neat distinctions between humoral antibodies and factors released by activated lymphocytes, like macrophage inhibitory factor, or MIF. Dudley Dumonde named these factors “lymphokines”—the name soon to become “cytokines.” At Albert Einstein College of Medicine, Barry Bloom and Boyce Bennett worked out the mechanics of lymphokine induction. At Rockefeller, Anthony Cerami and Bruce Beutler had isolated cachectin, soon found to be identical to tumor necrosis factor (TNF) and first isolated across York Avenue by Lloyd Old at Memorial Sloan Kettering. Vilcek wrote, “The fact that I was friends with Lloyd Old very likely influenced my decision to look for TNF in the materials we generated when producing IFN-gamma in my laboratory.”

  Vilcek moved briskly along, distinguishing leukocyte from fibroblast interferon, learning en route that human mononuclear cells are easier to handle than baby foreskin cultures. Then came “immune interferon” (IFN-gamma). The molecule wasn’t successfully cloned (cDNA) until 1982, but Vilcek’s lab soon found that culture medium of stimulated mononuclear cells contained cytokines other than interferons. One of these was TNF: “Having worked on various aspects of interferon for over 20 years, I felt that perhaps it was time to look for inspiration elsewhere. Why not TNF?”

  THE FIRST QUESTION WAS WHETHER TO EXPLORE the biology of TNF itself or the effects of blocking its actions. TNF was ineffective against human cancers, and antibodies to TNF failed trials in human sepsis, despite animal studies that supported these indications. But one of Vilcek’s tailored antibodies to TNF (called cA2) worked well in autoimmune diseases such as rheumatoid arthritis. In these ailments, a brew of cytokines cause inflammation, traditionally defined as “redness and swelling with heat and pain,” and cA2 blocked the critical cytokine: TNF.

  Love and Science tells the story of Vilcek’s trek from his “experiments with interferon to cA2, yet . . . the path was not always clear.” As early as 1984, Vilcek had reached a licensing agreement between NYU and a biotech venture, Centocor: the Vilcek lab would provide the company with diagnostic monoclonal antibodies against interferons and other cytokines such as TNF. In turn, Centocor agreed to support the lab (eventually for fifteen years!) and to pay royalties to NYU for any sales. The emphasis soon switched from diagnosis to treatment. By 1988–1989, the mouse antibody to TNF (called A2) was formulated by Jimmy Le in the Vilcek lab. Working together with Centocor scientists, the Vilcek lab turned the mouse antibody into a chimeric mouse-human antibody (that now famous cA2).

  Vilcek recalls milestones in the development of cA2 into the clinical drug Remicade (infliximab). Formulated in 1988, the drug first gained FDA approval for Crohn’s disease in 1998. Ten years from bench to clinic merits the modest claim of “no small accomplishment.” Remicade (produced by J&J/Janssen) is now also approved for rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and other disorders, and by 2014 three million patients worldwide had received the drug. It ranked among the top three drugs in the marketplace, with sales close to $10 billion a year. Some of this came back to First Avenue: Vilcek estimates that “Royalty payments collected by NYU . . . by now will have exceeded $1 billion.” More passed through to the inventor, permitting him to “acquire material wealth that I had never aspired to, catapulting me into a new world of philanthropy and art collecting.” He soon became at home in that new world.

  FOLLOWING THE EXAMPLE OF ANOTHER immigrant philanthropist, Andrew Carnegie, the Vilceks report that they have “given away an amount that is much greater than all of our personal assets combined.” The major recipients of that largesse were venerable institutions, such as Jan’s NYU and Marica’s Metropolitan Museum of Art. But by 2006 the Vilceks had launched a new effort, cash-rich annual prizes to recognize contributions made by American biomedical scientists and artists born abroad. Jan tells us, “Both of us are immigrants. I am a biomedical scientist and Marica is an art historian. Could we perhaps build a foundation program around combined experiences?”

  They did, and over the last decade the Vilcek prizes have featured a dazzling cast of recipients: from Rudolph Jaenisch (stem cells) to Mike Nichols (film), from Titia de Lange (telomeres) to Michael Baryshnikov (dance), from Richard Flavell (immunology) to Charles Simic (poetry), and more. Awards of promise have also been given to young tyros in the field, and a new foundation building has opened gallery space, film-making facilities, and research space in which to document the contributions of immigrants to art and science in America.

  A final note: there cannot be many scientific memoirs the author of which is familiar with the work of both polio pioneer Albert Sabin and modernist painter Marsden Hartley, of rheumatologist Ravinder “Tiny” Maini and the doyen of Wiener Werkstätte, Josef Hoffman. The last chapter of Vilcek’s memoir recounts the success of the Vilcek collection of American Modernist art and Native American artifacts, a collection meant to endure; its exhibition has traveled from Manhattan to Oklahoma. I’d say the same for Love and Science; its author is meant to endure, and the book is ready to travel worldwide. It’s a pleasure to read; indeed, we might conclude that for Jan Vilcek, the world is his oyster.

  21.

  Richard Dawkins Lights a Brief Candle in the Dark

  Brief Candle in the Dark is the most engaging—perhaps the best—book of the baker’s dozen or so that Dawkins has written. Subtitled My Life in Science, it’s billed as the second volume of his autobiography, but it casts a net far wider than its predecessor, An Appetite for Wonder. Volume 1 gave us his bio basics: an upper-class English childhood in Kenya, a coed independent school (Oundle) in Peterborough, then Balliol College, Oxford, followed by an Oxford MA and PhD with Nikolaas Tinbergen (Nobel Prize in Physiology or Medicine, 1973). He went on to a stint at Berkeley in the days of pot and protest. With stickers of Gene McCarthy’s presidential campaign on his Ford Falcon station wagon, he drove cross-country and returned on the SS France to Oxford for good. There he planted his foot on the shores of modern biology with The Selfish Gene (1976) and for over a generation, with wit and panache, has carried the news of Darwinian evolution to a general audience.

  In Brief Candle in the Dark, Dawkins brings his own contributions up to date, hoping that “taken together these might add up to a kind of biologist’s worldview, with an aspiration at least to coherence.” His formulations add up to more than a worldview, more than a weltanschauung like Immanuel Kant’s; he has presented testable concepts of daily use to experimental biologists.

  IN HIS Summa Theologiae (ca. 1270), THOMAS AQUINAS laid out a conclusive argument for the existence of God and why life on earth is God given. In Brief Candle in the Dark, Dawkins proclaims a “Summa Evolutionis,” so to speak: life evolves not by grace of God, but by “selfish genes,” a term based on notions of W. D. Hamilton that Dawkins formalized in 1976. Evolution is directed by successful replicators (for example, DNA, so
metimes RNA) that influence the development of vehicles (for example, humans, sometimes viruses) that make those vehicles good at reproducing. For almost a century, Darwinists assured us that individuals are the targets for natural selection. Dawkins proposes that genes are the ones on trial for fitness; individuals serve as their vehicles (“taxi-cabs” in a Japanese translation) to the gyms of selection. He rebukes the late Stephen Jay Gould for not quite getting the replicator–vehicle distinction right: Gould’s “genius for getting things wrong matched the eloquence with which he did so.” He’s also impatient with epigenetics, the mechanics of which he likens to origami. Authors of the approximately 14,000 articles on epigenetics cited by PubMed since 1964 might disagree.

  Brief Candle in the Dark presents cogent summaries of Dawkins’s other conceptual contributions to biology. One of these made it into the Oxford English Dictionary: the “meme,” which Dawkins explains as “a unit of cultural transmission or a unit of imitation. Examples of memes are tunes, ideas, catch-phrases, clothes fashions, ways of making pots or of building arches.” He’s perhaps proudest of the concept of the “extended phenome”: species-specific, extracellular structures such as beaver dams, termite towers, coral reefs, and so on (taxi ranks?). Next, we’re introduced to the “Concorde fallacy,” exemplified by the Anglo-French fiasco in supersonic investment. Dawkins and Jane Brockman use the term in a paper to describe the behavior of digger wasps: “it amounts to investing further in a project simply because one has invested in it heavily in the past.” Finally, Dawkins sums up his formulation of “arms races between and within species” as, “the rabbit runs faster than the fox, because the rabbit is running for his life while the fox is only running for his dinner.” “Arms Races . . . ” is also the title of his most cited scientific paper (1712 citations in PubMed).

  FILLED WITH SOLID SCIENCE, Brief Candle in the Dark is also larded with cameos of life among anglophone elites of science and the mass media. Dawkins’s reach is very wide and very cool, moving from high table at Oxford to film festivals in Cannes, from lunch with Claire Bloom to dinner with Bill Gates, from a spat with Ann Coulter to debates with the archbishop of Canterbury. He’s amused by a 3,000-year-old [sic] dinosaur skull at Liberty University in Lynchburg, Virginia, and he seeks a kraken off the Japanese coast. In the New Mexico desert, a “soft beauty” offers him Ecstasy (the drug); over lunch at Buckingham Palace, the queen of England comments on his hand-painted necktie. Some might consider the inclusion of these anecdotes to be shameless name-dropping, I’d call it “meme-dropping”: each conveys a unit of cultural transmission. I also find it refreshing to read a book the index of which places the author’s film The Genius of Charles Darwin immediately above the names of “George and Ira Gershwin,” or which lists the TV comedian “Maher, Bill” right above my favorite poet “Marvell, Andrew.”

  The book, a constant delight to read, is seasoned with snippets of Dawkins’s occasional verse. From 1995 to 2008, he was Simonyi Professor for the Public Understanding of Science at Oxford, and that understanding has been helped by his skill at both exposition and rhyme. Dawkins’s verses have clearly helped to form covalent bonds between his friends in the Two Cultures. These lines are in praise of Dawkins’s benefactor, the silicon billionaire Charles Simonyi, who owns the Villa Simonyi, a glass ziggurat featuring op art, on the shores of Lake Washington in Medina, Washington:

  Never mind about John Keats

  Or Newton’s scientific feats

  Forget your William Butler Yeats

  William Wordsworth, William Gates . . .

  There’s the finest champagne and the best from the deli

  (The walls are of glass, when they’re not Vasarely)

  The God Delusion (2006) was a bestseller that placed Dawkins among the “Four Horsemen of Atheism” along with Christopher Hitchens, Daniel Dennett, and Sam Harris. One dissenting critic, Nathaniel Comfort, called the book an “ecclesiophobic diatribe,” and stated, “The gospels of [the Four Horsemen] form the scripture of the ‘new atheism,’ a fundamentalist sect.” Dawkins’s Darwinian reproach of intelligent design and/or creationism, beliefs held by a majority of Americans, has earned him a high spot on the opponent list of the Creation Science Hall of Fame. (I’m not displeased to find that the FASEB Journal and I have also made it on that roll of honor). In Brief Candle in the Dark, Dawkins reviews a decade of jaundiced—and mainly humorless—responses to his earlier work: he’s aroused the ire of many and the fury of some. A resolution was even introduced in the Oklahoma legislature to prevent Dawkins from speaking at the University of Oklahoma “to present a biased philosophy of the theory of evolution.” But Dawkins prevailed, and describes other amusing encounters with televangelists and other troglodytes of the media on both sides of the Atlantic. To them he responds:

  For what is said in holy writ

  I’m one who doesn’t care a bit.

  Away with actuarial mystics!

  I’ll throw my lot with hard statistics

  The bible may be old and quaint . . .

  Necess’rily so . . . it aint

  Fittingly, at the site of the great Oxford “monkey debate” (1860) between Thomas Henry Huxley and Bishop Wilberforce, Dawkins faced down colleague John Lennox, a strong fan of his deity. With calm, Darwinian reason, Dawkins demolished the creationist cant of his opponent. Brief Candle in the Dark clearly establishes Dawkins as the natural heir to Huxley’s nineteenth-century mantle as “Darwin’s Bulldog” (in Oxbridge parlance, the “bulldog” is the campus cop.) At his seventieth birthday celebration, Dawkins rhymed a wish his many readers would surely support:

  [To] reach that bourn—the one we learn

  From which no travelers return:

  That decent inn—no Marriott—

  Presaged by time’s winged chariot . . .

  Time, yet new rainbows to unweave

  Ere going on Eternity leave.

  22.

  Eugenics and the Immigrant: Rosalyn Yalow

  My father, Simon Sussman, was born on the Lower East Side of New York, the Melting Pot for Eastern European immigrants. . . . Since I could type, [I] obtained a part time position as a secretary to Dr. Rudolf Schoenheimer, a leading biochemist at Columbia University’s College of Physicians and Surgeons (P&S). This position was supposed to provide an entrée for me into graduate courses, via the backdoor, but I had to agree to take stenography.

  —Rosalyn Yalow

  On 19 December 1946, Renato Dulbecco and I sailed from Genoa on board the Polish ship, the Sobieski, I headed for St. Louis and he for Bloomington. When the Statue of Liberty became visible against the sky of the port of New York . . . I felt as hundreds of thousands of refugees have felt, in the flight from recent as well as earlier persecutions upon arrival in New York Harbor. . . . My stay lasted thirty years.

  —Rita Levi-Montalcini

  THE BIOGRAPHIES OF ROSALYN YALOW AND RITA LEVI-MONTALCINI yield prima facie arguments for liberal immigration and visa policies. Yalow’s story particularly illustrates how bigotry and eugenic notions paradoxically led to scientific discovery—in her case, the discovery of radioimmunoassay—in the United States. Arrivals like those of Yalow’s grandfather from czarist Russia or Levi-Montalcini from fascist Italy are perhaps only small episodes in the story of America’s rise to pre-eminence in science. Indeed, other factors surely played larger roles: the GI Bill of Rights, James Shannon’s NIH, public access to higher education (Hunter College for Yalow), private philanthropy (Rockefeller, Hughes), and more. But we’d surely be many notches down in science had our borders been closed to arrivals from abroad.

  Thirty years ago, its repute at apogee, the United States accounted for about 40 percent of the total number of reputable scientific papers published in the world, the European Union for 33 percent, and the Asia-Pacific region for 14 percent.

  Those days are over: the seats of American power have been usurped by fans of unreason, Bible-thumpers who feel free to preach “creation science,” “alternati
ve medicine,” “faith-based” social service, and blatant homophobia. In consequence, the standing of American science has been eroded. By 2004, the EU had moved into the lead with 38 percent of total scientific papers published worldwide and the United States had slipped to 33 percent, while the Asia-Pacific region moved up rapidly to become the source of 25 percent of all papers.

  It is not helpful to disguise bans on scientific exchange under the scoundrel’s cloak of national security. “Scientists Denied U.S. Visa,” a headline screams, and the president of Intel complains to the Financial Times that

  America is experiencing a profound immigration crisis but it is not about the 11 million illegal immigrants currently exciting the press and politicians in Washington. The real crisis is that the U.S. is closing its doors to immigrants with degrees in science, maths and engineering.

  Data on the U.S. work force in science can be used to make another argument for liberal immigration and visa policies. The 2010 census documented that, whereas Asians are only 6.1 percent of the total work force in the U.S., 17.2 percent of all U.S. life scientists and 19% of all physicians are Asians! We can be grateful that, in deference to our wartime alliance with China, the Roosevelt administration in 1943 repealed the racist Chinese Exclusion Act, which had essentially excluded all Asians from the continental United States since 1881.

  I have further reason to thank FDR when I examine publications that crossed my editorial desk even a decade ago. In the March 2006 issue of the FASEB Journal, one counts 41 articles (Research Communications and FJ Express) with 312 authors listed, an average of 7.6 per article. Of those authors, 98 (31 percent) had overtly Asian surnames (Indian, Chinese, Japanese, etc.), split evenly between scientists working in U.S. labs and abroad. That squares with the 17 percent of Asians in the work force of life sciences overall in the United States.