The Not-Quite Nobels
Editor's note: Earlier this month, the 1999 Nobel Prize in Physiology or Medicine was awarded to Günter Blobel, a Howard Hughes Medical Institute investigator at The Rockefeller University in New York City.
As we did last year, we invited HMS Beagle readers to guess this year's Nobel laureate, and we're pleased to announce that two prescient readers, Leon Helfenbaum and Alvaro Monteiro, did just that. For their clever and correct predictions, they will each be awarded a copy of The Best of Annals of Improbable Research, the profoundly hilarious collection of dubious research reports from Annals of Improbable Research, the international science humor magazine, who also bring you the annual Ig Nobel prize.
Of course, many Beagle readers had their own ideas of who should have taken home the medal this year. So, in our own exclusive "ceremony," we here present the Not-Quite-Nobels.
Welcome to the Second Annual HMS Beagle Top Ten Awards, where the winners are the preeminent scientists whom Beagle readers think deserve a Nobel Prize. We are gratified and excited to announce that the list of this year's winners is . . . very nearly the same as last year's.
What do we conclude from intensive analysis of this remarkable consistency? That Beagle readers are remarkably consistent. A year ago they decided that a handful of research topics focusing on cell biology, neuroscience, and genetics, and two handfuls of researchers, have had enormous influence on the recent course of biology. And, by golly, they see no reason to change their minds. No matter what the Nobel Committee thinks.
Beagle readers are always right, so of course we agree with them. Herewith a primer on the folks most highly esteemed by those who should know: their fellow laborers in the world's labs. Are you listening, Stockholm? If not, why not?
1. Lee Hartwell
Lee Hartwell, president and director of the Fred Hutchinson Cancer Research Center in Seattle, Washington, is best known for his illumination of the cell cycle and discovery of the checkpoint genes in Saccharomyces cerevisiae. For this he shared the 1998 Albert Lasker Medical Research Award with Paul Nurse and Yoshio Masui, who are also among this year's Beagle Top Ten. At the Hutch, he is devising pragmatic ways of using knowledge from simpler experimental systems to forge a rational approach to human biology and disease. "It's so much more complicated to get meaningful data from human organisms, and there are so many more people that have to collaborate. It has become very much a sociological problem as well as a scientific one," he laments. "Can we create an institution where the culture is such that it is easy for people to get to know one another and cross disciplinary boundaries?" Hartwell professes amazement at his selection as the top of HMS Beagle's Not-Quite-Nobels Top Ten for two years in a row. He diffidently attributes this peer recognition to "the wonderful boost we are all feeling from the fact that it is possible to translate information across biological systems. This is really the era of rediscovering the unity of biology."
2. Mario Cappecchi
Mario Cappecchi, Howard Hughes Medical Institute neuroscience investigator at the University of Utah, may seem more like a geneticist. He invented transgenic mice, can build designer mice to order, and is more or less directly responsible for a vast proportion of what mouse models have taught us about human disease. A major project in his own lab is employing gene targeting to explore the workings of the 39 genes in the mouse (and human) Hox complex, the group of genes that supervise the vertebrate body plan. That work has recently focused on Hox genes that contribute to patterning the face. Mutations in these critical genes wreak all manner of developmental havoc, including defects in the brain.
3. Judah Folkman
Judah Folkman, of Children's Hospital in Boston and Harvard Medical School, is the hero (or perhaps antihero) of a decades-long tale of suspense about whether factors that inhibit angiogenesis will kill tumors by starving them of their blood supply. Although esteemed by many of his peers, Folkman continues to be handled roughly by some media. In the year since his first HMS Beagle Top Ten appearance (also at the #3 spot), the New York Times, among others, has reported that the National Cancer Institute could not repeat Folkman's success with endostatin in its own labs, although NCI scientists replicated the work in Folkman's lab. And Bristol-Myers Squibb has abandoned angiostatin because it, too, could not reproduce Folkman's results. A handful of other labs around the world, however, have reportedly made angiogenesis inhibitors and used them to shrink animal tumors. And in September 1999, Folkman described in Science a third anti-tumor factor, an anti-thrombin, that shrinks cancer by attacking its blood supply. The final act of this extended drama may have commenced last month. Clinical trials of endostatin as a therapy for cancer have begun at last.
4. Bert Vogelstein
Bert Vogelstein, a Howard Hughes Medical Institute investigator at Johns Hopkins University, appears routinely on the list of researchers whose work is most often cited by others. It happened again in 1998, with seven of his papers about the p53 tumor-suppressor gene and colon cancer, his specialty. What consumes him at present, Vogelstein told HMS Beagle, is trying to apply what is now known about the genetics of cancer to patients for better diagnosis, as well as new ways of preventing and treating it. "One of the things we are most excited about is early diagnosis, the ability to use specific genetic alterations in the patient as markers for the presence of neoplasia." He is optimistic, but it will be a long haul, he cautions. "I think it will be as difficult to apply this kind of knowledge to help patients as it was to discover the genetic basis of cancer. There is no clear path. It will require incredible creativity and hard work."
5. Paul Nurse
Paul Nurse, now director-general of Britain's Imperial Cancer Research Fund, extended our insight into the cell cycle - and then some. First he identified the same gene in fission yeast that Hartwell and company had unearthed in brewer's yeast. Nurse and his colleagues then went on to zero in on the human version of the gene. The unity of living things was suddenly dazzlingly apparent. So was the thrifty consistency of evolution, the patient recycler that, having fashioned a helpful molecule, uses it over and over. Now Sir Paul Nurse has become what the British journals call a boffin, and a prominent advocate for U.K. science, especially cancer research. But he also continues explicating the complexities of the Schizosaccharomyces pombe cell cycle.
6. Robert Weinberg
Robert A. Weinberg of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, is the first newcomer to this year's Not-Quite-Nobels, although he has been on everybody's list of top scientists and top cancer researchers for many years. What may have propelled him to the forefront of HMS Beagle readers' Nobel speculations is his most recent landmark in a singular career that began auspiciously with identification of the ras oncogene. In July 1999, Weinberg and his colleagues reported the first transformation of normal cells into cancer cells in vitro. They did it by changing just three genes. Now they are hunting for the control genes that orchestrate metastasis. "But to date the identity of these genes has been elusive," Weinberg told HMS Beagle. This polymath reports that his latest book, One Renegade Cell: How Cancer Begins (Basic, 1998), was written in just a few weeks. It has gotten what Weinberg calls "nice" reviews, although rhapsodic raves would be more accurate. He attributes his much-praised talent for clear explanations to the fact that he teaches freshman biology. Teaching, he declares, has a salutary influence on one's ability to communicate. Why did he write the book? "Scientists have been the object of great generosity by the American public in the last three decades, and I feel an obligation to show people what they have been paying for."
7. Roger Y. Tsien
Roger Y. Tsien, a Howard Hughes Medical Institute investigator in neuroscience at the University of California at San Diego, also makes his initial appearance among the Top Ten. He paved the way for investigations of the behavior of a single molecule within a single cell. Tsien calls his tools "molecular spies," and they are notable for both their precision and their loveliness. Among other firsts, he showed in 3-D why the jellyfish's green gluorescent protein (GFP) would be a marvelous marker for tagging genes of interest: its barrel-like structure, unique (so far) in biochemistry, protects a glow-producing dye that gets incorporated into the gene's product. GFP can also be modified to suit assorted research purposes.
8. Eric Kandel
Eric Kandel, a professor in what seems like most of the departments at Columbia, is, as everyone knows, monarch of learning and memory, lord of long-term potentiation, and nabob supreme of neuroscience. He and his colleagues have recently been investigating what they have called memory suppressor genes. These are analogous to tumor suppressor genes, and inhibit memory storage by restraining the growth of synapses. Kandel has also been applying the academic version of a cattle prod to psychiatrists with a 1998-1999 series of publications in the American Journal of Psychiatry. Among other derelictions, Kandel takes the field to task for, of course, insufficient attention to neurobiology, especially the biology of learning.
9. Yoshio Masui
Yoshio Masui is the final newcomer to the 1999 Beagle Top Ten. His name is additional evidence that Beagle readers think it is high time the Nobel Committee recognized how crucial revelation of the workings of the cell cycle has been to the life sciences. Now emeritus at the University of Toronto, where he did most of his research, Masui launched cell cycle studies almost thirty years ago by first identifying maturation promoting factor (MPF) in Xenopus oocytes. MPF turned out to be, of course, the frog equivalent of the products of the cell cycle genes Hartwell and Nurse later found. "His work was seminal," says Hartwell. "He was way ahead of the game."
10.Andrew Wyllie
Andrew Wyllie, who joined Cambridge University as head of the pathology department a year ago, could be said to have worked on the cell cycle too. He helped reveal its ultimate end, the process he and his colleagues termed apoptosis. Apoptosis is also known, perhaps inappropriately, as cell death. To be sure, uncontrolled death of cells is a hallmark of many fatal diseases. But thanks in part to Wyllie's pioneering, it is equally clear, as embryos take form and grow by pruning away surplus cells, that apoptosis is also essential to life. And for the definitive word on the origin and pronunciation of that irksome term, consult Wyllie's remarks on the occasion of last year's Not-Quite-Nobels.
Tabitha M. Powledge is a longtime science and medical writer-editor who keeps an eye on the intensifying fusion of genetics and neuroscience.
Andrzej Krauze is an illustrator, poster maker, cartoonist, and painter who illustrates regularly for HMS Beagle, The Guardian, The Sunday Telegraph, Bookseller, and New Statesman.
Endlinks
Bert Vogelstein - describes his work on cancer genes.
Fighting Cancer by Attacking Its Blood Supply - Judah Folkman explains the methodology in the September 1996 issue of Scientific American.
Mario Capecchi - on gene targeting.
