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When Too Much Is Just Fine
Medicine's Future Glimpsed at 15th Research Festival

By Rich McManus

Photos by Rich McManus

On the Front Page...

It isn't only the scientific authorities who are getting better at planning the yearly festivals of NIH intramural research — the consensus was that 2001 was an unusually strong year — but also attendees are getting more savvy; they have evolved a strategy that seems more ruthless each year: they go to the parts that interest them, and flee when the topics fail to stimulate.

Continued...

The result is a sort of energetic chaos, an intersection of Grand Central Station at rush hour with the leisurely ducking in and out characteristic of an endless film festival. No sooner would rooms darkened for slide presentations fill up for one speaker than attendance would ebb as someone perhaps less famous took the podium. Even the plenary sessions, which this year for the first time featured five institute directors peering into their crystal balls to predict the future of biomedical research, were not immune to the syndrome. The festival audience wants what's hot, and they vote with their feet.

Dr. David E. Dobbins (l) of NIAMS explains his poster on gene localization to Dr. Lutz Froenicke of NCI-Ft. Detrick.

But you get the feeling organizers wouldn't have it any other way — why else overload the 4-day event (the job fair that kicks it off and the sales show at the end don't strictly count as menu items) with more than any reasonable person could swallow?

For example, the mini-symposia choices for Thursday morning at 11 o'clock alone numbered six, forcing guests to choose between a discussion of groundbreaking work on islet cell transplantation as therapy for diabetes and an intimate schmooze with AIDS drug pioneer Dr. Robert Yarchoan, who let his listeners in on how ddI was developed at the Clinical Center in the mid-1980's to counter HIV, to name just two options. At the latter session, attendance ranged, over the course of 90 minutes, from just over half full to standing- and sitting-room-only as four scientists described basic laboratory studies that have ripened into commercial products. One of the speakers, Dr. Hynda Kleinman of NIDCR, described the development of Matrigel, an artificial basement membrane complex whose genesis — born of fear of an impending site visit by a distinguished cell biologist — required not only dogged persistence (the product and papers about it were initially pooh-poohed), but also such serendipitous moments as a research colleague's eventual contact with a manufacturer's representative "because she was cute." Such inside peeks at how science really works are just one facet of the festival's richness.

A panel on "Eureka!" moments in science, chaired by Steven Ferguson (c) of the Office of Technology Transfer, included (from l) NIAID's Dr. Robert Chanock, who has worked since 1958 to cure respiratory syncytial virus; NIDCR's Dr. Hynda Kleinman, who urged listeners never to give up on their ideas; NCI's Dr. Robert Yarchoan, who noted drily that "developing drugs is complex"; and NHLBI's Dr. Robert Balaban, who said, "You learn something really new when your experiment fails — that's something I emphasize with all my postdocs." Doomed hypotheses, he stated, can lead to new insight.

The glimpse into the future of medicine offered by a dais of directors was alternately encouraging and troubling: yes, we're living longer and healthier lives as medicine evolves new and more sophisticated tools to treat the most common ailments, but the world's burden of old, new and reemerging infectious diseases is certain to wreak political instability and immense human suffering, reported NIAID director Dr. Anthony Fauci. His talk, more about the effects of disease on world affairs than basic science, lit one major candle near the end: as the globe encounters afresh the likelihood of bioterrorism, particularly via smallpox and anthrax, the challenge is being answered by "good old-fashioned NIH in-the-trenches research."

Those trenches looked pretty high-tech in the talk given by NHGRI director Dr. Francis Collins, who led off a forecasting session cohosted by NIH acting director Dr. Ruth Kirschstein and NIH deputy director for intramural research Dr. Michael Gottesman. With 95 percent of the human genome available in working draft form, 55 percent of the human genome sequenced in "finished, highly accurate, no-gaps form," and the whole project due in 2003, the fields of genomics (medical, comparative and functional) and proteomics are rising to the fore, he said. A major effort has arisen to tease out the genes involved in susceptibility to a host of common diseases (Collins noted that virtually every disease, save perhaps trauma, has a genetic component), and a strategy has emerged to define "common haplotypes of the human genome." Genome-wide association studies that take advantage of a "gold standard" set of SNPs (single nucleotide polymorphisms — the smoking guns of genomic research) are on the near horizon, he said. And a public-private effort to define haplotypes, called SIMMmap, is under way and will be "something to stay abreast of."

Fauci's talk, "Biomedical Research, Global Health and Foreign Policy," pointed out that infectious diseases are the second leading cause of death worldwide, and the leading cause among children under age 5. "For respiratory diseases, tuberculosis and diarrheal disorders, we need the same degree of intensity as we now have with HIV/AIDS," he said. Some 36.1 million people worldwide are infected with HIV, he reported; in Botswana, one-third of the adult population is infected and rates of between 15 and 25 percent are common in other southern African countries.

"Political and economic instability will result" from these rates, he predicted. "NIH will take an ever-increasing responsibility in performing research aimed at controlling the epidemic." Fauci warned, "The epidemic in China is much more expansive than has ever been admitted before," and said there has been a massive increase of cases in Russia as well. "The epidemic will get worse in the first decade of the 21st century."

The group Protocol Violation belts out alternative rock under warm, summery skies behind the Natcher Bldg. Members include (from l) Darrel Drachenberg, lead guitar, NCI Urology Branch; Nick Costouros, bass, NCI Surgery Branch; Leroy Hwang, lead vocals, NCI Surgery Branch; Patrick Hwu, keyboard, NCI Surgery Branch; Erik Kass, rhythm guitar, NIDCD. Not visible is drummer Steve Libutti, NCI Surgery Branch.
Their T-shirts bore the slogan, "New Alternative Medicine."

Hopeful signs, he said, include a demonstrable reining-in of the AIDS death rate as the budget to study the ailment has grown (it is more than $2.5 billion at NIH in 2002), and recent success in deciphering the genomes of such other important killers in developing nations as Plasmodium falciparum (the cause of malaria) and Mycobacterium tuberculosis (which causes TB).

He called for sustaining the current momentum in biomedical research (with emphasis on new diagnostics, antimicrobials and vaccines), creating global multi-sector partnerships, and building research capacity and health care infrastructure in developing nations. "This will give us that satisfaction to know that we got the ball rolling," he concluded.

Dr. Patricia Grady, director of NIH's smallest institute — the National Institute of Nursing Research — gave an overview of her organization, now celebrating its 15th year. "At age 15, we face many of the developmental issues that teenagers do," she quipped. She summarized a slew of recent research advances, and noted that her institute spends twice the percentage of its budget on training, primarily at the predoctoral level, as other institutes. "We collaborate with virtually every institute across campus and benefit greatly from that," she said.

As each of the directors was introduced, either Kirschstein or Gottesman would reveal little-known personal details about them. Of committed weightlifter Dr. Richard Hodes, NIA director, Gottesman said, "It is said that 8 weeks of inactivity can result in the loss of 30 years' worth of the benefits of weightlifting — in which case Richard would look like the rest of us."

Dr. Roscoe Stanyon (l), a poster author from NCI-Frederick, stands by as his work is inspected by Montserrat Garcia (c), a visiting scientist from the University of Barcelona, and Barbara DeVinney of NICHD and the NIH Animal Center in Poolesville.

Hodes pointed out that more of the world's population is surviving into old age than ever before; there were fewer than 100,000 people age 85 or older in 1900, and there are more than 4 million at that peak now, he said. "This creates a certain urgency with respect to the health needs of the aging population," he said, but countered, "disability among the aging population is far from inevitable." There has been a decline in the rate of chronic disability among the aged since 1982, "and we don't fully understand the cause," he said.

A major worry of those approaching old age is the onset of Alzheimer's disease, which by age 85 claims nearly half the people who live that long, according to one study. Hodes said that transgenic mouse models of AD have been "enormously useful" and added that it seems possible, at least in murine models, to immunize against the agent causing the plaques characteristic of AD, and thereby to dramatically reduce symptoms.

The future-casting session ended with NIDDK director Dr. Allen Spiegel's description of the relatively crude investigations into the causes of diabetes characteristic of the 1950s, to today's very sophisticated molecular biological approaches. A swimmer, a patent-holder, and a runner-upper of the stairs, he called for "new quantitative approaches to handle the complexity of the new biology," including better functional imaging (it would be nice to image the loss of islet cell mass characteristic of incipient diabetes, he said), advances in structural biology, and more emphasis on developmental biology, particularly with stem cells, which he said have the capacity to open a new field of "regenerative medicine."

A line forms to enter the festival picnic tent, which included foods from a variety of local restaurants. Those (seated) who already have their food enjoy conversation and music from a live band on the Natcher lawn.

The panelists answered a few questions, and concluded with endorsements of NIH's intramural enterprise. Said Hodes, "Three of us (on the panel) came here for 2-year postdoctoral training sessions and ended up staying over a quarter of a century." He said the unique set of resources at NIH and the atmosphere of collegiality were key factors in attracting a prominent neurogeneticist to his institute. Concluded Fauci, "The intramural program is extremely important to the identity of the NIH. It is widely recognized by very many people as the prototypic model of what excellence in science really means." Kirschstein added, "We get more and more congressional visits that leave a great impression. When [HHS] Secretary Thompson came to visit, he was just blown away by the quality of work he saw coming from all the institutes."

Blown away. That's about what Research Festival accomplishes every year.


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