Michigan Today - November 2007

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Talking about science

We pay to study worms?

By Colin Duckett

Associate Professor of Pathology and Internal Medicine
Associate Director, Molecular Mechanisms of Disease Program

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It's a strange way to provide a medical service. Three times a year, around five thousand professors, with collective expertise of a vast range of biomedical research areas, kiss goodbye to their families and travel to various uninviting locations in the suburbs of Washington, DC. For around three days, they are locked up in groups of about thirty inside frigidly air-conditioned conference rooms in the basements of budget hotels, where they pore over and argue about enormous piles of grant applications.

These grants have been submitted by scientists around the country to the National Institutes of Health. Roughly $20 billion is at stake, to be doled out to worthy research projects that will improve Americans' health. The task before these hotel-bound professors—all of them recognized as experts in their field—is to sit in judgment of the applications and determine who is worthy to receive a chunk of those millions.

Not only the NIH, but most private funding agencies and charities use essentially the same system, albeit on a much smaller scale, to determine which scientists take a slice of the pie. This American Idol-style model, in which top experts sprinkle glowing superlatives on (or pour disdain over) the supplications of virtually the entire biomedical research community, has remained unchanged since money, it seems, was first printed. Despite a number of inherent problems in the system, it's the only one we know, and it's unlikely to change any time soon.

So here's a critically important question, one that is debated at every study section, as these gatherings are referred to. It's a question that is becoming ever more significant as the available pot of money diminishes. And it's one that the public should know something about, since it's their dollar: where does the money go? Put it another way: what kinds of research are funded, and why?

Most people probably assume that this money is and should be directed entirely towards specific, focused approaches to further the diagnosis, prevention and treatment of diseases. Testing and developing cancer drugs, for instance, or diabetes care.

At first glance, this would make perfect sense. Given the limited amount of research money, it would be only responsible to spend it directly on human health, and the more targeted and focused we are in that endeavor, the more successful we will be.

But history has repeatedly demonstrated how wrong this assumption is. It's not that scientists aren't smart, and it's not that targeted research isn't vitally important. It is. But many, maybe even most of the paradigm-shifting medical discoveries of the last century came out of basic research. That is, research that wasn't focused on curing any specific disease, but on understanding how the natural world works.

A perfect example of how basic research has yielded breathtaking, medically important insights is the story of how James Watson and Francis Crick, with their collaborators Rosalind Franklin and Maurice Wilkins, solved what might be considered the holy grail for biologists: the structure of DNA. Together with an appreciation of the stunning simplicity and beauty of that double helical structure was an instant realization of how nature uses a chain of four different molecules to convey information to the cell—using an alphabet with four letters, instead of twenty-six, and how this information can be passed on to future generations.

Back in 1953, when that discovery was made, nobody envisioned how much that discovery would change the world, how it would revolutionize the way we prevent, diagnose and treat human disease. And it came out of basic (not ailment-directed) research.

The ramifications of the double helix cannot be understated: they have changed the way we think about inherited diseases from male pattern baldness (you get it from your mother) to heart disease, as well as more hot-button issues, such as paternity suits and evolution. (For more on DNA and disease, see Talking About Science: Barrel of Monkeys, Michigan Today, October 2007) Last week a presidential candidate, vying for our vote, stated with apparent sincerity: "economics is in my DNA." Wow.

The skeptic might argue that fifty years later, examples such as the double helix no longer apply, that the low-hanging fruit has been picked, and that we now have all the tools and information we need to focus on curing diseases. While there may be a small but significant element of truth to that, in fact the pace of important basic research discoveries is actually accelerating. Important findings with implications for human disease are being made from research in flies, fish, frogs, yeast and bacteria have soared in recent years.

For example, in the late 1980s a type of enzyme called DNA polymerase was isolated from a strain of bacteria that thrives in the hot springs of Yellowstone National Park (who funded that research?). The finding, by a group of researchers from Indiana University, has had astounding implications for medicine.

This enzyme, commonly known as Taq polymerase, can withstand extremely high temperatures and is the central component of a Nobel Prize-winning technique termed PCR, which allows researches to detect and amplify impossibly small amounts of DNA. Today every geneticist, biochemist, and forensic scientist considers PCR and Taq to be an indispensable technique. Even O. J. Simpson has heard of PCR. It's probably in his DNA, too.

Back in the ballroom of the Bethesda Holiday Inn, as thirty exhausted scientists eye their watches, check their flights home, and ponder the final hardened muffin at the refreshments table, which grant applications finally get recommended for funding? Well, good ones, to be sure. Some have direct medical application, such as the one from a scientist with a lifetime of relevant background work, who proposes an elegant and plausible approach to prevent autoimmune cells from reacting against the patient's own body. Or the one that convincingly demonstrates that an extract made from the bark of a tree in Botswana can stop cancer cells in their tracks (though please, I beg of you, no more green tea or shark cartilage grants).

But yes, we might also recommend the proposal to study worms. Like that worm the size of a pin head which wriggles across a plate of bacteria. That one got funding years ago, and the researchers went on to win the Nobel Prize in 2002.

In other words, we try to fund the best science, knowing that sometimes, the fastest path to a cure for disease is not a well-marked superhighway, but that intriguing back road nobody's really noticed before.

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Colin S. Duckett, Assoc Professor, University of MichiganColin S. Duckett is an Associate Professor of Pathology and Internal Medicine, and is also the Associate Director of the Molecular Mechanisms of Disease Program, at the University of Michigan Medical School. He directs a research team focused on diseases of the immune system, with a particular emphasis on leukemia and lymphoma. His website has a more detailed description of his group's research.