Lost Horizon

In the film "Groundhog Day," Bill Murray plays a hapless TV weatherman who seems condemned to endlessly relive the same day over and over again, no matter what he does. The process of justifying long-term basic research in the life sciences often seems like just such a repetitive loop.

The case is made, evidence is marshaled, some projects may be saved, but the next morning we find that policies and initiatives continue their inexorable march toward goals that are short-term and practical. Not that there's anything wrong with it! But that is not where scientific breakthroughs come from, and it is not where ultimate cost-effectiveness comes from. The irony is that with federal and private funding of science at an all-time high, and with a record number of researchers working at laboratory benches, there is a narrowing of research activities and a shortening of the time horizon.

Back in the 1970s, when life science research was a relatively small enterprise by today's standards, the renowned cardiologist Julius Comroe made the case for basic research to the US Congress in the form of an unbiased statistical survey of medical breakthroughs. He took 10 major medical advances of the previous three decades, agreed upon by a panel of 70 clinicians and an equal number of scientists, engineers and administrators.

The advances included heart surgery, drug treatment of high blood pressure, chemotherapy for cancer, and prevention of polio. Comroe traced the origins of these advances back to the breakthrough discoveries that made them possible. After sifting through 2,500 published research reports, they identified 529 "key" papers, of which nearly two-thirds were basic in nature--defined as "research to determine mechanisms by which living organisms function." Their survey stands as solid scientific evidence in favor of basic research in life sciences. There is no reason to believe that this fundamental truth has changed since then.

Why? The answer lies in the nature of scientific mystery. If it is a mystery, we cannot know what the answer will be ahead of time, nor where that answer will come. Roentgen undertook experiments with X-rays in order to study the structure of the atom and found, to everyone's surprise, that X-rays also made living tissue transparent.

The Human Genome Project is often cited as an example of foresight and investment in the future. In one sense it does represent an exception, but in another, it is akin to the Apollo space program as a one-time, massive investment for one specific, long-range goal. It is also credited, however, as an advanced technology that makes old-time approaches obsolete. A recent scientific report belies this notion.

Last month, the Icelandic biotech company, deCODE Genetics, Inc., published a map of the human genome. Its findings are based on applying traditional gene mapping strategies to humans, making use of Iceland's unique historical circumstances of having a relatively isolated population, derived from a small founder group, with little immigration and extensive genealogical records. Their report contains substantial corrections of the genome map generated a year earlier by the high tech DNA sequencing efforts of Celera Genomics, Inc. and a large public consortium of labs.

The Icelandic gene map would not have been possible but for the ground-breaking work that generated the first gene map in the fruit fly Drosophila 90 years ago. Today, deCODE followed essentially the same gene-mapping approach worked out in the fruit fly, one which could never have been discovered if humans were the only subjects studied.

Back when Comroe made his study of medical advances, he was directing his arguments to the public and their elected representatives. There was scant need to convince scientists of the importance of basic research. One unforeseen consequence of the hefty budgets now devoted to science is that such vast funds have increased the pressure for practical outcomes. The more money, the greater the need to show usable results.

So there is a growing incentive to medical-ize, practical-ize and commercialize the research projects because these have greater currency--they get picked up by the news media and get preferential treatment in the initiatives that emanate from funding agencies. They have a shorter apparent time horizon, and the path towards their goal is apparently clear. One may dispute whether these appearances have any underlying reality, but whether they do or not, this defines the best strategy to get money.

Areas of research as esoteric and fundamental as fruit fly genetics have even succumbed. Genetic studies of the fruit fly have produced many breakthrough discoveries, three of which earned Nobel prizes--one early on for the discovery that genes are carried by chromosomes, another subsequently for the discovery that mutations can be produced by X-rays, and a third more recently for discovery of the genes underlying formation of the embryonic body plan. None was motivated by a wish for practicality; all three had enormous practical and medical payback.

Today's climate has spawned fruit fly research projects on cocaine and alcohol abuse, degenerative aging, and disease models for Parkinson's and Alzheimer's. Such efforts are not intrinsically bad, but a problem arises if the climate begins to obscure the value of the research defined by Comroe as aimed at "mechanisms by which living organisms function." Despite record levels of money and personnel, the playing field for asking basic questions has shrunk.

It is essential that we remember where and how our greatest advances arose. It requires only that we have faith in the notion that what worked in the past will continue to work in the future. Otherwise, we may find ourselves falling victim to the ultimate irony of spending more and more money with less and less of value to show for it.