Nature yields her secrets with the greatest unwillingness, and in basic research most experiments contribute little to further progress, as judged by the rarity with which most scientific reports are cited by others.
Basic research, the attempt to understand the fundamental principles of science, is so risky, in fact, that only the federal government is willing to keep pouring money into it. It is a venture that produces far fewer hits than misses.
Even the pharmaceutical industry, a major beneficiary of biomedical research, does not like to invest too heavily in basic science. Rather, it lets private venture capital support the small biotechnology companies that first try to bring new findings to market, and then buys up the few winners of this harsh winnowing process.
If basic research is fraught with such a high failure rate, why then does it yield such rich economic returns? The answer is that such government financing agencies as the National Institutes of Health and the National Science Foundation are like the managers of a stock index fund: they buy everything in the market, and the few spectacular winners make up for all the disasters.
But just as index fund managers often go astray when they try to improve on the index’s performance by overweighting the stocks they favor, the government can go wrong when it tries to pick winners.
This is why it was such a risk for California to earmark $3 billion specifically for stem cell research over the next 10 years. Stem cells are just one of many promising fields of biomedical research. They could yield great advances, or become an exercise in sustained failure, as gene therapy has so far been. By allocating so much money to a single field, California is placing an enormous bet on a single horse, and the chances are substantial that its taxpayers will lose their collective shirt.
Stem cell researchers have created an illusion of progress by claiming regular advances in the 12 years since human embryonic stem cells were first developed. But a notable fraction of these claims have turned out to be wrong or fraudulent, and many others have amounted to yet another new way of getting to square one by finding better methods of deriving human embryonic stem cells.
The major advances in stem cell biology have come from molecular biologists who study transcription factors, the master control switches that govern the cell’s operations. The Japanese biologist Shinya Yamanaka showed that with a mere four of these factors, which he cleverly guessed, he could force an ordinary cell to walk back to embryonic state.
But the finding illustrates what stem cell research is really about. It’s not about therapies and quick cures, it’s about understanding the basic nature of human cells and what makes one type different from another even though all have the identical genome. In other words, it’s a basic research program with little likelihood of producing therapeutic gains in the near future. Stem cell scientists, while generally avoiding rash promises themselves, have allowed politicians to portray stem cells as a likely cure for all the major diseases.
Strangely, for a project that is aimed at regenerative medicine, the arbiters of stem cell research have largely neglected the free lesson that nature is offering as to how regenerative medicine could actually work. Many little animals, like newts and zebra fish, do regenerate parts of their bodies. But their recipe is the reverse of that presented by the advocates of stem cell therapy. Instead of taking a stem cell and trying to convert it into a well-behaved adult tissue, animals like the zebra fish start with the adult cell at the wound site, and walk it backward into a stemlike state from which a new limb grows.
For the California Institute for Regenerative Medicine to invest its $3 billion in studying newts, rather than building new science buildings on every state campus, might seem the best way of understanding regeneration, but that would be hard to explain to California’s voters, who have been assured stem cell cures are just around the corner. Even if governments do better to avoid picking winners among basic research fields, they can play a necessary role in supporting specific scientific infrastructure that lies beyond the means of individual researchers or universities, like atom-smashers or the human genome project. But even these projects are not guaranteed success. More powerful atom-smashers let physicists explore new ranges of energy, but the expected new atomic particles are not always found there. The HapMap, a catalog of human genetic variation that grew out of the human genome project, was designed to uncover the genetic roots of common diseases and help develop new treatments. The project was well conceived and executed, but nature declined to provide many very useful answers. Still, there is nothing wrong with the National Institutes of Health having tried the experiment. The only shame would be in not having tried.
The same goes for the HapMap’s successor, the 1000 Genomes Project, which is an attempt to construct an even larger genetic catalog. It’s well worth trying, but success cannot be assumed — and should be the more applauded if attained.
To take scientific progress for granted is to underestimate the difficulties, professional and otherwise, that scientists must overcome. A researcher spends years in apprenticeship, mastering difficult techniques with a short useful life. He or she then has a few years to strike it lucky and become a lab chief, much of whose time is spent applying for grants and administering the work of the next generation of apprentice scientists.
It’s amazing that the system works as well as it does. But its successes are hard won, not the inevitable victories that scientific spokesmen sometimes suggest when on the fund-raising trail.
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