Loosening the Stem Cell Binds

The Senate easily approved a bill this week that would free embryonic stem cell research from the worst shackles imposed by the Bush administration. The House passed its version earlier. A substantial majority of Americans tell pollsters they support embryonic stem cell research. Yet one man, President Bush, and a minority of his party, the religious and social conservatives, are once again trying to impose their moral code on the rest of the nation and stand in the way of scientific progress.
Mr. Bush is threatening a veto, and neither house had enough votes for the bills on initial passage to override him. Concerned voters will need to ratchet up the pressure on recalcitrant Republicans to help stop the president from killing the second enlightened stem cell bill in less than a year.
Under the president’s current policy, federal funds can be used to support research on only some 20 stem cell lines that have limited scientific value. Many of the lines are deteriorating or contaminated, and the group as a whole lacks the diversity needed to conduct a wide range of studies. There is no doubt that progress is being hampered. The director of the National Institutes of Health, who had initially been a good soldier in trying to live within the president’s policy, told the Senate last month that American science would be better served if the nation let researchers have access to more stem cell lines.
The restrictions on federal financing have led to absurdly complicated and costly maneuvers. Scientists are forced to buy extra equipment and laboratory space with private money to perform off-limits research while using equipment and supplies bought with federal money on the permitted stem cell research. In a shocking example cited during Senate debate, a California researcher who had been cultivating stem cells in a makeshift privately financed lab suffered a power failure but was unable to transfer her lines into industrial-strength freezers in another lab because they were federally financed. Two years of work melted away because of this inanity.
The Senate bill would greatly expand the available stem cell lines by tapping into the thousands of surplus embryos left over at fertility clinics. The bill would allow federal support for research on stem cell lines derived from embryos originally created for fertility treatments but not needed for that purpose and thus doomed to be discarded. The donors would have to give their informed consent and could not receive any financial or other inducements to donate their surplus embryos. In a nod to the religious conservatives, the bill also calls for research on alternative techniques to derive stem cells without the use of human embryos, an approach that is certainly worth pursuing but is deemed less promising by most experts.
At the same time, the Senate passed a bill proposed by supporters of the president’s policy that seeks to derive stem cells from embryos that might be judged “naturally dead,” perhaps because they were considered unsuitable for transplantation at a fertility clinic. This is a poorly considered proposal that can only be deemed a diversion from the main business at hand — the need to free American science from the chains imposed by the president.

The Answer Is Inside

The great variety of cancers reflects the fundamental mechanism by which the disease arises: the different combinations of genetic variations that cause normal cells to grow excessively and behave badly. These cancer-causing mutations may be inherited or, more commonly, incurred after birth, and our ability to describe them offers entry to a world in which cancer can be better controlled. We already know a few hundred of the genes that are mutated in various cancers, and we are poised to discover virtually all of them through a new kind of “genome project” that is just beginning.
An obvious application of genetic knowledge about specific cancers is the development of drugs and antibodies that reverse the effects of the mutations in those cancers. Some success in this difficult endeavor has already been achieved — in the clinic, not just the laboratory. But new genetic knowledge can also be used to assess an individual’s inherited risk of developing certain kinds of cancer or to predict the likely behavior of any identified tumor.
Hereditary risks of developing cancer can now be determined by examining about 30 different genes that can cause changes associated with certain cancers. This information can be enormously beneficial by encouraging early screening or preventive surgery. But it can also create anxieties about genetic discrimination, upset families and raise disturbing questions about who should be tested and when. Most of the known mutations are so uncommon in the population and so expensive to find by DNA testing that it is not yet justified to examine people who aren’t from cancer-prone families.
Moreover, depending on the mutant gene, the risks that it will actually cause cancer can vary, from slightly above average to nearly 100 percent. And the absence of an inherited mutation, while reducing risk, does not preclude the cancer. In addition, there are doubtless more inherited variant genes to be discovered, especially variants that confer relatively weak risks of cancer. These features complicate genetic assessment of cancer risk, but I believe that the approach, on balance, can benefit affected individuals and public health.
These predictions will be especially important when tumors are found at very early stages. While not yet perfect, such tests are welcome harbingers of a more rational basis for making crucial decisions about treatment.

F.D.A. Rule Limits Role of Advisers Tied to Industry

Expert advisers to the government who receive money from a drug or device maker would be barred for the first time from voting on whether to approve that company’s products under new rules announced Wednesday for the F.D.A.’s powerful advisory committees.
Indeed, such doctors who receive more than $50,000 from a company or a competitor whose product is being discussed would no longer be allowed to serve on the committees, though those who receive less than that amount in the prior year can join a committee and participate in its discussions.
A “significant number” of the agency’s present advisers would be affected by the new policy, said the F.D.A. acting deputy commissioner, Randall W. Lutter, though he would not say how many. The rules are among the first major changes made by Dr. Andrew C. von Eschenbach since he was confirmed as commissioner of food and drugs late last year.
Advisory boards recommend drugs for approval and, in rare cases, removal, and their votes can have enormous influence on drug company fortunes.
“The $50,000 threshold is something that we think strikes an appropriate balance between” getting smart advisers and reassuring the public that their advice is not tainted, Dr. Lutter said.
The changes are intended to respond to a growing chorus of critics who contend that drug and device makers have hijacked the Food and Drug Administration’s approval process by paying those who serve on the agency’s advisory panels.
In one famous example, 10 of the 32 advisers who voted in 2005 to allow the painkiller Bextra to remain on the market and the painkiller Vioxx to return to the market despite safety worries had taken money from the drug makers. Under the new rules, their votes would not have counted and the committee would have voted to keep both drugs off the market.
In the end, the F.D.A. removed Bextra from the market anyway, and Vioxx has never returned. But the controversy surrounding that panel’s vote, and similar ones, tarnished the process and provided new fodder for critics in Congress.
Representative Maurice D. Hinchey, Democrat of New York, said he was delighted with the change, which will not become final until the end of a 60-day comment period.
“So many lives have been lost as a result of the failure of the F.D.A. to review drugs properly,” said Mr. Hinchey, who for two years has proposed legislation to ban agency advisers from having financial conflicts of interest. “The F.D.A. is now moving back to where it was supposed to be, a principled agency that protects the people.”
“F.D.A. is trying to strike a balance here,” Mr. Troy said, “and they would rather strike it themselves than have it struck for them.”
Drug makers routinely hire doctors as consultants for marketing and research. The New York Times reported on Wednesday that records in Minnesota show that at least 20 percent of licensed physicians in the state received money from drug makers between 1997 and 2005 — an average of $10,000.
Some conservatives were not happy with the new rule.
“I think it’s likely to improve the quality of the recommendations, remove the taint of the recommendations and improve the credibility of the recommendations,” Dr. Lurie said.
Advisory panels are important to the F.D.A. not so much because they provide the agency with expert advice — the F.D.A. can get that privately any time — but because they serve to increase public confidence in the agency’s decisions.

LOGICAL ENDINGS

Computers may soon be better than kin at predicting the wishes of the dying
When machines trespass into the area of medical ethics, though, hackles rise. Here it is not the doctor that is being second-guessed, but the patient's relatives. The question is, if you were in a coma, whom would you more trust to come to the conclusion that you would want: your spouse or a machine?
David Wendler, of the National Institutes of Health in Bethesda, Maryland, and his colleagues have looked into this question. Their answer, just published in the Public Library of Science Medicine, is surprising. At the moment, both are equally reliable—but only the machines are likely to get better at it.
Dr Wendler's study began last year, when his team reviewed all the experiments they could find that had attempted to test how well people predict the wishes of patients with life-threatening conditions. Some of these studies used real patients whose conditions might have led them to fall into a coma—when, obviously, they could not make the decision for themselves. Others employed surrogates who were asked to make “living wills” outlining their preferences for treatment (or the lack of it) in various hypothetical circumstances. The desires expressed by these patients, whether real or surrogate, were then compared with what those patients' kin predicted the patients would want, and also with the predictions of unrelated people (doctors, for example) who might be called on to make the decision if kin could not be found.
Dr Wendler found 16 published reports containing almost 20,000 pairs of decisions. His analysis showed that kin and patient agreed only 68% of the time. When they did not agree, kin were more likely to recommend treatment when the patient wanted treatment withdrawn rather than mistakenly to recommend withdrawal. Surprisingly, the bias towards treatment was equally strong when the decision was made by an unrelated person such as a doctor.
Other research has suggested that the variable most reliably governing whether a patient would want the machine turned off is the “1% rule”. This is that people seem to want life-saving interventions if there is at least a 1% chance they will recover the ability to reason, remember and communicate. Less than 1%, and it is time to pull the plug.
Calculating will
Using that rule of thumb, Dr Wendler and his colleagues wrote a computer program that assesses the prognosis for a patient, based on the sort of clinical criteria that the studies had described to both patients and predictors. Only 12 of the 16 original studies contained sufficient detail to be used, but the result was remarkable. In these 12 studies, human predictors guessed the patient's wishes rather more accurately than was true when all 16 were lumped together—getting them right 78.4% of the time. Dr Wendler's program achieved an almost identical result—78.5%.
At the moment, such data do not exist. No one has yet had a reason to collect them. But they do have a reason now. The decision about when to pull the plug on a patient who is not expected to recover is unlikely ever to be handed over completely to a machine. But when no kin can be found, the program's opinion might help. And even when a dying patient is surrounded by people who care about him, those people may welcome some guidance about what his wishes were likely to have been. Individuals are, indeed, individual. But that does not mean their dying wishes are all that different.