As a wet-behind-the-ears medical intern, a colleague of mine once greeted a new patient with a breezy, "So what's your problem?" "Oh, just a touch of leukemia," the pallid fellow answered.

But that was in the mid-1950s, when there was no such thing as "a touch" of leukemia or any other cancer. We knew almost nothing about the disease — its cause, or how to prevent, treat or cure it — except that it was a death sentence and a gruesome end.

A half-century of new drugs has changed all that. Blood-related malignancies such as leukemia and lymphoma now are among the most curable forms of cancer; no longer is the diagnosis a death sentence.

Similar treatment breakthroughs have occurred as well in other areas of medicine, such as arthritis, hypertension, abnormal lipids and heart failure, and new vaccines have virtually eradicated many dreaded childhood diseases.

Moreover, greater understanding of the molecular mechanisms of disease has provided the wherewithal to make these drugs safer and more effective.

These stunning successes notwithstanding, over the past decade the pharmaceutical industry has become a lightning rod for critics. Many influential members of Congress, in particular, have berated the FDA for being insufficiently concerned with drug safety and too cozy with industry.

And the FDA leadership, ever a reed in the political winds, now finds itself in a gale that is blowing in the direction of a more imperious and adversarial posture toward drug companies. Risk-aversion is now the rule.

Serious PR Issues

As a result, at a time when drug development should have been spurred by the exploitation of numerous new technologies and huge increases in R&D expenditures — which tripled to more than $45 billion between 1995 and 2007 — drug approvals have actually dropped. The 19 new medicines approved last year was the lowest figure in 24 years.

As the result of regulators' risk-aversion and pandering to Congress' dislike of the pharmaceutical industry, bringing a new drug to market now requires on average 12-15 years and costs more than $1.2 billion. And only one in five approved drugs garners sufficient revenue to recoup R&D costs for the manufacturer.

Several recent developments at the FDA will further increase the time and costs of drug development — bad news for developers of medicines and the sick and infirm who need new therapies.

The first is a Memorandum of Understanding between two groups within the FDA's Center for Drug Evaluation and Research. Under the agreement, the drug review and drug safety offices will share equal responsibility on "significant safety issues" for medicines that are under review or already have been approved for marketing.

Examples include: (1) changes in labeling that pertain to safety; (2) the establishment or revision of a drug's risk management plan (which can range from educational programs for physicians and pharmacists to highly restrictive limits on prescribing and advertising); (3) withdrawal of a drug from the market, and (4) the requirement for post-approval clinical trials or epidemiological studies.

Safety First?

To those unfamiliar with the inside baseball in the game of drug regulation, the implications of this change likely will be obscure, but they are important.

The officials in the FDA's Office of Surveillance and Epidemiology are focused so narrowly on "safety" that they ignore the fact that because all drugs have side-effects, safety cannot be evaluated in a vacuum but must be part of a cost-benefit judgment.

Their motto might be, "If you don't approve any new drugs, none will cause safety problems."

Worse still, some of them are true-believers — in the venality of drug companies and the inherent dangers of their drugs; and at least one zealot, a self-styled whistle-blower, seems never to have met a medicine he liked.

Up to now, the drug safety staff has had an advisory, largely subordinate role. The new arrangement gives the safety fanatics higher status and pits the FDA's new drug review divisions, who themselves have been exceedingly risk-averse toward new drugs, against the obsessive drug-safety minions.

Second, an advisory panel of the FDA has recommended that regulators require studies of the long-term cardiovascular risks of new diabetes drugs before they can be marketed, even if they show no sign of such problems in the usual large trials performed to demonstrate safety and efficacy.

This could add tens of millions of dollars and years of delay to drug development.

Third, the advisory panel recommendation follows recent guidance by the FDA itself to two companies that their new lipid-lowering drugs would need to show not only the ability to exert a favorable effect on laboratory values — such as lowering LDL, or "bad" cholesterol — but that clinical trials would need also to show a positive effect on "genuine" clinical outcomes, such as fewer heart attacks and strokes, or even lengthened survival.

This reminds me of a cartoon that shows two researchers in the laboratory, one of whom is holding up a flask.

He says to his colleague, "Well, it looks as though we've finally done it — discovered a drug that will confer immortality. The only trouble is, it will take forever to test it."

The bottom line: At a time when the U.S. population is aging and needs innovative new medicines for a wide spectrum of degenerative and infectious diseases, the nation's drug regulator is increasingly inefficient, slow, poorly managed and risk-averse.

Congressional oversight is misguided and self-promoting, more interested in public posturing than public health.

We need public policy strategies that will lower the costs and time of development — strategies that will stimulate the formation of new companies (the number of which is now shrinking) and enable them to pursue more drug candidates, including some that are medically needed but offer only modest revenue.

In the meantime, the feds will continue to batter a once-robust industry and Americans will go on dying for reform.