Curing Diversity

City Journal ^ | Autumn 2008 | Peter W Huber

[Lorianne]

The new medicine shows that we’re biochemically separate and unequal—and regulators are starting to catch on. ___

Life is unfair, and while others have suspected as much before, biochemists can now prove it. You have colon cancer—possibly because a flawed APC gene failed to produce the protein that helps prevent the disease. When the cancer spreads to your liver, you need Pfizer’s Camptosar. But if you’re the one-in-ten patient with a flawed UGT1A1 gene—find out with a Food and Drug Administration–approved test kit—you lack an enzyme to purge the drug from your body before it accumulates to toxic levels. Your oncologist may be able to adjust the dose so you can take Camptosar anyway. Or maybe not.

Washington can’t help. The Fourteenth Amendment doesn’t guarantee equal protection at the pharmacy. No privacy-protecting, discrimination-banning law, no promise that someone else will pay, will ensure that a drug that suits others will suit your genetic profile too. If Pfizer can’t make a gentler Camptosar, it will only do business with tougher patients. Meet “pharmacogenomics”—eugenics for drugs.

This is where diversity blather gives way to the rigorous diversity science that’s taking over the medical show. Drugs supply almost all the real health care these days, because human hands are too big to grapple with the microscopic things that cause most of our problems. Eugenic drugs reflect how biochemically separate and unequal people are. Some, indeed, target genes that track sex, race, or ethnicity; their FDA licenses affirm truths unmentionable in polite society and approve conduct illegal in every other sphere of commerce and public life. All are terrible news for anyone determined to pull people together, pool medicine’s costs, equalize its benefits, and lose diversity in the crowd. The doctors of equity promise universal access to the Mayo Clinic, where the real doctors now brew discriminatory cures and card your genes at the door.

So the stage is set for a long battle between radically new medical science and a senescent, unscientific vision of how diseases are cured and what the “health-care system” ought somehow to deliver. Much of the battle will be fought at the FDA, which is able to see things both ways, because it now has two separate brains humming away under its hat. What health care most needs is less of the old brain and more of the new. That policy alone will improve the quality of medicine and lower its cost more than any development since germs were exposed and immunology became a science almost a century and a half ago.

Soon after Watson and Crick published the blueprint for the double helix in 1953, George Hitchings and Gertrude Elion at Burroughs Wellcome began designing drugs systematically around the biochemistry presented by their intended targets. This logical approach foreshadowed the future of medicine and (in a weirdly circuitous way) the reinvention of the FDA almost three decades later. Scientists caught on much sooner, and “structure-based” drug design advanced rapidly as biochemists acquired the tools needed to read, configure, and build the molecules that choreograph life.

Drug designers take diseases apart. Iressa, for instance, targets a single receptor that proliferates in the most common form of lung cancer. The FDA licensed the drug in 2003, after clinical trials yielded good results. Follow-up trials involving almost 2,000 patients suggested, however, that the drug wasn’t working after all. Further analysis then revealed that Iressa had indeed worked—but only on receptors found in 300 patients of Asian ancestry. Similar variations apparently explain significant differences in the efficacy of drugs used to treat many other cancers. White Americans have less tolerance for some antidepressants, antipsychotics, and heart-disease drugs, while blacks respond poorly to certain drugs for high blood pressure and hepatitis. Eleven variations in just one gene affect responses to common antidepressants.

Drug designers take the rest of the patient apart, too. Tolerance for many drugs often hinges on how well patients metabolize and expel them, which seems to depend on a couple of thousand variants in a couple of hundred different genes. What were once inexplicable “side effects” are now predictable interactions between the drug’s chemistry and healthy parts of the patient’s. That lets medicine keep the drug and vote the too-delicate patient off the island.

.... excerpted

[Old Sarge]

Multicultural-diversity-tolerance.

The disease for which there is no cure, save death.

[OneWingedShark]

Wow, cynical.

[Gondring]

It's true, though. I haven't read the whole article (this is a self-ping for later, too :-), but another aspect is that drugs are prescribed in a different manner from how trials are run.

Clinically, drugs are often used in a sequential manner, targetted to a patient based on what has or hasn't worked in the past. It's not random, so a small percentage of patients might get great benefit from a drug that shows little promise in the overall picture (potentially because it harmed a patient who would never have been prescribed it in a clinical setting).

One-size-fits-all is a terrible way to run things that are based on human physiology.

[OneWingedShark]

I didn’t say it wasn’t true. But thanks for the reply, it was good/informative.

[count-your-change]

An interesting article indeed! I think the next great movement in medicine will be tailoring drugs to the individual.

[Gondring]

I didn’t say it wasn’t true.

Sorry if I gave the wrong impression...I was just adding to your comment, as I agree that it's a cynical (yet appropriately so) view.

But thanks for the reply, it was good/informative.

You're welcome. I should make it clear that I am not a physician, but this was a topic I once discussed with physicians when I was considering it as a topic for a column.