BIOTECH

Pharmaceutical labs are cooking up a new class of pills that make looking good feel better than ever.

It was chemical serendipity of billion-dollar proportions: a tanning drug with all the right side effects.

A hundred years ago, being tan was bad, because it meant you worked outside, which meant you weren't rich. By the 1970s, tan lines had become associated with exercise, tropical vacations, and bumming around in skimpy clothing while others worked. Tan was cultural, tan was affluent, tan was healthy. UV-induced tan was also, unfortunately, the cause of a sharp rise in skin cancer rates and premature wrinkles.

Hence a mid-'80s research push at the University of Arizona to attack the problem from inside. Being tan is healthy; ironically, people who work outdoors and see the sun every day are at low risk for skin cancer. But getting tan is where the danger lies. The faster it happens - worst case: a tanning booth - the more harmful it is. The U of A team, which included endocrinologist Mac Hadley and dermatologist Norman Levine, came upon a synthetic hormone a thousand times more potent than the body's own tanning triggers. They called it Melanotan and pinned high hopes on its sunless ability to protect, beautify, and gently fleece the pale peoples of the world.

But that was only the beginning: The molecule turns out to activate five different chemical systems throughout the body. It's a potent anti-inflammatory, and in 1996 further tests of the drug showed that it also promotes sexual arousal. Not simple vascular stimulation, as with Viagra, but a direct action in the hypothalamus, the brain's emotional switchboard. Impotence is largely an organic, mechanical problem, but here was something that could potentially address the murkier issues of frigidity, and even that old-time marriage killer: simple lack of enthusiasm. (On Melanotan, female lab rodents triple their levels of courtship behavior.) And as if that weren't enough, the molecule also targets an appetite-suppression receptor popular with the makers of weight-loss drugs.

Yesterday's drugs were about need; today's are about desire.

Call it the Barbie drug: a pill or nasal spray that can make you thin, tan, pain-free, and horny all at once, without effort. How much would you pay?

Melanotan is just a glimpse of the coming age of fantasy drugs - pills that will soothe (and, in fact, reinforce) social desires. In the days before tan was cool, overweight, depressed, bald, and impotent were merely descriptive terms, but today in America they're considered illnesses and are fought back with some $44 billion a year in direct medical expenses - fast approaching the $50 billion we spend battling cancer. And as the list of treatable disorders grows larger, so does our medical ability to reshape both body and mind. Yesterday's drugs were about need; today's are about desire. The unlocked human genome opens even our innermost passions to scrutiny and tinkering, blazing the way to an entirely new class of pharmaceutical. A more conservative, more religious culture than ours might want "doubt blockers" or "gnostogenics" to empower their spiritual side. But for better or worse, Americans who pay for quick-fix drugs will want beauty, happiness, and the illusion of wealth.

Nowhere is this more apparent than in the world of bodybuilding. Let's face it, building muscle is hard work, and the people most intent on it are eager to speed the process. But steroids have troublesome side effects - like liver damage and violent behavior. Fortunately, the pharmaceutical industry rides to the rescue, with an injectable called Insulin-Like Growth Factor One, or IGF-1. This is a muscle-mass promoter that occurs naturally in the body, and whose slow decrease after age 30 is probably responsible for the wasting process we associate with aging. Shots of IGF-1 directly into muscle tissue have been shown to aid in muscle growth and to reverse wasting not only from old age but also from diseases such as muscular dystrophy. But the effect, which is localized at the injection site, soon wears off, allowing normal (or subnormal) muscle mass to return.

Enter biotech, which can not only synthesize the protein from scratch but also package it in the form of engineered viruses that insert IGF-1 genes directly into muscle cells, allowing them to produce their own growth factor indefinitely. Researchers at the University of Pennsylvania have already created dozens of muscle-bound Mighty Mouse look-alikes from ordinary lab rodents. Injecting these viruses into people will be a slow, carefully monitored process, but it's only a matter of time before the street gets ahold of IGF.

If Melanotan is Barbie's drug, then surely the IGF-1 virus belongs to Ken, who'll use it to build the pecs and lats she so adores, without filling up his calendar or wiping the sunny boy-next-door smile off his face. In fact, with both these drugs acting in concert, Ken and Barbie will be prettier than ever and have a lot more time to spend together.

But what about Barbie's kid sister, Skipper? Locked in perpetual adolescence, too young for sex or drugs ... Does biotech hold any promise for her? Happily, yes: Food scientists in Garching, Germany, have developed a molecular big chill to turbocharge her snacks and soft drinks.

Special nerve endings in the skin, and especially on the tongue and cheeks and palate, are designed to measure temperature and give a gentle (or not so gentle) warning when they come in contact with surfaces that are too hot or too cold. Our mouths know the difference between ice cubes and hot soup. Still, these nerves are chemical machines, and there are chemicals that can fool them. Capsaicin, the active ingredient in peppers, is "hot" because its precise molecular shape locks onto our heat receptors, triggering physiological reactions like sweating and flushing. Similarly, menthol - the distilled essence of peppermints - triggers a sensation of cold that deadens pain in the same way ice does.

But menthol and capsaicin have very distinctive flavors and odors, which make them instantly recognizable and often offensive, even in tiny concentrations. The German molecule known as cyclic alpha-keto enamine, however, is a self-contained miniature ice age. It's cool to the touch and taste, like mint, but it produces a whopping 35 to 250 times the cooling sensation, with no intrinsic taste or smell. Large amounts of it can be added to anything. This could lead not only to bizarre new flavorings for Skipper to enjoy - SuperBerryIce and Hot Coffee Chiller, Megamint and even Frost Habanero - but also to cooling, time-release skin products for Ken and Barbie's day at the beach.

Being shallow never felt so good.

As the US grows more affluent, its cultural expressions have become more extreme, more competitive, one might say more professional. National cheerleading finals, recreational triathlons, octogenarian sex manuals ... Drugs have been a silent partner in the extreming of America, shedding their stigma and eroding the stigmas of the conditions they treat. Picture a cartoon spinach can in the pocket of every Popeye and Olive Oyl - and steroid poppers for every Bluto - and you begin to see just what fantasy is being realized here: the America of our collective inner child.

Melanotan, originally licensed to Princeton, New Jersey's Palatin Technologies, has been shelved precisely because of its broad, potent action in the body. Palatin is currently pursuing a slew of receptor-specific chemicals instead - none of them cosmetic - while the original compound has passed into the hands of EpiTan Limited of Melbourne, Australia. In the land of Oz, high rates of skin cancer make tanning a major health issue, and Melanotan - now in human trials - is expected to be approved for prescription use in the next few years. But with worldwide rights to the compound, EpiTan has its eyes on the US market as well and will likely petition for FDA approval at the same time. (more at link)