Imagine a drug, based on a molecule already found in our bodies, with the potential to treat conditions ranging from kidney stones to Alzheimer’s. In its natural form, it has been used in the world’s most populous country for thousands of years. There’s just one problem: According to many of its dedicated users, the only really dependable way to get it is by torturing an animal to death.

It sounds like an ethical dilemma from a freshman philosophy class, but that, more or less, is the story of bear bile and its key ingredient, ursodeoxycholic acid (UDCA)—a molecular magic bullet that seems to promote as much controversy as it does healing. It’s a classic example of medical tradition colliding with modern conservation values, with science playing traffic cop.

For more than 3,000 years, bear bile has been used as medicine in Asia, where it is thought to heal by expelling excess heat from the body. China’s state pharmacopoeia says that it relieves convulsions and improves vision. In China, Korea, Vietnam, Japan, and other countries with large Asian populations, traditional health practitioners prescribe extracts of bear bile for everything from flabby libidos to cancer.

Asia’s rising human population has increased the demand for bear bile products, even as the animals themselves are being squeezed into ever-smaller habitats. Prices for bear bile have soared; according to Animals Asia, a Hong Kong-based conservation group, bear bile powder cost $600 per kilogram in China in 2004, and a whole gallbladder can fetch $33,000 per kilogram in Japan.

The inevitable black market has spilled over into North America. Bears are poached from British Columbia to Virginia, and their paws and gallbladders exported legally or smuggled out to Asia. Levels of protection vary from state to state, country to country, and species to species, and different species’ gallbladders are virtually indistinguishable. The global illegal trade in bear parts, estimated at $2 billion annually, has stricken the population of seven of the world’s eight bear species. Asian bear species, including the Asiatic black bear (Ursus thibetanus) and the Malayan sun bear (Helarctos malayanos), are most at risk. Products made from Asiatic black bear bile are available throughout China, says Jill Robinson, founder of Animals Asia: “You see it everywhere—teas, tonics, wine, soda, even face masks in Beijing beauty stores for women to improve the glow of their skin.”

The most disturbing trend is the advent of bear farms in Vietnam, Laos, Cambodia, South Korea, and China. Animals are confi ned to small cages and fitted with metal catheters to “milk” their gallbladders, resulting in a continual supply of bile for as long as the animal stays alive. Conditions are often unsanitary, and bears frequently die from infection and other trauma. Even though the practice is illegal in Vietnam and South Korea and regulated by the government in China, thousands of bears languish on farms—an estimated 1,300 in South Korea, 3,400 in Vietnam, and more than 7,000 in China, according to the wildlife trade monitoring network Traffic.

Solving this dilemma would be simple, if not necessarily easy—persuade doctors and patients to use modern medicines instead of bear bile—except for one thing: Bear bile works. Specifically, UDCA works. This naturally occurring bile acid was first isolated from the gallbladders of polar bears by Swedish researchers at the beginning of the 20th century. It is found in the bodies of many vertebrates, including humans, usually at concentrations of 1 percent to 5 percent (of all biliary acids).

Most species of bears, however, have much more, from the sun bear, with 8 percent UDCA on average, to the brown bear (Ursus arctos), with 19 percent. The American black bear (Ursus americanus) has a bile acid composition of nearly 40 percent UDCA, more than twice as much as any other animal.

Recent studies have shown that UDCA’s therapeutic powers may be nothing short of astonishing. “It truly is one of nature’s great molecules,” says Clifford Steer of the University of Minnesota Medical School, who has either authored or coauthored more than two dozen papers on the subject. In a 2002 study, Steer and colleagues found that rats treated with tauroursodeoxycholic acid (TUDCA), a soluble form of UDCA, emerged from mechanically induced strokes with roughly half as much brain damage as rats that hadn’t received the molecule. A difference of 10 percent is striking; 50 percent is enough to give a researcher palpitations.

In a study in 2006, Steer and another group showed that TUDCA greatly slowed retinal degeneration in mice exposed to high light levels. (It’s no surprise, the authors noted, that among the 28 types of Chinese patent medicines that contain bear bile, 15 are ophthalmologic.)

UDCA’s effects come from its ability to keep cells alive, Steer says. Most cells, when they are damaged or reach the end of their preprogrammed lifespan, selfdestruct through a process called apoptosis. The molecule’s anti-apoptotic effects are so pronounced, Steer says, that it could potentially be used to treat degenerative disorders—such as glaucoma, Huntington’s disease, Parkinson’s, and Alzheimer’s—that affect millions of people worldwide.

This may also explain why bears have so much of it. Months of hibernation would leave most animals near death from muscle atrophy and other kinds of cell loss, yet bears emerge from dens every spring missing little more than excess fat. UDCA may make this possible, and Steer says he has considered suggesting to NASA that they give supplements to astronauts to help prevent the wasting effects of weightlessness. Preliminary data suggests that UDCA could also help victims of spinal cord injuries, and it may even have antiaging properties, since senescence is at some levels a form of cell death. If that’s true, then someday “people might reach for their coffee, vitamins, and a UDCA pill every morning,” Steer says. “I would.”

The molecule is nontoxic and has already been used in the United States for decades, with FDA approval, to treat gallstones and primary biliary cirrhosis in humans. Since the original patent from the early 1990s has run out, it is currently available in the inexpensive generic form ursodiol.

Best of all, UDCA doesn’t have to come from bears. Researchers like Steer rely on established commercial vendors, who in turn get their molecules and compounds from sources such as slaughterhouses. Compared with black market prices, the cost of UDCA derived from the gallbladders of cows, pigs, and turkeys is a steal; the purified form is available online for as little as $13.50 per gram. (It’s also possible to synthesize UDCA from scratch, but the process is complicated and expensive.)

The question of why Pfizer and Eli Lilly aren’t throwing money at Steer and his colleagues highlights the chicken-and-egg problem at the heart of the biotech venture capital industry. “When I first made these discoveries, I probably wrote 50 letters to big pharmaceutical companies,” Steer says. “But the molecule isn’t patentable—they said to come back when you have one.”

Since the original patent has run out, the only way to make money from UDCA today (besides marketing its generic form) is to patent a new, clinically proven use for it, or else discover a new formulation or application method. With this in mind, Steer and two partners formed SMG Therapeutics in 2006 to license the patents held by the University of Minnesota for new uses of UDCA. The next step is to raise funding to formulate the drug and run the difficult, expensive human placebo trials required by the FDA.

In the end, says Dennis McWilliams, one of Steer’s partners, “you have to be able to show investors that you can make money.” In other words, it takes money to make money and to heal people. “That’s how the industry works.”

“The preclinical work in animals is nothing short of astounding,” says Martin Carey of Harvard’s Brigham and Women’s Hospital. Still, he says, large-scale doubleblind clinical trials on people will be necessary to pass a final verdict. So far, all testing has been on animals, with the exception of ongoing studies on Lou Gehrig’s disease at the University of Minnesota. (These Phase 1 trials have already shown that UDCA can cross the blood-brain barrier, a crucial hurdle for any drug meant to treat brain disorders.)

With degenerative disorders such as Alzheimer’s, Huntington’s disease, and strokes, it’s especially difficult to set up clinical trials to prove that a compound works. The bar is typically higher, therefore, for pharmaceutical companies to become involved in treatments. Luckily, says McWilliams, “since the drug is already wellknown and well-tolerated, a lot of the safety and toxicity risks are eliminated.” They hope to start human testing in a year or two, depending on financing.

Ultimately, Big Pharma will almost certainly step in, says McWilliams, either to help with clinical trails or to market and distribute the new drugs. “There’s always a decision to make: At what point do you turn it over to them?”

If ursodeoxycholic acid has half the therapeutic potential researchers like Steer think it might, that raises another question: Could trumpeting the effects of an ingredient of bear bile encourage bear farming? Could the magic bullet backfire? Concerns like this bring people like Steer and Robinson together in a collaboration of conservationist and laboratory scientist trying to align their goals to make sure one doesn’t undermine the other.

“The only time I ever come in contact with bears is at a zoo,” says Steer, who nonetheless shares the results of his work with Animals Asia in part to help convince its audience that not only do bear bile acids work, but that there are alternatives to farmed sources.

It’s vital to persuade Asian doctors and patients, who prefer natural (i.e. farmed) sources of bear bile, to choose alternatives such as synthetic sources or herbs, says Robinson. It won’t be easy, when a single poached bear can equal a year’s income in Vietnam. The Chinese government has strongly resisted international pressure to close or regulate bear farms, claiming that the practice actually protects wild populations by satisfying consumer demand.

A showdown may be coming with the approach of the “green” Olympics in Beijing in 2008. The European Parliament has already called on China to end bear farming by the beginning of the games.

As groups like Animals Asia rescue caged bears (218 as of 2006), Steer and his colleagues explore UDCA’s inner workings and entrepreneurs like McWilliams woo VC funds. In the meantime, both animals and potential patients must continue to wait.