New drug discovery from unusual animal sources is just around the corner.
Reviewed By Brunilda Nazario
Unless you're a scientist, you might not find much to love about a pig's or cow's pancreas, horse urine, snake and spider venom, or Gila monster spit. Yet all of these are existing or potential sources of drugs, some of which are life-saving. These "pharmazooticals" represent just a small portion of drugs derived from natural sources. In western medicine -- plants rule.
Modern investigation of animal sources may have started in 1921, back when they called diabetes "sugar disease." The Nobel prize-winning work of Canadian surgeon Frederick Banting and his assistant Charles Best led to the discovery of insulin and its ability to lower blood sugar. It's estimated that since that time, insulin -- mainly derived from the pancreas of pigs and cows -- has saved the lives of 15 million people with diabetes.
Today, another creature brings hope to people with type 2 diabetes whose blood sugar levels remain high in spite of treatment. An investigational drug called exenatide comes from lizard spit, specifically an enzyme in the venom of the Gila monster. It also appears to promote weight loss.
We have the animal kingdom to thank for some very important drugs already in use. The ACE inhibitor Captopril used to lower blood pressure comes from the Brazilian arrowhead viper. ARA-C, modeled after compounds from the Caribbean sponge, treats leukemia and lymphoma. Integrelin, which comes from a protein in the venom of the southeastern pygmy rattlesnake, is used to treat acute coronary syndrome. Calcimar and Miacalcin are calcitonin hormones derived from Coho salmon and used to treat osteoporosis.
One of the most widely used and most controversial drugs derived from animals is Premarin, an estrogen given as menopausal hormone therapy. The drug is derived from the urine of pregnant horses, and the treatment of those animals and their foals on so-called PMU (pregnant mares' urine) farms have come under attack from animal rights groups.
Animal rights issues may be one reason most scientists look mainly at spiders, reptiles, and sea creatures rather than at mammals, says Elliott Sogol, PhD, spokesman for the American Pharmacists Association. "I think there's always been hesitation from researchers because of organizations that don't want to see any animals used for research, and maybe some concern about coming from an ethical standpoint. If you're just milking a snake you're not harming it." Another reason might be that reptiles and spiders are more readily available and easier to handle, says Sogol, who is pharmaceutical sciences director at Campbell University in Buie, N.C.Mother Nature Knows Best
Some scientists once predicted that doing drug discovery in nature would be made obsolete by laboratory synthesis of various molecules and computer simulations, a field known as combinatorial chemistry. But Mother Nature has a dazzling array of sophisticated, natural products.
It's hard to exaggerate the potential for drug discovery in nature's storehouse. Jerrold Meinwald, PhD, researches the role of chemistry in insect interactions, especially how they employ chemicals in mating, defense, and communication. Some of these chemicals, such as components of spider venom, may prove to have medical applications. "The venom they inject to paralyze prey contains novel neurotoxins that block certain receptors," he says. "It would seem very promising to go after spiders that haven't been looked at as potential neuropharmacological agents."
That would be a lot of spiders. Meinwald tells WebMD perhaps only 100 to 200 of the 30,000 known spider species have been studied. "There are many lifetimes of work," says Meinwald, who is Goldwin Smith Professor at Cornell University in Ithaca, N.Y.
One company, NPS Pharmaceuticals, specializes in researching and developing drugs based on spider and scorpion venoms. In the pipeline is a new class of drugs called "delucemines" (NPS1506) which act to protect brain cells and minimize brain cell death in stroke victims until blood flow can be restored. The drugs might also have potential in the treatment of depression.
With spiders, as with most species, the goal is to synthesize the active chemicals rather than depend on animals. "You can milk spiders' venom without killing them, but you don't get sufficient quantities," says Meinwald.
Synthesizing drugs to preserve the properties of a natural drug can be challenging. For example, Sogol tells WebMD some ingredients from saliva stay longer in the human body than a synthetic version. "They'll stay in the body longer, and that can be very positive. If you have diabetes and your current drug lasts four hours, it's better to have one that lasts 12 hours."From One Beautiful, Deadly Snail
The cone snail is celebrated for its beauty and feared for its poison, which on occasion has been known to kill swimmers. The deadly venom, however, is exceptionally rich in compounds called conopeptides that could be used or synthesized to make an array of pharmaceuticals. Cognetix, Inc., is researching applications for acute and chronic pain, epilepsy, local anesthesia, heart disease, stroke, neuromuscular back pain, multiple sclerosis, and spinal cord injury. Scientists are urging protection of the cone snail, which is on the brink of extinction.On the Horizon
Here are some of the areas in which drugs derived from animals are being investigated:
- Painkillers. ABT 594 comes from the skin of the South American frog. It appears to be more effective than morphine without being addictive.
- Cancer. TM 601 is derived from the Israeli yellow scorpion and attacks malignant brain tumors called glioma tumors responsible for two-thirds of the cases of brain cancer, without harming healthy cells. ET 743, which comes from sea squirts, is being tested for treatment of ovarian cancer and soft tissue sarcoma.
- Stroke. Ancrod, which will be marketed in the U.S. as Viprinex pending FDA approval, is an anticoagulant with potential to prevent cell damage and death when someone suffers a stroke. The active ingredient comes from the venom of the Malaysian pit viper. In Germany, where Ancrod has been marketed for a number of years, a specially built facility houses about 3,000 snakes. Several other sources of anticoagulants are being looked at. "We're still trying to find medicine that will be useful long-term for stroke victims," says Sogol. "There's saliva of vampire bats, for example. When they bite their prey, the enzyme in their saliva doesn't allow blood to clot. There's also something in the saliva of leeches that is an anticoagulant."
- Antibiotics. A substance called magainin 2 -- comes from the skin of frogs and looks promising in the search for antibiotics that bacteria can't develop resistance to. Studies began when biomedical researcher Michael Zasloff, MD, PhD, of Georgetown University in Washington, D.C., wondered how frogs could swim in filthy ponds without getting sick.
One of the most biodiverse and pharmaceutically promising regions of the world is the Brazilian rainforest, yet it's rapidly disappearing -- along with untold numbers of plant and animal species -- because of clearcutting. Moreover, fewer and fewer nations are now willing to collaborate with foreign researchers. "It's become very hard to establish any sort of international research effort because someone will say that the amount of financial reward offered to the supplier of natural products isn't fair," says Meinwald. "It's the concept of 'bio-piracy.' They think drug companies take their valuable resources, make a fortune and just give them crumbs. It's true that some drugs can sell at the level of a billion dollars a year. What people don't appreciate is that this happens, however, only after 10 or 12 years of research and investment. Most drug candidates fall through because of side effects or other problems."How Did It all Begin?
When you think about folk remedies dating back before the dawn of scientific discovery, what ever gave people the idea that, say, taking cod liver oil would relieve a cold or eating pearls would cure insanity?
"I don't know, but the same thing occurs to me about food," says Meinwald. "How in the world would people decide you could eat oysters? He surmises that people observed seagulls picking up oysters, dropping them from high in the air to break them open, then swooping down to eat them. Humans seem to have tried practically everything for eating. They may have noticed by similar experimentation that some things make you very sleepy or take away pain."
Published Dec. 8, 2003
SOURCES: Cognetix, Inc. "Strategies for Discovering Drugs From Previously Unexplored Natural Products," Drug Discovery Today, July 2000. Jerrold Meinwald, PhD, Goldwin Smith professor, department of chemistry & chemical Biology, Baker Laboratory, Cornell University, Ithaca, N.Y. NPS Pharmaceuticals. PBS A Science Odyssey: People and Discoveries, "Banting and Best Isolate Insulin." RSC Chemical Society Network. Smithsonian Ocean Planet web site. Elliott Sogol, PhD, spokesperson, American Pharmacists Association; director, pharmaceutical sciences, Academic Affairs for Clinical Research, Campbell University, Buie, N.C. WebMD Feature: "Lizard Spit Drug Helps in Diabetes."
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