Dr. Karen Lips remembers when she came across the first infected frog at her pristine research valley in the cloud forest of El Cope in Panama.

For eight years, a team of scientists worked with Lips, a conservation biologist at the University of Maryland, to stake out conditions at the site, logging the number of frogs, tadpoles, and eggs for each frog species. They surveyed almost 30,000 amphibians. The team also kept track of where the frogs lived, when they bred, and the types of predators they faced.

“Everything was great until one day we found an infected frog. The next week we found the first dead frog. And within the next 4 months, we found 400 dead frogs,” says Lips. The frogs were infected with an amphibian skin fungus. “Seventy percent of the species that occurred there were found either dead or infected.”

By the next year, all the frogs in the streams had disappeared. Now, above the mountain streams of El Cope, the cloud forest is eerily silent – devoid of once-ubiquitous frog calls, but also of the rustling of snakes and the scrambling of lizards. The streambeds grow slick with algae that blooms unchecked without interference from snacking tadpoles stirring up sediment. The tadpoles also infused the crystal-clear streams with nitrogen – important for plant growth.

“The minute the tadpoles are gone, the water quality changes,” says Lips. “Whatever happens in those headwaters has an impact downstream.”

The fungus epidemic at El Cope documented how the disappearance of frogs triggers a chain reaction in an ecosystem. The storm front of the amphibian fungus is advancing 14 to 62 miles per year on every continent but Asia. It’s probably responsible for the extinction of at least 100 amphibian species since the 1970s. But the biggest menace to frogs remains habitat loss from development, pollution, and global climate change.

With nearly a third of the known 6,300 species under threat, scientists are racing to better understand the role of the frog in our world. Frog science may evoke the smell of formaldehyde and the image of scalpels glinting by pinned and splayed legs, but scientists have been turning to frogs — while they’re still alive — to better understand the health of our ecosystems and our bodies.

The evidence of algae growth spurred by tadpole declines describes only one fractured link in the ecological chain anchored by frogs. Wasps and spiders eat frog eggs; shrimp, fish, and dragonfly nymphs eat tadpoles; birds, snakes, and lizards eat frogs; and frogs in turn eat a wide variety of worms and insects.

“Amphibians play a huge role in these ecosystems in terms of feeding on insects and flies, many of which are disease vectors for lots of human diseases,” says Lips.

By eating pests like mosquitoes and their larvae, frogs may control the spread of diseases like avian malaria and dengue fever.

As a side effect of filling their bellies with bugs, some frogs concentrate chemicals called alkaloids in their skins. The frogs act as vacuum cleaners, sucking up insects or mites that contain the alkaloids. Studying the skins of poison frogs has yielded a catalog of over 800 alkaloids.

Researchers are just beginning to explore the chemical goldmine to be found in the skins of frogs, especially tropical and Australian frogs – the very frogs that are hardest hit by the amphibian chytrid fungus. Chemicals secreted and sequestered by frogs may turn out to be very useful to humans.

In the wild, the one-inch-long poison dart frog secretes enough of an alkaloid called batrachotoxin to kill 100 people. The poison locks open the sodium channel in nerve cells, potentially leading to cardiac arrest. Scientists examine the channel’s mechanism to study drugs like anesthetics and antidepressants.

The lessons locked in alkaloids may be able to be used to create non-addictive painkillers, appetite suppressants, and medicines to fight Alzheimer’s disease. Several pharmaceutical companies — Abbott Labs and Cephalon Chemicals among them — are exploring chemical equivalents to the frog alkaloids.

Another pharmaceutical company, Genaera, examined another type of chemical secreted by frogs – protein-like molecules, or peptides, called magainins that help frogs’ skin heal quickly from wounds. Magainins can be antifungal, antiparasitic, antibiotic, and antiviral.

Researchers at Vanderbilt University Medical Center in Nashville, Tennessee, found magainins in the red-eyed Australian tree frog that may block infection by HIV – the virus that causes AIDS. The peptide punches holes in the virus’s cell membrane to destroy the virus – instead of attacking internal chemicals like most modern medicines.

And that’s just one peptide, from one frog. Another peptide — from the giant Mexican leaf frog — has shown promise as a potential treatment for high blood pressure. Yet another peptide from the same frog prevents blood clotting and could help scientists cure deep vein thrombosis and heart disease.

Frog toxins may hold keys to unlocking mysteries about our own bodies. But as frog populations face unexplained and unprecedented declines, what we can learn from frogs depends on how long they will be around.

“There are a lot of exciting things going on,” says Lips about the explosion of frog research. But she worries about the future for frogs. “At this point, we’re just keeping our fingers crossed and hoping for something to come through, because it’s not looking good.”

NOTE: Never intentionally provoke a poisonous snake to bite you. This video discusses early-stage medical research, not currently viable options for treatment. If you or someone you know is suffering from cancer, you are strongly urged to seek professional medical care.

When we are sick, or suffering discomfort from diarrhea or indigestion, we take medicines to make us feel better. We know what ails us, and we know what can help us. Monkeys, too, seem to have knowledge of the therapeutic. New cases are reported every year, and zoopharmacognosy, the study of self-medication in animals, is a growing field. The fur-rubbing white-faced capuchins and the charcoal-eating red colobus monkeys seen in Clever Monkeys are just two examples of medical ingenuity in primates. Across the globe, monkeys have figured out remedies for common ailments, just as we have.

One of the greatest dangers to monkeys, and one of the greatest annoyances, are insects and parasites. Ectoparasites like lice, ticks, and mosquitoes carry many diseases to which monkeys are susceptible. Evolutionary biologists believe that parasites coevolved with their hosts over eons, and both humans and monkeys have continually sought relief from these pests. Itching, scratching, and swatting are the only options for most animals, but primates have evolved several novel approaches. Grooming is an effective way to pick off pesky bugs, but the white-faced capuchins seen in Clever Monkeys take pest control to another level. They rub themselves with leaves from the piper plant, which is also used by some people in Costa Rica as an insect repellant. The piper leaves are also antiseptic, which helps ward off bacterial and fungal infections. Fur-rubbing episodes in the white-faced capuchin monkeys correlate markedly with increases in humidity. The capuchins know that increased humidity means an increase in the abundance of insects, and the risk of bacterial and fungal skin infections. Capuchins also sometimes rub their fur with millipedes that contain benzoquinones, chemical compounds that repel insects. Owl monkeys and lemurs have also been observed fur-rubbing with millipedes. Only in the capuchins does fur-rubbing play a social role. In Clever Monkeys, the white-faced capuchins become quite excited and enthusiastically gather together to anoint each other with the piper plant. What underlies this party-like behavior is a simple protective measure for the group: each member of the group benefits if the group as a whole is protected from parasites.

Primates also have to deal with intestinal parasites. Tamarins have been known to swallow large seeds that in effect dislodge and sweep worms out of their intestinal tract. This practice markedly decreases the parasitic load within their intestines. Other monkeys experience bouts of diarrhea brought on by parasites and viruses. The bonnet macaques of Southern India have taken to eating dirt from termite mounds. Why eat dirt from termite mounds? The dirt contains kaolin minerals, the same ingredient found in over the counter anti-diarrhetics such as Kaopectate. Rhesus macaques also partake in geophagy, the eating of dirt, for the same reasons. Clay also contains kaolin, and the rhesus macaques take extra care to only ingest clay-rich soils. Like the white-faced capuchins, which only select plants for fur-rubbing with insecticide properties, the macaques selectively choose the right kinds of dirt to sooth their stomachs.

Because their leafy diets contain high levels of cyanide, many monkeys, like the black and white colobus in Clever Monkeys, suffer from indigestion. The discovery by red colobus monkeys that eating charcoal absorbs the cyanide and relieves indigestion was revolutionary. The practice is transmitted from mother to infant by imitation. Knowledge is passed from generation to generation, just as the most tested and true remedies have been passed down by earlier generations of humans. With the toxins being absorbed, the red colobus monkeys are free to eat a wider array of plants that have a high nutritional value and are easily digested. The birth rates in red colobus monkeys that eat charcoal have exploded, proving an evolutionary advantage to self-medicating. It is their clever mind, their curiosity, and their novelty that have made them successful. The same could be said about us. 

Photo © Wiebke Lammers

When it comes to research on venom and converting it into useful drugs, studies involving exotic snakes or brightly colored frogs seem to attract the most attention. However, one of the most promising new venom-derived drugs actually comes from a very modest-looking sea snail.

Worldwide, there are more than 600 kinds of cone shells found mostly in tropical waters around the Pacific. Collectors love them because their shells are decorated with an amazing array of intricate patterns.

Biologists, however, have long been fascinated by the behavior of these clever hunters. Some cone shells target other snails, while others like to feast on fish. To sense food, cone shells filter water through a tubelike organ called a siphon, awaiting a whiff of the telltale chemicals emitted by their prey.

To sense food, cone shells filter water through a tubelike organ called a siphon.

Then, when its victim comes near, the cone shell extends a proboscis armed with a harpoonlike tip that injects venom filled with special chemicals called “conotoxins.” These toxins stop nerve cells from communicating with each other, causing paralysis within seconds and, eventually, death. Cone shells have even killed people who pick them up, unaware of the danger. Indeed, cone snail venom is so powerful and painless that victims can die unaware that they’ve even been bitten.

Conotoxins have long interested medical researchers because of their potential painkilling abilities. It turns out, however, that cone shell venom is very complex; each kind contains perhaps 50 or more different chemicals that target the brain and nervous system. Overall, researchers believe that more than 50,000 conotoxins may exist. That diversity has made it hard for them to isolate a specific chemical to work on.

But over the last few decades, conotoxins have begun to give up their secrets. Researchers have published more than 2,500 papers on the chemicals, and have described and identified more than 100 specific toxins which show promise for treating everything from arthritis to cancer. But the first new drug derived from a conotoxin, approved in 2004, targets chronic pain. Researchers estimate that the drug, based on the venom from the delicate gray and ivory magician cone shell, is a thousand times stronger than morphine, the most powerful traditional painkiller.

Even as cone shells show promise for medicine, however, their survival may be at stake. Collectors gather millions of the animals each year for the decorative shell trade. Demand from conotoxin researchers is growing too, since many shells may be needed to produce even small amounts of toxin. And coral reefs, which support more than half of all cone shell species, are under increasing threat from human activities.

To protect cone shells, biologists are asking nations in tropical zones to take new steps to monitor the shell trade and protect reefs. “To lose these species would be a self-destructive act of unparalleled folly,” researcher Eric Chivian of Harvard University in Cambridge, Massachusetts wrote in a 2003 paper published by the journal SCIENCE. “Tropical cone snails may contain the largest and most clinically important pharmacopoeia of any [group of animals] in nature.”

Animal Medicine

Some of the most gripping scenes in the NATURE program Animal Attractions show the drama of veterinary medicine at the San Diego Zoo and Wild Animal Park. Animal health care is an important part of the zoo’s mission, and staff members pay daily “house calls” to residents. Whether an infant gorilla is struggling for life, a cheetah is giving birth to a premature litter, or a white rhino is receiving hormone therapy, every creature’s case is taken very seriously in the zoo’s “animal E.R.”

Imani, a western lowland gorilla born at the zoo in 1997, arrived in the intensive care unit within 72 hours of her birth. The two-pound infant was weak and tiny, less than half the weight of a normal newborn gorilla. In addition, her blood showed dangerously high levels of bilirubin, a toxin that can cause brain damage.

Imani was bottle-fed, given ultraviolet light treatments to flush the bilirubin from her system, and watched as carefully as any human preemie. For days, veterinarians held their breaths: Would Imani make it? Luckily, they were able to stabilize the tiny primate, who grew to be a healthy toddler. When she joined the others in the zoo’s “Gorilla Tropics”, she was adopted by Alvila, an older female, and welcomed to the family.

A few months after Imani’s successful recovery, a cheetah went into labor. The mother had lost her previous litter, so zoo veterinarians decided to perform surgery to remove the four cubs inside her womb. The cheetah was put under anesthesia in preparation for her Caesarian section.

One by one, veterinarian Dr. James Oosterhuis drew out the tiny cubs from the mother’s open belly and cleaned off the protective sacs that held them. But something was wrong: the cubs were not breathing. Four veterinarians immediately began blowing baby-size breaths into the infants’ mouths and massaging their floppy bodies to stimulate their organs until the newborns began to squeal. The infants were placed directly into the incubator to gain strength. Sadly, the cubs’ luck did not hold. Too weak to withstand infection, the cubs died within the week. But Oosterhuis is hopeful that next time, the mother cheetah will be able to give birth successfully.

The northern white rhinoceros is in terrible danger of extinction: only about 30 remain in the world. The San Diego Wild Animal Park introduced Nola, a female who had never borne offspring, to Angie, a male who had travelled all the way from a zoo in Sudan. The veterinarians hoped he would become her mate. But at the relatively old age of 25, Nola was a tough customer.

Fierce and aggressive, she repelled Angie’s overtures, actually bowling him over when he tried to get to know her better. Hormone therapy brought Nola into heat, but did nothing about her continued aggression. Wild Animal Park workers knew something drastic had to be done. A decision was made to saw off her horn in the hopes that without it, Nola might be more receptive — and less dangerous — to Angie. After anesthetizing Nola for the procedure, the veterinarians took the opportunity to give her an examination — a difficult feat to manage when a beast weighing almost two tons is awake and less than cooperative. They trimmed Nola’s hooves, checked her eyes and ears, and monitored her vital signs.

Then they removed the horn. Rhino horns are made mostly of keratin, the same material as human fingernails, and sawing one off is a painless exercise. It is also temporary: Nola’s horn would eventually grow back.

Meanwhile, once the horn was cut off, Angie and Nola mated several times, although Nola has yet to become pregnant. The veterinarians at the San Diego Wild Animal Park continue to observe the rhinos’ behavior carefully, knowing that a baby rhino would be a big step towards ensuring the survival of this dwindling species. And every day, the veterinarians remain ready for animal medical emergencies, aware that the lives of these creatures are in their hands.