Perspectives On Line - Winter 2002: Feature Article / "Zero at the Bone"
Perspectives On Line: The Magazine of the College of Agriculture and Life Sciences

NC State University

Winter 2002 Contents Page Features Research and Response A Cotton Conundrum Zero at the Bone College Profile Noteworthy News Giving Alumni From the Dean College of Agriculture & Life Sciences  






































"Zero at the Bone" by Art Latham:  Snake encounters are routine for Dr. Harold Heatwole and his zoology students as they research the ecological relationships of reptiles and amphibians.
Heatwole (right) and student Jim Green subdue a copperhead long enough to get a venom sample. (Photo by Art Latham)


r. Harold Heatwole grasps the metal handle of the snake-pinner, warily eyes the four-foot-long copperhead slithering around the nearby terrarium and glares at the students gathered in the snake shed.

“We do this step by step,” he patiently explains of the venom-“milking” they are about to attempt. “We talk to each other at all times to be certain where we are in the process.”

Seemingly hypnotized like mongooses before a cobra, the students listen attentively.

After more than 45 years of handling thousands of snakes in the wilds and in labs, Heatwole has been bitten only once — by a venomous sea snake in the South Pacific — and he doesn’t intend for it to happen again, to him or his charges.

The bite was less traumatic than it could have been because Heatwole, then a zoology professor at the University of New South Wales, knew what to expect. And that expertise continually informs his concern for his students’ safety and his research.

Since he came to North Carolina State University’s College of Agriculture and Life Sciences in 1991, he and his students have continued researching the ecological relationships of amphibians and reptiles. For many years, he has concentrated on sea snakes and other venomous reptiles, as well as ants and tardigrades, microscopic, four-legged arthropods that live in water or damp moss.

A professor in the College’s Department of Zoology, Heatwole often works under extreme conditions in remote, wide-ranging locations from deserts to remote islands, including the Sahara, Gobi and Taklamakan deserts, sites along the Great Barrier Reef, in the Torres Strait north of Australia, in Central American rainforest canopies and in Antarctica.

Yet this certified challenger of the unknown — he’s a fellow of the prestigious Explorers’ Club, which requires a member’s exploits to be documented, is on the editorial board of the Journal of Arid Environments, is president of the Australian Coral Reef and the Australian Herpetological societies and was president of the Great Barrier Reef Committee — wants to make sure that his students get credit for their work.

He ticks off a few student projects, all designed to produce valid experiments, as well as research experience and training to add to the body of knowledge:

Bryan Stuart, looking at saliva enzymes in venomous and non-venomous snakes, found that even a harmless snake’s saliva has a much higher meat-digesting enzyme evolution than any other vertebrate group.

“Many snakes, if they have a meal say, late in the season, and can’t raise their body temperatures to digest it, then their digestion slows so much the meal putrefies, and they either regurgitate it or it can kill them,” Heatwole says.

“The role of venom in snake digestive processes indicates that in addition to subduing prey, venom allows snakes to digest food at lower ambient temperatures than they otherwise could,” he says. “Perhaps this is why more venomous snakes occur at higher elevations and latitudes — even above the Arctic Circle — than non-venomous ones.”

Adam Parry tracks magnetized mice through non-venomous corn snakes’ digestive tracts to learn how long it takes them to digest a meal at different temperatures.

“As expected, the higher the temperature, the quicker the digestion,” Heatwole says. “So we deduce the enzymes work faster at higher temperatures. Then we inject mice with cottonmouth venom — because the venom from the fangs of venomous snakes might contaminate the specimen — and feed them to harmless snakes to see the effect venom has on digestibility.

“That experiment is still in progress, but it looks like at higher temperatures, there is little difference in the digestion rate of treated or non-treated. But at low temperatures it looks like digestion is a lot faster, so a venomous snake is less likely to suffer possibly fatal indigestion than a non-venomous snake,” he says.

• Former student Mike Bower, sampling seven major cottonmouth venom toxins year-round at constant temperatures and light, found that venom changed seasonally, especially in the spring.

“The proportions changed,” Heatwole says, “but we don’t know why yet, although the hypothesis is that amphibians are much more abundant in spring and come into the water to breed, and in cottonmouths and other semiaquatic species, the venom is specifically tailored and seasonally adjusted to the available prey. In winter even the volume of venom produced decreases.”

Stephanie Gregory researched food selection by newborn cottonmouths, which, with no previous learning behavior, overwhelmingly selected frogs and fish.

Jim Green, looking for specific effects of venom in frog tissues has learned, among other things, that liver is much more venom-sensitive than muscle.


How do students obtain venom samples needed for such experiments? V-e-r-r-r-r-y carefully, as Heatwole demonstrates in the snake shed (photo sequence above and below). He pries the plastic top off the glass terrarium as the copperhead inside slithers around a bit more. He grasps the snake with metal pincers and, holding it a safe distance in front of him, carries the wriggling creature outside, where he and student Jim Green milk its fangs for venom. To do this, Green secures the snake's head with both hands as Heatwold holds out the edge of a small, clear-plastic cup, which the snake immediately strikes, locking on with jaws that lool large enough to accomodate a small rabbit. Green maintains a hand lock just behind the snake's head until a thin stream of orangish-yellow venom collects in the cup, then reverses the procedure. Together, they carefully unlock the cup from the snake's fangs, pin the snake on the ground, lock it with the grasper and carry it back to its glassy den. They've accomplished another venom-milking without injury to snake or humans, and science marches safely on. (Photos by Art Latham)

eatwole, a native-born American, conducted his ongoing work on snake venom at Australian universities for more than two decades.

In a recent conversation, he discussed one aspect his studies, a sort of arms race by creatures with no arms: the co-evolution of venom resistance by snakes’ prey and the converse evolutionary toxicity increase by the predators.

“There seems to be almost an arms race between the highly toxic sea snakes and the eels that are their prey,” Heatwole notes. “The snakes can swallow an eel almost their own size. To kill and swallow something that big that can attack you, you need something strong, and the snakes’ adaptation has been a gradual development of more virulent toxin over time.

“From the eels’ standpoint, they are selected to be more resistant to the venom as an adaptation that allows counterattack and escape. We injected one of those eels with the equivalent of 52 venom doses, which would have been lethal to humans, and it barely affected it,” he says.

Then Heatwole found an eel species on New Guinea reefs that was highly resistant to sea snake toxin and compared it with others that weren’t a recorded part of the sea snakes’ diet.

“The ones the sea snakes didn’t feed on didn’t live in the same habitat, so there had been no co-evolution, no buildup in resistance to the snake venom; they were more sensitive to it,” Heatwole says.

Suspecting that the venom-resistant eel might just be harder to kill, Heatwole and his researchers searched for comparative eels elsewhere, where no sea snakes live and the eels have no reason to adapt to venom. Since the venom-resistant Pacific eel is related to a Caribbean species, they wondered if the Caribbean eel might also be venom-resistant.

“But when we went to the Bahamas and tested them out, they were venom-sensitive, so it was co-evolution in the Pacific,” he says.

Heatwole’s research at N.C. State also includes a venomous water snake, the cottonmouth moccasin and its prey.

The deadly cottonmouths relish fish, frogs, lizards, other snakes, mammals or any vertebrate but two: bullfrog tadpoles and toads.

“This is almost a reversed situation from the eels,” Heatwole says. “An animal protected from a toxic snake by its own skin toxins is interesting. When the bullfrogs metamorphose, their skin changes and they’re eaten by the cottonmouth, although when they get larger, their size protects them. But as tadpoles, they are protected by their skin toxins.

“The toads, on the other hand, produce skin secretions throughout their lives, and cottonmouths won’t eat them. They have no immunity to snake venom, but they don’t need it, because in this case they’re the ones with the toxin. But some snakes, like the hognose, are resistant to toxic skin secretions from the toads and eat only toads, having developed a resistance to them,” he says. “This is also co-evolution.”


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