Ground squirrels that can take on rattlesnakes-and win-may offer humans a key to developing better treatment for snake venom, suggest findings by researchers at UC Davis.

Building on a quarter-century of UC Davis research on the age-old battle between snake and squirrel, the scientists found that resistance to rattler venom among California ground squirrels varies according to the local snake population density.

Squirrels from two areas where northern Pacific rattlesnakes are common-the rugged canyons near Sunol and hills near Winters-had high resistance to that particular snake's venom.

In the absence of rattlesnakes, squirrels' resistance fades-but slowly over tens of thousands of generations.

In Davis, blood samples from ground squirrels were as effective as blood drawn from their Winters cousins in neutralizing northern Pacific rattlesnake venom-even though the Davis squirrels' ancestors have lived apart from rattlers for 6,000 to 9,000 years.

Only in Sierra Valley north of Truckee had squirrels lost their biological protection against Northern California's only native rattler. Their ancestors apparently lived for tens of thousands of years in a cold setting free of rattlesnakes until colonizing Sierra Valley about 9,000 years ago.

UC Davis researchers say the study, reported in a recent issue of the journal Toxicon, provides an excellent model of an evolutionary arms race between predator and prey.

"Rattlesnakes have been an important part of the life history of ground squirrels for thousands of generations," said James Biardi, who studied the squirrels' venom resistance while completing his doctorate degree in ecology.

"In California, as ground squirrels have developed resistance to rattlesnake venom over thousands of years, rattlesnakes have had to adjust their venom," Biardi said. In turn, natural selection leads to ground squirrels adapting better resistance.

Ground squirrels make up close to 70 percent of the rattlesnakes' diet, particularly squirrel pups with small body sizes, unable to neutralize a full dose of venom.

However, in field studies beginning in the 1970s, psychology professors Donald Owings and Richard Coss have seen adult squirrels provoke snakes into striking, then brush off bites that could dangerously sicken or even kill humans.

"They can essentially beat up on a rattlesnake and not feel any ill effects," Biardi said.

Squirrels also will kick dirt and pebbles at snakes and sometimes attack and bite them-behaviors that the researchers believe helps squirrels identify and measure up their foe.

In staged encounters between squirrels and tethered rattlers in earlier studies, Biardi said the researchers "sometimes had to go save the snake."

In the latest study, the researchers live-trapped, anesthetized and drew blood samples from the squirrels before releasing them back into the wild.

The squirrels' blood serum was then tested to see how well it protected gelatin, cowhide and other animal substances from being digested by venom from three types of rattlesnakes.

Surprisingly, the Sierra Valley squirrels, while no longer resistant to California's northern Pacific rattler, showed the highest resistance of the four groups tested toward the prairie rattlesnake found in the Midwest.

However, in a puzzling discovery, their blood actually exaggerated the destructiveness of venom from the Western diamondback, common to the arid Southwest.

Other squirrel populations also showed varying degrees of resistance to prairie and Western diamondback rattlesnake venom. However, their protection was weaker for the non-native rattlers than for the northern Pacific rattlesnake.

Such differences, the researchers say, could provide clues for developing safer, more effective antivenin for people bitten by rattlesnakes.

Biardi and Coss suggested that by isolating and synthesizing venom-neutralizing proteins in the blood from a variety of squirrels and other rattler-resistant mammals such as the gray woodrat and Virginia opposums, biomedical researchers could develop an antivenin effective against the numerous rattler species found in the Western Hemisphere.