The New York Times,
November 22, 2005Link
Which came first, the snake or the venom?
Bryan Fry, a biologist at the University of Melbourne who has spent the last few years reconstructing the evolutionary history of snake venom, decided to find out.
He had already isolated genes for toxins in cobras, rattlesnakes and other deadly species. And he had discovered related genes in harmless species like garter snakes.
Those results, which Dr. Fry published in the spring, suggested the long history of snake venom. The common ancestor of living snakes, which existed 60 million years ago, produced venom, albeit a small, relatively low dose. Only later, in certain lineages, did snakes evolve a deadlier bite.
Since snake venom was so ancient Dr. Fry wondered whether those first genes for venom evolved after snakes had branched off from other reptiles or whether they were passed down to snakes from an earlier ancestor. It was possible that lizards, the closest relatives of snakes, might still carry these ancient venom genes. Dr. Fry set out to look for them.
"I just wanted to see how far back I could take snake venom," he said.
He joined forces with an international team of herpetologists to catch lizards in the wild and buy other species at reptile shows. They collected cells from the mouth secretions of the lizards and cataloged the genes that were active in them.
The researchers then began comparing these genes to those for snake venom. "We isolated some rattlesnake toxins from the bearded dragons and started getting really excited," Dr. Fry said. Further research turned up venom genes in other species.
Dr. Fry and his colleagues also found that the proteins encoded in these genes had the same effect as snake venom. One protein produced by the lace monitor, an Australian relative of the Komodo dragon, causes the aorta to relax suddenly.
Many venomous snakes use a related version of this toxin to bring on an abrupt drop in blood pressure, causing their prey to lose consciousness.
Dr. Fry gained a personal appreciation for lace monitor venom when a lizard he had collected bit his finger. The finger swelled and bled for half an hour, probably as a result of blood-thinning toxins produced by the lace monitor. "The first words out of my mouth to my wife were, 'Get the camera out,' " Dr. Fry said.
Lizard venom may have gone unnoticed for so long because it is not fatal. Yet it may help lizards catch prey.
"They can knock their prey out so it will struggle less," Dr. Fry said. "And while that may not kill the prey, it will still give these animals the chance to tear its head off."
Knowing that lizards had similar venom was intriguing, but did not solve the question of how and when it evolved. And scientists have long debated which of the 4,750 species of lizards are the closest cousins to snakes.
Fortunately, two of Dr. Fry's colleagues, Nicolas Vidal and S. Blair Hedges of Pennsylvania State University, had been putting together a large-scale DNA study. "We finally got enough data this year to resolve the problem," Dr. Hedges said. The venom came first, snakes later.
The new research indicates that when snakes first evolved 100 million years ago, their venom genes were already 100 million years old. Dr. Vidal and Dr. Hedges compared nine genes in 19 species of lizards and snakes. Snakes, the researchers found, are closely related to a group of lizards that includes iguanas, Komodo dragons, bearded dragons and Gila monsters. It's only among these lineages that the researchers have discovered venom. More distantly related lizards like geckos and skinks have no venom genes.
The new findings were published online by the journal Nature on Nov. 16.
"I think that it is a milestone study," said Dr. Christopher Shaw, a venom expert at Queen's University in Belfast who was not involved in the new research.
Dr. Fry found that the common ancestor of snakes and their close relatives, which lived 200 million years ago, already had a sophisticated arsenal of at least nine venoms. He also found that Gila monsters did not evolve their venom independently from snakes, as had been thought. A common ancestor bequeathed the same venoms to Gila monsters and snakes. Later, these lineages evolved more potent venoms.
Another twist concerns the Komodo, the largest lizard in the world. Scientists have long believed that bacteria in its the mouth cause a devastating infection. Dr. Fry argues that lizard venom calls that into question.
Komodos may actually cripple prey with venom. As the prey tries to run away, some of the venom molecules prevent clotting, causing it to bleed more. Other venom molecules cause muscle weakness and low blood pressure, further driving the prey to exhaustion.
"The old theory that the Komodo dragon killed prey by infecting them with bacteria never rested well in my breast," Dr. Shaw said.
Dr. Fry is now studying monitor lizard venom for potential drugs. For years, doctors have used medicines based on snake venoms to lower high blood pressure and break up clots.
Lizard venom may prove even more useful. For some reason, the molecules in lizard venom are much smaller than those in snakes. Small molecules are less likely to be noticed by the immune system, meaning that they are less likely to cause allergic reactions.
"I reckon we'll be able to get something useful out of them," Dr. Fry said.
Unfortunately, even as scientists discover these promising drug candidates, many of the lizards that produce them are threatened with extinction. "Here we have these animals that could potentially have the next wonder drug are literally getting wiped out before our eyes," said Dr. Fry.
Copyright 2005 The New York Times Company