Post by Bozur on Apr 8, 2005 16:35:28 GMT -5
NYTimes.com > Science
Open Wide: Decoding the Secrets of Venom
By CARL ZIMMER
Published: April 5, 2005
Tom McHugh/Photo Researchers Inc.
A red diamondback rattlesnake bares its fangs.
The inland taipan, a nine-foot-long Australian snake, is not the sort of creature most people would want to bother. Drop for drop, its venom is the deadliest in the world, 50 times as potent as cobra venom. Its fangs are so long they can poke through the snake's lower jaw. Its victims collapse in seconds and suffer a quick death.
Dr. Bryan Fry, a biologist from the University of Melbourne, will readily admit he is not like most people. He not only bothers inland taipans; he hunts them down in dense cane fields, pins them down and bags them. Later he grabs them by the head and squeezes venom from their fangs.
Besides inland taipans, Dr. Fry collects venom from death adders, rattlesnakes, king cobras, sea snakes and many others. He estimates that he handles 2,000 to 3,000 snakes a year.
"Working with some of these snakes is the biggest adrenaline rush you could ever do," he admitted. "I used to do extreme ski jumping and big wave surfing, but none of that can touch working with some of these animals."
Ultimately, this rush is not what drives Dr. Fry, who is 34. His goal is to decipher the evolution of snake venoms over the past 60 million years. Reconstructing their history will help lead to medical breakthroughs, Dr. Fry believes. For the past 35 years, scientists have been turning snake venoms into drugs. Just this February, Dr. Fry and his colleagues filed a patent for a molecule found in the venom of the inland taipan that may help treat congestive heart failure.
Understanding the evolution of snake venoms will speed up these discoveries immensely, Dr. Fry predicted. "You need a good road map to get your research going," he said.
Snakes produce venom in special glands on either side of their upper jaw. When they strike their prey, they squeeze the gland, causing the venom to spurt out. In some species, the venom simply pours into the wound. In other species, like cobras and inland taipans, the venom first flows into hollow fangs and then into the prey.
Once venom molecules enter a snake's prey, they become intimate assassins. Their intricate shapes allow them to lock onto particular receptors on the surface of cells or onto specific proteins floating in the bloodstream.
Some venom molecules can plug the channels that muscle cells use to receive signals from neurons to contract. Without the signals, the muscles go slack, leading to asphyxiation. Other venoms send the immune system into a tailspin, making it attack the prey's organs. Still others loosen blood vessel walls, leading to shock and bleeding. Rather than rely on one of these attacks, most venomous snakes produce a cocktail of molecules.
Dr. Fry says he has been fascinated by venomous snakes ever "since I could walk." By the time he started his dissertation research on the inland taipan in the late 1990's, he was already experienced at catching snakes and milking their venom. To find new toxins, he would weigh the molecules in the venom, and when he found molecules that were close in weight to known venoms, he would isolate them for a closer look.
As Dr. Fry discovered more venoms, he began to wonder how they had evolved. "It's been an area of great controversy," he said. Many researchers have argued that different lineages of venomous snakes, like rattlesnakes and cobras, evolved venom independently. They observed that the closest relatives of these venomous snakes were nonvenomous.
Dr. Fry discovered that they were wrong. "Most of the snakes that we think of as nonvenomous are actually venomous," he explained. Garter snakes and many other supposedly nonvenomous snakes actually produce tiny amounts of venom.
Dr. Fry is quick to point out that this does not mean that garter snakes are dangerous. "All they need to do is stun a frog or slow it down a bit, and it's enough to help them," he said.
These discoveries prompted Dr. Fry to carry out a large-scale study of the evolution of snake venom. His project would have been impossible a few years ago, because traditional methods for identifying new venoms are painfully slow. But the technology developed for the Human Genome Project has changed all that.
"Instead of spending a couple months and getting two or three protein sequences done, in a month I can get up to 2,000 sequences done," Dr. Fry said. "It's an amazing increase in efficiency."
"Fifteen years ago, this wouldn't even be thought of," said Alejandro Rooney, a molecular evolutionist at the National Center for Agricultural Utilization Research in Peoria, Ill., who has collaborated with Dr. Fry on some of his venom research.
Dr. Fry is able to identify all of the genes that are active in venom gland cells, and then read their DNA sequence. About half of the genes that are active in a venom-gland cell produce well-known "housekeeping" proteins that are essential to any animal cell. Most of the others are venoms.
After identifying new toxins, including many that represent entirely new types of venom, Dr. Fry said, "I think we've just scratched the surface."
Open Wide: Decoding the Secrets of Venom
By CARL ZIMMER
Published: April 5, 2005
Tom McHugh/Photo Researchers Inc.
A red diamondback rattlesnake bares its fangs.
The inland taipan, a nine-foot-long Australian snake, is not the sort of creature most people would want to bother. Drop for drop, its venom is the deadliest in the world, 50 times as potent as cobra venom. Its fangs are so long they can poke through the snake's lower jaw. Its victims collapse in seconds and suffer a quick death.
Dr. Bryan Fry, a biologist from the University of Melbourne, will readily admit he is not like most people. He not only bothers inland taipans; he hunts them down in dense cane fields, pins them down and bags them. Later he grabs them by the head and squeezes venom from their fangs.
Besides inland taipans, Dr. Fry collects venom from death adders, rattlesnakes, king cobras, sea snakes and many others. He estimates that he handles 2,000 to 3,000 snakes a year.
"Working with some of these snakes is the biggest adrenaline rush you could ever do," he admitted. "I used to do extreme ski jumping and big wave surfing, but none of that can touch working with some of these animals."
Ultimately, this rush is not what drives Dr. Fry, who is 34. His goal is to decipher the evolution of snake venoms over the past 60 million years. Reconstructing their history will help lead to medical breakthroughs, Dr. Fry believes. For the past 35 years, scientists have been turning snake venoms into drugs. Just this February, Dr. Fry and his colleagues filed a patent for a molecule found in the venom of the inland taipan that may help treat congestive heart failure.
Understanding the evolution of snake venoms will speed up these discoveries immensely, Dr. Fry predicted. "You need a good road map to get your research going," he said.
Snakes produce venom in special glands on either side of their upper jaw. When they strike their prey, they squeeze the gland, causing the venom to spurt out. In some species, the venom simply pours into the wound. In other species, like cobras and inland taipans, the venom first flows into hollow fangs and then into the prey.
Once venom molecules enter a snake's prey, they become intimate assassins. Their intricate shapes allow them to lock onto particular receptors on the surface of cells or onto specific proteins floating in the bloodstream.
Some venom molecules can plug the channels that muscle cells use to receive signals from neurons to contract. Without the signals, the muscles go slack, leading to asphyxiation. Other venoms send the immune system into a tailspin, making it attack the prey's organs. Still others loosen blood vessel walls, leading to shock and bleeding. Rather than rely on one of these attacks, most venomous snakes produce a cocktail of molecules.
Dr. Fry says he has been fascinated by venomous snakes ever "since I could walk." By the time he started his dissertation research on the inland taipan in the late 1990's, he was already experienced at catching snakes and milking their venom. To find new toxins, he would weigh the molecules in the venom, and when he found molecules that were close in weight to known venoms, he would isolate them for a closer look.
As Dr. Fry discovered more venoms, he began to wonder how they had evolved. "It's been an area of great controversy," he said. Many researchers have argued that different lineages of venomous snakes, like rattlesnakes and cobras, evolved venom independently. They observed that the closest relatives of these venomous snakes were nonvenomous.
Dr. Fry discovered that they were wrong. "Most of the snakes that we think of as nonvenomous are actually venomous," he explained. Garter snakes and many other supposedly nonvenomous snakes actually produce tiny amounts of venom.
Dr. Fry is quick to point out that this does not mean that garter snakes are dangerous. "All they need to do is stun a frog or slow it down a bit, and it's enough to help them," he said.
These discoveries prompted Dr. Fry to carry out a large-scale study of the evolution of snake venom. His project would have been impossible a few years ago, because traditional methods for identifying new venoms are painfully slow. But the technology developed for the Human Genome Project has changed all that.
"Instead of spending a couple months and getting two or three protein sequences done, in a month I can get up to 2,000 sequences done," Dr. Fry said. "It's an amazing increase in efficiency."
"Fifteen years ago, this wouldn't even be thought of," said Alejandro Rooney, a molecular evolutionist at the National Center for Agricultural Utilization Research in Peoria, Ill., who has collaborated with Dr. Fry on some of his venom research.
Dr. Fry is able to identify all of the genes that are active in venom gland cells, and then read their DNA sequence. About half of the genes that are active in a venom-gland cell produce well-known "housekeeping" proteins that are essential to any animal cell. Most of the others are venoms.
After identifying new toxins, including many that represent entirely new types of venom, Dr. Fry said, "I think we've just scratched the surface."