Reuters, May 27, 2010
Researchers say it may be best way to treat lethal virus.
A gene silencing approach can save monkeys from high doses of the most lethal strain of Ebola virus in what researchers call the most viable route yet to treating the deadly and frightening infection.
They used small interfering RNAs or siRNAs, a new technology being developed by a number of companies, to hold the virus at bay for a week until the immune system could take over.
U.S. government researchers and a small Canadian biotech company, Tekmira Pharmaceuticals, worked together to develop the new approach, described in the Lancet medical journal on Thursday.
"The delivery system is the real key," said Thomas Geisbert of Boston University School of Medicine, who did some of the work while at the U.S. Army Medical Research Institute of Infectious Diseases in Fort Detrick, Maryland.
Ebola viruses are a family of viruses that can often cause very serious hemorrhagic fevers. They have caused dozens of frightening and deadly outbreaks across Africa and threaten endangered gorilla populations as well as people.
There is no treatment and no vaccine against Ebola, which passes via close personal contact.
The siRNAs are little stretches of genetic material that can block the action of a specific gene. This particular one attaches to three different areas on the Ebola virus, preventing it from replicating.
Geisbert's team worked with a strain called Zaire that comes from the Democratic Republic of Congo and kills up to 90 percent of those infected.
"We have just had very difficult times developing treatments — antivirals or just any kind of a strategy," Geisbert said in a telephone interview.
"It's been a very tough nut to crack."
The team has announced a number of near-successes, most recently a vaccine that provided partial protection in monkeys in 2006. Then Geisbert got a call from Ian MacLachlan at Tekmira.
The methodology MacLachlan described sounded promising, so they teamed up.
Tests in guinea pigs suggested the siRNAs delivered in little lipid particles would work. But to get Ebola to sicken rodents requires changing it substantially from the strain that attacks people and monkeys, Geisbert said.
Tests in four rhesus monkeys showed that seven daily injections cured 100 percent of them. And Geisbert said the researchers gave the monkeys an extremely high dose of Ebola.
The treatment holds the virus in check while the immune system gears up to fight it, Geisbert said. "There is a critical threshold for virus load and if you go over that, you die," he said.
"This drug is knocking down enough of the virus so it tips the balance."
Now the company and researchers are seeking U.S. federal funding to continue their work, Geisbert said. For new drugs to treat lethal infections, the Food and Drug Administration requires proof that the treatment does not hurt people and is effective in at least two animal species.
Tekmira has deals with a number of pharmaceutical companies, including Bristol-Myers Squibb and Pfizer.
Last week a team at the National Institutes of Health reported they had developed a vaccine that protects monkeys against several strains of Ebola.
lundi 31 mai 2010
Congress hears benefits of synthetic biology
Reuters, May 17, 2010
Controversial scientist tells lawmakers: ‘It is not life from scratch’.
Craig Venter, founder, chairman and president of the J. Craig Venter Institute, came to Capitol Hill on Thursday to testify before the House Energy and Commerce Committee about synthetic genomics.
Synthetic biology can be used to make nonpolluting fuel, instant vaccines against new diseases and inexpensive medicines, but it will take time, collaboration and a nurturing regulatory environment, scientists said on Thursday.
The researchers, along with an ethicist and members of Congress, agreed the technology does not pose immediate environmental, security or ethical concerns but said everyone needs to keep an eye on developments.
Most of the hearing before the House of Representatives Energy and Commerce Committee was spent outlining the potential of the technology.
The hearing was scheduled last week after a team at the J. Craig Venter Institute announced that they had used an artificially synthesized genome to bring back to life a bacterium that had its own genetic material scooped out.
"It is not life from scratch," Venter, who founded the institute, told the hearing, calling the work "a baby step" in the field of synthetic biology, with the eventual goal of building organisms directly to order from digital DNA.
As BP Plc battled an enormous oil leak in the Gulf of Mexico, prompting questions about where to look for oil and what threats petroleum products pose to the environment, scientists held out the prospect of microbes that can synthesize clean fuel and gobble up pollutants.
"Our optimistic estimates are that it is going to be at least a decade before there are replacements for gasoline and diesel fuel," said Venter, whose privately held Synthetic Genomics Inc. has a contract with Exxon Mobil Corp to try to make algae that can produce biofuel.
New ventures
Jay Keasling of the Lawrence Berkeley National Laboratory in California and the University of California Berkeley Synthetic Biology Engineering Research Center said his team's work had already been used as the foundation for two biofuel companies — Emeryville-based Amyris Biotechnologies and South San Francisco-based LS9, the Renewable Petroleum Company.
Keasling said vaccine maker Sanofi Aventis has licensed technology to make engineered brewer's yeast that produces the anti-malarial drug artemisinin. He expects production to provide the drug at cost to the developing world within two years.
Venter said microbes engineered to make fuel from carbon dioxide could solve energy needs by pulling excess gases from the atmosphere that contribute to global warming.
The same technology could be used to design new vaccines in the computer, he added. But changes to human biology are far away.
He defended moves to patent the technology. "This is clearly the first life form out of a computer and invented by humans," he said.
Some researchers have said they fear Venter or other groups could patent the process and lock them out.
Only 'microbes' at this point
Bioethicist Gregory Kaebnick of the nonpartisan Hastings Center said he saw no immediate ethical challenges.
"I believe concerns about the sacredness of life are not undercut by the science," Kaebnick told the hearing. "We are just talking about microbes at this point."
Dr. Anthony Fauci, director of the National Institute for Allergy and Infectious Diseases, agreed and said there were no special worries about biological attacks using the technology, noting that it took Venter's team years to make their organism.
"We also must keep in mind that nature itself is already an expert at creating microbes that can cause great harm to humans," Fauci said. "Do not overregulate something that needs care, integrity and responsibility," he urged the committee.
Copyright 2010 Reuters.
Controversial scientist tells lawmakers: ‘It is not life from scratch’.
Craig Venter, founder, chairman and president of the J. Craig Venter Institute, came to Capitol Hill on Thursday to testify before the House Energy and Commerce Committee about synthetic genomics.
Synthetic biology can be used to make nonpolluting fuel, instant vaccines against new diseases and inexpensive medicines, but it will take time, collaboration and a nurturing regulatory environment, scientists said on Thursday.
The researchers, along with an ethicist and members of Congress, agreed the technology does not pose immediate environmental, security or ethical concerns but said everyone needs to keep an eye on developments.
Most of the hearing before the House of Representatives Energy and Commerce Committee was spent outlining the potential of the technology.
The hearing was scheduled last week after a team at the J. Craig Venter Institute announced that they had used an artificially synthesized genome to bring back to life a bacterium that had its own genetic material scooped out.
"It is not life from scratch," Venter, who founded the institute, told the hearing, calling the work "a baby step" in the field of synthetic biology, with the eventual goal of building organisms directly to order from digital DNA.
As BP Plc battled an enormous oil leak in the Gulf of Mexico, prompting questions about where to look for oil and what threats petroleum products pose to the environment, scientists held out the prospect of microbes that can synthesize clean fuel and gobble up pollutants.
"Our optimistic estimates are that it is going to be at least a decade before there are replacements for gasoline and diesel fuel," said Venter, whose privately held Synthetic Genomics Inc. has a contract with Exxon Mobil Corp to try to make algae that can produce biofuel.
New ventures
Jay Keasling of the Lawrence Berkeley National Laboratory in California and the University of California Berkeley Synthetic Biology Engineering Research Center said his team's work had already been used as the foundation for two biofuel companies — Emeryville-based Amyris Biotechnologies and South San Francisco-based LS9, the Renewable Petroleum Company.
Keasling said vaccine maker Sanofi Aventis has licensed technology to make engineered brewer's yeast that produces the anti-malarial drug artemisinin. He expects production to provide the drug at cost to the developing world within two years.
Venter said microbes engineered to make fuel from carbon dioxide could solve energy needs by pulling excess gases from the atmosphere that contribute to global warming.
The same technology could be used to design new vaccines in the computer, he added. But changes to human biology are far away.
He defended moves to patent the technology. "This is clearly the first life form out of a computer and invented by humans," he said.
Some researchers have said they fear Venter or other groups could patent the process and lock them out.
Only 'microbes' at this point
Bioethicist Gregory Kaebnick of the nonpartisan Hastings Center said he saw no immediate ethical challenges.
"I believe concerns about the sacredness of life are not undercut by the science," Kaebnick told the hearing. "We are just talking about microbes at this point."
Dr. Anthony Fauci, director of the National Institute for Allergy and Infectious Diseases, agreed and said there were no special worries about biological attacks using the technology, noting that it took Venter's team years to make their organism.
"We also must keep in mind that nature itself is already an expert at creating microbes that can cause great harm to humans," Fauci said. "Do not overregulate something that needs care, integrity and responsibility," he urged the committee.
Copyright 2010 Reuters.
mardi 11 mai 2010
Genetic tests on shelves - Usefulness of consumer screenings questioned
By Keith Darcé, UNION-TRIBUNE STAFF WRITER
Tuesday, May 11, 2010 at 12:02 a.m.
Consumer interest in genetic testing could receive a major boost this week when kits from Pathway Genomics of San Diego hit the shelves of Walgreens drugstores nationwide, even as some scientists question the usefulness of the screenings.
Pathway and the three other big companies that make genetic-testing products, sold mainly on the Internet or through doctors’ offices, have attracted relatively few customers since debuting the items less than three years ago.
Estimates put total sales at 50,000 to 100,000 tests.
Prices have been part of the problem. The cost ranges from about $400 to $2,000 for a comprehensive genetic-marker test that seeks to identify risks for adverse drug reactions, passing on mutations to children or developing certain diseases and health conditions.
Pathway’s kit will sell for about $20 in Walgreens stores. The buyer spits into a specialized container and then ships the saliva to the company for an analysis that costs $79 to $249, depending on the tests requested.
On Pathway’s website, the company offers a single testing package for $399.
“We are really doing this to increase consumer awareness, not just for us but for the entire genetic-testing industry,” said Jim Woodman, vice president of corporate strategy for Pathway.
The move represents a big step for the privately owned company, which launched its service in September. About 50 people work at Pathway’s laboratory and headquarters in the Sorrento Valley area of San Diego.
Interest in genomics has soared as the pace of research in the field has accelerated. Scientists are regularly uncovering new mutations in human DNA sequences that are tied to cancers, chronic health conditions, Alzheimer’s disease and illnesses that run in families.
More than 60 prescription drugs, including the anti-blood-clotting medications Plavix and Warfarin, have been associated with genetic markers indicating that a patient might have trouble taking them.
Not everyone welcomes the services of Pathway and its counterparts.
Officials for the American Medical Association said genetic tests shouldn’t be done without direct supervision of a doctor who can help interpret the results and recommend care based on the findings.
Consumers can easily misunderstand the test results if left on their own, said Dr. Eric Topol, a cardiologist and geneticist who serves as chief academic officer for San Diego-based Scripps Health.
Several states have banned direct sales of genetic tests to consumers.
In California, companies that offer such services must obtain a laboratory license from the Department of Public Health. The state has issued licenses to all of the major genetic-testing businesses — Pathway, 23andMe of Mountain View, Navigenics of Forest City and DECODE Genetics of Reykjavik, Iceland.
For the past year, Palomar Pomerado Health has sold 23andMe test kits at its “expresscare” retail clinics inside Albertsons grocery stores in Escondido and Rancho Peñasquitos.
The Federal Trade Commission, which oversees labeling for the tests, is the only federal agency that regulates the industry.
One concern about the retail genetic testing involves what isn’t covered.
Some scientists believe accurate measurements of each person’s disease risk aren’t possible without looking at all 3 billion DNA base pairs that make up that individual’s genome. That process costs more than $10,000 and requires the work of supercomputers.
Instead, the companies offering consumer genetic testing isolate only several hundred thousand genetic variations for review.
The results can be misleading, Topol said.
For example, a test could indicate that a person has a 30 percent risk of developing a particular type of cancer while the average risk is half that amount. The difference might seem alarming, but it may not matter if the likelihood of getting the cancer is more strongly driven by rare genetic variances occurring in particular family lines, Topol said.
In another case, a person might take false comfort in test results showing genetic markers for lower-than-average risk of a heart attack. The patient might push aside the more important fact that numerous relatives going back several generations have suffered congestive heart failure.
“Our ability to look at an individual’s DNA sequence and tell them their risk for these types of health conditions is low,” said Kelly Frazer, chief of genome information sciences for the department of pediatrics at the University of California San Diego’s School of Medicine.
The main businesses offering retail genetic testing said they’ve been careful to market their products as educational information rather than medical advice or a diagnosis.
“We make it very clear that this doesn’t mean (customers) are going to get a condition, but it’s something they should be aware of, and here are things they can do to mitigate that risk,” Woodman said.
But even among these companies, there often is wide variation in how genetic results are explained.
Francis Collins, director of the National Institutes of Health, reported in an October article in The New England Journal of Medicine that he sent his personal DNA sample to the three leading genetic-testing companies.
“They were not consistent in how they interpreted the results,” said Collins, a geneticist who helped guide the Human Genome Project. “I think all the companies probably overrepresented the degree to which we already can predict people’s future risk of illness and underrepresented how much of heritability has yet to be discovered.”
Keith Darcé: (619) 293-1020; keith.darce@uniontrib.com
By Keith Darcé, UNION-TRIBUNE STAFF WRITER
Tuesday, May 11, 2010 at 12:02 a.m.
Consumer interest in genetic testing could receive a major boost this week when kits from Pathway Genomics of San Diego hit the shelves of Walgreens drugstores nationwide, even as some scientists question the usefulness of the screenings.
Pathway and the three other big companies that make genetic-testing products, sold mainly on the Internet or through doctors’ offices, have attracted relatively few customers since debuting the items less than three years ago.
Estimates put total sales at 50,000 to 100,000 tests.
Prices have been part of the problem. The cost ranges from about $400 to $2,000 for a comprehensive genetic-marker test that seeks to identify risks for adverse drug reactions, passing on mutations to children or developing certain diseases and health conditions.
Pathway’s kit will sell for about $20 in Walgreens stores. The buyer spits into a specialized container and then ships the saliva to the company for an analysis that costs $79 to $249, depending on the tests requested.
On Pathway’s website, the company offers a single testing package for $399.
“We are really doing this to increase consumer awareness, not just for us but for the entire genetic-testing industry,” said Jim Woodman, vice president of corporate strategy for Pathway.
The move represents a big step for the privately owned company, which launched its service in September. About 50 people work at Pathway’s laboratory and headquarters in the Sorrento Valley area of San Diego.
Interest in genomics has soared as the pace of research in the field has accelerated. Scientists are regularly uncovering new mutations in human DNA sequences that are tied to cancers, chronic health conditions, Alzheimer’s disease and illnesses that run in families.
More than 60 prescription drugs, including the anti-blood-clotting medications Plavix and Warfarin, have been associated with genetic markers indicating that a patient might have trouble taking them.
Not everyone welcomes the services of Pathway and its counterparts.
Officials for the American Medical Association said genetic tests shouldn’t be done without direct supervision of a doctor who can help interpret the results and recommend care based on the findings.
Consumers can easily misunderstand the test results if left on their own, said Dr. Eric Topol, a cardiologist and geneticist who serves as chief academic officer for San Diego-based Scripps Health.
Several states have banned direct sales of genetic tests to consumers.
In California, companies that offer such services must obtain a laboratory license from the Department of Public Health. The state has issued licenses to all of the major genetic-testing businesses — Pathway, 23andMe of Mountain View, Navigenics of Forest City and DECODE Genetics of Reykjavik, Iceland.
For the past year, Palomar Pomerado Health has sold 23andMe test kits at its “expresscare” retail clinics inside Albertsons grocery stores in Escondido and Rancho Peñasquitos.
The Federal Trade Commission, which oversees labeling for the tests, is the only federal agency that regulates the industry.
One concern about the retail genetic testing involves what isn’t covered.
Some scientists believe accurate measurements of each person’s disease risk aren’t possible without looking at all 3 billion DNA base pairs that make up that individual’s genome. That process costs more than $10,000 and requires the work of supercomputers.
Instead, the companies offering consumer genetic testing isolate only several hundred thousand genetic variations for review.
The results can be misleading, Topol said.
For example, a test could indicate that a person has a 30 percent risk of developing a particular type of cancer while the average risk is half that amount. The difference might seem alarming, but it may not matter if the likelihood of getting the cancer is more strongly driven by rare genetic variances occurring in particular family lines, Topol said.
In another case, a person might take false comfort in test results showing genetic markers for lower-than-average risk of a heart attack. The patient might push aside the more important fact that numerous relatives going back several generations have suffered congestive heart failure.
“Our ability to look at an individual’s DNA sequence and tell them their risk for these types of health conditions is low,” said Kelly Frazer, chief of genome information sciences for the department of pediatrics at the University of California San Diego’s School of Medicine.
The main businesses offering retail genetic testing said they’ve been careful to market their products as educational information rather than medical advice or a diagnosis.
“We make it very clear that this doesn’t mean (customers) are going to get a condition, but it’s something they should be aware of, and here are things they can do to mitigate that risk,” Woodman said.
But even among these companies, there often is wide variation in how genetic results are explained.
Francis Collins, director of the National Institutes of Health, reported in an October article in The New England Journal of Medicine that he sent his personal DNA sample to the three leading genetic-testing companies.
“They were not consistent in how they interpreted the results,” said Collins, a geneticist who helped guide the Human Genome Project. “I think all the companies probably overrepresented the degree to which we already can predict people’s future risk of illness and underrepresented how much of heritability has yet to be discovered.”
Keith Darcé: (619) 293-1020; keith.darce@uniontrib.com
mercredi 5 mai 2010
Mammoth Hemoglobin Offers More Clues to Its Arctic Evolution
By NICHOLAS WADE, New York Times, May 3, 2010
For the first time in 43,000 years, a woolly mammoth has breathed again on earth.
Well, not the mammoth itself but its hemoglobin, the stuff in red blood cells that takes on oxygen in the lungs and offloads it in the tissues. By reconstructing the mammoth’s hemoglobin, a team led by Kevin L. Campbell of the University of Manitoba in Canada has discovered how the once-tropical species adapted to living in arctic temperatures.
Dr. Campbell’s work raises a somewhat astonishing possibility: that much of the physiology of extinct animals may one day be recoverable from the DNA extracted from their remains.
“It is a very exciting result and opens a new chapter in paleontology, a subject usually constrained to examining old bones and teeth,” said Adrian Lister, an expert on mammoth evolution at the Natural History Museum in London.
Mammoths, despite their association with the frozen north, originated in the tropics when they split apart from elephants some seven million years ago. To adapt to the cold of northern latitudes, they developed smaller ears, a thick fur coat and glands in their skin to keep the fur well oiled.
So much is clear from their remains. But other kinds of adaptation, which have not survived, would also have been necessary. Most arctic animals arrange their blood vessels so that the arteries going down a leg can transfer heat to the veins coming up. The blood reaching the toes is thus quite cold, and the animal conserves lots of heat while it stands on frozen ground.
But this arrangement raises a problem for the hemoglobin, the protein of red blood cells that takes on oxygen in the lungs and delivers it in the tissues. The offloading process becomes much less efficient at low temperatures. So animals like the arctic fox, whose foot temperature is just a degree or so above freezing, have changes in their hemoglobin genes that enable the protein to release oxygen more easily at very low temperatures.
Dr. Campbell set out nine years ago to see if the same was true of mammoths. His first problem was to figure out which of several globin genes were active in the species. Globin genes make the four globin chains from which the hemoglobin molecule is assembled. Humans have at least four globin genes — alpha, beta, gamma and delta. Most hemoglobin molecules in human blood consist of two alpha chains and two beta chains, but in 10 percent of the blood, delta chains substitute for the betas. The gamma globin gene is active only in the fetus.
Dr. Campbell figured that the hemoglobin system of living elephants would offer the best guide to how mammoth globin genes operate. After a frustrating effort to get permits to take samples from wild elephants, he acquired blood from an Asian elephant called Caesar at the Bowmanville Zoo in Ontario.
It turned out that way back in the elephant lineage, the beta and delta globin genes had swapped DNA to create a hybrid beta-delta chain. Elephant hemoglobin molecules are composed of two chains from the alpha globin gene and two from the fused beta-delta gene, and it is reasonable to assume mammoths had the same system.
With this knowledge, Dr. Campbell and his colleagues could construct the tools to fish out the alpha and beta-delta globin genes from the ancient DNA of three permafrost-preserved Siberian mammoths that lived between 25,000 and 43,000 years ago. They found the alpha chain differed in one of its amino acid units from that of Asian elephants, and the beta-delta chain differed in three units from its counterpart, they report in Nature Genetics.
The team’s next step was to synthesize copies of the mammoth’s two globin genes. Instead of doing that from scratch, Dr. Campbell used a technique for altering DNA units one by one and simply converted the Asian elephant’s two globin genes at the four differing sites to the mammoth version. The mammoth genes were then inserted into bacteria, which synthesized the two mammoth globin chains, inserted the required iron atoms, and assembled the chains into working hemoglobin molecules. With the mammoth hemoglobin in hand, Dr. Campbell could at last address the question of whether its genetic changes had been shaped by natural selection to help mammoths survive in the cold.
“It’s the same as if I went back 43,000 years in a time machine and took blood from a mammoth,” he said.
The answer was yes: In a chemical environment like that in red blood cells, the reconstructed mammoth hemoglobin let go of its oxygen much more readily at cold temperatures than did that of Asian elephants.
The DNA changes in the mammoth hemoglobin genes differ from those in other arctic animals, an instance of convergent evolution or attaining the same end by a different genetic route.
One species that did not modify its hemoglobin genes to cope with arctic temperatures is that of humans. “With our ability to make mitts and hats, we’ve not needed these sorts of changes,” Dr. Campbell said.
He is now reconstructing important proteins of other extinct species such as the mastodon, the woolly rhinoceros and the Steller’s sea cow, a huge dugong that lived in the arctic.
Two years ago, scientists at Penn State University sequenced a large part of the mammoth’s genome from a clump of hair. They published the sequence along with the arresting suggestion that for just $10 million it might be possible to complete the sequence and use it to generate a living mammoth.
The suggestion was not as wild as it might seem, given that the idea came from George Church, a leading genome technologist at the Harvard Medical School. The mammoth’s genome differs at about 400,000 sites from that of the African elephant. Dr. Church has been developing a method for altering 50,000 sites at a time, though he is not at present applying it to mammoths. In converting four sites on the elephant genome to the mammoth version, Dr. Campbell has resurrected at least one tiny part of the mammoth.
Reconstructing the whole animal will take a little longer. “I’m 42 years old,” he said, “but I doubt I’ll ever see a living mammoth.”
For the first time in 43,000 years, a woolly mammoth has breathed again on earth.
Well, not the mammoth itself but its hemoglobin, the stuff in red blood cells that takes on oxygen in the lungs and offloads it in the tissues. By reconstructing the mammoth’s hemoglobin, a team led by Kevin L. Campbell of the University of Manitoba in Canada has discovered how the once-tropical species adapted to living in arctic temperatures.
Dr. Campbell’s work raises a somewhat astonishing possibility: that much of the physiology of extinct animals may one day be recoverable from the DNA extracted from their remains.
“It is a very exciting result and opens a new chapter in paleontology, a subject usually constrained to examining old bones and teeth,” said Adrian Lister, an expert on mammoth evolution at the Natural History Museum in London.
Mammoths, despite their association with the frozen north, originated in the tropics when they split apart from elephants some seven million years ago. To adapt to the cold of northern latitudes, they developed smaller ears, a thick fur coat and glands in their skin to keep the fur well oiled.
So much is clear from their remains. But other kinds of adaptation, which have not survived, would also have been necessary. Most arctic animals arrange their blood vessels so that the arteries going down a leg can transfer heat to the veins coming up. The blood reaching the toes is thus quite cold, and the animal conserves lots of heat while it stands on frozen ground.
But this arrangement raises a problem for the hemoglobin, the protein of red blood cells that takes on oxygen in the lungs and delivers it in the tissues. The offloading process becomes much less efficient at low temperatures. So animals like the arctic fox, whose foot temperature is just a degree or so above freezing, have changes in their hemoglobin genes that enable the protein to release oxygen more easily at very low temperatures.
Dr. Campbell set out nine years ago to see if the same was true of mammoths. His first problem was to figure out which of several globin genes were active in the species. Globin genes make the four globin chains from which the hemoglobin molecule is assembled. Humans have at least four globin genes — alpha, beta, gamma and delta. Most hemoglobin molecules in human blood consist of two alpha chains and two beta chains, but in 10 percent of the blood, delta chains substitute for the betas. The gamma globin gene is active only in the fetus.
Dr. Campbell figured that the hemoglobin system of living elephants would offer the best guide to how mammoth globin genes operate. After a frustrating effort to get permits to take samples from wild elephants, he acquired blood from an Asian elephant called Caesar at the Bowmanville Zoo in Ontario.
It turned out that way back in the elephant lineage, the beta and delta globin genes had swapped DNA to create a hybrid beta-delta chain. Elephant hemoglobin molecules are composed of two chains from the alpha globin gene and two from the fused beta-delta gene, and it is reasonable to assume mammoths had the same system.
With this knowledge, Dr. Campbell and his colleagues could construct the tools to fish out the alpha and beta-delta globin genes from the ancient DNA of three permafrost-preserved Siberian mammoths that lived between 25,000 and 43,000 years ago. They found the alpha chain differed in one of its amino acid units from that of Asian elephants, and the beta-delta chain differed in three units from its counterpart, they report in Nature Genetics.
The team’s next step was to synthesize copies of the mammoth’s two globin genes. Instead of doing that from scratch, Dr. Campbell used a technique for altering DNA units one by one and simply converted the Asian elephant’s two globin genes at the four differing sites to the mammoth version. The mammoth genes were then inserted into bacteria, which synthesized the two mammoth globin chains, inserted the required iron atoms, and assembled the chains into working hemoglobin molecules. With the mammoth hemoglobin in hand, Dr. Campbell could at last address the question of whether its genetic changes had been shaped by natural selection to help mammoths survive in the cold.
“It’s the same as if I went back 43,000 years in a time machine and took blood from a mammoth,” he said.
The answer was yes: In a chemical environment like that in red blood cells, the reconstructed mammoth hemoglobin let go of its oxygen much more readily at cold temperatures than did that of Asian elephants.
The DNA changes in the mammoth hemoglobin genes differ from those in other arctic animals, an instance of convergent evolution or attaining the same end by a different genetic route.
One species that did not modify its hemoglobin genes to cope with arctic temperatures is that of humans. “With our ability to make mitts and hats, we’ve not needed these sorts of changes,” Dr. Campbell said.
He is now reconstructing important proteins of other extinct species such as the mastodon, the woolly rhinoceros and the Steller’s sea cow, a huge dugong that lived in the arctic.
Two years ago, scientists at Penn State University sequenced a large part of the mammoth’s genome from a clump of hair. They published the sequence along with the arresting suggestion that for just $10 million it might be possible to complete the sequence and use it to generate a living mammoth.
The suggestion was not as wild as it might seem, given that the idea came from George Church, a leading genome technologist at the Harvard Medical School. The mammoth’s genome differs at about 400,000 sites from that of the African elephant. Dr. Church has been developing a method for altering 50,000 sites at a time, though he is not at present applying it to mammoths. In converting four sites on the elephant genome to the mammoth version, Dr. Campbell has resurrected at least one tiny part of the mammoth.
Reconstructing the whole animal will take a little longer. “I’m 42 years old,” he said, “but I doubt I’ll ever see a living mammoth.”
Inscription à :
Articles (Atom)