Human clones in the making?
Scientists claim they've come close to creating artificial life
By Jean-Louis Santini, Agence France-Presse
WASHINGTON
Scientists in the United States have taken a major step toward creating the first-ever artificial life form by synthetically reproducing the DNA of a bacterium. The move, which comes after five years of research, is seen as the penultimate stage in the endeavor to create an artificial life form based entirely on a man-made DNA genome-something which has tantalized scientists and sci-fi writers for years.
"Through dedicated teamwork we have shown that building large genomes is now feasible and scalable so that important applications such as biofuels can be developed," said Hamilton Smith, from the J. Craig Venter Institute, in a study published in Science.
The research has been carried out at the laboratories of the controversial celebrity US scientist Craig Venter, who has hailed artificial life forms as a potential remedy to illness and global warming. However, the prospect of engineering artificial life forms is highly controversial and arouses heated debate over the ethics and its potential ramifications. It is one of the Holy Grails of science, but also one that stirs deep fears as foreseen in Aldous Huxley's 1932 novel Brave New World, in which natural human reproduction is eschewed in favor of babies grown artificially in laboratories.
Venter said in a statement: "This extraordinary accomplishment is a technological marvel that was only made possible because of the unique and accomplished ... team." His researchers had "dedicated the last several years to designing and perfecting new methods and techniques that we believe will become widely used to advance the field of synthetic genomics," he added.
Lead author Dan Gibson said the team had completed the second step in a three-step process to create a synthetic organism. In the final stage of their research which they are already working on, the Maryland-based team will attempt to create a bacterium based purely on the synthetic genome sequence of Mycoplasma genitalium bacteria. The bacterium, which causes certain sexually transmitted diseases, has one of the least-complex DNA structures of any life form, composed of just 580 genes. In contrast, the human genome has some 30,000.
The chromosome that Venter and his team has created is known as Mycoplasma laboratorium and, in the final step of the process, will be transplanted into a living cell where it should "take control," effectively becoming a new life form.
"When we started this work several years ago, we knew it was going to be difficult because we were treading into unknown territory," said Smith.
But other scientists remain cautious, saying Venter and his team are still a long way from being able to create artificial life.
And ETC, a Canadian watchdog that uncovered Venter's patent application for M. laboratorium, worries about accountability. "Venter is claiming bragging rights to the world's longest length of synthetic DNA, but size isn't everything. The important question is not 'how long?' but 'how wise?'" said ETC's Jim Thomas. "While synthetic biology is speeding ahead in the lab and in the marketplace, societal debate and regulatory oversight is stalled, and there has been no meaningful or inclusive discussion on how to govern synthetic biology in a safe and just way."
Eckard Wimmer, professor of molecular biology at New York University, said it was clear from Venter's study that the team had not yet created artificial life. He said he was left with "the unpleasant feeling whether or not the synthetic DNA was indeed proper and able for biological function."
His fears were echoed by Helen Wallace, a biologist and spokeswoman for GeneWatch UK, who said that while Venter's team has managed a technical feat, it is some way from being artificial life. "Venter is not God.... He's a long way from creating life," she said. "It's a type of genetic engineering which would allow people to make much bigger genetic changes, which means that in the future you could create organisms with new gene sequences."
Life, version 2.0
Is the world ready for synthetic biology?
Marlowe Hood, Agence France-Presse
PARIS
From Frankenstein's monster to Blade Runner replicants, the prospect of assembling life from inert matter has long tantalized the imagination with hope and fear. The alluring but unsettling goal of artificial life comes a step closer with the announcement by the American maverick Craig Venter, opening what experts predict will be a fierce debate on medical, ethical, and safety issues.
Venter's team, reporting in Science, stripped down a species of tiny microbe, Mycoplasma genitalium, to the barest genetic components to support life. They then replicated strips of the germ's DNA code using lab chemicals and reassembled these sections to make a synthetic, pared-down version of the original, which they called M. genitalium JCVI-1.0.
The paper is a bioengineering exploit, showing that the toolkit and knowledge exist for making the world's first man-made species of microorganism-a goal that Venter, a consummate self-promoter, sketched last year to a media frenzy. He says artificial bugs hold the key to solving innumerable problems, including the world's energy crisis and climate-change peril.
Other voices, in science and also religion, say that so far Venter is way short of his goal, for cut-and-paste of DNA does not constitute the making of life. Even so specialists say that, outside the lab, the world is totally unprepared for the looming dawn of synbio, as synthetic biology is called.
"If you were to poll people on synthetic biology, you would be hard put to find one in a thousand who had heard of it," said Nigel Cameron, president of the Institute on Biotechnology and the Human Future, part of the Illinois Institute of Technology. Even governments and international organizations charged with monitoring and regulating major new technologies are in the dark about this new field, he said.
A canvassing of ethicists by Agence France-Presse last October, when Venter trailed his ambition to create a brand-new microbe species to be called M. laboratorium, revealed several areas of concerns.
"Synthetic biology is advancing at breakneck pace in the absence of any public debate or regulatory oversight," said Hope Shand of the Canadian watchdog ETC. "It needs to be considered by a much wider public before it is allowed to progress further," she said.
Ownership of synthetic life forms is another big problem area. "You have a new, and potentially very powerful platform for producing chemicals, fuels, drugs, and other things. This raises a number of monopoly issues," said Jim Thomas, also of ETC, adding that some experts have predicted a fifth of all chemicals could be made through synthetic biology by 2015.
A third concern is safety, which Cameron said is likelier than ethics to prompt any government ban. "Synbio could wind up giving enormous asymmetrical power to people who are not as well intentioned as Venter to build bugs" such as anthrax, smallpox, or some as-yet undreamed of toxin, said Cameron.
Another question is the impact from releasing man-made bugs into the environment. Green activists say there could be unknown consequences if novel genes mix with soil bacteria and other species.
"He (Venter) dreams of making bacteria which for instance will clean up oil spills," Jean-Claude Ameisen, said chair of the ethics committee at France's National Institute for Health and Medical Research (Inserm). "If the idea is to release them into the wild, the same issues will arise as with genetically modified crops."
Venter himself appears to have sought to address some of the ethical and regulatory concerns by issuing a kind of white paper with recommendations for policymakers.
But watchdog groups are not buying. They want national government and international organizations to take the lead.
How governments respond to the challenge of synbio will be a central question of the 21st century, said Cameron. "[The rows over] genetically modified organisms and stem cells are only a small sample of what is going to happen if we can't find a way to bring tech policy into the heart of our politics," he said.
SCIENTIST OR MEGALOMANIAC?
Maverick Venter wants to be first to create artificial life
WASHINGTON
Craig Venter is a maverick US scientist and pioneer of biotechnology with a single over-riding ambition-to create the first form of artificial life to aid humanity battle 21st century problems. Venter says his cutting-edge research could help resolve some of the world's most pressing ills, by creating man-made bacteria that could help tackle such issues as dwindling fuel resources and mounting garbage dumps. But to his critics, the 61-year-old researcher is a megalomaniac determined to write his name into history, and along the way slap a patent on artificial life forms.
In 2001, Venter almost beat a public-sector international consortium in being first to decode the human genome, and in early 2007 his institute unveiled the first fully sequenced genome of an individual: himself.
His controversial approach and his thirst to be the first to crack one of science's Holy Grails have driven his research on.
In 2006, his laboratory, the J. Craig Venter Institute, filed for a US patent on a single-cell organism, claiming exclusive ownership of a set of essential genes and a synthetic "free-living organism that can grow and replicate."
The single-cell organism, which the Canadian bioethics organization ETC Group has labeled "Synthia," is piloted by a chromosome with just 381 genes, the limit necessary to sustain the life of the bacterium so it can feed and reproduce. The ETC publicized the patent application, which would apply in the United States and 100 or so other countries in June 2007.
Venter told the British daily The Guardian in October that the synthetic chromosome built using chemicals in a laboratory would be "a very important philosophical step in the history of our species." Said Venter: "We are going from reading our genetic code to the ability to write it. That gives us the hypothetical ability to do things never contemplated before."
Venter, named by Time magazine in 2007 as one of the world's 100 most influential people, is also a prolific author, having published some 200 scientific articles. He is also a member of the National American Academy of Arts and Sciences.
M AFP
Gene research: A timeline
PARIS
Here is a timeline of events in gene research, following the announcement by US scientists on January 24 that they had synthesized the DNA of a bacterium, a key step toward the goal of making artificial life.
1953
Britain's Francis Crick and American James Watson describe the double-helix structure of DNA, the chemical code for life.
1973
US scientists Herbert Boyer and Stanley Cohen graft a foreign gene to a bacterium, opening the door to genetic engineering.
1981
First genetically engineered mice are created-lab rodents to which genes have been added in order to replicate disease to help medical research.
1990
Launch of the Human Genome Project (HGP), a US$3-billion international public-sector initiative to unravel the human genetic code over the next 15 years.
1996
Birth of Dolly the Sheep, the first mammal to be cloned from an adult cell.
2000
HGP consortium and a rival private-sector bid steered by maverick US scientist Craig Venter tie in the race to publish the first draft of the human genome. Birth of the first genetically modified primate, a rhesus monkey called ANDi.
2003
HGP team publishes final, polished version of genome, two years ahead of schedule.
2005
Scientists at Britain's Newcastle University announce they have created a cloned human embryo in an investigation into stem cells, the versatile cells that develop into different tissues.
2007
Venter's team transplants the genome of a species of microbe into a related species, an important step toward making an artificial life form.
2008
In another technical feat, Venter's team says they have used lab chemicals to replicate the stripped-down genome of a small microbe, Mycoplasma genitalium.
AFP
Heart from the dead
With innovative technique, researchers coax hearts from rat cadavers into beating
Marlowe Hood, Agence France-Presse
PARIS
In experiments that would make Dr. Frankenstein jealous, US scientists have coaxed recycled hearts taken from animal cadavers into beating in the laboratory after reseeding them with live cells. If extended to humans, the procedure could provide an almost limitless supply of hearts, and possibly other organs, to millions of terminally ill people waiting helplessly for a new lease on life.
Approximately 50,000 patients in the United States alone die every year for lack of a donor heart, and some 22 million people worldwide are living with the threat of heart failure.
"The idea would be to develop transplantable blood vessels or whole organs that are made from your own cells," said lead researcher Doris Taylor, director of the Center or Cardiovascular Repair at the University of Minnesota.
While there have been advances in generating living heart tissue in the lab, this is the first time an entire, three-dimension bio-artificial heart has been brought to life.
The core procedure making this possible is called decellularization. In this process, all the cells from an organ-in this case the heart of a dead rat-are stripped away using powerful detergents, leaving only a bleached-white scaffolding composed of proteins secreted by the cells.
In the experiments, this matrix was then injected with a mixture of cells taken from newborn rat hearts and placed in a sterile lab setting, where the scientists hoped it would grow. After only four days, contractions started, and on the eighth day, the hearts were pumping, according to the study, published in Nature Medicine.
The researchers were stunned.
"When we saw the first contractions, we were speechless," said Harald Ott, a surgeon at Massachusetts General Hospital.
"We certainly were surprised that it worked so well and so quickly," Taylor said. "There are so many places this could have gone wrong."
In humans the objective would be to inject stem cells drawn directly from the recipient of the donated organ, thus eliminating the danger that the new heart would be rejected by the immune system. Recent breakthroughs in stem-cell research from nonembryo sources mean that new tissues should be easy to generate, according to the authors.
Many patients who might one day benefit from a transplanted bioartificial organ are currently not even listed as potential recipients, said Ott. "If organs derived from a patient's own cells would become available on a large scale - maybe even as an off-the-shelf product - millions of patients suffering from organ failure would benefit," he said in an e-mail.
In these "proof of concept" experiments, the bioartificial rat hearts grown in the lab pumped after eight days with a force equivalent to about two percent of an adult rodent heart.
Taylor and her team are now working on making the recycled organs more efficient, and have even transplanted some of these hearts into the abdomens of rats and connected them to the animals' aortas, a standard way of testing whether a donor organ can keep an animal alive.
Decellularization could change the way scientists thinks about engineering organs, according to the study.
"It opens a door to this notion that you can make any organ: kidney, liver, lung, pancreas-you name it and we hope we can make it," Taylor said.
Though not reported in this study, the Minnesota researchers have also successfully applied the technique to pig hearts, which are closer to human hearts in size and complexity.
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