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"Knockout mice" designers win Nobel Prize
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Three researchers who pioneered the creation of "designer mice" to demonstrate the roles of different genes in human development and disease won the 2007 Nobel medicine prize on Monday. Mario Capecchi, 70, Martin Evans, 66, and Oliver Smithies, 82, won the prestigious 10 million Swedish crown ($1.54 million) award for helping forge a new and fundamental branch of medicine -- gene targeting. "Gene targeting in mice has pervaded all fields of biomedicine. Its impact on the understanding of gene function and its benefits to mankind will continue to increase over many years to come," Sweden's Karolinska Institute, said in awarding the prize bearing the name of 19th century dynamite inventor Alfred Nobel. Their work led to the development of mouse "models" of human disease and is widely used to study the function of genes in both disease and in normal biology. It is also a basis for gene therapy -- correcting faulty genes to treat disease. The Italian-born Capecchi lived as a street urchin and almost starved while his mother was imprisoned in the Nazi concentration camp of Dachau during World War II. He later became a U.S. citizen, as did the British-born Smithies. Evans is British. Evans, of Cardiff University, laid the groundwork for making so-called knockout mice when he discovered that days-old embryos are made up of super-powerful cells later dubbed embryonic stem cells. Each one of the cells has the power to give rise to all the cells and tissues in an animal. Evans and colleagues figured out how to genetically manipulate these cells and implant the embryos back into a female mice, which gave birth to genetically altered offspring. Capecchi of the Howard Hughes Medical Institute and the University of Utah, and Smithies, now of the University of North Carolina, developed precise methods for changing desired genes one by one. These discoveries led to the development of deleting, or knocking out, genes to discover their function. "If for example, you see a little finger disappear, then you know that gene is important for making little fingers," Capecchi said in a telephone interview. PREVIOUS RECOGNITION In 2001, the trio took the Albert Lasker Award for Basic Medical Research, seen as the U.S. version of the Nobel since many of its recipients have gone on to become Nobel laureates. Smithies reacted calmly to the award. "I was not so much excited but rather it was a feeling a peace. That recognizes this body of work of a lifetime, and now I can go on and do what I want," he said in a telephone interview. "Most of the time you won't get the result you would like, you won't achieve anything very special, so if you don't enjoy what you were doing, you are disappointed at the end of the day," added Smithies, who also designed "knock-in" mice whose genetic manipulation cures them of diseases. "But if you enjoy what you are doing, then the disappointment is not very great. You will say, 'Ah, the next day it will work'." Capecchi said part of his prize money would go toward his team's research into a type of cancer called sarcoma. "What is needed is an understanding of that cancer and each step that gives rise to that cancer. Once you identify those you can make specific drugs that will affect that type of cancer," he said. The science community said the Nobel marked well-earned recognition of a branch of research that could lead to treatments for illnesses from cancer to cystic fibrosis. "Gene targeting, a way of altering gene structure and hence function in animals, provides a direct way to investigate the role of particular genes," said Dr. Paul Sharpe, Head of Craniofacial Development at King's College London. Jeremy Berg, director of the U.S. National Institute of General Medical Sciences, which helped fund the work, said using embryonic stem cells was fundamental to the discovery. Scientists now are working with human embryonic stem cells but the research is controversial because some people oppose the manipulation of human embryos. President George W. Bush has vetoed two bills that would expand federal funding of such study, although it is actively encouraged in Britain and elsewhere. Medicine is traditionally the first of the Nobels handed out each year. The Nobel Laureate for physics will be announced Tuesday, followed by chemistry Wednesday, literature Thursday and the Nobel Peace Prize Friday in Oslo. The prizes bearing the name of Alfred Nobel were first awarded in 1901 according to the will of the Swedish dynamite millionaire. (Additional reporting by Julie Steenhuysen in Chicago, Niklas Pollard, Emma Bengtsson, Sarah Edmonds and Adam Cox in Stockholm, Maggie Fox in Washington, and Michael Kahn in London) |
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How Safe Are Our Bio-Labs?
On Thursday Congress held the first of a series of planned hearings on the recent — and some might say reckless — proliferation of high-security bio-laboratories in the U.S. The questions at hand: How many such labs, which handle virulent toxins and germs like anthrax, avian flu and SARS, are currently operating in the U.S.? And has the research they've conducted made us any safer today than we were six years ago, just after 9/11?
The answers range from "No" to "We don't know." "[Given] that there is so much that is unknown at the moment, I would have to say we are at greater risk," Keith Rhodes, chief technologist with the General Accountability Office (GAO), told Congress, "because, as the number [of bio-labs] increases, the risk increases. And it's not just the increase in material, it's the increase in laboratories that have less experience than others."
Hundreds, if not thousands, of new labs are now conducting high-risk biological experiments in the U.S., with at least 15,000 technicians working daily on the world's deadliest pathogens — the vast majority of them for the first time. Though FBI background checks are required for people who handle so-called select agents — a government-drawn list of 73 highly lethal pathogens, such as Ebola, ricin and monkeypox — the vetting focuses on security, not bio-safety competence. Yet most lab accidents are due to simple human error, says Dr. Gigi Gronvall, Senior Associate at the Center for Biosecurity at the University of Pittsburgh. Newbies to the lab are typically indoctrinated to safe lab habits through a mentor-apprentice process, but the recent, rapid expansion of bio-labs has stretched thin the pool of experienced lab workers.
The most dangerous research is done in the country's Level 3 and Level 4 labs. Since the anthrax letter attacks of 2001, which killed five people and infected another 17, the government has spent billions on bioterror and infectious-disease research, and on building the high-risk labs that house those experiments. But nobody knows exactly how many such labs exist today. A 2005 survey by the National Institute of Health, which funds much of the country's bio-defense studies, tallied 277 Level 3 labs in the U.S.; meanwhile, a Homeland Security and Health and Human Services report the same year found more than 600. The GAO's Rhodes told Congress, however, the number is "surely in the thousands." Level 4 labs, which handle the most dangerous pathogens — those for which there are no known therapeutics or vaccines, such as smallpox, Ebola and other hemorrhagic fevers — are fewer in number, partly because they're very expensive. Before 2001 the U.S. had five Level 4 labs; now there are 15 in operation or coming on line soon, including the planned $470 million National Bio and Agro-Defense Facility (NBAF), which will cover as much acreage as five Wal-Mart stores. On the short list of states in contention to host the NBAF is Mississippi, which has zero prior experience with such high-risk research. "While some expansion [of labs] may be justified," says Rhodes, "unwarranted expansion without adequate oversight is proliferation, not expansion."
Worse, there is no centralized regulatory body that oversees bio-labs or their work — 17 federal agencies are involved in biological research in some way, but no single agency is tasked with tracking and managing the risks. "Several agencies have a need to know the number and the location of these labs to support their missions," says Rhodes, but no agency actually has this information. The Centers for Disease Control and Prevention (CDC) has primary responsibility for monitoring the use of select agents — but according to critics, it's working with an outdated list. The last revision to the list occurred in 2005, with the addition of the re-created influenza virus that killed some 40 million people in 1918. Still missing from the register: SARS, Hantavirus and other deadly viruses, which, as a consequence, are subject to virtually no regulation at all.
Lack of oversight means lack of policing, which often leads to underreporting of potentially fatal accidents. Labs are required by law to report mishaps with select agents immediately to the CDC, but that doesn't always happen. Case in point: Last year, a bio-lab worker at Texas A&M University became infected with the deadly brucellosis virus. The university did not report the case and may never have admitted it if an industry gadfly, Edward Hammond of the Sunshine Project, had not persuaded a local district attorney to strong-arm the university into giving up its internal records. The CDC then dispatched investigators who uncovered a host of other violations, including unauthorized experiments, failure to report three other infections of Q fever, failure to have all technicians vetted by the FBI, and missing pathogens and infected animals. "Unfortunately, the CDC's August investigation revealed not only shortcomings on Texas A&M's part, but also shortcomings on the part of CDC's own oversight," said Bart Stupak, chairman of the House Oversight and Investigations Committee. "It turns out that the CDC had inspected the very same Texas A&M lab prior to the disclosure of these incidents and found only minor problems."
Responding to intense criticism, the CDC is looking into forming external peer review panels to re-examine select-agent regulations and lab-safety procedures. The agency may also modify reporting requirements — possibly allowing some measure of anonymity, for example, to minimize disincentives for revealing accidents. "This is a relatively young program [which] is providing much improved oversight, but clearly there is more than we can do," says Richard Besser, director for the CDC's Coordinating Office for Terrorism Preparedness and Emergency Response, who defends the recent lab expansion in the U.S., saying it will lead to better diagnostics and make next-generation vaccines accessible to more Americans.
But many experts disagree, calling into question the focus of biological research in the U.S. — on anthrax and plague instead of, say, drug-resistant tuberculosis or the hepatitis viruses — which may be doing the country a disservice. In a 2005 open letter, organized by Richard H. Ebright, a Rutgers University chemistry professor, 758 American microbiologists complained that NIH priorities favoring research of "high bio-defense significance but low public-heath significance" were misguided and jeopardized public health progress.
Controversial celebrity US scientist Craig Venter has announced he is on the verge of creating the first ever artificial life form which he hails as a potential remedy to illness and global warming.
Venter told Britain's The Guardian newspaper Saturday that he has built a synthetic chromosome using chemicals made in a laboratory, and is set to announce the discovery within weeks, possibly as early as Monday.
The breakthrough, which Venter hopes could help develop new energy sources to combat the negative effects of climate change, would be "a very important philosophical step in the history of our species," he told the newspaper.
However the prospect of engineering artificial life forms is highly controversial and likely to arouse heated debate over the ethics and potential ramifications of such an advance.
Pat Mooney, director of the Canadian bioethics organization ETC Group, told the paper that Venter was creating "a chassis on which you could build almost anything.
"It could be a contribution to humanity such as new drugs or a huge threat to humanity such as bio-weapons."
The chromosome which 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.
The single cell organism, which ETC has coined "Synthia," is piloted by a chromosome with just 381 genes, the limit necessary to sustain the life of the bacteria so it can feed and reproduce.
The new bacteria will therefore be largely artificial, though not entirely, because it is composed of building blocks from already existing organisms. The idea is to make it into a universal tool for biologists by according it the genes necessary to accomplish certain tasks.
The project, which Venter has been working on for five years along with a team of researchers, has been partially financed by the US Department of Energy in the hopes that it could lead to the creation of a new environmentally friendly fuel.
"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 said.
A Venter spokeswoman however declined to confirm any breakthrough.
"The Guardian is ahead of themselves on this," Venter spokeswoman Heather Kowalski told AFP.
"We have not achieved what some have speculated we have in synthetic life," Kowalski said. "When we do so there will be a scientific publication and we are likely months away from that."
Venter's laboratory, the J. Craig Venter Institute, filed in 2006 for a US patent on the organism, claiming exclusive ownership of a set of essential genes and a synthetic "free-living organism that can grow and replicate."
The ETC group publicized the patent application, which would apply in the United states and 100 or so other countries, in June.
"Venter and his colleagues have breached a societal boundary, and the public hasn't even had a chance to debate the far-reaching social, ethical and environmental implications of synthetic life," Mooney said in a statement at the time.
The group also added that "patent experts consulted by the ETC Group indicate that, based on the language used in the application, the Venter Institute researchers had probably not achieved a fully-functioning organism at the time of the filing."
Nevertheless, "many people think that Venter's company has the scientific expertise to do the job," Mooney added.
When male birds know they're about to get it on, that action is more likely to spawn a bigger brood of eggs compared to spontaneous copulation, a new study finds.
Previous studies have shown that when two male birds mate with a female in a competition to pass on their genetic material, they end in a draw and both become fathers to an equal number of eggs.
But researchers wondered whether Pavlovian conditioning (the process that set Ivan Pavlov's dogs drooling for meat whenever they heard a ringing bell) could give one male an advantage over the other.
Using male quails, Nicolle Matthews of the University of Texas and her colleagues placed each of two birds into two differently designed chambers for 30 minutes over a period of five days.
Whenever the males were in one of the two chambers, they were then allowed access to a female, and so learned to anticipate having the chance to mate when placed in that chamber (so it functioned sort of like the avian equivalent of a Barry White album).
On test day, each male was placed in one of the two chambers and then allowed to copulate with the female. Researchers then tested the paternity of the female's eggs.
The results, detailed in the September issue of the journal Psychological Science: the quail in the "Barry White chamber" fathered more of the eggs.
How Do Artists Portray Exoplanets They've Never Seen?
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Image: COURTESY OF GEOFF MARCY |
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WHY SO BLUE? A planet recently discovered around the star Gliese 436 was depicted in blue in this artist's rendering because its atmosphere was likely baked into small molecules that scatter blue light like Earth's does. CLICK HERE FOR MORE ON THE LOGIC OF EXOPLANET IMAGES |
Naturally, people can get confused. When San Francisco artist Lynette Cook painted a particularly striking image of a newly discovered planet passing in front of the star HD 209458 for a 1999 NASA press release, she received e-mail asking what kind of amazing image processing software she had used. "A lot of people didn't understand that it was a rendering," she says.
Well aware of the double-edged sword they wield, artists and astronomers who dream up images of astronomical exotica often spend considerable time deciding how best to illustrate new discoveries. In the case of exoplanets, they are guided by a few key pieces of information and a healthy dose of educated guesswork.
Researchers frequently discover exoplanets by searching for regular variations in the color of a star's light. A planet circling in orbit will tug its star back and forth like a wispy figure skater spinning around a heavier one.
If the system is aligned so that the star wobbles toward and away from us, the light will appear to oscillate between bluer and redder as the wavelength expands or contracts along the line of sight to Earth.
This oscillation, which would not be especially eye-catching plotted as a graph, contains several crucial bits of information. Encoded in the timing of the oscillating light are the shape and distance of the planet's orbit around its star, which in turn determine how warm it is likely to be and, therefore, whether it could have liquid or frozen water, in the case of a rocky, Earth-like planet.
The degree of the color shift indicates the planet's mass and makeup. Astronomers believe that a planet as hefty as the solar gas giants Saturn (95 Earth masses) or Jupiter (318) would almost certainly be gaseous. Smaller planets of up to a few dozen Earth masses might range from those made mostly of rock and ice to larger ones with a solid core enshrouded by a mixture of thick gas.
Orbital distance would also influence a planet's color, says astronomer Geoffrey Marcy of the University of California, Berkeley, whose team has discovered 145 of the known exoplanets.
Jupiter and Saturn have brownish-orangey tints because their atmospheres swirl with carbon-based molecules that reflect light of those colors, Marcy says; a hotter atmosphere would evaporate water clouds and break down those molecules into carbon dioxide and methane, which scatter blue light. The effect might result in "deep blue billiard balls," he says.
Less familiar colors may also be out there. In May astronomers reported that planet HD 149026 b seems to absorb so much light that it should appear nearly black.
Today's instruments have too little resolution to detect details found in some images, including moons, rings and volcanic activity. Cook takes her cue from astronomers when deciding how or whether to depict such enhancements. "Most of them are really pretty open to show what might be there," she says.
Robert Hurt, a self-described visualization scientist for the Spitzer Space Telescope, says he ups the realism of his depictions of distant gaseous planets by matching the size and shape of their roiling clouds with those of known solar gas giants.
Marcy says the artists he works with (including Cook) typically develop two drafts of an image before creating the final masterpiece [click here for examples]. Of course, he doesn't always have final say on the illustration that accompanies press releases. When his team discovered the first Saturn-like exoplanet, for instance, NASA commissioned an image of a reddish gas giant covered in white spiral clouds.
"This makes me cringe," he says. "It looked like the planet was wearing paisley pajamas." But it was out of his hands. "There's not much you can do when NASA says they want a [certain] depiction. You can't stop them."
Some observers say that an emphasis on realism might be a touch deceptive. "My problem with so much of the beautiful stuff that artists do is that we are not privy to the decision-making process," says Felice Frankel, a senior research fellow and science photographer at Harvard University. "The more, quote, 'real' something looks, the more you accept it as fact."
For Frankel, labeling something an artist's rendering is not enough, because an image leaves a lasting impression. She advocates literally showing viewers where the interpretation lies by providing multiple possible views—something Marcy and Cook have tried—or making images sketchier and more interactive.
"My fantasy is, for example, that you see a picture online and, with your cursor, you kind of travel around the artist's concept and you see a rollover of information," she says. "Why not say right at that spot, 'this is supposed to represent this but we're not sure about that and this and that'?"
Nobody disagrees that colorful, detailed images may carry a risk of misconception. But for the image makers—tasked by funding agencies to convey new findings to the public—the benefits outweigh the risk.
"It's alright to have pictures as long as they generate intelligent discussion," Marcy says. "Pictures allow people to imagine, where otherwise their imaginations might be somewhat limited."
Capturing a true image of an exoplanet, Marcy says, may have to wait until NASA scrapes together the money to launch the proposed Terrestrial Planet Finder, which would include a telescope equipped with a tool for blotting out distant stars, thereby creating an artificial eclipse to reveal orbiting planets.
Until then, the problem of realism versus abstract renderings has no easy solution, Hurt says, noting that the goal generally dictates the answer. "If a casual observer notices an artist's concept of a planet in an article in USA Today, [and] thinks 'wow, we're observing planets,' and [then] turns to the sports page, was that a success?" he asks.
Probably so, in his view. "If the image was dull or diagrammatic," Hurt says, "he might not have even noticed the article at all."
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