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April 2003

Bio-Terrorism & SARS
Posted: Saturday, April 26, 2003
The world has been whipped up into hysteria over terrorist attacks and 'weapons of mass destruction'. Governments want to ban the publication of sensitive scientific research results, and a group of major life sciences editors and authors has concurred. Some even suggest an international body to police research and publication. Dr. Mae-Wan Ho looks at the current SARS epidemic and argues why all of those measures to control bio- terrorism are misplaced, and what's really needed.

The SARS episode

In the weeks that the 'allied forces' were wreaking destruction and death in Iraq to hunt down Saddam Hussein and his elusive 'weapons of mass destruction', a SARS epidemic has been criss-crossing continents carried by air-passengers and spreading like molecular cluster bombs that explode to liberate further millions of infectious particles soon after a target is struck.

SARS – Severe Acute Respiratory Syndrome – is a completely new infectious disease spread by human contact, and kills about four percent of the victims. The epidemic originated in Guangdong Province, South China. The Chinese authority has admitted mishandling the crisis and to have been slow to inform its citizens.

The disease first struck last November. In March, Liu Jianlin, 64 year-old medical professor who was involved in treating patients, went from Guangdong to Hong Kong to attend a wedding. He was taken ill soon after arrival and admitted to hospital. He asked to be put into quarantine, but was ignored; nor did the hospital warn his contacts. As a result, nine guests in the hotel where he stayed caught the disease and carried it to Singapore, Canada, Vietnam and other hospitals in Hong Kong.

On 10 February, news of the disease was posted on ProMed, an international e-mail notification service for infectious diseases outbreaks. The next day, China informed the World Health Organisation (WHO), but refused to let the WHO team into Guangdong until early April. By 8 April, there were 2671 confirmed cases of SARS in 19 countries and 103 deaths.

A palpable sense of panic has gripped the health authorities around the world. "Mother nature is the ultimate terrorist," says an editorial in the journal Nature. "Powerless to stop the spread", says New Scientist magazine, whose editor decries the lack of international control when it comes to disease epidemics: "The international community has weapons inspectors poised to force entry into a country at the first hint that it may possess chemical weapons. But when it comes to disease, we have no international body empowered to take charge, even though the disease may be vastly more dangerous." (italics added)

Eleven laboratories around the world participated in the hunt for the disease agent, a collaborative effort organised via teleconferencing, since March 17, by virologist Klaus Stφhr at the WHO headquarters in Geneva.

The journal Science says that Malik Pieris of the University of Hong Kong was the first to identify coronavirus (which causes colds and pneumonia) just four days later. This finding was replicated in other laboratories. The virus and antibodies against the virus were detected in many, though not all infected patients, but were not found in more than 800 healthy controls tested.

The New Scientist says it was the death of Carlo Urbani, the WHO doctor who first recognized SARS as a new disease that led to the discovery of coronavirus. It was isolated from his lungs and sent to Joe DiRisi in University of California at San Francisco who made the identification. The virus has since been named after Urbani.

There is some remaining doubt, however, whether the coronavirus is the complete story. John Tam, director of virology at Prince of Wales Hospital in Hong Kong, found another virus, the human metapneumovirus in 25 out of 53 SARS patients, as have laboratories in Canada and Germany. Metapneumoviru belongs to the family Paramyxoviridae, which includes viruses responsible for parainfluenza, mumps and measles, as well as the Nipah and Hendra viruses in recent outbreaks.

Coronavirus showed up in only 30 patients tested while the bacterium Chlamydia has been identified in all samples in Hong Kong, though that strain of Chlamydia is not known to cause disease.

Could it be that both viruses are bystanders of the disease while an as yet unidentified virus could be responsible for SARS?

The coronavirus was atypical. It rapidly infected cells in culture dishes, something that other human coronaviruses do not do. Viruses from the lung tissue in Toronto patients readily infected monkey kidney cells, and no known human coronavirus infects that cell line.

DiRisi's laboratory has a virus detector chip capable of screening for 1 200 viruses all at once. When samples sent from the Centers of Disease Control and Prevention in the United States (CDC) were screened, several species of coronaviruses lit up, the strongest spots – indicating the closest identity - were the avian bronchities virus and a bovine coronavirus. This appears to fit China's statement that the earliest cases were in bird handlers.

However, more detailed analysis using polymerase chain reaction (PCR) by two groups who just published their results online in the New England Journal of Medicine indicate that the new virus is not closely related to any known virus at all, human, mouse, bovine, cat, pig, bird, notwithstanding.

Furthermore, the virus was isolated from cell cultures only, and not from the tissues of patients. The PCR fragments of the new coronavirus were not detected in any healthy subject tested so far. But not all patients with SARS tested positive for one of the PCR fragments. Where did this new virus come from?

Genetic engineering super-viruses

While the epidemic has still to run its course, a report appeared in the Journal of Virology, describing a method for introducing desired mutations into coronavirus in order to create new viruses. A key feature of the procedure is to make interspecific chimera recombinant viruses. It involves replacing part of the spike protein gene in the feline infectious peritonitis virus (FIPV) - which causes invariably fatal infections in cats - with that of the mouse hepatitis virus. The recombinant mFIPV will no longer infect cat cells, but will infect mouse cells instead, and multiply rapidly in them.

These and other experiments in manipulating viral genomes are now routine. It shows how easy it is to create new viruses that jump host species in the laboratory, in the course of apparently legitimate experiments in genetic engineering. Similar experiments could be happening in nature when no one is looking, as the SARS and many other epidemics amply demonstrate.

It is not even necessary to intentionally create lethal viruses, if one so wishes. It is actually much faster and much more effective to let random recombination and mutation take place in the test tube. Using a technique called "molecular breeding" (see "Death by DNA shuffling", this series), millions of recombinants can be generated in a matter of minutes. These can be screen for improved function in the case of enzymes, or increased virulence, in the case of viruses and bacteria.

In other words, geneticists can now greatly speed up evolution in the laboratory to create viruses and bacteria that have never existed in all the billions of years of evolution on earth.

Controlling bio-terrorism

John Steinbruner, University of Maryland arms control expert, has been calling for mandatory international oversight of inherently dangerous areas of biomedical research, specifically, an international body of scientists and public representatives to authorize such research.

He has taken the proposal to meetings of the American Association for the Advancement of Science and the World Medical Association in recent months, and in April 2003, to a London bio-terrorism meeting, sponsored by the Royal Society of Medicine and the New York Academy of Medicine.

The oversight system would be mandatory and would operate before potentially dangerous experiments are conducted. Access to results could also be limited to those who pass muster.

Requiring scientists, institutions and even experiments to be licensed "would have a devastating chilling impact on biomedical research," said American Society for Microbiology (ASM) president Ronald M. Atlas. His answer is self-regulation, already in line with ethical requirements to prevent the destructive uses of biology.

The ASM orchestrated and supports a statement released February 15 by a group of major life sciences editors and authors, acknowledging the need to block publication of research results that could help terrorists.

Critics say even the self-censorship espoused by the journal editors and authors group is an impediment to the rapid progress of science, which is the best way to defuse the lethal potential of some biological research. But Steinbruner fears that self-regulation does not go far enough to head off terrorists.

Both Steinbruner and Atlas agree, however, that any effort to keep good science out of the hands of ill-intentioned people must be international to be effective. And both point to existing efforts to push a treaty making bio-terrorism an international crime, one long espoused by Harvard University microbiologist Mathew Meselson and chemist Julian Robinson of the University of Sussex.

Steinbruner and his critics, and the critics of his critics are all missing an important point. They have yet to acknowledge that genetic engineering experiments are inherently dangerous, as first pointed out by the pioneers of genetic engineering themselves in the Asilomar Declaration in the mid 1970s, and as we have been reminding the public and policy-makers more recently.

Who needs bio-terrorists when we've got genetic engineers?

But what caught the attention of the mainstream media was the report in January 2001 of how researchers in Australia 'accidentally' created a deadly virus that killed all its victims in the course of manipulating a harmless virus. "Disaster in the making: An engineered mouse virus leaves us one step away from the ultimate bioweapon", was the headline in the New Scientist article. The editorial showed even less restraint: "The genie is out, biotech has just sprung a nasty surprise. Next time, it could be catastrophic."

The SARS episode should serve as a reminder of some simple facts about genetic engineering.

In the first place, genetic engineering involves the rampant recombination of genetic material from widely diverse sources that would otherwise have very little opportunity to mix and recombine in nature. And, as said earlier, some newer techniques will create in the matter of minutes millions of new recombinants in the laboratory that have never existed in billions of years of evolution.

In the second place, disease-causing viruses and bacteria and their genetic material are the predominant materials and tools of genetic engineering, as much as for the intentional creation of bio-weapons.

And finally, the artificial constructs created by genetic engineering are designed to cross species barriers and to jump into genomes, ie, to further enhance and speed up horizontal gene transfer and recombination, now acknowledged to be the major route to creating new disease agents, possibly much more important than point mutations which change isolated bases in the DNA.

With genetic engineered constructs and organisms routinely released into the environment, we hardly need the help of terrorists. That may be why we are coming up against new epidemics of viral and bacterial diseases with increasing regularity. Mother nature is not the ultimate terrorist, we are.

What needs to be done instead?

It is pointless to control the publication of sensitive scientific results because there is nothing special about the recombination techniques, they are already well known. "The only way we'll ever understand these natural outbreaks is by first-rate science and getting it published," says Lynn Enquist, editor of the Journal of Virology, referring to the creation of a coronavirus that crosses from cat to mouse that's a routine part of a genetic engineering technique.

Open publication is only half of the story. The other half is the importance of biosafety. An international instrument for regulating biosafety already exists, it is the Cartegena Biosafety Protocol agreed in January 2000, now signed by 43 countries including the European Union; though efforts to undermine it has continued unabated, principally by the United States and allies and the biotech industry. All we need to do is to strengthen the Biosafety Protocol both in scope and in substance.

There is also an urgent need for democratic input into the broad areas of scientific research that are to be supported by the public purse. Every sector of civil society has been called upon to be 'accountable', even corporations; so why not scientists?

We have drafted a discussion document, Towards a Convention on Knowledge, which contains some key ideas on how scientists could be socially responsible and accountable.

A long list of sources and references for this article is posted on ISIS Members' website. Details here.

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Is the Sub-continent immune to SARS menace?
Posted: Wednesday, April 23, 2003
Severe Acute Respiratory Syndrome (SARS)

by Shakti Sharma (
New Delhi, April 23

Are people from India and Indian sub-continent immune to the fast spreading SARS virus? This question is baffling the medical community, with doctors discussing the possibility of the virus being race-specific.

Some doctors are of the view that people of the sub-continent may have a higher level of immunity to the virus. They reason that with a large number of Indians, Pakistanis, Bangladeshis and Sri Lanka frequenting SARS-affected regions like Singapore, Hong Kong and other territories, hardly anyone has contracted the virus.

WHO (Delhi HQ) Information Officer, Harsharn Pandey avers: "It has been almost five months since the first case of SARS was reported from China, and the virus has spread to 23 countries, but not a single case of SARS has been reported from Pakistan, Sri Lanka, and Bangladesh".

AIIMS virologist, Dr Shobha Broor says," Viruses are never race sensitive but it could be possible that people from this part of the sub-continent could have developed antibodies to counter the SARS virus."

Although WHO has no race-wise record of SARS victims - both dead and those affected -- available information culled from various sources points out that no person from this part of the world has died of SARS so far.

Director of the Centers for Disease Control and Prevention of the US health department, Dr Julie L Gerberding, during a recent video conference, admitted about the typical race-specific behaviour of the virus and said that in China, Hong Kong and Singapore the ongoing transmission of this virus at a very accelerated pace in "certain communities".

Doctors are also pointing out at the fact that the local transmission of the virus has so far been reported from China, Hong Kong, Canada, Singapore, Vietnam, Taiwan, UK and the USA, while in the sub-continent, people who had tested positive for the virus had brought in the disease from infected nations and the recovery rate is cent percent.

Quoting incidents of SARS, doctors say, the first ever case of SARS in India was reported from Goa where a marine engineer tested positive. The patient, however, responded well to treatment and recovered in almost no time.

In the latest SARS case reported from Pune, three members of a family -- Stanley D'silva, his mother Vimla and sister Julie -- who came to India three weeks ago, tested positive. While Stanley has completely recovered, his mother and sister are responding well to treatment.

Indian Medical Association (Delhi Chapter) president, KK Aggarwal says the so called SARS positive cases reported cases in India may ultimately test negative, as the confirmatory test for the virus on the convalescent sample has to be done after 21 days.

Reproduced from:,001300090001.htm

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Combatting The Scourge Of SARS
Posted: Tuesday, April 22, 2003
L'Express (Port Louis)
by Ahmad Macky

Severe acute respiratory syndrome (SARS) is a respiratory illness that has recently been reported in Asia, North America and Europe. According to Medical Scientists, the illness usually begins with a high fever. This fever is sometimes associated with chills or other symptoms, including headache, general feeling of discomfort and body aches. Some people also experience mild respiratory symptoms at the outset.

This outbreak came like a bolt from the blue, as there is no sign and indication that it would go out in the same fashion. Such an outbreak has sprung on an unsuspecting world, claiming hundreds of precious lives in a short period. From Australia to Brazil to Sweden, the deadly SARS has swept across the globe, targeting rich and poor nations alike. Apart from the Aids epidemic, no other disease has spread around the world in so brief a period of time.

This viral disease similar to pneumonia, first appeared last November in China and began to spread internationally through travellers early this year. The disease, which is fatal in about 4% of cases and has no known cure, has killed more than 200 people and infected 3,600 people worldwide. In Hong Kong itself, the latest deaths took the toll to a world-leading 81. It has now 1 358 cases of SARS, almost as many as on the Chinese main land where the deadly virus first appeared in the Southern province of Guangdong. Doctors still do not have a specific test for SARS, but laboratories around the world are close to developing one.

The SARS outbreak proves very clearly that the world is still susceptible to new diseases notwithstanding the vast advances in medical science and health technology. Ironically, another modern phenomenon - air travel - has been cited as the main culprit for the rapid spread of affliction. Air transport has shrunk the world. An infected person can travel from his country to another in a matter of hours. No one anywhere is really safe.

Mauritius can count itself among the lucky countries, which have not reported SARS cases so far. Constant precautions are being taken by the Ministry of Health to prevent such a deadly disease in our island.

However, given the nature of the illness and its method of transmission, we should not scale down our defenses. Authorities should heighten surveillance at all entry points and especially screen passengers from highly affected countries. If a reliable SARS test becomes available soon, health authorities should get it down without delay.

Hospitals, public and private, should be geared fully to meet any contingency. The media should be used extensively to disseminate information on SARS, as thousands of Mauritians travel abroad daily.

All these should be implemented as soon as possible, because the cost of complacency could be astronomical. We too, like some of these countries that have reported SARS cases, depend heavily on tourism and labour migration. Any negative effect on these vital segments of the economy could indeed be very unhealthy for our country.

All is not lost, however. The world is fighting back. Health authorities around the world have joined hands to combat this scourge. The most encouraging news so far is that scientists in Singapore, US and Canada, with the backing of the World Health Organization, have broken the genetic code of the SARS virus, raising hopes of developing a proper diagnostic test, a vaccine and a cure.

A cure may not be unattainable, as Man has tamed a number of previously deadly diseases and even eradicated some altogether. Smallpox is a good example. Vaccines and effective medicines are available for many other serious diseases. Of course, there is no guarantee that a cure may eventually be available for SARS - AIDS and cancer cannot still be cured completely and permanently after decades of medical research.

While the world literally holds its breath for an effective cure, the pictures streaming across our TV screens of men, women and children wearing masks to evade an invisible enemy remind me once again how vulnerable our society is ! Man is powerful, but Nature is supreme.

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Posted: Monday, April 7, 2003
Source: University Of Michigan

It's A Nova ... It's A Supernova ... It's A HYPERNOVA

ANN ARBOR, Mich. --- Two billion years ago, in a far-away galaxy, a giant star exploded, releasing almost unbelievable amounts of energy as it collapsed to a black hole. The light from that explosion finally reached Earth at 6:37 a.m. EST on March 29, igniting a frenzy of activity among astronomers worldwide. This phenomenon has been called a hypernova, playing on the name of the supernova events that mark the violent end of massive stars.

With two telescopes separated by about 110 degrees longitude, the Robotic Optical Transient Search Experiment (ROTSE) will have one of the most continuous records of this explosion.

"The optical brightness of this gamma ray burst is about 100 times more intense than anything we've ever seen before. It's also much closer to us than all other observed bursts so we can study it in considerably more detail," said Carl W. Akerlof, an astrophysicist in the Physics Department at the University of Michigan. Akerlof is the leader of ROTSE, an international collaboration of astrophysicists using a network of telescopes specially designed to capture just this sort of event. The collaboration is headquartered at U-M and funded by NASA and the National Science Foundation (NSF).

Just recently, the ROTSE group commissioned two optical telescopes in Australia and Texas and were waiting for the first opportunities to use the new equipment. The burst was promptly detected by NASA's Earth orbiting High-Energy Transient Explorer (HETE-2) but human intervention was required to find the exact location. Despite sporadic clouds and rainstorms in Australia, the ROTSE instrument at Siding Spring Observatory in northern New South Wales was able to record the decaying light from the blast. Twelve hours later, the second ROTSE telescope in Fort Davis, Texas was picking up the job of monitoring this spectacular explosion.

"During the first minute after the explosion it emitted energy at a rate more than a million times the combined output of all the stars in the Milky Way. If you concentrated all the energy that the sun will put out over its entire 9 billion-year life into a tenth of a second, then you would have some idea of the brightness," said Michael Ashley, faculty member in the astrophysics and optics department at the University of New South Wales and a member of the ROTSE team.

Akerlof became interested in studying gamma ray bursts in the early 1990s. While they are the most powerful explosions in the universe, gamma-ray bursts are extremely hard to study because they are extremely distant, occur randomly in time and seldom last more than a minute. Small, fast, and relatively inexpensive robotic ground-based telescopes like ROTSE offer the best chance of catching early optical emissions from the bursts. ROTSE attracted national notice in 1999 when it captured the rise and fall of GRB990123, one of the brightest bursts prior to this latest event.

"The ROTSE equipment is quite modest by modern standards, but its wide field of view and fast response allow it to make measurements that more conventional instruments cannot," Akerlof said. "We have two telescopes online now, and installations in Namibia and Turkey will follow soon. Our goal is to have telescopes continuously trained on the night sky. Our motto is "The Sun never rises on the ROTSE array." That's why we want them spread as widely as possible."

Another role for ROTSE and other small telescopes is to alert larger facilities about gamma ray bursts and other transient phenomena. "One of the most exciting things about an event like this is the way the global community of scientists pulls together, pooling their data and their different capabilities," Akerlof said.


For more information about ROTSE, visit To learn more about physics at the U-M visit For more about Carl Akerlof, see

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Stone Toolmaking Also Done By Women
Posted: Monday, April 7, 2003
Source: University Of Florida

Despite Male Image, Stone Toolmaking Also Done By Women, University Of Florida Scientists Say

GAINESVILLE, Fla. --- Move over, man the toolmaker: The idea of men as stone tool producers may need some rechiseling, say University of Florida scientists who found women sometimes are the masters. The research among an Ethiopian group indicates stone tool working is not just a male activity, but rather that women probably had an active part in creating stone tools, one of the most ubiquitous materials found on prehistoric sites.

"It really gives women a presence in the archaeological record and a chance for us to reflect upon a place in prehistory where women basically have been invisible," said Kathryn Weedman, a UF anthropology lecturer who led the National Science Foundation-funded research, which just completed its second year.

"There has always been this image of 'man the toolmaker' because it's generally perceived by the public, and many archaeologists, that males were the ones who made stone tools," said Steve Brandt, a UF anthropology professor and co-leader of the research team. "But we found that among one ethnic group, the Konso of Ethiopia, women dominate the activity."

The Konso women create a stone tool called a scraper to clean animal hides to be made into bedding and clothing, he said.

Stone tools are important because they were the first recognizable object people made, marking the beginning of the archaeological record dating back as early as 2.6 million years ago, Weedman said. Not until 5,000 to 10,000 years ago were pottery and metal tools introduced, she said.

"Stone artifacts are critical for identifying a wide range of activities that will help us learn what life was like," she said. "Basically, they trace the evolution of human culture because, for better or worse, they are often the only things preserved."

If people were found to be scraping antelope hides 100,000 years ago, for example, that might help tell us when they started making prepared clothing, Brandt said.

The Konso project "is vitally important both in documenting how stone tools are made and used – most people who used stone tools have been dead for hundreds or thousands of years – and in the social context of their use," said Michael Shott, an anthropology professor at the University of Northern Iowa.

The tradition of stone toolmaking continued into the 20th century in isolated parts of Africa, Australia and Siberia, but in the last couple of decades it has virtually disappeared as an everyday activity, except perhaps for the hide workers of Ethiopia, Brandt said.

The project is unique because it provides evidence that women actively flake stone to produce tools, Brandt said. "This project changes our perspective dramatically because theoretically we can talk about gender issues – the role of men and women in ancient societies," he said.

In the study described in the September/October issue of Archaeology magazine, the UF researchers identified 119 Konso hide workers who used flaked stone, glass or iron to scrape hides. Seventy-five percent of the hide workers were women, and most – 73 percent – were 40 or older, Weedman said.

Members of this group are born into the hide-working profession and remain locked into it, Weedman said. The products they make have not yet been completely replaced by Western industrial products, she said. "No one is living in the stone age," Brandt said of today's stone toolmakers. "They're wearing Western clothes, they have radios, they may even know about 9-11," he said. "They make these stone tools because the tools work. Stone is still the superior material – they prefer it over glass and iron."

The research team is seeking to determine why the scrapers look different from one village to the next, which may relate to differences in cultural traditions and ethnicity.

There is a sense of urgency to the research because humanity's first and longest-lasting cultural tradition is being lost rapidly, Brandt said. Many Konso hide workers are elderly and have not taught the craft to their children, and some are beginning to abandon stone for bottled glass because they can more easily pick up pieces off the road instead of having to hike two hours for chert, he said.

In the United States today, stone toolmaking has undergone something of a renaissance with the organization of various fairs and events that give amateurs a chance to try their hand at it, Brandt said.

"The great thing about our work is these are one of the last people in the world using stone tools on a regular basis, and they are living people whom we can directly observe, rather than base our understanding of the archaeological record strictly on experimentation and history," Brandt said.

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A New Branch On The Tree Of Life
Posted: Monday, April 7, 2003
Source: Lawrence Berkeley National Laboratory

That Bug Is No Insect: A New Branch On The Tree Of Life

The family tree of life has a newly discovered branch. Genetic studies comparing mitochondrial DNA have revealed that what has long been thought to be the group from which insects arose, the Collembola -- wingless hexapods (or "six legs") commonly called springtails -- turns out not to be closely related to insects after all.

Instead, these creatures belong to a separate evolutionary lineage that predates even the separation of insects and crustaceans. The research was carried out at the U.S. Department of Energy's Joint Genome Institute (JGI) by scientists with the Lawrence Berkeley National Laboratory (Berkeley Lab), working with a team of Italian researchers.

"Based on the similarities in their body organization, their six legs, and other morphological characteristics, it has been generally accepted that the collembolans were the basal stock from which insects arose," says Jeffrey Boore, a biologist with Berkeley Lab's Genomics Division who heads JGI's Evolutionary Genomics Department. "Our study shows that they evolved separately from insects and independently adapted to life on land."

Collaborating with Boore on the project were Francesco Nardi, Giacomo Spinsanti, Antonio Carapelli, Romano Dallai and Francesco Frati, all with the Department of Evolutionary Biology at the University of Siena in Italy. Their research was reported in the March 21 issue of the journal Science.

"The collembolan appear to branch off the evolutionary line leading to the insects at a much earlier stage than previously thought -- earlier than some if not all of the crustaceans," says Nardi. "In fact, the few crustaceans that we've analyzed so far using mitochondrial genomics appear to be more closely related to the true insects than are the collembolans."

Mitochondria are organelles, found in living cells, that play a central role in vital life processes such as metabolism. They have been called "the powerhouses" of cells because they produce the ATP molecules that provide cells with chemical energy. But mitochondria were actually once independent organisms that long ago evolved into a symbiotic relationship with the nuclei of cells.

The former independence of mitochondria has been preserved in a tiny genome, separate from the genome of the host cell, with its own genes and its own system for DNA replication and translation into proteins. Much simpler than nuclear genomes but governed by the same rules of genetic conservation, and closely interacting with host-cell genomes, mitochondrial genomes can serve as a powerful tool for the study of evolutionary biology.

"The small size and compact arrangement of mitochondrial genomes make it possible to study and do comparative genomics with many different organisms," Boore says. "Plus, these genomes are usually circular, which allows them to be physically isolated from nuclear genomes. And their biochemistry is relatively well understood."

Insects have been thought to be the dominant group of Hexapoda, also thought to include the Collembola and a few other wingless groups. Together these groups have been included as part of the phylum Arthropoda (the name means "jointed feet"), which constitutes nearly 85 percent of all known species of animal life. Other arthropod taxa include Myriapoda (for example, centipedes and millipedes), Chelicerata (for example, spiders), and Crustacea (for example, crabs and lobsters).

Using classic approaches to evolutionary biology, such as comparative morphology or paleontology, it has long been held that Hexapoda is a "monophyletic" taxon, meaning all members of the group are descended from a single ancestor. However, by doing comparative analyses of the DNA from entire mitochondrial genomes, Boore and Nardi and their collaborators found that Collembola should not be included within Hexapoda.

"Based on our results and consequent phylogenetic reconstruction, we can say that collembolans, which have until now been classified as the sister group to the insects within the hexapods, should be separated so that they constitute a separate evolutionary line," says Nardi. "The next step will be to assign a class level status to Collembola, but this decision probably won't be made on the basis of a single study, even if the results we present seem to be quite strong."

Nardi says he and his Italian collaborators sought out Boore to work on this project because they consider him the "world's leading expert" in the study of mitochondrial genomics. "Jeff provides his expertise on mitochondrial genomics and is a bridge between us and the huge sequencing and technical capabilities of the JGI."

The JGI headquarters in Walnut Creek, California, houses one of the nation's fastest and most powerful genome sequencing operations. JGI is a collaboration between Berkeley Lab, Lawrence Livermore, and Los Alamos National Laboratories, funded by DOE's Office of Biological and Environmental Research.

Nardi says, "This has been a very fruitful collaboration so far, and we are planning to do more studies along this line."

 The original news release can be found here.

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Clearest Picture Of All Genes Of An Animal
Posted: Monday, April 7, 2003
Source: Dana-Farber Cancer Institute

New Technique Gives Scientists Clearest Picture Yet Of All The Genes Of An Animal

BOSTON – Dana-Farber Cancer Institute scientists have used a powerful gene-mapping technique to produce the clearest picture yet of all the genes of an animal – the microscopic worm Caenorhabditis elegans (better known as C. elegans). Scientists believe the same technique may be used to bring the current, somewhat blurry picture of the human genome into sharper focus.

The study, which will be posted on the Nature Genetics website ( April 7 in advance of its publication in the journal, describes an effort to locate and precisely identify all of the approximately 19,000 genes that have been predicted to exist in the genome of C. elegans. The success of the technique in the worm, whose catalogue of genes is relatively small and well-mapped, is a strong indication that it can be applied to the human genome as well, the authors say.

"The completion of a 'rough draft' of the map of the human genome a couple of years ago was an important milestone in our understanding of how cells work," says the study's senior author, Marc Vidal, PhD, of Dana-Farber. "But the fact is, our current picture of the 'parts list' of the human genome is rather fuzzy. Computer programs have been used to predict the position and structure of genes. However, we don't know exactly where most genes begin and end, and there are literally thousands of gaps in our picture of how the building blocks of genes are arranged. Even the frequent claim that there are about 30,000 genes within the human genome is only an estimate."

Gaining a more accurate picture of the genome is crucial to future advances against cancer and other diseases. One of the goals of cancer research, for example, is to discover the complete set of proteins, the chief tools of cell life, that are involved in the disease, either directly or indirectly. To understand what such cancer-related proteins do and how they do it, scientists need to be able to generate pure samples of them. And because genes contain the instructions for producing proteins, it is vital that researchers know exactly what those instructions say, where they are, and how to obtain them.

The current, somewhat sketchy map of the human genome was created with computer programs that predict where genes are likely to be found on a cell's chromosomes, not necessarily where genes actually are, Vidal observes. "It's the difference between a soft-focus image of an object and a crisper image that shows the outline in detail."

Moreover, the current map also gives an incomplete view of genes' internal organization. Genes are often portrayed as a string of beads along the length of a chromosome. In fact, genes themselves are made up of alternating bands of DNA: sections known as exons, which contain coded information for producing proteins, alternate with sections known as interrupting introns. For a great many genes, scientists do not know exactly where these sections begin and end.

"Of the 30,000 genes believed to be in the human genome, only about 5,000 have been well defined," remarks Vidal, who is also an assistant professor of genetics at Harvard Medical School. "The structures of the other 25,000 have yet to actually be confirmed. Plus, there are long stretches of the chromosomes that remain terra incognita – that may contain genes yet to be discovered."

In their study, Vidal and his colleagues checked the accuracy of the map of the C. elegans genome using a technique of their own design. (Conventional techniques tend to miss less-active genes, and they don't offer a useful way of converting genetic information into proteins.)

The strategy involves blocks of genetic material called open reading frames, or ORFs. These include most of the exons in a gene, after the introns have been removed or spliced out. "ORFs are the actual blueprints for proteins," Vidal explains. "Introns don't seem to participate in the actual make-up of proteins."

C. elegans produces ORFs as a natural part of living, as do all creatures. When a cell creates a protein, the recipe – or ORF – for it is transferred from a gene to RNA, which carries it to the cell's protein-making area. By capturing the RNA within C. elegans cells and converting it into complementary DNA (known as cDNA), investigators were able to gather the creature's full set of ORF instructions. The segments of cDNAs – representing each of the animal's genes – were then compared to the sections of chromosome thought to contain those genes.

Investigators used this technique to examine all 19,000 predicted worm genes. They found that in more than half the cases – 56 percent – the predicted genes did not completely match the actual genes isolated in their study.

"This demonstrates that even in C. elegans – whose genome is better understood than humans' – the genome map needs a great deal of correcting and refining," Vidal says. "We're still a long way from having a perfect picture of the parts list encoded by the worm genome, let alone the human one."

The technique developed at Dana-Farber has a further benefit for scientists in the emerging field of proteomics, which deals with the complete set of proteins produced by cells. By isolating each of the ORFs in the worm's genome, reproducing them millions of times, and inserting them in tiny structures that convert their molecular information into proteins, it is possible to collect large, pure samples of the proteins for study.

In the case of genes that are active at relatively low levels, Vidal says that it has been nearly impossible to collect enough of their associated protein to study. The new method, however, makes it possible to collect equal amounts of all the proteins produced by a cell.

"The success of this technique with C. elegans suggests that it can be equally successful with the genomes of other creatures, including humans," saysVidal. "It brings us closer to a completely accurate map of the human genome. And it lays the groundwork for another map – the human proteome, the list of all proteins produced by human cells."

Contributing to the study were researchers at the Unite de Recherche en Biologie Moleculaire, in Belgium; Research Genetics, in Huntsville, Ala.; Life Technologies, of Rockville, Md.; Protedyne Corp., of Windsor, Conn.; McGill University; the Public Health Research Institute, in Newark, N.J.; Yale University; Albert Einstein College of Medicine; and Genome Therapeutics, of Waltham, Mass. The work was supported by grants from the National Cancer Institute, the National Human Genome Research Institute, the National Institute of General Medical Sciences, and the Merck Genome Research Institute.

Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.

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