Researchers crack the code of the common cold

Scientists have begun to solve some of the mysteries of the common cold by putting together the pieces of the genetic codes for all the known strains of the human rhinovirus. Researchers at the University of Maryland School of Medicine in Baltimore and colleagues at the University of Wisconsin-Madison have completed the genomic sequences of the viruses and assembled them into a "family tree," which shows how the viruses are related, with their commonalities and differences. The study will be released on the online version of the journal Science (Science Express) at 2 p.m. EST on February 12.

The researchers say this work provides a powerful tool that may lead to the development of the first effective treatments against the common cold.

"There has been no success in developing effective drugs to cure the common cold, which we believe is due to incomplete information about the genetic composition of all these strains," says the study's senior author, Stephen B. Liggett, M.D., professor of medicine and physiology at the University of Maryland School of Medicine and director of its Cardiopulmonary Genomics Program.

"We generally think of colds as a nuisance, but they can be debilitating in the very young and in older individuals, and can trigger asthma attacks at any age. Also, recent studies indicate that early rhinovirus infection in children can program their immune system to develop asthma by adolescence," says Dr. Liggett, who is a pulmonologist and molecular geneticist.

Major discoveries of the study

The researchers found that human rhinoviruses are organized into about 15 small groups that come from distant ancestors. The discovery of these multiple groups explains why a "one drug fits all" approach for anti-viral agents does not work. But, says Dr. Liggett, "Perhaps several anti-viral drugs could be developed, targeted to specific genetic regions of certain groups. The choice of which drug to prescribe would be based on the genetic characteristics of a patient's rhinovirus infection."

Dr. Liggett adds that while anti-viral drugs seem to be the most likely to succeed, "the data gathered from these full genome sequences gives us an opportunity to reconsider vaccines as a possibility, particularly as we gather multiple-patient samples and sequence the entire genomes, to see how frequently they mutate during a cold season. That work is underway now."

The researchers also found that the human rhinovirus skips a step when it makes its protein product, a shortcut that probably speeds up its ability to make a person feel sick soon after infection. "This is a new insight," says co-investigator Claire M. Fraser-Liggett, Ph.D., director of the Institute for Genome Sciences and professor of medicine and microbiology at the University of Maryland School of Medicine. "We would not have had any sort of intuition about this had it not been revealed through genome analysis. Information that comes from this discovery might present a completely different approach in terms of therapy."

The analysis shows that some human rhinoviruses result from the exchange of genetic material between two separate strains of the virus that infect the same person. Such a swap, known as recombination, was previously not thought possible in human rhinovirus. During cold season, when many different strains of rhinovirus may be causing infections, recombination could rapidly produce new strains.

Multiple mutations (as many as 800) were evident in virus samples taken recently from patients with colds, compared to older rhinovirus reference strains. Some viruses mutate by making slight changes in certain proteins to avoid being destroyed by antibodies from a person's immune system. "Mutations were found in every area of the genome," says Dr. Liggett.

The study's lead author, Ann C. Palmenberg, Ph.D., professor of biochemistry and chair of the Institute for Molecular Virology at the University of Wisconsin-Madison, notes, "As we begin to accumulate additional samples from a large number of patients, it is likely that hotspots for mutation or recombination will become apparent, and other regions resistant to mutational change may emerge. This will provide clues as to how flexible the virus is as it responds to the human environment, important hints if you are designing new therapeutics."

Study background

Human rhinovirus infection is responsible for half of all asthma attacks and is a factor in bronchitis, sinusitis, middle ear infections and pneumonia. The coughs, sneezes and sniffles of colds impose a major health care burden in the United States—including visits to health care providers, cost of over-the-counter drugs for symptom relief, often-inappropriate antibiotic prescriptions and missed work days—with direct and indirect costs of about $60 billion annually.

Prior to the start of this project, the genomes of only a few dozen rhinoviruses had been sequenced from what was considered the reference library, a frozen collection of 99 different rhinovirus strains taken from patients over a span of more than two decades. During this team's work, several other groups began to report the full genomes of some of these viruses, as well as some odd rhinovirus-like strains from relatively sick patients.

"It was clear to us that the spectrum of rhinoviruses out there was probably much greater than we realized. Further, we needed to develop a framework from which we could begin to figure out ways to combat these viruses and use their genetic signatures to predict how a specific virus would affect a patient," says Dr. Fraser-Liggett.

The current study adds 80 new full genome sequences to the rhinovirus library and 10 more acquired recently from people with colds. Each sequence was modeled and compared to each other. Dr. Liggett says, "Now we can put together many pieces of the human rhinovirus puzzle to help us answer some fundamental questions: how these rhinoviruses might mutate as they spread from one person to another; which rhinoviruses are more associated with asthma exacerbations and why rhinovirus exposure in infancy may cause asthma later in life. With all this information at hand, we see strong potential for the development of the long-sought cure for the common cold, using modern genomic and molecular techniques."

"With recent improvements in technology, including next-generation DNA sequencing tools, it has become easier to generate whole genome sequence information," says Dr. Fraser-Liggett. "There is no reason any longer to focus on a very limited part of the rhinovirus molecule to learn what it's doing, what the predominant strain is in a population, or to try to infer what the evolution of the entire molecule might be. Instead, by studying the complete genome sequence, we can answer multiple questions in parallel."

Source: University of Maryland Medical Center

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Can geo-engineering rebuild the planet?

By Sanjida O'Connell

; http://link.brightcove.com/services/link/bcpid1488655367/bctid13335878001 http://www.brightcove.com/channel.jsp?channel=1139053637

In the 1960s, two Russian scientists set out ambitious plans to reshape the world around us: to reverse the flow of rivers, shoot tiny white particles into space to illuminate the night sky, and melt the Arctic to water fields of Soviet wheat. "If we want to improve our planet and make it more suitable for life," wrote NP Rusin and L Flit, "we must alter its climate."

Four decades later, we have done plenty to alter the climate, but not for the better. And as we grapple with the problems of global warming, the standard prescription – cutting greenhouse gas emissions – is proving problematic. "I cannot see that we will be able to keep carbon levels low enough to prevent catastrophe," says Professor Brian Launder, of the University of Manchester. "Over the past five years, emissions have gone up, not down."

Which means that "geo-engineering" – using technology on an almost unimaginable scale to tinker with the environment and correct our mistakes – could move from fantasy to necessity. Professor James Lovelock, who came up with the "Gaia" hypothesis, in which the Earth is thought to behave rather like a living, self-regulating organism, thinks we have exceeded the planet's natural capacity to counteract the changes we have made, and are rapidly heading towards a situation that will be calamitous for our species.

"Whatever we do is likely to lead to death on a scale that makes all previous wars, famines and disasters small," he says. "To continue business as usual will probably kill most of us during the century."

Even those of a less alarmist bent are worried enough to be taking geo-engineering seriously. Last September, Prof Launder co-edited a special edition of a Royal Society journal which examined various proposals, such as injecting sulphur into the stratosphere to reflect sunlight back into space.

Most of the schemes suggested, there and elsewhere, involve dramatic alterations to the Earth's weather systems, whether by deflecting the Sun's rays, removing carbon from the atmosphere or cooling the oceans. Prof Lovelock has come up with one of the most ambitious: he and Professor Chris Rapley, from the Science Museum, would like a system of pipes to be held vertically below the ocean's surface. These tubes, each 100 metres long, would draw cold water from below; wave action would then mix four tons of cooler water per second into the ocean at the surface. Cooler oceans mean a cooler planet, while the nutrient-rich water brought up from the bottom could encourage algal blooms, which use carbon to grow and thereby remove it from the atmosphere.

Supporters of another approach, known as Oceanic Iron Fertilisation, believe that promoting the growth of algae should be our main objective, rather than just a side effect. According to Dr Victor Smetacek, of the Alfred Wegener Institute for Polar and Marine Research in Bremerhaven, Germany, the theory is that adding iron to the oceans will encourage algal blooms. When the algae die, they sink to the bottom of the ocean, locking away their cargo of carbon.

There are plans to test this proposal off the island of South Georgia in the Atlantic. At the very least, Dr Smetacek hopes that large blooms of algae will act as food for krill, helping resurrect declining populations of squid and even some whales.

A third oceanic idea has been suggested by Professor Stephen Salter, from Edinburgh University's School of Engineering: a wind-driven fleet of Flettner ships. Originally designed by German engineer Anton Flettner, these vessels have no sails and are powered by rotors; the first one sailed across the Atlantic in 1926.

The ships would drag propeller-like turbines behind them to generate electricity, and pump out a very fine spray of seawater into the air. These tiny drops would join low clouds, with the salt making them whiter and better at reflecting sunlight back into the atmosphere, thus cooling the oceans. The beauty of this system is that it uses natural materials – seawater – and is powered by a renewable source of energy.

Finally, instead of reflecting sunlight using sea-level contraptions, some scientists have suggested shading the Earth from space. The most recent idea was put forward by Dr Roger Angel at the University of Arizona: to launch into space trillions of thin transparent discs, each about 60cm across. This cloud of 100,000 lenses would reflect sunlight back into space, shielding us from 1.8 per cent of the Sun's radiation.

But as intoxicating as such ideas are – and as tempting as a "quick fix" to the climate would be – they are not the finished article. Not only would the costs be enormous, but in a recent paper in Atmospheric Chemistry and Physics Discussions, Dr Tim Lenton of the University of East Anglia compared the possible effectiveness of 17 different geo-engineering techniques, and found severe problems with many of them. The Lovelock/Rapley plan to cool the oceans would, he says, be ineffective at reducing carbon on a global scale, and he is similarly sceptical about the algal blooms.

"There's huge disagreement in the scientific community about ocean fertilisation," agrees Prof Launder. "The ocean is very complex – elsewhere, perhaps thousands of miles away, you might be causing an adverse effect." Scientists from Britain's National Oceanography Centre, writing in the journal Nature, have demonstrated that adding iron to the ocean does boost algae growth rates by up to three times, and lock away carbon on the sea floor. But they added that geo-engineers overestimated the amount of carbon removed by between 15 and 50 times.

Prof Salter's Flettner ships have also sailed into stormy waters. Dr Lenton has calculated that they could cope with half the projected carbon emissions during the coming century, but Professor Stephen Schneider, from Stanford University, says that oceanic currents and winds might distribute the cooling effect unevenly, resulting in even greater climatic change.

As for Dr Angel's sun shield, Dr Lenton believes it would do the most to compensate for carbon emissions – but there is a downside, in that the sunshades would need to be launched in stacks of 800,000 units every five minutes for 10 years. "They might well work," says Prof Launder, "but this system wouldn't be ready soon enough."

So instead of alleviating global warming by trying to cool the planet or creating giant algal blooms, why not simply remove the carbon? Trees are pretty good at doing this naturally – but according to Prof Lovelock, we do not have enough forested regions left and could not plant enough trees to save us.

Instead, Dr Klaus Lackner, of Columbia University in New York, has come up with the idea of an artificial tree that directly "scrubs" carbon from the sky. Each one would be around the size of a shipping container and would, he estimates, be able to capture a ton of carbon dioxide a day. Of course, the carbon dioxide still has to be disposed of; Dr Lackner suggests pumping it into greenhouses to be absorbed by crop plants.

"In a way, this sort of scheme is the most desirable," says Prof Launder, "because it doesn't just reflect sunlight, it grabs carbon dioxide in the atmosphere. Sadly, I don't think these 'trees' can sequester anything like the amount of carbon required."

The grim conclusion is that while some of these schemes have potential, there is no magic answer. "Geo-engineering is not a solution," says Prof Launder, "but it could give the world a chance to come to its senses. In 50 years we'll have carbon-free energy schemes in place, but we need a solution that can be put into place shortly, and will gain us breathing space."

Yet even if any of these schemes could be made to work, a global scheme requires global co-operation. Given how hard that has proved over the financial crisis, it is difficult to imagine world leaders reaching an agreement over a radical – and expensive – alteration to the environment.

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Earth facing critical climate decline

(UPI) -- A U.S. scientist says Earth's atmospheric greenhouse gases are increasing more rapidly than expected, resulting in worsening global warming predictions.

Chris Field, a member of the Nobel Prize-winning Intergovernmental Panel on Climate Change, says decisive action is needed to prevent the planet's climate system from crossing a critical threshold by the end of the century.

Field, director of the Carnegie Institution's Department of Global Ecology, said studies indicate greenhouse warming could trigger a vicious cycle in which carbon dioxide released from thawing tundra and increasingly fire-prone forests drives global temperatures even higher.

"The data now show that greenhouse gas emissions are accelerating much faster than we thought," said Field, with new studies also revealing potentially dangerous feedbacks in the climate system that could convert current carbon sinks into carbon sources.

"One thing that seems to be certain, however, is that as a society we are facing a climate crisis that is larger and harder to deal with than any of us thought," Field said. "The sooner we take decisive action, the better our chances are of leaving a sustainable world to future generations."

The research was presented this week in Chicago during the annual meeting of the American Association for the Advancement of Science.

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