Common cold: Shown here is the structure of the protein shell, or capsid, of the human rhinovirus. Credit: J. Y. Sgro, UW-Madison

The sneeze-inducing DNA shows why it’s so difficult to find a cure for the common cold.

MIT Technology Review, February 17, 2009, by Emily Singer — We may be one step closer to defeating that small but mighty bearer of human misery: the common cold.

Scientists have now sequenced all of the 99 known strains of cold virus. The research, published February 12, 2009, in the journal Science, sheds light on the bug’s ubiquity–different viruses can swap DNA sequences, generating new strains that can evade the immune system.

According to a statement from the University of Wisconsin:

The newly sequenced viruses also show … why it is unlikely we will ever have an effective, all-purpose cold vaccine: The existing reservoir of viruses worldwide is huge and, according to the new study, they have a tendency to swap genetic sequences when cells are infected by more than one virus, a phenomenon that can lead to new virus strains and clinical manifestations.

“Having sequenced the complete genomes of these things, we now know you can be infected by more than one virus at a time and that they can recombine (their genes),” [lead author of the new study Ann] Palmenberg [of UW-Madison’s Institute for Molecular Virology] explains. “That’s why we’ll never have a vaccine for the common cold. Nature is very efficient at putting different kinds of paint on the viruses.”


Missing links: Shown here is a three-dimensional reconstruction of a Neanderthal skull based on a CT scan of a skull found in 1909 in La Ferrassie, Dordogne. Using DNA isolated from Neanderthal bones such as this one, scientists have generated a draft of the Neanderthal genome.
Credit: Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology

Scientists announce the first complete draft of our closest relative’s genome.

MIT Technology Review, February 17, 2009, by Lauren Gravitz — Man’s closest ancestors, the Neanderthals, disappeared about 30,000 years ago, leaving little more than their bones behind. But those bones may help decipher what makes us human, and they are beginning to divulge their ancient secrets. Now researchers have revealed a first draft of the complete Neanderthal genome, a sequence of three billion or so base pairs.

At a joint press conference held during the annual meeting of the American Association for the Advancement of Science, Svante Pääbo, head of the project and director of genetics at the Max Planck Institute for Evolutionary Anthropology, in Leipzig, Germany, said that this first overview covers about 63 percent of the Neanderthal genome. Most of it derived from just a half gram of bone removed from 38,000-year-old fossils excavated from Vindija Cave in Croatia. “The attraction of the Neanderthal genome,” Pääbo says, “is that it’s our closest relative in all categories, and we diverged only about 300,000 years ago.”

“Studying them will tell us what makes modern humans really modern, and really human; why we are alone; why we have these amazing capabilities,” says Jean-Jacques Hublin, who is the director of human evolution at Max Planck and was involved in the research.

Despite its draft quality, the genome is already beginning to reveal a few of our ancestors’ traits. As researchers expected, Neanderthals lacked the lactase gene, present mostly in European humans, which allows adults to digest milk. But the researchers confirmed that the ancient hominid did share with us the only gene known to be implicated in speech and language, FoxP2, which earlier studies had only suggested was the case. “There’s no reason to assume they couldn’t articulate as we do,” Pääbo says.

However, the new data do little to further the idea that humans and Neanderthals interbred–something that has been the subject of much debate, but for which most experts agree there is little evidence. “We have looked at the contribution from Neanderthals into the present-day [human] gene pool–that is very little, if anything,” Pääbo says. “But the cool thing is that interbreeding is a two-way street, and for the first time we can look at it the other way, from human ancestors into Neanderthals. So we’re currently analyzing if we see evidence in the Neanderthal genome of a contribution from human ancestors.”

A little over two years ago, Pääbo and his colleagues, including a team headed by Michael Egholm at 454 Life Sciences, published the first proof that they could extract genetic material from Neanderthal bones. This is an incredibly complex, obstacle-riddled task when dealing with such ancient DNA. The longer bones lie in the ground, the more their DNA degrades, leaving researchers with only short fragments with which to work. Microbes also invade a skeleton and saturate it with their own DNA; in even the most well-preserved bones, only 4 percent of the DNA belongs to its original owner. Because the genome in question is from man’s closest relative, things get even more complicated. Human contamination is inevitable, and researchers must find a way to differentiate between human and Neanderthal DNA, even while the two species share almost all the same genes.

The proof-of-principle papers published in 2006 were a huge advance, made possible through high-throughput sequencing technology developed by 454 Life Sciences. Their sequencing machine can analyze millions of strands of DNA all at once, in a process that uncouples the double-stranded DNA, chops it up into fragments, attaches those fragments to minute beads, and creates millions of clones of the original fragments. These beads are then packed into individual wells on a slide, and analyzed in a machine that determines the fragments’ sequences by recording the identity of every base as it binds with its complementary nucleotide.

The new results, Egholm says, relied both on the 454 machine and on one made by Solexa, which can analyze hundreds of millions of wells at once. Speed was key: since only 4 percent of what was sequenced actually belonged to a Neanderthal, the researchers had to sequence over 100 million base pairs of unrelated DNA just to get 3 million base pairs of Neanderthal DNA. “With lower throughput sequencers, it would have been really difficult to generate enough data to sequence the entire genome,” says Rachel Mackelprang, a postdoc in genetic analysis at the Department of Energy Joint Genome Institute.

Using previously sequenced genomes from other species was also crucial, says John Hawks, a biological anthropologist at the University of Wisconsin. “Bootstrapping computer information about genomes really made all of this possible,” he says. “To be able to take snippets of DNA of 50 base pairs or less and have the computer say that it’s the same as a bacterial sequence has enabled the reconstruction of genuine Neanderthal sequence.”

But more than anything, the largest challenge has been finding ways to detect and eliminate sequences from human DNA from the Neanderthal samples. The 2006 research was scrutinized heavily by Pääbo and Egholm’s peers. Despite the researchers’ caution, human DNA had infiltrated the samples and been included in the original sequence. This time around, to correct for contamination, they used a number of technological innovations, including the placement of genetic tags on all bone-derived DNA, which allowed them to detect and discard all untagged DNA as contaminants.

“Having a genome allows us to look for things that we can’t see in fossils,” Hawks says. “It’s so much more than the bones that we have. It’s exciting for me because here’s this ancient group of people, and you’ve opened a new door into what their lives are like.” More than anything, he says, he just wants to get his hands on the data. “If you think about everything that’s been written on Neanderthals for the past 150 years . . . we have the potential to change everything.”

Scientists Unravel Neanderthal Genome

Extraordinary feat will shed light on what it means to be human

A model of an elderly Neanderthal man. Photograph: Federico Gambarini/EPA

Guardian.co.uk, February 17, 2009 — Scientists have unravelled the genetic make-up of the Neanderthal, the long-faced, barrel-chested relative of modern humans.

Anthropologists analysed more than a billion fragments of ancient DNA plucked from three Croatian fossils to reconstruct a first draft of the Neanderthal genome.

The extraordinary feat gives scientists an unprecedented opportunity to clarify the evolutionary relationship between humans and Neanderthals that may ultimately shed light on the great mystery of how we became the most formidable species on the planet.

Neanderthals were the closest relatives of modern living humans. They lived in Europe and Asia until they became extinct around 30,000 years ago. The reason they died out is not clear, but likely factors are dramatic swings in the climate that affected the availability of food, and competition with early humans.

By comparing the genomes of modern humans with Neanderthals and chimps, scientists hope to unravel the genetic differences that define what it is to be human.

The Neanderthal genome was built up from strands of DNA, most of which came from a 38,000-year-old fossilised leg bone unearthed in a cave in Vindija, Croatia. Other material came from older remains dating back 70,000 years. Together, the fragments make up more than 60% of the Neanderthal genome.

Svante Pääbo, who led the project at the Max Planck Institute for Evolutionary Biology in Leipzig, Germany, said the team would spend the rest of the year analysing the DNA. They will focus on genes linked to modern human evolution, such as FOXP2, which is involved in speech and language.

The draft genome was announced at the American Association for the Advancement of Science meeting in Chicago.

Two years ago, the same group used the ancient DNA to pinpoint the moment, about 500,000 years ago, when modern humans split from Neanderthals.

The analysis should clear up once and for all the ongoing debate as to whether Neanderthals and modern humans continued to mate with each other after separating along the path of evolution.

Remains of Neanderthals dating back to 400,000 years ago suggest they were proficient at crafting basic tools and weapons and buried their dead. The last Neanderthals died out shortly after Homo sapiens migrated to Europe and settled.

Neanderthals were stocky and well-adapted to a cold climate, with brains that were on average larger than those of modern humans. Some fossil evidence suggests they were occasionally cannibalistic, though they more commonly hunted large animals including horses and mammoths.


Muscle power: This hamster is wearing a jacket affixed to a nanogenerator that harvests biomechanical energy as it runs on an exercise wheel.
Credit: Zhong Lin Wang

Researchers use a running rodent to test their device.

MIT Technology Review, February 11, 2009, by Katherine Bourzac — Sunlight, wind, and waves aren’t the only sources of renewable energy. For researchers hoping to power nanoscale devices, there’s also muscle power.

Every heartbeat and every fidgety movement that a person makes while sitting at a computer carries with it a small amount of energy that could potentially be scavenged. However, harvesting this biomotion is challenging because so much of it is irregular. Now, for the first time, researchers have demonstrated that a nanogenerator can be driven by irregular, low-energy biomotion, including the tapping of a human finger and a hamster’s erratic running and scratching.

The researchers’ nanogenerator harnesses the piezoelectric effect–the way some crystalline materials produce an electrical potential when placed under mechanical stress. The team, led by Zhong Lin Wang, a professor of materials science and engineering at Georgia Tech, has been making generators using piezoelectric nanowires since 2005. The latest nanogenerator consists of a series of zinc-oxide nanowires mounted on top of a flexible plastic surface. The wires are connected to one another and to an external electrical circuit by metal electrodes. When the plastic bends, the wires bend too, and this motion creates an electrical potential in the wires that drives current through the external circuit.

In a paper published online this week in the journal Nano Letters, Wang’s group describes using the nanogenerator to harvest different kinds of biomechanical energy. The researchers attached the nanogenerator to a person’s index finger and recorded the power output when it tapped on a surface. They also harvested energy from a hamster wearing a small jacket affixed to the device as the rodent ran on an exercise wheel and scratched itself.

Other researchers have developed piezoelectric cantilevers that can also harvest biomechanical energy, but these systems rely on regular mechanical resonance at a specific frequency. Most biomotion–stretching muscles, swinging arms, walking, even the beating of a heart–produces mechanical energy that’s more irregular. Wang says that his group has made the first generator that can truly harvest small, irregular motions.

The energy generated by the device is currently small (about a nanowatt), but Wang says that this is still an important step along the road to developing useful power sources for nanoscale devices. Exquisitely sensitive nanoscale sensors require very little power–about a microwatt–to do things like detect pathogens or cancer proteins. But part of what’s holding back their development is the size and lifetime of existing power supplies. Implantable nanosensors need a power source that is both nanosized and long-lasting, eliminating the need for it to be surgically removed and replaced.

Wang’s group hasn’t made an implantable version of the nanogenerator yet, but Wang says that, in theory, it should be possible. The nanogenerators might, for instance, be encased in biocompatible polymers and implanted in muscle tissue.

The researchers are working on increasing the power of the device by adding more piezoelectric wires arranged in series. In addition to powering nanoscale devices, the piezoelectric generators could perhaps be coupled to larger devices. Over the next five to ten years, Wang hopes to significantly boost the power output of the generator so that it could be woven into the fabric of a human-sized jacket and harvest enough energy to charge batteries for portable electronic devices.


Darwin’s delight: By comparing the genomes of humans, chimps, macaque monkeys, and orangutans (pictured clockwise), scientists discovered that the ancestor to the great ape lineage, which includes humans, underwent a burst of evolution about 12 million years ago. Charles Darwin (pictured lower right), born 200 years ago today, would have been proud.
Credit: Macaque, Scott Liddell; Orangutan, Tom Low; Chimpanzee, Aaron Logan; Charles Darwin, Julia Margaret Cameron

Regions of DNA prone to duplication may have played a vital role in human evolution.

MIT Technology Review, February 12, 2009, by Emily Singer — About eight to twelve million years ago, the evolutionary ancestor to humans, chimpanzees, and orangutans appears to have undergone a burst of evolution, driven by duplicated sequences of DNA. This mechanism of genetic change, which has only recently come under scientific scrutiny, may have endowed primates with an evolutionary flexibility that drove the development of different great ape species, including humans.

When a stretch of DNA is mistakenly duplicated, extra copies of the gene or genes within that region are added to the genome; those genes can then mutate separately. “Duplications are really important from an evolutionary perspective because they add a lot of variation to the genome,” says Tomas Marques-Bonet, a scientist in Evan Eichler’s lab at the University of Washington, in Seattle, who led the research. “These regions are rapidly evolving.”

Most estimates of genetic similarity between humans and other primates have focused on single-letter changes to the genome as the primary basis for evolutionary change. But scientists are now discovering the importance of structural changes to the genome, which include deletions or duplications of segments of DNA between 1,000 and 100,000 letters in length. These regions are flanked by repetitive stretches that are thought to trigger errors in the cells’ DNA replication process, resulting in duplicated genes.

“It’s only recently that we have had the sequence data and the genomic tools to study this and understand its role in evolutionary history,” says George Perry, a scientist at the University of Chicago, who was not involved in the research. The chimp genome was released in 2005, and the orangutan and macaque genome projects are ongoing. In addition, scientists can now create custom-designed gene microarrays to quickly detect a large number of specific duplications.

Marques-Bonet and his colleagues analyzed the genome sequence of four primate species: humans, chimpanzees, orangutans, and macaques. Humans, chimps, and orangutans descend from the African great ape lineage, sharing a common ancestor about 12 million years ago, while macaques, classified as old-world monkeys, split from the common primate lineage more than 25 million years ago. Comparing areas of DNA duplication in the genome sequence, researchers found a burst in the rate of duplications right before orangutans split from the tree, and a second burst before chimps and humans diverged, according to research published today in the journal Nature. This increase happened even as rates of single-letter changes decreased.

Scientists are hesitant to speculate about precisely how the acceleration in the rate of duplication arose in the human and chimp lineage, and how it affected human evolution. For example, it’s not yet clear whether the duplications that occurred during this time period conferred an evolutionary advantage on their bearers. “We think that duplications make the genome more dynamic,” says Marques-Bonet. “But having a dynamic genome creates both sides of the coin: these rearrangements can be beneficial, or they can be linked to disease.” Recent research shows that duplications in the human genome play a role in a variety of diseases, including autism, schizophrenia, and mental retardation.

It’s also unclear if the acceleration seen in the chimp and human ancestor is unique. “These basic kinds of mutations have been going on for at least 90 million years,” says Nick Patterson, a geneticist at the Broad Institute, in Cambridge, MA. “The question is whether there is something unusual in what happened in human lineage; I doubt we have enough data to answer that.” This type of comparison would require genome sequences for many related mammal species.

Duplications are likely to have very different evolutionary properties than single-letter changes. Both arise from mistakes at the molecular level, which can then either help, harm, or do nothing to the reproductive fitness of the organism. Most single-letter changes fall into the neutral category. But because duplicative changes often increase the number of copies of a gene and thus potentially increase the concentration of protein that gene produces, they are more likely to exert an effect on the carrier.

In addition, while single-letter changes may make a particular protein more or less effective by slightly tweaking its structure, duplications that create additional copies of specific genes free up the new copies to evolve an entirely new purpose. “You havetwo copies that can diverge from each other,” says Perry. “One copy can then experience mutation and attain a new function that could be important for the biology of that organism.” For example, color vision in primates arose thanks to the duplication of the gene for visual pigment. “With this kind of analysis,” says Perry, “we can begin to identify other genes specific to different lineages, and then study the potential effect they might have on the biology of these species.”

Most of the duplications analyzed in the study–more than 80 percent–are shared by humans, chimps, and gorillas. But the genes in duplicated regions unique to humans are largely ones that have not yet been characterized. “We found more than 30 genes that are duplicated only in humans,” says Marques-Bonet. “But we still don’t know what they do.”


A corn-ethanol plant in western New York State.
Credit: Western New York Energy / Photos by Bruce and Associates

Pollutants emitted as a result of corn biofuel production could have serious impacts.

MIT Technology Review, February 17, 2009, by Anna Davison — Switching from gasoline or corn-based biofuels to cellulosic ethanol–made from the stalks and stems of plants–could have more health and environmental benefits than previously recognized, according to a study of different types of transportation fuels.

The environmental and health costs associated with cellulosic ethanol are less than half those of gasoline and of corn ethanol, the study found.

The analysis looked at the impacts of cellulosic and corn-based biofuels and of gasoline. It accounted for many possible impacts, including those from the energy used in refineries, the pollutants pumped out of car tailpipes, and the consequences of cultivating corn or other plants used to make biofuel.

This is the first study to focus not just on the environmental impacts of fuels, which have already been the subject of considerable scrutiny and debate, but also on the consequences for human health. Air pollutants emitted as a result of fuel production and consumption can cause breathing problems and aggravate asthma, and have been linked to premature death.

“We wanted to see which fuels are in the best interests of society to develop,” says Jason Hill, a resident fellow in the University of Minnesota’s Institute on the Environment and the lead author of the study, which was published online in the Proceedings of the National Academy of Sciences on February 2.

Cellulosic ethanol was the clear winner in the analysis. Switching to cellulosic ethanol from gasoline could significantly reduce the amount of pollutants emitted during fuel production and consumption, Hill and his colleagues found. Ethanol burns more cleanly than gasoline, and crops cultivated to produce biofuel also absorb carbon dioxide. Cellulosic ethanol is a better alternative to corn ethanol because it requires less fertilizer than corn ethanol to produce, and there’s no energy required for heat at biorefineries. Biorefineries that produce cellulosic ethanol actually generate excess electricity by burning lignin.

Biofuel produced from corn grains has environmental and health costs that are equal or greater than those of gasoline, depending on whether natural gas, coal, or corn stover is used to generate heat during the production process, the study found.

The findings aren’t unexpected, according to Roger Sedjo, a senior fellow with Resources for the Future, a nonprofit group that conducts independent research on environmental, energy, and natural-resource issues. But he adds that they are “interesting and important.”

Lester Lave, a Carnegie Mellon University professor who has written extensively on energy economics, lauds Hill and his colleagues for their efforts to quantify fuel impacts. “It’s a brave paper,” he says. “It does as good a job as you can do at this stage.”

To estimate the environmental and health costs of fuel production and consumption, Hill and his colleagues focused on the two most harmful emissions: fine particulate matter, which can aggravate lung diseases and has been linked to heart attacks in people with heart problems, and greenhouse gases. They used an analysis from the U.S. EPA to monetize the health impacts of fine particulate matter, including lost work days, hospital visits, and early deaths. They also used independent estimates of carbon mitigation costs, carbon market prices, and the social cost of carbon to calculate the cost of greenhouse gases.

Hill and his colleagues calculated the emissions associated with a billion-gallon increase in ethanol production and consumption, or the equivalent amount of gasoline–about the same as the rise in U.S. gasoline production from 2006 to 2007.

For gasoline, the combined climate-change and health costs of that increase are $469 million, the researchers concluded; for corn ethanol, they range from $472 million to $952 million, depending on the production method; and for cellulosic ethanol, they are between $123 million and $208 million, depending on the plant material that’s used to produce it.

Evidence against corn ethanol has been accumulating in recent years. It takes a lot of energy to grow corn and to ferment the kernels to produce ethanol, and considerable amounts of greenhouse gases are produced in the process. Hill’s analysis suggests that corn ethanol could also create more health problems than gasoline.

However, Satish Joshi, an environmental economist at Michigan State University, who wasn’t involved in Hill’s study, says that he “wouldn’t rule out corn ethanol” yet: “It’s proven, well-established technology.” Although Joshi says that he’s pleased to see more evidence of the advantages of cellulosic ethanol, it’s a newer development, and there isn’t yet a way to produce it economically. Conversely, “corn has the longer history and the established manufacturing base . . . Cellulosic ethanol is still technologically unproven,” Joshi says.

Hill’s study compared three ways of making ethanol from corn–using natural gas, coal, or corn stover to generate heat at biorefineries–and four processes that produce cellulosic ethanol–from corn stover, switchgrass, prairie grasses, or Miscanthus, a tall perennial grass–and he says that the results show how much difference production methods can make in the overall impacts associated with fuels.

The impacts associated with fuels vary according to where the fuel is produced, Hill found. The health costs associated with airborne particles vary considerably, he says, depending on atmospheric conditions and population density.

“Maybe there’s a way to spatially locate production of biofuel to get maximal health benefits” out of a switch from gasoline, Hill says–something that he plans to investigate.

His analysis assumes, for the sake of simplicity, that the additional corn or other plant material needed to produce biofuel is grown on grasslands that are currently part of the U.S. Conservation Reserve Program. Hill says that in reality, increased biofuel production will likely encroach on land that’s now used to produce other crops, triggering a cascade of land-use changes. If rain forests in other countries are cleared to make way for crops, for example, the impacts in terms of climate change could negate the benefits of switching to biofuel to reduce greenhouse-gas emissions.

By taking into account the health consequences of fine particles, Hill looked at “one additional thing off a huge list” of possible effects that also include erosion, pesticide contamination, and petroleum spills”, says Soren Anderson, an assistant professor at Michigan State University, who focuses on biofuels as part of his research on energy and environmental economics. “That additional thing made clear that corn ethanol is actually worse than gasoline, and cellulosic ethanol looks to be better.”