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Dead for 32,000 Years, an Arctic Plant Is Revived By NICHOLAS WADE Article #1 Published: February 20, 2012 Living plants have been generated from the fruit of a little arctic flower, the narrowleafed campion, that died 32,000 years ago, a team of Russian scientists reports. The fruit was stored by an arctic ground squirrel in its burrow on the tundra of northeastern Siberia and lay permanently frozen until excavated by scientists a few years ago. Enlarge This Image Svetlana Yashina OLD DNA A plant has been generated from the fruit of the narrow-leafed campion. It is the oldest plant by far to be grown from ancient tissue. This would be the oldest plant by far that has ever been grown from ancient tissue. The present record is held by a date palm grown from a seed some 2,000 years old that was recovered from the ancient fortress of Masada in Israel. Seeds and certain cells can last a long term under the right conditions, but many claims of extreme longevity have failed on closer examination, and biologists are likely to greet this claim, too, with reserve until it can be independently confirmed. Tales of wheat grown from seeds in the tombs of the pharaohs have long been discredited. Lupines were germinated from seeds in a 10,000-year-old lemming burrow found by a gold miner in the Yukon. But the seeds, later dated by the radiocarbon method, turned out to be modern contaminants. Despite this unpromising background, the new claim is supported by a firm radiocarbon date. A similar avenue of inquiry into the deep past, the field of ancient DNA, was at first discredited after claims of retrieving dinosaur DNA proved erroneous, but with improved methods has produced spectacular results like the reconstitution of the Neanderthal genome. The new report is by a team led by Svetlana Yashina and David Gilichinsky of the Russian Academy of Sciences research center at Pushchino, near Moscow, and appears in Tuesday’s issue of The Proceedings of the National Academy of Sciences of the United States of America. “This is an amazing breakthrough,” said Grant Zazula of the Yukon Paleontology Program at Whitehorse in Yukon Territory, Canada. “I have no doubt in my mind that this is a legitimate claim.” It was Dr. Zazula who showed that the apparently ancient lupine seeds found by the Yukon gold miner were in fact modern. But the Russians’ extraordinary report is likely to provoke calls for more proof. “It’s beyond the bounds of what we’d expect,” said Alastair Murdoch, an expert on seed viability at the University of Reading in England. When poppy seeds are kept at minus 7 degrees Celsius, the temperature the Russians reported for the campions, after only 160 years just 2 percent of the seeds will be able to germinate, Dr. Murdoch noted. The Russian researchers excavated ancient squirrel burrows exposed on the bank of the lower Kolyma River, an area thronged with mammoth and woolly rhinoceroses during the last ice age. Soon after being dug, the burrows were sealed with windblown earth, buried under 125 feet of sediment and permanently frozen at minus 7 degrees Celsius. Some of the storage chambers in the burrows contain more than 600,000 seeds and fruits. Many are from a species that most closely resembles a plant found today, the narrow-leafed campion (Silene stenophylla). Working with a burrow from the site called Duvanny Yar, the Russian researchers tried to germinate the campion seeds, but failed. They then took cells from the placenta, the organ in the fruit that produces the seeds. They thawed out the cells and grew them in culture dishes into whole plants. Many plants can be propagated from a single adult cell, and this cloning procedure worked with three of the placentas, the Russian researchers report. They grew 36 ancient plants, which appeared identical to the present day narrow-leafed campion until they flowered, when they produced narrower and more splayed-out petals. Seeds from the ancient plants germinated with 100 percent success, compared with 90 percent for seeds from living campions. The Russian team says it obtained a radiocarbon date of 31,800 years from seeds attached to the same placenta from which the living plants were propagated. The researchers suggest that special circumstances may have contributed to the remarkable longevity of the campion plant cells. Squirrels construct their larders next to permafrost to keep seeds cool during the arctic summers, so the fruits would have been chilled from the start. The fruit’s placenta contains high levels of sucrose and phenols, which are good antifreeze agents. The Russians measured the ground radioactivity at the site, which can damage DNA, and say the amount of gamma radiation the campion fruit accumulated over 30,000 years is not much higher than that reported for a 1,300-year-old sacred lotus seed, from which a plant was successfully germinated. The Russian article was edited by Buford Price of the University of California, Berkeley. Dr. Price, a physicist, chose two reviewers to help him. But neither he nor they are plant biologists. “I know nothing about plants,” he said. Ann Griswold, a spokeswoman for PNAS, as the journal is known, said the paper had been seen by an editorial board member who is a plant biologist. Tragedy has now struck the Russian team. Dr. Gilichinksy, its leader, was hospitalized with an asthma attack and unable to respond to questions, his daughter Yana said on Friday. On Saturday, Dr. Price reported that Dr. Gilichinsky had died of a heart attack. Eske Willerslev, an expert on ancient DNA at the University of Copenhagen, said the finding was “plausible in principle,” given the conditions in permafrost. But the claim depends on the radiocarbon date being correct: “It’s all resting on that — if there’s something wrong there it can all fall part.” If the ancient campions are the ancestors of the living plants, this family relationship should be evident in their DNA. Dr. Willerslev said that the Russian researchers should analyze the DNA of their specimens and prove that this is the case. However, this is not easy to do with plants whose genetics are not well studied, Dr. Willerslev said. If the claim is true, then scientists should be able to study evolution in real time by comparing the ancient and living campions. Possibly other ancient species can be resurrected from the permafrost, including plants that have long been extinct. This article has been revised to reflect the following correction: Correction: February 22, 2012 An article on Tuesday about a plant generated from tissue that had been preserved in the Siberian tundra for almost 32,000 years misidentified the organization with which Ann Griswold is affiliated. She is a spokeswoman for Proceedings of the National Academy of Sciences, the journal in which the work was reported, not for the National Academy of Sciences itself. Company Unveils DNA Sequencing Device Meant to Be Portable, Disposable and Cheap Article #2 By ANDREW POLLACK Published: February 17, 2012 DNA sequencing is becoming both faster and cheaper. Now, it is also becoming tinier. A British company said on Friday that by the end of the year it would begin selling a disposable gene sequencing device that is the size of a USB memory stick and plugs into a laptop computer to deliver its results. The device, expected to cost less than $900, could allow small sequencing jobs to be done by researchers who cannot afford the $50,000 to $750,000 needed to buy a sequencing machine. It might also help doctors to sequence genes at a patient’s bedside, wildlife biologists to study genes in the field, or food inspectors to identify pathogens. “You don’t need to buy instruments,” Clive G. Brown, the chief technology officer of the company, Oxford Nanopore Technologies, said in an interview. “It’s pay-as-you-go sequencing.” Oxford presented details of the device, as well as of a new, somewhat larger sequencer that it also plans to begin selling late this year, at the Advances in Genome Biology and Technology conference in Marco Island, Fla., which has become the sequencing industry’s annual boast-fest. Both the tiny MinIon and the larger GridIon look likely to be the first sequencers to use nanopore sequencing, in which a strand of DNA is read as it is pulled through a microscopic hole, sort of like a noodle being slurped through rounded lips. Outsiders have not tried the machines, and there can be a big difference between rosy specifications and how well a machine works when it finally reaches the market. Some other sequencers that initially dazzled the field have faltered in the marketplace. Still, many experts at the conference were dazzled anew. “If it does work, it will be a game-changer,” said Elaine Mardis, co-director of The Genome Institute at Washington University in St. Louis. Chad Nusbaum of the Broad Institute in Cambridge, Mass., called it “impressive, credible, possibly amazing.” Isaac Ro, an analyst at Goldman Sachs, said in a note Friday that the Oxford technology had “impressive performance specs” that suggested it would be a “significant competitor” to Illumina and Life Technologies, the leaders in the sequencing business. Illumina has a bit of a hedge. In 2009, it invested $18 million in Oxford Nanopore, and owns a 15 percent share. But Illumina does not have the marketing rights to the machines unveiled Friday. Rather, it has the rights to an alternative Oxford technology that is further back in development. Illumina shares fell nearly 4 percent Friday to $51.82, while Life shares dropped nearly 8 percent to $45.92. Sequencing involves determining the order of the chemical units of DNA, which are known as bases and are usually represented by the letters A, C, G and T. The order of these bases helps determine inherited traits, like susceptibility to some diseases. As the cost plummets, sequencing is moving from research laboratories into patient care. Some cancer centers, for instance, sequence genes to determine the best drugs to use. The growing importance of sequencing in medical care is what motivated Roche to make its current $5.7 billion hostile bid to acquire Illumina. Known mostly for pharmaceuticals, Roche also has a large diagnostics business. Nanopore sequencing is easy to envision but has been deceptively difficult to carry out, despite two decades of research by universities and companies. Oxford, which is privately held and based on technology developed by a professor at Oxford University, uses pores made from bacterial proteins. An electric current flows through the pore. The bases interrupt the current in different ways as they go through. The initial GridIon machines will have 2,000 pores. A machine due in 2013 will have 8,000 pores. One big advantage of the nanopore sequencing, Dr. Mardis of Washington University said, is that preparing the sample is quick and easy. The technology also offers the promise of being able to read tens of thousands of bases in a stretch. Most sequencers read from around 30 to a few thousand bases at a stretch, and these small fragments then have to be pieced together. A drawback is that the Oxford machine has a 4 percent error rate, too high for many applications, including diagnosis. The MinIon, while entailing no capital cost for a machine, can be used only once and will sequence up to one billion bases. That is a cost of up to $1,000 per billion bases. A GridIon might cost around $30,000, Oxford executives said. The company said that if 20 of the secondgeneration GridIons were used together, a human genome could be sequenced in 15 minutes at a cost of around $1,500. By then, however, rival machines might be able to do genomes for that cost or even less. Ion Torrent, a subsidiary of Life Technologies, last month announced it was developing a machine that could do a human genome in a day for $1,000. “We’re not losing sleep,” Jonathan M. Rothberg, chief executive of Ion Torrent, said Friday. “But they definitely have the Twitter airwaves today.” #3# MOUNTAIN VIEW, Calif. — In Silicon Valley, the line between computing and biology has begun to blur in a way that could have enormous consequences for human longevity. Enlarge This Image Ramin Rahimian for The New York Times Complete Genomics has produced more than 3,000 sequences at about $5,000 each this year. Bill Banyai, an optical physicist at Complete Genomics, has helped make that happen. When he began developing a gene sequencing machine, he relied heavily on his background at two computer networking startup companies. His digital expertise was essential in designing a factory that automated and greatly lowered the cost of mapping the three billion base pairs that form the human genome. The promise is that low-cost gene sequencing will lead to a new era of personalized medicine, yielding new approaches for treating cancers and other serious diseases. The arrival of such cures has been glacial, however, although the human genome was originally sequenced more than a decade ago. Now that is changing, in large part because of the same semiconductor industry manufacturing trends that opened up consumer devices like the PC and the smartphone: exponential increases in processing power and transistor density are accompanied by costs that fall at an accelerating rate. As a result, both new understanding and new medicines will arrive at a quickening pace, according to the biologists and computer scientists. “For all of human history, humans have not had the readout of the software that makes them alive,” said Larry Smarr, director of the California Institute of Telecommunications and Information Technology, a research center that is jointly operated by the University of California, San Diego, and the University of California, Irvine, who is a member of the Complete Genomics scientific advisory board. “Once you make the transition from a data poor to data rich environment, everything changes.” Complete Genomics, based in Mountain View, is one of more than three dozen firms hastening to push the cost of sequencing an entire human genome below $1,000. The challenge is part biology, part chemistry, part computing, and in Complete Genomics’ case, part computer networking. Complete Genomics is a classic Silicon Valley start-up story. Even the gene sequencing machines, which are housed in a 4,000-square-foot room bathed in an eerie blue light, appear more like a traditional data center than a biology lab. In 2005 ,when Clifford Reid, a successful Silicon Valley software entrepreneur, began to assemble his team, he approached Dr. Banyai and asked if he was interested in joining a gene sequencing start-up. Dr. Reid, who was also trained in physics and math, had spent a year as an entrepreneur-in-residence at the Massachusetts Institute of Technology, where he had become a convert to bioinformatics, the application of computer science and information technologies to biology and medicine. Dr. Banyai had even less experience in biology. Formerly with the Internet networking start-ups GlimmerGlass and Silicon Light Machines, he in turn began by reading a pioneering 2005 article in the journal Science in which a group of researchers in George Church’s genetics laboratory at Harvard describe a new technique intended to speed gene sequencing. Today Dr. Banyai is finishing the second generation of a machine that blends robotics, chemistry, optics and computing. It is emblematic of the serendipitous changes that take place when a manufacturing process is transformed: performance increases and cost falls at an accelerating rate. “Genomes are now being sequenced incredibly cheaply,” said Russ B. Altman, who is a founder of Personalis, a start-up based in Palo Alto, Calif., that is developing software to interpret genomes. “On the discovery and science side we will be able to do clinical trials. We’ll be able to check the entire genome.” Recently, on the company’s Web site, Dr. Reid predicted that the cost of gene sequencing could eventually be as low as that of a blood test: “I believe that the impact on the medical community of whole human genome sequencing at a cost comparable to a comprehensive blood test will be profound, and it will raise a host of public policy issues (privacy, security, disclosure, reimbursement, interpretation, counseling, etc.), all important topics for future discussions,” he wrote. Dr. Banyai said he had found that Silicon Valley start-up ideas tracked well. “There is this remarkable thing that happens in start-ups. You make up this plan and then you step off a cliff and magically a little bridge appears,” he noted, as new technologies appear in the nick of time. In the case of Complete Genomics, the company is riding in part on big advances being made in industrial digital cameras that are capable of capturing the fluorescent molecules that are used to “read” small sequences of DNA. In the last half-year, a new generation of cameras, more frequently used for factory inspection systems, has made it possible to speed up the Complete Genomics sequencing process tenfold. That, the company has said, will drive its capacity to 100,000 genomes annually from 10,000. The parallels between the evolution of the nascent gene sequencing industry and the Valley’s chip makers are striking. By placing more circuits on a silicon wafer at an exponentially increasing pace since the early 1960s, the semiconductor industry transformed the cost of computing. As a result, today the world’s most powerful supercomputer from the 1980s nestles comfortably in your hand and costs several hundred dollars. Complete Genomics’ competitors are also exploiting designs to drive costs down. For example, Life Technologies, based in Carlsbad, Calif. uses a direct approach to read the bases in the genome from an array of sensors on the surface of a semiconductor chip. As more sensors are packed onto each successive generation of technology, the cost of sequencing will also fall sharply. Last month, Oxford Nanopore Technologies created an industry sensation when it introduced a machine that sequenced genes using an alternative approach called nanopore sequencing, in which a strand of DNA is read as it is pulled through a microscopic hole. The system is scheduled to be available later this year. However, it has an error rate much higher than that of the Complete Genomics system, which has independently been given high marks for accuracy. Because there is no clear winner yet, all of the companies are pushing hard to get down the cost curve as fast as possible In 2011, Complete Genomics became one of the market leaders. This year, it has produced more than 3,000 sequences at a cost of about $5,000 each. Dr. Banyai’s higher capacity second generation system is now being installed and will begin production during the first half of this year. A third generation design has been completed. What initially set Complete Genomics apart from the field was its strategy of offering gene sequencing as a service, rather than selling a machine to laboratories. More recently, Illumina, one of its crucial competitors, has also begun offering sequencing as a service, in addition to selling its machines. “Our competitors have to supply kits that can be executed by a graduate student rolling out of bed with a hangover,” said Dr. Reid. “We don’t live with that standard, and that can be tremendously liberating. Ours can be horrifically complex as long as it can be executed by a robot.” The company also began with the business intent of sequencing only the human genome, rather than those of other species, too — a strategy that was heresy in 2005, when the founders set out to raise money. At that time, only two human genomes had been sequenced. However, Complete Genomics founders argue that focusing just on the human genome has given them a leg up. “You make a whole bunch of decisions that don’t work well for corn or bacteria, but they work very well for humans,” Dr. Reid said. The Texas Tribune #10 Putting Pieces Together in Decades-Old Cases Evan Lewis/Texarkana Gazette Delma Banks Jr. is on trial again for the 1980 murder of Richard Whitehead, 16, whose parents are in the front row. By BRANDI GRISSOM Mark Norwood will be led into a Georgetown courtroom Wednesday to face capital murder charges for a killing that took place more than 25 years ago. If Mr. Norwood, 57, goes to trial in the 1986 beating death of Christine Morton, prosecutors and defense lawyers will have to piece together a decades-old crime. That was what lawyers did for the trial of Dennis Davis last year, when he was convicted of the 1985 murder of his former girlfriend. With the advent of DNA science and other technological advancements, it is no longer unusual for juries to see evidence from crimes that happened as long ago as the 1970s. But old cases present unique challenges for prosecutors and defense lawyers: Key witnesses may have moved or died, documents could have disappeared, and evidence collection standards are now much stricter. “The farther back in time you’re talking about, the more those things fray and disintegrate,” said Rob Owen, a University of Texas School of Law professor who specializes in death penalty cases. Mr. Norwood was arrested in November for the Aug. 13, 1986 murder of Mrs. Morton. Michael Morton, Mrs. Morton’s husband, was convicted of her murder in 1987 and spent 25 years in prison. But he was cleared last year after DNA testing was performed on a bandanna found about 100 yards from the Mortons’ North Austin home, where she had been beaten to death in bed. Tests showed the biological material on the bandanna was not Mr. Morton’s, and a national database search revealed the DNA matched Mr. Norwood’s. His DNA was also linked to a similar Austin murder that happened on Jan. 13, 1988. Like Mrs. Morton, Debra Masters Baker was beaten to death in her bed, and Mr. Norwood is a suspect in that cold case. Russell Hunt Jr., Mr. Norwood’s lawyer, expects the judge to delay this week’s hearing to allow him and state prosecutors more time to investigate. “People change over time. People’s memories change over time,” Mr. Hunt said, adding, “Physical evidence gets moved. Physical evidence is stored in different ways.” Mr. Hunt said that verifying other information and determining its relevance to Mr. Norwood could be a challenge. For example, other evidence that recently came to light in the Morton case includes a check cashed after Mrs. Morton’s death with her forged signature and a report that her credit card was fraudulently used days after her death. “We don’t know if it’s possible to go back and find people involved or records involved,” he said. “Things get lost, and people get lost.” When Mr. Davis was convicted last year of murdering his former girlfriend, he was represented by Wade Russell, an Austin lawyer. “There’s just myriad problems” mounting a defense in a two-decades-old case, Mr. Russell said. Natalie Antonetti was beaten in the head while she slept on her couch on Oct. 13, 1985. The case was cold until 2006, when Mr. Davis’s estranged wife told the police her husband had said that he had “sinned against God and man.” She later reconciled with Mr. Davis, and refused to cooperate with police. But investigators reopened the case and focused on Mr. Davis. The woman Mr. Davis told police he was with the night of the murder told investigators who reopened the case that she did not have an entry in her journal noting that she was with him when the police called, and it was something she would have recorded. A quarter-century after the murder, Mr. Russell began digging through the old police file to investigate his client’s case. The original police investigator had died. The police case file was incomplete and unorganized, he said. “I would find handwritten notes from various people,” he said. “You have a lot of sketchy information, and you don’t know how it fits into the picture.” A neighbor had told police that shortly before the murder he saw a large man carrying a bat wearing a T-shirt with a band logo. The neighbor refused to testify. He originally described a man who was larger than Mr. Davis. A police sketch of the man made in 1985 based on the neighbor’s description was missing. And Mr. Russell said finding other witnesses to challenge the credibility of those who testified against Mr. Davis was tough. “I couldn’t track them all down,” he said. “They were scattered so far.” Mr. Davis was found guilty and sentenced to 36 years in prison. Efrain De La Fuente, a Travis County assistant district attorney who worked on the Davis case, said compiling evidence was just as challenging for prosecutors. There was no DNA linking Mr. Davis to the crime, but prosecutors found other women who testified about abusive relationships with him, and one said he had confessed to her. Friends of Mr. Davis said he owned a bat and had a screaming match with Ms. Antonetti hours before the murder. “The crime scene speaks to us that it was someone known to her and that it was personal,” Mr. De La Fuente said, adding that nothing was stolen. “He took a bat and just inflicted numerous blows to her head.” Old cases do not come to court based only on new charges, though. Delma Banks Jr. was sentenced to death for the 1980 murder of Richard Whitehead, 16, in Texarkana. Mr. Banks, who was 21 when the crime was committed, was convicted of killing Mr. Whitehead to steal his car. In 2004, the United States Supreme Court overturned his sentence, finding that prosecutorial misconduct had led the jury to give Mr. Banks the death penalty. This year, Mr. Banks is scheduled to face another trial to determine whether his death sentence should be reinstated. Mr. Banks’s lawyers must try to find mitigating evidence, information that might prompt jurors to consider a more lenient sentence. Typically, that comes from family members or others who know about the defendants’ past. In Mr. Banks’s case, though, many who knew him before he went to prison are dead. Others have moved away. “It’s hugely problematic that the state would pursue the death penalty in a situation like that,” said Mr. Owen of the University of Texas School of Law, who has worked on Mr. Banks’s case in the past. “The jury is inevitably going to be presented an incomplete set of facts.” James Elliott, a prosecutor on the case for more than 30 years, has maintained that he will pursue Mr. Banks until he “gets what he deserves.” In the Norwood case, however, prosecutors have not indicated whether they will seek the death penalty. Lisa Tanner, a special prosecutor in the Texas attorney general’s office, will lead the state’s case. She declined to speak specifically about Mr. Norwood, but she discussed the challenges in trying old cases. She prosecuted two men in the so-called KFC murders. In 1983, five people at a Kentucky Fried Chicken restaurant in Kilgore were robbed and killed. The crime went unsolved until DNA evidence linked two cousins to the scene. They were arrested in 2005; each was sentenced to five consecutive life sentences. In old cases, Ms. Tanner said, DNA evidence is often the key to convincing a jury of a person’s guilt. “We are able to do things that were utterly inconceivable back in the ’70s, ’80s or even the early ’90s,” she said. “In cold cases, it seems like that is the difference.” Spotted Horses in Cave Art Weren’t Just a Figment, DNA Shows ARTICLE #4 French Ministry of Culture and Communication SEEING SPOTS Drawings of horses from the Chauvet cave in France, right, and a horse from the Lascaux cave, also in France. By HILLARY ROSNER Enlarge This Image Thomas Hackmann A modern horse with leopard spots like those seen in France's Pech-Merle cave. Comparing DNA from the present and the Stone Age convinced scientists that those spotted depictions were based on existing animals. Today, the art at the Pech-Merle cave, and in hundreds of others across Europe, is a striking testimony to human creativity well before modern times. But what were these cave paintings, exactly? Were prehistoric artists simply sketching what they saw each day on the landscape? Or were the images more symbolic, diverging from reality or representing rare or even mystical creatures? Such questions have divided archaeologists for years. Now, a group of researchers has used distinctly modern techniques to help decipher the mystery, at least in the case of Pech-Merle’s famous spotted horses. By comparing the DNA of modern horses and those that lived during the Stone Age, scientists have determined that these drawings are a realistic depiction of an animal that coexisted with the artists. The research, published online on Monday in the journal Proceedings of the National Academy of Sciences, grew out of an effort to discern the coat colors of ancient horses to help figure out when the animals were domesticated, a pivotal moment in the development of human societies. In general, domesticated species exist in a far greater variety of colors than wild ones, so understanding color variation in fossil animals can help pinpoint the timing. Previous research on DNA from the bones and teeth of horses that lived 7,000 to 20,000 years ago showed that those animals were either black or bay (a brown coat with a black mane and tail). That work was published in the journal Science in 2009. Since then, geneticists have deciphered the underlying code for the spotted pattern, known as leopard, in modern horses. So the scientists went back to their samples, looking for the leopard sequence in horses that lived in Europe 11,000 to 15,000 years ago. “There is a striking correspondence between the coat-color patterns of horses painted in Paleolithic caves of France with what geneticists found in the genotypes” — the specific genetic sequences — “of color genes,” said Hopi E. Hoekstra, an evolutionary biologist at Harvard who studies pigmentation. Dr. Hoekstra was not involved in the study but called it “very convincing.” An author of the study, Michael Hofreiter, an evolutionary biologist at the University of York in England, said: “Why they took the effort making these beautiful paintings will always remain a miracle to us. “It’s an enigma, but it’s also nice to see that if we go back 25,000 years, people didn’t have much technology and life was probably hard, but nevertheless they already endeavored in producing art. It tells us a lot about ourselves as a species.” Extracting DNA from such old material is a complex process, and the potential for contamination is huge. Early studies of Neanderthal DNA were marred by contamination from humans, and led to skepticism about the field’s future. Since then, researchers have adopted strict procedures to ensure they are not contaminating ancient samples with modern-day DNA. The procedures include analyzing ancient and contemporary material in physically separate facilities and replicating results multiple times. “This is a whole different level of clean,” said Jessica L. Metcalf, a postdoctoral researcher at the University of Colorado who also works with the Australian Center for Ancient DNA in Adelaide, where the labs that work on ancient and modern DNA are more than half a mile apart. “We have sealed rooms with HEPA filter air flow, UV lights that sterilize when you come in,” she said. “We spend over half our time cleaning. We use a lot of bleach. You’re in this ridiculous-looking clean suit with a face shield on.” In fact, Dr. Hofreiter said, researchers who work with ancient horse genes should not even go horseback riding. “Traces of DNA,” she said, “they just stick to people.” Dr. Hofreiter, 38, began his career working with a pioneer of ancient DNA research, Svante Paabo. Though he intended to study taxonomy, he was so intrigued by the idea of extracting DNA from ancient material that he switched his focus. “You have this 30,000-year-old piece of feces in your hand,” he said, adding: “Well, you should wear gloves. And you can actually get to the genetic code from the animal. And I thought, this is so fascinating.” He and his colleagues did not set out to study cave art. They were simply continuing their work on coat color in prehistoric horses. Only after they found the spotted horse gene in their ancient samples did they realize they could say something about archaeology. “What we found is that there were really only these three color patterns — spotted or dappled; blackish ones; and brown ones,” he said. “These are the three phenotypes we find in the wild populations. And then we realized these phenotypes are exactly the ones you see in cave paintings.” Terry O’Connor, an archaeologist at the University of York who collaborated on the study, said spotted horses in particular had been used to argue that cave art was more symbolic than realistic, and that as a result the finding could cause a stir. But now it is clear that some horses had a gene for that coat color. “People drew spotty horses,” he said, “because they saw spotty horses.” Last summer, exploring a cave in the Dordogne region, Dr. O’Connor said he became transfixed by a series of line drawings of mammoths. “They were absolutely superb, some using contours of the cave itself, capturing the size and shape and movement,” he said. “You look at that and say, ‘These guys know what the animals looked like, and they can draw.’ ” As techniques for working with ancient DNA have matured, scientists are now using it to answer an increasing variety of questions about the past — from what happened to a species’ genetic variation as its environment changed to how humans recolonized Europe after the last ice age to what type of microbes lived in the guts of people and animals thousands of years ago. “One of the things that most pleases me about this paper as a piece of ancient DNA science,” Dr. O’Connor said, “is it kind of begins with a question. These spotty horses, were they magical or real? “And then science answers that. It’s not just, ‘Let’s rip the DNA out of ancient bones and see what it tells us.’ ” Why Has the Black Death Paled? Article #5 Published: October 25, 2011 The Black Death killed 25 million people — roughly half of Europe — between 1347 and 1351. In Britain alone, 1.5 million died, including the victims whose teeth and bones yielded the DNA used in the reconstruction. The cause, as suspected, was a strain of the bacterium Yersinia pestis, the ancestor of all modern strains of the plague. Behind this research, which was published in Nature, lie two basic questions. How is the medieval plague related to other plague epidemics, like the one that ravaged the eastern Mediterranean in the 6th century? And why is the modern plague, which kills some 2,000 people a year, so much less virulent than its medieval ancestor? The answers are important contributions to epidemiology. In fact, there is no link between the Black Death and earlier plagues. They were caused either by an extinct strain of Yersinia or by something else entirely. And there is nothing in the genetic code of the medieval Yersinia that makes it inherently more lethal than modern strains, even though, as the scientists write, the epidemics they cause “have their origins in the medieval era.” In other words, the origins of the Black Death are not the result of a killer bacterium alone. They may lie in the complex interaction of any number of factors, including climate, social conditions, the genetics of its victims and interactions with other diseases. The plague still with us — which is treatable with modern antibiotics — lacks its medieval virulence because the conditions we live in are not medieval. We have our own plagues, but Yersinia, at least, has outlived its time. Scientists Solve Puzzle of Black Death’s DNA By NICHOLAS WADE Published: October 12, 2011 After the Black Death reached London in 1348, about 2,400 people were buried in East Smithfield, near the Tower of London, in a cemetery that had been prepared for the plague’s arrival. From the teeth of four of those victims, researchers have now reconstructed the full DNA of a microbe that within five years felled one-third to one-half of the population of Western Europe. Enlarge This Image Museum of London A draft sequence of the Yersinia pestis genome has been reconstructed using DNA extracted from victims of the Black Death. Museum of London Advancing science: the remains of plague victims in a 14th-century London cemetery. The bacterium that causes plague, Yersinia pestis, is still highly virulent today but has different symptoms, leading some historians to doubt that it was the agent of the Black Death. Those doubts were laid to rest last year by detection of the bacterium’s DNA in plague victims from mass graves across Europe. With the full genome now in hand, the researchers hope to recreate the microbe itself so as to understand what made the Black Death outbreak so deadly. So far, the evidence points more toward the conditions of the time than to properties of the bacterium itself. The genome recovered from the East Smithfield victims is remarkably similar to that of the present-day bacterium, says the research team, led by Kirsten I. Bos of McMaster University in Ontario and Johannes Krause of the University of Tübingen in Germany. This is the first time the genome of an ancient pathogen has been reconstructed, opening the way to tracking other ancient epidemics and how their microbes adapted to human hosts. The bacterium’s genome consists of a single chromosome, about 4.6 million DNA units long, and three small rings of DNA called plasmids. In the 660 years since the Black Death struck, only 97 of these DNA units have changed and only a dozen of these changes occur in genes and therefore would affect the organism’s physical properties, the researchers report in Wednesday’s issue of the journal Nature. Dr. Krause and others reported the DNA sequence of one of the plasmids in August. The changes in the genome will be studied one by one to see how each affects the microbe’s virulence. The researchers hope eventually to modify a living plague bacterium so that its genome is identical to that of the agent of the Black Death. Such a microbe could be handled only in special secure facilities. But even if it did infect a person, the bacterium would be susceptible to antibiotics, like its living descendants, said Hendrik Poinar of McMaster University, a team member. If the microbe’s genome is so little changed, the deadliness of the Black Death may reflect the condition of its medieval victims. Harsh as the economic stresses assailing Europe today may be, they are a breeze compared with problems in the mid-14th century. The climate was cooling, heavy rains rotted out crops and caused frequent famines, and the Hundred Years’ War began in 1337. People were probably already suffering from malnutrition and other diseases when the plague arrived like the fourth horseman of the apocalypse. “People honestly thought it was the end of the world,” Ms. Bos said. Recovery of the medieval plague bacterium’s full genome is a technical tour de force. The DNA had been degraded into millions of small fragments that were overwhelmed in number by DNA from the human host and from the bacteria that consumed the body after death. Dr. Krause’s team fished out the plague DNA by using DNA from the modern bacterium, relying on the fact that DNA strands bind to DNA of complementary sequence. “This is a major technological step forward, a great advance for the entire field of DNA and pathogens,” said Mark Achtman, an expert on ancient plague at University College Cork in Ireland. But Dr. Achtman disagreed with one issue in Dr. Krause’s findings, that of whether Yersinia pestis also caused the outbreak in the sixth century known as the Justinian plague. When the full genome of the medieval bacterium is compared with DNA recovered from other known human outbreaks, a tree of descent can be constructed. The Black Death genome lies so close to the root of the tree that the human pathogen probably did not exist much earlier or, if it did, has vanished without any descendants, Dr. Krause’s team says. This implies that the Justinian plague was caused by some other agent. Dr. Achtman said this conclusion was incorrect because the Krause team had omitted DNA from several human cases that place the root of the tree much further back in time. Dr. Krause said he had left these cases out because they seemed unreliable. The modern plague bacterium changes its DNA units slowly, but it does quite often rearrange the order of its genes. Some experts believe gene order can affect pathogenicity. Dr. Krause had available only tiny fragments of DNA, so although he was able to reconstruct all the medieval bacterium’s genes he could not establish the exact order in which the genes were arranged, leaving open the possibility that the bacterium was inherently more pathogenic because its genome was differently organized. Paul Keim, an expert on infectious bacteria at Northern Arizona University, said that work by Dr. Achtman and Dr. Krause had shown that the Black Death “was really a series of epidemics coming out of China and sweeping across the susceptible ecological situation” created by the culture of medieval Europe. The plague in each outbreak probably did not persist very long and was repeatedly re-established by new infections from East Asia, where the bacterium is still endemic in small rodents like marmots. “We don’t have a human ecological situation comparable today, plus it is really easy to break the transmission cycle with antibiotics and public health,” Dr. Keim said. There are still small outbreaks, like one in Madagascar in the 1990s, but “a multiyear large human outbreak is inconceivable in this day,” he said. Besides the Justinian plague and the Black Death, a third great wave of plague swept out of China in 1894, causing an epidemic in San Francisco in 1900 and killing millions of people in India. All the teeth used in the study will be returned to the skulls from which they were taken, now in a London museum whose archaeologists excavated the East Smithfield cemetery in the 1980s. Tracing Unscooped Dog Waste Back to the Culprit By KATIE ZEZIMA #6 Published: July 1, 2011 Sherlock Holmes had the case of the dog that didn’t bark, but it has taken two dozen apartment complexes and a testing company in Tennessee to bring the art of canine detection into the “CSI” age. Enlarge This Image Jim Cole/Associated Press Deborah Violette, a property manager, takes dog waste seriously. Related Scoop It Up or Pay: On Patrol With Enforcers of the Dog Law (June 5, 2008) And the evidence is right underfoot. Canine DNA is now being used to identify the culprits who fail to clean up after their pets, an offense that Deborah Violette, for one, is committed to eradicating at the apartment complex she manages. Everyone who owns a dog in her complex, Timberwood Commons in Lebanon, N.H., must submit a sample of its DNA, taken by rubbing a cotton swab around inside the animal’s mouth. The swab is sent to BioPet Vet Lab, a Knoxville, Tenn., company that enters it into a worldwide database. If Ms. Violette finds an unscooped pile, she can take a sample, mail it to Knoxville and use a DNA match to identify the offending owner. Called PooPrints, the system costs $29.99 for the swabbing kit, $10 for a vial to hold the samples and $50 to analyze them, which usually takes a week or two. The company says that about two dozen apartment complexes around the country have signed up for the service. In 2008, the Israeli city of Petah Tikva created a dog DNA database for the same purpose. “It’s kind of like the F.B.I., but on a much smaller scale,” said Eric Mayer, director of franchise development for BioPet Vet Lab, which makes the kits. Ms. Violette said that at her complex, which opened in December and has a designated building for pet owners, unwanted surprises have sometimes been found on lawns. “We had a little bit of a problem,” Ms. Violette said. “Enough that I wanted to try to nip it in the bud.” Dog owners were notified about the testing last week, and most are now taking their pets in to provide DNA samples. But not everyone. “I’ve had some people say it’s completely over the top and ridiculous,” Ms. Violette said. “I’m sure I’ll have a few people who won’t come in, and I’m sure those are the people we’ll have to chase and those are the people who are doing it.” Tom Boyd, the founder and chief executive of BioPet Vet Lab, said the company made the kits in response to the large of numbers of the dogs in the United States and to health concerns connected to dog feces. According to the American Society for the Prevention of Cruelty to Animals, there are about 75 million dogs in the United States. “If you took 75 million Americans and said they no longer have a commode, can you imagine what would happen in a week?” Mr. Boyd asked. Not everyone is on board with the idea, though. Karen Harvey of Forest Property Management in McCall, Idaho, said her company was not prepared to collect canine samples along with the rent checks. “If you allow pets, that sort of comes with it,” Ms. Harvey said. “I guess I would never take the issue of dog poop that far.” Roots of Disease Found to Vary by Continent By NICHOLAS WADE Published: July 4, 2011 A new survey of the human genome shows that common diseases are likely to have a different set of genetic roots in Africans, East Asians and Europeans. The finding may represent yet another serious complication in the post-genome quest for the roots of common disease, since it implies that each disease may need to be investigated separately in different populations. After the human genome was decoded in 2003, biologists completed a follow-up project called the HapMap that cataloged the genome’s common variations, meaning the sites on the DNA where one unit often differs from the standard sequence. They then scanned the genomes of patients with common diseases to look for statistical links between having a disease and having a particular variation. These expensive scans, called genomewide association studies, required recruiting hundreds of patients. Many such scans have now been done for most of the common diseases, but the results have been disappointing. With a few exceptions, common variations account for little of the genetic risk of common disease. The basic premise of the HapMap — that common diseases were caused by common variations — turned out to be largely incorrect. Back at the drawing board, biologists decided that if the genetic roots of common disease did not lie in the common variants, they should lie in the rarer variants. With partners in England and China, the National Institutes of Health in 2008 undertook a follow-up to the HapMap, the 1,000 Genomes Project, to catalog rare variants in the human population. The project is not yet complete, but a team led by Simon Gravel and Carlos D. Bustamante of Stanford University has analyzed the data so far available and predicts the rare variants will be found to be almost entirely different in the Chinese, European and African populations. This means that almost all of the rare variants developed after the three populations had split apart. “Genomewide association studies aiming to correlate common disease susceptibility with rare variants may need extraordinarily large sample sizes,” the scientists concluded in the journal PNAS. David B. Goldstein, a geneticist at Duke University, said that it had long been known that rare variants tend to be specific to particular populations, but that it was too early to tell how hard it will be to find those that cause disease. Some rare variants can greatly increase the risk of disease and should be easier to detect than others. But the jury is still out on the catalog of rarer variants being developed by the 1,000 Genomes Project and how useful it will be, Dr. Goldstein said. It may be more effective to decode the entire genomes of patients with a particular disease. “We are more interested in the variants we see in patients than in a generic catalog,” he said. These variants are so rare that even 1,000 Genomes is unlikely to pick up many of them, he said. The Stanford study also sheds light on major aspects of human population history, like the time at which the first modern humans emigrated from Africa. Archaeologists believe it was about 50,000 years ago, since no modern human remains older than this have yet been found outside of Africa, but geneticists have long favored much earlier dates. Dr. Gravel and Dr. Bustamante now calculate that 51,000 years ago, give or take several thousand years, is the date best supported by genetic data, bringing the geneticists’ date into alignment with the archaeologists’ favored time for the exit from Africa. The common variations in the human genome were mostly present in the ancestral human population in Africa and have been inherited by all the descendant populations around the world. The rare variants occurred more recently. “Most of the common variants hark back to pre-Out of Africa,” Dr. Bustamante said. “Most of the rare variants come after the Neolithic revolution.” This is the event that marked the beginning of agriculture about 10,000 years ago and led to significant increases in the size of human populations. A Blood Test Offers Clues to Longevity #7 By ANDREW POLLACK Published: May 18, 2011 Toni Albir/EFE, Via European Pressphoto Agency Elizabeth H. Blackburn shared a Nobel Prize in 2009 for discoveries related to telomeres. Blood tests that seek to tell people their biological age — possibly offering a clue to their longevity or how healthy they will remain — are now going on sale. But contrary to various recent media reports, the tests cannot specify how many months or years someone can expect to live. Some experts say the tests will not provide any useful information. The tests measure telomeres, which are structures on the tips of chromosomes that shorten as people age. Various studies have shown that people with shorter telomeres in their white blood cells are more likely to develop illnesses like cancer, heart disease and Alzheimer’s disease, or even to die earlier. Studies in mice have suggested that extending telomeres lengthens lives. Seizing on that, laboratories are beginning to offer tests of telomere length, setting off a new debate over what genetic tests should be offered to the public and what would be the ethical implications if the results were used by employers or others. Some of the laboratories offering the tests emphasize that the results are merely intended to raise a warning flag. “We see it as a kind of wake-up call for the patient and the clinician to say, ‘You know, you’re on a rapidly aging path,’ ” said Otto Schaefer, vice president for sales and marketing at SpectraCell Laboratories in Houston, which offers a test for $290. A company in Spain, provocatively named Life Length, has begun selling a test for 500 euros ($712), that says that it can tell people their biological age, which may not correspond to their chronologic age. Another company, Telome Health of Menlo Park, Calif., plans to begin offering a test later this year for about $200. It was co-founded by Elizabeth H. Blackburn of the University of California, San Francisco, who shared a Nobel Prize in 2009 for discoveries related to telomeres. Calvin B. Harley, the chief scientific officer at Telome Health, said the test would be akin to a car’s dashboard signal, a “check engine light.” He compared it with a cholesterol test, but more versatile since it can predict a risk of various illnesses, not just heart attacks. But among the critics of such tests is Carol Greider, a molecular biologist at Johns Hopkins University, who was a co-winner of the Nobel Prize with Dr. Blackburn. Dr. Greider acknowledged that solid evidence showed that the 1 percent of people with the shortest telomeres were at an increased risk of certain diseases, particularly bone marrow failure and pulmonary fibrosis, a fatal scarring of the lungs. But outside of that 1 percent, she said, “The science really isn’t there to tell us what the consequences are of your telomere length.” Dr. Greider said that there was great variability in telomere length. “A given telomere length can be from a 20year-old or a 70-year-old,” she said. “You could send me a DNA sample and I couldn’t tell you how old that person is.” Dr. Peter Lansdorp, a telomere expert at the British Columbia Cancer Agency, also had doubts. “If telomeres are short for you or me, what does it mean?” he said. Dr. Lansdorp started a company, Repeat Diagnostics, which conducts telomere testing for medical researchers only. Recent media reports speculated on the tests and their possible implications, including ethical problems. “You could imagine insurance companies wanting this knowledge to set rates or deny coverage,” said Jerry W. Shay, a professor of cell biology at the University of Texas Southwestern Medical Center in Dallas, who is an adviser to Life Length. Test vendors say the speculation is running wild. “It doesn’t mean we will tell anyone how long they will live,” said María Blasco, a co-founder of Life Length and a molecular biologist at the Spanish National Cancer Research Center in Madrid. Even if a 50-year-old has the telomere length more typical of a 70-year-old, she said, “This doesn’t mean your whole body is like a 70year-old person’s body.” Still, she said, “We think it can be helpful to people who are especially keen on knowing how healthy they are.” Generally tests offered by a single laboratory do not have to be approved by the Food and Drug Administration. But the F.D.A. has been cracking down recently on some tests offered to the public, saying they may need approval. The FDA said in a statement Wednesday that it was aware of the tests, and had not come to any conclusions. Executives at both Telome Health and Life Length say they will require a doctor to be involved in ordering the test, though SpectraCell said it allowed individuals to order the Telomeres are stretches of DNA linked to certain proteins that are at the ends of chromosomes. They are often likened to the caps at the end of shoelaces. Each time a cell divides, the telomeres get shorter. Eventually, the telomeres get so short that the cell can no longer divide. It enters a state of senescence or dies. Life Length María Blasco is a co-founder of Life Length, a company in Spain that sells a test for 500 euros ($712) that says that it can tell people their biological age. One study in Utah, using blood samples from 143 elderly people collected in the 1980s, found that those with shorter telomeres were almost twice as likely to die in the ensuing years as those with longer ones. Another study, published in The Journal of the American Medical Association last July, followed 787 people in Italy, all initially free of cancer. Those with the shortest telomeres had three times the risk of developing cancers in the next 10 years as those with the longest telomeres. Still, not all studies have found such strong correlations. In any case, correlations do not prove that the shorter telomeres are causing the problems, although experts say some animal and cell studies do suggest causality. Some say that the telomere test might not tell people much that cannot be learned in other ways. “You can pretty much look at people and determine their biological age,” said Michael West, who founded Geron, the biotechnology company that sponsored and conducted some important research on telomeres. He now runs BioTime, another biotechnology company. It is also unclear what to do about short telomeres. At the moment, there is no drug that can lengthen telomeres, though researchers are working on drugs and stem cell therapies. There is some evidence, however, that stress is associated with shorter telomeres and that stress relief, exercise or certain nutrients such as omega-3 fatty acids might at least slow the decline in telomere length. But healthy lifestyles are already recommended for people without having to know their telomere length. There are also disputes about how to measure telomeres. Life Length says its technique, while more expensive, can detect not only average telomere length but the shortest telomeres in cells. The shortest telomeres cause the health problems, said Dr. Shay, the adviser to Life Length. Telome Health and SpectraCell use a DNA amplification technique called polymerase chain reaction, or P.C.R., which is cheaper but provides only an average length. And there are some questions about the accuracy. Dr. Harley of Telome said the P.C.R. test was more relevant because virtually all the studies correlating telomere length with disease had used that test. For those wanting to know how long they might live, there are already some indexes that are used by geriatricians to estimate the chances of a patient dying in anywhere from six months to nine years. A patient with a short expected lifespan, for instance, might no longer need to undergo annual screening for cancer. These estimates rely on factors such as person’s age, gender, smoking history, whether they have certain diseases and whether they can perform certain functions, like walking several blocks, pushing an armchair or managing their finances. Dr. Sei Lee, an assistant professor at the University of California, San Francisco who developed a test that estimates the probability of dying within four years, said he was not sure how much telomere length testing would add. “The chance of any single factor being a great predictor is probably low,” he said. Phys Ed: How Exercising Keeps Your Cells Young By GRETCHEN REYNOLDS Article #9 Chev Wilkinson/Getty Images Recently, scientists in Germany gathered several groups of men and women to look at their cells’ life spans. Some of them were young and sedentary, others middle-aged and sedentary. Two other groups were, to put it mildly, active. The first of these consisted of professional runners in their 20s, most of them on the national track-and-field team, training about 45 miles per week. The last were serious, middle-aged longtime runners, with an average age of 51 and a typical training regimen of 50 miles per week, putting those young 45-mile-perweek sluggards to shame. From the first, the scientists noted one aspect of their older runners. It ‘‘was striking,’’ recalls Dr. Christian Werner, an internal-medicine resident at Saarland University Clinic in Homburg, ‘‘to see in our study that many of the middle-aged athletes looked much younger than sedentary control subjects of the same age.’’ Even more striking was what was going on beneath those deceptively youthful surfaces. When the scientists examined white blood cells from each of their subjects, they found that the cells in both the active and slothful young adults had similar-size telomeres. Telomeres are tiny caps on the end of DNA strands — the discovery of their function won several scientists the 2009 Nobel Prize in medicine. When cells divide and replicate these long strands of DNA, the telomere cap is snipped, a process that is believed to protect the rest of the DNA but leaves an increasingly abbreviated telomere. Eventually, if a cell’s telomeres become too short, the cell ‘‘either dies or enters a kind of suspended state,’’ says Stephen Roth, an associate professor of kinesiology at the University of Maryland who is studying exercise and telomeres. Most researchers now accept telomere length as a reliable marker of cell age. In general, the shorter the telomere, the functionally older and more tired the cell. It’s not surprising, then, that the young subjects’ telomeres were about the same length, whether they ran exhaustively or sat around all day. None of them had been on earth long enough for multiple cell divisions to have snipped away at their telomeres. The young never appreciate robust telomere length until they’ve lost it. When the researchers measured telomeres in the middle-aged subjects, however, the situation was quite different. The sedentary older subjects had telomeres that were on average 40 percent shorter than in the sedentary young subjects, suggesting that the older subjects’ cells were, like them, aging. The runners, on the other hand, had remarkably youthful telomeres, a bit shorter than those in the young runners, but only by about 10 percent. In general, telomere loss was reduced by approximately 75 percent in the aging runners. Or, to put it more succinctly, exercise, Dr. Werner says, ‘‘at the molecular level has an anti-aging effect.’’ There are plenty of reasons to exercise — in this column, I’ve pointed out more than a few — but the effect that regular activity may have on cellular aging could turn out to be the most profound. ‘‘It’s pretty exciting stuff,’’ says Thomas LaRocca, a Ph.D. candidate in the department of integrative physiology at the University of Colorado in Boulder, who has just completed a new study echoing Werner’s findings. In Mr. LaRocca’s work, people were tested both for their V02max — or maximum aerobic capacity, a widely accepted measure of physical fitness — and their white blood cells’ telomere length. In subjects 55 to 72, a higher V02max correlated closely with longer telomeres. The fitter a person was in middle age or onward, the younger their cells. There are countless unanswered questions about how and why activity affects the DNA. For instance, Dr. Werner found that his older runners had more activity in their telomerase, a cellular enzyme thought to aid in lengthening and protecting telomeres. Exercise may be affecting telomerase activity and not telomeres directly. In addition, Stephen Roth has been measuring telomeres and telomerase activity in a wide variety of tissues in mice and has found, he says, the protective effects from exercise only in some tissues. Another question is whether we must run 50 miles a week to benefit. The answer ‘‘can only be speculative at the moment,’’ Dr. Werner says, although since he jogs much less than that, he probably joins the rest of us in hoping not. Given his and his colleagues’ data, ‘‘one could speculate,’’ he concludes, ‘‘that any form of intense exercise that is regularly performed over a long period of time’’ will improve ‘‘telomere biology,’’ meaning that with enough activity, each of us could outpace the passing years. Hello Kitty, Hello Clone #8 By ANNE EISENBERG Published: May 28, 2005 Ordinarily it is hard to predict how a kitten will look when it is grown. But not for David Cheng, who plans to buy a clone of his much-loved short-haired black-and-white cat Shadow. After all, the cloning company guarantees that Shadow's successor will bear a close resemblance. Andy Manis for The New York Times Peaches, right, 9 months old, is a clone of Mango, 2 years old. Forum: Gaming Andy Manis for The New York Times Peaches and Mango's owners are Leslie Ungerer, left, feline surrogate manager for Genetic Savings and Clone, and Philip Damiani, the chief scientist. When Mr. Cheng, who works as a technology auditor for a Wall Street investment bank, discovered that Shadow had a tumor that would soon prove fatal, he had the cat's cells saved, cultured and frozen. Now, he is preparing for the next step: paying for Shadow's cloned replacement. "I'm saving up some money," he said. "It's a lot like buying a car." The financing for Shadow's successor won't be trivial. Preserving the cells, a necessary beginning for anyone interested in creating a clone, can run $300 to $1,400, not including veterinarian costs and yearly storage fees. But these expenses pale in comparison with the cost of the clone itself: at Genetic Savings and Clone, the company that stored Shadow's DNA, the price is $32,000 - reduced from the original $50,000, but still an impressive sum. Mr. Cheng said that he would pay whatever it cost - although he is waiting until the price drops a bit - because he misses his cat so. "Shadow had two really long, funny-looking teeth like sabers," he said. "Everyone loved him." The cloning and sale of pets has its critics, who call it wasteful and inhumane. Some point to shelters bursting with pets in need of homes, or remind buyers that cloning is still a relatively new process, with the health of future generations of offspring still unknown. And the $32,000 lavished on one kitten clone would certainly pay for the care of many a needy animal. But Kathy Hudson, director of the Genetics and Public Policy Center at Johns Hopkins University, said affection for lost pets was a powerful motivator. "People pay outrageous sums for unusual breeds and purebreds, and, now, clones," she said. "Some people become adoring of a particular pet, and want another one exactly like it." Mr. Cheng is one of hundreds of customers of Genetic Savings and Clone in Sausalito, Calif., who have already banked samples of pet DNA, said Ben Carlson, a company spokesman. People sign up for many reasons, sometimes because their animals have been spayed or neutered and can't be bred, or because they were the product of a unique genetic cocktail the company calls a breed of one. "We have many people whose pet is a mutt with the perfect blend of characteristics," Mr. Carlson said. "That person can't go to a breeder, but he can get what amounts to an identical twin from us." Right now, Genetic Savings is selling only cat clones, although Lou Hawthorne, the chief executive, said the company would probably produce its first cloned dog this year. So far, the company has sold two cat clones at $50,000 each, and has sent out several contracts under the new, reduced price, which it plans to lower again as the cloning process becomes more efficient. To display its work and perhaps to help demystify its science, the company is opening an 8,000-square-foot research site outside Madison, Wis. It will have plate-glass windows set into the U-shaped perimeter of a laboratory so that people can view this modern version of a maternity ward. They may also catch a glimpse of a local cat celebrity, Peaches, cloned last year from Mango, owned by Leslie Ungerer, who oversees most of the feline projects at the lab. "They are fast friends," she said of mother and clone, who spend part of their time at the lab and part at her home. Mr. Hawthorne said all clones come with a one-year health guarantee. And, "We give an absolute, money-back guarantee for physical resemblance," he said. Dog owners can hardly wait. About 200 of them have signed up at Genetic Savings to preserve their pets' DNA. Rebecca Alford, an opera singer who lives in Manhattan, has stored cells from her dog Missy, a Maltese mix, now dead. Today Ms. Alford has five dogs, including two purebreds (one Shih Tzu and one Maltese) she rescued when they were abandoned on the street. But they have not replaced Missy, she said. "I probably would have had her bred, but I did the responsible thing and had her spayed," she said. "I won't get Missy back, but it will be like getting her puppies." People who want to save their pets' DNA usually start the process with a visit to a veterinarian, who collects the tissue and mails it to Genetic Savings. Then the company cultures the cells, taking samples and growing new cells, in a process that takes about three weeks and costs about $900, said Philip Damiani, the chief scientific officer. Then the cells are frozen and stored in liquid nitrogen. After the first year, an annual $100 storage fee is charged. For a lower price, $295, customers can simply store biopsy samples, and wait until they are ready to clone to have the culturing done. Mr. Hawthorne said business had been brisk for both the stripped-down process and the more elaborate cell banking, and the procedures are almost always successful. "Most of the time, the tissue grows well in culture," he said. "The marginal situations are when someone calls and says they buried their dog three days ago." Dr. Damiani said the procedures that people would be able to see in the display laboratory were straightforward, and would show that the animals were treated well. The company receives cat reproductive tracts by contract from large spay clinics. Eggs are taken from the tracts and the DNA is removed. DNA from the animal to be cloned is placed in the egg, which is then grown into an embryo. "Once the egg is formed, we do a surgical procedure," he said, placing the embryo inside a surrogate cat mother. "The procedure is no more invasive than a typical spay." That is not the view of Crystal Miller-Spiegel, senior policy analyst at the American Anti-Vivisection Society, in Jenkintown, Pa., a Philadelphia suburb. "We are concerned about what's happening to cats in laboratories," she said. "They are harming animals for no reason." The society is a founding member of Californians Against Pet Cloning, a group that supports legislation to ban the sale of genetically modified and cloned animals in California. Indeed, ethical issues like the treatment of animals used for cloning will need to be addressed systematically, said Lori B. Gruen, an associate professor of philosophy at Wesleyan University, particularly as cloning grows more efficient and therefore less expensive, and its popularity expands. "There are legitimate ethical worries that people are expressing about the suffering of animals," she said. "But these problems can be adequately addressed with an appropriate oversight body." Such debates mean little to Mr. Cheng, who has a second cat named Nana that looks a lot like Shadow and is one reason he has not opted to clone immediately. "I have to think about the other cat; she might not like having another cat," he said of Nana, now 8 years old. "After she passes away, I may start all over again with one new Shadow and one new Nana."