News this Week

Science  17 Jan 2014:
Vol. 343, Issue 6168, pp. 234
  1. Around the World

    1 - Milan, Italy
    Italian Animal Rights Fliers Get Personal
    2 - Tokyo
    Allegations Mar Alzheimer's Study
    3 - London
    Public Encouraged to Share Medical Data

    Milan, Italy

    Italian Animal Rights Fliers Get Personal

    Attacked.

    One animal rights flier reads, "call this executioner and tell him what you think of him."

    CREDIT: A FAVORE DELLA SPERIMENTAZIONE ANIMALE

    An anonymous group against animal experimentation shocked the Italian research community last week by posting leaflets that show photos, home addresses, and telephone numbers of scientists involved in animal research at the University of Milan and labeling them "murderers." The posters targeted physiologist Edgardo D'Angelo, parasitologist Claudio Genchi, pharmacologist Alberto Corsini, and biologist Maura Francolini.

    Although the fliers didn't contain a specific call to violence, Italian scientists say the implicit threat is unmistakable. "It's unacceptable that those who work for the good of science and public health are called murderers by someone who publicly incites violence against them," says Dario Padovan, president of Pro-Test Italia, an organization that seeks to defend and explain animal research. Many politicians, including Maria Chiara Carrozza, Italy's minister of education, universities and research, also condemned the tactic. The University of Milan has filed a complaint and the city's police department has started an investigation.

    Animal research has recently generated intense debate in Italy; a bill to drastically limit animal testing is expected to be approved soon, over scientists' protests. http://scim.ag/_fliers

    Tokyo

    Allegations Mar Alzheimer's Study

    A $31 million Japanese study looking for early signs of Alzheimer's disease is plagued by falsified data and other problems, according to an article published last week by one of the country's most respected newspapers. Based on an interview with one of the researchers and a review of project documents, the Asahi Shimbun alleges that scientists behind the ongoing Japanese Alzheimer's Disease Neuroimaging Initiative manipulated details of some memory tests after they were completed and included patients that were probably too ill for meaningful study.

    Japan's Ministry of Health plans to investigate the allegations; an official says the scope and timing of the investigation are still being determined. The study involves 38 medical institutions and has received funding from the health ministry, the education ministry, and a consortium of 11 pharmaceutical firms.

    London

    Public Encouraged to Share Medical Data

    U.K. medical research charities last week launched a colorful advertisement campaign in the national press, urging residents to allow scientists to access patient data from the country's National Health Service (NHS). The records in NHS—which is free for all and paid for through taxation—are now held by a patient's general practitioner. But in a few months, doctors will begin sending that data to a central NHS database known as care.data, where it will be made available, anonymously, to researchers and possibly also to drug companies. Some physicians have criticized the database for intruding on the trust between doctor and patient, while civil liberties groups worry that the anonymity of the data cannot be guaranteed.

    This month, the government will send a leaflet to all 22 million U.K. households explaining the data-sharing and telling people how to opt out. But the charities behind the new ads, including Arthritis Research UK, Cancer Research UK, Diabetes UK, the British Heart Foundation, and the Wellcome Trust, are hoping that not too many will take that option. http://scim.ag/_share

  2. Random Sample

    ScienceLIVE

    Join us on Thursday, 23 January, at 3 p.m. EST for a live chat with experts on a hot topic in science. http://scim.ag/science-live

    They Said It

    "[T]he chances of being successful just by sprinkling something on your food, rubbing cream on your thighs, or using a supplement are slim to none. The science just isn't there."

    —Jessica Rich, director of the Federal Trade Commission's Bureau of Consumer Protection, in a statement last week after charging four companies with deceptively marketing weight-loss products.

    Noted

    CREDIT: NASA

    NASA's request to keep the International Space Station alive for an additional 4 years beyond 2020 was approved last week by the White House. The 15-year-old station, operated by a partnership of 14 nations including Canada, Russia, and Japan, was originally set to be decommissioned in 2016. It's unclear whether the partner countries will join the United States in funding it through 2024.

    The Unlikely Link Between Federer and Marsupials

    CREDIT: © ERIC AND DAVID HOSKING/CORBIS; ROB GRIFFITH/AP PHOTO

    Robbie Wilson, a performance biologist at the University of Queensland in Australia, thinks we're too obsessed with record-setting feats. Although it is tempting to focus on just how fast an animal can run, or how high it can jump, such "peak" performances can obscure a more important ecological issue: the trade-offs that shape an organism's optimal performance. Gathering the data needed to quantify optimal performance in nature is difficult, however, so Wilson's team turned to a more easily observed ecosystem: the 2013 Australian Open Tennis Championship. (This year's tourney began on 13 January.) They analyzed some 13,000 serves to find the optimal strategy for winning a point. For most players, accuracy dropped off sharply as speed increased, so players who delivered first serves at about 90% of their peak speed, and second serves at 75%, tended to maximize points, he reported last week at the annual meeting of the Society for Integrative and Comparative Biology in Austin.

    Now, Wilson and his colleagues are trying to apply such concepts to performance trade-offs among quolls, endangered carnivorous marsupials. By analyzing how the creatures run and turn, for instance, they're hoping to tease out how certain human activities, such as mining, might be influencing their fitness. But Frank Fish, a biomechanicist at West Chester University in Pennsylvania, says there are limits to what tennis can teach us about wild creatures. Tennis players get a second serve should they miss the first one, Fish notes, but "there's no do-over" in nature.

  3. Newsmakers

    Agency Veteran Tapped to Head USGS

    Kimball

    CREDIT: USGS

    President Barack Obama has nominated coastal geologist Suzette Kimball, the acting head of the U.S. Geological Survey (USGS), to become the $1 billion agency's permanent director. If confirmed by the Senate, Kimball would be "the first director in 20 years to come from within" the agency, notes Charles "Chip" Groat, who led USGS from 1998 to 2005. She's an "excellent choice," adds Mark Myers, USGS director from 2006 to 2009. "She is a skilled scientist, very good communicator and talented manager."

    Kimball joined the agency in 1998 after stints with the National Park Service, the College of William & Mary in Virginia, and the U.S. Army Corps of Engineers. She earned a Ph.D. in the environmental sciences from the University of Virginia in Charlottesville, specializing in the processes that shape coastal zones. Kimball would succeed Marcia McNutt, who resigned in February 2013 and is now editor of Science. http://scim.ag/_Kimball

  4. Gut Instinct

    1. Jop de Vrieze

    Do bacteria in the guts of African hunter-gatherers hold the key to a healthier life? An American anthropologist plans to find out.

    CREDIT: COURTESY OF JEFF LEACH

    MANG'OLA, TANZANIA—Jeff Leach hasn't showered in a month. Living in a small dome tent close to Lake Eyasi in northern Tanzania, he stopped washing one day because he wants to know how that will change the microbial populations in and on his body. Leach is taking daily samples of his own stool and skin, which he carefully stores in a liquid nitrogen tank until they can be shipped to the United States.

    Later this month, the 46-year-old graduate student at the London School of Hygiene & Tropical Medicine (LSHTM) will also adopt the lifestyle of the local people here. He will sleep in their open grass huts, eat their food, and share their tools, to see if his gut flora become more like theirs.

    Leach, who obtained a Ph.D. in anthropology in 2005, is studying the Hadza, one of the last true African hunter-gatherer communities, because he thinks their gut microbes may hold clues to improving human health worldwide. The Hadza's lifestyle is thought to resemble that of early humans; they also seem to suffer far less from "modern" diseases, such as diabetes, cancer, and cardiovascular problems.

    Leach believes there is a connection. An increasing body of evidence has shown that gut microbes regulate their hosts' immune systems and assist them by eliminating dangerous bacteria, and several studies have linked changes in microbial populations to specific illnesses. The Hadza's close contact with the vast diversity of microbes in soil, water, and wild food may somehow help protect them, he says—and he plans to spend two full years living here to sample microbial diversity in the people and their environment. His own experiment in Hadza living, which will last a month, will test whether the microbial ecology of a Texan apartment dweller can shift to that of an African hunter-gatherer.

    Some scientists are skeptical of the premise. They don't believe our ancestors had such healthy lifestyles or that modern-day Hadza are models of health—and even if they are, their gut microbes may have little to do with it. But many agree that the Hadza project will offer new insights into the complex relationship between humans and their microbiota and that Leach's roots in anthropology make him the right man for this study. "With his unique background and perspective, Jeff sheds light on questions that I have been thinking of, but haven't had an avenue to pursue," says Justin Sonnenburg of Stanford University in Palo Alto, California, one of many microbiologists who will study his samples.

    Sterile environment

    Leach's motivation is highly personal. Eleven years ago, at age 2, his daughter was diagnosed with type 1 diabetes. After digging through the literature and contacting leading scientists, Leach came to the conclusion that, in addition to a genetic predisposition, a lack of contact with bacteria caused her disease. Leach's daughter was delivered through a cesarean section, which prevented her from being exposed to the maternal bacteria that most babies encounter in the birth canal. She was breast-fed for a few months instead of the 2 years or more seen in traditional societies, and grew up in a rather sterile suburban U.S. home dominated by antimicrobial soaps and chlorine-wiped tables.

    This led to an imbalance in her gut microbiota, Leach says, which caused the gut to become inflamed and leaky; that allowed bacterial products to enter the bloodstream and inflame insulin-producing cells in the pancreas, which were then attacked and destroyed by immune cells. (Several recent studies support this hypothesis.) "Realizing there was a causal relationship between my daughter's health and the environment my ex-wife and I had created made me feel guilty and angry," he says.

    It motivated him to drop his studies of ancient cooking techniques and focus on a crucial question: How can we rebalance our microbiota to improve health? In 2011, Leach enrolled at LSHTM to obtain a master's and a Ph.D. in microbiology; a year later, he co-founded the American Gut project, which maps the gut microbiota of thousands of people in the United States.

    His Tanzania study is the first to compare lifestyle and microbiota in pure hunter-gatherers with those of Westerners. Previous studies have looked at rural and traditional people in Burkina Faso and Malawi and at several Amerindian communities, but the subjects all practiced agriculture or ate farm products. The Hadza don't have cattle and don't grow crops; their diet varies seasonally and consists of fresh game, baobab fruits, berries, tubers, and honey.

    On a sweltering day in late October, Leach drives his Land Cruiser through arid terrain dominated by baobab, acacia trees, and small bushes, on his way to a settlement called Kipamba. The day before, he had provided about 40 villagers with plastic tubes and, with the help of his local translator, instructed them how to collect about a tablespoon of their stool in the morning. At our arrival, a young English-speaking boy leads us to a place close to the village where the subjects have gathered.

    Ready to ship.

    Leach collects fecal samples from the Hadza and has them studied at U.S. labs.

    CREDIT: JEFF LEACH

    Leach sets up a table and three chairs, a scale, and a measuring stick. One by one, the men, women, and children hand in their tubes. Leach swabs their right hand for a skin sample, and two local assistants fill out a short diet questionnaire for each subject and measure basic body characteristics such as height and weight. Then Leach takes a series of samples from the environment: drinking water, tubers, animal stool, honeycombs, and fresh meat.

    On our arrival, the boy had warned us not to go into the village. "A group of men has been drinking since dawn," he said. The warning reflects a reality in the 21st century Hadza community: Not all its members are exclusive hunter-gatherers anymore. Some 200 Hadza—mostly those living higher up in the hills—practice the "pure" lifestyle most consistently, Leach says. The 900 or so people living closer to the nearest town, Mang'ola, are leading more Western lives; many have cell phones and regularly consume maize and alcohol. Sodas and snacks are for sale in town.

    Sweet tooth.

    The Hadza, a hunter-gatherer community in northern Tanzania, often gorge on honey in the wet season.

    CREDIT: JEFF LEACH

    Leach sees this as an opportunity rather than a problem. By sampling subgroups, he hopes to see reflections of the transitions our ancestors went through, from hunter-gatherer communities to basic agriculture and small-scale farming, and eventually to high-sugar, high-fat Western diets and life in a built environment. The Hadza, who have been studied extensively by Western scientists for more than a century, are happy to help Leach, whom they call Dr. Mavi, which is Swahili for Dr. Shit.

    Like other scientists before him, Leach is aware that he's bringing change to the very lifestyle he's studying. The Hadza seek benefits from their participation, such as knives, clothes, and, increasingly, money. Leach refuses to pay them directly but makes contributions to community funds for emergency care and education.

    That night, as he sits by a fire at his camp and sips cheap scotch from a coffee mug, Leach talks incessantly about the Hadza's eating habits. Their average daily fiber intake is 75 to 100 grams, seven times the U.S. average, mostly from pulp and seeds of baobab fruits. Gut microbes turn these fibers into short-chain fatty acids that nurture intestinal cells and increase the acidity of the colon, he says, which has been shown to thwart opportunistic pathogens. He describes how the Hadza occasionally gorge on meat from a fresh kill, and the huge amounts of honey they eat when it's plentiful during the wet months of February, March, and April. "From a registered nutritionist perspective, the diet makes no sense," Leach says. "Yet it does not seem to harm them at all."

    Dying from other causes

    Underlying Leach's research is the assumption that, in their lifestyle and diet, these modern-day hunter-gatherers are as close to humanity's ancestors as we can hope to get and that they may be healthier because of the way they live. Modern-day humans, in this view, have strayed far from these ancient eating habits and microbes, and our bodies haven't had the time to adapt.

    Not everyone accepts this picture. Humans haven't stopped evolving since they took up agriculture and settled down some 9000 years ago, says evolutionary biologist Marlene Zuk, the author of the 2013 book Paleofantasy, a sharp attack on the idea that we should emulate our forefathers. European farmers, for instance, evolved lactose tolerance, enabling them to digest cow milk.

    Yale University anthropologist Brian Wood, who has studied Hadza health and demography, is also skeptical that the Hadza enjoy rude health. "It seems like they have less cancer and cardiovascular disease than we do, but we do not have good data to evaluate the actual incidence," he says. In any case, he notes, accidents, malaria, tuberculosis, and other diseases limit the Hadza's life expectancy at birth to only 34 years, too short for cancer and heart disease to be significant killers. If the Hadza really are healthier than, say, the average German or American, Wood says there's an explanation that has little to do with microbes: His own research has shown that they eat far fewer calories and are much leaner than Westerners.

    Meat and microbes.

    After killing a kudu, Hadza hunters eat raw meat and rub the content of the animal's stomach—including billions of bacteria—on their arms.

    CREDITS: JEFF LEACH

    As a result, says anthropologist Herman Pontzer of the City University of New York's Hunter College, the Hadza lifestyle can't be translated into health recommendations. Leach agrees, but says the research can still tell us a lot about the interaction between humans and microbes before the modern era. "We do not regard the Hadza as a disease-free society," he says. What he's most interested in, he says, is "their microbes, their origin, and their interaction with the body. How do these people assemble their microbiota?"

    The real payoff of Leach's research, Pontzer says, could be to show how ancient habits affected the microbiome. "Seasonality in diet and lifestyle is a universal thing that modern societies dropped," Pontzer says. "The high fiber consumption is likely to have been universal, too. The same for the intimate relationship with environmental microbes."

    Dream team

    The next day, during a visit to another Hadza community, Leach points at a man who is sharpening his arrows for a hunt. "He's the perfect guy for our study," he says. "Born vaginally, breast-fed for 2.5 years, has not had malaria or any Western medication, has never been to town. His shit will probably end up in a germ-free mouse."

    Leach is referring to the fate of his samples: Sonnenburg and his colleagues will infuse stool from Hadza people into the guts of mice that have been born in a sterile environment, allowing the researchers to test the effects of specific microbial communities. They will compare the animals' physiology and metabolism with those of mice colonized by the microbes in Western poop.

    Leach says he's "not a lab rat"; he relies on what Sonnenburg calls a "dream team" of collaborators to carry out most of the analyses. Labs in Colorado and Chicago will do basic taxonomical and functional analyses. Rob Knight at the University of Colorado, Boulder, and Jose Clemente of Mount Sinai Hospital in New York City will compare the Hadza data with American groups, including people following paleo diets, also known as "caveman diets." Other researchers will use germ-free mice to test the hypothesis that gut microbes help Hadza women, normally quite skinny, put on fat during pregnancy.

    The comparison between pure hunter-gatherers and more westernized Hadza will be done by Maria Dominguez-Bello of New York University in New York City, who also wants to compare the Hadza with Amerindians in South America, who have a far more diverse gut flora than U.S. residents. Traditional Africans should have the highest microbial diversity of all, she says, because other populations probably lost species as they went through evolutionary bottlenecks. "I am interested in the disappearance of these microbes," she says. "Have we lost functions?"

    Scientists think that people in modern societies have so little exposure to microbes in the environment that their diets largely determine the composition of their gut microbiota. But in the Hadza, exposure to a daily microbial bombardment from the environment may override any impact of the food, Leach hypothesizes—and he hopes to test that. "Hadza men eat more meat and less plant foods than women," he says. "If their microbiota turn out to be similar, the environment is the great equalizer."

    Just how intense that exposure can be becomes clear the next day, when Leach receives news that Hadza hunters have killed a huge female kudu, a great antelope, with their poison arrows. One of the men slits the animal's throat. Then they cut open its belly, blood spilling everywhere. The men take out the stomach and intestines and hang them in a nearby tree. They cut out the ribs and chew on the raw flesh. Leach starts taking swabs of the men's hands and their prey.

    Next, the men take the stomach, cut it open, and start rubbing its content all over their arms to wash off the sticky blood. As they do so, Leach explains, the hunters are transferring billions of bacteria to their skin. They cut the stomach in pieces and eat it; then they squeeze the green, fibrous content from the intestines, another rich source of microbes, and eat them, too, still screaming with excitement. The rest of the meat is stripped from the carcass and given to men arriving from other villages.

    Tonight, men and women in several Hadza camps will be eating meat. As they hand each other the pieces, they will be passing on many strains of microbes as well—just as they swap bacteria from honeycombs, tubers, berries, and drinking water. This "social network of humans and their microbes," as he calls it, may be the most important thing missing from Westerners' disinfected lives, Leach says—and it's the one thing he failed to provide for his daughter.

  5. The Second Act

    1. Dennis Normile*

    After his first turn on the world stage ended in scandal, Woo Suk Hwang has quietly rebuilt his scientific career.

    Back to work.

    Barred from handling human tissue, Woo Suk Hwang concentrates on animal cloning.

    CREDIT: DENNIS NORMILE

    SEOUL—Watching a pair of German shepherd puppies frolic on the lawn of a research institute, Chang Hyun Choi likes what he sees. Few puppies from breeders have the temperament and trainability required in a police dog, says Choi, an officer with the police canine unit in the city of Busan. The look-alike pups scampering about may well have the right stuff to sniff for bombs and track down missing people: They are clones of one of the country's top police dogs. With clones, Choi says, "there is less chance of rejection" during training. Before driving off, Choi and a couple of colleagues pose for a photo with the puppies, and with the man who oversaw the cloning: Woo Suk Hwang.

    Eight years after Seoul National University (SNU) dismissed him for his central role in one of history's most notorious scientific frauds, Hwang, 61, is in a position many researchers would envy. He heads Sooam Biotech Research Foundation, a nonprofit institute with a staff of 40, a $4 million annual budget, and a new, well-equipped six-story building. His team publishes a steady stream of papers. Devoted dog owners from around the world, as well as the Korean police, seek their services. The institute is applying its cloning know-how to rescuing endangered species and improving livestock breeds, as well as to fundamental research in developmental biology. And Hwang reportedly hopes to someday resume work with human embryonic stem cells.

    Some say that the disgraced icon of science in South Korea has come far on the road to rehabilitation. "For animal cloning, his team is one of the best in the world," says Yang Huanming, chair of the Chinese sequencing powerhouse BGI-Shenzhen. Eventually, Yang predicts, Hwang "will regain respect from the scientific community."

    Others are not so sure. "I highly doubt that Hwang will gain respect in the scientific community at large, even with his ongoing successes in animal cloning," says Insoo Hyun, a bioethicist at Case Western Reserve University in Cleveland, Ohio, who once advised Hwang. "[Hwang's] scientific fraud was simply too great."

    Meteoric rise and fall

    At the start of 2004, Hwang was toiling in obscurity in South Korea, engaged in routine livestock cloning. Then on 12 February, in a paper published online in Science, Hwang's team claimed it had created stem cells from a cloned human blastocyst (Science, 13 February 2004, p. 937). From out of nowhere, the group had leapt ahead of dozens of labs worldwide seeking to generate stem cells genetically matched to individual patients; such cells, researchers hoped, would evade immune rejection and be used someday to treat or cure diseases like diabetes and Parkinson's. Hwang's team took another apparent step toward this goal with a second Science paper, published online on 19 May 2005, describing the creation of 11 embryonic stem cell lines using genetic material from patients suffering spinal cord injuries, a genetic immune deficiency, and diabetes. And in August, the team unveiled in Nature the f irst cloned dog, an Afghan hound named Snuppy.

    Better days.

    Hwang and Snuppy in 2005. The world's first dog clone was his only achievement of that era to withstand scrutiny.

    CREDIT: AP

    In 18 months, the once-anonymous veterinarian had become a superstar. Colleagues described his findings as "a breakthrough" and "spectacular." Time magazine named Snuppy 2005's "Most Amazing Invention." In South Korea, Hwang became a national hero. The government proclaimed him the country's top scientist and launched a generously funded World Stem Cell Hub just for him. It issued a postage stamp featuring the expected fruits of Hwang's research: a silhouetted figure rising from a wheelchair and leaping, with the caption referring to embryonic stem cells. Hundreds of women volunteered to donate eggs for his use.

    As fast as he shot to fame, Hwang's career began to unravel. A May 2004 news report in Nature claimed that one of Hwang's Ph.D. students had said she and another member of the group donated their own eggs for Hwang's research, a dubious practice that ethicists feel could reflect lab heads pressuring junior researchers. For more than a year, Hwang denied he'd used their eggs, until a Korean TV broadcast in November 2005 showcased hard evidence from a whistleblower on Hwang's team. In the days that followed, Korean bloggers started pointing to duplicated images and questionable data in Hwang's papers. That drew an SNU investigation; on 29 December, the university's panel reported that none of the 11 embryonic stem cell lines described in the second Science paper ever existed.

    In their final report on 10 January 2006, the investigators cast doubt on the first Science paper as well, stating that the human stem cell line was probably not derived from a cloned blastocyst but rather from an unfertilized oocyte that started developing into an embryo, a phenomenon known as parthenogenesis. The panel concluded that virtually all the images and data in the two papers had been fabricated. Hwang's sole legitimate achievement was Snuppy: The panel confirmed that the dog really was a clone.

    Hwang did not challenge the SNU panel's findings. During a 12 January news conference broadcast on national TV, he tearfully admitted that both Science papers were bogus and pointed the finger at junior researchers, who he claimed had deceived him. Science retracted both papers in a notice posted online on 12 January.

    SNU dismissed Hwang in March 2006. In October 2009, a South Korean court found him guilty of embezzling research funds and of illegally buying human eggs. Completing his downfall, an appeals court upheld the conviction in December 2010 and sentenced him to 18 months in prison. The sentence was suspended for 2 years, and he did not serve any jail time.

    Starting over

    As the disgraced researcher faded from view, a small band of supporters rallied to his cause. "I thought there was going to be no chance of helping disabled people and many other patients if we lost him from the scientific community," says Byung Soo Park, a Korean electronics industry businessman and philanthropist who chairs the Sooam Foundation, which is separate from the research foundation and provides scholarships for Korean students. Park had known Hwang before he became famous. In 2000, on a mission to war-ravaged East Timor that Park organized, Hwang offered advice on improving cattle breeds and later hosted East Timorese scholars for training at SNU. "I was deeply touched and inspired by his effort and commitment," Park says.

    With the ax about to fall on Hwang at SNU, Park raised $3.5 million and in July 2006 helped launch the Sooam Biotech Research Foundation to allow Hwang to continue his research activities. Many members of his group remained loyal to Hwang, a charismatic figure who inspired staff members through his long hours in the lab and dedication. "I believed that the team could prove it had the cloning technology" described in the Science papers, says Yeon Woo Jeong, a veterinarian who was among a couple dozen members of Hwang's SNU lab to decamp to the fledgling institute.

    At Sooam, barred by the government from working with human eggs and stem cells, Hwang returned to his roots in cloning livestock. But he soon had a chance to build on his one real accomplishment. After the birth in 1996 of the first cloned mammal, Dolly the sheep, U.S. billionaire John Sperling had bankrolled a venture to clone dogs—specifically Missy, a collie-husky mix owned by his friend Joan Hawthorne and her son Lou (Science, 4 September 1998, p. 1443). The Missyplicity Project and related pet cloning efforts ended up producing several cat clones, but no dogs.

    In cloning Snuppy, Hwang's SNU group showed that it had mastered the complexities of dog cloning. Doing so requires synchronizing the reproductive cycles of egg donors and surrogate mothers, harvesting eggs at the right moment, and figuring out where in the reproductive tract to insert cloned oocytes—riddles that had all proved trickier to crack in dogs than in other cloned species. In early 2007, the Missyplicity Project sent Sooam tissue from Missy, who had died in 2002. Sooam promptly succeeded in cloning her. "The first surrogate got pregnant" and produced a pup that December, says In Sung Hwang, a Sooam researcher not related to Woo Suk Hwang.

    Fresh off that success, Lou Hawthorne started marketing dog cloning services through BioArts International, a business venture he set up to invest in biotechnology, with Sooam doing the cloning. BioArts gave up on dog cloning in 2009, citing the tiny market, the unpredictable results of cloning, and other issues. But determined pet lovers continued to find their way to Sooam.

    In 5 years, the institute has cloned about 200 pet dogs, charging $100,000 each time they are successful. (To prove that the puppies are genetic copies, the institute says it has an outside lab perform a genetic analysis on the original dog and the clone.) Sooam has also cloned another 200 or so dogs for the police, to preserve rare or valuable breeds, and for research purposes. While producing Snuppy required more than a thousand embryos and 123 surrogates, Sooam now typically needs only three surrogates, each of which gets three embryos, according to In Sung Hwang.

    Mass production

    In a clean room at Sooam, Kyung Hee Ko, a technician from Hwang's SNU days, peers through a microscope, wielding manipulators that control needles and probes. With metronomic constancy, she positions a bovine oocyte, sucks out the nucleus, replaces it with a somatic—or mature—cell from the target cow, and then positions the next oocyte. It's essentially the same somatic cell nuclear transfer technique used to create Dolly.

    Woo Suk Hwang declined to be interviewed for this article. But in the surgery down the hall, there he is in blue scrubs and a white mask, slicing into the belly of an anesthetized dog and inserting a clutch of cloned oocytes into her oviduct. The dog is sewn up and wheeled out; in all, the procedure takes less than 10 minutes. Then, in quick succession, two pregnant dogs are wheeled in and Hwang performs cesarean deliveries of cloned puppies.

    Recipe for a clone.

    Dog eggs must be harvested after they enter the oviduct, rather than taken from ovaries, as is done with livestock. Cloned oocytes must be implanted quickly into surrogates, rather than allowed to mature into blastocysts in culture before implantation.

    CREDIT: G. GRULLÓN/SCIENCE

    Sooam had never advertised its dog cloning service. But as a first foray into marketing, last year it launched a contest in which pet owners described on the United Kingdom's Channel 4 why they believe their dogs deserve to be cloned. The winner of a cloned pet will be announced on TV later this year.

    One objective of the contest is to "figure out what the public thinks about cloning," In Sung Hwang says. Some researchers are critical. Robin Lovell-Badge, a developmental geneticist at the MRC National Institute for Medical Research in London, points out that the cloning process in general is inefficient, that clones may not be identical physically to the original because of developmental factors, and that many cloned pups die as embryos or soon after birth. Surrogates, meanwhile, bear the hardships of pregnancy and losing embryos and newborns. "Is the outcome worth it?" Lovell-Badge asks.

    In Sung Hwang responds that Lovell-Badge's impressions of dog cloning are out of date. Experience acquired through cloning hundreds of animals and continual tweaking of the process has dramatically improved efficiency and reduced the number of clones with birth defects, he says. But he agrees that the issue of whether it is right to impregnate surrogates for the benefit of human pet owners "is a moral question that should be answered through discussion."

    The Korean police need no more convincing. They point to a case that began in March 2007, when a 9-year-old girl went missing on Jeju Island. After a futile monthlong search, the Jeju police put their best bomb-sniffing dog, Quinn, through a crash course on searching for human remains. Less than an hour after being put on the job, Quinn found the girl's body in a barn near her home, leading to the arrest of her murderer. The Korean police do not allow working dogs to mate. Hoping nevertheless to propagate Quinn's talents, Jeju's police chief in 2009 asked Sooam to clone the champ. All five clones completed training and were put into service. Three were sent to Incheon, where they work in security at the airport, and two went to Jeju, where one died of a congenital heart defect. The other is healthy and "doing pretty well" working alongside Quinn, says Yong Shik Choi, a Jeju police department dog trainer.

    While about one in three puppies from breeders complete police training and enter service, 90% or more of cloned puppies make the grade, claims Yongsuk Cho, Sooam's chief administrator, pointing to data released last May by the Rural Development Administration. Sooam provided more than 30 cloned dogs to police departments last year.

    Working on dogs is allowing Sooam researchers to tackle fundamental questions in developmental biology. For example, apparently female puppies born occasionally when cloning a male dog could yield clues to why sexual development sometimes goes awry in human embryos. Sooam molecular biologist Kyu-Chan Hwang (unrelated to the other Hwangs in this story) says the team has determined that the gene on the Y chromosome that controls testes development is sometimes blocked by methylation in cloned canine embryos. He hopes further work in dogs might lead to a better understanding of Swyer syndrome, a rare condition in which a person with a Y chromosome has female genitalia—though no ovaries.

    Hwang's team also clones prize livestock and uses the technique to generate transgenic cows that produce human drugs in their milk and transgenic pigs for xenotransplantation of organs into humans. Such work accounts for most of the 45 or so papers Hwang's team has published since 2006, including in respected journals such as PLOS ONE. These applied efforts also attract government grants—from Gyeonggi province, the city of Seoul, and the Rural Development Administration of Korea—which cover about 80% of the institute's annual budget.

    To the rescue

    Hwang's team is trying to extend their cloning know-how to endangered and extinct species. The scheme for both involves obtaining DNA for the species to be cloned and inserting it into the egg of a closely related living species to create an embryo that can be implanted into a surrogate. Interspecies somatic cell nuclear transfer has worked in seven species to date, including the Boer goat, a wild sheep known as a mouflon, two species of wild cats, and a gaur, an endangered wild ox native to Southeast Asia, according to a paper that appeared online on 13 September in Cellular Reprogramming. Hwang had a hand in creating the remaining two beasts in this menagerie—a gray wolf, reported in Cloning and Stem Cells in 2007, and coyotes, described online in Reproduction, Fertility and Development in December 2012. (Coyotes are not endangered, but Sooam wanted to develop expertise in interspecies cloning.) The team is now working on the endangered Lycaon pictus, or African wild dog. In a near miss, a Lycaon fetus in a surrogate dog mother died 2 weeks shy of expected delivery.

    A more quixotic quest may be Sooam's project to revive the woolly mammoth. The team hopes to produce a clone using DNA from frozen mammoth remains and the eggs and womb of an elephant. Working with North-Eastern Federal University in Yakutsk in Russia, Sooam has sponsored two expeditions to hunt for mammoth remains preserved for thousands of years in Siberian permafrost.

    "Cloning the woolly mammoth using the approach envisaged by the Sooam team is with all certainty never going to work," says Love Dalén, a paleogeneticist at the Swedish Museum of Natural History in Stockholm. Even in the best preserved mammoth samples, he says, "the nuclear genome is fragmented into some 50 million pieces. There is simply no way such a fragmented genome would be viable if transferred into an elephant cell." Sooam's In Sung Hwang acknowledges that the project is "a long shot."

    Reporting for duty.

    Korean police officer Chang Hyun Choi says clones like this one make good police dogs.

    CREDIT: DENNIS NORMILE

    The chance to work on everything from dog cloning to mammoth resurrection has attracted a cadre of young researchers willing to ignore Hwang's past. "Of course, there was a little bit of hesitation" about joining Sooam, says In Sung Hwang, who started at the institute in February 2010 after earning a master's in biomedicine at Duke University. However, he says, "I could see potential in what was being done here." Hanna Heejin Song, who studied veterinary science in Hungary and joined Sooam in 2012, had no qualms. "In Korea [animal cloning] really happens, and it's really good, so why not be in my own country?" she asks.

    Resurrection team.

    Hoping to clone a woolly mammoth, Hwang (second from left) and colleagues have ventured twice to northern Siberia in search of well-preserved remains of the extinct beast.

    CREDIT: SOOAM BIOTECH RESEARCH FOUNDATION

    Established scientists are more skeptical. "Hwang's rehabilitation faces an uphill climb," says George Daley, a stem cell researcher at Harvard Medical School in Boston and Boston Children's Hospital. Hwang's fraudulent papers, he says, "were a setback to the field at a time when human embryonic stem cell research was vulnerable and under attack from political opponents here in the U.S." Nonetheless, Daley is sympathetic. "We are all flawed and imperfect, and I believe everyone deserves a chance at redemption," he says.

    Jeong-Sun Seo, a geneticist at SNU's College of Medicine, sees little chance that Hwang can achieve his ultimate goal: working on human cloning again. Many in the Korean scientific community oppose allowing Hwang to resume work with human material because of his past ethical lapses and his use of massive numbers of eggs to get a few viable embryos, Seo says. This approach may be acceptable in animals, he adds, but it would be problematic if applied to humans.

    The Korean health ministry has turned down two applications from Sooam to work on human stem cells. And Sooam's Jeong notes that any in-depth stem cell research would require collaborations with hospitals, physicians, and biomedical researchers that will be difficult to forge. "There are a lot of limitations on what we can do," says Jeong, who blames "prejudice" against Sooam because of Hwang's past.

    According to In Sung Hwang, Woo Suk Hwang "still has dreams about [human embryonic] stem cell research." Woo Suk Hwang has risen further from his disgrace than many predicted, but those dreams are unlikely to come true.

    • * With reporting by Mi-Young Ahn.

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