Life scientists have been challenged more than ever this year not just to critically analyze data, but to better interpret those data for an increasingly critical public. Here at The Scientist, we looked for touchstone events for the life sciences in 2005. Our picks not only defined this year, but will continue to shape and test the nature of research, education, the cohesiveness of the scientific community, and the ever important public discourse. And we didn't neglect the scandals, deals, and technical achievements that have defined the business of bioscience this year (see page 18). But don't just take our word for it. If the lessons learned from Hurricane Katrina are any indication, life science is strong only for the community that supports it. Join that community online http://www.the-scientist.com to rate our choices, nominate your own, and offer your predictions as to how the biggest bioscience stories...

1. A Ruff Year for Cloning


In the Chinese zodiac, 2006 is the year of the dog. But in the cloning zodiac, 2005 belonged to Snuppy, the Afghan hound named for Seoul National University, home to the cloning powerhouse lab of Woo-Suk Hwang. With Snuppy, born on April 24 and announced in August,1 Hwang beat others – such as the kitty revivalists working at Genetic Savings and Clone – to the Holy Grail of pet cloning with a combination of brute force and technical skill. His lab overcame obstacles in canine reproductive physiology by being able to predict and manipulate the dogs' complicated estrus cycles, and performing a mind-numbing 1,095 nuclear transfers.

With that kind of efficiency, cloned dogs won't be on the market anytime soon (Savings and Clone, meanwhile, dropped the price of a copied cat to just $32,000 in February). But Snuppy wasn't Hwang et al.'s first triumph of the year. Outside of the pet clone-obsessed press, the pup's importance was arguably overshadowed by the group's derivation of patient-specific embryonic stem cells via somatic cell nuclear transfer, as reported in May.2 Such cells "are anticipated to be of great biomedical importance for studies of disease and development and to advance clinical deliberations regarding stem cell transplantation," the authors of the paper noted. The work presaged the announcement last month that Hwang would create and head the World Stem Cell Hub, based at his university and with satellites in the San Francisco area and in England.

Unfortunately, collaborators have been distancing themselves from the group ever since the University of Pittsburgh Medical Center's Gerald Schatten, who had worked closely with Hwang, broke ties with him last month. It seems Schatten now has reason to believe that the eggs used to create the world's first cloned human embryo in 2004 had been donated by a junior researcher in Hwang's lab, an ethical breach – implied coercion, the charge goes – that Schatten says Hwang lied to him about last year. Hwang has since made public statements that junior researchers had approached him about donating eggs, but that he persuaded them not to. He said he did not follow up to find out whether or not they took his advice. Meanwhile, Sung-Il Roh, chairman of the board at Mizmedi Hospital where the eggs were collected, revealed that he had paid some 20 women in late 2002 for their eggs. The purchase was not illegal at the time, but violates Hwang's donations-only policy. (Update: After this article went to press it was reported that Hwang had admitted ethical lapses and resigned from “all posts” including leading positions at the Seoul stem cell team and the World Stem Cell Hub. But he will continue to conduct research.) An E-mail sent to Schatten requesting an interview was answered by a medical center spokesperson who said Schatten had "nothing more to say about the disassociation with Professor Hwang" and was taking a "media break."

What's on tap for 2006? Hwang says he sees animal disease models and endangered species on the horizon, although he wasn't specific. Cloning researchers have worked their way through much of the Chinese zodiac – Hwang himself cloned a cow in 1999, then a pig in 2002 – but there's always the dragon. They have until 2012 to beat the cycle on that one.

2. Avian-Flu Reality Check

<p>Avian Flu Timeline</p>

Is the sky falling? Governments, scientists, and public health workers continue to prepare for what has been forecast as the largest potential pandemic since the 1918 Spanish influenza, which killed as many as 50 million people.

3. Design on Trial


The tiny rural town of Dover in south-central Pennsylvania (population 2,000) hardly seemed a likely target for international media attention until a change in the high-school science curriculum brought about a lawsuit fron II local parents. Lawyers and activits on both sides descended upon Harrisburg where the six-week trial ended early this past month. Staff members of the National Center for Science Education, a nonprofit organization that defends the teaching of evolution in public schools, were in attendance. Executive director, Eugenie C. Scott, and deputy director, Glenn Branch, offer their assessment:

"Kitzmiller v. Dover, represents the most important American creationism/evolution trial in 23 years. Its 1982 predecessor, McLean v. Arkansas, involved a law requiring "equal time" for "creation science" along with evolution. The court's decision, based on overwhelming and authoritative scientific testimony, was that because creation science was scientifically worthless and inherently religious, it was unconstitutional to teach it in the public schools. The Supreme Court concurred in 1987.

"From the legal ashes of creation science arose the phoenix of intelligent design (ID), which flew into public awareness in the late 1990s and early 2000s, as school boards and legislators began flirting with it. Flirtation resulted in marriage in Dover last year when the school board passed a policy requiring biology teachers to present ID as well as putative 'gaps/problems' in evolution, described as 'a theory ... not a fact.' Eleven local parents took the school district to court.

"Kitzmiller replays McLean, with ID substituting for creation science. Again, the scientific testimony was devastating, exposing ID's pretensions to scientific credibility as a sham cloaking a sectarian religious agenda, and the plaintiffs' legal team argued that the school board had a religious purpose in imposing the policy.

"With the recent electoral rout of the Dover school board, the defendants are unlikely to appeal if the plaintiffs prevail. Because higher courts will thus remain mute on the constitutionality of teaching ID, additional Dovers may be anticipated, until the issue finally reaches the Supreme Court. Meanwhile, savvier antievolutionists are likely to emulate the Kansas state board of education by promoting policies impugning evolution without directly requiring creationism.

"Nevertheless, such approaches may fare no better. A federal court decision in January 2005 ruled 'theory not fact' disclaimers to be unconstitutional, partly because of the connections between creationism and portrayals of evolution as 'a theory in crisis.' This case, Selman v. Cobb County, is under appeal, and its legal fate is linked to the ultimate destiny of the antievolutionist strategy."

4. Lessons from Katrina


Courtesy of Seth Pincus

Displaced Louisiana State University scientists are being housed at the Research Institute for Children at Children's Hospital, New Orleans.

A record-breaking hurricane season levied a devastating, but not wholly unpredicted, blow to the Southeastern United States. Many researchers from New Orleans found a welcoming science community around the country that donated lab space and resources. Others have begun to piece together New Orleans' small but economically important life- and health-science sector. Brain-drain is a major concern. Arthur Lustig a Tulane University molecular biologist, now working out of a lab at Northwestern University says he plans to return, but worries about, among other things, lost time from a second move. The National Institutes of Health has yet to address the impaired competitiveness of researchers in similar situations with actual funding.

Arthur Haas, chair of biochemistry and molecular biology at Louisiana State University Health Science Center says that the timetables for getting his dispersed faculty back to campus have been the hardest thing to organize, especially in light of crumbling budget. Although LSU had a pretty effective hurricane plan in place, Haas says, there were factors that simply could not be accounted for. "All plans predicated on the government getting in within 24 to 48 hours and taking over." Seth Pincus, the director of research at the LSU-affiliated Children's Hospital has begun piecing together his department, and preparing for the future. "The thought of going through it all again is sickening, but living in New Orleans requires that I seriously consider the possibility." Here's what he learned:

Family matters. Possessions don't. Everyone who had the ability to do so, sought out family following the storm. Many who lost a lifetime of treasured possessions not only survived the loss, but seemed surprisingly OK about it. As I discarded 30 years of scientific specimens cooked in the tropical heat and encased in mold, I felt a strange giddiness realizing that all the experiments I should have done, could now be put out of mind.

Planning counts, but so does providence. I made it through the hurricane and the ensuing days in safety and relative comfort, due to impeccable planning by the Children's Hospital administration. But a barge could have easily broken loose and pounded through the adjoining Mississippi levee, as one did in the Industrial Canal.

Don't depend on the government, but don't rule out their ability to help. The failure of the federal government was a major disappointment, but eventually various arms of government did come through. I have my fingers crossed regarding NIH.

Everyone needs an alternate e-mail address. Keep contact lists up-to date, and print out hardcopies. It took almost two weeks to contact the entire faculty in our Institute. It shouldn't have.

Liquid nitrogen dewars are best for emergency storage. Decisions to turn off hospital generators rarely take into account researchers' desires. Dewars can last more than a month without tending, are portable, and can be manually filled. The big ones can hold the same size storage boxes used in -80°C freezers. Plan ahead to have sufficient liquid nitrogen on hand to fill tanks when needed.

Back up your files. Even if infrastructure holds, it will take longer than you think to access critical files from off site. Meanwhile, you can fit 80 gigabytes on a drive the size an iPod. In the end, we FedEx'd these tiny drives to our scientists.

5. Investing in Human Variation


Large-scale public-private collaboration continues to play a major role in life sciences. Influential scientists are pursuing plans to develop a Human Cancer Genome Project along the same lines as the Human Genome Project. The price tag has been estimated at $1.5 billion in the next 10 years. And just as these plans are ramping up, we've seen plans fulfilled for the last great push in variability investigation. The $135 million International HapMap Project announced the completion of Phase I this year. David R. Bentley, former head of Human Genetics at Wellcome Trust Sanger Institute recently joined genetic-analysis technology company, Solexa, as chief scientist. Here's his take on the next step in understanding human variation:

"Just as the Human Genome Project began to provide the first answers to the question, 'What makes us human?' the International Haplotype Mapping Project provides the first real answer to the question, 'How similar are we to each other?'

"The first phase of the Haplotype Map (HapMap) is now complete, with more than one million SNPs analysed in 269 people – members of the general public from distinct parts of the world who volunteered to give a sample of their DNA for this type of work. The HapMap team developed ways to look at the emerging patterns of common variation. Naturally enough, each individual is genetically different; but the similarity between us all is equally striking, and lends credence to the claim that the freely accessible tools from HapMap are likely to benefit medical research more or less worldwide. The information from HapMap, which includes SNPs, haplotypes, patterns of variation in populations, and practical and ethical guidelines on their use, will enable researchers to carry out association studies with comprehensive marker sets to search for common variants that contribute to common disease. The HapMap has also revealed much more than this. A new high-resolution picture of recombination has been derived from the data, showing hotspots in abundance. Early hints at signatures of natural selection have emerged, and it is clear that the HapMap sheds some light on the forces that drive evolution and the present-day patterns of variation in our genomes.

"So what is still missing? To nail the causal variant, you need the sequence of a number of individuals – whether the sequence of a gene, or a region, or the whole genome – to be sure that you are seeing the whole picture. There is no substitute for complete sequence, but for now, the HapMap has not only given us something tangible to work with, but an all-important glimpse of what the future might look like."

Compiled by Ishani Ganguli, Brendan A. Maher, and Ivan Oransky

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