Animal models are useful for testing and developing future treatments and procedures before they are tried in humans. Before bone marrow transplants were first tried clinically in the 1950’s for the treatment of radiation poisoning or leukemia, they had already been shown to work in rats, dogs, and primates. But even after the proven success of the method to replenish a patient’s hematopoietic stem cells - the precursors of all the different types of blood cells - animal models continued to be useful for improving the procedure and better understanding the system’s biology. Now, more than 50 years after those first experiments, a new animal model for transplanting marrow has been developed - under water.

Zebrafish, the tiny, striped fish often found in pet stores, lead a double life as scientific heroes. Because of their fast reproductive cycle, translucent embryos (seen above), and well-studied genome, zebrafish are an increasingly popular animal model for scientists to study embryonic development, genetics, and diseases such as cancer. The ability to easily mutate zebrafish genes and screen for interesting biological changes makes the species an ideal fit for studying the function of hematopoietic stem cells and how they can be better used in medical procedures. But there was only one problem for a team of researchers at the Harvard Stem Cell Institute: nobody had tried to do a marrow transplant in zebrafish before.

“We wanted to be able to have an assay where you could compare mutant marrow with wild type marrow and see whether the hematopoietic stem cells function differently,” said Jill de Jong, member of the Harvard research team and now assistant professor of pediatrics at the University of Chicago Medical Center. “The only way to do that was with a transplant assay. Since you’re talking about mutants in fish, it really would have to be a transplant assay in fish - and that didn’t exist.”

Translating a stem cell transplant procedure developed in mammals to fish required several modifications. For one, zebrafish do not carry their hematopoietic stem cells in bone marrow, but rather in their kidneys. In recipient fish, nobody had calibrated the amount of radiation needed to knock out the native marrow cells, or the amount of donor cells needed to successfully replenish the marrow and blood. And while it is easy to match mice for transplantation purposes - because they are inbred and immunologically identical - the fish require more precise matching of donor and recipient, just like humans. The low success rate in the first batch of zebrafish transplants reflected this difficulty.

“These fish were like random donors, they were not immunologically matched at all,” de Jong said. “In some ways, it’s kind of miraculous that it even worked at all.”

But one by one, the kinks were worked out and the procedure was standardized (and published earlier this year in the journal Blood). A number of the immune system MHC genes, which are carefully matched in human bone marrow transplants, were located on chromosome 19 of the zebrafish genome. Each fish could then be genotyped and paired with a closer match for the transplant, which raised the success rate of the procedure.

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ScienceLife ran 219 posts in 2010, and choosing the best of them is as hard as picking a favorite gene.  So here’s a month-by-month scan of a busy year at the University of Chicago Medical Center, full of exciting discoveries in the laboratory and the clinic. The impact of some of this research is already being felt by patients receiving improved, evidence-based medical care. For other studies, the clinical benefit may be years in the future, and may take unpredictable forms. As a closing message for 2010, we’ll re-quote the recently departed Eugene Goldwasser, whose laboratory research isolating and purifying the hormone erythropoietin has helped millions of people worldwide.

“It is a particularly impressive example of how basic research can pay a dividend that could not be anticipated at the start,” Goldwasser wrote about his life’s work, “and it is a pity that the lesson still has not been learned by those who control public funding of science.”

January: Tong Chuan-He looked at how cancer may result from cells who don’t want to grow up. Scientists studied how sleep affects the language learning skills of starlings (with painstakingly acquired video of the experiment!). Richard Jones combined two laboratory staples - Western blots and DNA micro-arrays - to develop a new method for studying protein networks. While physicians such as Tammy Utset treat patients with lupus, UChicago scientists are looking for the genetic origins of the autoimmune disorder.

February: Many Medical Center employees returned from volunteering with relief efforts in Haiti, and we filmed video interviews with Rex Haydon, Tiffany Cupp, Richard Cook, and Dima Awad on their experiences. Most of the human genome is “junk” between protein-encoding regions, but Marcelo Nobrega developed a way to find important regulatory elements in that genetic sea. Like birds, human learning can be affected by sleep, and Leila Kheirandish-Gozal reported on the impact of obstructive sleep apnea upon learning in children. Can a single protein in the brain create behaviors associated with drug addiction in rats?

March: Everyone knows air travel is stressful, but did you know that eastbound flights cause stronger cortisol changes than westbound trips? The laboratory of Milan Mrksich found a way to direct stem cells to form fat or bone by shaping them into stars or flowers, a brilliant example of bioengineering. Computational neuroscientists discovered how touch is like vision in the brain, knowledge that could be used to someday re-engineer Luke Skywalker’s robot hand. Dartmouth president and Partners in Health co-founder Jim Yong Kim visited to talk about a new, needed area of research: health care delivery.

April: Researchers at the Field Museum and the University of Chicago teamed up for the Emerging Pathogens Project, an effort to find new viruses in animals before they jump to humans. Cardiologist Martin Burke tested out a new type of internal defibrillator device that can go under the skin, instead of into the heart (the clinical trial, reported in May, was a success). In a lecture to the MacLean Center of Clinical Medical Ethics, transplant surgeon J. Michael Millis described his efforts to bring American organ transplant practices to China.

May: A trial testing the erectile dysfunction drug Viagra for a rare, untreatable lung disease failed, but pulmonologist Imre Noth found a silver lining. Lauren Sallan and Michael Coates uncovered evidence of a previously unappreciated mass extinction event 360 million years ago that changed the path of life on Earth. Researchers from the University of Chicago and around the world presented science at the frontier of biotechnology at the annual BIO conference.

June: In a study that is literally the size of an entire country, epidemiologist Habibul Ahsan measured the toll of a tragic, accidental exposure of millions to arsenic in Bangladesh. Putting a gene from fireflies into the pancreas of mice isn’t mad science, it’s an imaging tool that will help study cures for diabetes. Epigenetics, the modifications that turn genes on and off, took off in 2010, and cardiologists Stephen Archer and Jalees Rehman linked one epigenetic factor to pulmonary artery hypertension.

July: Scientists don’t often get to see the fruits of their research in the flesh, but the Celebrating the Miracles gathering of diabetic children weaned off injected insulin thanks to genetic research was a moving exception (video of the event can also be viewed). Another hot topic in science and medicine this year was the use of computational analysis to sift through rapidly accumulating data, topics explored by Gary An and Andrey Rzhetsky. Or you can build a computer model of a brain network to study the dynamics of epilepsy, like neurologist Wim van Drongelen.

August: Air pollution is a problem indoors as well as outdoors in developing countries where dung and firewood are used to cook food - a problem being tackled in a project led by Sola Olopade. A study of the hormonal changes induced by a stressful test revealed a surprising protective effect of marriage and long relationships. Microbiologist Olaf Schneewind’s laboratory developed two new strategies against MRSA, the most-wanted cause of hospital-acquired infections.

September: To study multiple sclerosis, neurologist Brian Popko’ s laboratory developed a new mouse model that can replicate the disease, then spontaneously recover. Meanwhile, a new drug to treat MS, originally isolated from fungus found in wasps, was approved by the FDA and is being studied for broader uses at the Medical Center. The micro-organisms that live in humans were analyzed as part of a “microbiome” study looking at the protective effects of breast-feeding against a intestinal disease.

October: Common wisdom on quitting smoking says to stay away from cigarette-associated cues, but research from psychiatrist Harriet de Wit’s laboratory revealed that abstinence could make craving even worse. A study of how getting a good night’s rest affects dieting results suggested that “sleeping off the pounds” isn’t merely a fantasy. Graduate student Daniel Matute solved a 100-year-old riddle about how quickly new species become reproductively incompatible with each other.

November: In perhaps our favorite study of the year, geneticist George Perry found a way to acquire the genomic information of endangered species from…poop. The evolutionary biologist Leigh Van Valen passed away, but his Lewis Caroll-inspired Red Queen Hypothesis lives on. Sometimes statistics don’t tell the whole truth, as in the curious case of the aspirin paradox - why the cardio-protective drug may actually predict worse outcomes after heart attack.

December: Evolution textbooks may need a rewrite after geneticist Manyuan Long’s laboratory discovered that new genes can be just as essential as old genes. A study by neurobiologist Nicholas Hatsopoulos proved that the only thing better than a thought-controlled device is a thought-controlled device equipped with a robot arm. Ripped from the headlines: microbiologist Jack Miller weighed in on the hype over arsenic-based bacteria, and ethicist/physician/friar Daniel Sulmasy discussed the Presidential Bioethics Commission’s report on synthetic biology.

All told, it was a great year of science and medicine. Let’s do it again in 2011! Regular posting will resume Jan. 3rd. Happy Holidays.

In recent weeks, stem cell research has once again been drawn into a battle over political, ethical, and legal questions. Given all the controversy, it’s easy to forget that there are still many scientific questions surrounding stem cells and their potential for medical use. The ability of such cells to grow into different types of organs and tissue is exciting, but harnessing that ability has remained a challenge for scientists. Much work remains to be done in finding the control panel for pushing stem cells in a particular direction - and some of that work continues despite recent court rulings.

Mesenchymal stem cells are less controversial than their embryonic cousins because they can be harvested from adult bone marrow. But they are also more restricted in their potential, with their future limited to three destinies: bone, fat, or cartilage. Of course, those three fates alone would be very useful in medicine, with applications for orthopedic surgery, arthritis, and wound healing. So scientists are looking for the best ways to manipulate mesenchymal stem cells (MSCs) toward one of those forms.

In the laboratory of Tong-Chuan He, associate professor of surgery at the University of Chicago Medical Center, the desired outcome for mesenchymal stem cells is bone.

“Our goal is try to develop an efficient way to promote cells to making bone,” He said. “Ideally, we can create a treatment where we don’t have to use protein, deliver genes or modify cells. It can be a form of cell-based therapy.”

He and colleagues tested different growth factors from the appropriately-named bone morphogenetic protein (BMP) family on the basis of their ability to drive stem cells to become bone. The majority of research and therapy development focused on two members of the family, BMP2 and BMP7. But a 2007 study by He’s lab found that a neglected underdog, BMP9, was the real heavy hitter in pushing stem cells into a career as a bone cell.

But identifying BMP9 only gave researchers the key to bone differentiation, and it was necessary to find the lock as well. A new paper published by He’s lab last month in the Journal of Biological Chemistry, in collaboration with a team of Chinese researchers, tested out different receptors for BMP9 to determine which were critical for bone differentiation. The team tested a series of type I receptors (ALK1 through ALK7) to see which ones helped BMP9 drive MSCs - harvested from adult and embryonic mice - to become bone.

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When President Obama signed an executive order last March loosening the restrictions on embryonic stem cell research, it seemed like the shackles were finally off for good. The new policy rolled back the “Bush compromise” forbidding federal funding of research on any newly created stem cell lines, leaving only 21 lines (at most) eligible for the grants that support the vast majority of laboratory research in the United States. After Obama’s decision, the floodgates didn’t exactly open, but embryonic stem cell research received a significant boost, with more than 300 projects receiving nearly $150 million in National Institutes of Health funding. In the 18 months since the executive order was signed, the number of eligible stem cell lines has expanded from 21 to 75.

But just as American stem cell research was starting to enjoy the regained momentum, an emergency brake was pulled this week by a federal judge in the District of Columbia. Judge Royce Lamberth issued a temporary injunction Monday that found Obama’s executive order in violation of the “Dickey-Wicker amendment,” a ban on giving federal money to research involving the destruction of human embryos that has been attached by Congress to each year’s federal spending bill since 1996. Lamberth interpreted research conducted on embryonic stem cell lines, even long after the original destruction of an embryo to create those lines, as being illegal under the amendment. Despite previous rulings that differentiated between research on an embryo and research using stem cells derived from an embryo, Lambeth ruled that (at least temporarily) NIH funding of embryonic stem cell (ESC) research must stop.

“ESC research is clearly research in which an embryo is destroyed,” Lamberth wrote in the injunction. “To conduct ESC research, ESCs must be derived from an embryo. The process of deriving ESCs from an embryo results in the destruction of the embryo. Thus, ESC research necessarily depends upon the destruction of a human embryo.”

The reaction from the scientific community, as you might guess, has been less than celebratory.

“This decision has the potential to do serious damage to one of the most promising areas of biomedical research, just at the time when we were really gaining momentum,” said Dr. Francis S. Collins, director of the National Institutes of Health. The ruling, he added, “just pours sand into that engine of discovery.” (New York Times, 8/25)

“‘I have had to tell everyone in my lab that when they feed their cells tomorrow morning, they better use media that has not been funded by the federal government,’ said Dr. George Q. Daley, director of the stem cell transplantation program at Children’s Hospital Boston, referring to food given cells. ‘This ruling means an immediate disruption of dozens of labs doing this work since the Obama Administration made its order.” (New York Times, 8/24)

“Basically, they are saying that all ESC research is a part of a broader system of research that includes the initial destruction of embryos. Which would be kind of like saying that all research into nuclear power stems from the Manhattan Project,” he says. (Hank Greely, director of the Center for Law and the Biosciences at Stanford University, Nature News, 8/24)

The ruling hit close to home too, as our own John Cunningham, professor of pediatric and director of hematopoietic stem cell transplantation, told Chicago Public Radio yesterday. Cunningham, who hopes to use embryonic stem cells to study leukemia and other blood diseases, expressed his frustration at having to once again put all such projects on hold due to politics and legal rulings.

“As we go through this process of stopping and going and stopping and going, it really retards our ability to make decisions based on science,” Cunningham told WBEZ.

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This is the second day of our coverage of the 2010 BIO International Convention, a massive biotechnology conference being held this week at McCormick Place in Chicago. Come back all day for reports from panels, lectures, and the exhibit floor on how scientists, government leaders, and industry hope to use the combined forces of science and technology to tackle some of the world biggest problems. For day one of our coverage, click here.

5:30 PM - Regulators, Mount Up!

The boogeyman of the BIO conference has been those faceless regulators, the bureaucracy that speakers have often blamed for the bulk of the slowdown that occurs between scientific innovation and its debut on the marketplace and in the clinic. Though never named directly, the big boss of those regulators in the United States is the Food & Drug Administration, whose stamp of approval is required for each and every new treatment or device. And as much as the biotechnology and patient advocacy choruses cry “more and better drugs, faster!,” one must remember the importance of government oversight in monitoring new products for safety and efficacy - illustrated again today in the FDA-directed recall of 200,000 medical infusion pumps. Late afternoon Tuesday, the industry finally got to hear from the woman at the head of that regulatory boogeyman, in the form of Margaret Hamburg, commissioner of the FDA.

Appearing at a session sponsored by the pharmaceutical company Merck, the reception for Hamburg was of course, polite and gracious - everyone knows not to bite the hand holding that magical FDA stamp. But Hamburg’s speech appeared to be quite reassuring as well, a promise to the assembled drug companies and scientists that President Obama’s FDA was committed to science and new, better, faster ways of approving medical technology. In fact, Hamburg argued for no less than a new field - regulatory science - that would study how best to judge drugs in an era where older models of clinical trials may be obsolete.

“Just as biomedical research evolved in the past decade, regulatory science must also evolve,” Hamburg said. “We cannot use 20th century science to review products using 21st century science.”

If regulatory science sounds like the dullest thing ever, Hamburg doesn’t blame you. In the Q&A session, she said the FDA looked for a different, punchier name, saying that regulatory science “sounds like such a snooze,” and conjures images of bureaucracy and intrusive government. But in the end, Hamburg said, they decided “you can only put so much perfume and fancy clothes” on the concept of improving the country’s regulatory processes. The trick now is to attract promising scientists to a field that is considered to lack the creativity of other scientific realms, and to expand the FDA workforce to keep up with the active pipeline of biotechnology

Such regulatory scientists will have some big problems to tackle. The new world of biomarkers and potentially personalized medicine have complicated the clinical trial process, which has previously relied on lumping large numbers of patients together despite individual differences in disease. New kinds of trials, such as the “adaptive” format pioneered in the BATTLE trial at MD Anderson Cancer Center, will be needed to match the best drug to the best patient in a way that can be regulated, Hamburg said. New devices, such as software that will connect glucose monitors to insulin pumps to produce automated control in diabetes patients, will also need inventive study design to quickly and properly weigh the benefits and safety risks for patients.

“We want the FDA to serve as a gateway, not a barrier, for products people need every day,” Hamburg said.

(Apologies to Warren G - ed.)

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It’s easy to grasp the medical miracle of the organ transplant, where a kidney or heart is passed from one person to another to restore the life of the recipient. Stem cell transplants are a little more abstract in concept, with the life-saving exchange happening via blood donation and infusion rather than the drama of dual surgeries. But the effects upon patients who receive a stem cell transplant are no less transformative, providing them with a new future free from leukemia, myeloma and other bone marrow cancers and the health issues and unpleasant treatments those conditions entail.

As such, it made sense to organize an opportunity for stem cell transplant patients to share that experience with each other, just as recipients of other types of transplants have their own events. The 2nd annual Celebration of Life - a reunion of patients, donors, family members and medical staff - was held this past weekend at the University of Chicago Medical Center, drawing more than 200 people to hear and share stories of the procedure’s success. Held in the atrium of the Duchossois Center for Advanced Medicine, a beautiful spring day appropriately bathed the attendees in sunlight as they talked about the new beginning offered by the treatment.

While patients and their families mingled at the event, we pulled some aside to hear the stories of life before and after stem cell transplant. In the video below, you can view several of those stories, from patients who had their transplant in recent months to patients who received a stem cell transplant more than 15 years ago. We also heard from Koen van Besien, director of the stem cell transplant program at the Medical Center, about why he is “humbled” to see so many patients living healthy lives after the procedure.

A common thread throughout the event was the ever-widening window for people to be eligible for stem cell transplant. By coincidence, van Besien and Lucy Godley have a commentary in this week’s issue of the Journal of the American Medical Association, describing the advances that have allowed doctors to treat more patients with stem cell transplant. For people who are unable to receive autologous transplants from their own blood, the search for compatible donors has been a major obstacle for the procedure. But as the JAMA commentary describes, innovation in the immunological testing of potential donors, preservation of umbilical cord blood, and drugs that enable the use of partially-matched donors are giving more and more patients access to the treatment. As Andrew Artz says in the video below, the hope is that the procedure will become so widely available that future reunions will need to take place in Soldier Field.

For more on stem cell transplants, see our Dr. FAQ videos with Dr. Godley posted last week.

Another species added to the library of sequenced genomes: the zebra finch. Published in Nature and explained in the New York Times, the finchonome could provide answers about the development of language and - most intriguingly - the epigenetic influence of language upon gene expression. Previous studies have shown that gene expression changes in finches that are singing or listening to birdsong, and the Nature study discovers that those expressed proteins, in turn, have effects upon other genes. This cascade effect is very large - the act of singing alone changes the expression of more than 800 genes! Our very own Daniel Margoliash studies birdsong learning in zebra finches, and is no doubt excited to have the entire genome to play with in his research.

Earlier this week, scientists in Russia and the US plugged a hole in the periodic table with the discovery of element 117, a super-heavy element which flashed into existence for a total of 78 milliseconds. The element currently bears the placeholder name of ununseptium - fancy Latin for element #117 - so the fun part now comes in naming the particle. Recent element naming has gotten creative, with names like Copernicium, Promethium, and the rather presumptuous Nobelium, so everyone’s got an idea for #117: see the naming suggestions on twitter for a funny read. My personal submission evokes the element’s super-heaviness: Sabbathium.

Daniel Levitin reviews Nature editor Philip Ball’s new book, The Music Instinct: How Music Works and Why We Can’t Do Without It, and nails a succinct answer for the question in the title:

The secret to composing a likeable song is to balance predictability and surprise. Because most music has a beat and is based on repetition, we know when the next musical event is likely to happen, but we don’t always know what it will be. Our brains are working to predict what will come next. The skillful composer rewards our expectations often enough to keep us interested, but violates those expectations the rest of the time in interesting ways.

Cool news from the other side of campus: the University of Chicago Oriental Institute has uncovered an 8,000-year-old city in Syria, one of the oldest civilizations ever discovered. Called Tell Zeidan, the site is expected to yield decades of data about what life was like in the 5,000s and 4,000s BC - Oriental Institute director Gil Stein told the New York Times, “I figure I’m going to be working there till I retire.” It’s enough to make a biologist jealous.

I am pro-stem cell research, of course, but am still slightly creeped out by the anthropomorphic stem cells in this children’s book, Super Stemmys: Doris and the Super Cells, which has drawn mixed reviews from scientists according to, er, The Scientist.

More cool things happening at Argonne that I barely understand: a green way for making the decidedly un-green-sounding chemical propylene oxide (money quote: “This is basically a holy grail reaction.”) and a venus fly-trap for radioactive waste, gamely tackled by Ted Gregory of the Chicago Tribune.

With good timing for Masters week, Jonah Lehrer talks to University of Chicago associate professor of psychology Sian Beilock about her studies on clutch performance in golfers.

There are probably few medical topics more plagued by online misinformation than stem cell transplants. Part of this confusion is down to people mixing up embryonic stem cells, which have yet to be adapted to clinical use, with hematopoietic stem cells, which have been used in transplants for over four decades. Hematopoietic stem cells are found in bone marrow and circulating blood and are less versatile than their embryonic counterparts, as they are only capable of turning into blood cells. But for patients with blood disorders and cancers such as leukemia or multiple myeloma, a transplant of stem cells from a healthy, compatible donor can be a life-saving procedure.

This weekend, dozens of stem cell transplant patients and their families will come to the University of Chicago Medical Center for a reunion event to celebrate the impact the procedure made on their lives. Many will also reconnect with the physicians and nurses who helped them through their transplant experience, which involves strong chemotherapy and very careful (and sometimes lengthy) screening for compatible donors. Lucy Godley, assistant professor of medicine, is one of the Medical Center’s stem cell transplant experts, serving in both the clinic and the laboratory to help patients and push forward the frontiers of the procedure. We sat down to talk about the basics of stem cell transplants: what diseases it is used for, what the experience is like for donors and patients, and how research is expanding the number of patients eligible for the treatment.

Enjoy the videos, and tune in next week for interviews and footage from the stem cell patients’ reunion.

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Stem cells are a little like teenagers, full of potential but not sure what they’re going to be when they grow up. It’s that uncertain destiny that makes stem cells so exciting to scientists and physicians, who hope to someday use them for everything from spinal cord repair to organ regeneration. But corralling the uncertain power of stem cells requires learning how to push them toward a desired fate, convincing them to become bone cells or liver cells or neurons. Most laboratories have figured out ways to accomplish this goal with chemicals, exposing stem cells to growth factors and other signals that lead it down a particular developmental path. But there may be another way to play guidance counselor to an indecisive stem cell - changing its physical shape.

This process, called cell patterning, is a primary research focus of Milan Mrksich, professor of chemistry at the University of Chicago. On the surface, cell patterning sounds like a mix of science fiction and Play-Doh art: cells are grown on a plate stamped with a special mold that forces the cells to form a particular shape chosen by the researcher. Those shapes can be as simple as circles or squares of various sizes or as complex as flowers, stars, and pentagons. And far from being mere aesthetic lab trickery, this shape-shifting can have dramatic biological effects upon the cell, its underlying skeleton, and even the expression of particular genes.

In a paper published in PNAS earlier this month, Kristopher Kilian, a postdoctoral fellow in Mrksich’s laboratory, applied the cell patterning technique to a particular type of stem cells. Mesenchymal stem cells, harvested from bone marrow, are the slightly less ambitious cousins of the more-hyped pluripotent embryonic stem cells that can change into virtually any cell type. As multipotent cells, MSCs are generally restricted to one of three career paths: fat cells called adipocytes, bone cells called osteoblasts, or cartilage cells called chondrocytes. But despite being limited, those outcomes are potentially very useful therapeutically should scientists learn how to reliably control the differentiation of these cells.

So Kilian, with colleagues Branmir Bugarija and Bruce Lahn, tested out cell patterning on his supply of MSCs. The first experiments confirmed that size and aspect ratio mattered: when given larger or wider areas to grow, the stem cells preferred to become bone cells instead of fat cells. Kilian then kept the size of the stamp constant, but altered the shape, forcing the cells into either a “flower” with curved edges (top row above) or a “star” with sharp edges (bottom row). Both cell shapes were then grown in the same media - a “cocktail” of signals promoting fat cell or bone cell growth, and fates were chosen.

The results? “Flowers make fat and stars make bone,” Kilian summarized. “The view is that, when you introduce the cocktail, the cells are driven one of two ways…the geometry dictates which path the cell goes toward.”

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Last Friday the Obama administration published its new guidelines for federal funding of embryonic stem-cell research, ending the Bush-era restrictions on that work.

Except they didn’t end all of the restrictions. The new rules do not allow for work on cells made via research cloning (somatic cell nuclear transfer), and they require an informed consent process that may exclude some cell lines already derived with different consent procedures. Advocates at both antipodes of the stem-cell debate found something to criticize in the Obama rules. Researcher Irv Weissman of Stanford said the rules maintain an “ideological barrier” that will hinder progress, while Douglas Johnson of the National Right to Life Committee said the guidelines herald “an incremental strategy to desensitize the public to the concept of killing human embryos for research purposes.”

For now Obama seems to have struck an ideological balance, and some conservatives are giving him credit for it. Yuval Levin, a former Bush bioethics adviser who recently appeared on this blog, wrote on Friday that the new guidelines “certainly could have been worse” from a conservative’s perspective.

At the same time, the new rules mean that federally funded research can move beyond 2001-era technology. Bush’s guidelines, which restricted funds to lines derived before August 2001, allowed researchers to work with just 21 cell lines. Obama’s rules open the door to hundreds of additional lines created since 2001, many of them with genetic defects that can help scientists understand how diseases develop.

In moral terms this may even be a clearer approach than Bush’s policy, which claimed to protect nascent life but did allow some funding of research that required the destruction of human embryos. Those rules allowed fewer stem-cell lines to qualify for funding, yet the restriction was based on an arbitrary cut-off date. Why was it moral to allow funding of research on stem cells taken before August 8, 2001, but beyond the pale to allow funds for cells taken after that date?

Levin, who also served as executive director of the President’s Council on Bioethics, wrote that by keeping some limits on stem-cell research funding, Obama’s NIH has conceded “that the destruction of embryos for research is not an innocent and unproblematic practice, but must be constrained for ethical reasons.” So far, so good. As the bioethicist Art Caplan once told me in an interview, “A human embryo may not be a legally protected person, but it’s also not just any old stuff.” Levin then goes further: “These rules raise the question of why limits are necessary, and any serious answer to that question would lead us to conclude that these rules are inadequate. ”

That’s not at all clear to me. Under Bush’s old rules, an embryo’s fate might depend solely on the date when it was created. Under Obama’s new rules, the embryo’s fate is governed by something far less arbitrary - the parents’ intentions, informed by all the options available to them. It seems reasonable to trust that whatever parents decide, they will see their embryos as something more than raw material.

[Note: This post originally contained a quotation from a private classroom setting, which has been removed at the speaker's request.]

This was a long but exhilarating day for Janet Rowley, who was at President Obama’s side as he signed the executive order creating a new stem-cell policy. I caught up with her by phone in D.C. this afternoon as she waited for her plane back to Chicago. Rowley said the day’s events made her think back to the first meeting of President Bush’s Council on Bioethics, where her views in favor of embryonic stem cell research put her at odds with the administration.

“To be there today at the White House and see this signing, for me it was like coming full circle,” Rowley said. “When you saw the enthusiasm of the scientists who were there, the people from Congress, the patient advocates who were so important in keeping this issue alive during the dark years, if you will. It was just an unbelievable experience.”

For Rowley and other researchers, one of the most welcome themes of the day was what Rowley called “the de-linking of science and politics.” In fact, despite the historic nature of the stem-cell policy change, the other document Obama signed may have more far-reaching effects - a presidential memorandum on scientific integrity. That directive calls for more transparency in science and technology issues before the government, without suppression of findings for political reasons.

Although the Bush administration is over, the Council on Bioethics is slated to last until at least November of this year, and Rowley continues to serve on it. She said she believes some of the group’s reports have made an impact, if only to reflect how divided the country was on many issues in bioethics. Such groups can continue to address legitimate moral concerns; as Rowley said, “It’s very important because scientists have to reassure the rest of the country that we’re not out to make a bunch of clones or zombies.”

Another note: Friday’s analysis of the next steps for the NIH is up at the Huffington Post’s Chicago site; you can see it here.

The Washington Post reported this afternoon that President Obama plans to lift the Bush-era restrictions on stem-cell research funding via executive order on Monday. Now comes the hard part - implementing a stem-cell policy that’s meaningful, has full ethical protections and unlocks the scientific talent that’s been held back the last eight years.

One insider point to watch on Monday is whether someone from the National Institutes of Health will help explain the new funding channels for this research. It’s a question of some urgency. Just this week, the NIH released a set of “challenge grant” topics that are eligible for a pool of $200 million as part of the new federal economic stimulus act. The NIH site describes the qualifying projects as those which “address specific scientific and health research challenges in biomedical and behavioral research that will benefit from significant 2-year jumpstart funds.” Embryonic stem-cell research would seem a natural fit - especially since the Bush administration held it back for years - but it’s not clear yet that Obama’s rule change has come in time for stem-cell grant seekers to get a share of the stimulus money. That’s one reason why Obama’s delay in announcing changes to the stem-cell policy was a bit puzzling. Many observers - including me - expected him to lift the restrictions his first week in office.

Around research centers like the University of Chicago, stem-cell scientists are poring over such details. I just spoke with John Cunningham, M.D., a specialist in pediatric stem-cell transplantation, who directed me to the brand-new NIH list of “Highest Priority Challenge Topics.” (You can see a more researcher-oriented application guide here.) Stem-cell research is on the list, but not specifically the embryonic stem-cell research that’s been subject to Bush’s limits. I count five topics that relate to iPS cells - short for induced pluripotent stem cells - which were discovered in 2007 and seem to have many of the properties of embryonic stem cells but are derived from adult cells. That’s fantastic because iPS cells deserve more study. But embryonic stem-cell research never appears by name, except to say that “iPS cells act like embryonic stem cells.”

This is an important point because as Cunningham said, “One of the things that lifting the current ban should allow us to do is really test whether iPS cells and embryonic stem cells have similar properties.” In theory the current challenge grant list could include work with embryonic stem cells, since some of the topics are broad enough to encompass work with several different cell types. For example, Topic 11, “Regenerative Medicine,” contains a broad opportunity to “Develop cell-based therapies for cardiovascular, lung, and blood diseases.” That could cover some work with embryonic stem cells, as could some of the items under the general category of stem cells.

But none of this is set in stone. What the president says on Monday may signal whether broader embryonic stem-cell funding will begin with the stimulus package, or whether scientists - and patients - will have to wait longer to start seeing more progress. Stay tuned.

UPDATE: Here’s a take on the news in an e-mail from embryonic stem-cell researcher and friend of the blog George Q. Daley, M.D., of the Harvard Stem Cell Institute and Children’s Hospital Boston: “I am brimful of hope and excitement about the announcement on Monday. I’ll be there, and I expect Obama to lift the restrictions and usher in a whole new era of scientific openness and opportunity for stem cell research. The future looks bright indeed for stem cell research.”

Suddenly George W. Bush is no longer the easiest target for anyone frustrated at the pace of scientific progress.

He started to occupy that position at 9 p.m. Eastern time on Aug. 9, 2001, when he went on national television to outline restrictions on federal funding for the new field of embryonic stem cell research. It seemed an arbitrary and even arrogant policy. No federal funds could be used for research on cell lines derived after the moment Bush began his speech - exactly 9:00:00 p.m. He portrayed the decision as a compromise - the original intention was to give no funds at all - but many researchers saw it as a fiat that would stifle a promising field and send a message that scientists served at the pleasure of the president. Science-related decisions in subsequent years tended to bear out that early impression.

Now there’s no obvious scapegoat for the obstacles facing researchers and patients eager for new treatments. President Obama has pledged to lift Bush’s restrictions on stem cell research, and to “put science back in its rightful place.” But we still don’t have a good sense of what that means.

This could be a rare opportunity to make a new strategy for American biomedical research. It would be a massive undertaking, centered on the sprawling National Institutes of Health, which currently lacks a permanent director. The $28 billion NIH budget supports 27 centers and institutes, and an army of researchers around the country.

A blog post last week by Stanford researcher Stephen Quake suggested that this is “the time to rethink the basic foundations of how science is funded.”  He proposed more long-term grants to scientists and better incentives to pursue creative projects. The current system has some incentives for researchers to follow the agencies’ institutional priorities, rather than give reign to their best ideas.

My op-ed last Monday in the Chicago Tribune suggested creating a new NIH institute devoted to stem cell research. Yet some of the response to that piece reflected a widespread wariness of doing anything to complicate the federal research bureaucracy. My e-mail friend Yuval Levin, a National Review writer who worked in Bush’s domestic policy office, said that if anything the NIH needs a simpler management structure, not more institutes. He echoed Quake’s point that the current system doesn’t do enough to support younger investigators or new ideas.

In the short run, how Obama handles the NIH may be a better test of his managerial success than the outcome of the stimulus plan. It’s one thing to sign a piece of paper and reverse Bush’s stem-cell policy; it would be a much greater feat to free the awesome creativity of America’s scientists.