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A display on adult stem cells, here at the SMM: In fact, this exhibit features Catherine Verfaillie herself. (Good looking out, BK)
Courtesy bryankennedyFollowing the results of an evaluation by a panel of experts at the University of Minnesota, the magazine New Scientist published an article last week announcing that some of the data used in a groundbreaking study on adult stem cells had been falsified.
The study, performed at the University of Minnesota under the supervision of Catherine Verfaillie, is part of a line of research that seemed to indicate that adult stem cells, taken from bone marrow, are pluripotent—that is that they have the potential to develop into any type of cell. Previously, only embryonic stem cells were thought to be pluripotent, and Verfaillie’s research looked like it could eventually offer an alternative to the ethically complicated use of embryonic cells for research (which requires the destruction of an embryo).
Unfortunately, other scientists had trouble replicating Verfaillie’s results, which were published in the journal Nature. New Scientist began examining the research done by Verfaillie and her team, and found that key images in the research appeared several times in papers for different experiments, and, in the case of a related study in the publication Blood, were used twice in the same paper, but had been visually altered slightly, and flipped 180 degrees. New Scientist reported their findings to the University, which began a formal investigation of the matter.
The University just recently completed the investigation, and found that data in the blood article had indeed been falsified (the images in particular), by a former PhD student of Verfaillies’, Morayma Reyes. The University and Catherine Verfaillie have asked Blood to redact the study.
Verfaillie has stated that she was unaware of the problems with the published study, and while she didn’t believe that the data was deliberately falsified, she takes ultimate responsibility for the errors.
Reyes, who now works as an assistant professor at the University of Washington, denies that the images represent deliberately altered data, and blames the errors on inadequate supervision and training. She claims that she had neither the equipment (photo editing software) nor knowledge required to alter the images. The differences in the reoccurring images were likely the result of the inadvertent use of the image adjusting tools built into lab equipment, she says, and the duplication of a figure within the Blood paper was accidental. Reyes also feels that she has been treated unfairly by the University, and that the expert panel in the investigation demonstrated a clear “lack of expertise” in the field of stem cell biology.
Reyes’ full position can be read here. The University’s response can be found here.
The altered images, Reyes asserts, shouldn’t change the results of the paper, but the whole incident brings up some interesting issues on the process of vetting science. While the errors in the paper never should have made it past Verfaillie and the rest of her team, the process of peer review should have caught them anyway. Generally, before research is published in a scientific journal, the editors select several scientists in the particular field of the paper to evaluate and comment (often anonymously) on the paper. The review panel is meant to confirm that the methodology of the experiments and the interpretation of the results are sound. Research can then be recommended (or not) for publication.
Publishing research essentially formally submits it to the scientific community, and it’s common for other scientists to attempt to attempt to replicate experiments, especially if a study makes particularly striking claims (like adult stem cells being pluripotent). The work of other scientists in replicating results is, obviously, essential to the scientific method—in this case is was what finally drew attention to some of the irregularities in Verfaillie’s team’s work.
Reproducibility can be a tricky thing, though—difficulty in repeating results doesn’t necessarily mean that they aren’t reproducible. (Here’s a good article on repeating and reproducing results.) But the problems in reproducing these results drew attention to the questionable data, which brought up another aspect of scientific vetting: the University’s investigation into academic misconduct. If the problems with reproducibility seem to come from data being changed, added, or omitted to strengthen a conclusion, then there could be a serious problem. This sort of misconduct undermines scientific progress, and can call into question the reputation of the institution it came out of and the validity of other research performed there. And if Morayma Reyes seems a little extra defensive in her letter, it’s understandable, because being accused of academic is a big deal, and no good for your career and future work.
The subject of the research further complicates the situation—this isn’t the first time issues of academic dishonesty have come up with regards to stem cell research. In 2006, a Korean scientist’s claims that he had cloned human embryos (thereby eliminating the need to destroy new embryos for stem cells) turned out to be based on lies. There’s a fear that the potentially huge medical payoff of stem cell research, as well as the ethical debate surrounding the use of human embryonic stem cells, could lead to science that is less than completely thorough, or even situations like the Korean controversy. And that’s bad for science in general. There’s also the thought that errors that are unintentional (as may be the case with Reyes’ images) could be the result of “pathological science,” where results are steered in a particular direction by scientists because of “subjective effects, wishful thinking, or threshold interactions.” It doesn’t have the same ethical problems, but pathological results aren’t a whole lot better for science than straight-out misconduct, but it’s a serious potential pitfall with the benefits of stem cell research waiting out there.
So there you go. It looks like things are, for the most part, being handled appropriately in this situation, but it’s an interesting window into scientific process.
Any thoughts? Does it seem like the vetting process of science is lacking in some way? Or is it maybe too thorough? Professor Reyes, I imagine, would argue that too much has been made of this situation, and there are many who argue that the process of peer review limits the communication and dissemination of scientific ideas.
Or, even better, does it seem like I got something wrong here?
Let’s have it, Buzzketeers.
University of North Carolina researchers have transformed cells from human skin into cells that produce insulin (click to read).
“Not only have we shown that we can reprogram skin cells, but we have also demonstrated that these reprogrammed cells can be differentiated into insulin-producing cells which hold great therapeutic potential for diabetes,” said study lead author Yi Zhang, Ph.D., Howard Hughes Medical Institute investigator, professor of biochemistry and biophysics at UNC and member of the Lineberger Comprehensive Cancer Center.
Using the new induced pluripotent stem cell (iPS) technique, researchers from Harvard Stem Cell Institute produced a robust new collection of disease-specific stem cell lines. Having these disease-specific iPS cells will allow researchers to watch the development of diseases in petri dishes, outside of the patients. HSCI iPS Core will produce these disease-specific cell lines for use by scientists around the world.
The cell lines the researchers produced carry the genes or genetic components for 10 different diseases, including Parkinson’s Disease, Type I diabetes, Huntington’s Disease, Down Syndrome, a form of combined immunodeficiency (“Bubble Boy’s Disease”), Lesch-Nyhan syndrome, Gaucher’s Disease, and two forms of Muscular Dystrophy, among others. Havard Stem Cell Institute Spotlight
The work is described in a paper published in the online edition of the journal Cell. Click here to read the full text of the paper titled, Disease-Specific Induced Pluripotent Stem Cells.The chief researchers were George Q. Daley, associate director of the Stem Cell Program at Children's Hospital Boston, and Chad Cowan and Konrad Hochedlinger of Massachusetts General Hospital.
Click hear to listen to an 08/06/08 press conference with George Daley and Doug Melton (who is also co-chairman of Harvard's new interfaculty Department of Stem Cell and Regenerative Biology).
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Stephan Hawking has ALS
Courtesy NASA
Stephen Hawking has amyotrophic lateral sclerosis (ALS), a disease that destroys motor neurons. So far, progress in understanding this disease has been relatively slow, mainly because it has been difficult to obtain a decent supply of living motor neurons affected by the condition. New research done by John Dimos and Kit Rodolfa from the Harvard Stem Cell Institute has created in the laboratory a plentiful supply of cells that have the same genetic makeup as a patient with a particular disease.
A paper published online in the journal,Science, describes how they created the first stem cell lines from the skin of an elderly sick person, then coaxed these cells to become nerve cells genetically matched to those that had gone bad in a patient's spinal cord. By comparing diseased cells to normal cells in a Petri dish, scientists hope to better understand what causes disease and test new drugs.
This research builds upon the research we posted Jan. 18 titled Human embryo cloned from skin.
Learn more:
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Embryo - 5 weeks
Courtesy Ed Uthman Lesbian couples could one day have children who share both their genes. Karim Nayernia, Professor of Stem Cell Biology at Newcastle University, has applied for ethical approval from the university to use bone marrow stem cells from women to start experiments to derive female sperm.
“I think, in principle, it will be scientifically possible,” Prof Nayernia told New Scientist.
Other research is setting the stage for a gay man to donate skin cells that could be used to make eggs, which could then be fertilized by his partner’s sperm. A surrogate's uterus would be needed to bring the baby to term.
In Brazil, a team led by Dr Irina Kerkis of the Butantan Institute in Saõ Paulo claims to have made both sperm and eggs from cultures of male mouse embryonic stem cells in the journal Cloning and Stem Cells.
A whole class of hereditary diseases, including some forms of epilepsy, result from faulty DNA related to mitochondria. Starting with 10 severely abnormal embryos left over from traditional fertility treatment, researchers removed the nucleus, containing DNA from the mother and father, from the embryo, and implanted it into a donor egg whose DNA had been largely removed. The only genetic information remaining from the donor egg was the tiny bit that controls production of mitochondria. The embryos then began to develop normally, but were destroyed within six days.
"We believe that from this work, and work we have done on other animals that in principle we could develop this technique and offer treatment in the forseeable future that will give families some hope of avoiding passing these diseases to their children." said Patrick Chinnery, a member of the Newcastle team.
If you have an opinion on these types of research, feel free to comment.
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Cut spinal cords, destroyed brain tissue, or damaged heart muscle can be repaired by injecting stem cells into the damaged area. Embryonic stem (ES) cells are like blank cells that give rise to every type of cell and tissue in the body. Using human embryos or unfertilized human eggs as a source of stem cells raised show-stopping opposition. Now stem cells have been produced from skin.
Two separate teams of researchers announced on Tuesday they had transformed ordinary skin cells into batches of cells that look and act like embryonic stem cells -- but without using cloning technology and without making embryos.
Both teams call the new cells induced pluripotent stem (iPS) cells and say they look and act like embryonic stem cells.
The research was published online Tuesday by two journals, Cell and Science. The Cell paper is from a team led by Dr. Shinya Yamanaka of Kyoto University; the team published by Science was led by Junying Yu, working in the lab of stem-cell pioneer James Thomson of the University of Wisconsin-Madison.
Thompson said the technique is so simple that "thousands of labs in the United States can do this, basically tomorrow." In contrast, the cloning approach is so complex and expensive that many scientists say it couldn't be used routinely to supply stem cells for therapy.
Remember the fraudulent research of South Korean scientist Hwang Woo-suk? A new analysis of Hwang's research indicates that the disgraced scientist actually did reach a long-sought scientific goal. It's just not the one he claimed.
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Stem cells from mouse tails: Photo adapted from Kadath
Stems cells can self-renew or go through numerous cycles of cell division while maintaining their undifferentiated state. Stem cells also have the capacity to differentiate into any mature cell type. These unique properties make stem cells very promising in research toward fixing damaged nerves, diabetes, and Alzheimer's. But research involving stem cells has been limited because obtaining stem cells involved destroying human embryos.
Researchers found a way to use skin cells from an adult mouse to create stem cells like that of an embryo.
Four genes, which code for four specific proteins known as transcription factors, are transferred into the cells using retroviruses. The proteins trigger the expression of other genes that lead the cells to become pluripotent, meaning that they could potentially become any of the body's cells. Yamanaka calls them induced pluripotent stem cells (iPS cells). "It's easy. There's no trick, no magic," says Yamanaka. Nature.
But the iPS cells aren't perfect, and could not be used safely to make genetically matched cells for transplant in, for example, spinal-cord injuries. Yamanaka found that one of the factors seems to contribute to cancer in 20% of his chimaeric mice. He thinks this can be fixed, but the retroviruses used may themselves also cause mutations and cancer.
"This is really dangerous. We would never transplant these into a patient," says Jaenisch.
In his view, research into embryonic stem cells made by cloning remains "absolutely essential". ScienceBlogs.com
"Human embryonic stem cells remain the gold standard for pluripotent cells, and it is a necessity to continue studying embryonic stem cells through traditional means." Jaenisch, MIT.edu/news
After more than two years of legal wrangling, California is free to spend over $3 billion during the next decade on stem cell research. California Institute for Regenerative Medicine (CIRM) is now free to raise some $300 million per year by selling bonds. New Scientist
In the United Sates Congress, the House gave final approval on Thursday to legislation aimed at easing restrictions on federal financing of embryonic stem cell research, but Democratic leaders in both chambers conceded they were short of the votes needed to override a veto threatened by President Bush. Any effort to override a veto would begin in the Senate, where the bill passed April 11 on a 63-45 vote. Even counting the three Senate Democrats who were not present for the vote, passage was one vote shy of the two-thirds majority needed to override a veto. New York Times.
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Mouse embryonic stem cells stained with a fluorescent green marker.: Image courtesy: Niels Geijsen, Massachusetts General Hospital/National Science FoundationMeri Firpo, a former featured Scientist on the Spot, has been accused by a member of the Minnesota House of Representatives of breaking the law. According to Representative Dan Severson (R-Sauk Rapids) a 1973 state statue on human research appears to make the embryonic research that Dr. Fripo conducts illegal. The accusations came as state lawmakers debated in committee funding for embryonic stem cell research.
According to a recent Star Tribune article, “At the Stem Cell Institute, much of Firpo's work takes place within a locked, windowless 250-square-foot lab where every pen, every vial -- even the lab's share of ventilation -- must be carefully documented to ensure that it isn't paid for with federal dollars. The university is scrupulous about not using any of its state funding as well. With a budget of $250,000 scrounged from private donations, Firpo and others hunt for the information that will eventually, they believe, lead to cures for diabetes and other illnesses.”
Many other states, like Wisconsin, support stem cell research with state funding. Minnesota does not. Governor Tim Pawlenty campaigned for reelection as a supporter of stem cell research, but since the election has slid on the issue, and now says he would only support public funding if it did not include destroying embryos. The alternatives he supports, such as research that uses stem cells which are found in adults and in umbilical cords is not generally considered controversial.
As for the stem cells that come from embryos, the embryo is always destroyed in the process of harvesting the stem cells – a method of harvesting stem cells without destroying the embryo has not been developed. Dr. Firpo stated in her Scientist on the Spot feature, “The embryos we used to make human embryonic stem cell lines were from donors undergoing fertility treatments in a clinic. There were two types of embryos donated to my research program. The first (and most common) were those embryos that were discarded because they were determined to be too poor quality to make a woman pregnant. The second source was embryos that were frozen for the donor's use that were good quality, but were not needed for the donor's fertility treatment. The donors choose whether to keep the embryos, donate them or discard them. If they are discarded, they can choose to destroy them or to donate them for research.”
The University of Minnesota’s own Center for Bioethics has some great questions about embryonic stem cells and their use in medical research:
• When does a human embryo become a person?
• Should we use research methods that destroy human embryos to search for new therapies that could help people in the future?
• How far are we as a society willing to go to improve our health and lives?
• Where should the embryos for stem cell research come from?
• Will stem cell research lead to future genetic manipulation of cells? Will we cease to be human if that happens?
• What are we willing to spend on medical research and who should decide what is morally appropriate?
As for the accusations that Firpo’s research is illegal, Firpo states that she has been assured by the University that her research is legal, and that the statue Representative Severson referred to does not apply in this case.
Doctors in Israel have created beating heart tissue from stem cells. However, some commenters at this medical blog are underwhelmed.

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