One of the world’s leading authorities on stem cells is quitting the UK for a more balanced and fair scientific environment in France. Dr. Colin McGuckin, professor of regenerative medicine at Newcastle University, announced this week that he is relocating his entire laboratory and staff to France, claiming that there is insufficient support for adult stem cell work in the United Kingdom.

“You would barely know adult stem cells exist”, says Dr. McGuckin, in reference to the unfairly biased environment that exists in the UK, in which the immediate benefits of adult stem cells, which are already being realized in clinics today, are ignored while most attention is instead given to the vague and remote possibility of uncertain future benefits from embryonic stem cells, which would not be attainable until after another decade or more of research, if such benefits are attainable at all.

Dr. McGuckin is the UK’s leading specialist in stem cells of umbilical cord blood origin, having pioneered the method of derivation for these stem cells in 2005. Since then he has been successful in regenerating various types of tissue from umbilical cord blood stem cells, including liver tissue which is one of the most highly specialized and complex types of tissue in the human body. Despite such success, however, his pioneering work has not received as much attention in his homeland as has embryonic stem cell research, to the dismay of many scientists. Not only to Dr. McGuckin but to many other stem cell experts, the unjustified prioritization of embryonic stem cell research above adult stem cell work is a serious issue, especially in light of the fact that adult stem cells have already been used in the clinic with immediate benefits to patients, while embryonic stem cells have proven to be highly problematic in the laboratory and have never advanced beyond the laboratory stage precisely for that reason. By sharp contrast to adult stem cells, embryonic stem cells have never been used to treat anyone for anything, and any possible clinical viability of embryonic stem cells is at least another decade away, if not farther, if such a viability is achievable at all.

Because of such an unfavorable scientific atmosphere in the UK, Dr. McGuckin plans to leave Newcastle University for France where he will reestablish himself at the University of Lyon in January. In addition to his entire laboratory, Dr. McGuckin will also be bringing his research team of approximately ten other scientists with him to France, including Dr. Nico Forraz, another leading stem cell expert. After the relocation to Lyon, Dr. McGuckin and his colleagues will open the world’s largest institute devoted first and foremost to umbilical cord blood and adult stem cell research.

Although adult stem cells are often cited as being ethically and politically noncontroversial, since embryos are not destroyed in the extraction of adult stem cells, it is primarily for scientific reasons that adult stem cells are so successful in treating a wide variety of diseases, while embryonic stem cells are thus far completely unsuccessful in treating anything. Ethics and politics aside, adult stem cells and embryonic stem cells behave very differently from each other, and it is purely because of the scientific nature of these cells, not because of politics or ethics, that adult stem cell therapy is already a clinical reality with immediate benefits, whereas embryonic stem cells are not yet clinically viable and any therapeutic potential which embryonic stem cells might ever possibly offer will require at least another decade of technological advancement, if not more, before embryonic stem cells could even be considered as a clinical therapy. Meanwhile, there are many patients who cannot wait another decade before being treated for their various diseases or injuries, and such patients can benefit from adult stem cell therapy today.

Pointing out that his primary professional obligation is toward the treatment of his patients, Dr. McGuckin states, “The bottom line is that my vocation is to work with patients and help patients and unfortunately I can’t do that in the UK.” France, however, offers “a much better environment to cure and treat more people”, and “a much more reasoned balance” between adult and embryonic stem cell research. Many researchers agree with Dr. McGuckin that in the UK there is an irrational over-emphasis on embryonic stem cell research to the detriment of all else. As Dr. McGuckin states, France “is very supportive of adult stem cells because they know that these are the things that are in the clinic right now, and will be more likely in the clinic. A vast amount of money in the UK from the government has gone into embryonic stem cell research with not one patient having been treated, to the detriment of adult stem cells, which have been severely underfunded.”

Indeed, this is not the first time that the UK has forced a leading stem cell scientist to leave for another country. In 2006, Dr. Miodrag Stojkovic also decided to quit the UK, taking his laboratory and adult stem cell research team to Spain. Consequently, Dr. McGuckin, Dr. Stojkovic and many others are critical not only of UK academics in general, but also of Parliament and the media in the UK, for the unjustified attention that is consistently given to embyronic stem cells at the deliberate and systematic exclusion of adult stem cells.

In addition to suffering from a lack of laboratory space in the UK, Dr. McGuckin says he has been forced to decline an investment offer of 10 million pounds due to a lack of receptivity and organization on the part of Newcastle University. He also states that he has been forced to put more than 1.8 million pounds of grant funding on hold because of insufficient space and facilities in which to conduct the work. According to Dr. McGuckin, “I kept getting told our situation would get better, but it never did.”

Although the pro vice-chancellor for the faculty of medical sciences at Newcastle University, Chris Day, has expressed surprise over Dr. McGuckin’s concerns, and despite disagreement over some of Dr. McGuckin’s claims from organizations such as the UK National Stem Cell Network, many other researchers agree with Dr. McGuckin that there is currently a research environment in the UK which is unjustifiably and irrationally biased in favor of embryonic stem cell research, and that this bias must change toward “more balanced research.” According to Dr. Anthony Hollander, professor of rheumatology and tissue engineering at the University of Bristol, “We desperately need more funding for adult stem cell research because with these cells we really can make a difference to patients’ lives, and we can do it now, not in ten years time as is promised for embryonic stem cells.”

According to the group known as “Comment on Reproductive Ethics” (CORE), the loss of Dr. McGuckin would create a “huge hole” in Newcastle’s research portfolio.

Scientists at the University of Michigan have discovered that four genes which were already known to be involved in the control of cancer are also actively involved in the aging process and in stem cell regulation. The four genes, which are known to suppress tumor formation, also regulate the ability of endogenous adult stem cells to replace worn out tissue. When a person’s own adult stem cells fail to replace such tissue, the aging process occurs.

As cells age, these four genes switch on and off in a coordinated fashion in order to reduce the risk of cancer, although such a process also hinders the capacity of stem cells to regenerate tissue. The findings illuminate the shared genetic pathways between natural stem cell regeneration, aging and cancer.

According to Dr. Sean Morrison, director of the University of Michigan Center for Stem Cell Biology, “All four of these genes had been implicated in the regulation of cancer, but only one of them had been implicated in the regulation of stem cells and aging. So this is a pretty significant expansion of our mechanistic understanding of the connections between these vital processes.”

Commenting on the three-year study of mouse brain cells which led to the discovery, Dr. Morrison added, “The genes identified in this study work together to reduce the function of adult stem cells as they age. Embryonic stem cells offer the advantage of not aging, not turning on this pathway.” In order to use embryonic stem cells as an actual medical treatment for something, however, the embryonic stem cells would have to undergo a certain degree of differentiation, which would therefore involve the aging of cells and the activation of these four genes. Meanwhile, the point is somewhat irrelevant at least for the foreseeable future since embryonic stem cells have never been used as a clinical therapy to treat any disease or injury, and the likelihood of embryonic stem cell technology advancing to the stage of a safe and effective clinical therapy is at least another decade away, if not further, by unanimous scientific consensus. By sharp contrast, adult stem cells have already been proven to be a viable treatment modality and have already been used in a wide range of clinical settings to treat a vast array of medical conditions for many years.

Specifically, the four genes under consideration are Ink4a, Arf, Hmga2 and let-7b, which were examined in this particular study by breeding mice that lacked combinations of these genes, and then measuring the effects of the missing genes on stem-cell function and brain-cell formation at different life stages. According to Dr. Jinsuke Nishino, a postdoctoral fellow in Dr. Morrison’s lab, “We have now identified an entire pathway that changes gene expression within stem cells as they age, and that helps to explain why old tissues have less stem-cell function and less regenerative capacity.”

In a 2006 publication in Nature, Dr. Morrison and his colleagues demonstrated that the Ink4a gene, which was already understood for its role as a tumor suppressor, becomes increasingly active with age, not only in the suppression of tumors but also in the suppression of stem cell replication, at least in mouse models. At that time, however, no one understood what it was exactly that causes Ink4a to become increasingly active with age. Now, Dr. Morrison and his colleagues have demonstrated that the activity of Ink4a is regulated by Hmga2, which in turn is controlled by let-7b. In light of these recent findings, the ability of the Ink4a gene to become activated with age would appear to be a type of defense mechanism against cancer-causing genetic mutations, which accumulate with the repeated cell division that is associated with aging. Although the studies were conducted with mice, the same molecular processes are believed to be at work in humans, who also possess the same four genes.

As Dr. Morrison explains, “The tumor-suppressor mechanisms ramp up with age. And the good news is that it allows us to get older before getting cancer. The bad news is that your tissues lose their regenerative capacity, making you older. The more we study this issue, the more we think that tissue aging exists as a by-product of mechanisms that were created to protect us against cancer.”

As scientists understand more and more about the cellular, molecular and genetic processes of life, such discoveries will no doubt play a major role not only in the suppression and treatment of diseases such as cancer, but also in the development of increasingly precise medical tools, such as stem cells.

Researchers at the Salk Institute for Biological Studies in La Jolla, California, have successfully generated a new type of iPS (induced pluripotent stem) cells from the keratinocytes that are attached to a single human hair. The procedure represents a doubling of the speed and a 100-fold improvement in the overall efficiency of generating iPS cells when compared to the original methods that were initially used in early experiments, in which only one out of every 10,000 cells was successfully reprogrammed into an iPS cell. According to Dr. Juan Carlos Belmonte, who led the study, “Having a very efficient and practical way of generating patient-specific stem cells, which, unlike human embryonic stem cells, wouldn’t be rejected by the patient’s immune system after transplantation, brings us a step closer to the clinical application of stem cell therapy.”

After a single human hair is plucked from the scalp, the keratinocytes are reprogrammed into “keratinocyte-derived iPS cells”, or KiPS cells, to distinguish them from ordinary iPS cells which are derived from fibroblasts in the skin. Keratinocytes, which develop from the basal layer of the epidermis to form the uppermost layer of skin, produce the protein keratin which is the primary constituent not only of hair and skin but also of nails. According to Dr. Trond Aasen, a postdoctoral fellow at the Center of Regenerative Medicine in Barcelona who collaborated on the research, “We plucked a single hair from a co-worker’s scalp and cultured the keratinocytes, which are found in the outer root sheet area”, and which were then reprogrammed into KiPS cells. As Dr. Belmonte explains, “We checked a whole rainbow of cells and found keratinocytes to be the easiest to reprogram. It is still not clear exactly why that is, and knowing it will be very important for the technology to develop fully.”

The results of the research offer a fast and relatively simplified way to mass-produce cells which resemble embryonic stem cells in their pluripotency, yet which are obtained from an easily accessible source with noninvasive methods.

In 2007, a team of researchers in Madison, Wisconsin, led by the renowned stem cell pioneer Dr. James Thomson, announced their success in creating iPS (induced pluripotent stem) cells from the mature, non-stem cell, somatic cells of adult human skin. Such iPS cells exhibit the same pluripotency as that of embryonic stem cells, but no embryo is involved in the process. Such an announcement was a “shot heard ’round the world”, since it seemed to solve the ethical controversies that surround embryonic stem cells, by avoiding embryonic stem cells altogether. Now, the methods for conducting the iPS cell procedure are being replicated in hundreds of new laboratories across the nation and around the world.

In total, 812 new laboratories have sprung up in dozens of countries in recent months, the exclusive focus of which is iPS cells, according to the Massachusetts-based company Addgene, which is a repository for the laboratory supplies. According to Dr. Thomson, “People are jumping in very rapidly, much more rapidly than they did ten years ago,” in reference to his own, groundbreaking discovery that he made a decade ago.

Dr. James Thomson is the first person ever to have isolated an embryonic stem cell, first from a rhesus monkey in 1995, and then from a human in 1998. Human embryonic stem cell science in general, therefore, which is exactly one decade old this year, owes its very existence to Dr. Thomson, who invented the embryonic stem cell techniques that are now used throughout the world, and who is widely regarded as “the founder of the field”. With his success last year in reprogramming mature, adult human skin cells into iPS cells, Dr. Thomson once again pioneered a new direction in regenerative medicine which has very quickly become a booming industry.

Even Dr. Thomson, however, has expressed his reservations regarding the applicability of embryonic stem cells and of iPS cells to clinical therapies, at least in the foreseeable future. Many technical hurdles still remain, and any hope of being able to use embryonic stem cells or iPS cells for the actual treatment of human patients is generally considered to be decades away. According to Dr. Thomson, “It’s certainly going to happen, but it’s going to be hard, and people are not prepared for how hard it’s likely to be.”

Indeed, the only medical application of embryonic stem cells that is not still decades away is in the field of drug screening. In other words, instead of testing newly developed pharmaceuticals on live people, the new drugs could be tested on human tissue, derived from embryonic stem cells, in the laboratory. As Dr. Thomson explains, “It simply means that for the very first time we have access to the human body in the lab. And for drug screening and drug discovery, that’s going to make a huge difference. When you use one of those drugs you won’t know that human embryonic stem cells or iPS cells were involved. It won’t make the front pages at all.”

Yet one, critically important problem still remains unsolved. As pluripotent cells, iPS cells do, by definition, cause the formation of teratomas, which is a very particular type of tumor. Like embryonic stem cells, non-embryonic iPS cells are prized for their pluripotency, which is formally defined as a capacity to differentiate into the tissues of all 3 germ layers – the ectoderm, the mesoderm and the endoderm – as specifically found in teratomas. To date, scientists have not yet been able to guarantee that such cells will not also cause teratomas in the patients whose diseases they are intended to treat. The creation of iPS cells may have solved the ethical problems that are inextricably intertwined with embryonic stem cells, since embryos are not needed at all for iPS cells, but iPS cells have not solved the technical, medical and health problems that are an inherent part of all pluripotent cells, especially the very high risk of teratoma formation. By sharp contrast, adult stem cells do not pose such risks since adult stem cells cannot form teratomas since adult stem cells are not pluripotent.

Additionally, the exclusive use of embryonic stem cells for drug screening brings us back once again into the very same ethical dilemma as before, since the destruction of human embryos is required even for this type of drug screening. Meanwhile, however, approximately 70 new iPS cell laboratories are springing up around the world every month.

Although the topic was at one time front and center in the debates among U.S. presidential candidates, stem cells have receded somewhat from the public consciousness in recent months, due in part to breakthroughs with iPS (induced pluripotent stem) cells, which avoid the need for embryos and which thereby sidestep the related ethical controversies, and also due in part to the exigencies of more urgent matters such as the recent global financial crisis.

Nevertheless, stem cells remain a subject of intense interest and fierce argument among the general public if not among the presidential candidates, although the topic did resurface briefly during the final presidential debate. While both candidates endorse the idea of relaxing restrictions that currently exist on embryonic stem cell funding, subtle differences separate their policies. A brief summarization of such policies and of the most immediate historical background is provided herein.

As every stem cell scientist clearly remembers, in excrutiating detail, August 9 of 2001 was the day that President George W. Bush banned the use of federal funds for research on embryonic stem cell lines created after that date. He did not ban the use of federal funds for research on embryonic stem cell lines that already existed prior to that date, nor, contrary to widespread misperception, did he ban the use of private funds or state funds for embryonic stem cell research. Indeed, embryonic stem cell research is flourishing in laboratories across the entire U.S., precisely because the restrictions imposed by President Bush had the reverse effect of galvanizing private investors and scientists who were determined to pursue embryonic stem cell research even without federal funding. Harvard University is an excellent example, where the Harvard Stem Cell Institute is heavily involved in embryonic stem cell research and yet it is entirely privately funded. The state of California is another example, where the approval of Proposition 71 allowed for the allocation of $6 billion worth of state money – $3 billion in principal created through bonds, and $3 billion in interest, to be repaid over 30 years – for the funding of embryonic stem cell research, and which thereby also established the California Institute for Regenerative Medicine. It may be noted that Proposition 71 passed by a narrow margin of only 59.1% of voters, and was strongly opposed by many individuals and groups including the organization known as “Doctors, Patients and Taxpayers for Fiscal Responsibility”. Nevertheless, having been voted into state law by a narrow majority, Proposition 71 and the embryonic stem cell research that it finances are fully legal and in full accord with President Bush’s restrictions on embryonic stem cell research, which apply neither to private funding nor to funding by state tax or bond dollars. Contrary to common belief, therefore, President Bush’s restrictions on embryonic stem cell research – which consisted of a specific ban only on the use of federal tax dollars for embryonic stem cell research conducted on embryonic stem cell lines created after August 9th of 2001 – did not preclude embryonic stem cell research in the U.S. but in fact had the exact opposite effect by igniting a number of very strong and active privately and state funded embryonic stem cell institutes and projects.

Fast-forwarding several years, the U.S. now awaits a change of administration and with it a probable change in embryonic stem cell policy, although the exact nature of such changes in policy has not yet been explicity defined. Contrary to the GOP platform, John McCain – along with 57 other, mostly Democratic, senators – signed a letter to President Bush in 2004 requesting that restrictions on the federal funding of embryonic stem cell research be relaxed. Similarly, in 2006 and 2007, both Senators John McCain and Barack Obama voted for a bill to expand the federal funding of embryonic stem cell research. Both Senator Obama and his running mate, Senator Joe Biden, support a complete overturn of President Bush’s restrictions on embryonic stem cell research, while Senator McCain’s running mate, Governor Sarah Palin, adheres more closely to the official GOP platform by opposing embryonic stem cell research. Although some people question whether or not Senator McCain’s position on the issue may have shifted, or will shift, as a result of his running mate’s views, McCain spokesman Brian Rogers asserts that, if elected president, McCain would “absolutely” support embryonic stem cell research. Rogers adds, “He bucked his party and the Bush administration in supporting stem cell research, including embryonic stem cell research, and will continue to do so.” Previously, however, Senator McCain has stated that, “Recent scientific breakthroughs raise the hope that one day this debate will be rendered academic”, in a direct reference to recent breakthroughs with iPS (induced pluripotent stem) cells. Precisely because of such statements made by Senator McCain, a number of people, such as Father Tadeusz Pacholczyk, education director for the National Catholic Bioethics Center, which opposes embryonic stem cell research, have said that “a certain level of ambiguity” may still be found in McCain’s stance. In other words, the full extent to which McCain might “relax” or “expand” the restrictions imposed by President Bush are not entirely clear.

Nevertheless, the day when embryonic stem cell scientists and their laboratories throughout the U.S. might be competing for N.I.H. (National Institutes of Health) grants may not be very far away, but voters will have to wait until after November 4th to learn the exact details of such a prospect.

Led by Dr. Thomas Skutella, a team of researchers at the University of Tubingen in Germany has reported the creation of “germline stem cells” from the sperm-producing testicular tissue of 22 men, via a culturing process which is similar to that of culturing human embryonic stem cells. Following the standard, global test for pluripotency, the scientists then injected the new “germline stem cells” into immune compromised mice, where the newly created cells formed teratomas and hence are now celebrated for their similarity to embryonic stem cells.

According to Dr. Gerd Hasenfuss of the University of Gottingen in Germany, who has published similar studies involving the transformation of mouse testicular cells into pluripotent cells, “My summary is, it is a nice paper, they made big progress in getting to a pluripotent cell, and they show pluripotency with a teratoma experiment. But I think we are not completely there where we want to be, namely, at pluripotency absolutely comparable to that of embryonic stem cells.” In particular, although the “germline stem cells” were shown to differentiate into most cell types of the body, they did not differentiate into cardiomyocytes, from which heart tissue is formed.

Nevertheless, Dr. Skutella and his colleagues have demonstrated that the transformation and reprogramming of the cells may be accomplished through growth factors in the culture medium rather than through retroviral and oncogenic vectors, as were originally used in the first experiments conducted with iPS (induced pluripotent stem) cells. According to Dr. Dirk de Rooij, professor emeritus of endocrinology at the Utrech University in the Netherlands, “In comparison to the mouse studies that have been done, there is a big leap forward in efficiency with which these people get these germline stem cells.”

Similarly, as Dr. Peter Donovan of the University of California at Irvine explains, “The ability to make a pluripotent stem cell from an individual without the ethical and immunological problems associated with human embryonic stem cells is a big deal.” He adds the following caveat, however: “I suspect people would be much more willing to give up a piece of skin to make an iPS cell than to have a testicular biopsy to give rise to an adult germline stem cell.”