Adult Stem Cell Therapy for Diabetes Shows Progress

Once again, the biotech company Opexa Therapeutics announces strong preclinical data for its proprietary diabetes therapy, developed from autologous adult stem cells. The new study demonstrates that adult stem cells harvested from the mononuclear cells of peripheral blood are differentiable into pancreatic-like cells, which mimic the morphology and function of the beta islet cell clusters of the pancreas in their ability to secrete insulin, glucagon and somatostatin, as well as in the expression of pancreatic and endocrine-specific biomarkers and in the high levels of C-peptide, a byproduct of insulin synthesis.

Derived from both healthy and diabetic subjects, the mononuclear cells have yielded strong in vitro as well as in vivo data in animal studies, and further preclinical studies will be conducted for the determination of optimal dosing, delivery, route-of-administration and toxicology. As Opexa advances toward a Phase I clinical trial, primary endpoints for which have already been identified, a protocol for the clinical trial has also already been established in consultation with the FDA and Opexa’s Clinical Advisory Board.

According to Neil K. Warma, president and CEO of Opexa, “I am pleased to see important advances with our stem cell therapy as this technology could offer benefits not only for the treatment of diabetes but also in other disease areas. We are also hopeful to be able to derive one course of treatment from a single blood draw from a diabetic patient which, ideally, would lead to a readily available source of patient-specific beta-cells suitable for autologous cell transplantation.”

As Donna Rill, senior vice president of Operations, adds, “We have developed a manufacturing process based on a small-scale, bag-based system which we believe should yield significant cost savings over typical embryonic stem cell and cadaveric cell manufacturing processes. We have extensive experience with cell therapy technology, having just completed a 150 patient Phase IIb clinical study with our T-cell therapy and we have applied many of the same principles to our stem cell manufacturing process. Much work still remains but we are encouraged with these data.”

Opexa Therapeutics is focused on the development and commercialization of patient-specific autologous cellular therapies for the treatment of autoimmune diseases such as multiple sclerosis and diabetes. In the treatment of multiple sclerosis, Opexa has already achieved excellent results with its lead product candidate, Tovaxin, which is a novel T-cell vaccine that is specifically tailored to each patient’s disease profile and which has recently completed Phase IIb clinical trials. Opexa holds the exclusive worldwide license for the technology that allows the derivation of adult multipotent stem cells from the mononuclear cells of peripheral blood, and which in turn makes possible the large-scale efficient production of monocyte-derived stem cells, without the risk of immune rejection. (Please see the related news article on this website, entitled, “Opexa to Present Data on its Cellular Therapies for Autoimmune Diseases”, dated November 10, 2008, and originally reported in The Wall Street Journal, for more information on Tovaxin).

Opexa therapeutics deals exclusively with adult stem cells, not embryonic stem cells.

Teeth as a Form of Health Insurance

In Mid Cheshire, England, young women with toddlers are being taught to consider their children’s teeth as a form of family “medical insurance”. For £950 (approximately 1,400 U.S. dollars), the company Bio-Eden will store a tooth’s soft pulp, which contains a plentiful amount of adult stem cells that have already been shown to differentiate into a wide variety of tissue types, and which can be used in the future, if necessary, not only to treat the individual from whom the tooth originated but also blood-relatives of that individual.

Bio-Eden supplies participating mothers with a collection kit that includes storage containers and cooling packs for children’s teeth, which parents are instructed to collect as soon as the teeth fall out. If the proper collection containers are not immediately available, the mothers are encouraged to store the teeth in fresh milk in the refrigerator until the teeth can be sent to Bio-Eden along with the appropriate collection supples. According to Vanessa Weeks, sales manager of Bio-Eden, “The process is simple and easy, it is non-invasive and allows you to use something that is normally discarded. The mums are wowed by the possibilities.”

Once the teeth are sent to Bio-Eden, the soft pulp is then divided and stored simultaneously at two separate physical locations. As Ms. Weeks explains, “It means that, in the unlikely event of a major physical threat at our lab, there will still be another sample available.”

Adult stem cells harvested from dental pulp have been shown to differentiate into a diverse range of tissue types which include, most notably, neurological tissue. As such, dental pulp-derived adult stem cells are believed to constitute an excellent source of stem cell therapies that could be used in the treatment of conditions such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, traumatic brain injury and spinal cord injury, among others. (Please see the related news article on this website, entitled, “Brain Tissue Formed From Monkey Teeth Stem Cells”, dated November 12, 2008, and first reported in the journal Stem Cells).

During the sixth week of embryonic development, human deciduous teeth begin forming in utero from the dental lamina which is a band of epithelial tissue that develops from the ectoderm, the outermost germ layer from which cells and tissues of the nervous system also develop. Hence, it is hardly surprisng that adult stem cells which are present in dental pulp are easily differentiable into neurological tissue. Since the outer part of the integumentary system including the epidermis also develops from the ectoderm, it is also not surprising that dental pulp stem cells have been found to develop into a number of cell types that compose these tissues as well. Interestingly, dental pulp has also been found to contain a variety of cell types from the mesoderm, which include chondrocytes (which are found in cartilage and which produce and maintain the cartilaginous matrix), osteoblasts (which are responsible for bone formation), adipocytes (fat cells) and mesenchymal stem cells (highly potent adult stem cells that are also found in bone marrow and umbilical cord blood). Dental pulp stem cells are therefore also believed to be useful as therapies in the treatment of heart disease, diabetes and in the reconstruction of damaged bones and joints, among other ailments. Indeed, the full range of therapies to which dental pulp-derived adult stem cells may be applicable is potentially unlimited.

Even though Bio-Eden is a U.S. company, headquartered in Austin, Texas, Bio-Eden has international laboratories in the U.K. and Thailand which provide services throughout Europe and Asia. Additional sites are currently be planned for Russia, India, Australia and the Middle East.

Bio-Eden is the first company to collect, harvest and cryogenically store adult stem cells that are extracted from deciduous teeth, also known as baby teeth. Bio-Eden is registered with and approved by the U.S. FDA.

As Bio-Eden states on the homepage of their website, next to a picture of a nurse with wings, “One day, the Tooth Fairy could save your child’s life.”

Growing a New Heart With Adult Stem Cells

Some species have a natural capacity for regenerating large quantities of their tissue whenever they suffer damage, the ultimate example of which is the salamander, in which spontaneous regrowth of entire limbs and even of large parts of its heart and brain have been well documented. Similarly, the popular aquarium resident, the zebrafish, has also been found to be capable of regrowing entire pieces of its heart, whenever necessary, due either to unfortunate accident or to the deliberate experimentation of curious humans. In any case, and regardless of the species, such regeneration is possible because of naturally occurring, endogenous, adult stem cells which exist within the organism precisely for this very reason: namely, to wait patiently until activated by injury or illness, at which time the adult stem cells valliantly come to the rescue to repair and replace damaged or missing tissue. However, biological regeneration is generally believed to be inversely proportional to evolutionary complexity, so that, in other words, the more biologically advanced a species is, the less natural regenerative ability that species possesses, and vice versa. Such a theory would explain why, for example, regeneration of entire limbs and organs is spontaneously seen in amphibians and fish but rarely in humans or other mammals.

However, such a theory may be incorrect.

Generally considered (at least by themselves) to be the most highly evolved and advanced species on the planet, human beings are now showing a natural ability for biological regeneration, at least at a cardiovascular level.

In developed countries such as the United States and Canada, cardiovascular disease continues to rank as the number one cause of death, and conventional medical therapies which consist of surgical procedures in combination with pharmaceuticals have not offered a satisfactory treatment for the disease and its numerous complications. Now, adult stem cells offer the first actual therapy which is capable not only of restoring full function to the damaged heart but also of regrowing healthy heart tissue; and such therapies are most successful when they work in combination with the body’s own reservoir of endogenous adult stem cells.

Dr. Christopher Glover, an associate professor of medicine at the University of Ottawa and a cardiologist at the University of Ottawa Heart Institute, has been conducting a clinical trial in which endogenous adult stem cells are activated in patients following a heart attack. The clinical trial consists of 86 heart attack patients to whom a proprietary “drug” was given which activates the migration of each patient’s own endogenous adult stem cells from the bone marrow into the bloodstream, from which the stem cells then automatically “home in” on, and target, the damaged tissue of the heart. As Dr. Glover describes, “There are some repairs that our bodies can [automatically] do. If we amplify the response, perhaps we’d get more repair.” This treatment is meant to amplify the body’s natural response mechanisms, and although the clinical trial is still in progress and has not yet concluded, the patients are already improving “even better than expected”, according to Dr. Glover.

A similar study was conducted last year in an animal model in which an organic, collagen-based gel was injected directly into damaged tissue in laboratory rats and was subsequently found to stimulate angiogenesis, which is the formation of new blood vessels. The use of various agents, including externally derived stem cells, to stimulate naturally occurring endogenous adult stem cells is a popular and widely validated procedure that has been independently corroborated by a number of scientists in a number of studies conducted around the world.

The successful stimulation of the body’s own adult stem cells extends far beyond the cardiovascular realm, however, and has already been applied to a wide range of therapies that require much more than mere angiogenesis. In fact, even in humans, a number of sources have documented the natural ability of the body’s own adult stem cells to repair damaged tissue, even without external stimulation. For example, in human children prior to the age of approximately 10 years, the regrowth of entire fingertips that have been lost in accidents has been reported, as long as the wound is not deliberately sealed with a skin flap, which, unfortunately, is the usual de facto emergency treatment that is administered to such accidents, and which reliably prevents the natural regrowth of the finger by the artificial physical barrier that it creates. Without such physical barriers, however, and with a more enlightened medical approach, regrowth of digits is not uncommon in humanns. A particularly remarkable demonstration of such regeneration involved the case of Lee Spievack who, in his 60s, accidentally sliced off the end of one of his fingers in the propeller of a hobby shop airplane, after which he was treated with a powder that was applied directly to the injured area. Within four weeks, the missing half-inch of his finger completely regrew, including not only the flesh and blood vessels but also the bone and nail. The powder contained a proprietary extracellular matrix compound which stimulated and cooperated with the man’s own endogenous adult stem cells in regrowing his missing finger. Likewise, the U.S. Army has already been applying adult stem cell technology to the regrowth of limbs for wounded soldiers returning from Iraq and Afghanistan. (Please see the related news articles on this website, entitled, “Grow Your Own Replacement Parts” and “Growing Miracles”, dated February 6th and February 7th of 2008, respectively, each originally reported by CBS Evening News).

Regardless of the species, and across all species, the physiological body of each organism has a natural and strong genetic tendency to heal itself; even in humans, our very DNA is programmed to repair the cellular damage that results from the various injuries and illnesses of life. Regardless of the specific type of medical therapy that is used for any particular ailment, the greatest medical successes will result from those therapies that harness, to the fullest possible extent, the body’s own natural healing abilities. In the realm of stem cells and regenerative medicine, we are thus far only barely able to glimpse the tip of the iceberg.

As Dr. Marc Ruel, a cardiac surgeon at the University of Ottawa Heart Institute, puts it, "We know it’s going to work. We are living proof of it. Nature proves this concept every day."

Heart Patients Report Dramatic Improvement with Adult Stem Cell Therapy in Clinical Trials

Aaron Cathcart was told by his doctor that he barely had a year to live, because his heart was so weak that he would not be able to survive surgery. That was over two years ago.

On June 26th of last year, however, Mr. Cathcart received autologous adult stem cell therapy in which his own adult stem cells, derived from his own bone marrow, were administered directly into his heart during open-heart surgery. Prior to receiving the therapy, his heart had an ejection fraction of less than 20%, whereas a normal ejection fraction range is considered to be between 55% and 75%. Three months after receiving the adult stem cell therapy, his ejection fraction had improved to 36%, and by January it had improved even further to 41%. Now, he no longer needs a defibrillator and is almost within the normal range for a healthy ejection fraction.

As Mr. Cathcart now describes, “It used to be that I couldn’t walk a couple hundred feet in the yard without getting pains. I couldn’t go out if the weather dropped below 50 degrees because my heart would strain in the cold.”

Since stem cell therapies are still plodding their way through the multi-year, highly expensive and lethargic FDA clinical trial process that is required for government approval of such therapies in the U.S., most stem cell therapies are not yet available in the U.S. at all, except through FDA-approved clinical trials. In fact, this is exactly how Mr. Cathcart discovered the therapy, since he was fortunate enough to find a clinical trial with adult stem cells that was being conducted not far away from his hometown. The company TCA Cellular Therapy was seeking patients who had suffered heart attacks but had never undergone heart surgery, conditions which applied to Mr. Cathcart and which made him eligible to participate in the trial. The therapy utilized autologous adult stem cells which were taken from each patient’s own bone marrow, expanded in the laboratory and then administered back to each patient according to his or her particular medical condition. Although such therapy usually eliminates the need for surgery, in Mr. Cathcart’s particular case the doctors determined that heart surgery was necessary due to the advanced pathology of his heart, so his own adult stem cells were injected directly into the dead tissue of his heart during bypass surgery.

Embryonic stem cells were never used in the therapy, due to the numerous medical risks and dangers that embryonic stem cells pose, not the least of which is the formation of teratomas (tumors). By sharp contrast, adult stem cells pose no such risks.

As Mr. Cathcart explains, “People hear ‘stem cells’ and they think ‘killing babies’. People are not distinguishing between the two. These were my own stem cells they used. Everyone’s body has them, and if you increase them in concentration, they can repair your body much better than normal.”

The company TCA Cellular Therapy, which is headquartered in Covington, Louisiana, is focused exclusively on the research and development of adult stem cell therapies, not embryonic stem cell therapies. Their latest successes in the treatment of various cardiac conditions hold great promise for the safe, effective and ethical treatment of diseases that afflict a growing number of people each year. In 2005 alone, it was estimated that over 35% of all deaths in the United States were related to cardiovascular disease, and every day approximately 2,400 Americans die from complications of this “silent killer”. Additionally, over 6 million people in the U.S. alone are believed to have blood-flow problems to their legs, which is a contributing factor to cardiovascular disease.

TCA Cellular Therapy owns two patents for proprietary autologous adult stem cell processes and products that are derived from the patient’s own bone marrow, and currently the company is in four separate FDA-approved Phase I and Phase II clinical trials, for the use of autologous bone marrow-derived stem cells in: 1/ the treatment of infarcted myocardium during bypass surgery, 2/ the non-surgical rescue and repair of cardiac muscle following acute myocardial infarction, 3/ the treatment of severe limb ischemia and 4/ the treatment of severe coronary ischemia. Further clinical trials for spinal cord injury and ALS (amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease) are still pending FDA review, and future protocols are currently being designed for the treatment of Parkinson’s disease and idiopathic cardiomyopathy with autologous adult stem cells.

Common Enzyme Sheds Light on Health and Disease

Researchers at the Washington University School of Medicine in St. Louis report some interesting discoveries with the enzyme known as adenosine monophosphate-activated protein kinase (AMPK). Already known to be involved in a number of diseases, AMPK has been well studied by scientists for many years, but these new findings are the first of their kind to demonstrate that the enzyme is essential for the health of neural stem cells.

In a study led by Jeffrey Milbrandt, M.D., Ph.D., the researchers found that when they selectively deactivated the enzyme in mouse embryos, the overall brain size of each mouse shrunk by 50%, with dramatic shrinkage in both the cerebrum and the cerebellum to such an extent that the mice died within 3 weeks of birth. AMPK, it turns out, is a critical component for the survival of neural stem cells which in turn create and maintain the cells of the central nervous system, including the cells that are necessary for learning and memory. When AMPK is deactivated or absent altogether, normal neurological health cannot be maintained at the cellular level.

According to Dr. Milbrandt, “For years, scientists have shown how AMPK regulates multiple metabolic processes, and revealed how that influence can affect cancer, diabetes, and many other diseases. Now, for the first time, we’ve shown that AMPK can cause lasting changes in cell development. That’s very exciting because it opens the possibility of modifying AMPK activity to improve brain function and health.”

AMPK is directly involved in the regulation of cellular energy usage, and the enzyme is specifically activated whenever energy resources are low, such as during times of caloric restriction or sustained physical exercise. When activated, AMPK promotes cellular glucose uptake, mitochondria formation, fatty acid oxidation and other energy-producing cellular processes, while simultaneously inhibiting protein and fatty acid synthesis as well as cell reproduction and other energy-consuming cellular processes.

When activated, there is one particular version of AMPK that is capable of making its way into the nucleus of cells where it inactivates the retinoblastoma protein, “a master regulator” of cell production, which in turn allows neural stem cells to survive and proliferate. That particular version of AMPK, which contains the beta 1 subunit and which is only one of several versions of AMPK, is capable of penetrating both the cytoplasm and the nucleus of cells, whereas other versions, such as that which contains the beta 2 subunit, have only been found in the cytoplasm but never in the cell nucleus. As Dr. Biplab Dasgupta, a lead author of the paper, describes, “Inhibiting AMPK is something that most cells don’t like. It can lead to a variety of consequences, including cell death, but many cell types can tolerate it. In contrast, neural stem cells undergo catastrophic cell death in the absence of AMPK containing the beta 1 subunit. We also suspect loss of this form of AMPK may cause severe problems for other stem cells.”

Because of the role of cancer stem cells in some types of cancer, and the possibility of manipulating AMPK in cancer therapies, ideally the trick would be to inactivate AMPK in the cancer stem cells themselves, while simultaneously activating AMPK in the normal, non-cancerous cells.

Since the protein retinoblastoma, which the AMPK version with the beta 1 subunit regulates in the cell nucleus, plays such an important role in the differentiation of stem cells, these findings also have possible implications for the long-term health effects of malnutrion. According to a study that was conducted in 1977 on the children of women who were starved by the Nazis during World War II, these children remained at a high risk of various diseases throughout their lives, which included diabetes, heart disease and stroke. Even though these children, themselves, had never been subjected to starvation, their mothers may have incurred long-term damage to their stem cells as a result of their experiences, which in turn influenced the cellular health and development of their offspring.

On a lighter note, Dr. Dasgupta adds, “Exercise activates AMPK and improves cognitive function. Our results suggest brain function may improve because additional activated AMPK makes it easier for adult neural stem cells to reproduce and become new brain cells.”

As Dr. Milbrandt concludes, “Manipulating this regulation may enable us to encourage the development of new brain cells. We might use that not only to treat medical conditions where brain development is hampered, but also to improve cognitive function generally.”

A High-Profile Proponent of Embryonic Stem Cell Research Sharply Criticizes Obama’s Policy

When President Obama signed the Executive Order last week which overturned President Bush’s policy on stem cell research, the White House extended a warm invitation to the noted Dr. Charles Krauthammer, among other distinguished guests, to attend the official signing ceremony. Dr. Krauthammer declined the invitation, and vehemently refused to attend the ceremony. In his op-ed article in The Washington Post today, entitled “Obama’s ‘Science’ Fiction”, Dr. Krauthammer explains precisely why, and in no uncertain terms.

During the 5 years that Dr. Krauthammer served on President Bush’s President’s Council on Bioethics, and despite the fact that he had been personally appointed to the council by President Bush himself, Dr. Krauthammer consistently argued, as he explains, “that, contrary to the Bush policy, federal funding should be extended to research on embryonic stem cell lines derived from discarded embryos in fertility clinics.” The words, “derived from discarded embryos in fertility clinics” constitute the key point in Dr. Krauthammer’s stance under the Bush administration, which is precisely why he refused to accept President Obama’s invitation. “I declined to attend,” Dr. Krauthammer states. “Once you show your face at these things, you become a tacit endorser of whatever they spring. My caution was vindicated.” Dr. Krauthammer has now made it perfectly clear that he certainly does not endorse President Obama’s policy on stem cells, and far from remaining tacit on the subject, Dr. Krauthammer has authored an eye-opening and blunt assessment of President Obama’s mistakes in this matter.

Dr. Krauthammer begins his Washington Post op-ed piece by reminding the reader of the context within which the new administration’s actions have taken place. “President Bush had restricted federal funding for embryonic stem cell research to cells derived from embryos that had already been destroyed (as of his speech of August 9, 2001),” Dr. Krauthammer explains. “While I favor moving that moral line to additionally permit the use of spare fertility clinic embryos,” he continues, “President Obama replaced it with no line at all. He pointedly left open the creation of cloned – and noncloned sperm-and-egg-derived – human embryos solely for the purpose of dismemberment and use for parts.”

Lest anyone misunderstand Dr. Krauthammer, he further clarifies his stance by adding, “I am not religious. I do not believe that personhood is conferred upon conception. But I also do not believe that a human embryo is the moral equivalent of a hangnail and deserves no more respect than an appendix. Moreover, given the protean power of embryonic manipulation, the temptation it presents to science and the well-recorded propensity for evil even in the pursuit of good, lines must be drawn. I suggested the bright line prohibiting the deliberate creation of human embryos solely for the instrumental purpose of research – a clear violation of the categorical imperative not to make a human life (even if only a potential human life) a means rather than an end. On this, Obama has nothing to say. He leaves it entirely to the scientists. This is more than moral abdication. It is acquiescence to the mystique of ‘science’ and its inherent moral benevolence. How anyone as sophisticated as Obama can believe this within living memory of Mengele and Tuskegee and the fake (and coercive) South Korean stem cell research is hard to fathom.”

Dr. Krauthammer echoes the sentiments of many other scientists and doctors, few of whom enjoy the distinction, as Dr. Krauthammer does, of having won a Pulitzer Prize and of having been a former U.S. Presidential Science Advisor and of having their views and opinions deemed to be so insightful and valuable that they are regularly featured in the nation’s, and indeed the world’s, leading newspapers. Nor are there many scientists and doctors who personally received invitations from the White House to attend Obama’s signing ceremony, as Dr. Krauthammer did; perhaps even fewer would have had the courage and integrity to decline such an invitation, if they had been invited. Additionally, Dr. Krauthammer does not hesitate to make the point that, even if he had somehow managed to convince himself to go to the White House for the ceremony, he would not have stayed long.

As Dr. Krauthammer continues, “That part of the ceremony, watched from the safe distance of my office, made me uneasy. The other part – the ostentatious issuance of a memorandum on ‘restoring scientific integrity to government decision-making’ – would have made me walk out. Restoring? The implication, of course, is that while Obama is guided solely by science, Bush was driven by dogma, ideology and politics. What an outrage. Bush’s nationally televised stem cell speech was the most morally serious address on medical ethics ever given by an American president. It was so scrupulous in presenting the best case for both his view AND THE CONTRARY VIEW that until the last few minutes, the listener had no idea where Bush would come out. Obama’s address was morally unserious in the extreme. It was populated, as his didactic discourses always are, with a forest of straw men. Such as his admonition that we must resist the ‘false choice between sound science and moral values.’ Yet, exactly 2 minutes and 12 seconds later he went on to declare that he would never open the door to the ‘use of cloning for human reproduction.’ Does he not think that a cloned human would be of extraordinary scientific interest? And yet he banned it. Is he so obtuse as not to see that he had just made a choice of ethics over science? Yet, unlike Bush, who painstakingly explained the balance of ethical and scientific goods he was trying to achieve, Obama did not even pretend to make the case why some practices are morally permissible and others are not.”

The outrage that Dr. Krauthammer expresses so eloquently is mild in comparison to that which many other people feel, such as, for example, the numerous distinguished scientists and doctors who work exclusively with adult stem cells, not embryonic stem cells, and to whom Obama’s new policy, not to mention his insulting and confrontational remarks, are a direct and blatant affront. Most scientists and doctors, however, even those who work only with adult stem cells, stop just short of engaging in ethical debate. Dr. Krauthammer, however, is not so timid, and fortunately for the rest of us he is unafraid to call a spade a spade. As Dr. Krauthammer puts it, in regard to Obama’s actions, “This is not just intellectual laziness. It is the moral arrogance of a man who continuously dismisses his critics as ideological while he is guided exclusively by pragmatism (in economics, social policy, foreign policy) and science in medical ethics. Science has everything to say about what is possible. Science has nothing to say about what is permissible. Obama’s pretense that he will ‘restore science to its rightful place’ and make science, not ideology, dispositive in moral debates is yet more rhetorical sleight of hand – this time to abdicate decision-making and color his own ideological preferences as authentically ‘scientific’.”

Dr. Krauthammer’s words for Obama are not to be taken lightly, nor is Dr. Krauthammer’s stance on stem cell research. Having been paralyzed in an automobile accident in 1972 during his first year in medical school, Dr. Krauthammer has been a paraplegic and confined to a wheelchair for nearly 4 decades. If anyone could benefit from stem cell therapies, it would be Dr. Krauthammer. Despite the automobile accident, however, and despite the resulting year-long hospitalization and his permanent paraplegia, Dr. Krauthammer graduated with the rest of his class from Harvard Medical School in 1975 and went on to become a leading psychiatrist at the prestigious Massachusetts General Hospital in Boston. His seminal work, discoveries and publications during these years are still repeatedly cited today in the leading textbooks of the field. Although he is board certified by the American Board of Psychiatry and Neurology, he chose to leave medical practice in 1978 when he was appointed Presidential Science Advisor to President Carter. Since then, his views and analyses on a variety of national and international issues have been widely respected and specifically sought by presidential administrations of both parties; indeed, his views and analyses have helped to shape the very structure of formal U.S. national and international policy over the years.

In 2006, Charles Krauthammer, M.D., was named the “most influential commentator in America” by the Financial Times, which wrote: “Krauthammer has influenced U.S. foreign policy for more than two decades. He coined and developed ‘The Reagan Doctrine’ in 1985 and he defined the U.S. role as sole superpower in his essay, ‘The Unipolar Moment’, published shortly after the fall of the Berlin Wall. Krauthammer’s 2004 speech ‘Democratic Realism’ set out a framework for tackling the post 9/11 world, focusing on the promotion of democracy in the Middle East.”

In 1987 Dr. Krauthammer was awarded the Pulitzer Prize for his “distinguished commentary” and highly influential work at The Washington Post. To this day, his weekly column still appears in The Washington Post and is syndicated in more than 200 newspapers and media outlets around the world.

Even as a member of the President’s Council on Bioethics under President George W. Bush, Dr. Krauthammer did not hesitate to oppose President Bush’s stance on stem cell policy, even though he respected President Bush’s attempts to balance opposing views of the argument. Now, however, through Obama’s pretentious and grossly ill-advised statements on this gravely serious matter, the new president has not only disappointed but directly offended many people who had higher hopes for him, especially within the scientific and medical communities.

Dr. Krauthammer concludes his Washington Post op-ed article by quoting none other than Dr. James Thomson, the mild-mannered developmental biologist who suddenly skyrocketed to international fame when he became the first person to isolate a human embryonic stem cell in the laboratory in 1998, and who is now revered throughout the world as the “father” of embryonic stem cell science. As Dr. Krauthammer writes, “Dr. James Thomson, the pioneer of embryonic stem cells, said ‘if human embryonic stem cell research does not make you at least a little bit uncomfortable, you have not thought about it enough.’ Obama clearly has not.”

As someone whose keen insights have been so indispensable to so many U.S. presidents for so many years, on so many of the most pressing domestic and foreign policy issues of the day, Dr. Krauthammer has long been seen and valued by both political parties as someone whose expertise, and whose extraordinary breadth and depth of understanding on a wide range of issues, are invaluable. Today, especially on the topic of stem cells, Dr. Krauthammer’s analyses are particularly relevant not just because they come from someone who has been a prominent political advisor to U.S. presidents for nearly 40 years, but also because of Dr. Krauthammer’s accomplishments as a physician, as a medical researcher at one of the leading research hospitals in the world, and as a paraplegic. The current, new U.S. president, however, would seem to be the first U.S. president, ever, since prior to the Carter administration in the 1970s, who has chosen to ignore entirely what Dr. Krauthammer has to say.

Geron Seen as Scientifically and Financially Risky

During a conference call for institutional investors held Monday by Summer Street Research Partners, an independent health care research firm, a spinal surgeon and stem cell researcher offered a negative and cautionary view of Geron’s research. Subsequently, TheStreet.com decided not to disclose the doctor’s name due to privacy concerns, “since the call was not intended for public dissemination.” The doctor stated, however, that he has no financial ties to Geron, nor does he own, nor has he shorted, any of Geron’s stock. Nevertheless, the doctor pointed out that the highly publicized upcoming clinical trial for which Geron recently received FDA approval is clinically dubious because the entire rationale for the study is “based on a single experiment in 8 rats.”

In a highly controversial ruling, the FDA granted approval to Geron in January of this year to begin the first clinical trials ever to be conducted in the U.S. with human embryonic stem cells. The clinical trial will administer human embryonic stem cells to patients who have been paralyzed from the waist down with spinal cord injury. Since the primary objective of Phase I clinical trials is to test safety, efficacy will not be tested until years later – assuming, that is, that safety can be proven, although this remains the subject of widespread speculation. Without concrete evidence of safety, the proposed therapy cannot advance to further clinical trials.

In the days immediately following the FDA’s announcement, Geron’s stock soared from $5 a share to more than $48 a share, but such dramatic gains were quickly sold and the stock has steadily fallen ever since then, plummetting to a low of $3.79 on March 5th. According to Adam Feuerstein of TheStreet.com, “Even President Obama’s lifting of the federal research ban on stem cell research Monday failed to provide more than a marginal lift to Geron’s stock price, which closed Tuesday at $4.27”, up a mere 1.4%.

As Mr. Feuerstein further explains, “Wall Street’s health care investors, most notably biotech-focused hedge funds, have been more inclined to steer clear of Geron or short the company’s stock. Geron’s short interest has risen from 8 million shares to 17 million shares over the first two months of the year. Conference calls for Wall Street health care investors with experts critical of Geron’s research, like those held by Summer Street Research on Monday, explain why. The doctor on the Summer Street conference call, a spinal cord injury expert who has also conducted stem cell research, was skeptical about Geron’s study because there is very little animal data to support the theory that a therapy derived from [embryonic] stem cells will benefit patients with severe spinal cord injury.”

Indeed, as the doctor stated, “The fact that Geron’s entire study hinges on this one experiment in eight moderately injured rats is tenuous in terms of efficacy.”

This laboratory experiment upon which Geron’s upcoming clinical trial is based, was conducted by Dr. Hans Keirstead of the University of California at Irvine, using 8 rats in whom spinal cord injury had been deliberately inflicted in order to induce hind-leg paralysis. Rats that were treated with Geron’s human embryonic stem cell product saw a partial return of some function to their paralyzed legs after 7 days, but all of the rats were considered to have “moderate” spinal cord injury. However, when the start of treatment was delayed for more than a week, and also when the experiment was conducted on rats with severe spinal cord injuries, Geron’s therapy had no effect. The human patients who will participate in Geron’s clinical trial will not have moderate spinal cord injury, but instead they will have been chosen for the clinical trial because they suffer from severe spinal cord injury.

According to the doctor who spoke during the conference call, “We don’t know what will happen when these cells are placed into a human, which is the reason immune suppression is required. The risk is that these are not patients you would otherwise want to have on immune suppressants because the severity of their spinal cord injuries, the trauma they’ve suffered, their surgery and wounds make them more susceptible to infection.”

In Geron’s upcoming Phase I clinical trial, human embryonic stem cells will be injected directly into the spinal cords of the human patients. Ordinarily, after undergoing any type of transplantation, immune suppression is required for the remainder of the patient’s life, but the patients in Geron’s clinical trial will be removed from immunosuppressive drugs after 42 days, at which time there is a high risk of immune rejection by the patients’ bodies to the stem cells. In and of itself, this type of immune rejection has the potential to be life-threatening. As Mr. Feuerstein adds, “Another safety concern is the risk that the cells in Geron’s therapy may grow uncontrollably and form tumors on the spinal cord,” to which the doctor from the conference call further adds, “If one patient gets a tumor from the Geron therapy, it will be catastrophic.”

While the CEO of Geron, Tom Okarma, has tried to downplay expectations of efficacy by reminding the public that none of the patients are expected to be instantly cured from the Phase I clinical trial, it is a bit more difficult to dispel concerns about safety.

Despite the fact that Geron’s preclinical data is based upon only one experiment with only 8 rats, Geron’s FDA application nevertheless included a staggering 22,000 pages of data. Although such an unwieldy number might impress those who are uninitiated in “the scientific method”, Mr. Feuerstein points out that such an enormous FDA application “has not stopped some experts from questioning Geron’s science.” One such expert is Dr. Evan Snyder of the California- and Florida-based Burnham Institute for Medical Research, who wrote in an article that was published in the January 30th issue of the journal Science that, “There’s a lot of debate among spinal cord researchers that the preclinical data itself doesn’t justify the clinical trial.” Similarly, in the January 23rd edition of The New York Times, Dr. John Kessler, a neurologist and director of the Stem Cell Institute at Northwestern University, wrote, “We really want the best trial to be done for this first trial, and this might not be it.”

As every investor knows, financial markets are forward-looking, and the price of any particular stock at any particular time is a measure of confidence in that company. In Geron’s case, as with all other biotechs, the financial details are inextricably tied to the scientific details. Precisely for that reason, therefore, at least at this particular moment in history, institutional investors are growing increasingly wary of Geron because of the serious words of caution that are echoed throughout the medical and scientific communities.

Obama Signs Law Restricting Federal Funding of Embryonic Stem Cell Research

A mere two days after supposedly reversing President Bush’s restrictions on the federal funding of human embryonic stem cell research, President Obama today signed into law a ban on the use of federal funding for human embryonic stem cell research. Contrary to popular misunderstanding, therefore, legislative restrictions have not been reversed.

Without any publicity or fanfare whatsoever, and in a move that counteracts and contradicts his highly publicized action a mere two days earlier, President Obama today signed a law that bans the federal funding of any procedure that involves either the creation or the destruction of a human embryo for research purposes. Since the process by which embryonic stem cells are extracted from an embryo results in the immediate destruction of that embryo, such a law makes the federal funding of embryonic stem cell research on human embryos, and the derivation of new human embryonic stem cell lines from those embryos, illegal.

The specific piece of legislation under consideration is the Dickey-Wicker Amendment, which was first signed into law in 1995 under the Clinton Administration. It is this Amendment which remains the primary legislative “obstacle” to embryonic stem cell research – not the comparatively trivial funding restraints which Obama overturned two days earlier and which were mistakenly interpreted by many to represent a grand, sweeping change in national policy; in actuality, the only policy that Obama was able to change two days ago was an increase in the applicability of federal funds to a few hundred human embryonic stem cell lines, instead of to the approximately 21 human embryonic stem cell lines that were already created prior to President Bush’s Executive Order on August 9th of 2001.

The Dickey-Wicker Amendment was included today in the 465-page Omnibus spending bill that will fund government agencies through September 30th of this year, which is the end of the fourth quarter of the 2009 fiscal year (FY09). As the Amendment specifically states, “None of the funds made available in this Act may be used for: 1/ the creation of a human embryo or embryos for research purposes, or 2/ research in which a human embryo or embryos are destroyed, discarded or knowingly subjected to risk of injury or death.” Since the extraction of embryonic stem cells from an embryo results in the immediate destruction of that embryo, as already explained, such language pertains directly to the creation of new human embryonic stem cell lines.

It is the creation of new human embryonic stem cell lines, however, that embryonic stem cell scientists covet the most, not the authorization to spend federally awarded grant money on already existing human embryonic stem cell lines. In regard to the creation of new human embryonic stem cell lines, President Obama has changed nothing, nor does he have the power to change this law by himself since only Congress, not the president, can overturn such an Amendment. Not surprisingly, some members of Congress are actively mobilizing their efforts to do exactly that. Nevertheless, the Dickey-Wicker Amendment only applies to the use of federal money, not to the use of private (non-taxpayer) money, so it is still perfectly legal, as it has always been, to create and destroy as many human embryos as one wants, as long as it is done with private (non-taxpayer-derived) funding.

Named after its authors, Representatives Jay Dickey of Arkansas and Roger Wicker of Mississippi, the Dickey-Wicker Amendment was originally passed in 1995 under the Clinton Administration as a rider attached to the appropriations bill for the Department of Health and Human Services, and Congress has actively voted to renew the Amendment every year since then, although that could change by the end of this year. To reiterate, it was President Bill Clinton who signed this Amendment into law, not President George W. Bush, who merely inherited it.

At least until September 30th of this year, therefore, it will still be illegal to spend federal funding (i.e., NIH grant money, which comes directly from the U.S. taxpayer) on any human embryonic stem cell research that involves newly created human embryonic stem cell lines, since, by necessity, the creation of such stem cell lines requires the destruction of the human embryos from which the cells are derived.

Democratic Representative Diana DeGette of Colorado and Republican Representative Mike Castle of Delaware, who twice failed to overturn Bush’s funding restrictions, are now trying to pass legislation to repeal the Dickey-Wicker Amendment. Similarly, an editorial in The New York Times on Tuesday called for Congress to repeal the Dickey-Wicker Amendment, but opposition still remains strong.

According to Douglas Johnson, spokeman for the National Right to Life Committee, “This sets the stage for an attack on the Dickey-Wicker law. Any member of Congress who votes for legislation to repeal this law is voting to allow federal funding of human embryo farms, created through the use of human cloning.” In his highly publicized and widely applauded though generally misunderstood speech on Monday, Obama assured people who have ethical concerns about embryonic stem cell research that his policy is designed so that it “never opens the door to the use of cloning for human reproduction”, which he described as “dangerous, profoundly wrong, and has no place in our society or any society.” However, the overturning of the Dickey-Wicker Amendment would be seen by many as a slippery slope that would inevitably lead not only to cloning but also to a number of other consequences that would be “dangerous” and “profoundly wrong”, to use Obama’s own words.

Nevertheless, only Congress, not the president, can overturn the Dickey-Wicker Amendment, which still remains in effect as the law, at least until September 30th of this year. Contrary to popular misconception, therefore, President Obama has not entirely reversed the legislative policies that he seems to be credited with reversing, and which he inherited from his predecessor – who, in turn, inherited the Dickey-Wicker Amendment from his predecessor, President Bill Clinton.

One can only marvel at how and why Obama happened to legalize the federal funding of human embryonic stem cell research on Monday, while surrounded by carefully orchestrated applause and fanfare, and then immediately perform an about-face a mere 2 days later and ban human embryonic stem cell research on Wednesday, without any reporters or television cameras present and with no fanfare whatsoever.

(Please see the related news article on this website, entitled, “Obama Decrees Changes in Embryonic Stem Cell Research, Though Not What One Might Expect”, dated March 9, 2009).

How to Mend a Broken Heart

Former heart patients such as Howard Lindeman and Dick Dufala are strong advocates of adult stem cell therapy, and their enthusiasm is the result of personal experience. Along with many other people who share similar stories, Mr. Lindeman and Mr. Dufala have adult stem cell therapy to thank for the fact that they are no longer in danger from the life-threatening heart conditions with which they had previously suffered.

According to Mr. Lindeman, who chose to undergo adult stem cell therapy follwing a heart attack, “It’s the most amazing thing I’ve ever been through. I had the procedure done and since then, I’ve just been getting better and better and better. I’m going to be 58 years old in May and I’m on my way to being 35 again.”

Similarly, according to Mr. Dufala, who used to suffer from congestive heart failure before receiving adult stem cell therapy, “I think it’s improved my life and my life will be extended as a result of having the procedure. I feel like I don’t have congestive heart failure. I feel quite good.”

Both men underwent their adult stem cell therapies from the cardiologist Dr. Zannos Grekos, who uses autologous (in which the donor and recipient are the same person) adult stem cells derived from each patient. Speaking at a seminar recently in Naples, Florida, Dr. Zannos explained, “Because it is coming from the patient, there’s no [immune] rejection and there’s no risk of cancer because we’ve been using adult stem cells for about 40 years in treating cancers. We know that adult stem cells are effective.”

By stating that “there’s no risk of cancer”, Dr. Zannos is referring to the fact that embryonic stem cells are defined by their ability to form teratomas (tumors), which is the formal scientific definition of pluripotency, whereas adult stem cells are not capable of forming such tumors for the simple reason that adult stem cells are not pluripotent. Similarly, in his statement that “we’ve been using adult stem cells for about 40 years in treating cancers”, Dr. Zannos is referring to the fact that bone marrow transplants have been conducted for several decades now, and the mechanism-of-action by which bone marrow transplantation is effective is through the adult stem cells that are present in the bone marrow. More specifically, the first bone marrow transplant was performed in 1956, which was over 5 decades – over half a century – ago. It was Dr. E. Donnal Thomas of Cooperstown, New York, who performed this first successful bone marrow transplant that resulted in the long-term survival of the patient who subsequently enjoyed a complete remission of leukemia after being given a bone marrow transplant from an identical twin. For this first, pioneering medical procedure, Dr. Thomas was awarded the Nobel Prize in Physiology or Medicine, along with Dr. Joseph E. Murray, “for their discoveries concerning organ and cell transplantation in the treatment of human disease.” This revolutionary transplantation paved the way for numerous other transplants of a similar nature, which in turn were followed in 1968 by the first bone marrow transplant from a related donor in the treatment of a non-cancerous condition, namely, in the treatment of a four-month-old boy who had inherited severe combined immunodeficiency syndrome. This procedure in turn opened the door for numerous other bone marrow transplantations for non-cancerous conditions, which in turn were also followed in 1973 by the first bone marrow transplant using an unrelated donor, which was performed at Memorial Sloan-Kettering Cancer Center in New York City and which likewise paved the way for numerous other procedures of a similar nature. It has therefore been for over the past 50 years that bone marrow transplantation has demonstrated the safety and efficacy of the adult stem cells that are present in bone marrow. If one were to trace the history of umbilical cord blood therapies, one would find that these therapies extend back even farther in time and predate World War II by at least a decade, and for over the past 70 years the various uses of the adult stem cells that are present in umbilical cord blood have been documented in the medical literature for the treatment of a vast number of people for a variety of conditions, without adverse side effects. Although the concept of a human stem cell, per se, was not yet understood at these times, prior to World War II nor even in 1956 when the first bone marrow transplant was performed, today it is well known and understood that bone marrow transplants and umbilical cord blood work as effective treatments because of the adult stem cells that they contain. By contrast, the first human embryonic stem cell was only isolated in the laboratory in 1998, so embryonic stem cell science is barely a decade old, and in that short decade embryonic stem cells have never been used to treat anyone for anything. A clinical history, therefore, does not exist, at all, for embryonic stem cells, which thus far can be said to have a 0% success rate, which is the equivalent of a 100% failure rate. Since embryonic stem cells carry a number of inherent risks, not the least of which is their strong natural ability to form teratomas (tumors), even the most ardent of embryonic stem cell proponents has cautioned that an actual therapy based upon embryonic, not adult, stem cells is at least another decade away, if such a goal is attainable at all. Meanwhile, there are many patients who cannot wait that long for treatment, and fortunately adult stem cells are already being used as clinical therapies to help such people.

In reference to the natural regenerative ability of the body’s own adult stem cells, even in full-grown adults, Howard Lindeman adds, “The people who doubt it should stop doubting because it is a fact that our body can heal itself. If it didn’t, I’d be dead right now.”

Obama Rescinds Bush-Era Executive Order Pushing for More Ethical Stem Cell Research

The Executive Order which Obama signed yesterday formally and specifically rescinded Executive Order 13435, which President Bush signed into law on June 20th of 2007, and which was an initiative pushing the Secretary of Health and Human Services to “conduct and support research” on stem cells that “may result in improved understanding for treatments for diseases and other adverse health conditions, but are derived without creating a human embryo for research purposes or destroying, discarding, or subjecting to harm a human embryo or fetus” – such as, for example, therapies developed from research conducted on adult stem cells and on iPS (induced pluripotent stem) cells. Consequently, in response to President Bush’s 2007 Executive Order, the NIH (the National Institutes of Health) drew up a plan at that time for implementing President Bush’s order, in which the NIH authors stated that, “Adult stem cells, such as blood-forming stem cells in bone marrow … are currently the only type of stem cell commonly used to treat human diseases.” Indeed, the only type of stem cell research that has ever yielded an actual treatment for anything is adult stem cell research, which is already being used in clinics around the world for a wide variety of diseases and injuries. By sharp contrast, embryonic stem cells have never resulted in any therapies for anything.

President Obama is not without his critics, especially in his decision to rescind this particular Executive Order of President Bush, which did not prohibit anything but instead specifically encouraged further research with adult stem cells and other non-embryonic sources of adult stem cells, such as iPS cells. One such critic of Obama, the bioethicist Wesley Smith, points out that Obama is putting politics and ideology above science – the very thing that Obama accuses his predecessor of doing. According to Wesley Smith, “I can think of only two reasons for this action, for which I saw no advocacy either in the election or during the first weeks of the Administration: first, vindictiveness against all things ‘Bush’ or policies considered by the Left to be ‘pro-life’; and second, a desire to get the public to see unborn human life as a mere corn crop ripe for the harvest. So much for taking the politics out of science!”

The precise reasons why Mr. Obama decided to overturn an Executive Order that sought to attain stem cell therapies from non-embryonic sources such as adult stem cells and iPS cells, is anyone’s guess. One would think that “a man of faith”, as President Obama describes himself, would be in favor of such research and development purely on ethical grounds, if not also on scientific grounds, which are considerably more compelling for adult stem cells than for embryonic stem cells. To the contrary, however, yesterday’s actions by Obama demonstrate not only that he is strongly pro-embryonic stem cell research, at all costs, but also that he is strongly anti-adult stem cell research.

According to House Minority Leader John Boehner of Ohio, “Advancements in science and research have moved faster than the debates among politicians in Washington, D.C., and breakthroughs announced in recent years confirm that the full potential of stem cell research can be realized without the destruction of human embryos.”

As Republican Senator Richard Shelby of Alabama also adds, “My basic tenet here is I don’t think we should create life to enhance life and to do research and so forth. I know that people argue there are other ways. I think we should continue our biomedical research everywhere we can, but we should have some ethics about it.”

(Please see the related article on this website, entitled, “Obama Decrees Changes in Embryonic Stem Cell Research, Though Not What One Might Expect”, dated March 9, 2009).