BioTime Inc. has announced the addition of 4 new members to its Board of Directors: Neal C. Bradsher, Arnold I. Burns, Abraham E. Cohen, and Alfred D. Kingsley, with Mr. Kingsley appointed to serve as Chairman of the Board. The new members were elected on the basis of their experience in corporate finance, corporate governance, and the pharmaceutical industry.

Neal C. Bradsher, who holds a B.A. degree in economics from Yale and is a Chartered Financial Analyst, was previously a Managing Director at Whitehall Asset Management, Inc., and had formerly served as senior equity analyst at Alex Brown & Sons as well as at Hambrecht & Quist, in addition to having been a managing director at Campbell Advisors. Currently Mr. Bradsher is President of the private investment firm Broadwood Capital, and is also a director of Questcor Pharmaceuticals.

Currently Arnold I. Burns is Chairman of the strategic management consulting firm QuanStar Advisor Group, LLC. A practicing attorney for nearly 40 years with a J.D. degree from Cornell Law School, Mr. Burns was a managing director of Arnhold and S. Bleichroeder, Inc., and of Natexis Bleichroeder. He also served as Deputy Attorney General of the United States and as Chief Operating Officer of the Department of Justice, from 1986 to 1988. He has also been a partner with the New York law firm of Proskauer Rose, LLP.

Formerly Senior Vice President and President of the Merck Sharp & Dohme International Division within Merck & Co., Abraham E. "Barry" Cohen has enjoyed a long career in the pharmaceutical industry where he was instrumental in the development and expansion of Merck’s international business presence throughout Asia and Europe. Currently Mr. Cohen serves as a director of several public companies including Chugai Pharmaceutical Co., Teva Pharmaceutical Industries, and MannKind Corporation, among others. Additionally, he is an independent international business consultant and is also Chairman and President of Kramex Company, a privately owned consulting firm.

Currently Alfred D. Kingsley is the general partner of Greenway Partners, L.P., a private investment firm, and President of Greenbelt Corp., a business consulting firm which served as BioTime’s financial advisor from 1998 until earlier this year. He holds a B.S. degree in economics from the Wharton School at the University of Pennsylvania, and a J.D. degree and LLM in taxation from New York University Law School. Mr. Kingsley also held the position of Senior Vice President at Icahn and Company and its affiliated entities for more than 25 years.

BioTime’s two largest shareholders are Broadwood Parners, L.P. – the investment partnership managed by Neal Bradsher through its general partner, Broadwood Capital – and Alfred Kingsley, both directly and indirectly through his affiliated investment and management companies.

As BioTime’s CEO, Dr. Michael West, announced, "We are deeply grateful for this commitment from such an accomplished group of individuals. The breadth of their experience in business, governance, and finance will be of great benefit to the Company’s management in building BioTime’s new businesses in the field of stem cells and regenerative medicine. The creation of an independent board of directors for BioTime is an important step in building the company and is consistent with the corporate governance requirements of national securities exchanges. Moreover, the participation of Mr. Bradsher and Mr. Kingsley will advance the interests of corporate democracy by giving our two largest shareholders a direct voice on our Board."

Mr. Kingsley replied by stating, "The Board looks forward to working with BioTime’s management in realizing the potential of the revolution in regenerative medicine initiated by Dr. West."

Headquarterd in Alameda, California, BioTime is focused on the development and commercialization of technology and products related to blood plasma volume expanders for use in emergency trauma treatment, surgery and related applications. Its wholly owned subsidiary Embryome Sciences is "focused on developing an array of research and therapeutic products using human embryonic stem cell technology", as described on the personal website of Michael West, Ph.D., molecular gerontologist and BioTime’s CEO. Prior to his work with BioTime, Dr. West founded the Geron Corporation, which received FDA approval earlier this year to commence the first human clinical trials ever to be conducted with hESCs.

(Please see the related news articles on this website, entitled, "BioTime Receives Second Round of Funding", dated July 13, 2009, and "BioTime Announces Agreement With Millipore", dated July 9, 2009).

Scientists at the Institute of Human Genetics in the Northeast England Stem Cell Institute at Newcastle University in England have announced the creation of human spermatozoa from embryonic stem cells. Their study, published in the medical journal Stem Cell and Development, addresses an issue that influences the lives of approximately 7.3 million Americans: infertility.

In an article entitled, “In Vitro Derivation of Human Sperm from Embryonic Stem Cells”, Dr. Karim Nayernia and his colleagues describe a procedure by which human male gametogenesis is modeled in vitro. From human embryonic stem cells (hESCs), the scientists established male germline stem cells (GSCs) which were then stimulated to enter meiosis, thereby generating haploid motile “sperm-like” cells in vitro. Most strikingly, these “sperm-like” cells were able to mimic many of the properties of functional human sperm. While the current study used embryonic stem cells, which thus would not be viable for practical use in the treatment of infertility, the scientists are now trying to generate sperm from iPS (induced pluripotent stem) cells, a type of stem cell derived from somatic (non-stem cell) cells which mimic embryonic stem cells in its pluripotency. (More information about iPS cells may be seen on the video available at this link: iPS cells video). However, a full elucidation has not yet been provided for the precise ways in which these “sperm-like” cells – which the researchers have named in vitro derived (IVD) sperm – may or may not be identical to naturally occurring sperm.

As Dr. Nayernia explains, “We have a system which enables us for the first time to produce human sperm from stem cells. Studying sperm maturation is not accessible in vivo. You cannot follow the system. Now we have a system to monitor the stages of male infertility. This is very amazing and very exciting. They have heads, they have tails and they move. The shape is not quite normal nor the movement, but they contain the proteins for egg activation.”

The abnormal motility and morphology of the IVD sperm are of serious concern to a number of other scientists, however, for whom such a procedure raises a number of questions. According to Dr. Edmund Sabanegh Jr., director of the Center for Male Infertility at the Cleveland Clinic, “Some groups have raised questions about the research. There are huge ethical and safety implications of this. In theory, it’s exciting for couples that are struggling with this problem.” As Dr. Byron Petersen, associate professor in the Department of Pathology at the University of Florida, adds, “I would be very skeptical at this point and really look at what they define as sperm. An actual moving sperm cell or just a haploid cell that can be used to implant into an egg cell? The devil is in the details and it will be how they define their cell phenotype and what-not.”

This recent publication is an extension of previous studies that Dr. Nayernia and his colleagues conducted three years ago, at which time they developed a similar in vitro process for mouse sperm. When the IVD mouse sperm were used to inseminate mice in order to produce offspring, however, the newborn mice that were created from the artificial sperm died shortly after birth. A number of scientists therefore question the genetic viability of the IVD sperm as well as the viability of the technique by which each spermatozoon is artificially derived.

Although it is currently illegal in the U.K. as well as in the U.S., among other countries, to try to use the artificially derived human IVD sperm to fertilize human ova in order to create human offspring for reproductive purposes, it is still legal under U.K. law to use the IVD sperm to fertilize human ova in order to create human offspring for research purposes, as long as any embryos created by this method are destroyed by 14 days of age. Even if it were legal to allow such embryos to continue developing for reproductive purposes, the consequences could be disastrous if the IVD sperm were genetically unstable or flawed.

Although embryonic stem cells (ESCs) are so highly coveted because of their alleged pluripotency, in actuality the single celled human zygote – from which all ESCs develop – is totipotent. While totipotency (from the Latin “totus”, meaning “total” or “complete”) describes cells that are capable of differentiating into embryonic as well as extra-embryonic cell types, by contrast, pluripotency describes cells that are only capable of differentiating into embryonic cell types – namely, all cell and tissue types of the body, from all 3 germ layers – but not extra-embryonic cells and tissue, such as the placenta. Both male and female haploid gametes – spermatozoa and ova – are derivable from a population of “primordial germ cells” (PGCs) and “germline stem cells” (GSCs) which arise in early embryogenesis and later develop into the gonocytes that are responsible for gametogenesis, namely, spermatogenesis in males and oogenesis in females. In males it is not until long after birth that the gonocytes begin differentiating into adult male germline stem cells, known as spermatogonial stem cells (SSCs), which are both self-renewing and capable of producing spermatozoa. As the authors describe, SSCs “are unique stem cells in that they are solely dedicated to transmit genetic information from generation to generation.” While somatic (mature, non-stem cell) cells throughout the body are diploid (containing 46 chromosomes), gametes (ova and spermatozoa) are haploid cells (containing 23 chromosomes). The ability to generate such a highly specialized cell as a haploid spermatozoon from a diploid ESC is therefore significant not only because of the possible therapeutic medical applications but also because of the particular pathway by which primordial and germline cells are used for the in vitro acceleration of gametogenesis. As Dr. Nayernia further points out, “Other cell types don’t generate the next generation. This makes a very big difference between our study and the study of other cell types from embryonic stem cells.”

While the particular focus of this study was male gametogenesis, some scientists have begun to extrapolate similar procedures that may be applicable to female gametogenesis. Although Dr. Nayernia and his team were unsuccessful in trying to differentiate IVD sperm from female embryonic stem cells – as one would logically expect, since the Y chromosome must be present for sperm maturation – nevertheless other researchers are hypothesizing ways in which it might be possible to differentiate IVD ova from female embryonic stem cells, which contain only the X chromosomes.

As more and more people are waiting until later in life to have children, infertility is a growing problem around the world, especially in developed nations. According to a 2002 National Survey of Family Growth conducted by the Centers for Disease Control and Prevention in Atlanta, Georgia, it has been estimated that approximately 7.3 million people in the U.S. alone suffer from infertility, more than one third of whom are male.

If it could be possible to create safe and viable human spermatozoa from an alternate source, such as from embryonic stem cells, the procedure could have widespread therapeutic applications in reproductive medicine. In the wrong hands, however, there is also the risk of commercial exploitation.

Dr. Robert Lanza is adjunct professor at the Institute of Regenerative Medicine at Wake Forest University School of Medicine and chief scientific officer of Advanced Cell Technology Corporation (ACTC) – the company previously directed by the pioneering molecular gerontologist Michael D. West, Ph.D., who served as chairman of the board, chief scientific officer, CEO and President of ACTC from 1998 until 2007. ACTC specializes in the cloning of animals, including transgenic animals (hybrid species containing the genes of different species, usually human genes in combination with nonhuman genes), as well as in the controversial technique known as “therapeutic cloning”. Nevertheless, according to Dr. Lanza, and in specific reference to the possibility of creating artificial sperm, “What’s most concerning about this potential technology is that anyone, young or old, fertile or infertile, straight or gay, could potentially pass on their genes to a child from just a few cells. For instance, if you had a few skin cells from Albert Einstein – or perhaps even a hair follicle from the Pope or Queen Elizabeth – you could generate pluripotent stem cells. Any couple could go to an IVF clinic and have a child that is half, say, Albert Einstein, or perhaps Brad Pitt or Elizabeth Taylor.” It seems as though a number of technical hurdles remain to be overcome, however, before such concerns could materialize. Nevertheless, no doubt it is just a matter of time before such technological glitches are resolved, and many people wonder how the national laws and scientific guidelines of regulatory and oversight agencies will be able to address such changes. As CBS reporter Peter Allen cautions, “What these and other researchers are doing is ripping up the codes of law and morality by which we conduct our lives. The pace of discovery has left our legislators floundering.”

Indeed, while Dr. Lanza’s concerns may sound like science fiction, the generation of iPS cells has previously been performed from many types of tissues that can easily be stored across decades if not also centuries. Although it is somewhat of a barrier that iPS cells have not yet been made into sperm cells, thus far every cell type that has been generated from embryonic stem cells has also been generated from iPS cells. Accordingly, the ethical questions of using such technology should be addressed as soon as possible, since scholars believe it will be within the next decade that frozen somatic cells such as skin cells will be successfully used for the generation of new sperm.

Dr. Nayernia and his colleagues used a special “cocktail” of growth factors, nutrients and retinoic acid (a derivative of vitamin A), among other chemicals, to create the IVD sperm from embryos that were discarded from IVF clinics. As previously mentioned, Dr. Nayernia and his colleagues are now working on developing a similar method for the creation of IVD sperm from mature somatic skin cells derived from infertile men.

As the authors conclude in their publication, “Understanding the mechanisms of germ cell specification, development and its differentiation to sperm is important for elucidating the causes of male infertility. … While the full potential of the human ES-derived germ cells and sperm remains to be demonstrated, this in vitro modeling of human gametogenesis provides a new approach for studying the biology of human germ cells and for the establishment of therapeutic approaches in reproductive medicine.”

On the other hand, the findings of Dr. Nayernia and his colleagues, although exciting, still have several drawbacks. For example, these cells have not been able to successfully fertilize a human egg and generate offspring. This is actually the vital test, although it has not yet been successfully performed – and given the problems that were encountered when Dr. Nayernia and his colleagues attempted the procedure three years ago in mice, it might be quite awhile before such a procedure is successfully accomplished in humans – with or without the laws that forbid such experimentation.

Perhaps an even more significant and relevant study for male infertility, which did not receive as much media exposure as Dr. Nayernia’s, was that reported by Swerdloff’s group from Los Angeles. (Lue et al., ‘Fate of bone marrow stem cells transplanted into the testis: potential implication for men with testicular failure’, Am J Pathol 2007 Mar;170(3):899-908). In this study the scientists found that the administration of bone-marrow-derived adult stem cells into the testicles of mice could generate new cells that look and act like sperm. Implications of such a study might include new procedures for the treatment of infertile males that involve the therapeutic use of the patient’s own bone marrow. Additionally, an independent German group (Dursenheirmer et al., ‘Putative human male germ cells from bone marrow stem cells’, Soc Reprod Fertil Suppl. 2007;63:69-76) has also reported that bone-marrow-derived adult stem cells can be induced to become the cells that give rise to sperm cells based on the expression of specific proteins on the surface of the cells. From studies such as these, one can only conclude that the prospects for developing infertility treatments with stem cells are encouraging, with advances being made both from bone-marrow-derived adult stem cells and from embryonic stem cells, despite the many technological hurdles that still remain.

Certainly no one is more aware of such technological hurdles than Dr. Nayernia, who adds, “We think, for normal structural development, sperm needs the testes environment. In the human, sperm development is a very long process. It takes more than 15 years and is not an accessible system. With this system, we can now watch that development in three months.”

But in regard to the ethical and legal dilemmas that are engendered by such procedures, we are only just beginning to see the tip of the iceberg. As Dr. Insoo Hyun, a bioethicist at Case Western Reserve University, explains, “We have the potential therapeutic use of a technology that pushes the boundaries of what people feel comfortable with ethically. This area has potential powerful clinical applications mixed with people’s concerns over embryo research. All the ingredients are there for a really, really lively ethical debate.”

Attempting to establish a new direction for national policy, today the National Institutes of Health released the final copy of its Guidelines on stem cell research.

The Guidelines are in response to President Obama’s Executive Order 13505, issued on March 9, 2009. According to NIH, "These Guidelines implement Executive Order 13505, as it pertains to establish policy and procedures under which the NIH will fund such research, and helps ensure that NIH-funded research in this area is ethically responsible, scientifically worthy, and conducted in accordance with applicable law. Internal NIH policies and procedures, consistent with Executive Order 13505 and these Guidelines, will govern the conduct of intramural NIH stem cell research."

On April 23 of this year, NIH published a draft of the Guidelines for research involving human embryonic stem cells (hESCs), after which a "comment period" lasted for approximately the next month, until May 26, during which time NIH accepted comments from the general public.

Under the new Guidelines, NIH has established a review process by which scientists will be able to use many of the hESC lines that already exist and which were created by private funding. Newly established hESC lines will qualify for research provided certain criteria are met, such as rules pertaining to "voluntary and informed consent" from the donors. In other words, the donors must be informed in writing of other options for their surplus embryos, as well as of the fact that any embryo donated for scientific research will be destroyed in the process. Financial as well as nonfinancial compensation of any kind is forbidden in return for the donated embryos. Additionally, embryo donors must be allowed to change their minds within a specified time frame, and they must not expect medical nor financial benefits from their donated embryos. Additionally, NIH funding will only apply to hESCs that are obtained from the surplus embryos of IVF clinics and which were created specifically for reproductive purposes, not for scientific research.

Issues relating to informed consent were among the most hotly debated points of the earlier draft version of the Guidelines, which would render most of the already existing hESC lines ineligible for funding. In order to address such concerns, NIH has agreed to establish a review panel to determine if some of the already existing cell lines might still qualify for federal funding.

In the new Guidelines, NIH has still banned the federal funding of any hESC lines that might be created from so-called "therapeutic cloning" methods, more correctly known as somatic cell nuclear transfer (SCNT), which is also the same procedure used in reproductive cloning. Despite the fact that no one has ever actually succeeded in deriving a hESC line from SCNT, nevertheless there are many ESC scientists who had hoped that NIH would allow funding of hESCs that might someday be created by this highly controversial procedure.

By some accounts, as many as 60% of the comments that NIH received in regard to their earlier draft of the Guidelines had come from people who expressed disapproval of the use of taxpayer money for research that will destroy human embryos. According to the Catholic News Service, at least 30,000 of the 48,955 comments which NIH received were from individuals and organizations who voiced opposition to hESC research but who strongly favored adult stem cell research instead. However, NIH dismissed such comments as being "not responsive to the question put forth." In a July 6 telephone briefing to the media, Dr. Raynard S. Kington, acting director of NIH, reacted to this fact by stating, "We did not ask them whether to fund such funding, but how it should be funded."

According to Cardinal Justin Rigali, Chairman of the U.S. Catholic Bishops’ Committee on Pro-Life Activities, "The comments of tens of thousands of Americans opposing the destruction of innocent human life for stem cell research were simply ignored in this process. Even comments filed by the Catholic bishops’ conference and others against specific abuses in the draft guidelines were not addressed."

According to Cardinal Rigali, NIH failed to address specific abuses of hESCs which might potentially occur after the cell lines have been obtained. Even though Section IV of the Guidelines specifically prohibits the introduction of hESCs into "primates," as well as the "breeding" of human cells with the cells of primates, nevertheless the laboratory creation of other types of "chimeras" and human-nonhuman mixed species is still allowed. As Cardinal Rigali adds, "For example, federally funded researchers will be allowed to insert human embryonic stem cells into the embryos of animal species other than primates. Federal grants will be available even to researchers who themselves destroyed human embryos to obtain the stem cells for their research. Existing federal law against funding research in which human embryos are harmed or destroyed is not given due respect here."

Both conservative and liberal critics of the new NIH Guidelines point out that the final version differs minimally in substance from the earlier draft proposed in April. Those who are in favor of hESC research criticize the new Guidelines for complications that may result from the "voluntary and conformed consent" rules, as well as for not allowing funding of future hESC lines that might be obtained from SCNT. Pro-life supporters, on the other hand, criticize the new Guidelines for having ignored nearly two-thirds of all comments received from people who advocated adult stem cell research over embryonic stem cell research.

Even though the new Guidelines forbid the federal funding of any research conducted on human embryos that are deliberately created only for research purposes, the Legislative Director of the National Right to Life Committee, Douglas Johnson, echoes the concern of many scientists as well as non-scientists when he states that, "This seeming restraint is part of an incremental strategy intended to desensitize the public to the concept of killing human embryos for research purposes. The Obama Administration today slides further down the slippery slope of exploiting non-consenting members of the human species – human embryos."

The full NIH Guidelines may be read in their entirety on the website of NIH, at: http://stemcells.nih.gov/policy/2009guidelines.htm.

(Please see the related news articles on this website, entitled, “NIH Receives Nearly 50,000 Comments”, dated June 5, 2009; “Pros and Cons of the New NIH Guidelines”, dated June 3, 2009; “Embryonic Stem Cell Advocates Protest NIH Guidelines”, dated May 25, 2009; and “NIH Issues Guidelines Restricting Embryonic Stem Cell Research”, dated April 17, 2009).

The embryonic stem cell company Geron, and the multinational conglomerate General Electric, have announced the signing of a global licensing agreement in which Geron will provide human embryonic stem cells (hESCs) to GE’s Healthcare division for the toxicity testing of drugs. The hESCs will not be used for the development of cell-based therapies.

According to a statement that GE made in 2005, "GE will not be associated with the primary harvest of human embyro-derived cells or tissues. We acknowledge the considerable debate and take very seriously the ethical and societal issues associated with research using stem cells derived from embryonic or fetal tissue. We conduct our research in an ethically and scientifically responsible manner."

Therefore, according to Geron, the hESCs that are to be provided to GE were derived from human embryonic stem cell lines that were approved under policies established by the Bush administration in 2001. Contrary to popular misconception, hESC research was not forbidden under the Bush administration but in fact was conducted in laboratories and corporations across the entire United States during the entire Bush presidency. As long as the research met specific guidelines, it even received federal funding, and if it did not meet those guidelines then the research was usually conducted anyway, but with private funding instead of federal funding.

Under the new agreement between GE and Geron, Geron will provide the hESCs to GE who will develop and commercialize lab equipment that facilitates the use of the hESCs in drug development and toxicity screening. The lab equipment will then be marketed to pharmaceutical companies and research labs. According to Konstantin Fiedler, general manager of cell technologies at GE’s Healthcare division, the market for toxicity testing is expected to be in the hundreds of millions of dollars by 2020, from which Geron will begin receiving royalties by 2010.

Scientists from both companies will collaborate in the venture, with GE Healthcare providing all R&D funding. According to David Earp, senior vice president for business development and chief patents counsel at Geron, "We had an asset that we were not able to exploit fully." According to Konstantin Fiedler, general manager of cell technologies at GE Healthcare, "This agreement marks a further step in GE Healthcare’s cell technology strategy aimed at addressing the potential of stem cell applications in the drug discovery and therapy markets."

In 2008, GE earned over $17 billion in revenue, of which approximately $1.5 billion was through its life-sciences related business, which GE began expanding in 2003 with a number of acquisitions and parnerships that included the $9.5 billion acquisition of Amersham PLC, a biotech firm based in the UK which had developed specialized technology in nucleic acid blotting, radiochemical labeling and detection. Other acquisitions and partnerships in the biotech sector have included an agreement between GE and the StemSource technology division of Cytori Therapeutics, a stem cell banking company whose products GE will commercialize in ten European countries. (Please see the related news article on this website, entitled, "Cytori and General Electric Agree Upon Collaboration", dated May 8, 2009). In the past, most of the revenue generated from GE’s Healthcare division has come from diagnostic and imaging equipment, sales of which are declining in response to the efforts by public and private insurers to reduce costs. GE is now in the process of plans to reposition its business strategies.

In January of this year, Geron received FDA clearance to commence the first hESC clinical trials ever to be performed, which were to begin in the summer. Results of the trials will not be obtained for years, however. (Please see the related news article on this website, entitled, "FDA Approves First Human Embryonic Stem Cell Trial", dated January 23, 2009).

Contrary to popular misconception, actual cell-based therapies are still years away for hESCs, and even decades away by some accounts – which is precisely why this new licensing agreement between Geron and GE involves the use of hESCs not for the development of cell-based therapies, per se, but for the use of the hESCs in the development and toxicity testing of drugs. Even Dr. James Thomson, "the father of embryonic stem cell science", who was the first person ever to isolate a hESC in the laboratory, has emphasized this point on a number of occasions. His own company, Cellular Dynamics International (CDI), which he cofounded in 2004, also specializes not in the development of clinical therapies from hESCs, but instead in the use of hESCs for drug development and toxicity testing. (Please see the related news article on this website, entitled, "Cellular Dynamics and Mount Sinai Sign Licensing Agreement", dated May 29, 2009).

Financial details of the agreement between Geron and GE were not disclosed.

Geron’s shares rose 15% after the announcement, to $7.67, while GE’s stock fell to $11.72.

New York has become the first, and thus far the only, state to designate the use of taxpayer money to compensate women for selling their eggs to embryonic stem cell research. According to the new policy, taxpayer-funded researchers will be allowed to pay women up to $10,000 for selling their ova for embryonic stem cell experimentation. Critics of this bold move fear that the new policy will lead to the exploitation of women, especially those of low income.

The new policy was announced by the Empire State Stem Cell Board, which is responsible for deciding how to spend $600 million in state tax dollars. According to David Hohn, vice chairman of the Board’s two committees that endorsed the new policy, "We want to enhance the potential of stem cell research. If we are going to encourage stem cell research as a solution for a variety of diseases, we should remove barriers to the greatest extent possible. We decided to break new territory."

One of the goals of the new policy is to produce custom-tailored cells and tissue through the process known as somatic cell nuclear transfer (SCNT), the same procedure that is used both in reproductive cloning and in so-called therapeutic cloning. An extraordinarily large number of ova, however, are necessary for the procedure, which has never actually successfully produced a human stem cell line, and attempts to solicit the uncompensated donation of eggs have largely failed. According to Dr. Douglas Melton, codirector of the Harvard Stem Cell Institute, "The lack of compensation has meant it’s been nearly impossible to get enough eggs." Paying women to sell their eggs is therefore presumed to correct the problem, although many people find this to be flawed reasoning.

The new policy is contrary to that of every other state in the country and, most notably, it is defiantly in violation of the scientific guidelines on embryonic stem cell research as issued by the National Academy of Sciences. Furthermore, the initial draft of the stem cell research guidelines issued by the National Institutes of Health has specifically forbidden SCNT, per the specific recommendation of President Obama, whether for purposes of reproductive cloning or therapeutic cloning. When the final version of the NIH guidelines is issued next month, thereby establishing official national research policy within the U.S., this new state policy of New York will most certainly be in violation of national research laws unless NIH specifically legalizes SCNT for therapeutic cloning, which thus far NIH has indicated it is unlikely to do. Paying women for the sale of their eggs, regardless of the intended purpose, is also likely to be specifically forbidden in the NIH guidelines.

Not surprisingly, however, the move is welcomed by those proponents of embryonic stem cell research who are aggressively focused on embryonic stem cell research, and only embryonic stem cell research, at the expense of all else. According to Susan Solomon, for example, cofounder of the private, nonprofit organization known as the New York Stem Cell Foundation, "This is a really great, appropriate policy. This could help us to pursue some critical experiments that we hope will lead to treatments for devastating diseases."

Many others, however, question the wisdom of such a policy, including many who are strong advocates of embryonic stem cell research. According to Dr. Jonathan Moreno, professor of bioethics at the University of Pennsylvania, "In a field that’s already the object of a great deal of controversy, the question is, are we at the point where we really need to go that route in order to do the science? I’m not convinced."

There are many risks, medical and otherwise, which are known to be associated with the buying and selling of human ova. As described today in The Washington Post, "Donors must undergo weeks of hormone injections to stimulate their ovaries to produce eggs, and then a painful procedure to extract the eggs. The procedure can in rare cases cause a dangerous overstimulation of the ovaries, and there are concerns about the possible long-term risks of hormonal stimulation."

In addition to the medical risks of egg donation, there is also the risk of commercial exploitation, especially among those women in the lower income demographics. According to Father Thomas Berg, director of the Westchester Institute for Ethics and the Human Person, who is also a Catholic priest and a member of the Empire State Stem Cell Board’s ethics committee, "With the economy the way it is, you don’t need to be a rocket scientist to know that when a woman is looking at receiving up to $10,000 to sign up for a research project, that’s an undue inducement. I think it manipulates women. I think it creates a trafficking in human body parts."

Many people agree. According to Laurie Zoloth, a bioethicist at Northwestern University, "Whenever society starts to pay for relationships that are traditionally done with altruism and generosity within families, it raises the issue of whether there is anything that is not for sale."

Proponents of "therapeutic cloning" claim that the technique potentially offers a new mode of treatment in the repair and regeneration of tissue and organs. Especially in the field of organ transplantation, where immune rejection is common, therapeutic cloning is often seen as a way of eliminating this problem of immune rejection. A number of highly respected scientists insist that this view is incorrect, however, and that immune rejection still exists in therapeutic cloning, along with a myriad of other complexities and problems.

In therapeutic cloning, stem cells are created from a donor for the main purpose of providing tissue, such as for organ repair, in the event that the donor might need such treatment at a future date. The way in which this is done is through somatic cell nuclear transfer (SCNT), the same procedure by which scientists created Dolly the sheep – the world’s first cloned mammal who was "born" in 1996 and had to be euthanised in 2003 at the age of 6 because of a progressive form of lung cancer.

In SCNT, the nucleus (which contains the DNA) from a somatic (mature, differentiated, non-stem cell) cell from an adult donor is transferred into an enucleated egg (an egg from which the nucleus has been removed), thereby yielding a new type of cell which is then given an external stimulation to begin mitotic division, in the same way that a single celled embryo would begin to develop. In actuality, the resulting cluster of dividing cells constitutes a cloned embryo. When the egg has divided into approximately 100 cells (known as a blastocyst, the stage in embryogenesis that precedes the embryo and is preceded by the zygote), the inner cell mass is then removed and cultured into an embryonic stem cell line, which is expanded to produce the desired, healthy, "therapeutic" cells – such as nerve cells, muscle cells, organ tissue, etc.. These new cells are then transplanted back into the patient, who is presumed to be the same person as the donor of the original somatic cell, in order to avoid immune rejection. A single cell, cultured in a dish by itself, will divide to form a population of identical cells such that the resulting cloned embryo and its cells, in this particular case, are therefore genetically identical to the donor. A problem remains with the mitochondria, however, which originate with the egg, not the donor nucleus, so consequently the mitochondria in the resulting cells are not genetically matched to the donor, and this fact can still cause immune rejection. Nevertheless, since therapeutic cloning requires the deliberate creation and disaggregation (destruction, in other words) of a human embryo, even President Obama has referred to the process as unethical, and NIH has thus far vowed not to allow federal funding for such a procedure.

Ethical controversies aside, however, David A. Prentice, Ph.D., Senior Fellow for Life Sciences at the Family Research Council in Washington, D.C. and formerly a professor of medical and molecular genetics at the Indiana University School of Medicine, adds that cloning is unsafe purely for scientific reasons, and he points out that even apparently healthy clones have abnormalities in gene expression. "A review of all the world’s cloned animals suggests that every one of them is genetically and physically defective," he says. He also cites Ian Wilmut, the creator of Dolly the sheep, who points out that, "There is abundant evidence that cloning can and does go wrong and there is no justification for believing that this will not happen in humans." (Quoted in "Gene defects emerge in all animal clones", Sunday Times of London, 4/28/02).

Indeed, the success rate of SCNT is extremely low, as 277 nuclear transfers were required to enucleated the eggs from which Dolly the sheep was created. It has been pointed out that even when animals are successfully cloned, every one of them, without exception, suffers from numerous genetic abnormalities. Even Dolly the sheep was "born" with incomplete epigenetic reprogramming – the heritable erasure and remarking of genes that determines either normal or abnormal development. Currently, the highest efficiency rate of SCNT cloning in any species is 7% (with pigs), and in most species the success rate is below 1%. However, even when successful, from 10,000 genes that were analyzed in cloned mice, approximately 400 of these genes were found to express genetic abnormalities. Dr. Prentice offers some further alarming statistics on the success rates, or the lack thereof, of cloned animals:

Dolly the sheep, the first cloned animal: 1 live birth out of 277 cloned embryos. Success rate = 0.4%.

Cloned mice: 5 live births out of 613. Success rate = 0.8%.

Cloned pigs: 5 live births out of 72 cloned embryos implanted. Success rate = 7%.

Cloned goats: 3 live births out of 85 cloned embryos implanted. Success rate = 3.5%.

Cloned cattle: 30 live births out of 496 cloned embryos implanted. Success rate = 6%.

Cloned cat: 1 live birth out of 188 cloned embryos. Success rate = 0.5%.

Cloned gaur: 1 live birth out of 692 cloned embryos. Success rate = 0.1%.

Cloned rabbits: 6 live births out of 1852 cloned embryos. Success rate = 0.3%.

Somatic cell nuclear transfer is such a can of worms, scientifically as well as ethically, that the procedure has never actually produced a human stem cell line, despite claims in 2005 by Hwang Woo-suk of South Korea that he had done so. His claims were later proven to be fraudulent, and the resulting scandal had a lasting impact upon South Korea’s national stem cell research policy. (Please see the related news article on this website, entitled, "South Korea Conditionally Lifts Embryonic Stem Cell Research Ban", dated April 29, 2009).

Merely attempting the procedure, however, whether for purposes of reproductive or therapeutic cloning, is enough to place women at a number of risks, and the statistics alone render the procedure impractical. For example, in order to treat all of the 17 million people in the U.S. who suffer from diabetes, Dr. Prentice has made some sobering calculations. Allowing for 10 eggs harvested per donor, and allowing for a generous 20% cloning efficiency to achieve the blastocyst stage, as well as a generous 10% efficiency rate at initiating the embryonic stem cell culture, a minimum of 850 million eggs would be required, which translates into 85 million women of childbearing age who would be required as donors. This would be more than one-third the population of the United States, who would be needed as egg donors for the treatment of a group of people roughly one-sixteenth as large in population size.

While high dose hormone therapy and surgery have been developed to obtain eggs in large numbers, such techniques nevertheless pose significant health risks by jeopardizing the donor’s immediate health and future reproductive success. Additionally, it has already been seen in other countries that the possibility for commercial exploitation puts economically disadvantaged women in particular jeopardy. Overall, as Dr. Prentice concludes, therapeutic cloning may be judged as unsuccessful. Transplantation remains one of its many problems, and Dr. Prentice cites W.M. Rideout as having stated, "Our results raise the provocative possibility that even genetically matched cells derived by therapeutic cloning may still face barriers to effective transplantation for some disorders." (W.M. Rideout et al., "Correction of a genetic defect by nuclear transplantation and combined cell and gene therapy," an online publication in Cell, 3/8/2002).

It has been proposed by a number of researchers that cloning is not able to provide the claimed medical treatments, and Drs. James Thomson ("the father of embryonic stem cell science") and Alan Trounson, among others, add that there is a very low chance of success in the clinical use of therapeutic cloning. (Dr. James Thomson, "Multilineage differentiation from human embryonic stem cell lines", Stem Cells, 2001; Dr. Alan Trounson, "The derivation and potential use of human embryonic stem cells", Reproduction, Fertility and Development, 2001). Additionally, Dr. Irving Weissman of Stanford University and Dr. John Gearhart have both stated before the President’s Council on Bioethics (when it existed, although this week President Obama abolished the Council) that transplant rejection will still occur, even though the cells from the cloned embryos are considered "genetically identical" to the donor. (Dr. Irving Weissman, 2/13/2002, before the President’s Council on Bioethics; Dr. John Gearhart, 4/25/2002, before the President’s Council on Bioethics). Even Dr. Thomas Okarma, President and CEO of the Geron Corporation, the leading embryonic stem cell company, has pointed out that cloning is not commercially viable, stating that, "The odds favoring success are vanishingly small, and the costs are daunting. It would take thousands of [human] eggs on an assembly line to produce a custom therapy for a single person. The process is a nonstarter, commercially." (Quoted by Denise Gellene in, "Clone Profit? Unlikely", Los Angeles Times, 5/10/2002). Corroborating such views, Drs. Odorico, Kaufman and Thomas have written, "The poor availability of human oocytes, the low efficiency of the nuclear transfer procedure, and the long population doubling time of human embryonic stem cells make it difficult to envision this becoming a routine clinical procedure." (Odorico JS, Kaufman DS, Thomson JA, "Multilineage differentiation from human embryonic stem cell lines," Stem Cells, 2001).

Dr. Prentice adds, however, that it is unlikely that large numbers of mature human oocytes would actually be available for the production of embryonic stem cells, particularly if hundreds are required to produce each embryonic stem cell line. "The technical capability for nuclear transfer would also need to be widely available, and this is unlikely," he says. As Dr. Alan Trounson adds, "In addition, epigenetic remnants of the somatic cell used as the nuclear donor can cause major functional problems in development, which must remain a concern for embryonic stem cells derived by nuclear transfer. Although it is possible to customize embryonic stem cells by therapeutic cloning or cytoplasmic transfer, it would appear unlikely that these strategies will be used extensively for producing embryonic stem cells compatible for transplantation." (Alan O. Trounson, "The derivation and potential use of human embryonic stem cells," Reproduction, Fertility and Development, 2001). As Dr. Irving Weissman, director of the Institute of Stem Cell Biology and Regenerative Medicine at Stanford University, stated in his testimony before the President’s Council on Bioethics (when it existed, prior to President Obama abolishing the Council), "I should say that when you put the nucleus in from a somatic cell, the mitochondria still come from the host. And in mouse studies it is clear that those genetic differences can lead to a mild but certainly effective transplant rejection, and so immunosuppression, mild though it is, will be required for that." (Dr. Irving Weissman, 2/13/02, before the President’s Council on Bioethics). Similarly, Dr. Alan Trounson, the Australian embryonic stem cell scientist and president of the California Institute for Regenerative Medicine, stated as early as 2002 that cloning had become "unnecessary and obsolete". He says that stem cell research continues to advance so rapidly, every day, that therapeutic cloning has been surpassed by other, safer and more effective procedures. "My view," he stated in 2002, "is that there are at least three or four other alternatives that are more attractive already." Emphasizing the point that therapeutic cloning faces too many "logistical problems," and that other techniques show "greater promise" and offer "better options," Dr. Trounson adds, "I can’t see why, then, you would argue for therapeutic cloning in the long term, because it is so difficult to get eggs and you’ve got this issue of [destroying] embryos as well." ("Stem cell cloning not needed, says scientist", The Age [Melbourne], 7/29/2002; "Stem cell research outpaces cloning", The Australian, 7/29/2002; "Therapeutic cloning no longer necessary: expert", AAP Newsfeed, 7/29/2002).

Additionally, therapeutic cloning – which has never successfully produced a human stem cell line but instead is still in the hypothetical stage – has been rendered irrelevant and unnecessary in light of mounting clinical success over the past few years involving "immune privileged" adult stem cells such as mesenchymal stem cells (MSCs) which have been shown to be "universal donor" cells, meaning that anyone can receive these cells without the risk of immune rejection. MSCs have been shown to differentiate into a wide variety of tissue types and are abundantly available and easily obtainable from noncontroversial sources such as adult bone marrow and umbilical cord blood. Precisely for reasons such as these, MSCs are already therapeutically available in clinics throughout the world, and in the United States a number of adult stem cell companies have products developed from MSCs which are advancing through FDA-approved clinical trials. MSCs are merely one example of a large number of different types of adult stem cells which have already demonstrated clinical success in the treatment of a wide range of diseases and injuries, and which have already advanced far beyond the hypothetical laboratory stage, unlike embryonic stem cells and cloning. Many scientists whose research had been focused on SCNT in the past – including Dr. Ian Wilmut himself, the creator of Dolly the sheep – have since moved away from SCNT and have turned their attention to other, more viable, sources of stem cells, which include not only iPS (induced pluripotent stem) cells but also adult stem cells. To claim that no alternative exists to embryonic stem cells and cloning is to be entirely ignorant of some of the greatest and most dramatic breakthroughs in the history of medical science.

It would seem as though the authors of the newly announced New York state policy have not done their homework. Nevertheless, those individuals who are personally responsible for establishing the new policy remain defiantly confident that they have made the right move, despite unanimous advice to the contrary, from all the leading embryonic and adult stem cell experts throughout the world.

Even staunch embryonic stem cell advocates are calling the new policy an "unnerving precedent".