Human embryonic stem (ES) cells

"Do adult stem cells have advantages over human embryonic stem cells?" Michael Cook of MercatorNet asked James Sherley, an associate professor of biological engineering at the Massachusetts Institute of Technology.

"The main advantage is that adult stem cells are already programmed to function in adult tissues and organs." Sherley answered. "In addition, they do not form tumors when transplanted from one person to another."

By "programmed" Sherley refers to the turning "on" or "off" of genes within cells – how the genetic code is "expressed." Humans keep the same genetic code throughout life, but the way that code is expressed in the embryo differs sharply from the fetus, which in turn differs from adult (postnatal) genetic expression. This little-known point has immense relevance to stem cell basic research and clinical applications, but such details seldom reach the public.

In a talk entitled "Hype, Hope and Hair-raising: How the British press saw it," former Science Editor Tim Radford of the UK's The Guardian recently acknowledged that he and his fellow science journalists hype stem cell research to sell more newspapers.

Because of the moral debate over using embryos for research, personal feelings concerning abortion, religion, and politics can also influence the reporting of stem cell issues.

One Washington-based science reporter, an avowed atheist, often writes that embryonic stem (ES) cells "can become every cell in the body." But he fails to mention that nine months of fetal development in the fetus are needed to do this. Nor does he report that ES cells matured in vitro (in a petri dish) tend to be genetically unstable and often function abnormally. Yet issues such as these determine whether publicly funded science leads to medical treatments in a foreseeable future, in a decade or two, or never.

Most reporters would accurately report the facts regarding stem cells, but they're seldom given information that suggests long-range basic research and industry goals may conflict with public interests.

"Many scientists who do not support human embryo research are afraid to speak out," says Prof. Sherley, "because of possible reprisals from powerful scientists who can affect grant success, publication acceptances, tenure promotion, and employment."

Regardless of the reasons, the public is not being given the information it needs to make well-informed, sensible decisions concerning the direction and purpose of publicly funded science. If public research resources are ineffectively used because of biased or missing information, eventually all mankind will suffer when medical advances are delayed or blocked.

ES cell research is promoted primarily for two uses – to provide replacement cells for cell-based medicine, and to act as research tools for studying disease. It would be foolish to claim that embryonic stem cells cannot have medical or research uses. However, for the sake of those whose hopes for health depend on science, these issues are not about possibility, they're about clinical practicality.

In 2002 my support for ES cell research changed to opposition when I considered its practical worth.

Cell-based medicine:

Several issues make embryonic stem cells impractical for direct therapeutic use. Because ES cells do not genetically match patients, they face immune rejection. Because ES cells are designed to function in the embryo, they're incompatible with adult tissues. Coupled with explosive ES cell growth, this can result in the formation of lethal tumors if ES cells are implanted in adults. Therefore ES cells must be brought to fetal stages for therapeutic use.

Adult cells outperform fetal cells in head to head myelination tests (the coating of nerves with a fatty insulation needed for conduction). Adult stem cells have been turned into fully functional insulin-producing cells and reversed diabetes-like symptoms. A human Parkinson's patient treated with his own stem cells went into remission for three years. Patients treated with fetal cells grew worse.

Replacing cells that have been lost or damaged through disease, regardless of the source of replacement cells, cannot be considered a "cure," since the cause of disease would remain.

"Until you can stop the underlying disease it's irrational to think you can treat it by sending in healthy replacements," said Ashley Bush, an associate professor of psychiatry and pathology at the University of Melbourne, to The Weekend Australian in 2002. He compared using stem cells to replace brain cells affected by Alzheimer's to "throwing troops into a nuclear war."

Australia's Prof. Alan Mackay-Sim refutes the most common denials heard in connection with adult stem cell potentials – that they're too scarce, too hard to grow, and too limited in their applications:

"These adult olfactory stem cells appear to have the same ability as embryonic stem cells in giving rise to many different cell types but have the advantage that they can be obtained from all individuals, even older people who might be most in need of stem cell therapies. Stem cells obtained from and transplanted into the same person would not be rejected by the immune system.

"Stem cells from the human nose are relatively easy to harvest and grow very well in the lab. We can multiply them from small samples into millions of cells and these cells can then be directed to turn into different types of cells. These attributes make them good candidates for cell transplantation therapies and tissue reconstruction."

Of possible sources of replacement cells, including stem cells from embryos, fetuses, adult tissues, and cord blood, embryonic stem cells have the most biological hurdles to overcome, will take the longest to develop, will use the most resources and offer the least certainty of success.

"No matter what the hurdles are for success with adult stem cell-based therapies," Sherley told MercatorNet, "embryonic stem cell research faces the same hurdles and more."

Summary: Developing ES cells for cell-based medicine will require the extensive use of limited research resources that should be put to more clinically productive use, as suggested by the following facts:

1) Replacing cells without removing the cause of disease cannot be a "cure." 2) ES cells have the most basic research hurdles to overcome. 3) Unlike stem cells from adult tissues and cord blood, ES cells cannot be used directly in treatments. 4) ES cells matured in vitro (in a petri dish) tend to be genetically unstable and often function abnormally. 5) Adult cells have outperformed fetal (and embryonic-derived) cells for myelination, insulin production, and Parkinson's clinical results. 6) Adult stem cells already treat 65 medical conditions safely and effectively – ES cells treat none.

ES cells as tools for studying disease:

According to the Institute of Science in Society (ISIS), an organization of 560 scientists from 58 nations, the "overwhelming" causes of human disease are lifestyle and the environment. Genetic defects can increase the risks of contracting disease. But most human disease is triggered by exposure to chemicals or toxins, or through poor diet and lack of exercise. It is difficult to imagine how studying embryonic stem cells will point to cures for such conditions.

For diseases with definite genetic causes, the public is being sold "therapeutic cloning" as a research tool. In theory, cloned embryos will perfectly match patients with genetic disease, allowing researchers to study defects in embryonic development that might contribute to disease in adults. However, this theory falls apart on close examination.

— Cells taken from cloned embryos do not perfectly match the nuclear donor. The cloning process incompletely reprograms the adult genetic code to an embryonic one. This leads to random defects in genetic expression (how genes are turned "on" or "off") and to defective embryonic and fetal development.

— Cells contain important energy-producing structures called "mitochondria." In embryos these come from the egg. Therefore, cloned embryos from men (or infertile woman) cannot contain the (nuclear) donor's mitochondria. Many diseases are linked to defective mitochondria, or to defects in mitochondria DNA.

— The theory that studying embryonic defects will point to treatments in adults is highly doubtful. Embryonic development results from interactions between embryonic genetic expression and the embryonic environment. Neither exists in adults.

ES cell pioneer James Thomson once described the research cost of cloning as "astronomical."

Summary: When one considers that, 1) ES cells from any source are unlikely to shed any light on the most prevalent causes of human disease – lifestyle and the environment. 2) ES cells from cloned embryos contain widespread, random defects and mitochondria that do not match the donor. 3) Cloning research will divert "astronomical" resources away from studying active causes of disease in adults, such as autoimmune defects in Type I (Juvenile) Diabetes. 4) The theory that studying defective ES cells will lead to cures in adults may be faulty. It seems highly impractical to use extensive public resource to pursue ES cell research as a research tool.

Conclusion:

In 2002 I changed my stem cells course because of a horrifying vision – the image of millions of desperate and trusting humans holding plates of hope to an empty sky.

The actions of scientists have confirmed my course. While telling the American People that they only want "to keep all research options open," science and industry convinced the people of California to commit three billion dollars to ES cell research and human cloning – ten times the annual NIH budget for adult stem cell research. They're pursuing an additional billion dollars in public funds in both New York and Illinois, and another $750,000,000 from Wisconsin.