Stem Cells & Cloning

Stem cells are undifferentiated cells capable of becoming all cell types. Separate one from its fellows and identical twins may result. This happened spontaneously to five separate cells in Canada in the 1930s resulting in the Dione quintuplets, all of whom survived to adulthood. They and identical twins have identical genetics, natural clones in every sense of the word clone as currently used. Such individuals accept grafted organs from each other as if the organ or skin had simply been moved from one part of a person to another place on the same body. There is no threat of graft vs. host disease or rejection.

The modern great increase in multiple births is the result of in-vitro fertilization because of the practice of implanting many embryos at one time to increase the success rate, with too much success once in a while. Proposals are being floated to prohibit implanting of more than 2 or 3 embryos to reduce complications, especially prematurity and threats to the mother’s health. These children are only as related as other siblings of different ages. Harvesting ova for in-vitro fertilization is an elaborate and expensive procedure. One drug-induced super ovulation can produce enough embryos for several years of attempts at implantation. If early attempts succeed, there are many embryos left over in the freezer. Great increases in the success rate of implantation cannot be expected, because many defective embryos are rejected before pregnancy is apparent or could even be detected by the most sophisticated methods. Down’s Syndrome occurs when chromosome 21 is redundantly duplicated. In this case, survival is possible but with physical and mental abnormalities. Similar redundant duplication of other chromosomes occurs, but the abnormal fetus does not long survive, a menstrual period may not even be missed. Most miscarriages are best looked at as nature culling factory defects. This puts some perspective on the technical problems of in-vitro fertilization. Now I touch on some public policy problems with in-vitro fertilization.

Explornography is a word coined in honor of the Mt. Everest disasters of 1996. Explornography occurs when people with obscene amounts of money hire somebody to take them someplace where they had no business going. In a way, in-vitro fertilization is a little bit like explornography in that both are so expensive that they border on poor public policy because of the opportunity cost (what you could have had of greater value, if you hadn’t already spent the money), and they represent different dimensions of an ego trip. When I read of tens of thousands of dollars per successful in-vitro fertilization, this sounded like a vanity compared to adopting an otherwise unwanted child. Obviously having oneself cloned is considered poor public policy by the vast majority and rightly so for reasons more compelling than blunting personal vanity.

Now that we have accepted embryonic stem cell research as a beneficial side effect of in-vitro fertilization and the large number of resulting embryos, of which only a tiny fraction can ever be implanted, let me tell why we need two words for cloning, one for what we have just discussed, “ego trip cloning” and the other “therapeutic cloning”. A likely example of an early therapeutic triumph of stem cell research is implanting of stem cell derived islet cells, the pancreatic cells that produce insulin. Persuading a stem cell to become an islet cell should be orders of magnitude easier than persuading it to multiply into diverse cell types and organize them all into a kidney or some other organ. Islet cells have already taken as grafts in experimental animals’ livers. Already diabetic patients have had pancreas transplants successfully curing their diabetes. This means normal blood sugar and relieving complications of diabetes. Many of these patients have double transplants of kidney and pancreas. They needed the kidney to save their lives and were going to get immunosuppression treatment indefinitely anyway to prevent rejection of the foreign kidney. A pancreas transplant by itself trades the hazards of diabetes against the hazards of immunosuppression, a more or less even trade with close to equal life expectancy and quality of life.

Childhood onset diabetics seldom live more than 40 years after diagnosis. Early treatment with injected islet cells should greatly improve their prospects especially if it could be done without the need for immunosuppression or the threat of rejection of the transplanted islet cells. Therapeutic cloning (it’s ok with me if a new word is invented for this) could solve this problem. A stem cell with its nucleus removed and replaced by a nucleus of a cell from the recipient would be treated by a method to be devised (hopefully) to transform it into islet cells. These cells could survive in the recipient without immunosuppression and cure the diabetes. This transfer of nuclei is what was done in Scotland to produce Dolly, the cloned sheep, but with entirely different motivation and consequences: hence the need for different words for the two kinds of cloning. The same logic described for pancreatic islet cells applies to transplantation of other tissues such as bone marrow.

I have tried to provide some biological perspectives on an important current public debate. A very brief political perspective: Great Britain permits all stem cell research including therapeutic cloning. Germany permits less than we do. The experts already speak of reproductive cloning and therapeutic cloning. Therapeutic cloning does have the potential of permitting tissue transplantation without the threat of rejection.

John A Frantz, M.D.

Chairman, Monroe Board of Health

8/27/01

Atomic Waste

Here is an idea about what to do with high-level radioactive waste: make it into glass pellets as the French do (they simply bury the pellets in France and hope that no one digs them up for tens of thousands of years); use the pellets as aggregate for concrete spheres; add a layer of normal reinforced concrete to make larger, stronger spheres; dump them on the steep side of a deep ocean subduction trench where they will roll to the deepest part of the bottom and ultimately be subducted into the earth’s mantle. They will remain there for millions of years, their radioactivity meanwhile becoming no stronger than the nearby ordinary magma and therefore “harmless” if their material were to be erupted as lava.

Of course some experimentation would be needed to assess the adequacy of the containment considering the time the spheres would wait to be subducted. This time interval would need careful estimation perhaps involving long-term observation of what happens to merely tagged but not dangerously radioactive similar spheres. Please remember this is a brainstorm---not a competent engineering analysis---the latter obviously outside my area of expertise.

It is comforting to know that physicists, engineers, and geologists are sifting and winnowing ideas for disposal of radioactive waste and vigorously promoting the most useful ones. Maybe this idea is not new. If I stumble on another one, perhaps even more useful, I promise to pass it on. However, we cannot win them all—see below.

John A. Frantz, MD, May 13, 2005

“Nuclear worry over undersea volcanoes” from The Guardian (a British newspaper) for September 16, 2005

Burying nuclear waste in trenches that suck the ocean floor towards the Earth’s interior is a bad idea, according to a study published in Geology. Darren Tollstrup and James Gill from the University of California-Santa Cruz have shown that sediment near the Mariana trench, on the floor of the Pacific Ocean, is partially recycled back to the surface via submarine volcanoes. Using a small submarine, the researchers collected sediments from around the Kasuga seamounts in the Philippine Sea. They used chemical isotopes of hafnium and neodymium to trace the path taken by lava emerging from these seamounts. The isotopes suggested that sediments are compressed and melted to a depth of about 100km beneath the sea floor before being spurted out again in a submarine volcano.

Or would the several tens of thousands of years required for subduction to 100km depth be sufficient for decay of our nuclear waste especially that from breeder reactors and thorium based reactors that consume long lived plutonium.