|
August 2001 Stem CellsAs far as the first item is concerned the fate of Ms. Chandra Levy and that of her paramour Representative Gary Condit has become a boon to cable news channels, because there is too much air time to fill and the genuine news are not sufficiently sensational. The entire story can be summarized in a few sentences. Ms. Levy has been missing for about three months. Nobody knows her or her body's whereabouts and it becomes increasingly likely that her case will end up like that of Jimmy Hoffa's, who also vanished without a trace. Mr. Condit on the other hand failed to obey the Prime Directive which ought to govern human behavior. Simply put it states: Whenever you find yourself in trouble tell the truth immediately and fully, without making excuses. Qui s'excuse, s'accuse (whoever excuses himself, accuses himself) the French say and they are right. This is the sum and substance of the story over which TV newscasters, hosts and guests drool endlessly for hours day in and day out. The discussion of Global Warming will be postponed for another update. At any rate it is supposed to stay with us for at least another hundred years, so what's the hurry? I am currently in the process of gathering my own data in regard to temperature forecasts and these will be published in due time. The third item on the agenda, stem cell research, does merit discussion today because President Bush is being pressured by the media to immediately release federal funds for embryonic stem cell research. The media bolster their argument by promising the general public the blue from the sky about the benefits the human race will reap from this type of research. The moral and religious pro and con arguments are endlessly hashed out but the legitimate medical issues which can be raised for or against embryonic stem cell research have, to the best of my knowledge, never been aired by the public media to the extent that they should have been. We are only being told that this research might lead to cures for Parkinson's disease, Alzheimer's disease, diabetes and a host of other chronic degenerative illnesses. With other words we are finally on the way to realize Ponce de Leon's dream. The fountain of youth is around the corner and embryonic stem cells will relieve us from all the burdens associated with aging. The key word in all of this, which by the way this type of propaganda shares with Global Warming, is the word "might." It is not being taken merely as some faint hope, which springs eternal, but is regarded as "will" and action must be taken now, immediately, and by the federal government or an irretrievable chance will be lost. In order to find out what the implantation of embryonic stem cells really does in the human being I searched the medical literature on the Internet and came up empty handed. There are no data! As a neurologist I was, of course, most interested in Parkinson's and Alzheimer's disease but even the animal data are so far exceedingly sparse and inconclusive. It just so happened that the July issue of Neurology Reviews had a lead article entitled: "Shooting for the Moon. Bolstered by a New Research Agenda, Parkinson's Researchers Aim High." In this article, which will also available on the web in due time under www. neurologyreviews.com, the several techniques which are currently under investigation are discussed. These are: transplantation of a) neural tissue, b) embryonic stem cells, c) adult stem cells, and d) xenotransplantion. Before explaining these terms further in everyday language some fundamental facts about Parkinson's disease must first be presented. The condition results from a loss of nerve cells (neurons) in certain regions of the brain which produce a critical chemical called dopamine. This discovery, in the early sixties of the past century, led to a Nobel Prize because dopamine could be produced in the laboratory and patients could take the drug in pill form. The early results were exceedingly exciting but, as everything else in life, first love wears off, and the "fine print" becomes noticeable only after some time. Although improvements in the compound in form of levodopa (L-dopa) were made, which is the current preferred form of treatment; there are still a great many problems. Not only does the effect of the medication wear off after some time but some patients also develop uncontrollable writhing movements especially of the head and limbs (dyskinesias or dystonia) which make their lives miserable. For this reason the search for "the cure" continues. Hippocrates, "the father of medicine" who plied his art on the island of Cos in the Aegean around 400 B.C. wrote in his aphorisms: "What medicine [drugs] cannot cure, the knife [surgery] will cure, what the knife cannot cure fire [radiation] will cure, and what fire cannot cure is wholly incurable." Genetic modification of the organism could not be imagined at that time but on the whole the dictum still holds. Since L-dopa failed to live up to its promise neurosurgeons began to practice their art by destroying certain structures or pathways in the brain with their knives, or by targeted radiation. This led to some good and some bad results. At any rate the disease remained for the most part progressive and only long term follow-up of ten years or more would allow one to speak of an arrest or even cure of the disease. This brings us to the article in Neurology Reviews and stem cells. The whole purpose of the exercise is to create neurons which produce dopamine in the patient's brain not only in the right amount but also nothing else. This statement alone should give one pause, because the problem is obviously far from trivial. The solution will not only require funding but equally or even more importantly time, measured not in years but decades! Let us now look at the upside and downside of the mentioned research programs. Neurontransplantation. The good news according to Dr. Dunnett of the Brain Repair Group at Cardiff University in Wales is that "There is convincing evidence that fetal tissue grafts can have a functional effect in animal models of Parkinson's disease" and "When such cells are implanted they survive, grow, connect with denervated [have lost their functional connections] areas, and alleviate some of the simpler motor deficits associated with Parkinson's disease. This provides proof of the principle that dopamine deficiency can be restored by transplanted dopaminergic [dopamine producing] cells." So far so good. Now comes the fine print. The study involved an "animal model" rather than the human disease and in contrast to the human illness Dr. Dunnett's model produced acute rather than chronic effects. Furthermore, he stated that "Fetal cell transplants can work with dramatic efficacy in some cases but can also seriously go wrong." Even when the method worked it should be noted that the beneficial effect on the symptoms of the animal, rather than on the brain slices at autopsy, improved "some of the simpler motor deficits." This leads one to assume that some of the more complex motor functions on which we depend, were not alleviated. As far as human results are concerned there is only one relatively long term scientifically controlled study mentioned in the article. This involves the work of Dr. Curt Freed at the University of Colorado. Dr. Freed's team transplanted precursors of dopaminergic cells from 6-10 week old human fetuses into the brains of 19 patients with severe Parkinson's disease. These patients were compared with others who had been sham operated where only burr holes were placed in the skull. The study was "double blind" which means that neither the patient nor the team of examining physicians knew whether or not the patient had received a transplant. The result of the follow-up of "up to three years," which means that this was the maximum and most patients had shorter observation times, was that a "statistically significant 28% improvement over baseline" was observed. This held true for the total group, when the patients were not taking their morning dose of medications. When the group was subdivided between older and younger patients it became apparent that a 38% improvement (highly significant statistically) had occurred in the younger individuals while it was only 14% in the older group, and as such not statistically significant. Furthermore, even in those patients who had benefited the total effect was only comparable to about half the effect of their usual morning dose of levodopa. Now comes the bad news. Fifteen percent of transplant patients had a recurrence of disabling dystonias and dyskinesias in the second or third year after the operation. All of these patients were 60 years or younger and had experienced these symptoms when on levodopa but now had the problem even when the medication was discontinued. Inasmuch as review articles might be slanted I obtained subsequently Dr. Free's and colleagues' original paper which was published in the March 6, 2001 issue of the New England Journal of Medicine. While the review as cited above was in essence correct, the full article did provide additional information. Embryonic tissue was obtained with the consent from the mother during elective abortions seven to eight weeks after conception. There were initially two groups of 20 patients each in the transplant and in the sham operation (placebo) group. One transplant patient died in a car accident when a tree fell across the road during a storm and the outcome of the operation could, therefore, not be evaluated at the one year final comparison point. Although some patients were followed for up to three years, the figures cited above refer to the one year outcome after the code was broken. At that point the sham operated patients were given the option to have transplants and 14 patients of the placebo group consented. Thus, the figure of up to three years follow-up covers 33 rather than 19 patients. Apart from the development of dyskinesias, which occurred later than the first year, and in some younger patients, there were also during the 12 months of follow-up 9 serious adverse events. Although these were in all probability unrelated to the transplants it is noteworthy that eight of these occurred in the transplant group and only one in the placebo group. Percentage wise this would give a difference of 40 percent vs. 5 percent. The investigators realized that inasmuch as the operation benefited only patients under 60 years of age and that younger patients tended to develop intractable dyskinesias, they did not suggest the operation to the last 6 individuals of the remaining placebo group. We are, therefore, confronted with these facts: Embryonic neuronal tissue containing dopaminergic neurons can be transplanted into key regions of a recipient's brain. They grow, multiply, and establish connections with surrounding tissue, regardless of the age of the patient. The growth of these cells is, however, not directly reflected in improvement of the patient's symptoms because only younger patients benefited, and the maximum effect tends to be essentially only half of what would have been accomplished with a full dose of levodopa. The late occurrence of uncontrollable dyskinesias, even when levodopa is no longer given, represents a serious and disabling complication. The amount of tissue to be transplanted and the best brain region for the transplants to be inserted will be the task for the future. Embryonic stem cells. In contrast to embryonic tissue containing dopaminergic neurons, the embryonic stem cells have been called "omnipotent." This means that these cells, taken from the earliest stages of human development, can develop into any type of tissue. With other words they can become liver, brain, bone, heart or whatever. It should be noted that embryonic stem cell studies have so far been performed only in rodents. There are no data on higher animals or, of course, humans. While these cells can develop into neurons, there is no guarantee that they will do so, especially dopaminergic ones. In Petri dishes they have so far produced other types of neurons as well as glia cells which are the other main cellular structure of the nervous system. Dr. Mc Kay of the National Institute of Neurologic Disorders and Stroke whose work is quoted in the article stated that "we are trying to improve the efficiency of differentiating to dopaminergic neurons ...in animal studies... [but] we need to demonstrate that the cells we make will actually work in animal studies." This is indeed all that is known about the effectiveness of embryonic stem cells to cure diseases. Thus, the entire media circus is about a gleam in the eye of some researchers based on hope and faith. Are our promoters of public information, who urge immediate action for embryonic stem cell research, aware of this paucity of facts? Do they also know that these omnipotent cells, when implanted into a brain, might just continue to grow and produce tumors? Once implanted they will do whatever they like and neither Federal Money nor Federal Regulations will be able to control them. Quite apart from moral and ethical considerations this is another Pandora's Box which we are about to open. Adult stem cells. Neural adult stem cells have been harvested from nasal passages of cadavers up to 18 hours after death as Dr. Roisen's group from the University of Louisville has demonstrated. The disadvantage of using adult stem cells is that they get old after some time and lose their potency, although they did live longer when taken from an 11 month old infant. Whether or not any of these Petri dish neurons could be coaxed to become dopaminergic is not yet known. The other argument against the use of adult stem cells is that the supply is not as plentiful as for embryonic stem cells. But as long as we are dreaming, and this is really what all of stem cell research is about at this time, one could readily foresee a scenario where we donate in our youth some of our nasal neural stem cells and keep them in a freezer until the time comes when we might need them. Xenotransplants (use of adult animal tissue) have become commonplace to repair human heart valves and dopaminergic pig cells have already been transplanted into human Parkinson patients. Studies about their effectiveness are currently under way in Tampa, Atlanta and Boston. This might bring up an interesting religious question. Since orthodox Jews as well as Muslims refrain from putting pork into their mouths and stomachs would they be willing to have pieces of pig brain inserted into their own? Additional work is being carried out on Neuroprotective agents which are supposed to stop the progression of Parkinson's disease and thereby obviate the need for implants of any kind. It is, therefore, obvious that Parkinson research is alive and well. It will continue to prosper around the world, without federal tax dollars and federal regulations. Not only is there another Nobel Prize in the offing but drug companies are likely to reap a financial bonanza. There is still the question whether government should control the research or private industry? The answer is obvious from past history. All major advances in medicine were achieved through private initiatives and personal ingenuity which can only flourish in a free society. Those of our citizens who believe that government is the answer to all of mankind's woes should really take a good look at the "achievements" of the defunct Soviet Union, even in the medical field, and compare them with what the Free World has accomplished. Furthermore, money is not unlimited. If tax dollars go to stem cell research other investigations will inevitably have to be curtailed, although they may actually have more immediate prospects of success. The argument is also made that only government can enforce ethical rules. This is another fallacy. Universities and drug companies, the only places where work of this type can proceed, are already tightly regulated and in case of serious untoward outcomes there are armies of malpractice lawyers chomping at the bit to get a piece of the action. So what is really at work here with this entire stem cell hullabaloo? The overriding goal seems to be politics and expansion of government. President Bush is to be maneuvered into a position where he can be attacked regardless of whatever decision he takes. He has to be tarred and feathered; his administration has to be turned into a failure because, according to some of our Democrats, he didn't deserve the presidency anyway. The current interregnum which the Left reluctantly has to put up with needs to be crippled by a democratic congressional landslide next year. Subsequently George W. can be returned to Texas in 2004 and we are all assured of a socialist government for the subsequent eight years. This will then finally usher in the real millennium and bring us in line with those European socialist governments who currently hate our guts and call us names. The reason for their dislike of America is simply that at least some of us still regard ourselves as free citizens who want to live and work under our own initiative and thereafter enjoy the fruit of our labors, with minimal government interference. Unfortunately the Bush administration seems to be singularly inept in explaining the rationale for its actions and is thereby leaving the field to its adversaries. As far as stem cell research is concerned the facts are really quite simple and if the President's spokespersons were to present them to the media, in a manner similar to what is outlined above, even the most hostile critics might have to concede that it would be useful not to rush in where angels fear to tread. |
| Feel free to use statements from this site but please respect copyright and indicate source. Thank you. |
Please E-mail this article to a friend
Return to index!
Return to index!
