Wednesday, August 04, 2004

Review of Issues Regarding Embryonic Stem Cell Research, Part I

Some people agree that embryonic stem cell (ESC) research should be permitted, under guidelines that are strict, but not so strict as those imposed under the current Administration in the United States of America.  Others think that such research should not be permitted at all.  I have posted on this topic here before, most recently on July 14  and 20, 2004.  Those posts link to and discuss the editorials published in the world's two leading medical journals.  The reasons to go ahead with ESC research are documented extensively in those journals. 

As far as I can tell, there are basically four arguments against human ESC research:
  1. We should not do it, because it results in the destruction of an human embryo, and since ensoulment occurs at conception, destruction of embryos always is wrong.
  2. We should not do it because it is an affront to human dignity.
  3. We should no do it, because adult stem cells are the same as embryonic stem cells.
  4. We should no do it, because it is not an especially promising line of research.
I first encountered the term 'ensoulment' in the editorial  written by Michael Sandel, D. Phil., in the New England Journal of Medicine, July 15, 2004.  This is a clever term, as it is used to make an important distinction.  Society would like to have a bright line that demarcates the distinction between those entities that are human -- and thus are deserving of certain inalienable rights -- and those things that are not.   Some say "life begins at conception," but that is not really a clear divider, since single egg cells are alive, as are sperm cells.  Some say that a human embryo is "capable of developing into a complete person."  But that is not so distinct either, since any randomly selected carbon atom has the potential to become a human. 

From a scientific standpoint, there is a smooth linear progression in the formation of a human life: atoms come together, form the building blocks of life, those come together, create cells, and so forth, until a human exists.  There is no point at which you can say that the assemblage now has the potential to become a human, whereas it did not have that potential the moment before.  These niggling technicalities disappear when one abandons the idea of finding a scientific definition of when human life begins.  I would argue that, for the purposes of social discourse, human life begins at that point that society agrees it begins.  That is the point of ensoulment.

The use of the term 'ensoulment' correctly takes the controversy out of the realm of science, and places it into the realm of social or religious constructs.  If an entity has a soul, then society grants to it inalienable rights.  So far, science has not supplied us with an objective test for the presence or absence of a soul.  Thus, ensoulment is a subjective process.  By this I do not mean to discount it; on the contrary, as a social construct, it is supremely useful.  Notice that people are free to come up with their own definitions of 'soul', just as they are free to come up with their own definitions of a higher power.  People are may choose to adopt one of the ready-made definitions, such as those provided by various churches; or, they can come up with a custom definition, according to personal values.   

The problem with that, is that society cannot come to an agreement.  Absent that agreement, we still have to find some way of making a decision about ESC research, for the purposes of defining policy and law. 

So, should ESC research be allowed, and if so, should it be supported by the federal government?

First, we should decide if there is any scientific rationale for pursuit of this line of research.  This is not 100% clear-cut.  As mentioned above, there are editorials in the world's two leading medical journals indicating that at least some knowlgeable, respected scientists believe there is.  Countering this, there is a statement  put forth by the Christian Medical Association that argues for investment in research that uses other types of stem cell.  (In addition to embryonic stem cells, there also are adult stem cells, and stem cells derived from umbilical cord blood.) 

Stem Cells: Over 2,000 Christian Medical Association Doctors Petition Congress to Invest in "Affordable Cures for Our Patients in the Quickest Time"
July 30, 2004 10:03 AM US Eastern Timezone


As Democrat convention speakers promoted human cloning and embryonic stem cell research, over 2,000 Christian Medical Association doctors signed a letter sent today to Congress and the President urging investment in adult stem cell research that is already providing therapies for patients.

Executive Director David Stevens, M.D. noted, "As the nation's largest faith-based organization of physicians, we have a vested interest in such research because we care for patients every day who desperately need cures that might arise from regenerative medicine. We also have the motivation, knowledge and experience to analyze stem cell research without the inherent bias of fund-seeking firms and researchers who have hyped embryonic stem cell research far beyond scientific integrity."

Stevens said, "Cloning human beings for stem cells--as Ron Reagan Jr. urged in his convention speech Tuesday--would produce abnormal embryonic stem cells while exploiting women to gain the millions of human eggs needed for human cloning. Ron Jr.'s speech was "political science" of the worst sort."

Stevens noted, "We want to see cures quickly as our patients do. Adult stem cells are giving results now, but even the most optimistic predictions put any possible help from embryonic stem cells 10-15 years away. Adult stem cell treatments are economical while embryonic stem cells are prohibitively expensive. Private investors are not investing in these so called miracle cures, so scientists seeking fame and fortune are making outrageous promises and using gullible celebrities to help them pick the public's pocket."

The CMA doctors' letter emphasized scientific evidence that human embryonic stem cells have proven difficult to develop and maintain, are unstable and mutate in culture, often act abnormally and tend to form cancerous tumors.

The letter highlighted adult stem cell benefits: "Verified accomplishments of adult (non-embryonic) stem cell research are already providing hope and therapy for patients suffering from heart muscle injury, diabetes and brain damage from stroke--with realistic promise for treating other diseases on the horizon."

Stevens said, "We reviewed the literature over the last three years since President Bush's policy was initialized and have found that he made the right choice. The government needs to put taxpayers' money into ethical research that will get us the most affordable cures for our patients in the quickest time."

This sentiment is found in a number of places, among those who seem opposed to ESC research.  For example, it is seen in this article  at the New Trommetter Times.  It strikes me as an odd kind of argument to make.  It does not mean that ESC research is unethical per se.  However, it implies that it is relatively  unethical to pursue ESC research over adult stem cell (ASC), because ASC research is more promising.  

The problem with the argument is that, when more than one line of research is available, it does not make sense to abandon completely the line that seems less likely to produce results quickly.  If that were the case, all we even would do would be applied research.  We would not do any basic research, because applied research, by definition, is more likely to produce usable results quickly.  If such a strategy were invoked, we eventually would run out of lines of applied research: it is basic research that supplies the material for applied research.  Likewise, in the case of stem cell research, if we abandon ESC completely, and pursue only ASC, we eventually would get to the end of the line.  Perhaps an argument could be made, that it would be better to put the majority of research funding into ASC research, just as it may be reasonable to put more money into applied research over basic research.  That is a policy matter, though, not an ethical one.

In my view, this dismisses the fourth out of the series of four objections listed near the top of this post. 

The third objection is equally dismissable.  There is an article  on the LewRockwell.com  site.  It contains this quote:

You see, the thing about stem cells is that they are undifferentiated. They have not yet specialized. That’s what the hubbub is all about. The whole promise of stem cell research lies in turning cells from generalists to specialists. Kind of like grad schools make doctors and engineers out of regular old undergrads. We are attempting to take a generic cell and turn it into one that specializes in producing insulin or making a heart beat or some other necessary function. It is wonderful and amazing stuff. But a stem cell is a stem cell is a stem cell. That’s the point. 
This simply is not true, although the reasons are highly technical.  To illustrate, I have quoted two excerpts from a text, Stem Cells and the Future of Regenerative Medicine. (Committee on the Biological and Biomedical Applications of Stem Cell Research, Board on Life Sciences National Research Council, National Academy Press, Washington, D.C., 2002.)  This book is readable online, although the text is from an uncorrected OCR scan.  For that reason, the online version has errors introduced by the process of scanning it and running optical character recognition.

I have taken the liberty of correcting it.  The original, erroneous text is included in strikeout format.  I can assure you that I have not changed the meaning.  The original scans are available at the National Academies Press website, if you care to check.

The full potential of bone marrow transplantation to restore a healthy blood system in every needy patient is currently limited by the unavailability of HSCs in the quantity and purity that are crucial for successful transplantation. Because of their relative rarity (one in every 10,000 bone marrow cells) and the difficulty of separating them from other components of the blood, so-called bone marrow stem cell trans- plants are generally impure (NIH, 2001~). The significance of such impurity is great. AD cells of the body express on their surface a set of molecules called histocompatibility (i.e. tissue compatibility) antigens. If a patient receives a transplant of HSC cells from a donor that has histo- compatibility antigens different from his own, the patient's body wiD will recognize and react to the cells as foreign. To increase the likelihood that histocompatibility antigens will match, it is preferred that donors be a related sibling of the transplant recipient. Even if their histocompat- ibility antigens do match, however, HSC transplants can be contami- nated by T cells from the donor's immune system. That contamination can cause the recipient's body to reject the material or can produce an immune reaction in which the T cells of the transplant attack the tissues of the recipient's body, leading to a potentiaDy potentially lethal condition known as graft versus host disease. Although autologous transplants, in which material from a person is implanted into the same person (for example, when a cancer patient stockpiles his own blood in advance of chemotherapy or irradiation) solve the problem of immune system rejection, the inability to purify the material leads to the risk that diseased or cancerous cells in the transplant will later be reintro- duced to the patient along with the stem cells.

If HSCs derived from human ESCs could be successfully trans- planted into the blood system of a transplant recipient (by using immu- nosuppressive drugs), any further implant tissue (say kidney or pancreas) developed with the same ESCs would not, in theory, be rejected by the recipient because the immune cells produced in the recipient's blood by the HSCs would see the implant tissue as "self''. But that is a Tong long way off, as Marcus Grompe noted, in as much as no one has yet demonstrated any in viva in-vivo reconstitution of an organ's function in either humans or experimental animals with cells derived from human ESCs. Moreover, ESCs in tissue culture give rise to a mixture of cell types all at once, and biochemical, tissue-culture, and molecular-biolOO~y -biology techniques to control and limit differentiation require much further investigation. Because human ESCs have only recently become available for research, and because public funding for such research has been limited, studies of how wed well ESCs or their differentiated tissues perform physi- ologic functions has been largely conducted with mouse models.
These quotes illustrate some of the hurdles that have to be surmounted before ESCs would have any therapeutic use.  They are not trivial by any means; no one can guarantee that clinically-usable results will be possible.  The point is, though, that ASCs are not equivalent to ESCs. 

As it is getting late, I am going to post this now, even though it is not finished.  I will post the rest as time permits.

(Note: The Rest of the Story/Corpus Callosum has moved. Visit the new site here.)
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