Comments on "Draft National Institutes of Health Guidelines for Research Involving Human Pluripotent Stem Cells (December 1999)" -- A written statement of Libertarians for Life, submitted on behalf of LFL by Doris Gordon, National Coordinator, to the NIH panel on Stem Cell Guidelines, February 2000

First, I wish to put myself and Libertarians for Life clearly on the record as objecting to the acquisition of human pluripotent cells by such illicit means as abortion and donation of "surplus" embryos created by in vitro fertilization.

Although the Draft Guidelines for Research Involving Human Pluripotent Stem Cells refers only to the latter means, both means take the life of the human being who is the source of those pluripotent stem cells; both means are aggression.

In my comments on the Draft Guidelines, however, I am going to focus on only four areas that I find particularly disturbing. Regardless of one's position on abortion or embryo research, these aspects of the Draft Guidelines have severe problems even within the context of the National Institutes of Health's (NIH's) own stated positions.

Two of these areas may be seen as substantive and concerning human embryo research as such; the third and fourth areas may be regarded as procedural, but I think they have major negative implications for the role played by the NIH in American society.

I must also note that while the Draft Guidelines address only human pluripotent stem cells, the current language opens the door to questions about totipotent cells. Totipotent cells extracted from a human embryo would appear straightforwardly to be embryos within the meaning of the present Congressional ban on Federally funded human embryo research. I hope that NIH does not disagree on so fundamental a matter, but it is certainly raised by the Draft Guidelines and must be addressed.

The four points I will make are:

A. It is impossible for NIH to disentangle itself from the destruction of human embryos.

B. The description of "human pluripotent stem cells" is inadequate, and raises the question of totipotency.

C. There are too many weaknesses in restrictions on conflict of interest, etc.

D. Accountability is needed.

Although I will address each of the four general points in greater detail below, my concerns may be summarized as in terms of areas in the Draft Guidelines as follows:

A. Regarding the interpretation of the Department of Health and Human Services (DHHS) that NIH is not precluded by current legislation from engaging in the research envisioned by these Draft Guidelines:

DHHS may interpret the current Congressional ban on human embryo research using Federal funds as it will. Nonetheless, it is realistically impossible in fact for the NIH to insulate itself or disentangle itself from the destruction of embryos that takes place in non-government facilities.

B. Regarding the description of "human pluripotent stem cells" in I. Scope of Guidelines:

As currently framed, the description is inadequate. Given changing technologies both of extracting and of manipulating human pluripotent stem cells, the Draft Guidelines' wording does not necessarily preclude NIH sponsorship of research it admits itself to be prohibited from funding. Specifically, the Draft Guidelines' use of the term "potential" is ambiguous. Wording should be added to make clear that supported efforts cannot — at any stage in the research — involve the use of cells that have the inherent potential to develop and mature as a normal human zygote or embryo would. The Guidelines must make it unambiguous that NIH cannot support research on or creation of cells that are in fact "totipotent".

C. Regarding the practical limitations on conflicts of interest stated in II. 1. b., on payments in II. 3. e., and on the related question of whether "donated" stem cells may be transferred out of NIH:

The Draft wording on conflicts of interest and on payments has serious shortcomings in meeting the Guidelines' stated intents. Those who would wish NIH to be active here should agree that there must be more separation between the extraction of any human pluripotent stem cells and the research efforts supported by NIH. And such a separation must equally apply to the products of such research.

D. Further, there must be clearly understood accountability and enforcement mechanisms — with teeth — and these should be stated in the Guidelines document itself.

I. SOME GENERAL OBSERVATIONS

A. Important preliminary distinctions

As I indicated above, the research proposed by NIH entails the destruction of human embryos — which is illicit per se. Libertarians For Life cannot support or condone the destruction of human embryos under any circumstances — whether in the private sector or in government. It is certainly worse in the case of government, though, because like it or not we are all compelled to support such activities through taxation.

Were human pluripotent stem cells to be derived only from embryos who died in spontaneous abortions, or as a byproduct of prenatal surgery aimed at the benefit of the fetus, I would not object to research per se. (I would, of course, object to similar research on totipotent cells. Since they have the capacity to repair themselves when extracted from an embryo, we would be dealing with a human embryo, not merely a part thereof.)

In articulating my concerns, therefore, I should also make clear that my comments should not be interpreted as condoning the research envisioned — even if the Guidelines were changed to respond to the concerns I will discuss here. The research envisioned necessarily entails the destruction of human embryos, and that is unjust — regardless of legislation, regardless of the informed consent of those who donate cells, and regardless of how carefully NIH conducts itself in supporting research on human pluripotent stem cells.

I hope it is clear here that the suggestions I make below should not be construed as being able to make NIH's planned activities acceptable. I hope NIH would make that clear if it chose to respond to them.

The suggestions in the second, third, and fourth areas would seem to be fully acceptable to NIH within the context of its public statements. I think these changes to the Draft Guidelines would be in NIH's interests as an institution. Moreover, I think the manner in which NIH handles this area will be crucial to how NIH perceives itself and how it is perceived by others.

B. Libertarians for Life's point of view

Interestingly, as a libertarian, I would not ordinarily be much concerned with the details of NIH policies. I hold, as do virtually all libertarians, that such scientific research is rightly conducted independently — outside government and not supported by the inherently coercive mechanism of taxation.

I am concerned with NIH actions here, first, because I believe that if there is to be any government at all, its primary function is to defend against aggression, and its unavoidable obligation is not to support or engage in aggression. Science has demonstrated that we are new human organisms, human offspring, human beings from fertilization onward. And a realistic philosophy must conclude that we are persons with the right to be free from aggression, the initiation of force, from that time also. I necessarily conclude, therefore, that destruction of the zygote/embryo/fetus is homicide, and doing so deliberately is aggression and violates libertarian principles. (Libertarians for Life makes a case for immediate personhood and rights from fertilization. Our reasoning is expressly scientific and philosophical, rather than either religious or merely pragmatic. For details, you may wish to see the articles on LFL's Web site: http://www.L4L.org.)

C. NIH's role in society

I recognize that many other libertarians disagree with me on abortion, just as many nonlibertarians disagree with me and libertarians in general on whether there should be tax-supported institutions like NIH to begin with.

I must also note that the current wording of the Draft Guidelines seems to view NIH's role much more expansively than the facts would support. In "Supplementary Information," the Draft states, "Federal funding will provide oversight and direction that would be lacking if this research were the sole province of private sources of funding...."

On the contrary, whether one supports the research or opposes it, the scope of NIH's oversight and direction will be limited to those efforts it actually funds. It may be the case, as the Draft continues, that NIH funding "will also help ensure that the results of research will be accessible to the public." But the practical effect of that may well be that research in the private sector will be subsidized by NIH — not that it will be overseen or directed by NIH.

In any event, I recognize that the first two areas I will discuss here raise issues of continuing controversy in American society. As such, some may argue that NIH can only accept what it regards as the generally accepted legal framework and support such research and experimentation as it concludes is permitted by that framework.

But, uniquely in the third and fourth areas, we are also discussing the role that NIH is perceived as playing in society, and the confidence that people place in NIH regardless of their political persuasion or their stand on such issues as abortion or human embryo and fetal experimentation.

In a free society, the underlying factor of trust and perceived truthfulness may sometimes be more important than whether people agree or disagree on substantive philosophical or political issues. With that in mind, it is of particular importance that NIH has recently come under increasing fire from across the political spectrum, and from those who have no particular political agenda. Serious lapses have been charged, and some widely documented, in scientific rigor, in institutional integrity and independence, and even in so rudimentary a matter as informed consent of persons involved in NIH-supported clinical trials.

I believe it is no longer sufficient for NIH to ask what line of research is permitted by law. It must ask how such research is conducted and how it is monitored by NIH. Even with relatively noncontroversial issues, NIH must ensure strict accountability. This is even more true — as the Draft Guidelines document itself states — with an issue like stem-cell research.

In this regard, unfortunately, the Draft Guidelines appear to fall dangerously short of NIH's assurance that it "understands the ethical, legal, and social issues relevant to human pluripotent stem cell research and is sensitive to the need to subject it to oversight more stringent than that associated with the traditional NIH peer review process."

II. DETAILS OF MY CONCERNS

A. It is impossible for NIH to disentangle itself from the destruction of human embryos.

Regarding DHHS's interpretation of the present Congressional ban on Federally funded human embryo research:

DHHS has stated that human pluripotent stem cell research is permitted so long as the government does not itself engage in or support the act of destroying embryos or fetuses in order to secure the human pluripotent stem cells:

"Federal law currently prohibits DHHS from funding research in which human embryos are created for research purposes or are destroyed, discarded or subjected to greater than minimal risk. ... DHHS concluded that the Congressional prohibition does not prohibit the funding of research utilizing human pluripotent stem cells because such cells are not embryos." (Draft Guidelines, Supplementary Information)

I would say that the DHHS interpretation runs counter to the clear intent of the law. (In which regard, it is disturbing that the interpretation, at least as reported in the Draft Guidelines document, is silent on the use of human totipotent stem cells.) However, we must also ask whether it is possible for NIH to conduct itself in the manner that would be required by DHHS's own interpretation.

To be sure, NIH-funded researchers will not be extracting the cells. Also, proponents of the activity will argue that NIH will not be billed for such activity per se, but merely for expenses incurred. But the question is whether a significant amount of that activity will take place only because NIH efforts will accept the "product" thereof, the human pluripotent stem cells — and will allow those who perform the activity to recoup a significant amount, perhaps all, of the costs of "producing" that "product."

If NIH Guidelines were to require that researchers accept only human pluripotent stem cells given strictly free of charge, how many would be given? Some, to be sure; but I think it highly unlikely that the number would be sufficient to support the research NIH envisions.

NIH and its supported efforts, then, are not merely "accepting" such cells. Rather, they are establishing a nexus of expectations, implied mutual obligations, and remuneration whose purpose — arguably, whose only purpose — is to produce such cells. In effect, NIH is saying that while it is prohibited from performing the action itself, it can essentially "subcontract" it.

I find such an argument unpersuasive. Inevitably, NIH is actively encouraging the creation of "excess" human embryos.

Conceding that DHHS's interpretation might nevertheless carry, however, we must still ask whether the Draft Guidelines adequately protect against activities that DHHS itself regards as forbidden. And I would say that they fail that test.

B. The description of "human pluripotent stem cells" is inadequate, and raises the question of totipotency.

The description of human pluripotent stem cells occurs in Section I. There, "human pluripotent stem cells" are described as "cells derived from human embryos or fetal tissue that can divide for indefinite periods in culture without specializing and have the potential to develop into all of the three major tissue types."

1. Different kinds of cells

In order to meet the conditions expressed elsewhere in the Supplementary Information and in the legislation cited, the Guidelines would have to add words to make explicit that no such cells have the inherent potential to develop and mature as a normal human embryo would. And by this, I do not mean that researchers ought not to permit such development; I am concerned specifically with whether such cells have the capacity to so develop — even if lethally impaired, for instance, by an inability to produce a placenta.

Further, the wording should indicate that supported research may not so alter the stem cells that they would have the capacity to develop as a normal zygote or embryo would, even though they were prevented from exercising that capacity.

Please note that I am concerned here with two situations independently: first, with stem cells that may be received by an NIH-supported research effort; thereafter, with any alteration that may occur during such research.

2. The ambiguity in "potential"

Frankly, I initially found the description of human pluripotent stem cells to be either self-contradictory or in need of considerable amplification. How, I asked, can the cells be said both to have a "potential" but continue "indefinitely" without expressing it?

Obviously, much hinges on the meaning of the word "potential." This is a term that NIH must carefully and honestly define in a realistic manner. Partially, this can be addressed by making clear that human totipotent stem cells are not permitted as the subjects of NIH-supported research.

However, the term "potential" must still be clarified on its own. Does it simply refer to the sense in which we would refer to the zygote as having the potential for further growth and development into its later stages as embryo, fetus, and infant, etc.? That is, in this normal sense of the term "potential," the zygote mainly requires a suitable environment and appropriate biochemical signals made available in that environment in order to simply grow and develop further as a human being. Or are the Draft Guidelines also using "potential" in the sense that one might, for instance, talk of somatic or germ cells at some stage in a cloning process — where experimenters can change a cell itself "back into" a zygote?

While it is true that human pluripotent stem cells cannot — left to themselves — develop into an embryo, even lethally impaired, it is also true that current technology can already so alter a pluripotent or even a highly differentiated somatic cell so as to return it to the zygote stage. And future technology could provide the means for even further genetic manipulation of such cells.

Will still newer technologies provide NIH with cells that can still be called "human pluripotent stem cells" within the Draft Guidelines' current description, but which will have the potential to develop along the lines of a normal embryo, and whose development must be actively inhibited in order to stay within the Guidelines' description?

I can hardly project the course of future technology. More to the point, however, I do not think that very many others can either.

3. Alteration by researchers

We do not need to move outside the realm of current technology, however, in order to be concerned about the manipulation of human pluripotent stem cells after they have been received by a research project. We must already deal with the reality of Dolly, and any number of other cloned animals that have been already successfully produced from differentiated somatic and germ line cells. The use of human pluripotent stem cells to produce a new human embryo is clearly technologically near — if not a fait accompli. So long as normal development were restrained, such an alteration would not seem to be precluded by the Draft Guidelines' current wording.

The Draft Guideline's current wording (in III. Areas of Research Involving Human Pluripotent Stem Cells that are Ineligible for NIH Funding) does note research goals that cannot be supported (such as the production of chimeras, etc.). But the current wording does not set boundaries on how the potential of the stem cells may affect the permissibility of research on them (again, not even to the extent of stipulating that the use of totipotent cells is not permitted).

Precisely because of DHHS's own legal reasoning, I believe that the Guidelines' language must make absolutely clear the possible boundaries of future developments in which NIH cannot take part — not merely with regard to the goals of research, but also with regard to the subject of the research, the nature and capacities — normal or altered — of the stem cells themselves.

4. Some possible responses

It may be argued that distinctions in the meanings of "potential" are an excessively abstract or philosophical realm for NIH to concern itself with.

Nonetheless, such distinctions can be expressed in operational terms that should pose no difficulty of understanding for the research community and the public at large.

It may further be responded that concerns about the nature of the cells would fall within the purview of the Human Pluripotent Stem Cell Review Group (HPSCRG) and its review of any "newly derived line of human pluripotent stem cells that has not been reviewed previously."

But the HPSCRG itself needs guidance. A strict reading of the current wording of the Draft Guidelines would seem to permit NIH researchers to alter pluripotent cells so that they become totipotent — so long as the researcher prevents the cells from developing as a normal embryo would.

The current wording speaks primarily of what the stem cells will not do; it does not speak of what they could do.

5. A critical distinction

From a libertarian pro-life perspective, the critical distinction in principle is whether or not a particular cell or group of cells are merely parts of an embryo, and will remain such. The critical practical question is whether these parts or cells can be manipulated in such a way as to return them to a state where they would have the same inherent capacities as a naturally occurring zygote or embryo — which embryo could then be allowed to develop further as a human being.

If the cell or group of cells has the inherent capacity to act like a normal zygote or embryo, then it is already a zygote or embryo.

At some point, the cells that became Dolly started to act as a normal sheep embryo. The fact that this point was reached through an artificial process is irrelevant to the fact that there was now a new, complete, whole biological individual. The same principle holds true with human cells — even if development is permanently inhibited or is terminated by the researchers.

Either way, the obvious issue is whether we are dealing with the killing of a human being. If the cell or group of cells can never behave in the manner of a zygote or embryo, or must themselves be altered to do so, then — to make the distinction in bluntly pro-life language — destroying them is not homicide or aggression. But, even in this case, a homicide would still have occurred in the "subcontractor's" laboratory, although not in the stem-cell researcher's lab.

However, if technology provides NIH-supported researchers with a human "pluripotent" stem cell that can behave like a zygote or embryo, and must be inhibited from doing so, then there would be homicides in both cases: those in the "subcontractors'" laboratories; and those in the NIH-funded laboratories. Similarly, there would be two homicides if a stem cell (or group) were returned to the state of a zygote or early embryo.

Obviously, I recognize that many would insist such destruction would in no way be homicides. Regardless, in these latter events human embryos would have been destroyed, and NIH would be unambiguously complicit and in violation of the law.

6. The nature of the cells

In the case of human pluripotent stem cells received by researchers from outside NIH, it may be argued by some that the "two-homicide" case is not technologically possible at the moment. Regarding research on such stem cells, however, alteration is all too easy.

Therefore, the question here is whether NIH is indeed "sensitive to the need to subject [this research] to oversight more stringent than that associated with the traditional NIH peer review process." To that extent, I believe it would be well to make thoroughly explicit what NIH will not accept for research in the future.

Again, it is not merely that the use of the word "potential" with regard to human pluripotent stem cells is open to differences in interpretation, or that the Guidelines' wording may be overtaken by changes in technology. The nature of human pluripotent stem cell itself is already close to the edge of what we mean by a zygote or embryo.

A human pluripotent stem cell or group of such cells may not have the "potential" to develop as a normal zygote or embryo would develop. But such cells are remarkably receptive to alteration such that they would so develop. Considering both policy, and the nature of the entities being studied, the Guidelines should not be susceptible to ambiguity on the nature of the cells to be studied and on alterations that would not be permitted.

Others would be better qualified than I to suggest appropriate wording, but I do find that the Draft Guidelines need amplification in this area. This, however, is merely one case in which the Guidelines will serve as an indication of how seriously NIH takes the assurances those Guidelines would offer the public. The third area in which I am concerned is much more concrete.

C. There are too many weaknesses in restrictions on conflict of interest, etc.

1. Conflicts of interest

In II. 1. b., it is stated that, "To avoid possible conflicts of interest, the attending physician responsible for the fertility treatment and the researcher or investigator deriving and/or proposing to utilize human pluripotent stem cells should not have been one and the same person."

Realistically, it would seem necessary to add that such persons should not have any continuing business or research association. It is precisely the point of "conflict of interest" that it is not limited to individuals but is critically important in an organizational and business sense.

2. Payments

In II. 3. e., it is stated that an investigator's application should provide "an assurance that stem cells to be used in the research were or will be obtained through a donation or through a payment that does not exceed the reasonable costs associated with transportation, processing, preservation, quality control and storage of the stem cells."

Unfortunately, the scope of costs permitted to be incurred is sufficiently wide that it appears all to easy for an organization or enterprise to establish a significant revenue source in the activities described. The potential for abuse or simple misinterpretation of "reasonable costs" is sufficiently strong that the Guidelines themselves should give strong and clear indication of the boundaries of such costs.

Additionally, the wording of the limitation appears to refer primarily to the initiation of an effort. It is a statement of intent, with no discussion of whether or how that intent will be verified.

The Guidelines should make clear that the activities permitted for cost coverage should be not such that they can establish themselves as part of an organization's economic expectations or viability; moreover, the organization should not be able to subcontract the activities in such a way that the subcontractor would be able to conduct the activities as a profit-making venture. Further, the Guidelines should indicate that NIH will expect reasonable evidence of this, both before and after the activities take place.

3. Transfers of stem cells

Also, the Draft Guidelines do not articulate in any manner whether NIH may or may not transfer "donated" stem cells outside NIH — either in their normal state, or in any altered state — and whether such transfer may be made to other Federal government departments or offices, or to researchers, labs, or organizations outside the Federal government. To the extent NIH is serious about its assurances, it should add clear and unambiguous language to the Guidelines indicating whether such transfers are permitted and if so, under what conditions.

Such transfers would seem of dubious propriety, at best. The Draft Guidelines already allow the possibility of NIH establishing a continuing economic nexus supporting the destruction of human embryos; to permit transfers of stem cells after NIH-supported activities would establish NIH as a conduit to subsidize these activities in commercial and other nongovernmental research.

D. Accountability is needed.

And in all these issues, as I said at the beginning, there must be clearly stated accountability and enforcement mechanisms — with teeth.

It may be responded that other NIH policies already provide the needed mechanisms, that describing them here would be redundant. Nonetheless, given the gravity of the issues involved, I believe the principles involved should be clearly restated here. If that is redundant, redundancy is no disadvantage. (It might even assist in a wider review of NIH policies.)

Unfortunately, parts of the Draft Guidelines highlight the fact that wording alone is insufficient. In II. 2., the Draft Guidelines indicate the need for informed consent. This is hardly a matter of controversy. But it is in precisely this noncontroversial area that NIH has come under fire in recent months. It is not that there was anything particularly wrong with NIH's policy statements and regulations on informed consent for human subjects. The problem is that they were not followed. The problem is that research was not adequately monitored.

The principle of accountability must certainly be unmistakable in the Guidelines. However, no matter how well the Guidelines are formulated, there must be follow through; there must be monitoring; there must be clearly understood and enforced sanctions for noncompliance.

Any limitations on the nature of the cells to be worked on must be observed both before research begins, and thereafter. NIH must follow through in a manner that is clearly understood, predictable in advance, and conducted without any attempt to gloss over or ignore unpleasant facts. "Business as usual" seems no longer to be an option for NIH, particularly in regard to an issue like human pluripotent stem cell research.

III. IN CLOSING

It is unlikely that we are going to come to a quick agreement on the underlying controversies, nor is it realistic to think that NIH would be a major instrument of such a process. But how NIH conducts itself will have a major impact on how research is perceived in general, and on how NIH is perceived in particular.

As I have said above, even if NIH were to attempt to accept as many of my comments as possible, I would still find research in this area to be unacceptable. Human embryos, who are human beings, persons with rights, must necessarily be destroyed in order for the research to take place.

I must admit, therefore, that I find myself in an unusual position here. As you may know, a majority of libertarians support choice on abortion, and many emphatically support embryo research. Nonetheless, the cynical among libertarians have indicated no surprise at all at recent reports of problems in NIH's handling of human subjects. Similarly, people that I regard to be quite liberal have proven to be equally jaundiced with regard to NIH.

Some of them have told me that I should not care whether NIH conducts itself in a way that undermines its own legitimacy. In fact, they would welcome that.

Given the stakes, I hope NIH disagrees with them on this — and proves them wrong.