Meeting Transcript
December 3, 2004

The Stephen Decatur House
1610 H Street, NW
Washington, DC 20006

COUNCIL MEMBERS PRESENT

Leon R. Kass, M.D., Ph.D., Chairman
American Enterprise Institute

Daniel W. Foster, M.D.
University of Texas, Southwestern Medical School

Michael S. Gazzaniga, Ph.D.
Dartmouth College

Robert P. George, D.Phil., J.D.
Princeton University

Mary Ann Glendon, J.D., L.LM.
Harvard University

Alfonso Gómez-Lobo, Dr. phil.
Georgetown University

William B. Hurlbut, M.D.
Stanford University

Peter A. Lawler, Ph.D.
Berry College

Paul McHugh, M.D.
Johns Hopkins University School of Medicine

Gilbert C. Meilaender, Ph.D.
Valparaiso University

Diana J. Schaub, Ph.D.
Loyola College

James Q. Wilson, Ph.D.
University of California, Los Angeles

INDEX

• Session 5: Biotechnology and Public Policy: The New Canadian System
  
• Session 6: Seeking Morally Unproblematic Sources of Human Embryonic Stem Cells
  
• Session 7: Public Comments

SESSION 5: BIOTECHNOLOGY AND PUBLIC POLICY: THE NEW CANADIAN SYSTEM

CHAIRMAN KASS:  Good morning.  I think we should probably start.  I think there are a couple of our members who've indicated that they will be coming late, but I don't think we should delay any further.  This morning we continue our attention to the subject of the regulation of new biotechnologies.  And as everybody here, I think, knows, the Canadian Parliament last spring enacted major legislation creating a new broad and comprehensive system of regulation of assisted reproductive technologies.  The legislation is the culmination of a very long and careful process that was begun by the work of Royal Commission, the chairman of which, Patricia Baird, addressed this Council, I want to say more than two years ago.

But between activity of the Commission and the enactment of the law, it was not an easy or simple task and we are very fortunate to have with us some people who are heavily involved in that legislative activity.  Three gentlemen at the table, Ian Shugart, who is the Assistant Deputy Minister of Health Canada, Health Canada being the equivalent of our Department of Health and Human Services.  He is joined by Michael Vandergrift, who is the Director of Health Science Policy Division and Glen Rivard, who is the general counsel of Health Canada.  Welcome to all three of you. 

We had the privilege at the office, the staff and I, of hearing a presentation by these three men about two months ago, describing not just the content of the law but in the discussion exploring how it was possible for them to bring this about and while Canada and the United States, though friends, are not identical twins in political matters, we thought that it would be extremely useful for this body, as we continue our thoughts on regulation, to learn about what the Canadians have done and how they did it and so thank you very much for returning, for offering us your thoughts and we look forward to the presentation.

MR. SHUGART:  Thank you very much, Dr. Kass and it is very much a pleasure for us to be here and to have sat in the public rows yesterday and enjoyed and benefited enormously from the discussion of the range of issues that you have on your agenda at this meeting.  We do appreciate the honor of being invited to present to the council and we hope it will be useful for you and we know that it will be useful for us as you share your views and your reactions with us.  Canada/US relations have been very much at the top of our minds over the last week as the President visited Ottawa and Halifax and both the Prime Minister and the President reiterated the desire of both countries to work closely together on a range of issues and it may be that in our own small way on this topic, we can contribute to the relationship between Canada and the United States.

In this presentation, we intend to provide some context for the experience that we've had in Canada, give an overview of the content of the legislation and then provide some thoughts really drawn from the experience that we have been through and indeed are continuing to go through.  In the presentation, I think it will be useful to touch on some of the issues that were discussed yesterday afternoon in the presentation by Professor Fukuyama.  We'll touch, for example, on the key role of legislators in this process.  That was, I think, an important issue that you touched on and with reference to Dr. McHugh's comments, the Canadian Parliament didn't set out to put up its dukes, but we certainly did deal with the issues of research in the context of an emphasis on addressing the health and safety implications of this particular area of biotechnology and bioethics. 

The Chairman has referred to the history of this experience in Canada.  It has been a complex one and a long one.  One might say that it had a greater than 10-year gestation.  The Canadian policy environment had been driven by the Royal Commission on Reproductive Technologies that was established in the late 1980s.  It's interesting to note that the Commission came about as a result of pressure from the public to address new developments in the area of assisted human reproduction and these technologies, particularly from women's groups, bioethicists and geneticists, and also faith-based groups and some others.

Since the report of the Royal Commission was tabled,  Canada has had a voluntary moratorium on a variety of practices: Regulations governing the safety of sperm donation and their storage and three different legislative processes.  The first legislative attempt focused only on prohibitions.  It was fairly roundly criticized on the grounds that it did not provide a regulatory framework to deal with some of the issues that were relevant. 

The second attempt was a draft bill for pre-study by a parliamentary committee and then finally the last initiative saw legislation passed by our Parliament in April — excuse me, March of this year, almost two years after its first introduction.  I personally on this file have worked with three different ministers of health and with the fourth now working on the process of the developing the regulations to implement that act. 

In the end, a key factor in achieving passage of this legislation was the fact that it had been over 10 years since the Royal Commission first dealt with it.  For some this has been perhaps a symptom of a broader issue in which the challenge of keeping public policy responsive and keeping pace with developments in science and technology is, I think, a profound challenge for our societies. 

Very quickly, let me describe to you the environment for assisted human reproduction in Canada.  As a general rule of thumb, you can take the population of Canada and other factors and multiply by 10 in the United States context.  Not everything follows that rule but it's a general idea of the size of the country.  We estimate that one in eight Canadian couples turns to AHR techniques to deal with the problem of infertility.  In 2001, over 1200 children were born in Canada using these procedures.  Most of the services are provided in physician's offices, private clinics, which are corporately constituted as independent commercial entities.

Approximately 25 of these centers mostly in the largest urban centers, Vancouver, Toronto and Montreal and about 104 facilities, are involved in either sperm distribution, importation or processing.  We also need to set as part of the context, that Canada, like the United States, is a federation and the constitutional division of powers is an important feature of how we have addressed the bill and also the Charter of Rights and Freedoms which was put into our constitution in the early 1980s is an important dimension of addressing the issue as well.

The major aspects of the bill that we're going to refer to and in a moment, I'll invite my colleague Glen Rivard, to give you a brief synopsis of the different components of the bill.  The Canadian legislation contains, as we heard yesterday afternoon from Professor Fukuyama, a Declaration of Principles, a set of prohibitions, a number of controlled activities, and the rules by which those controlled activities can occur, a section dealing with the reporting of information related to health, rules for the licensing, inspection and enforcement of the provisions of the bill, and then finally, the establishment of the Assisted Human Reproduction Agency of Canada. 

It's important to know that the legislation is established under the criminal law head of power in our Constitution.  This gives us the ability to regulate health and safety, our Food and Drugs Act, for example, which roughly corresponds to the legislation governing your own Food and Drug Administration.  It takes place under the criminal law head of power.   And one of the purposes of the criminal law is to, in the rather old language, prevent a public evil and under that category, some of the ethical dimensions of these technologies are addressed. 

Glen, I'll invite you take us briefly through the scope of the Act and the subsequent pages.

MR. RIVARD: Thank you, Ian.  The diagram in front of you is an attempt to pictorially summarize what is and what is not covered by the legislation and of course, the first major distinction is to realize that the legislation focuses on assisted human reproduction only and, in particular, this encompasses then the collection and treatment of the gametes that would be used for these processes, the processes surrounding artificial fertilization and then if you will, the uses or the outcomes of that process, the uses of the resultant embryo.  The primary purpose for this, of course, under the legislation, would be creation of embryos for reproductive purposes and the legislation governs the treatment of that embryo and the process of its transfer into the woman.

And it is at that point that the legislation ceases to apply.  At that point, the woman is pregnant as in any other fashion and the legislation really has nothing more to say about the pregnancy, the embryo within the woman, birth, anything of that sort.  It's — the legislation is concerned with and only with assisted human reproduction.

There are other outcomes pertaining to, or possible outcomes with respect to, the resultant embryo.  The embryos can — artificial embryos or embryos can only be created artificially only for the purpose of reproduction, but given the state of the technology, if you will, there are embryos that are surplus to that process and the legislation does envisage as well, the ability to donate them to third parties for reproductive purposes, research on the very limited circumstances or the possibility of disposal of the embryos as well. 

The only notable exceptions to this framework are the provisions that deal with surrogacy, particularly the commercial aspect of surrogacy. And the legislation basically allows for surrogacy but prohibits payment for surrogacy with an exception relating to expenditures.  But other than that, all the activities fall within that framework.

I'm going to focus on really four aspects of the bill, the first being the Declaration of Principles.  This serves, I suppose, many purposes, but at least in terms of the legal use of the provision, it really in Canadian law has two effects.  The first is where there is ambiguity in the application of the Act, a particular situation, the courts can refer to the Declaration of Principles to provide some guidance and secondly, the Act specifically provides that the  Agency must operate in accordance with the principles.  So that in the process of granting licenses, for example, to undertake in vitro fertilization procedures or any other regulated procedure, it must pay attention and apply the principles. 

The — the principles are not organized in — there's no priority to the principles with one exception and, therefore, the process of applying them will be a matter of considering the ones that are relevant to the particular decision and balancing of these factors.  The one exception is the first principle where the language explicitly gives priority to the health and well-being of children who would be created as a result of these procedures. 

The other principles of importance include the benefit — reference to the benefits of the technology and the need to protect health, safety, dignity and rights.  As well, there's a reference to the protection of the health and well-being of women, importance given to free and informed consent as a fundamental principle for these activities, reference to non-discrimination, a reference to the concerns relating to commercialization of donations, for example, and a principle pertaining to the need to protect the integrity of the human genome. 

As Ian mentioned, the legislation is based on the criminal law power, which under the Canadian Constitution is an exclusive federal jurisdiction and therefore, makes it relatively easy for us to pass legislation that's applicable across the country.  The criminal law power has a rather wider interpretation — wide interpretation in Canada.  It includes the ability, of course, to legislate with respect to matters of public morality, which is what most people think of when they think of criminal law, but it has also been interpreted by the courts to include legislation with the purpose of protecting health and safety of Canadians and it's under that heading, for example, that we regulate food and drugs under our Food and Drugs Act.

This is very similar in approach.  The legislation can be conceived of achieving two objectives.  The first is the — the first objective is really that covered by the prohibitions in which we set out limitations on activities, limitations that are primarily driven by ethical concerns and the second pertains to provisions that are intended to protect the health and safety of those participating in activities that are deemed to be basically ethical and those are the controlled activities and we'll come to that very shortly.  But just to quickly run through the prohibitions, you can see that — I won't go into great detail on all of them, but clearly human cloning is prohibited.  All forms of human cloning and for any purpose is prohibited under this legislation, as is germ-line genetic alteration.  Sex selection for non-medical purposes is prohibited.  There has been some, I know, concern around this Commission about phenomenon such as the parentless child.  There is a prohibition against creating an embryo from a cell of another embryo or fetus. 

The — an artificially created embryo must be implanted within a woman within 14 days to — we were quite concerned about the notion of embryos developing sort of to who-knows what end point outside the body of a woman.  The 14 days is 14 developmental days.  So if the embryo is frozen as is typically the case in the in vitro fertilization process, the clock stops ticking on that particular provision.  There are also, again, provisions dealing with prohibiting chimeras and hybrids for most purposes, for reproductive purposes.  And again, I've mentioned in the past, commercialization of the reproductive capacities of individuals, this — there's no prohibition against commercialization of the industry and this is a common misunderstanding.  It is a private sector industry as it were, and that's not affected by this except that there are provisions that address the reproductive capacities of individuals who deal with — who basically make it illegal to pay for donation of gametes, to pay for embryos, to pay for surrogacy.

The second major head of activity is what we call the controlled activities.  These are essentially activities that are prohibited unless they are carried out in accordance with the Act and the regulations created under the Act.  And these activities all require a license that will be issued by the agency.  These are the activities that we feel are fundamentally acceptable but that we have concerns about the need for measures to protect the health and safety of people participating in them.  And they are defined in very general terms which will allow us, in turn, to a great deal of flexibility in developing the regulations.  So the two primary heads are the provisions allowing us to regulate collection, storage, handling and use of human reproductive material to create an embryo, and then the storage, handling and use of an in vitro embryo for any purpose.  As well, there is authority that allows us to authorize the reimbursement of expenditures of donors and surrogate mothers.  Just to note, both the prohibitions and the controlled activities carry some very significant penalties as well. 

A last key element of the legislation, at least the last I'll speak to, is that of health information and the council, I know has identified — or the Commission has identified the importance of creating good information in this area so that we can make more informed decisions about the health and safety aspects of this technology.  That is a very — very much something that we hope to be able to do as a result of the information and privacy provisions in the Act.  The provisions provide — they create a fairly wide authority to collect, retain, use and disclose health information of people who are undergoing these procedures and also people who are donors.  They create a privacy framework that is — applies both to the licensees under the Act for example, the in vitro fertilization clinics, and also the agency that Mr. Shugart mentioned.  The — precisely because — well because of the sensitivity of the information and because of the fairly broad scope pertaining to the collection of the information, this is balanced in the legislation with a privacy regime that, in fact, is stricter than the general privacy regime that applies to information in the hands of the Federal Government.

So there's been a balance struck there, a balance which received favorable comments from the Privacy Commissioner in Canada. 

MR. SHUGART:  Thank you, Glen.  Three points which I think are particular advances for our country in this area are the creation of the agency, the information framework that Glen has just talked about and the comprehensiveness of the approach.  The agency is, of course, modeled to some extent on the United Kingdom model.  It will be independent of the Department of Health, although within the portfolio of health agencies reporting to the Minister of Health, no different than what occurs within the domain of several agencies here reporting to the Secretary of Health and Human Services.  It will be governed by a board that will be broadly representative, although the appointments to the board are to the person.  They are not formally representative of specific sectors of Canadian society and it will be led by a chief executive officer to be styled a President.

The agency's mandate is to implement the  Act, issue the licenses, and operate the information registry.  The ongoing policy responsibility remains with the Minister and assisted by the Department.  In fact, it's our view that the Agency will be a home over time, to the debates that continue related to this field.  It is inevitable that these debates will occur in Parliament as well and in other parts of society but in a coherent and ongoing way, the agency at the level of the Board will undoubtedly be a vehicle, a forum, for transparent and systematic debate about these issues as the field continues to develop.

It will provide an anchor for debate in what is sometimes a slippery slope and it will be a focal point for Canadians as that — as the field evolves.  The information framework is, in our view, hugely important because it provides a view over time of what is actually going on in the sector.  We do not have today any reliable or comprehensive information about the nature of the activity, the extent of the activity, the effects of the activity and this information framework over time will provide us with that. 

The comprehensiveness of the package is something that can be turned to, providing some principles.  They may not be universally accepted but it will provide stability in this sector and ultimately for the families who benefit from this sector as well as the research enterprise relevant to it. 

Let me focus then, on three challenging issues which we encountered and which will continue to be, I suspect, hotly debated from time to time.  The first is donor identity.  These issues are a challenge to the proposition that it is only the issue of research relative to embryos that is bioethically significant and important.  The question of whether offspring should have access to the identity of their biological parents, that is the donors of sperm or ova, without the consent of the donor, was key and central to this debate.  Many offspring gave passionate stories about how they felt they needed this information to understand themselves, their roots, their identity and this view was strongly supported by many parliamentarians. 

Here there was a difficult tension at play.  The potential for injury to the infertile given the serious concern that removing donor anonymity would deter donations and reduce the supply of gametes, reducing the chances to have a family through these technologies over against the legitimacy of the desire of the offspring to understand their identity.  There was a further factor, somewhat technical rooted in law, given that most provinces had not amended their family law, which occurs at the level of provinces, to insure that a donor is not considered the parent in law.  As such the provinces were very opposed to a system of mandatory donor identification without having made the changes in family law. 

In our study of this issue, we found that all countries that have mandatory donor identification have clarified the legal status of the donor.  With respect to identity, the Canadian legislation uses a two-key approach.  The offspring can request information about the identity of the donors and the  agency will receive such a request and seek the consent of the donor in a neutral way, not applying pressure but simply exploring whether the donor would consent to provide that identity.

The offspring, however, will receive health related information on the donors.  This is part of the information regime that is established by the legislation.  This whole question of donor identification was resolved in the parliamentary committee studying the bill by one vote and that carried through into Parliament where the decision of the committee was retained. 

The second issue which, again, is very significant from the perspective of bioethics is commercialization.  This issue was raised most frequently in the context of sperm donation and of surrogacy.  And again, there were two principles involved.  On the one hand, a principle of the legislation, that is that these procedures and the human capacity for reproduction ought not to be commercialized and the pragmatic effect on the other hand of insuring the availability of reproductive material to provide the basis for building families.

As we mentioned, payment for gametes is now prohibited.  The prohibitions are in effect as a result of the law.  However, concerns over the continued availability of gametes in this environment of non-commercialization is easily the single most significant issue heading into the implementation phase.  We're in a transition period right now. Payment is prohibited but the requirement of receipted expenditures for expenses is not required.

This regime will require Canada to  develop an altruistic culture of donation such as applies now with blood and with organ donation.  We believe that it can be done, but it is going to require work and effort to bring that culture about and help it to mature.  And I might just note that it is an interesting complexity in the Canada imports - donated sperm from the United States.

Finally, embryo research; the legislation was considered in the context of the debate over embryonic stem cell research.  However, the legislation again, to restate what Glen pointed out, applies only to embryo research in general.  It does not cover the broader issue of research using existing stem cell lines.  The legislation prohibits the creation of embryos for research purposes other than a carefully constructed provision that allows research to improve IVF treatments themselves. 

Therapeutic cloning is prohibited in Canada, which is a key point of contrast, as you know, with the approach in the United Kingdom.  The legislation permits research using IVF embryos created for reproductive purposes but no longer required for these purposes.  This is only permitted under the operation of a license and that license will be granted taking into consideration factors such as evidence of full consent from donors, ethics review through the normal procedures and the use of the in vitro embryo must be deemed by the agency to be necessary to the purposes of the research.

These provision cause concern amongst those opposed to embryo research.  Many others thought the legislation was too restrictive in prohibiting and regulating certain areas of scientific inquiry.  And in our view, it was between those two perspectives impossible to achieve a compromise that everyone would be satisfied with.  However, we tried in the legislation to clearly set out that embryo research is unique and requires more oversight than any other type of research.  This will be the only basic research in Canada that requires a government license.  And the continuum of views on the research involving embryos is well-known.  At the one end, this is really tissue morally indistinct from any other.  At the other end that the embryo is an entity with the full moral status of human life and in the middle a view that this is an entity with potentiality for full personhood worthy of special consideration.  The middle view was not proposed by the government as a formal philosophical proposition.  This case about as a result of debate, that is to say that the debate across that spectrum of views was thorough, was forcefully expressed by parliamentarians.  In the end, this was a combination of legislative pragmatism, philosophical outlook and an intuition on the part of the Minister and of the Government and of legislators about what would be acceptable in the end to the largest number of Canadians. 

Now, despite these controversial issues, how did we actually move to having legislation?  Let me mention three aspects.  There was much debate and disagreement about the issue.  This was not easy to resolve in the end but there was more than the intensity of debate, a consensus that this issue had to be addressed.  It was the type of legislation that no one is 100 percent comfortable with.  Probably every member of Parliament and Senate wanted to change something but in end there was a strong feeling that we had to start somewhere.  We had to fill a void.  Secondly, towards the end of the debate when it seemed that nothing was going to be certain. Several groups, women's groups, social advocates, bioethicists and so on, became even more vocal in support of the legislation even though they were not 100 percent happy.  Their argument was that the real impact of the bill was to protect the health and safety of women and their offspring.  And it went right back to the origins of the study of the Royal Commission.  They pleaded for decision makers not to lose sight of the origins of the bill which was that these are technologies which have enormous potential and they need to come under the scrutiny of the public's fear and need to be ruled by the public's fear.

The fact that Canada did not have any legislative provision covering human cloning, particularly reproductive cloning, was a key driving factor and some developments in the commercial scientific sector in the United States and an announcement by a group called the Raelians in 2002 which created a certain amount of public controversy, brought into relief the void that existed at the time.

We'll conclude with subsequent steps.   We made good progress as I think is evident, but we have not finished this journey by any means.  The legislation, while on the books, in some respects is only half complete.  It requires an extensive set of regulations to be developed in order to commence the licensing of the procedures that are controlled and the related research.  And this is a major area of activity in which we are engaged right now through consultation with the public and with experts. 

There is also a clause in the legislation requiring Parliamentary study of all proposed regulations.  We don't anticipate that there will be that much free time in the day ahead.  We need to establish the agency.  We need to recruit the chief executive officer and the Board of Directors.  This will be done again, through a public process.  The legislation provides for a review of the Act three years following the creation of the agency.  This is a clause right in the law that Parliament will engage in a review of the law.  The purpose of this is to enable Parliamentarians to be up to date with the latest developments and to satisfy themselves that it still reflects the public's views on the issue.  We're more than happy, members of the council, to exchange views and provide any further elaboration.  We hope that's been of some use to you.

CHAIRMAN KASS:  Thank you very much for a clear and concise and comprehensive presentation of the essence of what you've done.  The floor is open for questions and discussions and could we have the lights.  It's very hard to converse in the dark.  Jim Wilson, please.

PROF. WILSON: Could you clarify, Ian, for me, one or two provisions?  What led you to ban the purchase or sale of gametes and to rely instead on a voluntary contribution system akin to the supply of blood that occurs in some countries, although not in this country?  Isn't that likely to reduce substantially the supply of gametes?

MR. SHUGART:  There was concern about that, Professor Wilson, no question.  The prohibition really flowed directly from the principle that these activities and the materials that are used on the activities should not be the basis of commercial exchange.  That these are societally important decisions that families make and the view of the Royal Commission, this was one of the main conclusions that they came to was that this should not be the subject of commercial activity.  And by extension, the implications were for surrogacy, paid surrogacy and also for the purchase of gametes or the sale of gametes.  So it really was that simple an extension of that principle.

PROF. WILSON: Well, since I don't understand the objection to commercialization, and please forgive me if I press a bit more on this, extracting sperm is not an especially difficult matter.  Extracting an egg is a difficult matter and to not pay women for the sometimes burdensome procedure involved, it seems to me restricts substantially the supply of eggs for those persons for whom an egg should happen to be necessary.  But the argument against commercialization in your view covers that ban without exception.

MR. SHUGART:  Well, it is what underlies the ban and there's no question that that was the tension the Parliamentarians faced and it, in fact, is one of the reasons why Parliament said, "We want to — we want to look at this law again.  We want to see what the effect is".  We will, through the information, the reporting requirements, be able to know over time what the effect is, the supply of gametes and as we mentioned, there's no question that the development of a culture of altruistic donation which applies in some other countries and has been developed, is going to require some focus and some work. 

Whether in that area the law will absolutely remain the same, I can't predict, but in our Parliament, there was a very strong view that this was as important a principle as virtually any other within the scope of the bill.

PROF. WILSON: If I could just pursue this one more moment, you do not wish sex selection to be engaged in for anything other than correcting a sex related disorder.  So that a family that has four girls and would very much like a boy, this cannot be done under Canadian law by using some PGD procedure increase the odds you're selecting a male sperm.

MR. SHUGART:  That's correct.

PROF. WILSON: But that can be done in the United States, so should we open up another flight from Canadian Airlines to Chicago to accommodate the customers?

MR. SHUGART:  Well, we rejected any notion of extraterritoriality, so all we could do was put in place the regime that reflected a Canadian perspective but it is absolutely true that there is an open border between our countries.

CHAIRMAN KASS:  We can also fly to Hong Kong and take advantage of the, you know, nice Chinese offer.  I understand.  And a tiny point in this, Mike Gazzaniga wants the floor in a moment, but just to clarify, one of the ways in which American fertility clinics are dealing with this question of the supply of donated materials is to provide reduced costs to the first couple if they are willing to make their surplus embryos available to other couples.  That's not exactly the buying and selling — I mean, you could say that's not exactly the buying and selling of the materials but the question is, does your law deal with that and would that be — would that be a way around this that's acceptable in Canada or not?

MR. RIVARD: That practice has been known in Canada and it is caught by the prohibition.

CHAIRMAN KASS:  I'm sorry?

MR. RIVARD: It is prohibited.  It is part of the prohibition.  So the purchase of gametes includes exchange for services, for example, any exchange of value.

CHAIRMAN KASS:  Now, let me repeat.  If a couple comes to an in vitro clinic and says, "We're prepared to allow the surplus embryos to be donated" and the doctor says, "In that case, we will give you  a reduced rate for the services here", that is explicitly covered by this prohibition?

MR. RIVARD: I think what would be caught in the prohibition would be the second part of that phrase, in that case you'd benefit from a reduced rate.

CHAIRMAN KASS:  Okay.

MR. RIVARD: The donation of the surplus embryos is by no means prohibited.

CHAIRMAN KASS:  Not a problem.  Clear.  Michael Gazzaniga.

DR. GAZZANIGA:  I'm curious in the history of the debate that led up to the legislation, the way it's structured now is the stem cells harvested from leftover IVF embryos can go forward under licensing; whereas, there is absolutely no capacity to use therapeutic or biomedical cloning to reap stem cells.  We've been through these moral arguments on that point and a lot of people have trouble distinguishing those two cases.  How did the discussion go in Canada and when it finally came down to whether this bill was going to go forward or not, did it turn out to be a vote that some people simply rejected the view and some didn't and could you have predicted it by what people believed in their personal lives?

MR. SHUGART:  I would say a couple of things on that.  First of all, I think that the starting point of the debate was influential in this sense.  The government in our system for the most part proposes to the legislature a piece of legislation.  It is not built from the ground up to the same extent as perhaps the congressional system could be described as doing.  So that the decision of the Minister and of Cabinet in coming down on some of the key provisions was important as a starting point for the debate. 

Of course, the full range of views was expressed by individual Parliamentarians.  It would seem in retrospect that the Minister and the Cabinet had predicted with some accuracy and reflected with some consistency the views of a majority of Parliamentarians.  So that while there were opposing views on whether the creation of embryos for research purposes should be allowed, in the end that was supported by a clear majority of Parliamentarians. 

I understand that objection that fundamentally there is no distinction in terms of the moral status of an embryo, regardless of its purpose in coming into being.  That does seem, however, to be a point of gradation along that spectrum of views, that purpose is an important factor in bioethics.  And that the existence of supernumerary embryos as a result of another purpose is capable of differentiation from a different purpose which is to produce an embryo for research for therapeutic purposes.  I fully appreciate that that distinction is not accepted by everyone but I think in the range of views, it is a qualitatively different point on the spectrum. 

We did not, as civil servants, really engage in any predictive exercise on the basis of members of Parliament, although as we interacted with them, the views of different Parliamentarians became clear.  We advised and implemented the views of Ministers and the Government and did our best then with Parliamentarians to provide explanation and awaited the outcome along with everyone else.

CHAIRMAN KASS:  Gil Meilaender?

PROF. MEILAENDER:  In our discussion yesterday afternoon, Paul McHugh expressed, if I'm — if my memory is serving me all right, a certain kind of skepticism with respect to the surplus embryo question, the kind of skepticism that one might express by saying, "Well, if we're going to allow those surplus embryos to be used for research, the IVF industry will indeed produce plenty of them.  So that technically they're produced for reproductive purposes  but in fact, that's not quite what's going on.  Did that sort of issue get raised and discussed at all? Is it deemed sort of an overly suspicious and too skeptical kind of view?  Did it just — did it not make its way into the debate at all?  I'm just curious to know whether it even came up and was considered.

MR. SHUGART:  Well, Professor Meilaender, I'm trained to be skeptical but not suspicious.  But indeed it did come up and one of the provisions in the regulations again, driven by Health and Safety, is to — or will be to put limits on the number of embryos that can be produced from a particular cycle.  The purpose of that will indeed be to address the health concerns of the subject of the procedure.  The effect of it may well be to provide a check on the phenomenon of deliberate over-supply of embryos.

CHAIRMAN KASS:  Please.

MR. VANDERGRIFT:  If I could just mention something, two other factors that were prominent during the debate, one driven by news media reports of various developments, one dealt with the issue of ova freezing and to the extent to which that might be the solution to this question.  And members of Parliament accepted that the science may not be there yet but I think one could anticipate that there will be a watching brief on developments in that field as the regulatory framework moves forward.

The second was discussion about the relationship between investigators or researchers and clinics themselves and what might be — how that relationship might be sorted out, for example, in the question of who can obtain informed consent, for example.  So I think this speaks to what Parliamentarians felt as being the importance of having an overall regulatory framework because it provides tools to get at some of these issues as they develop.

MR. RIVARD: If I can add just a point on that, too, I would be a little more concerned about that if the — if we had simply adopted prohibitions in the absence of a governing framework for say the IVF clinics.  These clinics, therefore, they will all have to be licensed.  They will be subject to government inspection and a fair degree of control and insight into their operations.  So while it's always possible for somebody to try to evade the law, it's — there's certainly not — they will not be operating in a vacuum.  They will be subject to a fairly tight regulatory and inspection regime.

CHAIRMAN KASS:  Paul McHugh.

DR. McHUGH:  Well, I celebrate this enterprise of our Canadian friends and I think that it will accomplish just want I certainly look forward to hear by having a forum where coherent discussions, as well as overall regulations that can be altered, changed and developed over time by thoughtful citizens.  And therefore, I was very pleased by this wonderful presentation you gave us.  I did just — this is just a simple question tied to this, and that was, first, this interim voluntary moratorium on non-applications of reproductive technologies in 1995, did that moratorium cease?

MR. SHUGART:  As a result of the coming into force of the prohibitions in the bill, yes.

DR. McHUGH:  So it ceased in 2004.

MR. SHUGART:  Yeah.

DR. McHUGH:  So it went from 1995 to 2004.

MR. SHUGART:  Uh-huh.

DR. McHUGH:  And that moratorium was —

MR. SHUGART:  As far as we can tell —

DR. McHUGH:  Uh-huh, uh-huh.

MR. SHUGART:  — in the absence of any reliable information to know for certain.

DR. McHUGH:  Right, but government supports were not given to that kind of enterprise in research during that time.

MR. SHUGART:  No. 

DR. McHUGH:  And the other thing is, we have had a presentation here by a person who was the representative of groups of people who had anonymous donations in their conception and she made a heartfelt plea for the idea that this was a practice, this anonymity was a practice that caused considerable suffering on their part.  And given what you've put here in place and given that there will, if this is the case, be more and more of these people, presumably your enterprise will be the forum for these people to re-plea their case, will it, or will it go back to Parliament where one vote swung the decision?

MR. SHUGART:  In terms of any change in the legislative and regulatory framework, then Parliament would have to decide but the issue will no doubt be debated in the forum.  I have absolutely no doubt whatsoever that the Board will be able to advise the Minister of Health and the Government on regulatory change over time and therefore, it is by no means irrelevant or secondary to that issue but again, the potential in the individual case for the link to be made notwithstanding the law supports anonymity, the individual may well appeal to the agency to approach the donor and if that exchange is successful in that case, then there is every possibility of the donor consenting to the information, the identity being released but it's a regime that requires the informed consent of the donor to give that identifying information.

So in the individual case, there is no reason to believe that identity will always be anonymous.

DR. McHUGH:  Yes, that's very interesting.  By the way, does the same apply to adoptions?  Is similar anonymity, informed consent still applied to adoptions — adoptees who later in life wish to know their parental origins?

MR. RIVARD: That is generally speaking the rule in Canada.  I think  historically there was a pure system of anonymity.  Increasingly jurisdictions are moving to a situation where they have the records that allow an individual to make a request to find their biological parent's identity and then can provide that with consent.  So it's somewhat parallel.

DR. McHUGH:  So once again, it's in parallel.  The biological parent also has the option of saying no.

MR. RIVARD: That's correct, yeah.

MR. SHUGART:  And that is governed by provincial law not federal law.

CHAIRMAN KASS:  Mary Ann Glendon.

PROF. GLENDON:   I'm wondering if you could say a little bit more about informed consent.  How detailed would you expect the regulation to be?  For example, would the clinics be required to give women information about the success rate, the health risks to the woman, information such as it is that we have concerning possible health risks to any children that might be brought into being through this process?

MR. RIVARD: First, I would say that the concept of informed consent in Canadian law is very similar, if not identical, to American law.  All the fundamental principles are the same.  The — and the legislation expressly incorporates that common law and applicable provincial statutes into the legislation.  It's also foreseen, however, in the legislation that specific information requirements will be set out in the regulations and therefore, for example, if you are a woman going to an IVF clinic, that clinic will have to provide the information that the regulations require.   We haven't yet reached the stage of defining what that data will be and we haven't yet consulted on that also but certainly those are all issues that I think would be addressed in that process.

MR. VANDERGRIFT:  If I might, this was an issue that came up during the parliamentary proceedings and, in fact, a member of Parliament succeeded in amending the bill to add a provision that regulate — the clinics in this case must provide to prospective patients information on success rates so that was actually specified in the legislation and the rest will be spelled out in further regulation.

CHAIRMAN KASS:  I have a series of things and I don't know whether you prefer I do them one by one or whether you — why don't I start and then you can — if there's too much we'll — you can just interrupt me.  I, and I think not only I, am interested in how what you've done differs from what the British have done and also how it relates to what might be done here.  So let me begin with an observation or comment and see whether you think this is correct and what might account for it.  If you look simply at the prohibitions or at the things being regulated, the difference between this and the British system seems small in some ways.  You could sort of point to cloning for biomedical research prohibition as perhaps the major difference but if you look at the overall — at the overall package, a number of things strike me as being very different. 

First of all, in the way that domain in the scope and its definition, even in the very name of the Act is different.  I mean, to talk about fertilization and embryological authorities as opposed to assisted human reproduction or — you seem to have taken a broader view and the question is not what do you do with embryos, but how do we think about human reproduction given these new assistances. 

Second, the list of the principles strike me as different.  I don't have the HFEA Act firmly in mind but I would be surprised if the language, among other things, of protecting human dignity occurs in that context, and finally, the origins of this, if we allow the Royal Commission to be part of the history of this story, suggests that this is not to begin with — well, this may be somewhat unfair to the Brits but that was undertaken with, I think, not only the participation of, but I think probably at the instigation of, the scientific community, that saw that unless they got something like this in place, that there would be hell to pay and the research couldn't go forward and in some ways that is a research facilitation act, whereas this looks to be something which comes from the public at large and is not somehow driven from inside the community; that has some bearing on the question of what enabled you to succeed and what might prevent us from succeeding here.  So I wonder if you'd first comment on whether those perceptions are accurate and what difference it might make.

A second question has to do with how it was that you were able to effect this kind of compromise.  I mean, you did indicate in the slides, and they impressed me, as to what the key factors were that enabled you to move this forward.  And one additional thing might be to ask, I mean, is it the case that you don't have the kind of polarization that's been caused here by the Roe v. Wade decision as the kind of political background and that somehow made life a little easier for you?  Why is it that you didn't have an aggressive sort of scientific community lobbying against this, and is it that the lobbying practices in Canada are different from what they are here? How was it that you were able to get people who might be very powerfully unhappy either with certain prohibitions or with certain permissions to say, "Okay, this is the best that we can do"? Because that isn't the spirit that has governed these discussions in this country at least not to the present time and especially if Frank's proposal comes in with his dukes up, he is unlikely to succeed in the current Congress for the foreseeable future.

MR. SHUGART:  Could I stop you there?

CHAIRMAN KASS:  Please. 

MR. SHUGART:  Please, sir, may I leave the room, my brain is full?  I'll respond to those and invite my colleagues to join in.  The difference with the UK and prospects for the United States, I will sidestep that question precisely as you put it, particularly anything predictive about the United States.  I would make a couple of observations.  I think in retrospect it would be difficult to overstate the importance of the fundamental purpose of the legislation being to address health and safety issues.  I think that provided the debate about the ethical principles, certainly not to disappear, not to be diminished in their importance, but put in the company of principles and purposes that were, in their own right, profoundly important.  In other words, constraining these technologies and the use of these technologies in the interest of couples, of women in particular, and of children in particular.

I think that there's no question that that had a salutary benefit on the whole public discussion, including consideration of the ethical principles.  And there as a trail of purpose, there was a clear public record, outlining that was the kind of issue that was driving this discussion. 

Secondly, the government was confronted on occasion with suggestions to split the bill and hive off the issue of cloning from the regulatory dimensions.  In other words, makes some prohibitions about human cloning.  The government held fast on the holistic view that these issues needed to be addressed as a piece.  There were, in fact, implications of the prohibitions for the controlled activities and the need for regulations.  And that if one split the bill, that would potentially lose the grounds on which one could develop a regulatory approach and would put at considerable jeopardy the prospects of ever returning to the health and safety considerations which were hugely responsible for initiating the discussion in the first place.

And secondly, there was prime facie, no reason to believe that splitting the bill would provide a peaceful resolution of issues in regard to cloning, for example.  So it was very important that the government held to that proposition.  And it was able to do so largely because of the time in question, the government of the day commanded a majority in the House of Commons.  At the moment, that is not the case.

Thirdly, with respect to researchers, I'm not a sociologist, I'm not a scientific sociologist, I don't know the extent to which different views among and of researchers would compare with the United States.  It is a continental if not global fellowship, of course, but it may have something to do with the nature of public discourse in our two countries.  I did say that as a general rule of thumb take what happens in Canada and multiply it by 10.  It may be that that principle could apply to intensity of public debate as well.

But it was very important that the positioning of scientists themselves was supportive overwhelmingly supportive of the approach that the government was taking.  Scientists in Canada in this field and in related fields, were saying we need a regulatory regime.  Self-regulation in this domain is not in the long run appropriate and so at no point did the government find itself face-to-face, toe-to-toe with the research community.  On specific points, yes, of course, there was variation of views within that community and there were some who took the view that the criminal law was an utterly inappropriate way of dealing with this whole field. 

It was important to make the distinction between a jurisdictional head of power and a law that would be written to criminalize certain kinds of activity but again, the government took the view that some provisions of this bill were enormously important for the nature of human life and of reproduction and of society and if the criminal head of power was not appropriate for some of these issues, where was it appropriate.

But in the main, there was a strong view from researchers that this was — this regulatory framework was a necessary thing to do.  With respect to the issue of polarized debate, I have a hunch that while it was awkward and difficult at times, the serialization of this debate over a number of years may actually in the end have been helpful in achieving some resolution because it gave a profile to some of the issues and time for views to mature, time for exchange to occur and ultimately in Parliament there was a recognition that it was time to move.  The requirement that the government table with the committee the regulations that were proposed and the Parliamentary review that is built into the legislation where I think safety valves as well that allowed ultimately a decision to go ahead, it reduced somewhat the enormity of the stakes as some would have viewed them.  I think all of those are factors.  I don't know, colleagues, if I've left out anything serious?

MR. RIVARD: I guess I would just add, too, that the — really the primordial issue was the question of legislation versus no legislation.  I mean, that was the reality in Canada.  There was no legislation in this area.  And so you know, at some point everyone who had some issue or some question with the bill, had to face that reality and there's sufficient consensus developed that, although not perfect in anyone's eyes, this was a much better state of affairs than what existed.

MR. VANDERGRIFT:  I would also just quickly add that I think one could easily anticipate a very vigorous three-year review of the act as a number of issues that people accepted for the time being will definitely, I think, come back on the table again at that point in time.  So I think, the depiction of that as a safety valve, I think was quite accurate.

CHAIRMAN KASS:  If I might, I have two more.  One is the question of the importance of gathering the information and the issue of privacy.  This is a difficult problem here.  And in fact, one of the arguments against doing longitudinal studies for outcomes, one of the reasons we haven't had it is the patient groups are — zealously guard the privacy of the information and our own recommendations in the Reproduction And Responsibility report that we should in fact, have supported longitudinal studies — until we got in there, the participation should be voluntary, et cetera, et cetera — we were really very much badgered on this question.  And we also have the Privacy Act, what's the technical — the HIPAA Act, which gets in the way of — I believe we were talking about this yesterday — gets in the way of getting all kinds of indispensable information out. 

So if you could say something about how you have managed to steer the course to get the kind of information — outcomes information that you need while dealing with this privacy question, that might be useful to us.  And then finally, something on the composition, the idea for the composition of the — of the regulatory body itself, not only membership but to — refer to a question that came up in Frank's presentation yesterday, how do they conceive of their task?  Are they merely the enforcers of the norms tacitly set by Parliament, or have you indicated that this really is going to be the place where this debate is going to take place and they're going to be making some decisions probably on new developments that the Parliament hasn't had an opportunity even to anticipate? 

Are these going to be the followers of public opinion, the shapers of public opinion, the conscience of Canada?  I mean, what sort of — the anticipated spirit of their activity and what kind of idea for their composition governs, I don't mean the particular members, but what's the idea of who these people should be ideally?

MR. SHUGART:  With respect to the information and privacy, I think a number of — I'll ask Glen to comment briefly in this area as well, but I think that the regulations will need to pass the standard that the information sought through that regulatory authority would be appropriate for the public policy purposes behind it.  In other words, it's not simply enabling the gratuitous collection of information.  There needs to be — there needs to be purpose.  The privacy regime and the regulations need to deal with the issue of the use and disposition of that information, in other words, provide the safeguards against inappropriate use. 

Clearly, the centerpiece of the information requirements is the medical information that may be particularly germane to the offspring as well as information relevant to procedures themselves which over time would be important baseline information for enhancing the safety of those and efficaciousness of those procedures.  This is an area where we have the interface of the individual clinical experience and the public health requirements of information where conceptually the way of dealing with those two things is inherently different.  In public health, typically information is only useful to the extent that information collected individually is aggregated for the benefit of more than the individual who provided the information.  So there's an important balance here in terms of the purposes for which the information is collected and the safeguard is the management of that information once collected.  Glen, is there anything that you think we should add to that and then I'll address your second question, Dr. Kass?

MR. RIVARD: Well, I just would add that there are provisions that will allow for the collection of information up front if you will, that is prior to donation, prior to participation in a regulated procedure like IVF.  But if by longitudinal studies you mean the ongoing following of the mother and even more particularly the offspring, that will require voluntary participation and the department will have to develop strategies to do that sort of research. 

The — I'm familiar with HIPAA.  There's similar legislation in Canada.  What we did in effect under this act was, we created a privacy regime specific to the collection and the use of the information under this Act.  Now, our starting point was compliance with generally accepted privacy principles and we made this as congruent as we could  conceivably with existing privacy legislation.  As I indicated, there are some fairly broad provisions up front for collection of information that's balanced by actually a more restrictive regime governing the disclosure of that information than is generally applicable. 

And that received the endorsement of our privacy commissioners, so that's how we dealt with that particular problem. 

MR. SHUGART:  With respect to the Board, I'll answer a question you didn't ask if I may.  It's germane to your question, however, and that is the provision in the legislation fairly strong provisions, I would argue, with respect to conflict of interest of board members.  Licensee's, for example, may not serve on the board.  As one reflection of guarding against conflict of interest.  Of course, there was a discussion about the nature of the board, whether or not to have a board in the first instance.  Once that was resolved, what should be the basis upon selection of board members, what's the overall character of the board and it was decided that the board should not simply be a vehicle for resolving differences of interest or of view.  In that sense there is an echo of yesterday afternoon's discussion with respect to the history good and/or bad of commissions versus other regulatory bodies styled somewhat differently.

The selection of members of the board will undoubtedly in the end reflect a diversity of views and of interests but the basis upon which board members are selected is individual and not representativeness of a particular view and that is deliberate.  We do believe that while the board is charged with the oversight of the agency, it therefore, has an element of good governance practice about it, quite apart from everything else.  The — it also does serve as a forum for discussion and debate.  I would anticipate without prejudging anything, for example, that the board will have a series of vehicles for informing itself and the public thereby, of developments in the field, and the issues that are — seem to arise as a result of those developments.  It will advise the government but the legislation is quite clear that the policy responsibility rests with the Department of Health so as to constrain the ability of the agency simply to define its own future absent broader considerations of public policy and so on.  So that, itself, is a careful balance. 

There have been different attempts to characterize it as quasi-judicial, purely a forum for debate and so on.  It's difficult to imagine after a period of what might in the end be somewhat more organic development exactly how it will come out, but those constraints are there.  One interesting point to observe is that the — in the granting of licenses, that task cannot be delegated to staff of the agency.  Granting of licenses must be done by members of the Board so they do have an important administrative and decision making role which makes them more than just a collection of interest groups.

There was a debate about whether scientists should be eligible to serve on the board because "everyone knows what their view will be."   It was resolved in the end that this should be an informed board and that exclusion of scientists from the board would not serve that objective.  So as you can tell, the discussion was actually quite varied and extensive.  The goal in the end was to provide oversight, ensure that — given the societal sensitivities and importance of these issues — that a group visibly charged with oversight in this area should have that responsibility and actually in very real terms carry it out, but that it should not be a vehicle for resolution of narrow interests. 

CHAIRMAN KASS:  Thank you very much.  We've come up to the time for the break.  I want to thank Ian Shugart and his colleagues for a really very clear, forthcoming and very helpful presentation.  We have a very full next session, so let's be back at 10:15 and we will start then promptly.  Thank you very much. 

(A brief recess was taken.)

SESSION 6: SEEKING MORALLY UNPROBLEMATIC SOURCES OF HUMAN EMBRYONIC STEM CELLS

CHAIRMAN KASS:  In this last session before the session for public comment, the council returns to the subject of embryonic stem cell research, not to continue to argue about the moral issues or to discuss the wisdom of the current federal funding policy, but to explore two very interesting proposals demanding public attention that suggest means of deriving embryonic stem cells that would get around the morally charged necessity of doing so

This council, I think, has distinguished itself in the discussion of these questions, notwithstanding our sharp differences of opinion about the conclusion, in recognizing that all parties to the existing debate, in fact, have something vital to defend — not just for themselves, but for all of us.  We have recognized the importance of the scientific research and the medical benefits to which it will lead.  We recognize the supreme and important value of respecting human life, indeed in all of its stages.  People may differ about how much respect and at which stage, but these are important human goods and it would be very exciting if ways could be found in which these two goods did not have to be pitted against one another, but, in fact, could be embraced by all people whichever way they pitch the balance amongst them.  And therefore it's, I think, of great interest to this council that we have for presentation today two such proposals: one presented by Howard Zucker and Don Landry, both from the College of Physicians and Surgeons at Columbia University, Howard Zucker from the Department of Pediatrics, Don Landry from the Department of Medicine.  And their proposal, which we will have had occasion to read, talks about the possibility of deriving human embryonic stem cells from no-longer-living, not merely just non-viable, not merely doomed-to-destruction, but actually no-longer-living embryos. And our own colleague, Bill Hurlbut, has a proposal for deriving — that would enable people to derive human embryonic stem cells from embryoid-like bodie,s but which are not in the strict sense embryos proper.  We look forward to the presentations.

I should say, so that there won't be any misunderstanding, these are not at the moment presented as council proposals.  The council is simply eager to hear about this and we will see in the discussion afterwards what council members think about these things. But first, we have to inform ourselves about them both with respect for the question of the ethical issues and of the scientific feasibilities.  So Howard Zucker and Don Landry, welcome to you and the floor is first yours and then we'll proceed to Bill.

DR. ZUCKER:  Thank you, Dr. Kass, and Don and I would like to thank the entire Bioethics Council for giving us the opportunity to present before this illustrious panel.  We recognize that the stem cell controversy has resulted in a very polarized and heated debate but it is our personal opinions that there is a common ground for medicine, for law, science, and ethics that can be reached, and we published this view in the Journal of Clinical Investigation last month which you all have a copy of.

Scientists cannot go anywhere without a laptop and visuals and so, in the interest of efficiency, Don will present our paper, after which we will be happy to answer any questions that you have for us, thank you. 

DR. LANDRY:  I also thank you for the opportunity to present our ideas to you.  Let me say also that I'm Director of the Division of Experimental Therapeutics in the Department of Medicine at Columbia.  I don't engage in stem cell research, so I don't have a vested interest in this beyond that of a concerned citizen.  I do take care of critically ill patients in a small private practice and I think it's the context of seeing death in a close and personal way and seeing the issues of organ donation that informs to some extent the ideas we're going to present today.

I'm going to present some things that are painfully obvious to you but I think are important just to state the premises upon which the proposal was based.  The creation of human embryonic stem cells involves the destruction of an embryo, well known to you.  What that means to an individual depends on how they answer certain questions.  When it's formulated in the most general sense, when does life begin, it doesn't make very much sense to me but these are my answers to these questions.  Life begins two billion years ago, human life begins 200,000 years ago.   A new human life, a new human being, a genetically unique entity begins at conception.  A human person, however, is not a question — the origin of a human person is not a question that science alone can answer.  And so this tension between human being and human person results in a conflict.  We have on the one hand a requirement for respect, for human dignity, to treat humans as subjects and not objects, pitted against the drive to relieve human suffering. 

And there is no easy compromise.  This is not an economic matter.  The differences cannot be split.  And so between, on the one hand, persuasion, which is difficult to achieve, and imposition of will, which is unseemly, there's a third way, a search for a common ground, which I think is one of the central activities of this committee.  Our general notion is that death is such a common ground because the death of the human being subsumes the death of the human person and so whatever the disagreements about the origin of a new person, with the death of a new human being that issue of person is also resolved. 

Some background from the death of a developed human person can inform our thoughts on the death of the developing human person, and so just a quick review of some recent history and our notions of death for developed individuals.  Prior to the 1960s going back for thousands of years, irreversible cessation of cardiopulmonary function was the definition of death and improvement in respiratory technology led to a crisis.  It was possible to maintain ostensibly dead individuals for extended periods of time and this crisis was addressed by an ad hoc committee of the Harvard Medical School with a definition of irreversible coma that becomes the basis of our modern notion of brain death.

And in that context of a definition of brain death, not driven by it but in the context of it, cadaveric organ donation went from speculation to standard of care and so I would abstract from this slide the idea that the availability of material, if obtained in an ethically reasonable fashion, can actually drive research and drive progress. 

Some comments also about the legal definition of death.  First of all, it's a specific question of fact, not a question of law, and so it's determined by physicians.  And yet there are legislative attempts to codify it.  Originally, there were two separate definitions of death contingent on the desire to harvest organs, clearly a problematic issue.  This was resolved by Capron and Kass in 1972 articulating a single concept of death, but application of a particular criterion would depend on the circumstances, the circumstances of machinery maintaining a dead individual that makes the application of one or another criteria particularly difficult or facile.  A variety of laws follow, tend not to precede some consensus on the issue and we conclude with the Omnibus Reconciliation Act of 1986 that, at brain death, the removal of vital organs for transplant is legally and ethically permitted.

We have criteria for brain death.  Our notion is an irreversible action critical in brain stem function that gets translated through observational studies, when does someone no longer wake up, finally to diagnostic tests, unresponsiveness to pain, inability to breathe off ventilators, certain eye movements upon putting cold water in the ear canal, a flat EG and the absence of conditions that might otherwise suppress EG activity.

Embedded in all of this is the concept of organismic death, the human — the adult or developed human that has died is not thoroughly dead.  Organs are alive, they're available for transplant.  The tissues that make up those organs, the cells that make up those tissues are alive, and so we like to extend this idea to the developing human. The developing human, just as for the developed human, is more than the sum of the lives of constituent cells, and so just as the nervous system integrates tissues and organs in the developed human, so too there's a system of chemical communication and surface recognition that integrates cells in the developing human.  Deprived of the necessary internal signals, an irreversible arrested cell division can occur.

Our specific proposal, then, is a new definition of death for the human organism, an organism in development, and that is the irreversible arrest of cell division. 

Now, what are the prospects for producing normal cells from dead embryos?   Just as a backdrop to this consideration, consider for a moment that 60 percent of IVF embryos fail to meet criteria for viability.  Non-viability is one of those vague terms.  It's an incapacity to develop to live birth and so it contains a number of categories embedded in it, but there is a morphologic criterion, abnormal appearances of one sort or another, also a functional criterion, failure to cleave at 24 hours.  Important to note, non-viability does not mean dead but the functional criterion, cleavage arrest, likely correlates.  Now, cleavage arrest most often reflects various genetic abnormalities and this might seem to eliminate any prospect for some useful development occurring from these considerations, not that the considerations are invalid but that nothing good would come of them. 

But there are several studies, two that I include in the binder, and summarize very briefly here, that suggest some prospect for producing normal cells from dead embryos.  So Laverge et al observed mosaicism and, briefly, from 166 frozen embryos that were thawed, 78 remained arrested at 24 hours, 71, no further sign of cleavage at 48 hours, and fluorescence in situ hybridization, which allowed examinations of chromosomes X, Y and 1, on all blastomeres of 63 arrested embryos, was performed.  Eighty percent showed chromosomal abnormalities.  Aneuploidy, severe aneuploidy was common but mosaics were present with normal diploid blastomeres embedded in this sea of abnormality.  Voullaire et al also observed mosaicism, 63 blastomeres from 12 unselected embryos thawed after five years of cryopreservation, two out of 12 were in cleavage arrest, partial arrest was observed in others. 

In this case, they used comparative genomic hybridization, a powerful technique that's able to look at all chromosomes with the exception of several that overlap, 17, 19, 20, 22.  Again, they noted marked aneuploidy, very common but also the eggs were identified —

PROF. WILSON: Excuse me.

DR. LANDRY:  — with no diploid blastomeres in five of 12 embryos.

PROF. WILSON: Could you define aneuploidy, please?

DR. LANDRY:  Aneuploidy is multiple copies of chromosomes, and so, instead of the normal diploid, we can have tetra and beyond, sometimes five full sets of chromosomes, and this is a marked abnormality that does not bode well. 

Now, if one could obtain live cells from dead embryos, are they truly normal, what is their developmental potential?  I've presented human data till now.  This is the one bit of animal data that I'm going to mention but it's so marked that — and understanding limitations in animal data, it's still worth mentioning here.  In one experiment, cloned tadpole embryos showed 99 percent irreversible arrest, 95 percent early on, 99 percent overall.

Now, cells from arrested blastocysts were aggregated and an individual cell is injected into a normal tadpole blastocyst.  Twenty-five percent resumed division and were stably incorporated into differentiated tissues, becoming muscle, for example.   And so blastomeres from an arrested embryo can be reprogrammed for differentiation and growth if placed in the proper environment.  And this is a natural environment, but in principle it could be an artificial environment made up of cell surface proteins and various chemical mediators. 

Back to human data, an experiment by Alikani and Willadsen, 107 "non-viable" human IVF embryos were disaggregated.  Two hundred forty-seven intact cells were isolated and they were combined in 36 aggregates, approximately six to seven cells per aggregate.  Thirty-three percent of these went on to develop and form normally organized blastocysts with defined inner cell masses, again indicating that a new environment can re-establish growth and development.

So a summary; we're proposing a new definition for human death, irreversible arrest of cell division.  The criteria for determining irreversibility would begin with the natural history study of cleavage arrest and progress to biochemical markers for irreversibility.  Many embryos generated for IVF are organismically dead.  Aneuploidy is present but, due to mosaicism, normal cells are found and it's at least arguable that they could have normal developmental potential. 

The signals required for transforming blastomeres into stem cells without recourse to the formation and destruction of human blastocysts is an area of current research.  Interest in this area would increase markedly if, in fact, there were material to pursue this work.  And we propose an ethical framework for investigating embryonic cells from organismically dead embryos, and this framework would parallel the cadaveric donation of central organs with consent of next of kin, in particular organs donated from children with the consent of parents. 

So, in conclusion, application of the ethical framework for central organ donation to the harvesting of human embryonic cells from organismically dead embryos maintains respect for human dignity and can advance biomedical research.  Now, two corollaries that do not appear in the paper but I would be interesting in hearing your thoughts on: with a clear and clean recognition of embryonic death also comes the recognition of embryonic life in extremis.   And one can apply the ethical norms for research on a patient in extremis, which are different from the average patient, to the embryo in extremis.  And so, for example, the extraction of a single blastomere from an embryo in extremis would not seem to be an enterprise that would have severe ethical or moral problems.  And I've engaged in research on adults in extremis with the approval of our IRB, engaging in interventions that would not be permissible with someone not in the last few hours of life.

This is not an idle consideration with respect to the embryo.  Consider on the one hand organs harvested from an executed prisoner, mesenchyme from an aborted fetus, versus cells obtained from an IVF embryo that died despite best efforts for its life.  It would seem that there's a very bright line separating these.  What if cells from a cryo-preserved embryo that is thawed after five years of storage and allowed to succumb, some may feel this is all right, some may feel it's problematic but certainly an embryo in that position is in extremis, and harvesting a single cell a potential risk but not a lethal, unnecessarily lethal event, might be considered morally acceptable.  And that concludes my remarks, and Howard and I are available to answer questions as best we can.

CHAIRMAN KASS:  I think that — let me suggest that we discuss each of the presentations briefly rather than have them both together and to raise any kind of technical question.  The presentation was luminously clear as is the paper.  I mean, I think everybody understands what this is about, so there might be people who have either technical questions about the scientific feasibility or what we might know about the likelihood of this, but let's take at least a few minutes to make sure that everybody understands what they need to and get ideas clarified.  Then we'll have Bill's presentation and then we can discuss the two things together.  So the floor is open to Doctors Landry and Zucker.

Now, Paul McHugh?

DR. McHUGH:  Just one question; you told us you could take a cell out of an embryo that you had demonstrated aneuploidy in the embryo and then those cells would reproduce when placed — this, I guess, was the tadpole work.  Aneuploidy cells can reproduce and they produce cancer.  How will we be sure that this method won't technically lead to the implantation and the use of cells that will have cancerous potential?

DR. LANDRY:  You can simply screen for that.  The cells you isolate, you know, are grown.  You can take one of those cells having now grown and analyze it, so I don't think there would be any risk of cancer in that circumstance.

DR. McHUGH:  Even after you've transplanted them?  I just need to understand the technology a little bit.  You have this embryo.  You say you find aneuploidy in it in various cells.  You find 33 percent of them will grow later in the tadpole.  Were those 33 percent of cells you grew in the tadpole demonstrated to lack aneuploidy in every one of them?

DR. LANDRY:  No, and remember that we're not suggesting that this be used for reproductive purposes.  This is meant for in vitro use and as such, while it's always possible that there could be unforeseen events, one gets to observe these cells for extended periods of time.  I mean, after all, the ultimate objective of stem cells, stem cells are indefinitely reproducing ideally by definition, and so it's possible to go and at any point now having produced this cell, to examine it and one would seek to eliminate, for instance abnormalities such as marked aneuploidy and —

DR. McHUGH:  Let me just continue on this because I just want to be sure I've got it.  And sticking with the tadpole experiment, the cells that were later put into the tadpole from frog embryos that were known to be non-viable for a variety of reasons including aneuploidy, that those cells had gone through a sufficient phase themselves to know that they did not carry an aneuploidy potential and a cancer potential.

DR. LANDRY:  The experiment on tadpoles involved arrested embryos.  They were not examined for aneuploidy. 

CHAIRMAN KASS:  Gil Meilaender?

PROF. MEILAENDER:  What is luminously clear to our Chairman is not necessarily so clear to me.  So can you just explain to me or help me be sure I'm clear, cleavage arrest correlates with death of the embryo according to your proposed definition.  And that's the — so that's the test that you'd use to determine whether an embryo was available for use in this way, and would you therefore be using some embryos which were dead and some which were conceivably still living according to your definition?  That's what I don't understand in terms of the correlation business. 

DR. ZUCKER:  They would be dead — if they're at 24 hours, they are not cleaving and 48 hours they're not cleaving, those are dead.  They wouldn't be — that's the concept that they would be organismically dead at that point.  It wouldn't be that we would take cells that were then dividing further and try to redefine that as being dead.

DR. LANDRY:  And the precise moment, also is something that's open to a natural history study and observation.  So the precise moment when, you know, a group of disinterested observers would reasonably conclude that death has occurred is — and to devise a definition for death, would occur as a result of observation by analogy to observations of, you know, comatose patients. 

DR. ZUCKER:  And as Don mentioned in the presentation also that we would be able to find specific markers to match up with cleavage arrest.

CHAIRMAN KASS:  What begins as phenomenological account of the natural history of this would then be supported by the discovery of various kinds of biological markers that would give one confidence that cleavage not only hasn't occurred, but isn't going to occur.  I think that's the —

PROF. MEILAENDER:  So it was luminously clear to you and it was luminously clear to you and not to me.

CHAIRMAN KASS:  It was not luminously clear to you.  Other — yes, Robby George.

PROF. GEORGE:  Thank you.  I'm trying to see if I understand what is new in what you're proposing and what is not new.  It sounds to me — and please correct me if I've misunderstood you — it sounds to me as though you're not proposing a new criterion of death or a different criterion of death.  It sounds as though the criterion of death you're proposing is what we might now call the standard one of the complete and irreversible loss of integrated or integral organic functioning.  Is that right?

DR. LANDRY:  I would call that the concept.

PROF. GEORGE:  It's the concept of death.

DR. LANDRY:  And then the criterion is what you take down from that concept.

PROF. GEORGE:  So the concept of death is the same whether we're talking about, you know, an 80-year old person or we're talking about an embryo.

DR. ZUCKER:  Correct.

PROF. GEORGE:  And so now what you're looking for is what is the reliable evidence and I guess this you would then call a criterion?  All right, what is the reliable evidence of the complete and irreversible loss of integrated organic functioning.

DR. LANDRY:  Correct, so we would define it as arrested cleavage and then the criteria for defining that arrested cleavage would come down from that, a certain amount of time, the absence of Oct4, you know, a series of biochemical markers in its fullest state.

PROF. GEORGE:  Okay, so just again to be very clear, there's no proposal here for a new concept of death —

DR. LANDRY:  No.

PROF. GEORGE:  — in order to accommodate the harvesting of stem cells from embryos.

DR. LANDRY:  No.

PROF. GEORGE:  Okay, a second point, just a minor point of clarification, I was interested in what you were saying about the legitimacy of interventions on patients, and let's again consider say an 80-year old person in extremis, that you were saying there were circumstances in which it's ethically legitimate to do certain things to patients in extremis that you couldn't do to patients who were not in extremis.   And I wonder if — what the norms are governing those interventions.  Are such interventions legitimate but only when the purpose is to benefit or attempt to benefit the patient himself, or is it sometimes permissible to do some things to patients in extremis that you couldn't legitimately do to patients not in extremis, not for the benefit of those patients but for the benefit of others?

DR. ZUCKER:  I guess one of those, you can use the analogy of a chid who is critically ill lying there in an intensive care unit and needs to be placed on let's say extracorporeal membrane oxygenation or life support, and one may say at that point that that person, you're doing a procedure on somebody and providing a new therapy obviously through an IRB that you wouldn't routinely do on other patients that weren't at that teetering on the edge, and in the same way, we would feel that — as Don mentioned before with the embryos in extremis, you could make that analogy.

PROF. GEORGE:  Perhaps I'm being obtuse here, but —

DR. LANDRY:  Since I've actually done this, maybe I can —

PROF. GEORGE:  Go ahead.

DR. LANDRY:  Maybe I can just —

PROF. GEORGE:  Please.

DR. LANDRY:  Okay, we're dealing with patients in extremis and by definition the intervention we're engaged in is not going to benefit that patient.  It is not anticipated that a patient in the last few hours of life is going to be pulled from that moment by the intervention.  With the approval of the IRB, with the assent of next of kin, it's possible to, for instance, provide experimental drugs to observe their physiologic effect, understanding that it's not a therapeutic effect.

PROF. GEORGE:  I see.  So it would be to benefit others and it would be considered legitimate.  But it wouldn't be considered legitimate to do precisely the same thing if a patient were not in extremis.

DR. LANDRY:  Exactly.

PROF. GEORGE:  And this is an accepted norm of medicine.

DR. LANDRY:  Right, accepted norm.

CHAIRMAN KASS:  Gil, I think, wants in on this subject.

PROF. MEILAENDER:  Yeah, just the very same thing; you wouldn't extract the organs of that infant, though, right?

DR. LANDRY:  No, no, we're not talking about activities that would kill or that would immediately hasten death, but activities that might entail some risk and yet you would argue that, in the last few hours of life, that risk is less than incremental to that person at that time.  Of course, if they're looking at the next 80 years of their life, then perhaps this is not a risk that should be undertaken on their behalf.  And so removing a cell from an embryo that's about to expire, that activity  not killing the embryo necessarily although entailing a risk to that embryo if we wanted to implant that embryo, we could take direct analogy from that activity and the activity of experimentation in developed humans.

CHAIRMAN KASS:  This really — this matter if I understand, what you would be talking about would be the equivalent of single blastomere biopsy that's used say in PGD which, though we haven't had the studies to give us absolute confidence in this, there are lots of children who have been born perfectly, apparently perfectly normally, so that the removal of a biopsy or the removal of a cell is already practiced in that case, I suppose you could say for the benefit of that particular individual.  Here you would not be adding any extra risk and the act would be no more dangerous to that embryo in extremis than that act is to an embryo that's headed for implantation in the diagnostic procedure at PGD.

DR. LANDRY:  Yes.

CHAIRMAN KASS:  Is that —

DR. LANDRY:  That's correct. 

CHAIRMAN KASS:  Now Gil.

PROF. MEILAENDER:  But these are two different sorts of justifications that you're thinking through.  Am I right about that?  That is to say one sort of justification is if we have an embryo that in terms of the criteria you've developed is dead, we may use it in these ways.  The other sort of justification is that the rules for what we may do experimentally with a human organism change when the organism though not dead is in extremis.  That's a different kind of justification.  Am I correct on that?

DR. LANDRY:  That's why I included it after the conclusion.

PROF. MEILAENDER:  Yeah, and that general issue there's actually a long history of discussion and argument about and I would be more inclined to worry about — I would want to think that one through considerably more.  It gets to do with the issue about whether equal treatment must involve identical treatment, whether you can wrong someone without harming them and various kinds of questions like that and there is a long history of discussion about that.  So I just want to be clear, these are two different sorts of justifications, and one might be persuaded by one but not the other, for instance.

CHAIRMAN KASS:  I want to turn to Bill, but only if there aren't any questions to simply clarify what this proposal is so that everybody should understand what Doctors Zucker and Landry are proposing here.  Alfonso and Jim Wilson, I think, have technical questions rather than argumentative ones.

DR. GÓMEZ-LOBO:  Yeah, this is, I think, a clarification question.  Of course, from a moral point of view, it seems to me the idea of using cadaveric tissue for instance, should be less problematic but I think we shouldn't forget that there's going to be questions about the cause of the death or what led to the death.  I'm thinking out loud about the circumstance in which say, a child or an older person is about to die, the death is expected, in order to extract organs in circumstances, say, where a rescue could have been possible.  So I'm just leaving that question open, because it is going to be ultimately of importance for the moral judgment on the whole project.

CHAIRMAN KASS:  Jim Wilson. 

PROF. WILSON: Should your techniques prove with further scientific inquiry to be valuable and the removal of non-viable embryos can become a routine medical —

DR. LANDRY:  Don't use the word "non-viable".

PROF. WILSON: I understand.  What would you like?  I like the —

DR. LANDRY:  Organismically dead.

PROF. WILSON: Organismically dead, thank you.   But at one point in their history, they were —

DR. LANDRY:  They were alive?

PROF. WILSON: Yes.

DR. LANDRY:  If they were classified as non-viable, they may have been dead, dying or doomed but we would restrict, you know, our inquiry to those that are organismically dead.

PROF. WILSON: Organismically dead, fine.  My question is, should this procedure become widespread, what would be the source, the principal source of these organismically dead entities?

DR. ZUCKER:  The IVF embryos that are presently frozen that then would be thawed for the purpose of creating life.

PROF. WILSON: And they would go through the test you've just described.

DR. ZUCKER:  Correct.

PROF. WILSON:  Thank you.

CHAIRMAN KASS:  Bill.

DR. HURLBUT:  Can I ask you what stage of development you anticipate most of these cells would come from?

DR. LANDRY:  Eight to 12 cells.

DR. HURLBUT:  It's my understanding that nobody's ever seen a single eight-cell embryo lose seven of its blastomeres as often happens after freezing and thawing, but is it absolutely clear that a single cell from an eight-cell embryo cannot form a full embryo?

DR. LANDRY:  That's our understanding.  And if evidence came to the contrary, then we would move to 12 cells but the idea is to avoid any question that that cell could by itself go on.  The loss of aggregate cytoplasm when you're dealing with a single cell out of eight, would seem to preclude it.

DR. HURLBUT:  Yeah. 

CHAIRMAN KASS:  Let's just stop on this and invite Bill to make a presentation of his proposal and then we'll follow the same procedure and we'll still have some time to discuss both of these together and what we think about it. 

DR. HURLBUT:  Thank you.  So what I want to say has some similarity to the previous proposal.  Death is the loss of potential for future life through the disintegration of organismal life.  What we propose is the creation of entities that never rise to the level of integrated organismal existence essential to be designated human life with potential.  I want to present some ideas that seem worthy of discussion and possibly preliminary scientific investigation.  Those of us who have been working on these ideas have already explored some of the philosophical and technical dimensions but there are important theoretical and practical issues that need further consideration. 

We offer these ideas not as an assertion of certitude but as a promising avenue of inquiry, one that might move us beyond our current conflict over the procurement of embryonic stem cells by providing a third option, a technological solution to our moral impasse.  In the broadest sense, we propose a creative exploration of a full range of scientific approaches.  More specifically, we raise the possibility that, using the technique of nuclear transfer, it may be possible to produce embryonic stem cells within a limited cellular system that is biologically and morally akin to a complex tissue culture and thereby bypass moral concerns about the creation and distruction of human embryos.

I want to make two points very clear from the beginning. What is proposed here is a concept, an approach to a problem.  The specific examples, which may or may not be morally acceptable or scientifically feasible, are offered only to make clear the larger concept as a starting point for discussion.  Second, we are at the stage of a constructive dialogue; if these ideas are deemed feasible, extensive studies with animal models must follow.  We do not propose any projects involving human cells until we can be certain that embryos are not created by these methods. 

The present conflict over the moral status of the human embryo reflects deep differences in our basic convictions and is unlikely to be resolved through deliberation or debate.  May Americans oppose embryo destruction for the procurement of embryonic stem cells, believing that there is an implicit dignity and inviolability in the individual continuity of a human life from fertilization to natural death.

Many others, however, believe that the benefits of advances in biomedical science outweigh these moral concerns.  A purely political solution will leave our country bitterly divided, eroding the social support and sense of noble purpose that is essential for the public funding of biomedical science.  While there are currently no federal legislative constraints on the use of private funds for this research, there is a consensus opinion in the scientific community that, without NIH support for newly created embryonic stem cell lines, progress in this important realm of research will be severely constrained. 

Notwithstanding this apparently irresolvable impasse, we believe there may be morally uncontroversial ways to obtain embryonic stem cells.  Drawing on our increasing understanding and control of developmental biology, the techniques of altered nuclear transfer may allow us to generate embryonic stem cells even apart from the organismal system that is their natural origin.  In order to evaluate the potential solutions and allow forward progress within moral consensus, we have to understand the perspectives and address the concerns of those who believe that life begins at conception.  By this view, the most fundamental principle on which all other moral principles are built is the intrinsic dignity and inviolability of human life across all of its stages. 

In both constitution and conduct, the zygote and all subsequent embryonic stages differ from  any other cell or tissues of the body.  They contain within themselves the organizing principle for the self-development and self-maintenance of the full human organism.   The activation of an egg by the penetration of a sperm or the equivalent events in nuclear transfer cloning procedures, triggers the transition to active organismal existence with the potential to develop into an adult human.  But without all of the essential elements, the necessary complement of chromosomes, proper chromatin configuration, the cytoplasmic factors for gene expression, et cetera, there can be no living whole, no organism and no human embryo.  Recent scientific evidence suggests incomplete combinations of the necessary elements, failures of fertilization, are the fate of many, perhaps most early natural initiations in reproduction.  Altered nuclear transfer proposes the artificial construction of such a cellular system mimicking these natural examples, a system that lacks the essential elements for embryological development but contains a partial developmental potential capable of generating embryonic stem cells.

It is important to realize that many of these naturally occurring failures of fertilization may still proceed along partial trajectories of organic growth without being actual organisms.  For example, grossly abnormal karyotypes such as trisomies of Chromosome Number 1, the largest chromosome with the most genes, you may know that chromosomes are named by the largest to the smallest.  These grossly abnormal karyotypes will still form a blastocyst but will not implant.  Even an egg without a nucleus when artificially activated, has the developmental potential to divide to the eight-cell stage; yet, clearly is not an embryo or even an organism.

The messenger RNA in these activated enucleated cells has the protein already in it, the protein synthesis that drives the early cell divisions, it's generated during the maturation of the egg and then activated after fertilization.  Like a spinning top, the cells contain a certain biological momentum that propels a partial trajectory of development but unlike a normal embryo, they are unable to bootstrap themselves into becoming an integrated and self-regulating organismal entity.

Some of these aberrant products of fertilization that lack the qualities and characteristics of an organism appear to be capable of generating embryonic stem cells or their functional equivalent.