Meeting Transcript
September 8, 2006

COUNCIL MEMBERS PRESENT

Edmund Pellegrino, M.D., Chairman
Georgetown University

Floyd E. Bloom, M.D.
Scripps Research Institute

Benjamin S. Carson, Sr., M.D.
Johns Hopkins Medical Institutions

Nicholas N. Eberstadt, Ph.D.
American Enterprise Insitute

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

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

Carl E. Schneider, J.D.
University of Michigan

INDEX

• Session 5: The Council's Future Agenda
  
• Session 6: Genetic Information: Its Significance for Patients, Families, Health Professionals, Ethics, and Policy Development
  
• Session 7: Public Comments

WELCOME AND ANNOUNCEMENTS

CHAIRMAN PELLEGRINO:  Good morning.  Good morning.  Thank you very much for joining us on time to provide an opportunity for everyone who wishes to speak to speak.

I would like to start out first by stepping out of the agenda for one second, and it won't take very long, and asking Professor Eberstadt to give us a report on a question that was posed to him yesterday by Dr. George having to do with the economic literature.  Dr. Eberstadt?

DR. EBERSTADT:  Thank you very much, Dr. Pellegrino.

I wasn't prepared for Robby's friendly interrogatory about the state of the economics literature yesterday.  And so I don't think I was as informative as I could be to fellow Council members.

I went back last night to do a little bit of homework on this as I guess your sometime economist on the Council.  And I can report very briefly to you the state of the literature.

As I mentioned, there are indeed only about a literal handful of professional studies on questions bearing on organ donation or organ transplants.  However, that handful of studies has been offered by a very high quality of economist.  Of the maybe half a dozen studies I came across, two were by Nobel Laureates in economics.  A third is by a winner of the John Bates Clark prize, which is the prize that's given to the most promising economist under 40 years of age every 4 years.

Not all of the work was on the question of marketization or commoditization of donor markets.  Some of the work was on trying to quantify, for example, what the impact of presumed consent laws might be by looking at European data.  Like those laws or not, the conclusion of that work, the suggestion of that work was that this would substantially increase the supply of cadaveric organs.

Other work was analyzing the disparate impact or the disparities in areas with respect to waiting lines and other things under existing situations.  But I suppose the study which I would bring to your most immediate attention here was one by Gary Becker at the University of Chicago, not known, like Richard Epstein, as a famous libertarian, a person, very eminent economist, associated with work in human capital and crime and the family and many other areas.

He has attempted to model the impact of marketizing.  It's somewhat speculative, but he has attempted to estimate the impacts of marketizing organ donations, organ transplants.

In his approach, he comes up with the suggestion or the quantified hypothesis that an equilibrium price of about $30,000 might be expected for a market in human kidneys in the United States.  Now, how does he arrive at this conclusion?  He draws upon a literature in economics, so-called cost of life literature.

To many of us, the idea that you would put a price on human life may seem offensive or repulsive, but this, of course, happens all the time in the insurance industry and in many walks of life.

By drawing upon some findings in this cost of human life literature, he goes about the speculation which ends up with this suggested equilibrium price.

I am certainly no Nobel Laureate in economics.  It looks to me as if he is equating the marginal cost of a human kidney in the sense of the risk to a donor plus hospital expenses as being equal to its marginal price.  There is a different sort of economic perspective that might suggest that people have what economists call a reservation price, not just simply a marginal cost, for organ donations.  This shows the beginning of the work that is being done in this area.

I would also bring your attention to a popularized article that Steve Levitt, the winner of the John Bates Clark Medal and the author of the best-selling book, Freakonomics, did in the New York Times last summer.  It's a popular article, not a scholarly one.

He makes the observation that there is no serious economist who would agree with the way that the U.S. current organ donation arrangements are working.  And he mentions work being done by — he does, however, at the same time acknowledge what he calls the repugnance factor in what one would think about the somewhat ghoulish aspect of a market in human organs and brings attention to work that is being done at Harvard University and in New England by an economist named Roth, who is simulating some of the effects of a market through a kidney exchange program, the New England Kidney Exchange Program, thus reported.

CHAIRMAN PELLEGRINO:  Thank you very much.

Could I make you a request?  Would you submit that in writing so all of us can take a look at it and think about it?  It was very, very appropriate to our comments yesterday.  We do not have time to discuss.

Moving to the first part of the agenda, which — welcome, Paul, delighted to have you back.

DR. McHUGH:  There was some bomb package that delayed me getting here this morning.

CHAIRMAN PELLEGRINO:  Delighted to have you.

***

SESSION 5: THE COUNCIL'S FUTURE AGENDA

CHAIRMAN PELLEGRINO: The first morning session we have dedicated to the question of our future agenda.  That came up yesterday.  And I think this is the time to discuss it in some detail.

As we said yesterday, we have been operating now on a number of different topics for a period of about six or eight months and I think would like to know the mind of the Council with reference to what direction we ought to take in the future.

Dan Davis has done a wonderful job of collating your responses to the survey, which you were good enough to participate in.  And he has set that before you.  And I suggest you use that as a guide to whatever remarks you have in mind to make.

I would like to come out at the end of this with some notion of the preferences of the group.  And let me forewarn you.  I would like to have an open discussion for a period.  And then unless you rebel, I would like to go around the table and ask each of you to tell me what your thoughts are about — go ahead and put it right out.  What do you think is the direction we should be taking?

I ought to tell you what you know, I'm sure, that we'll try to take that under advisement and then come back with something that looks like an agenda but get started as soon as possible.

So let me then throw it open for discussion.  You have seen the grid.  Maybe Dan will take a second to tell you what the meaning of the gradation of colors is, although I think it's quite obvious.  Nonetheless, he can make it clearer.

DR. DAVIS:  Okay.  There were two topics that received the highest votes in terms of interest, number 4 and number 8, the ends and goals of medicine and citizens' personal responsibilities for health.

Those two were then followed by four topics that were neck and neck:  number 5, genetic information and knowledge; number 6, health care, which special interest or focus on obligations of society towards its members; and then nanotechnology; and, number 11, commercialization of clinical research.

And then following that there were two topics:  ethical formation of health professionals and the patient-physician relationship.  So that is how things sifted out with the tally.

And then two Council members have suggested other topics that were not on the list.  And those are at the bottom of the page.  And when we get into the swim of the discussion perhaps they would like to join the discussion and explain why they have offered those suggestions.

CHAIRMAN PELLEGRINO:  Thank you very much, Dan.

Now I would like to throw it open for general discussion and again repeat what is in the back of our mind of eventually getting, not so eventually getting, to your own personal opinions of what we should be doing.

First, general comments on the results of the survey and your own feelings about what would be appropriate and best directions for us to go.  Anyone?

(No response.)

CHAIRMAN PELLEGRINO:  If the silence continues, I think we will just start.  A few more moments of silence would be useful, but then if it goes on, we will start with individuals.  And I think that probably will be much more productive, frankly.  It looks like you prefer that.

Now the problem is who goes first.  And I will be accused either of partiality or of malevolence wherever I start, but — very good.  Thank you.

DR. EBERSTADT:  May I ask a question?

CHAIRMAN PELLEGRINO:  Yes, you may ask a question.

DR. EBERSTADT:  It's pertinent to the future agenda.  Where is the disposition of our deliberations on organ donations and organ transplants in re: the future agenda?  Is this —

CHAIRMAN PELLEGRINO:  Dan?

DR. DAVIS:  Well, we ended yesterday with a statement against, I think, continuing to pursue the topic.  And we also had a proposal for at least an outline of a report that we may issue on this topic.  So that is where I think the state of the debate is at this time.

CHAIRMAN PELLEGRINO:  And I think that should be part of our discussion.

Peter?

PROF. LAWLER:  Let me relate Nick's report to that.  I read the article in the New York Times by the Freakonomics guy.  And he reported what I already knew, that no serious economist can figure out why we don't have a market in kidneys.  And from the point of view of a political scientist, serious economist might be kind of an oxymoron or something.

But from another point of view, this economic way of thinking is ever more pervasive in our society.  So I think the fact that people who really think along these lines are perplexed.

I would suggest that a market in organs is a much more serious possibility than Carl was saying at the end of the meeting yesterday.  And with respect to the Professor Becker, who is a great economist report, he's so abstracted from the political context and coming up with that number... That study is worthless because obviously, as we talked about yesterday, the price of the kidney will be set in terms of the Medicare entitlement, which would make it much higher than that.  And, as you were alluding very gently, common sense would tell you $30,000 wouldn't be enough to generate many kidneys unless you globalized the market, which would be disgusting in certain ways.

So, strictly speaking, you didn't answer Robby's question, which was, do we have any data that shows how many more kidneys a market would generate, what they're really worth.

And the studies you brought us by eminent economists don't really address that question and, I would even suggest, are incapable of addressing that question, but the fact that they're thinking along these lines and these guys have so much influence on public policy and they are frequently on the cutting edge of public policy would suggest the importance of the kidney issue because I think any — I don't think like an economist, but if I did, I would think this is a problem that would have a market solution.  And this allows the libertarians in a certain way for the first time ever to be compassionately conservative.  This would be a compassionate market solution to a real human problem.

So I agree with Carl on many points, but on this particular point I disagree.  I think we need to rush in a deliberate sort of way to get this kidney thing done, this organ transplant thing done because I think it is an urgent issue facing the country.

CHAIRMAN PELLEGRINO:  Thank you.

I think we will undertake the procedure of going around and getting individual opinions about what would be the direction in which we ought to go as a Council.  So, Robby, would you be willing to kick us off in that direction?

PROF. GEORGE:  Sure.  I will be happy to make a few opening remarks perhaps.  And then I would like to weigh in a little later, if I could, after hearing some of the discussion from other Council members.

CHAIRMAN PELLEGRINO:  All right.

PROF. GEORGE:  Before beginning, can I say how wonderful it is to have our colleague Dr. McHugh back and looking so hale and hardy.

DR. McHUGH:  I want to thank the members of the Council for their kind thoughts and messages when I was ill.  I can tell you they were most welcome and brought cheer to me.

PROF. GEORGE:  It is wonderful to have you back, Paul.

Well, in addition to the matters that are laid out here, I would like to propose, Dr. Pellegrino, one other thing but not a major thing, on a small scale, a project on a small scale.

I think one of the most important instruments that we have as a Council produced over the four-plus years' life of the Council was our White Paper on Alternative Sources of Pluripotent Stem Cells.

I think that really had a wonderful impact that is stimulating thought and work among people who are qualified to search for alternative sources of pluripotent cells.  And it continues to have that impact.

In part, because of the report, work has now been done that renders our report out of date, work by people like Dr. Eggan at Harvard, Dr. Jaenisch at M.I.T., Dr. Trounson in Australia, Dr. Yaminaka from Japan.  And I noticed just yesterday a report of what looks like some very important work by Dr. Cibelli.

So what I would propose as a small project for the staff and for the Council is simply an updating of that white paper to take into account all the work that has been done and, of course, to treat some of the work that has come into the public in the form of a kind of controversy, such as the ACT exploration of the embryo biopsy proposal, which was one of the proposals that we outlined among the four proposals in the report.  So I think that would be a very useful contribution for the Council to make at this stage.

Well, let me also say that I think that a reflection on the ends and goals of medicine is just a very, very worthy and timely topic.  I think it's an area where the Council really does have an important contribution to make because we can sit back and reflect on just what it is that we're aiming at when we're aiming at health.

So many of these issues came onto the floor yesterday during our discussion.  Is health purely to be understood in a physical sense?  If that's true, what do we do with Professor McHugh's profession?  But if it's not true, where are the limits?  Is medicine in the business of making people happy?

We have, of course, already explored some of these issues in our "Beyond Therapy" report, but there is certainly more to be said.  And we have gained some strength, not least the addition of Dr. Pellegrino, who spent a lifetime reflecting on these issues since that report was issued.  So I think we probably would have some new and important things to say there.

I myself am very concerned about the eugenics issue.  I do notice that five members of the Council indicated that they have little interest in that and one member of the Council said no interest.  I was somewhat surprised by that, but people have different perceptions of the situation that we're in.

It hasn't been published yet, but Dr. Kass gave a wonderful, if disturbing because of the analysis of our current situation that he offered, talk at the Holocaust Museum.  It must have been about a year ago.  The paper hasn't yet been published.

He noted in that talk — and I can't remember the title, but it was the talk that he gave at the Holocaust Museum.  The ways in which what might be called the eugenics mentality has reappeared in a somewhat different form at the end of the Twentieth and the beginning of the Twenty-First Century from the form it took in the 1920s and '30s that although the form is different, the substance is similar or even the same.

And he brought to light some social facts that I myself had perceived only dimly, but, of course, Leon's powerful, illuminating intellect really did bring them into the light of day.

I hope that that talk will be published soon, but, even if it's not, I hope that it could be made available.  Perhaps we could ask Leon to do that.  And I wonder if it might shift some sentiment on the Council to move the eugenics issue further up the table.

So those are my remarks for now, Dr. Pellegrino.  Thank you.

CHAIRMAN PELLEGRINO:  Thank you very much.

I will point out that each of you as you do make your own preferences known, it doesn't mean that you have had your last say so we can come back.  And only time will limit your participation.

Dr. Lawler?

PROF. LAWLER:  My tendency is to be a follower in these matters and just go along with what others suggest, but I will still say something.

I agree with Robby that we should update the white paper on the acquisition of pluripotent stem cells.  And if you want to connect that with the issue we faced yesterday of something like this: it would be a disaster, disaster we are going through, for the country to change its understanding of life and related issues in response to a stage of science that will be very soon surpassed.

What the white paper has shown and recent studies have shown is that eventually we won't — and eventually could be any day now in a way — have to kill embryos to get pluripotent stem cells.  How this resolves itself is unclear.  But that it will resolve itself somehow I think is pretty clear.

In the same way, with respect to kidneys, the crisis or alleged crisis with respect to kidneys depends upon a very specific stage in science that, as Leon Kass pointed out, will be superseded eventually.  So it would be a disaster perhaps to have a market in kidneys given that eventually we will have another and better way with dealing with end-state renal disease.

With respect to the issues here, the ends and goals, medicine, the issue there is something like this.  Should we address this directly, look right square in the eyes of the ends and goals of medicine, or should we consider our present procedure of looking at it indirectly through specific issues?

So many of the reports deal with the ends and goals of medicine but in the context of organ transplantation and so forth.  So we're talking about freedom, talking about dignity, but not abstracted from particular issues.

One Council member yesterday and quite well said, "We don't want to speak too abstractly."  By looking at the ends and goals of medicine straight on, we might be accused of speaking too abstractly."  So I'm not sure about this.

I myself am interested in investigating nanotechnology; first, because it's become so important; and, secondly, to tell the truth because I know nothing about it.  And so this would be like a graduate education for me in an emerging issue that I am pretty murky on right now.

With respect to eugenics, I think Robby was right.  This is a powerful issue.  The change between the eugenics that caused the Holocaust and the eugenics today is the science that caused the Holocaust was simple baloney.  The late Nineteenth Century eugenics was simple baloney.  The eugenics around the corner may actually work.  And that is the scary thing.  So it might actually have a positive eugenics plan that might actually produce results.  And this is what is totally unprecedented about it.

The citizens' personal responsibilities for health, I agree with Floyd we have neglected this in certain ways.  But it might be a mistake there again to address this straight on but to include this as a component of reports issued in other specific topics.

And I guess that's what I have to say for now.

CHAIRMAN PELLEGRINO:  Thank you very much.

Dr. Hurlbut?

DR. HURLBUT:  Maybe since I have some additions, maybe I should come later.  What do you think?

CHAIRMAN PELLEGRINO:  You want the Fifth Amendment for the time being.

DR. HURLBUT:  What?

CHAIRMAN PELLEGRINO:  You want the Fifth Amendment for the time being.

DR. HURLBUT:  I think maybe that's easier.

CHAIRMAN PELLEGRINO:  Okay.  Gil?

PROF. MEILAENDER: Well, I would make two general comments and then a brief comment on the specifics.  The first general comment is that I think that we should think of whatever we turn toward as a supplement to finishing the organ project.

We have worked on several tracks on many occasions over the past four years.  I think we can do it.  The organ project is a very rich one.  We're well along.  I mean, we're in position for the staff to begin to take that stuff and turn it into the draft of a report now.  And I would hate to see us not complete what we have already put a lot of work in on.  So whatever we turn to in my mind is an additional topic that supplements the finishing of that one.

The second thing I would say is — I think I said something like this yesterday maybe, but to me the best topics for a body like ours are ones that are not purely theoretical; that is to say, that may at least result in some recommendations, some fairly focused recommendations, of one sort or another but that aren't just solving a practical question either, that, really, once you start to work on them compel us to think about deeper issues that bioethics raises about the nature of human life and the nature of the universe even.

So I always look for an issue or issues that, on the one hand, there might be something specific to say about, but, on the other hand, in order to get there and say that you'll just be forced to think in richer ways.  Lest we be too pedestrian along the way, I don't see why we should bother to do that.  There are plenty of other people that will see to that.

So when I look at the sheet here — and, to be honest, I realize that I can't even quite remember what my own rankings were at the time.  I wish I had made a copy of them or something so I could remind myself.

But if I look at the things that more or less rose to the top of the chart, I myself probably would incline in the direction of the number 5, the genetic information and knowledge.

We have already talked — I mean, we are not starting from scratch on that because we have done a few things that connect us with that.  We are actually going to be dealing with that in a second session this morning.  It has the character that I just described that, on the one hand, there are some very specific questions that arise that, you know, one might or might not make a recommendation about.

On the other hand, it raises some very deep questions that the Council on Bioethics ought to think about in a way about human life.  So that it has that kind of dual quality that I think has enriched our work over the four years.

And so whatever my original preferences may have been that I can no longer remember, if I were looking at the ones that seemed to rise highest, that is the one that stands out to me.

It would I think — Peter — I guess Peter is right.  Just as the organ project does, it would force you to think a little about things like the ends and goal in medicine, even about citizens' personal responsibility and so forth, though it would get at those questions, not for their own sake but through a somewhat more narrow prism.   And so that is where I turn.

I would be happy to have us try to, as it were, update the white paper also.  And that I think would not have to be a major undertaking.  We would need as few sessions that simply brought us up to speed on it in ways.  And then we would have to have a session deciding what having been brought up to speed, if anything, we wanted to say.

But I don't think it would be a major output of energy.  So that would be fine, too, as far as I'm concerned.  But that is sort of the direction that I would see us heading.

CHAIRMAN PELLEGRINO:  Thank you very much, Gil.

DR. BLOOM:  Well, I am very happy with the list as it came out.  I would say that these are the issues that were in my mind when I was interviewed to ask whether I could join this Council.  And so I think how we carve it up is the critical issue.

Genetics and health care seem to me to be the major problem that our nation is facing unaware that there is a problem.  Most people are healthy.  And so they don't understand that the capacity of our system is so strained that any major even modest disaster could compromise the health of the nation.

I think unless we start to train our new physicians to be aware of the genetic information that their patients bring to them and to be able to use that in a way to improve their health in the long term, we are pretending that our system is better than it is.  And to me that is the major ethical issue that we face.

I should have said yesterday that I support Gil's proposal that we finish off the organ transplant, even though to me that was not as pressing an idea as some of these that are on the list.  But because we have invested so much in it and we have so many good papers to inform others, certainly I was unaware of many of these issues.  And I think that we would do a service to the country by making those views public.

How we carve this up I think is a major step because we need to be able to take on something where we can have an impact, rather than just talk about it.  But I think these are the major issues.

CHAIRMAN PELLEGRINO:  Thank you very much, Dr. Bloom.

Dr. Carson?

DR. CARSON:  I agree that we need to spend a little more time updating the paper on pluripotent cells.  I think that is a very important contribution we could make.

Now that we have an esteemed economist on the Council, you know, the ideal of looking at resources in health care I think is very important, recognizing that there are 45 million people in this country who have no health care insurance, which is a travesty.  And I think there are ways that that can be addressed with the amount of money that is currently in the system.  And I don't think anybody has really been taking very serious looks at it.  They just complain about it.

Also, the whole concept of health care reform, which obviously is discussed at every national election, but nothing ever gets done about it.  I wonder if perhaps this body might be able to make some real recommendations because it is such an important issue for all of us, maybe even looking at a governmental role and taking care of such things as catastrophic health care, which completely skew the system and allow for all kinds of inequities to occur.  And it's not been looked at in any rational fashion.

So I think if we concentrated some energy on those areas, we could make a major contribution.

CHAIRMAN PELLEGRINO:  Thank you very much, Dr. Carson.  Thank the speakers thus far for being very much to the point and very much in the direction I was hoping you would take.  That is not to say a particular subject but to give you your own views on what you thought were critical for us to be doing.

I would like to go now to Professor Gómez-Lobo.  Thank you.

DR. GÓMEZ-LOBO:  I find myself in general agreement with many of the proposals that have been expressed.  First of all, I think it's wise to finish up the organ transplant project.  We have worked on that.  And I think there is so much that is real clear information that should be made public.

However, I do think that we have to come down one way or the other on the question of market for organs.  I mean, I think we would be remiss if we don't do that.  I think we have to have a position of that whatever it is or more than one position because I think that's what many people are going to be expecting from us.

In this case, it would be the odd thing of a moral judgment on an institution which is supposed not to be moral at all, but let it be.

Second, I strongly favor the idea of updating the alternative sources document.  That has to be done.  It is a pressing issue today.  It's almost every day in the press.  We all know about the Nature article a few days ago.  And it's important for people to know that we had thought about some of the problems long ago and that the science is moving forward.

I see a certain urgency there.  I would even say in terms of timing, maybe we should let it run ahead of the final organ transplant project.

Then with regard to new material, I tend to see certain things as connected.  For instance, the eugenics question to me seems very important.  I think it's of vital importance to call to mind what is being done and certain kinds of procedures and that they are eugenic in nature.

Interestingly enough, I see it connected to the question of under-treatment of pain.  And both I see as subsets of the question of the ends and goals of medicine; for instance, in the case of eugenics, to make clear that it cannot be a goal of medicine to eliminate the weak and just favor the strong or it cannot be a goal of medicine to leave, say, suffering and pain untreated.  So my tendency would be to incorporate those two topics under the ends and goals.

And, finally, it seems to me that what Ben has mentioned is extremely important as a public issue:  the question of the dismal health care resources for millions of Americans.  I mean, that just cannot be.

I would say even if we cannot provide something like a technical or a political solution, I mean, how do you get health care insurance for all of these people?  Even if we couldn't get to that point, just pressing the issue seems to me extremely important.  Now, if we could make some concrete recommendation, that would be great, but just bringing the issue to the floor seems to me important.

Thank you.

CHAIRMAN PELLEGRINO:  Thank you very, very much.

Professor Schneider?

PROF. SCHNEIDER:  Yes.  I agree with the last two people that there probably is no single thing that you could do that would make more difference to Americans' health and well-being in any way that we're connected with more than looking at this problem of the 42-45 million people who are uninsured.

I just spent several days in North Carolina interviewing people who have no way of paying for their health insurance.  And these were people who had virtually no education.  They had no way of even using the resources that were supposed to be made available to them because they didn't have the sophistication to call on those resources.

They were people who had no jobs because they were so ill.  And they were multiply ill and never taking care of themselves, not because of a moral failing but because they simply weren't being given the equipment to do that.

And since one of my criteria for selecting topics is doing good in the world in a reasonably perceptible way, I would be very enthusiastic about that topic.

Some of the other topics are probably more important than I realize.  And I am glad to learn how.

CHAIRMAN PELLEGRINO:  Thank you very much.

DR. FOSTER:  Also the most important thing I think we can do has to do with the economics of health care.  Ben and I had lunch yesterday.  And we already solved the problem about what needs to be done.

(Laughter.)

DR. FOSTER:  But we think that that would be number one.  Also, my number two thing, I think we do need to upgrade the discussion, including the ethical issues of stem cell work that we have talked about.

There are huge changes coming along.  For example, just yesterday two of these things that I haven't even had a chance to read yet, particularly the three papers in Nature, yesterday as all of you — if you read the Times yesterday, you saw that this famous tumor suppressor gene, which is called P16 INC 4A, has dual effects that are very interesting.  Its protein is made in huge amounts as we age.

And the teleological reason that these three labs that put this together and did not compete with each other on it — they all found exactly the same thing — think that because cancer increases as aging, that the universe has made it that one would try to keep you from getting cancer by producing this — it's not the most famous of the tumor suppressor genes, but it will do it.

But simultaneously it causes a disappearance of adult stem cells.  So that you have this Catch-22.  I mean, you make this protein.  And it will help you escape cancer.  But at the same time, it probably means that all the concerns about adult stem cells are very real.  And we have known for a long time that bone marrow transplants in older people don't work as well.

And so to readdress the issue of embryonic stem cells, as opposed to adult stem cells, would be a very important issue.  So I think that we need to look at that.

We came down on the view that biopsying an eight-cell morulae for pre-implantation genetics was fine for genetics but probably was not worth the risk of doing it to get stem cells and so forth.  So that would be my second view.

The third thing that Floyd was talking about that is in the new Science, which I haven't seen, is from the Vogelstein lab at Johns Hopkins.  You remember, to put this in perspective, they worked out the genetics of colon cancer.  And it came out that there were probably eight or nine genetic changes that lead to you.

Now, this new paper apparently says that when they look at the — they use examination of the whole genome — that cancer is involved with two or three hundred genes in every cancer.  And they found only five genes that would be crossed from one version of a colon cancer to the next.

So the idea of being able to attack specific genetic changes in the treatment of cancer, I mean, that's a remarkable thing when you think there are maybe 25,000 genes or something like that and 200 or 300 of them give you a fingerprint of a single cancer in you or me and that if — let's say Gil and I both had a colon cancer and you did the genomic evaluation.  We would maybe share only five genes involved in that.  So these are — I mean, the tremendous advance in the greatness of science is that it gives you new information to do that.

So, in summary, I am in favor, first of all, to say something about what I think is — the word I think you used was a "travesty" of health care that we're the last or next to last in all the developed countries in the world, the richest country in the world.  And we have this shameful, ethically shameful, fact about the care.

And, secondly, I would like to upgrade the ethics of stem cells and look at those things again; and, thirdly, the whole problem of the genomics for the future of health.

CHAIRMAN PELLEGRINO:  Thank you very much.

Paul McHugh?

DR. McHUGH:  I agree with much of what has been said, of course, here, but I want to remind the group that the method that we have used as a successful body, not only in the reports that we have taken but also for each of us as members after the meetings, we have become quite a well-informed body of people in relationship to contemporary science.  And much of our discussions and much of our learning and much of even our disagreements have come and have been based upon the growth of knowledge in this committee of contemporary science.

I want to encourage whatever method, whatever thing we do from this point on, since we have a relatively short life perhaps ahead of us, that we should continue this.

And so I am, first of all, very much in favor of what Robby and Dan and others have said about the follow-up and the contemporary discoveries related to stem cells to build up what we have done.

We can again, as we did before, bring in the world's experts.  It's wonderful.  They look forward to coming and talking to us and explaining the details, much as Dan has just done in relationship to Bert Vogelstein's new work.  I would like the opportunity again to see whatever ethical positions that I have that they have a certain scientific foundation and derive from real life.

I am concerned that if we go out and try to solve our big problems in our nation, all of us I think agree that the health problem of lack of insurance is a big one, but I'm not sure that we as a group will do anything more than add to the political process in one way or another, joining the red states or the blue states in relationship to that.  And I would rather leave that to others.

And then, finally, in relationship to the contemporary science, I believe that the genetic world and the world of genetics as it's emerging permit us to get the best scientists here.  We are very lucky to have Nancy here today and to see the direction things go in.

Let me just make a point.  Bert's work has been emphasized here today, but George Uhl just a few weeks ago was talking about the genes in relationship to alcoholism and other addictive substances in which he said, you know, "Look, now there are 32" or "52."  I can't remember exactly what George sid the number was, but it was clear that there are, again, a huge number of genes that come into play in relationship to behavior.

And the place of genetics, you know, people have been talking about alcoholism is a disease and there is a gene for it or there is a gay gene or an anorexia gene or other kinds.  Well, there's obviously that this is not true.  And we should perhaps have some of these behavioral geneticists come and talk to us about just the place of genes in relationship to behavior given that behavior is the essence of our ethical dilemmas often.

So, in essence, what I would like to say is I suppose what has been coming.  I would like in this list to emphasize the genetic information and knowledge as a place where we would get good traction in relationship, really, to many of the other things that come up.

Thank you.

CHAIRMAN PELLEGRINO:  Thank you very much, Paul.

Dr. Eberstadt?

DR. EBERSTADT:  I would mention three items.  I would second Dr. McHugh's vote for genetic information and knowledge, but I would say that an exploration of genetic information and knowledge I think naturally dovetails with Robby's questions about eugenics because the technological innovations in this area I think will naturally raise questions about eugenic interventions or, conversely, if we were to explore the question of eugenics, I think that would naturally lead us to the question of genetic information and knowledge.  It seems to me those two questions may be somewhat wed.

A second item of interest to me at least is the question of citizens' personal responsibilities for health.  Now, this fails Paul's test of new scientific knowledge.  I don't think, however, it fails entirely our mission of ethical reasoning.

We do know that personal behavior figures very strongly in health outcomes in the United States.  We do know that there is an enormous goal for preventive interventions that's currently not being made use of.  We know that what we might call irresponsible personal behavior imposes an enormous mortality burden in the humanitarian sense on our society and also an enormous economic burden on our society.

How do we think about this question without ending up as a nanny state and as health police and as all of the rest?  Where is the line that we can tread in there?  I mean, I would think that our Council members might be able to illuminate this question for the public very profitably.

Finally, I would get back to some of the things that have been said about the still unfinished question of organ donation and marketization.  From my own perspective, I think we could explore a little bit more in this area the whole relationship between economic reasoning and the organ shortage.

I don't happen to believe the organ shortage is a crisis.  My own perspective is that it's a problem.  For many families, it is a tragedy.  But until there is the technological fix that Peter described, it looks as if it's going to be a growing problem.  And it coincides with the relentless march in our society of market-like thinking.  These two things are conflating.

It may seem fanciful at this point to imagine that there will be an organ market in the United States or in the world, but this is not a completely fanciful possibility.  And, again, I think that our Council members are positioned at this point to examine and discuss and opine upon this possibility in a way that I do not see other groups possibly doing.

So I think there could be great comparative advantage, a great contribution to the public.  It will be a public service to have the input from our group on this evolving question.

CHAIRMAN PELLEGRINO:  Thank you very much.

PROF. GEORGE:  Thanks.  Two points.  First, I remembered the title of Leon's magnificent and profoundly disturbing talk at the Holocaust Museum.

CHAIRMAN PELLEGRINO:  Yes.

PROF. GEORGE:  The title is "A More Perfect Human."

And then the second point was I have a question for Dan.  I don't think that the Council has endorsed cell biopsy for purposes of pre-implantation genetic diagnosis.  Have we?  I thought your comment suggested that we had.  And I don't remember that we did.  Did we do that?

DR. FOSTER:  I didn't mean to imply that.

PROF. GEORGE:  Oh, okay.

DR. FOSTER:  I simply said that that methodology was available and it had been done.  You know, the guy in Chicago had already done this.  This new thing, they don't reference those two previous things.

What we did say is that we thought that under any circumstance that that seemed too risky for us.  That was all —

PROF. GEORGE:  Yes.  So we didn't really say anything about it one way or another, but we did address the cell biopsy question in relation to attracting —

DR. FOSTER:  Just in terms of the methodology that was already going on there.

PROF. GEORGE:  Yes.

CHAIRMAN PELLEGRINO:  Thank you.

Dr. Hurlbut, we have not heard from you as yet.

DR. HURLBUT:  In reflecting on what we should do in terms of topics, I would like to just suggest that, at some point at least, we talk a little bit more broadly about the mandate of the Council because I feel like, in retrospect, some of what we were mandated to do we haven't done.

And one of those dimensions was to engage and educate the public.  I just think it's worth at least having a discussion to see if there's a way we can get our reports out there a little better and our engagement and interaction with the American public better.

I remember when the Canadian person came and talked to us about how they engaged the stem cell issue.  They had public forums specifically around the country.  I know we're all very busy, but I also feel like there is some great value in at least discussing those kinds of possibilities.  So that's something I just wanted to add to the mix at some point in our discussions.

I also feel like there's an awful lot of misrepresentation, misunderstanding in the public arena, including through the media, of some of what our Council has said and done and also just of the general issues themselves.  It's very obvious from the last week's coverage of the stem cell announcement that there is a lot of misunderstanding in what the Council had said or inadequate assimilation of it.

Before I say a couple of subjects that I think we should also address, I want to make a plea for one of them that only got a four.  And that is international collaboration.

Now, I don't think we should go into that extremely complicated issue of the cross-cultural meaning of bioethics in a deep and serious way.  That could consume an entire lifetime of a Council.

But I do think there are a couple of valences that are really important for us to at least acknowledge and perhaps make some preliminary statement on.  I have traveled quite a bit in my adult life.  I have been in half the countries of the world.  And I have traveled a lot in the last four years while on the Council.  I'm very aware of how different the dialogue is in different countries.

For example, in the organ transplantation field, I was in Japan a few years ago and took a three-day trip with a physician from Tokyo who is a hepatologist, is a very profound thinker on the issues of transplantation.  And he and I had a long-running conversation on the different views of the body and why cadaveric transplantation is not done primarily.  They have only done something like 18 cadaveric kidney transplants in Japan in the whole history of the country.

And this is worth at least acknowledging how foundational the concepts of the body, the perspectives on broader metaphysical questions play into this.  It's an element our report ought to include, an acknowledgement at least.

But what worries me more than trying to solve all the different cultural variations on these kinds of themes is the practical issue that I think we can all see coming:  first, medical tourism; and, second, what I have been calling the outsourcing of ethics.

Clearly we have got a dilemma coming with the globalization of rapid transmission knowledge, the disbursement of research centers, the collaborations between both commercial and university-based research programs in the United States and those in other nations.

We should at least reflect on the potential dilemmas of getting things done elsewhere that we in our nation find unacceptable to do.  And I think we should acknowledge that there are commercial values and scientific advantages in terms of competition to be gained by violating ethical standards.

I mean, you could test drugs more quickly if you didn't have to worry about human subjects concerns.  You could get organs more readily if you didn't worry about some dimensions of human dignity.  Well, it is worth touching on.

But what I really wanted to say is this.  When I look out — I think you can see this — any day when you pick up Science magazine, read through it, you can see that the two major fields of scientific advance right now, all building on the foundations of a range of advances across biology but especially genetics, the two major fields of advance right now, and the two major fields of challenging ethical questions are developmental biology and neurobiology.  And it's notable that none of our 14 topics focused in very strongly on either of those.

So I have been trying to formulate in my mind how we would approach those very broad and difficult subjects, but first let me make a plea for why we need to.

Nancy and I have been involved in — this is Nancy Wexler I am referring to here, our next speaker — have been involved in thinking about the issues of genetics for a long, long time.  And I think we are probably both aware — I will speak for you a little, Nancy, and you can say not or yes, but I think we are both aware that had people talked about some of these issues before they became practical issues, it would have been helpful.  And we tried.

But we have a unique opportunity now with regard to some of the issues of development biology and neurobiology to anticipate the ethical questions, to define the terms and the concepts of the conversation, and to set a frame for the future.  Even if we can't precisely adjudicate some of the difficult issues, we could help frame them and make a big difference in the way they play out.

Just let me give as an example two specifics that I would like the Council to take up.  I admit that my case in making these isn't fully formed and so, therefore, a little inarticulate.  So I would actually like to have a chance to prove, maybe over the next few months, to the Council members why both of these issues are extremely important and we shouldn't dismiss them for their abstractness.

They might be summarized as an inquiry into what you might call the boundaries of humanity issues in developmental biology.  Most specifically, what is it that defines life, organism, human?  Let's just say those categories.

We obviously are going to have really valuable tools in biological inquiry if we can mix species cells together, chimeras.  And, yet, obviously there are great ethical challenges involved in that.  I think we have already done some on that, and I think it would be very valuable for us to continue.  But that is just a subset of a larger category defining what the boundaries of our moral concern actually are.

This has both basic principled concerns and, as I said yesterday, sort of semiotics.  What are the signs and symbols of humanity?  It may be that even just the appearance of humanity is enough, even if we don't think something is operating in a humanly conscious way.  Therefore, we might not want to create a sheep with a human face or with hands if that were possible.

So that borders on the issue we discussed yesterday a little bit of the definition of organism in relationship to organ transplantation and definition of death.

There is a whole industry emerging, as I said yesterday, of production of human parts apart from the human normal developmental process.  And somebody should address some of those issues.

The second thing I think is very important — and here I probably can't make a very compelling case, but I think there is a compelling case to be made.  And that is the subject of a neurobiologically related subject.  It could perhaps be covered under the ends and goals of medicine and maybe to some degree under genetic information and knowledge, but it's the subject of what you might call desire and disproportion.

In its most extreme form, it's not a subject of only specific advances in biology.  It's known as the subject of addiction.  But addictive behaviors in the broadest sense, broadly construed, are becoming an obvious problem in our civilization.

And here let me just outline briefly what I am concerned about.  I think that in the natural environment of our evolution or creation, whatever you want to frame it, desires have operated within natural constraints.  And, therefore, they have been stronger than what one might in the modern world consider necessary in order to get the job done.

Hunger is a very compelling drive.  So is sexual desire.  Fear is very powerful.  Now as we gain control and the ability to kind of manage our pains and pleasures or to bypass the natural constraints, we're looking at some very troubling potential dimensions.

And on a practical level, it's obvious that the biological revolution in a way, the first dramatic and unnoted milestone was perhaps the contraceptive pill, which separated off procreation from the unitive and pleasureful act of sexual intercourse.

And without passing any kind of moral judgment on contraception itself, it certainly raised important social questions and personal questions and challenging issues because the technology essentially disconnected and bypassed a natural connection in life.

We're going to do this on so many levels.  Already you can see that the abundance of food is creating a challenge.   Our society has a great many people suffering from obesity.  Our society has learned to promote and to commercialize dimensions of sort of managed experience, like the stimulation of gambling high or even commercialized recreation that stimulates the release of adrenaline.

And we should face the fact that we have short-circuited the connection between sexual stimulation and actual human encounter through internet pornography.

Those are perhaps a little beyond our purview, but there are some very important connections with advancing biotechnology and the potential to engage in and manage human pains and human pleasures.

There are also some very real social issues emerging.  You probably know there is now a movement to sue the fast food industry on the same grounds as the tobacco industry was sued.  And somebody needs to make some inquiry from a deep ethical perspective onto what the justification for such a perspective of how we should think about this really is.

As you probably all know, there are quite a lot of children's foods that have caffeine in them.  And I think there are some moral issues there.

And then one of the larger issues involved in this field of inquiry would be some kind of comment on the social dimensions of engaging in bypassing the constraints on impulsivity; in other words, what traditionally has been called indulgence, self-indulgence, of people.  And this leads, indulgence always leads, to injustice.

And in a world where the U.N. estimates that 30,000 kids a day on average die from starvation and diseases related to malnutrition, the over-engagement and over-stimulation of desire and its disproportions in the conduct of both individual and collective life has I think a compelling case to be at least clarified and brought out to help our society be aware that primary human desires are now being managed in such a way that might be disruptive of human life.

CHAIRMAN PELLEGRINO:  Thank you very much, Bill.

Dr. Lawler, did you want to make a comment?

PROF. LAWLER:  I am not going to address any of that, although I think many of those concerns could be folded into some of the topics we have here.

With respect to the stem cells, let me just emphasize something that emerged.  Robby's emphasis is on the innovations and acquisition of stem cells.  Paul's and Dan's emphasis is on innovations in the use of stem cells.  I don't see any reason why we couldn't bring those together in another white paper.

With respect to the issue of taking a position against market forces, the use of the market, in acquiring organs, I'm in favor of doing this, but I'm also in favor of giving the strongest possible case for the market to understand in a certain way, as Nick pointed out, how compelling it is and why we have to take a stand against it.   It's precisely because the case for it is so non-trivial.  I mean, there is actually something there.  We have to take a stand against it.

And obviously it emerged that there is a connection between, number five, genetics and, number nine, eugenics.  And they could easily be handled at the same time.

Obviously innovations and acquiring genetic information have eugenic implications.  And a lot of our wilder thoughts about eugenics depend upon, as Paul said, really overestimating how important genes are for human behavior.

In general, with respect to the health care, the economic side of health care, I was changing my mind every 30 seconds here concerning whether we should address this.

On the one hand, now that we have an economist, maybe we should.   To add to that some health care professionals throughout the country commented to me on our care-giving report, "There was a lot of beef there but no talk about money."  I mean, they said the whole report distracted from the economic dimension of the issue.

So it's not just that a large number of Americans don't have insurance.  Even the social safety net we have now is going to fall victim to harsh demographic realities, as we have an aging and frail population.  How exactly are we going to pay for their care?  We sort of abstracted from that in our report.

So there is an argument that we should address this that came from some of our M.D.'s and then an argument that we shouldn't address it that came from another one.  The argument against it would be it's too big technically and too dividing politically.  We would have to be on the red side or the blue side.

But there is an argument that we could just lay out the fact that we're not going to pay for it.  We have no way of paying for what we need to be able to pay for.  And I think that is sort of a nonpartisan part.  Even if you have a minimalist safety net, it's unclear how we're going to pay for it in the future.

That's all I have to say.

CHAIRMAN PELLEGRINO:  Thank you very much, Dr. Lawler.

I want to congratulate the Council members again for very, very promptly and concisely giving your thoughts on what are the agenda items of importance.  I think you have a fair return.

We have asked you for your comments.  And I think Dan and I will just give you ours very, very quickly.  Just to add to them, I, in particular, as a member of the Council, ought to at least express my opinion.

I think you know, I hope, from my behavior since I have taken over as Chairman, that I do not use this position to impose my views.  So, therefore, as I express them, they will be thrown into the pot with all of the others.  And I want to make that very, very clear.

The other point is that after we have expressed our views, I would like to have more discussion on what you want to go into in detail.  Peter had a comment.  Others have comments of others.

And then, finally, I'm sure you know we don't necessarily decide such things by plebiscite but, rather, looking at the strength of the arguments pro and con for these particular subjects.

I will ask Dan to give you his preferences or his thoughts and then mine very, very quickly.  And then we will go back to discussion because you have been so prompt and so responsive that we have the time for further discussion.

DR. DAVIS:  Let me talk about organ transplantation first.  To address some of the concerns that Professor Schneider raised yesterday, one of the things that the staff has been engaged in doing is talking with those divisions of the federal government that are engaged in this issue, the Institute of Medicine, the various societies, the American Society of Transplantation, et cetera, and attempting to figure out where is their play with regard to proposed policy.

We're still engaged in this activity.  We're going to meet on Monday with the Division of Transplantation at the Health Resources and Services Administration, which staffs the advisory committee to the Secretary of HHS on organ transplantation.

I think based on the survey thus far, there is something very important for this Council to say.  And it does deal with the market issue for the most part.  There is an expectation, I think, within the transplant community that we are going to issue a report on this issue because we can all tell you we are being lobbied by both sides.

There's not a week that goes by that I do not hear from Ben Hippen, Arthur Matas, who are very vocal proponents of markets, also from Frank Delmonico, from whom we have heard.  So I think there is an expectation that the Council is going to weigh in on this issue, that it's going to use its bully pulpit.  So I think if we say nothing, we will fail those expectations.

So I am glad to hear that there is a clear sentiment for doing a report on organ transplantation.  I think we need to capitalize on the investment that we have already made on the topic.

Genetics.  We have been engaged in this conversation about newborn screening.  And I think that the conversation by its very nature has pushed us beyond that particular point in the life cycle.

So I think, although we might consider doing something along the lines of a white paper on newborn screening, there is an immediate issue on the table and it's the proposal for a uniform approach across the 50 states.  I think we need to go beyond that.  And so I am also happy to hear that there is some sentiment in that favor.

And I agree with Floyd.  I think that if we ignore this issue, we should be taken to task for that.  And I hope that Dr. Wexler when she gives us her remarks can help us perhaps begin to understand what that broader inquiry might look like.

Obviously there is clear interest in updating the white paper.  And so I think you should consider that task done.  We'll walk away from here and begin to figure out how we wrap our heads around that.

So those would be my responses, at least at the time.

CHAIRMAN PELLEGRINO:  Thank you very much, Dan.  I will be as brief as I can as well.

First, I very much am in agreement with Paul McHugh's statement — and I think every member of the group shares that — of securing the scientific base of whatever we do.  Over and over again I have to in my debates and discussions point out that poor science makes poor ethics, not that science determines ethics, but the scientific foundations, the factual foundation is absolutely essential.

So I think a continuation of doing what we have been doing, perhaps even more in depth, on the scientific foundations of the questions we're dealing with is critical.  And I think that is uppermost, at least in my mind.

With respect to specific topics, I think we have invested a lot in transplantation.  And I think probably we should say something about that.  My own inclination is to take selected topics.  This topic has been discussed by other groups, other reports.  And I think we should take the difficult ones that have not been addressed, one of them being the question of paying for organs, et cetera, et cetera, but not the only thing.  But surely I think we should address that from the ethical point of view as well as the economic.

The third issue that is very much in my mind as well is the question of genetics.  And I'm not going to speak of a particular aspect of it.  It's so broad.  But we need to focus on it.

Particularly I think someone used the term — I believe it was my colleague on the left — "genetic medicine," the question of when it comes to the bedside.  As a clinician, I am always interested in the bedside and the gurney.  Some people find that rather stressing, but that is where my initial concerns about ethics lie.  And so I think that particular topic deserves consideration.

I very strongly believe that we need to bring up to date the stem cell situation, again, here because of the first point that I made, that the science is changing so rapidly.  And we are always in our ethics trying to catch up with science, kind of like, as I pointed out once or twice, those of you remember the movie and the story of Pinocchio, Jiminy Cricket running after Pinocchio and always trying to catch him.  And I think that ethics looks kind of like Pinocchio and never quite gets there.

So I think it is extremely important that we do address that topic because it is very much in the public mind, and there's no question that they will be looking for something from us, I believe.

And the way we have done it before I very much support the statements that have been made about the techniques we have followed, the idea of laying out the issues.  I think that is the most important function we can make.  When we can come to an agreement on a policy recommendation, we ought to do so but granting the disparate nature of this group, the different perspectives and so on, we can't always do that.

But we do a great service in the hopes that the policy-makers will, in fact, read what we have put out and use it as a starting point for their discussions, rather than the usual emotiveness that runs through all of the discussions.

I am very much disposed to an examination at the health care reform.  I don't use that terminology.  My concern, at least, — we're not necessarily going to follow up because it's my concern — to establish a moral foundation of a good society for the health of the system.  And that is a topic in its own.

And I think we could not get into at that point the economics, the mechanics, or any of those aspects.  We need to first answer the question, does a good society owe something to its sick members and its disabled members?  And what is the moral foundation for that?  That would be my preferred approach.

I think on the international cooperation, Bill, that you brought up, you might want to know that I am a member of the UNESCO — the only American on it, UNESCO International Bioethics Committee.  And I was a member of the drafting group that put out the universal declaration, which has its ups and downs and so on, but for a discussion at the international level, I think it's probably a pretty good document, particularly for those countries that don't have well-developed programs in bioethics or an interest in it, which was one of the foci.

Also, Dan has been associated with a group that met in Strasbourg.  And he has connections there.  So both of us at least are providing information to these international groups on where our Council is, not our opinions, I assure you, but what we have published and where the thinking is at the present moment.  And they have found it most salubrious.

They haven't had that in the past.  And they have been very, very interested in the fact that we are willing to share.  And, as a matter of fact, I was overwhelmed by the reception I received as the United States representative, particularly in this world when everybody is feeling a little bit negative about the United States outside our own borders and sometimes inside our borders.

So I think that is an important issue, but I don't think it would involve the whole Council except to the extent that you want to tell us what to tell those people abroad but keeping them going because I think ultimately — and I think, Bill, you made a point — there is no way we can keep these issues from being global issues.  The boundaries do not limit the implications of the ethical advances and the ethical problems that biotechnology is producing.

The other subjects are important.  I don't mean to depreciate them in any way, but since I have put you on the spot, I put myself on the spot.  And these are my own inclinations.

The last one that I am very, very much interested in as well personally, as Robby pointed out, of course, is the state of the health professions.  And I think the transformation of the offices that has been occurring is not necessary in the interest of patients.

And, after all, going back once again, — I don't defend myself.  I'll assert it.  Every policy we make, every decision we make, ultimately has an effect on someone on the gurney or someone in the bed if it's health care we're talking about.  And, therefore, I am very concerned about that translation.

And, finally, with reference to the point that you made, Robby, I am concerned about occult genetics, not about the overt, which is still unpopular but the occult genetics that occur whenever you begin to get into genetic questions and the selection and how you make it and who gets the model of the acceptable.

That will tie in with our coming report that Adam Schulman is handling on dignity, the human person, where there will be a variety of difference perceptions.  Nonetheless, we will be making our contribution to looking at that complex concept because I think, as we said in the UNESCO document and as the U.N. said 50 years ago, the dignity of the human person gets to be the foundation for much of what we decide in the ethical realm, end of speech.

Now, we have time left.  And we open it cone again to the members to add to, amend, expand on their comments, limited only by the fact that have a break at 10:00 o'clock and time to get to Dr. Wexler at 10:15.

Dr. Schneider?

PROF. SCHNEIDER:  I think I am obliged to say a couple of things.  And since the time really is limited, let me just mention a couple of the additional topics that I had in mind.

I was under the impression that everybody was supposed to come up with several of them.  And so I did.  And I discovered that I was rate-breaker and apologized.

Now that I have put myself out that far and committed myself, Dan let me go ahead and name a couple of topics.  The first one partly grows out of an experience I had on the hospital a number of months ago.

I was visiting.  A patient was transferred in from another hospital, actively dying of cancer, with pain wholly untreated.  He had ripped out the various tubes that were in him.  Blood was spilling everyplace and staining the sheets.  And he was writhing on the gurney and shouting over and over and over again, "Don't let your children die in pain like this."

I was unable to visit a hospital professionally for six months after that because I found this experience so wrenching.  And it made me feel obliged to try to bring to the attention of anybody who would listen thee facts that I have discovered on investigation, which are hardly secret but not well-known.

Those facts are that pain is very dramatically under-treated in American hospitals and by American doctors, very dramatically under-treated.  Let me very briefly give you a couple of samples of data.

The SUPPORT study, which was quite elaborate and careful, found that half of the very seriously ill patients with whom they did their research, were complaining of pain.  One-sixth of the patients were in moderately severe pain, at least half of the time, and/or were in extremely severe pain at some times.

There is another estimate that patients in nursing homes are suffering from unrelieved pain, much of which is persistent for at least 80 percent of the people who are in nursing homes.

If it were scientifically impossible to treat these people, it would be a misfortune.  The fact is that almost all of this pain that we're talking about is very much treatable.

One of the tantalizing things is that this is a solvable problem.  Patients at the worst hospitals dealing with pain suffer pain 75 percent more than those patients at the best hospitals.

Now, this isn't to say that is an early problem because there are an awful lot reasons why pain is untreated, starting with problems in medical education.  We can always attribute our problems to medical education or whatever you are interested in.

Doctors and nurses are very dramatically under-educated, not just in medical schools but in their own work with patients.  There is a complicated and important relationship between our drug policies and our pain policies.  And those cut in many different ways.

There are ethical questions about the willingness of many doctors to decline to give their patients adequate pain treatment because they say they are afraid of a legal response, a legal response which in statistical fact is almost impossible.

And even if it were a much more serious threat, it seems to me it is a real ethical questions that doctors face about saying, "I'm going to let my patient suffer because I feel some kind of legal response."

This is also an issue where the law is at a formative stage.  There are beginning to be tort suits in which physicians in nursing homes are being sued and in two cases losing cases.  One of the cases, for example, was a nursing home.

The physician had ordered a quite adequate pain treatment for the patient.  The nurse in the nursing home decided the patient was likely to become addicted.  And the nurse, therefore, refused to provide the medication.  And the nursing home did nothing about it.  That was a case in which there was a very considerable damage award.

In addition, of course, issues like physician-assisted suicide are in no small part driven by the fear of patients that they will die in pain, the very realistic and reasonable fear of patients that they will die in pain.

So this is an important, not simple but workable problem in ethics that would profit by being understood as an actual issue by Americans as I think most Americans do not realize that it is an issue, but repeatedly when I tell people about it, they have a story to illustrate the case.

It is a problem that can be solved, but it isn't an easy problem, which if solved would make a big difference in the lives of millions and millions of people.

The other thing that I should mention is informed consent.  And it must be hard to believe that anybody wants to say anything more about informed consent.  It is certainly an issue that has been beaten to death.  But I should tell you that it is also now an issue that somebody needs to speak about honestly because the sorry fact is that we know now beyond peradventure that informing consent in anything like the forms in which it was intended is a failure.  It does not work.  Patients do not get the information that they need, do not get in the sense of actually getting into their minds the information they need for making decisions.

Let me give you an example from a study that a colleague of mine named Angela Fagelin is about to publish.  She took one of the classic issues in informed consent, which is treatment for breast cancer.  And she found that fewer than half of the patients knew that the chance of survival after 5 years were the same for mastectomy and breast-conserving surgery with radiation and that only 19 percent knew that recurrence rates for the 2 treatments are different.  If you have only 19 percent of the people knowing a fact as basic as that, you have people who do not understand the decisions they are asked to make.

This study is not a sport.  It's not a freak, as she says.  Other analyses over many years in a considerable number of studies have reached similar conclusions.  I have read, I think, probably now hundreds of these studies.  They are all for the same effect:  Failure, failure.

Indeed, we know that in other areas, where the solution to a social problem is to try to give information to people in an unequal power relationship so that they will make good decisions, that everywhere that is tried, that fails.

The classic example for you is the Miranda rule.  You're worried about the disproportionate power that police have over suspects so that you say to the police, "Give the suspect the information they need to make a good decision."

I have heard the Miranda rule described as the most ignored, commonly heard warning in American life outside of what you read on cigarette packages.

We knew two things.  We know that, no matter how hard experimenters have tried to communicate information successfully, they have failed.  We also know — this is the Braddock study — that in only nine percent of the hundreds, if not thousands, of interactions between doctors and patients that they listened to, that in only nine percent of those cases given for making a decision.

Now, there are a lot of reasons why this doesn't work.  One of the reasons this doesn't work is because people don't listen.  And one of the interesting things that one encounters on trying to probe more deeply into the transplantation question, as I have been doing, is that when prospective donors are told about the possibility of donating, they very commonly decide instantly to donate or not to donate.

They decide before they have heard any of this information that we pour upon them.  And once they have decided, they are like all of us.  And they interpret every other datum they get as confirming the wise decision they have already made.

Now, if informed consent were not the solution to almost everything, it wouldn't matter that informed consent doesn't work.  But, of course, informed consent is the basis for our definition of how doctors and patients ought to deal with each other.

Currently there is a lot of writing that talks about the doctor-patient relationship and medical decisions in terms of what is now called shared decision-making.  What that means depends on who you are reading, but it, too, is essentially based on ideas about informed consent.

Human subject research is a very large problem, a very large part of which is solved by trying to give research subjects information.  And I suspect that all of you have heard and even seen the 25-page consent forms that IRBs now feel it wise to give to patients.  I don't know if you have ever tried giving such a form to a patient.  The patient or the subject will not read a two-page form.  And there is an interesting study of the forms proposed by IRBs themselves that suggest that they can only be read by people with a college education, which does not describe most of the people who are studied.

The latest idea in health care reform now that managed care is thought to have been rejected is consumer-driven health care.  The idea is that consumers are going to buy health insurance shrewdly and then are going to spend their own money in making medical decisions.  And that, too, depends on informed consent.

There are many other areas that I could list.  I will not because time is out.  But at some point we are going to have to acknowledge that our solution to so many things is a solution that has failed.

CHAIRMAN PELLEGRINO:  Thank you very much.  I think we have reached the time now for intermission.  Let's return at 10:20, instead of 10:15.  Thank you very much, Dr. Schneider.

(Whereupon, the foregoing matter went off the record at 10:06 a.m. and went back on the record at 10:20 a.m.)

****

SESSION 6: GENETIC INFORMATION: ITS SIGNIFICANCE FOR PATIENTS, HEALTH PROFESSIONALS, ETHICS, AND POLICY DEVELOPMENT

CHAIRMAN PELLEGRINO:  Our next topic will be on genetic information.  And we have the opportunity and the pleasure to hear from Dr. Nancy Wexler, who is Professor of Clinical Psychology at Columbia University.

I told her and for the benefit of those of you who haven't been here before, we do not provide extensive autobiographies.  The people who come here are distinguished by their very presence and by their titles.  And so we find it unnecessary and gilding the lily to go into the rest of it.  I hope that's a good excuse for not going into it.  Dr. Wexler, will you please take over?  We're at your service.

DR. WEXLER:  I am honored to speak here today and delighted that the President's Council is taking on the serious challenge both of newborn screening and potentially genetic testing in general.  This is a critical area in which we need to tread cautiously and with your advice.  I give you my biases right up front.  What we do today will have repercussions for many years to come.

I also appreciate your willingness to consider broadening your mandate to include genetic information and knowledge, whether obtained before or after birth in terms of its existential significance for individuals, families, society at large, its implications for policy, particularly insurance and employment.

I was asked to answer some specific questions in Dr. Davis' letter, which I will address somewhat throughout the presentation and come back to at the end.  Particularly I was asked to look at the question posed by Dr. Alexander and colleagues at your last meeting, whether the so-called dogma governing newborn screening — that is, not to screen unless you have a treatment, an effective treatment — should be discarded.  And I was also asked to really focus on the impact of the completion of the Human Genome Project.

The completion of the Human Genome Project I believe has placed us in a hitherto almost unimagined era of possibility, responsibility, and liability.  There will certainly be affordable gene chips, customized gene chips, beads, micro array technology, and genetic technologies which we have not yet fathomed, even nanotechnologies.  So I think that fits with one of your other topics.  We need to be ready for these advances.

In the light of public acknowledgement of my own biases, I would like to also say that my grandfather, two uncles, and mother died of Huntington's disease.  And my family has been very invested and involved in trying to find a cure for this particular disorder.  So I would like to use some of the experiences from our Huntington's world to address some of these issues specifically.

In 1968 — I would like to actually talk about finding the gene and how that reflects on where we are now with respect to the human genome and the future.

In 1968, my father began the Hereditary Disease Foundation when my mother was diagnosed.  We held small interdisciplinary workshops because at that point no one was really interested in looking at this tiny disorder.

In October 1979, 27 years from next month, we had a workshop entitled "Can You Use DNA Markers to Find the Huntington's Disease Gene?"  This was organized by David Housman of M.I.T.  The workshop included Ray White and David Botstein at the very beginning of their careers.  If you can imagine, remember back to that time.  There was nothing yet published about using DNA markers to find human diseases, that you could even find a marker.

We were talking about whether this was method or madness.  There were heated arguments, scribbles of calculations on the board, how many postdoc years it would actually take to even consider mapping the human genome.  And David Housman said he had a very talented graduate student named Jim Gusella and we should do it in Gusella years.

Now, at that point, there was a ferocious argument about whether or not we should actually look for the HD gene or wait until the human genome was finished.  Ray White and David Botstein felt strongly that the whole human genome had to be mapped first before we could look for a marker segregating with the HD gene.  They felt, in fact, it was unethical to do it any other way because we were over-promising.  That's how far away.  It had taken Ray about two years to find the first marker.

David Housman, on the other hand, said, "Look, why don't you look for markers segregating in a family?  Maybe you will get lucky.  You won't have to wait until the entire genome is mapped.  You'll be ahead of the game.  And every time you find a new marker, run it through a family."

In fact, David Housman encouraged me.  I had already been in Venezuela in a small study.  He encouraged me to go to Venezuela to study what turned out to be the largest kindred known anywhere with Huntington's disease to look for a marker segregating with the HD gene.

In 1981, I began traveling to Venezuela, which, unfortunately, still has many families living in the most unbelievable poverty, to collect pedigree information, clinical data, and DNA.

Astonishingly — this was in 1981 we started — in 1983, together with David Housman, Jim Gusella, Mike Conneally, we actually discovered a DNA marker which was 4 million base pairs beneath the Huntington's disease gene on the top of chromosome 4.

The jubilation and elation — you can remember that, Paul, right?  Remember that?  Nobody could believe that.  It was just shocking.  So the jubilation and elation were not only for Huntington's, which is an appalling disorder, but really that this was a proof of principle that you could use these strategies to find any genes, deleterious or not.

The Hereditary Disease Foundation then organized a collaboration of many of the early pioneers of the genetics world to go from this linked marker to actually finding the gene because without the gene, we still were sort of in Never Never Land.

David Housman; Jim Gusella; Francis Collins; Hans Lehrach; the late John Wasmuth; Peter Harper; Robert Horvitz, Nobel Prize winner; and many talented postdocs and graduate students worked for a decade of really arduous work to isolate the gene itself.

Its abnormality turns out to be an expansion of a CAG repeat that makes too much of the amino acid glutamine in the protein called "huntingtin."  When the research began, looking for the gene, the equipment — if you went to anybody's lab at that time, the equipment were these gel boxes literally put together with massive giant clips like that, paper towels, jolts of electricity, and radioactivity.  The thing just looked like a death trap.

And at that time, there was no PCR.  And the first gene-sequencing machine had just been discovered, which was almost like a kind of aesthetic work of art.  That's the technology 27 years ago, not that long ago.

So when the genome project began in earnest in 1990, it required innovative technology in order to succeed.  It also necessitated worldwide collaborations, cooperation in both public and private sectors, informatics previously unheard of, an unknown scale.  And, astonishingly, the project came in ahead of schedule and under budget, which astonishes everybody.

So as soon as the genome was finished, all the same groups got together to set up a HapMaps project to look at human variability.  So an example of the genetics of the future is now at the Broad Institute Center for Genotyping and Analysis at M.I.T. and Harvard.

The Broad Institute has brand new sequencing capability.  In a matter of weeks, you can put your DNA in.  They have new chips with 100,000 SNPs, which are sort of the RFLPs of today.  And the difference is shocking between where we started and what the capability is now.

So let me say a word again about some of the advances in HD to just talk about what is happening now, not only for Huntington's but many other different diseases.

In 1983, when we isolated the gene, we observed that the size of the expansion correlates extremely closely with the age of onset.  We also learned that the larger the repeat, the earlier the age of onset.  If you have about 40 repeats, the disease is fully penetrant.

If you live a normal life span, this disease will inevitably appear and is invariably fatal, over a course of 10 to 20 grueling years of loss of physical and mental capacities.  Uncontrollable movements envelop the body.  Cognition is profoundly impaired.  Severe psychiatric problems, such as depression, suicide, even hallucinations and delusions, appear.

The typical age of onset is the 30s or 40s, but the disease can appear as early as 2 and as late as 80.  If a person inherits a CAG size of 60, the disease starts at 12 or younger.

So once we had discovered the HD gene, we learned, much to our surprise, that some people with repeats between 35 and 39 may or may not get sick.  Sometimes they do.  Sometimes they don't.  But those people invariably give rise to new mutations.  When you pass on the gene from generation to generation, it expands, particularly in sperm.  Why this happens we don't know.

Huntington's is one of the most fully genetically determinant diseases known.  If you carry an expanded repeat of a certain size, you will get sick and die.  And, yet, there is this tremendous variability in when the disease appears, from 2 to 80.

So we were very interested to see whether or not there were modifiers that affect when the disease shows up because these could also be therapeutic targets pushing the disease out of the life span.

We went back to our Venezuelan data and started looking very closely at different families.  We found that in certain families who had 44 repeats, they had an onset in their 20s.  Other families with 44 repeats had an onset in their 50s, same repeats.  So obviously there was something else besides repeats.

We took the DNA.  We took this information.  We sent it off to the Broad Center.  And just a couple of weeks ago, after less than a month — the Broad Center sends you back all of this data.  And we have clear evidence of the presence of modifying genes which influence the age of onset of Huntington's.

The analysis points to certain regions on chromosomes as hot spots, which most likely contain modifying genes.  And, even more amazing, we can dial up the computer and actually look at the area in the chromosome and say, "Well, what genes should we pay attention to?"; which is astonishing.

I mean, when you start out in 1979 thinking that there's no way you're going to actually find this gene and you're dialing up to say, "Hey, can you just get that little tip of the chromosome a little bigger because that's the gene that's causing it to be starting at 2 or starting at 80?", that's shocking.  I mean, that is so mind-boggling that it's almost beyond comprehension how fast this field is moving.

Now, it's entirely thanks to the Human Genome Project that we're in this happy position.  And if Huntington's can be unraveled in the same way, if the rate of change is happening so rapidly, there's no doubt about what we can anticipate in the future.

Whatever our wild imagination about what could happen, it is going to happen.  And if we stop until it happens, we are going to be totally missing the boat.  We are going to be in serious, serious trouble.

I mean, if you walk down in the Broad Institute now, in the old labs where we were doing the work, you think you're on a different planet.  The driving motivator behind the Human Genome Project was to look for new diagnostics, treatments and cures for human disorders.  And that push is the same for technological advances in genetic diagnostics.

So I think we can assume that future tests will be DNA-based and accurate.  That was one of the questions posed to me.  I think we can posit that the same drivers that forced the cost of sequencing to tumble sufficiently to make large-scale sequencing feasible will also be dramatically lower, will lower the cost for accurate diagnostic testing, making it possible, not only throughout the states but probably throughout the world, to take advantage of these new technological advances.

The world, which welcomed the completion of the Human Genome Project, will certainly welcome its increasing medical relevance.  In my opinion, we are woefully unprepared as a society to deal with these changes.

The challenges span the range of issues from scientific to social to ethical.  Unless we prepare now, we won't be ready to take advantage of the benefits of technological advances.  We are like a freight train on a collision course with our future.

Let me try to get at some of these examples.  Certainly there's a huge amount of variability when you actually start looking at any of these diseases.  They're much more variable than you thought, even with Huntington's.  It turns out to have another disease, looks exactly like it, called HDL2, which is present in Africa and African Americans, another chromosome entirely.

So I always recommend that somebody get two genetic tests.  Everybody yells at me and says, "Oh, no."  You know, they're impugning the labs if you actually say, "Get one blood test and send it to this lab and another blood test, send it to that lab and make sure you get the same result because the importance of the data is much, much, much too critical."

One of the other problems we really have also is how the results are described and interpreted.  So with Huntington's, if you have an expansion at the DNA level, that can be picked up if you have newborn screening.  It's exactly the same when you have an embryo as when you have somebody that is actually diagnosed.

When people are given their diagnostic information, it's usually extremely unclear.  They say to somebody who is in their 30s, "You have been diagnosed with Huntington's disease," meaning that when they looked at the DNA, they found an expanded repeat but not that the person clinically had symptoms.  And so there is a huge amount of just lack of clarity and necessity for education about what actually these diagnostic terms mean.

The Human Genome Project is providing us with an opportunity to have personalized medicine.  I think that's one of the benefits of the information gained, but for me we're not ready to take advantage of these discoveries.

My personal view of personalized medicine is rather idiosyncratic.  I think that we look at each disease in an individualistic way as if the disease itself is a person.  In other words, the disease has its own personality based on symptoms, prognosis, treatment, or lack thereof, age of onset, and other characteristics.  And each individual in society is also distinctive.

Let me again use Huntington's as an example.  We know precisely the nature of the molecular mistake.  We have an accurate test, could be given at any time from conception to death.  Where do we stand clinically?  We are actually no different now than when my mother was diagnosed almost four years ago.  We have better medicines to treat the psychiatric aspects but really not very much else.

Tetrabenazine, which is the drug of choice, used for chorea for 40 years and Europe and elsewhere, has not yet been licensed by the FDA.  And we don't know whether it is going to be.  So there's nothing now to prevent, retard, or cure the disease, only the most meager symptomatic relief.

We are not really that different from when George Huntington described the disease in the 1800s.  So we need a tremendous amount more research, funding at every level, particularly at the NIH level, where it is being cut, which has the magnitude to make a difference, to develop new treatments and cures.

But having the gene in hand, you know, certainly has changed research.  We have in vitro systems, in vivo systems.  But, really, we don't know when any kind of really therapeutic breakthrough is going to happen.

And so what do patients and families do in the meantime while science is working hard at a slow, unpredictable pace?  For families, the experience of the expanded repeat means definite inexorable death.

When we discovered the HD marker in 1983, families and health professionals alike realized that we needed guidelines to help define how the test should be given.

I was part of a committee to develop guidelines formed by the major international organizations of families at the International HD Association and the major scientific group, the World Federation of Neurology.

We published a series of guidelines.  And it had to be revised slightly when the gene was found.  In fact, I think that the latest guideline publication is at your table.  We sent it around.  That was published in Neurology in 1994.

We realized that we were in a unique, unprecedented situation.  The HD DNA marker test could accurately diagnose, both pre-symptomatically and prenatally, the appearance of a disease decades before its onset, a disease which inexorably ravages body and mind.

Some even suggested we shouldn't give the test until there was a treatment, but others felt that it would be helpful to have it in order to help people, particularly for family planning and to resolve ambiguity.

The guidelines explicitly reject the notion of including Huntington's as part of newborn screening.  The guideline states, "The test is available only to individuals who have reached the age of maturity according to the laws of their respective country."

The committees and family professional groups adopting the guideline felt strongly that the choice to take the test should be only made when the person has the capacity to fully understand all of the ramifications and implications of the knowledge on his or her life.  For an individual to be tested prior to the age of majority was an invasion into the privacy of the child.  It violated the child's confidentiality and was not acceptable.

A related guideline states, "The decision to take the test is solely the choice of the individual concerned.  No requests from third parties, family members, or otherwise will be considered.  The individuals must freely choose whether to be tested and must not be coerced by family, friends, partners, or potential partners, physicians, insurance companies, employers, government, or others.

"Testing for adoption purposes will also not be permitted since the child to be adopted cannot decide for his or her self whether to be tested.  The privacy of children is an area as crucial as the confidentiality of adults with respect to insurance and employment."

So the committee felt that by the time you were 18, you were able to make some of these informed choices and to understand the tremendously serious repercussions that this information can have.  You cannot take back information once it's revealed.

What has been the experience of some of these people who actually have been tested?  So let me read a couple of excerpts from some of the people who have actually gone through testing.  And then I want to address some of the specific questions, and we'll stop.

"When you ask what it is like to be tested, you can prepare for testing cognitively.  You can have a support person that you talk to for 23 out of the 24 hours each day.  And that's the only thing you think about.

"You go to counseling to get prepared for testing.  And that can go smoothly.  And you think you have all of your ducks in a row.  But when you are delivered that information, you know, you have to remember to breathe again.  And then you have to figure out how to go on.  And for me, it was extremely difficult to assimilate that information while the world continues to go on.

"Initially I was prepared that this would be very difficult should I receive the results I was positive.  So my husband and I anticipated that I might need a period of time where I'm not accountable.  We would play it by ear.

"We cognitively prepared for that.  What we couldn't prepare for, though, was that the weight of that would be so grave.  So I think for a period, I was going through the motions and had my ducks in a row, but it was a huge struggle.  I was trying to put on a good front for my daughter.

"I thought it was a personal decision for me to get tested.  I largely did it for me, but an awful lot was done for my family, what I could offer.  I was hoping to say to my ten-year-old daughter, 'Sweetheart, you don't have to worry.  We're going to end this right here,' but I didn't choose to tell her I was getting tested.  We had all kinds of scenes about where I was going and why I would be away.  That wore down my energy keeping up a front for my daughter.

"I came home, trying to be a happy, normal mother so my daughter wouldn't worry, which is my big fear from childhood.  I didn't want my child ever taking care of me and having to do what I did for my own mother.  I didn't want her to deal with Huntington's.  I didn't want her to give up her childhood or early adulthood for me.  I wanted to spare her that grief.

"It was quite dysfunctional in my family after we had been such an open unit not to talk about it, very honest before.  So, of course, that didn't work.  One day she held me hostage and said to me, 'I know something is wrong.  Are you getting divorced?  Are you dying?  Is Grandma dying?  Don't you love me anymore?'

"I mean, it was horrible.  So I thought 'It's obvious I needed to tell her what had happened.'  I had been tested, and my results were positive.  I wasn't really prepared for that conversation either, but it was a relief.

"At that point, I had no choice but just to give up my life for six weeks and do nothing.  I didn't get paid for six weeks.  We relied on my income entirely.  My husband worked three jobs, did laundry, cooked dinner.  I walked the dog, went to the beach, and went to therapy three times a week.  I did nothing else.  And it was an accomplishment just to get up and walk the dog on the beach.  That's all I did for six weeks because that is all I could do. And cry.

"I felt that part of me completely vanished and that I had died.  I was stuck in my dead body to figure out how to pick up the pieces and go on because it wasn't over, but a large part of me was.

"I really thought after living in the dysfunctional household that I had grown up in, that I had pulled myself up by my bootstraps.  It was high time for me to live the way I wanted to live.

"I put myself through school.  I moved away.  I was on my road.  I was marching to my parade.  And, you know, the conductor stopped.  I really thought I worked very, very hard to offer myself and my daughter a life we deserved to live.  And now we were challenged with something that was much, much, much more devastating than I could possibly ever imagine.

"I knew whether I was gene-positive or gene-negative, it wasn't going to be over.  If I were gene-positive, in terms of my aspirations and my future, what I would do with my family, that would be terrible.  But if I received the information that I was gene-negative, it certainly would not be over either.

"I was scared of being gene-negative, too, because I know what it is like to have to take care of my mother.  So how much more would be expected of me to be even more strong?

"So I think there is no good news for this testing.  I don't think it's for everyone, but I think truly if you need to know, there are no two ways about it.  One must know.  And I don't regret that."

I asked her if she ever wished she hadn't pursued it.  She said, "No, never."

I said, "Would you ever like to take it back?"

She said, "Maybe that.  I was as very, very prepared, as possibly you could be.  I mean, years of being at different functions, having a lot of information, all the information possible in making a choice.  And still at the point when the information was real, it was painful.  It was deep.  It was almost like a death but not yet totally.  It was like a loss, a really big loss, of dreams."

The opportunity to do prenatal testing has been extraordinarily beneficial, a unique outcome of having the HD gene in hand, even though no new treatments have been forthcoming.

There are several options for prenatal testing through amniocentesis, chorionic villus sampling, or also through pre-implantation genetic diagnosis, PGD.  This procedure, as you know, involves selecting a single cell from an embryo at approximately the eight-cell stage.  PGD permits a critically important variant on prenatal testing, which is very appealing to many HD families, called non-disclosing PGD.

Many at-risk individuals don't want to know their own genotype, but they also don't want to pass on this horrific illness to the next generation.

Non-disclosing PGD provides an excellent solution to the dilemma.  People at risk for Huntington's have embryos.  They're guaranteed to be having a normal size allele implanted without knowing the genotypes either of the embryos or themselves.  This means that the IVF physicians performing the services are instructed not to say how many embryos there are since that could give it away.

One woman was also diagnosed inadvertently by a lab tech doing the sonogram who said to her, "Gee, isn't it good that your expanded repeat isn't so big?"  She was doing non-disclosing.  She didn't want to know her genotype.

With all the advantages that PGD can provide, there are some external disadvantages that must be overcome.  IVF is required for PGD, and IVF is still expensive and not covered by insurance, even if it's being utilized to avoid a lethal disease.

Privacy is a critical issue for HD families as well as families affected by other genetic diseases.  Health insurance, disability insurance, life insurance, people suffering from or even at risk from Huntington's are, in the words of the insurance industry, considered uninsurable unless they're part of a large group.

There is a Medical Information Bureau in Boston, which is a bank, which keeps a lot of health information.  And people have been denied insurance by having somebody in the family with Huntington's linked in the database and denied.

One of the problems about having these guidelines is that they are just guidelines and there is no way, really, to enforce them.  Who is to be the gatekeeper and enforcer?

The clinicians should know about the guidelines, but they don't.  The laboratories had been actually very helpful to enforce the guidelines, but they were chastised because they were losing money because they were not accepting certain samples.  So, really, one of the problems, even if you have beautiful guidelines, is who is actually going to enforce them?

Another problem is that the people's motivation to be tested is so great that sometimes they want to take the test but they do it anonymously.  And there is a protocol for being able to be tested anonymously.  If you just give a false name, sometimes the center will call up a telephone number.  And, all of a sudden, the anonymity is suddenly violated.

In one instance, a woman who was the sole support of her young son went to a general practitioner to get tested because the general practitioners haven't a clue about guidelines and just said, you know, "Test me for Huntington's disease."

When the results came back, she called me up in a panic.  And she said, "The doctor said to me, 'You have two als.  One is big.  One is little.  I don't know what this means.  Call for help."

What do you mean two als?  Well, an al was an allele.  And it turned out she had an expanded allele, but the GP didn't have a clue what that was.  And I had to tell her over the phone that she was going to get Huntington's in the future.  And I didn't know her name, and there wasn't any possibility of follow-up.  And doing that over the phone is a definite violation of any guideline.

Another problem, even in the best of circumstances, part of the guideline is to have a clinical examination, a neurological examination.  My cousin had two growing-up children, had two children who were in their teens.  She decided that she wanted to get tested just to clarify the risk for her children.  Left to her own devices, she wouldn't have gotten tested.  So I call her sort of the altruistic testee.

When she went to the center, part of this evaluation is the neurological exam.  They said, "No, you won't get feedback.  That's not part of the guideline."

She went on her own.  The neurologist took one look at her and said, "Why are you bothering to pay for a DNA test?  You obviously have clinical Huntington's disease.  Go home.  And don't see me."

After a year, she decided maybe she wo