What are the forces that are promoting and championing xenotransplantation?
Is there an element of hype involved in that?
Xenotransplantation is very dramatic. Not only are we taking an organ from an
animal, but we're saving a life. There are thousands of people on waiting
lists who will die without organ transplants. There are many researchers who
stand to benefit enormously from the breakthroughs that come here, not just in
terms of their honest interest in saving lives, but from the career and
prestige that comes from it, and now the huge amounts of money that will come
from this new industry. So there are a lot of vested interests interested in
showing that this technology has to move forward without obstacles. . . .
What about the mix of desperate patients, ambitious doctors who are willing
and wanting to help them, scientists who are stakeholders in ways, and drug
companies willing to fund them? What does that mix produce?
There's an explosive mix of people who are interested in promoting this
technology as well as others. We always see a desperate group of patients who
will die without some breakthrough. It could be cancer or it could be
something else, and a new technology down the road promises solutions.
Corporations are now heavily invested in promoting those technologies -- it
could be big pharmaceutical companies, it could be bioengineering companies --
and researchers who find themselves invested heavily in the technologies that
they are trying to promote.
This mix does not produce caution. . . . It produces a situation in which it's
very easy to forego caution. It's very easy to say that anybody who wants to
think twice about the rate at which we're proceeding and the process we go
through in order to proceed is simply sacrificing lives. And we hear that
message, that anybody who raises a question has lives on his hands.
That seems to me to be an unfair point, because one of the points being made
about xenotransplantation is that there are risks to third parties that have to
be evaluated. And those lives are also worth something.
What do you see as the key ethical issues being raised by
Let's start with issues that are distinctive for xenotransplantation. The one
that we've heard the most about internationally is the potential risk to third
parties. Of course, this is on the public's mind. Not only do we now know
that HIV was transmitted to people through a variation of an agent that came
from animals, but we're hearing all about Europe and mad cow disease and its
effect on people and on industry. The idea that we can become infected from
agents that come from animals is, to some extent, in the public mind.
What we now see as distinctive is that most medical research and most medical
treatment involves a tradeoff of risks and benefits. There are risks and
benefits to the same person -- the patient -- and the whole focus of medical
ethics has been on drawing attention to that, and providing informed consent to
Xenotransplantation has a different component. The benefits and risks are
again to a patient. But there is now a set of risks to third parties who are
not any part of the agreement between the doctor and the patient when an organ
is transplanted. It's the third-party risk that is distinctive about
What's the big fearful concern about what might happen?
The fear is that some virus that might be carried inside pig tissues will turn
out to be very dangerous to people when their immune systems are compromised,
as they often are in transplant settings. These viruses can transform
themselves when they cross species barriers. An agent that's not dangerous to
a pig may turn out to be very dangerous to people. A new agent may evolve
through combination between the material that's in the human and what was in
the pig, and it's the combination that may be distinctive and dangerous.
So if there is this risk, how do we quantify it?
The risk to third parties is something that we can't quantify at this point.
That, of course, means that some people want to dismiss it. Other people say
it's miniscule. But how small it really is isn't something we can put a number
on. And the stakes might be very high. For example, viruses that cross animal
boundaries that are not dangerous to their hosts are often deadly to other
animals when they do cross the boundaries.
We can't quantify the probabilities here, or the overall magnitude of the
payoff and the risk. But there is an enormous uncertainty. And what we have
to deal with is the fact of uncertainty.
A circle of experts who are highly engaged and involved in the research are
saying, basically, on some level, "Leave it to us. We know what we're doing.
Trust us. It is a tiny, tiny risk we're talking about."
My inclination is to believe experts, as many people would, because they do
know more about these things than we do. But that isn't really the issue. In
a medical setting, we have emphasized the importance of informed consent.
Patients don't know as much as their doctors, but they must give informed
consent to whatever procedures they go through. We've had a revolution in our
understanding of the power relationship between doctors and patients. And the
main weapon that's been used is to try to emphasize the importance of informed
But what is the consent here of the public to the will of the experts? There
has to be an adequate mechanism in place through which third parties can
consent to the kinds of risks that this procedure might impose. . . .
So is that mechanism in place? Who do we trust? Who will be making this
There is a set of guidelines that the FDA has announced, and many of the
features that you'd want to pay attention to are singled out in those
guidelines. Emphasis is placed on the importance of informed consent. But
there are a lot of loose ends to this problem that are not adequately addressed
in guidelines. . . .
Let's take the standard research protocols. Suppose somebody undergoes a
research experiment, and they know that they will be monitored over some short
period of time, usually for the effects of the experimental regimen that was
introduced. That person can later say, "I don't want to go through this
anymore. I've given enough blood, and I don't want to be tested anymore."
There's no risk to a third party in that person backing out of the experiment.
The person will simply reduce their value to the experimenter in producing the
information needed. That's the only risk.
But if somebody who's undergone a clinical trial, an experiment of an organ
such as this is now being asked to be monitored for years, and to inform the
researcher of all sexual partners or changes in sexual partners. We're
beginning to see a new level of intrusiveness in monitoring that we don't find
in any other setting. And we have no way to enforce agreements that people
made at the moment at which they undertook to get the organ.
Is there a simple way around that in xeno? Will it be a matter of a year or
two before we know that long-term monitoring is not going to come into
I'm not a scientist who can answer that question. But my perception is that we
can't know that there's no risk except over a period of years. Most of the
understanding of the research protocols calls for monitoring people over a
period of years. The reason for that is that the process through which viruses
could recombine within people might take a period of time. An agent that is
transmitted by an organ to a patient may take a while before some particular
recombination emerges from it that is dangerous, and we would have to find
that. We have no way to test in advance for what it is.
. . . What about the patients who are desperate at that moment for a cell
transplant or an organ transplant, and who say, "Yes, happily. I'm signing on.
Do you want my brain afterward? I'll give you that, too." How do you relate
that to what you just said, and to the situation that those patients find
A patient who would die without an organ is going to be desperate to undergo
some way of saving herself. . . . A patient like that poses what's often the
hardest case for informed consent. Not that it's irrational to take risks when
you have nothing to lose -- it isn't irrational. But we do want some
reassurance that a patient is well informed about what the risks are.
And here we have to give people enormous uncertainty as an answer. We can't
say that we know exactly what the risks are. . . . This is a research context.
We have to say to somebody, "Look, there may be a risk to you of getting a
disease that we've never encountered before. There may be a risk to your
family of encountering this disease. Now, would you like to save your life?
Of course, we can't tell you it's going to work. We only have results in
So now this is a very complicated problem for a patient. It's not just the
benefits and risks to the patient; it's the benefits and risks to the people
that that patient loves.
Is it reasonable for us to make those demands on a patient; to say, "We want
to monitor you for life, and by the way, in death, too, we need a few parts
back from you"?
It seemed quite reasonable to ask people for this kind of commitment, under the
conditions that we're operating. . . . We can't forget the promise in worrying
about the risks. The promise is that we will save many, many lives. There is
a public benefit that can result from this, and that is the driving force in
most people's minds.
Yet, we have to be cautious, and we do have to ask patients for a commitment on
this part. We have no way, however, and no institutional mechanisms and no
legal framework for enforcing those agreements that people make in the moment
of desperation. And that is of grave concern.
Let's go back to this other idea you mentioned before about third parties,
which in some sense, we tend to describe in terms of public health. If there's
a potential public health risk, who should be weighing and making the decisions
about whether to take it or not?
Let's suppose for a moment that there's a public health risk. We don't know
how to quantify it. This is a decision that the public has to undertake. And
my view is that this has to be through a fairly elaborate process that involves
a broad range of stakeholders in the decision. Not only the experts, who
obviously have to be involved, and the clinicians that are anxious to save
their patients, but representatives of a broader group of the public have to
participate in this. And the mechanism has got to be a broad one that engages
in education of the public over time.
Otherwise, we risk a harm that we haven't talked about yet -- the harm that, if
it turns out these are dangerous procedures, people who have been undergone
them may become stigmatized, may be viewed as Typhoid Mary, and will be the
object of enormous concern by the public. The people who did the procedures
will build public fears of new technologies. It seems very important to have a
process in place that undertakes a careful evaluation of the risk and gives the
public some broader way to consent to that risk, rather than simply leave it in
the hands of a narrow group of experts.
And what do you say to that transplant surgeon who says, "Look, process it
all you want. Debate it forever. Just remember, every seven minutes I've got
somebody dying here who could benefit from this thing." What do you
A lot of that is, after all, just promise. They don't have procedures now that
will save patients who are dying every seven minutes. They're hoping to
develop those procedures. And I don't think we should get stampeded in
ignoring what may be a public risk simply because there are people in need. We
probably could save many more lives than the lives of these patients through
other procedures we could follow in a public health domain, and nobody talks
about the risks to those patients here and abroad. We get caught in a kind of
avalanche of emotion to save this particular group of patients, when in fact
there are probably many things we could do to save larger groups of patients if
we attended to them.
So I don't think we should be so driven by the worry of these transplant
surgeons who are looking at patients facing death every day. Yes, there are
patients facing death every day, but there are many people facing death every
day. We all face death some time or other. And the issue is, how do we
evaluate the best ways to use a new technology, and are we being adequate in
our consideration of the risks?
Why broach these issues now? As you say, they haven't even technically
gotten to the point where they can show it works.
This is exactly the point at which we have to raise these questions -- before
we know it works. We can't know it works without running clinical trials on
people, without putting organs into people. We can do a lot of animal research
that will help pave the way, making those procedures on humans more safe, and
the risks better understood. But we can't get away without trying this on
And so what's needed is a public process that's well in place ahead of time.
What we don't want is to face is a particular patient on television saying, "I
will die tomorrow unless you let me have this organ tomorrow," and you haven't
thought about what the risks are to third parties. We have to think about it
now, before we have something that works.
You said we could be stampeded. But I'm wondering, in this era of awareness
of AIDS and mad cow disease, where is society's trust now with scientists when
they bring us an exciting and promising new technology like xenotransplantation
and say, "We're on the cusp. This could change things?"
I am not somebody who is skeptical about technology and the advances it can
bring, because all of us who are of my age have seen a revolution in what
medicine does, just within our adult lives. On the other hand, it's very
important to understand that the health of the public, the health of a whole
population, is not primarily the result of what medicine does for us. It's
primarily the result of a lot of social structures in the society and broader
public health measures. And yet we believe that it's the next magic bullet
that is going to suddenly revolutionize our lives. That isn't the main thing
that's contributed to our health and the longevity that we now see around
So we have to take with a grain of caution the concerns that are advanced when
experts say we are going to change the way the public lives. . . .
On what basis should the public decide to take this risk or not?
The public has to have a process in place that lets them understand the risks
to family members, to relatives, to sexual partners, and to the public at
large. And the public has to have an opportunity to play a role in designing
the institutional responses to those risks. When that's done, the public may
be very happy to take certain risks. We take risks all the time. We go
skiing, we take risks; we drive a car and we take risks. Life is full of
risks. The issue here is not how to live in a risk-free environment. The
issue is, how do you come to grips with the risks and have a sense that you are
somewhat in control of the risks you're taking?
It's fundamentally important that the public feel that it's controlling the
risks, and the risks are ones that it has considered. If the risks are risks
that other people are imposing on the public, then we get an exaggerated
response to the level of risk. Most of the cases in which the public has risen
up with an uproar against risks that they perceive have been because of the
lack of control of those risks. Genetically modified food is one example. Not
that there aren't risks that have to be considered, but the public feels it had
no control in the process.
Isn't it a fairly new kind of question, when we're talking about . . . the
possibility of public health risks from a major virus being introduced by
humans into the greater population?
It's common now, in public health discussions, to comment on the early death of
what we had taken to be the end of the era of infectious disease. We now see
that, on a global scale, we are not free of infectious diseases. There are
new kinds of resistance emerging in various very prominent diseases. And a
new agent, like HIV virus, that has created one of the worst epidemics we have
ever seen in the world is very much on people's minds.
The fear that we could accidentally create something of comparable stature is a
fear that has to be dealt with. It may be that it's an exaggerated fear. But
how do we know it's exaggerated until there's been a reasonable public
discussion? Simply listening to an expert say, "This can't happen," is to
repeat what we've seen throughout the century, where experts are often wrong
about things that they claim to know the most about. ...
Why, then, call for a moratorium?
The call for a moratorium was primarily a call to put a certain kind of public
process in place, and not to risk letting the cow out of the barn without
adequate caution. . . . My concern is that we could set back a useful and
valuable technology if we don't manage public perception of the risk properly.
And that management of the public perception carries an ethical requirement
that we give the public an opportunity to consent to that risk.
The call for a moratorium is a call to put into place the mechanisms that give
the public an opportunity to consent. This is the fundamental ethical issue
that is distinctive about xenotransplants.
What are the other ethical decisions here? What's the most controversial
aspect of xenotransplantation? Is it the queasiness people feel about the
unnaturalness of animal organs going into people? What's at stake here?
I don't think that's a huge problem. I don't think the problem of the fact
that we're using animal parts in people is something that people really feel
terribly about. We've been using valve parts for many, many years, and people
who've had pig valves in their hearts don't think that they've become pigs as a
result. I don't think people will be anything but grateful for the sacrifice
that the animal made for them. I don't think those are the central issues.
The central issue here is the ability for people to give appropriate kinds of
consent. And there are other important ethical issues, in addition to the
issue about consent. For example, how could we describe the benefits to people
and describe what counts as a success?
Suppose that pig hearts or pig livers only live for a short period of time in
people -- two or three years, or four years. Now, that's significant to
somebody who's dying. But if the technology only offered that prospect of
success -- because, for example, pig organs are programmed to live in an animal
that doesn't have a human life span, then perhaps we will find that we've now
using a technology that requires people to go through spark plug changes every
six months for three or four years. Not only are the costs phenomenal, but the
quality of life sacrifices are huge. And we will then be caught in a situation
where we have not evaluated what counts as success. So one of the important
pieces of research that has to be done here, and conceptualizing of the
problem, is to characterize what success is in this situation.
Is this organ transplanting the same as we're accustomed to thinking of, or
is this going to a different kind of mode -- where companies are developing a
product that they'll be able to shift onto man? How is it fundamentally
There's a fundamental difference between the kind of human giving that has been
a central component of the ethical framework around organ transplantation -- a
gift of life given by one dying person or their family members to another who
might then live. This has framed the whole problem of organ transplantation,
and it's very dramatic, and we think of it as a wonderful move that somebody
can make. There was a child who was killed in Italy, and his organs saved
seven people, and that family is now revered in Italy.
If we now shift to a new mode, we have benefits and perhaps a little bit of the
loss of the sense of giving. The benefit is obvious. We are now not dependent
on people being willing to give their organs. We have a commodity that we can
buy. And that's, in fact, probably a benefit overall, because it will mean
many more lives are saved. It's more important, perhaps, than the issue about
the donation of the life.
Is it also different that the people who are championing this stand are now
at the heads of biotech companies and stand to prosper from it?
It's very important to understand that there are features of the
xenotransplantation environment that are shared with many other areas of
medical research. There's a set of ethical issues here that are not
distinctive to xenotransplantation, but are common to many areas of new
research. We have large industries being started around new technologies, with
billions of dollars ultimately at stake, and huge rewards to the people who
found companies . . . that promote advance for people.
Is there a worry that the scientists who are most expert in this are not
just going for career fame, but are also going for fortune now, and in a big
It's certainly true that many scientists who are engaged in this piece of
research around xenotransplantation could make fortunes through their
investments or founding relationships to companies that stand to benefit from
this technology. But this is not a distinctive feature of xenotransplantation.
This is now the emerging feature surrounding all of biotechnology. And it's
not less of an ethical problem because it's not distinctive. In fact, it's a
fundamental problem facing the whole of technology in this world.
We're not used to dealing with the kinds of conflict of interest that will be
perceived to be present in this situation. What do we say when a researcher
who is now also a company owner and who stands to make tens or hundreds of
millions of dollars from a new technology, says, "Join my protocol; be a
research subject. I'm just interested in the generation of knowledge and in
saving lives." We can't . . . accept that fully at face value, even with
disclosure. We have to have a new understanding of how to address this
How do you balance that enthusiasm? Certainly in a program like this, you
hear from both the patients who are expressing need and doctors who are very
enthusiastic about each next step being taken. What is the voice tempering
There has to be public understanding of the benefits and risks of new
technologies. And we have to undercut a bit the infatuation that the public
has with new technologies -- an infatuation cultivated extensively by the media
and by the vested interests that stand to benefit from these technologies. . .
Part of the reason that these drug companies let in documentary filmmakers
to look at the process is that they hope to influence public perception. What
are the things to keep in mind?
We see a very interesting contradiction. After all, we're in an era of
direct-to-consumer advertising of drugs, and we see these drugs being pushed on
television and in newspapers and other media all the time. So clearly,
institutions like large pharmaceutical companies and bioengineering companies
know that public interest in an issue is a valuable commodity, if they can
shape it the right way. At the same time, there's an enormous fear that the
public will not understand the benefits that are being offered, and will react
in irrational ways that exaggerate risks.
So, on the one hand, we have companies that are trying to make people
enthusiastic about things that might benefit them, whether or not they are
really that important. And on the other hand, they shy away from having a
clear discussion of what the risks are, because they fear the public will be
irrational in the way it grasps risks. There's a kind of contradiction in
that. You want to trust the public to buy your products, but you don't want to
trust the public to make decisions about what's risky to them.
What do you think is motivating a company like Novartis to get involved in
Most large companies are motivated by two things. Many people in those
companies want to save lives and produce a benefit for a public. At the same
time, they have a responsibility to their shareholders to generate a profit.
And those two concerns have to interact within any corporation that is dealing
with medical benefits for people. And sometimes, the corporate considerations
clearly outweigh concerns about human welfare, which is why we have to take
government actions and have orphan drug laws and other ways of trying to
subsidize things that won't actually be profitable for particular companies.
Is this a patented product? How will the economics of this work?
It may well be possible to patent some of the components of these procedures.
And there may well be proprietary gains for companies. Companies wouldn't be
investing in this unless there was a way to exclude competitors from what
they're doing research in.
So my guess is that, down the road is probably a multibillion dollar industry
built around harvesting animal parts and selling them as commodities on a
medical market, where there will be considerable demand for them. There's
nothing wrong with that, in my view, provided that we deliver reasonable
benefits to a broad public, that there's adequate access for all parties to the
benefits that are delivered, and that we treat people in a just way in
distributing the benefits. Part of that issue of justice is distributing the
burdens fairly, and that means allowing for consent to risk where there is
some. . . .
And do you think that the FDA and CDC are taking a very active and cautious
approach on this, or not particularly so? Are they being overwhelmed and
swamped by the research and drug community efforts?
My sense is that the FDA has approached this problem the way it has approached
many other areas of technology development -- without adequate attention to the
concerns about public risk assessment, which is the distinctive feature of
Public hearings are held and guidelines are released, and the public is invited
to comment on them. But the kind of public education campaign and involvement
of people at a high level in a commission intended to review this from a broad
public perspective has not been done. A committee was promised several years
ago that, to my knowledge, has not been set up -- a committee that would have
addressed these public issues in a more appropriate way. . . .
How important, or not, as the case may be, are some of these other issues
that will clearly be raised in viewers' minds, despite the pictures they see?
Manipulating genes in animals, using animals in research -- how important are
all those things versus what you see as the real central question?
It's interesting that animal rights activists who have a history of being quite
militant in this country, with regard to, say, use of animals for furs or
cosmetics, are not saying anything about xenotransplantation. And it's
actually quite wise of them not to say something. They have nothing to gain by
saying something here. They're dealing with a line of research that has great
promise of saving human lives. And I don't think the animal activists will be
in a good position if they have to come out and say these animal lives are
worth more than human lives. There are many other cases where the main point
of their message can be gotten across, where we mistreat animals for what may
be thought of as frivolous human purposes. . . .
As far as manipulating genes and modifying animals, we have the pigs we have
only because we've been doing that for centuries. We have the dogs we have
only because we've been doing that for centuries. It seems to me that we
modify animals all the time for good and bad purposes. We breed dogs that are
vicious. . . .
Some of the research is coming here from England. Is there a sense that
there's a much more friendly and accepting and easier regulatory atmosphere in
the US for xeno?
In Europe and in England, there has been a lot of discussion on a more public
level about the risks. Parts of Europe have an explicit moratorium on clinical
research. The Netherlands is engaging in a process of public education and
deliberation about this before they authorize going forward with other
The regulatory climate in the United States has treated this line of research
as standard research, without giving adequate attention to the third-party
risks to the public. In that sense, there's been a different climate here than
What about the criticism that we're throwing money at to basically extend
people's lives and having people who are living too long anyway?
This raises this question about whether investing in this area is worth it,
compared to other things we could do with our resources. Are we worshipping
the extension of life at the sacrifice of other goods? That is a very broad
and deep question. I would not like to see the burden of it placed just on
this particular technology. It's part of a much broader question. How do you
improve population health in a society?
We have enormous amounts of evidence that the heavy investment in particular
medical technology -- xenotransplant and other technologies -- doesn't have a
major effect either on population health levels or the distribution of health
within that population. And there are many other things we could probably do
that would actually work to the benefit of the public health more than the
investment in these dramatic procedures that save individual lives and extend
So why the excitement over xeno?
I don't think it's excitement over xenotransplantation more than certain other
promises that were being offered in the medical arena. The genome project has
promised us revolutions up and down the line in the way we handle many other
diseases, not just organ failures. We are in the grip of a public demand that
is partly shaped by the drama that programs like this bring to issues like
xenotransplantation. The public is constantly educated about the next
revolution, at least as far as its promise goes. What it's not educated about
are the tradeoffs and the opportunity costs of investing in this, rather than
investing in something else.
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