JOHN Y. KILLEN, M.D.
                    DIRECTOR, DIVISION OF AIDS
                              NIAID
     DR. KILLEN:  Thanks very much, Bernie, and the other
commissioners.  It is a real pleasure for me to be here.  I
really jumped at the chance to do this--there is no graciousness
about it--for sort of two reasons.  
     One is because I think we have actually a pretty remarkable
experience now of the last decade, which I firmly believe is
exportable, and the other reason that I am interested is because
we have a huge investment in prospectively collected specimen
banks, so there is really two reasons for my wanting to be here.
     And then, having sat through this discussion this morning, I
must say I envy you all in some ways because I can't imagine that
anybody plopping into my day would find it anywhere near as
interesting as I found this morning's discussion already.
     I am a little off my turf on this and so I am feeling a
little disconnected from the discussion that you have had, but
what I do have I think are some thoughts about a model that has
operated in HIV research.  
     I can't pretend that everybody would agree with the model as
I am going to present it, which is one of the features I think of
this beast, but I think it is pretty close.
     Bernie asked me a few questions, which I actually found is a
useful framework for sort of structuring some comments.  He
specifically asked me:
     Is it helpful from a scientific point of view;
     Is it feasible;
     Does it allay public concerns;
     What are the pitfalls; and,
     What are some of the lessons that could be learned?
     I would like to go through those quickly and just make a few
comments about each one.  But first maybe spend just a couple of
minutes talking about what it is that I am talking about.
     The--  It is really actually--  I came here.  I walked here
through the tunnel from the other Marriott across the street
where right now today the AIDS Clinical Trials Group meeting is
going on.  
     It might have been a really interesting thing to do for you
all to have a field trip this morning to go see the ACTG meeting
in progress because what you would see is probably about 15
percent or 20 percent of the people at the meeting being of
community origin, participating fully in the process of this
research meeting, which I think is one of my sort of global
points about all of this.
     And that is that I think at the end of this, when the
stories are written, what will have come out of our experience in
HIV disease is a somewhat different paradigm of doing research
where, rather than the notion of researcher and subject and
somebody needing to protect, we have taken probably a first and
very crude step toward creating a partnership.  
     I think it has not, by any stretch of the imagination, been
a perfect partnership.  It has been really rough.  It has been
very personal.  It has been very messy and so forth.  But I think
at the end of the day that may be--  I would be--  I will be
wonderful if that is where it leads.
     The second thing is that I think involvement of community--the second bottom-line point--is that involvement of community is
essential.  The net benefit has far exceeded the costs.  And I
can't imagine now, from where I sit, doing clinical research any
other way than involving the community.
     So the model that we have basically is--  I will just use
the AIDS Clinical Trials Group as a prototype.  
     The fact that we have community involvement grew out in the
mid- to late-'80s when there was a lot of animosity, dissension,
distrust of the government apparatus, frustration at the slow
progress that was seen to be being made, a kind of an in-your-face attitude on the part of many, the activist community, that,
you know, "You guys can't do this research, so we will show you
how to do it."
     There was confrontation.  And basically what they were
demanding was a seat at the table; to participate in the research
planning and execution process.  There was a lot of resistance on
the part of a  lot of people, but a few folks with some vision
said, "What is the big deal?  Why not allow them in to the
process?"
     And what was created, without going into any of the detail
of it, is a system where, as I alluded to just a couple of
minutes ago, representatives of the community of participants in
the research studies are a part of all of the process, from
conceptualization of ideas through the design of the studies,
their execution, recruitment at a community level, analysis, and
everything in between.
     A lot of what we do is multicenter trials.  The individual
research sites each have what they call a community advisory
board, which consists of individuals drawn from their local
community--whatever that is--and those community advisory boards
theoretically are supposed to meet on a very regular basis.  
     And I will talk about what they do in just a moment, and
answer any one of Bernie's questions.
     There is also, above that, if you will, or aside from that,
what we call a community constituency group which is, at least in
part, drawn from the membership of those local community advisory
boards and sort of serves in the capacity of working with the
bigger multicenter cooperative group.
     The community people are fully vetted members of all of the
committees of the cooperative group.  The executive committee has
two community people sitting on it right at the table.  And all
of the other research committees and execution committees have
community representatives.
     I probably don't need to go into any more of the detail.  If
you have questions about it--  It might be more useful to talk a
little bit about what they do.
     I think then, to move on to the questions that Bernie
proposed to me:
     Is it helpful from a scientific view?  Yes.  Unequivocally
in a lot of ways.  
     There is a "but" that I will come to in a minute.  
     There is a lot of different kinds of ways that we see that
this has been helpful.  On occasion ideas of science, ideas of
studies that need to be done emanate from the community that
don't emanate from the scientists.  But there is a lot of other
areas where the community participation has enriched the science. 

     Asking us why we are not collaborating with this other group
of people doing behavioral research, and forcing that
collaboration, if you will, when it wouldn't be a natural act. 
Providing--  
     Particularly important--Bernie alluded to just a minute ago,
which is kind of alluding--is providing input on studies and
helping in the study design up-front, but also forcing the
question of why are inclusion criteria so narrow, listening to
the community's needs and desires.  Helping sell studies in the
community is a very important thing for outreach, to help accrual
retention, if the community understands it.
     I think the key in this--maybe the biggest thing that sort
of goes out of the particulars of HIV research--is the
transparency that we have tried to create, which I think is a
really key word.
     The openness, the trying to deal with the questions of
mistrust by opening the process and saying, "Here it is.  There
really aren't any secrets.  Sit down and look and be a player
with us in this."  That kind of transparency of the process is
very helpful in getting the science done.
     There has been a lot of other sorts of things that have spun
out of it--changing policy.  Inclusion of women of childbearing
age in antiretroviral studies is sort of one example. 
Challenging us all the time on why are you doing things that way. 
Challenging the status quo.  
     It is incredibly valuable to have people who are not in some
way--and I don't mean this in a negative way, as it might sound,
it is just a statement of fact--it is incredibly valuable to have
people who don't have a stake in the research other than the
knowledge asking questions about why things are being done the
way they are being done.  And I think that gets back, in large
measure, to the transparency of the process and the building of
trust.
     And then the other thing that has happened is that people
know each other.  At least in our environment, that sort of grew
out of an adversarial relationship--very much adversarial--it
becomes very difficult to demonize people when you get to know
them as people.  And that works both ways; the researchers and
the activists.  When you begin to know human beings, it is much
harder to read nefarious intent.
     I think there is a "but" in this that is important to put on
the table.  In our experience, I think community perspective can
be somewhat short-sighted, or short-sighted from a scientific
perspective.  
     Early on the drive, early on in our thing and in all of
this--the activists--the push was how many patients do you have
on trials?  In other words, how many people do you have getting
drug, rather than what are the studies that you are doing?  
     So the goal kind of became, you know, get a lot of people in
study instead of do the best possible science that there is to
do.  That is not a problem at this point.  That was a transient
thing.  
     I think there has been a lot of really remarkable stuff
happen in terms of accelerated approval of drugs.  That has come
with some cost of knowledge and information about long-term
follow up, and we are finding ourselves in a quandary today about
long-term follow up of some of the regimens that we are using for
therapeutics for treatment.  Not that that is bad.  Not that it
was wrong.  But it is just a statement of fact.
     And then, finally, I think the community does not have all
the answers.  The community does not have all the wisdom that
needs to be applied.  They have a perspective which is part of a
multidisciplinary effort.
     I think it is practical, very definitely.  As I said, I
can't imagine--  And I think you have to be imaginative about how
you conceive of it, but it is very definitely--  Practical could
be done in other circumstances.    There can be difficult
transitions.  It is costly in time and money, particularly time I
think.  You have to invest more time in education and you have
got to watch your language.  You have got to, you know--  Not so
much watch your language as watch your jargon and pay attention
to it and translate into English, or educate people about the
words that you are using.  
     And that works both ways also.  That works both ways.  All
this works both ways.  I don't mean to sound condescending.  I
hope I don't.
     There have been some really fascinating examples about
ethical questions that have come up, and if you are curious about
them we can go into them.  The ACTG 076 Trial was a perinatal
transmission study, placebo controlled, that gave AZT to mothers
and pregnant women and proved disruption of transmission from
mother to infant.
     There was an enormous amount of controversy about that study
at the start.  There were--  Meetings were disrupted and stopped
by protests and so forth.  But ultimately what swung the study
was community stepping up and saying, "This needs to be done." 
And particularly the community of women most likely to be the
participants in that study.
     More recently, we have dealt with a thalidomide trial, and
inclusion of women in a thalidomide trial, women of childbearing
age in a trial of thalidomide for aphthous ulcers, which is a
complication of HIV infection.
     I alluded a little bit ago, in the first session this
morning, to a more recent community consultation on this business
of creating immortalized cell lines from a prospectively followed
cohort of individuals.  That sort of seemed--
     When the idea came up, it was a sort of a scientific
nobrainer.  I am not sure that is the right phrase but, you know,
it was obvious it was the right thing to do from a purely
scientific point.  It was--  
     It came up at exactly the same time as Dolly the sheep and,
you know, there was all this--  There was I think some concerns
on some people's part that the difference between creating an
immortalized cell line and cloning, and all that--  
     What we did was go to the community advisory boards and the
Multicenter AIDS Cohort Study and talk with them about it, and
got a lot of reassurance that, yes, that was the right thing to
do.  It just felt good.  
     And I think that is a different kind of a model for going
back retrospectively, for going back and getting consultation on
an issue that is problematic and difficult, but doing it on the
material that was collected retrospectively from a fraction of
the cohort that the material was collected from.  
     I think it is workable, and that particular case may be a
little more germane to some of the discussion that we have had
here this morning.
     There are a lot of pitfalls.  It is work.  It is uneven. 
There is--  There are concerns now I think that many people have
that we have created professional activists.  We have created an
activist industry in AIDS that now comes with its own agenda and
its own set of politics which are somewhat removed from the grass
roots, if you will.  
     I am not sure that that is an inevitable--  I am not sure
that that is accurate.  I don't know.  And I am not sure that it
is--  It certainly is not inevitable.
     The other pitfalls--what has been talked about this morning--what is community?  Obviously in HIV disease we have dealt with
ethnic communities and risk communities and so forth.  But even
within the same city there is ACT UP San Francisco, and ACT UP
Golden Gate, and they are basically at their throats most of the
time with vehement disagreements.
     I think--  What are some of the lessons that might be
useful?  I think I can easily envision a model where community
consultation is very helpful in allowing you to take the leaps of
faith, if you will, that Zeke talked about this morning, where
you can't--  I don't know that you--  I don't know that you can
go and get consent.
     But you certainly can go and get either consensus or a very
good feeling for whether an issue is problematic or not by
consulting with the community or, more accurately maybe, or
better or even more optimal is the ideal of trying to discuss
with community in partnership.  I think consultation implies, may
have an implication that is a little more paternalistic than is
perhaps ideal.
     The second lesson is that you can't please all the people
all the time.  And there is going to be disagreement, and this is
a little messy, but you can certainly get a good flavor for what
is going on.
     And then the third thing I think is that community, whatever
you do, it has to be linked in some way to the research.  It has
to be people who have a stake in the research and ideally you
would like it to be participants in the studies.  
     We have actually had systems evolve that that is not the
case and they are not directly stakeholders, if you will; they
are not directly from the community, but they call themselves
community and there are problems there.  There are perhaps other
things that might come up.
     Bernie's final question was will such input be possible when
a community is not informed or organized or active?  I think,
yes, very definitely yes.  It is very possible.  It is very
achievable and can be done.  It might be harder.  
     We have had a little bit of flavor of that in trying to
organize community input around vaccine research where the
prevention constituency is not nearly as well organized as the
treatment constituency, not just in AIDS but everywhere in our
world.
     On the other hand, it might be easier to do if you didn't
have the dynamic of confrontation or mistrust as such a prominent
feature, so I am not really sure which way it might go.
     But those are some comments off the top of my head.
     DR. LO:  Okay.
     DR. KILLEN:  Thanks for the opportunity to offer them.
     DR. LO:  Are there questions?
     DR. EMANUEL:  I have a questions and follow up.
     One is you talked about a problem which we have been
confronting and banging our heads with, which is what happens
when you have a lot of different groups?  Who is the legitimate
political leadership you go to in a community?  And what do you
do when you have disagreement, as you suggested there is in a
variety of spots?  
     And I think this is--I might preface my question by saying,
in some sense--I think this is somewhat separate because it goes
to a lot of the details of the processes for community
deliberation, consultation, consent--whatever we are going to end
up calling it--and those may be different things actually.
     DR. KILLEN:  It is hard.  We have lots of different groups
in AIDS and HIV.  You have to make an effort to include them. 
You have to make an outreach kind of an effort to include them.  
     If you went over to the ACTG meeting this morning, I think
you would see, among the community participants, you would see a
conscious effort to be inclusive not in the sort of Noah's Ark
way that committees, you know, two of this and two of that, and
federal advisory committee sort of law sort of approach, but much
more--
     One of the things that we did was actually sort of charge
the community people.  And they embraced this charge so it wasn't
like, "You do it," but said, "Be inclusive, find people, go out
and recruit other communities."  And so it is not--  You ask the
community for help in defining the relevant community and you ask
them for help in recruiting it.
     It takes a lot of work.  It is a lot of work.  When there is
disagreement, you deal with disagreement like you deal with
disagreement in science, or any other field; you do your best to
come to some conclusions about what is the right answer.  You
have in place a mechanism for making the decisions.  
     And I think people usually respect, if they have had--  I
think the big thing is that people respect a decision that they
feel like they have had an opportunity to provide their input
into it.  If there is a well-defined process for that input being
gotten; that that is the real issue.  
     The disagreement happens in everything you do and I don't
think--  I don't see it as any different fundamentally.  The
community is not right all the time.  That is the important
point.  The scientists are not right all the time. 
     DR. EMANUEL:  I think I would second that.  I think, to some
extent, we are constantly being confronted by the question of,
you know, what if there is not a unanimity or consensus?  Well--
     DR. KILLEN:  There won't be.
     DR. EMANUEL:  --you know, in our political system, we don't
have it all the time and it doesn't grind to halt.  I mean, we
have a system for dealing with it.
     (Laughter.)
     DR. EMANUEL:  Well, speaking loosely here in Washington.  I
think it is a bogeyman.  One should not expect unanimity.  That
is the not the standard.
     DR. KILLEN:  It will not be.
     DR. LO:  Tom?
     DR. MURRAY:  This is terrific, John.  Thank you.  It really
helps ground me in what I think is probably the richest
experience we have in, as far as I know, in human subjects
research and trying to involve communities.  And I am struck with
admiration and gratitude.  
     But I am also struck with the disanalogies to our situation. 
And let me just list some of them and see if you or other members
of the commission can help me think through how we can apply some
of these things that you have learned.
     You have an active and informed community.  And a
sophisticated community has become increasingly sophisticated
about the research that is to be done.  Furthermore, you have a
kind of natural, if you will, sanction or power on the
community's part; that is, they can simply decline to enroll in
one of these clinical trials.  Right?
     DR. KILLEN:  Uh-huh.
     DR. MURRAY:  So it flows pretty well.  If the community
leadership says, "This stinks," the word gets out to the
community that is sophisticated and well networked and the word
is, "Don't participate in this trial," and people don't
participate in the trial.
     With one exception that I can think of, namely family
pedigree studies where you may go back repeatedly to families who
then may become sophisticated about interacting with researchers,
with that aside--and that may well be identifiable in all cases
anyway--that those things I think are untrue, by and large, of
the cases we have been thinking about.
     Where you are dealing with tissue samples and they have been
collected decades beforehand, where they are being anonymized,
where it may be that the community of interest, which may be
difficult to define in the first place, has sort of little
sophistication and little continued interaction with researchers
and, in fact, no good way to--no sort of natural sanction--no way
to say, "We refuse to enroll."  Here are the issues.  That we
give the community a kind of veto over it.
     Now, I want to figure out how to make all the disanalogies
go away, but I have to--  We have to--
     DR. KILLEN:  I think, to the extent that there is an AIDS
community, which there isn't, I think it is--but there are a lot
of them, in fact--it is probably also not a valid generalization
that the community is well informed; that, you know, that--  
What we saw--
     Let me answer it a different way.  I mean, what happened was
that the community that got this ball rolling was the gay white
men.  Early on in the epidemic, other communities were not
interested, they were very poorly informed about or, maybe more
accurately, they had a completely different set of priorities
than research.      Their priorities--the minority community; the
African-American female community's main issue--was access to
health care, and all other issues were basically, you know, not
germane.
     I think it has required education to raise the level of the
community, but you can do it.  So I don't accept the fact that
the AIDS community is informed and active.  It is partly.  It is
a lot more informed--  I am sorry.  It is a lot more informed
than it was some time ago.  I think it is not a good
generalization.  
     DR. MURRAY:  You understand--
     (Simultaneous discussion.)
     DR. KILLEN:  And it requires education and outreach.
     DR. MURRAY:  You understand I am glad to have you show me
that my concerns are not--  And I think you are right.  I guess
what I had in mind were those people who tend now to be brought
into your meeting; they have gotten pretty sophisticated about
how research works, I assume.
     DR. KILLEN:  Yes.  Yes.  That has been one of the huge
values.
     DR. MURRAY:  That could also happen in these tissues,
couldn't it?
     DR. KILLEN:  Absolutely.  Absolutely.  It might not be the
people who contributed the material, but it could be people of a
similar ilk who could provide advice, assurance, tell you, "Yes,
that makes a lot of sense.  If I had donated that, I would really
want to be a part of--  I would want that study to go on," or, "I
want that information now."  
     DR. EMANUEL:  Maybe the active verb there--gotten informed--is the right issue.  That they didn't necessary start out, but
the process in part helped us.
     DR. KILLEN:  Yes.  Even, you know, even the starter
community had to get informed.  And then the active involving
them in the process is what has created the informed community.
     DR. LO:  Carol, then Trish.
     DR. GREIDER:  My question was answered.
     MS. BACKLAR:  Isn't that a little bit of concern.  There was
a sentence you had about selling studies in the community.  I am
a little concerned about that.  Perhaps a conflict of interest
when one is selling the work that one is doing.
     DR. KILLEN:  I meant that.  I don't know how that was heard.
     (Laughter.)
     DR. KILLEN:  I meant that in the sense of helping
recruitment.
     MS. BACKLAR:  But I am also a little--  I understand, in a
sense, this is a kind of special community who were very eager to
be recruited.  You also made that point.
     DR. KILLEN:  I don't think that that is necessarily the
case.  
     MS. BACKLAR:  It is not?
     DR. KILLEN:  I think that most of the communities who have
been involved in HIV research, on the contrary, are communities
that traditionally have been disenfranchised from the health care
system and the scientific establishment, so the process--
     What I meant to say was that the process of educating
representatives of the community, about what the research is
about and what it is trying to accomplish and how it is going to
do it, has been extremely valuable in opening up what is going on
and helping the studies get done.
     The information exchange from peers, in this case, is
extraordinarily important.  When you are reaching into a
community where there is mistrust, peers have vastly more
credibility than the scientists who you don't trust, and that is
really all I was trying to say.
     The creating mechanisms of outreach to help the research get
done is extremely valuable when you are beginning with a dynamic
of mistrust, but what it means is that you have had to educate
people to become part of the process.
     Am I addressing--
     MS. BACKLAR:  Right.  But I am also thinking about the fact
that many people in this group may have felt that they would get
better care in a research protocol--
     DR. KILLEN:  I am sure.
     MS. BACKLAR:  --than they would have outside of a research
protocol, and that is something that we are quite concerned with
in research generally.  
     And Ruth Faden's(?) committee certainly pointed that out;
the therapeutic misconception.  
     So that there are some dangers that, some of the words you
spoke alerted me to, that one would have to consider when one is
educating a community in terms of research.
     DR. KILLEN:  Yes.  I think I don't see it so much as sort of
educating the activists to go out and be recruiters as much as
the fact that you have involved them in the process, up front and
all the way through, makes them valuable participants and makes
the process of getting the research that you have designed with
their help done more quickly.  
     Are you co-opting people?  Yes.  To some extent.  But that
is not a bad thing necessarily.
     DR. LO:  Larry, then Steve.
     DR. MIIKE:  I guess this is more directed to the people on
our panel who are knowledgeable about research.
     How representative can this process be?  Are we--  When we
are looking--  What we are talking about is a sustained research
effort in our community, however one defines it.  How
representative of that is this in the area that we are looking
at?  Are we dealing with one-shot deals, or are we dealing with
sort of a whole research agenda around a particular community?
     DR. EMANUEL:  I think it much depends upon the research
questions.  But let us just focus in on--  I mean, the BRCA-1
case is, you know, you may go into it, or start out thinking it
is a one-shot deal, but in fact the point is, if you identify it
within a community, it is unlikely to be a one-shot deal.  Right? 
It is unlikely--
     I mean, one of the I think retorts to Tom's question is
usually these kinds of studies I think, especially if they are
positive, end up being part of a larger research agenda which
inevitably involves going back to that community and working with
them over all sorts of issues that spin out of the research.
     I mean, I think, you know, when we think about the relevant
communities, yes, it is definitely possible that some of the
research could be a one-shot agenda, which would make all this
effort necessary to community building seem very inefficient,
very much of a waste.
     On the other hand, if it is part of a bigger research
question, where a positive finding in the community means that
you are going to be involved with them over a prolonged period of
time, you know, this may just be the start.
     DR. GREIDER:  But that is not necessarily the case, right?  
     I am a researcher sitting at University X and I am just
interested in a particular gene and I want to get, you know,
100,000 people and test them for that, and then I am not
interested in following up on the community.
     DR. EMANUEL:  Right.
     DR. GREIDER:  Does that mean that I then am drawn into
having to be involved in that community in an ongoing process?  I
mean, it is--  One question, I think--
     DR. MIIKE:  Because it is the ongoing process that I think
has been what has been worthwhile.  I mean, you say that they
have gotten more sophisticated, you have gotten more involvement
as time goes through so, yes, and I am looking at that versus
informed consent or participation.      I don't see how you can
get informed consent if it is--  Especially--  Even in a group
such as yours, I don't think you could get informed consent in
the early stages because it was more a question about just
learning about what the process was.
     Does that help?
     DR. KILLEN:  Oh, I am not sure I understand.
     DR. MIIKE:  Well, I don't see how one can get informed
consent in the front-end of a process where, as time goes by, you
get more and more knowledgeable about the whole research
enterprise around the question, so it is more like an
introduction into the issue at the beginning than truly knowing
what is going on and giving informed consent, however one defines
a community.
     DR. KILLEN:  Yes.  I don't think that I would portray most
of what is going on here as informed consent nearly as much as--
     DR. MIIKE:  Well, that was my point.
     DR. KILLEN:  --consultation.  And consultation and--
     DR. MIIKE:  Well, that is exactly my point, where what we
have been talking about is the participation rather than a sort
of like a yes or no kind of thing.
     DR. LO:  Well, I think--again, to go back to the example--I
mean, it may well be, if you talked to some members, some
representatives of the group from which the sample is gathered,
they would say, "Dr. Greider, we have no problems with that, you
know, no problem at all; go ahead and do it," or they may say,
"Although the last person had no problem with it, we think there
are some things very different about your protocol that we would
like to discuss further."
     I think I would agree with you, Larry, that I am not sure
that--  I mean, in a sense, formally, as I understand it, FDA's
representatives are part of each committee and they participate
fully, but they don't necessarily have--any one of them--a veto
power.  
     I mean, their ideas are heard and sort of taken into account
but, you know, there are scientists or other people in the
community that also have votes and they could be out-voted.
     DR. KILLEN:  Yes.  I mean, I really conceive of this as the
participants in the study have an expertise that they bring to
the table which is as valid, but no more or less valid, than the
virologists and the statistician and the data manager in the
planning of research.  I don't know if that gets to--
     DR. LO:  Do you want to--
     MR. HOLTZMAN:  Just take Carol.
     DR. GREIDER:  I just want to--  You made a statement in your
discussion of your experiences.  You said you have to have a
mechanism in place for making a decision, and discussing the fact
that there is ACT UP San Francisco and ACT UP Golden Gate, but
there is going to be some disagreement within the community.
     What kind of mechanism are you talking about if we are not
talking about a consent?
     DR. KILLEN:  Well, it could be a lot of different things.
     There is a process within the AIDS Clinical Trials Group
that decides whether or not to go with a study or not.
     One could imagine the funding, the process that is the
funding of a grant to be the process of decision.  You include
community consultation in the input into the design, but it leads
to the decision to fund the grant and do the study.
     Those are just two things that pop off of the top of my
head.  That is what I meant.
     DR. GREIDER:  Because we had discussions around the table--I
think what Larry was referring to--about a possible veto from the
community and how you could do that, which is very different than
what you characterized as input from the community leading to
them inputting into a decision-making process that then says go
ahead or don't go ahead.
     DR. KILLEN:  Yes.
     DR. GREIDER:  It is a different structure than a veto from
the community in some ways.
     DR. KILLEN:  I think, at least in our experience, when you
hear a veto, for the most part when you hear a veto it is a de
facto veto that is pretty obvious.  And I don't know.  
     I don't--  There is something about this that I am not--  I
feel like I am not connecting with in some way.
     DR. LO:  Jack, it may be that some people may be thinking--
     REPORTER:  Your microphone, please?
     DR. LO:  Some people may be thinking that community
participation is another level of approval that you have to
achieve, so that you go to the IRB, or you may have to go to the
IRB, they may have to approve it.  
     But one model is that you then have another sort of
community approval process you actually go through.  And the
specter that might raise for researchers is that, you know, it is
just another roadblock that they have to go through--
     DR. KILLEN:  Yes.  No.  Absolutely not.
     (Simultaneous discussion.)
     DR. LO:  --and you say that is not.
     DR. KILLEN:  Absolutely not.  No.  No.  They are
participants in the process.  If you were doing a--  If you were
doing multidisciplinary research, they would be another
discipline at the table.  The community discipline is another
discipline at the table.
     DR. GREIDER:  Yes.  But, again, if we take the example of
BRCA-1, where, you know, I am just interested in studying
mechanism of disease and now there is this community; that I am
going to look in the Ashkenazi Jewish community.  They aren't
involved in my research in any way.  It is not like they are
already a participant.  And so I, you know, define this group of
people and it is a relatively homogeneous group where I could
actually get information from.  
     So how am I going to go about beginning to involve them; to
ask for community input into this study of genetics?
     DR. KILLEN:  I can only answer in a generic sense.  You go
to the community leaders and talk with them about the
characteristics of the community and you find the best ways to
reach into that community.  That is a quick answer.  It may--
     DR. GREIDER:  So it is an additional thing?
     DR. KILLEN:  I am sorry?
     DR. GREIDER:  It is, as Bernie just characterized it, an
additional--  There is the IRB approval and then there would be
this community consent.  So, in that case, it really is an
additional--
     DR. KILLEN:  I think community.  I don't like consent.  I
don't like that word because that is not how it operates.  There
isn't an approval veto mode.  But there is--
     DR. GREIDER:  But consultation.
     DR. KILLEN:  Go back--  Let me go back to the example that
we had.  Just there is a repository of material from the
Multicenter AIDS Cohort Study that people have contributed--every
six months, cells and blood and tissues and so forth--to.
     Some of the material there was being exhausted by requests
for samples to do genetic research on, and the idea came about
that it would make sense to create immortalized cell lines so
that at least the DNA would be renewable, and we wouldn't have to
worry about exhausting the valuable specimens, could save the
valuable stuff for non-renewable things, et cetera.
     I can easily imagine that, even if the community advisory
boards were not in place, we could find a way to carry out a
consultation with gay white men, which is who this cohort is all
about--or gay men, not white men; gay men--that you would sit
down with them, talk through what it is all about, and provide
yourself with reassurance that you were doing something that made
sense; that was something that these people were interested in;
that they felt should happen.  
     But the approval process for the research should be the
approval process that exists already.  So the IRB does the IRB
thing.  But what you have is a level of input and reassurance and
building of trust and faith in the scientific establishment; that
it is doing good.
     And that works both ways.  It works for you and it works for
the community.
     DR. LO:  Okay.  A whole lot of people want to get in. 
Steve, Zeke, Tom, and then Bette.
     MR. HOLTZMAN:  When we get to filling in box 3b--okay?--at
least we will be potentially composing a situation of what
happens when the consultation provided by the relevant community--I didn't say consent--says, "Do not do the study."  Yet there
are a sufficient number of individuals who would eventually agree
to participate in the study and it would be a valid study.
     Did you ever run into that kind of case and, if so, was the
consultation which said, "Don't do the study," just positive, or
was the individuals who consented just positive?
     Alex Capron would ask that question if he were here.
     DR. KILLEN:  I don't know Alex Capron.  I am having a hard
time thinking of an example.
     DR. LO:  Well, there are some examples.
     DR. KILLEN:  There certainly have been studies prospectively
designed where there has been a lot of controversy and a lot of
heat.  The decision was made to go ahead.  In some cases the
community that said no was right, and in some cases the community
that said no was wrong.
     But, again, the decision-making process about whether or not
to do the research operates somewhat independently of this
involvement as--
     DR. MIIKE:  What do you mean by right or wrong in that
example?
     DR. KILLEN:  Produced useful and important information, or
was a successful study.  So when I said--  Is that what you mean? 
Does that answer--
     MR. HOLTZMAN:  You see, in the case of AIDS, if we are
talking about a drug study, you may be able to get some
objectivity there at the end by saying, "Did I or did I not get a
useful drug?"
     DR. KILLEN:  Yes.
     MR. HOLTZMAN:  Whereas in the kind of study which really
brought this group together on this kind of issue you are not
going to have that--right?--because you are going to have a--
     DR. EMANUEL:  Even if you get a gene, people could see that
is a mistake.
     MR. HOLTZMAN:  Right.  I mean, we have got this fundamental
problem.  In an age of political correctness, one--  You could
take a view where you are very suspect of a group, or a group of
authority speaking for a group, saying, "Don't do that research." 
Right?
     On the flip-side, you want to be sensitive to group concerns
and that is--  I think we have run into that and--
     DR. LO:  Well, there is a real disanalogy here I think
because what I think what has happened a couple of times in the
clinical trial situation is where the ACTG has decided that a
certain study or a certain research question doesn't come up high
enough on their list of priorities to be done.  
     But some elements of the community say, "Well, we just
totally disagree," and they go off and do the study sort of on
their own.  And the Compound Q Study that was done in San
Francisco may be an example.
     But I think it is different when there is only sort of one
repository, so to speak, or one repository you are thinking of
going to.  
     And it is hard to imagine how, you know, if you have some
people who make the decision to either approve the study or you
don't, how the members of the community who say, "Oh, well, we
disagree with what our community representative said and we
eventually would like to do the study," how you would actually
manage that with the tissue sample, or whatever.
     DR. KILLEN:  Well, I would say that just the model of
consensus here I think is a good one; that it would seem to work
for me at a very simplistic level.
     You have consensus or you don't.  You know, not a majority
vote, or whatever.  You have got a good, solid sense that the
community agrees or doesn't.
     MR. HOLTZMAN:  Well, Zeke gave a real live example.  In the
Boston community, the Partner's Group--right?--decided to go out
and seek input on whether or not they ought to conduct the BRCA-1
and other genetic studies in the Ashkenazi women in the Boston
area.  And what came back was input that said, "Don't do it."
     DR. KILLEN:  Right.
     MR. HOLTZMAN:  And the hospitals decided not to do it.  
     DR. KILLEN:  Uh-huh.
     MR. HOLTZMAN:  It probably had more to do with the sources
of contributions than anything else, or one could ask that
question.  Right?  Because now what about the individual
investigator who says, "No.  I want to do this study and there
are a group of individuals who consent and say we are happy to
participate in it.  We don't care what the community said."
     And I am just asking whether, if we are going to take your
experience as a paradigm--that comes back to Tom--to what extent
have you run into these situations and how were they handled?
     DR. KILLEN:  Somehow they seem very different to me because
it sounds like you are talking about a prospective study, or a
study where one group of individuals--  You could certain
construct a study where a group of individuals consents to
participate and you do the study with them.       But, in the
first case, it sounded like you were talking about a study where
individuals might participate without their explicit consent. 
Right?
     MR. HOLTZMAN:  No.  
     DR. KILLEN:  Am I--
     MR. HOLTZMAN:  I didn't explain it well maybe.
     DR. EMANUEL:  Well, I think the example is, in Boston, they
have not been able to launch a BRCA-1 study because the community
won't--  You know, it has been up in arms.  Now, no one knows
whether that is the majority of the people.  They haven't really
gone out and tried to do it over the objections of, you know,
very articulate members of the community.
     And I guess part of Steve's question is what do you do in
that situation?  Or what would you--  Have you confronted such a
situation where you might have some people individually who would
say yes but, you know, your advisory group would say, "We don't
want you to go ahead with that."
     DR. KILLEN:  Sure.  Yes.  
     The ACTG 175 was a very large antiretroviral study--without
going into the details--a randomized several-arm clinical trial. 
A large faction of the activists involved in the ACTG completed
that study.  They campaigned against it.  They said it was a huge
waste of money and resources and better things could--  You know,
all sorts of things.  There were a few that supported it.   The
group went ahead and did it.  It turns out, in this case, that
the study should have been done because it yielded incredibly
important and valuable information so--
     MR. HOLTZMAN:  But at the time the decision was made to go
ahead, in the face of that community opposition, what was the
basis of the decision?
     DR. KILLEN:  A scientific--  A scientific decision, and a
decision that it was an ethically sound study.  It was the same
kind of decision-making that would go on--  I don't--  You know,
we don't treat this process as more than advisory or input.
     DR. EMANUEL:  Here is the other disanalogy.  It is not clear
that the results of that study were going to lead to a
discrimination against the group, or potential discrimination. 
Right?
     DR. KILLEN:  Yes.  I guess.
     DR. EMANUEL:  So, I mean, there the--
     DR. GREIDER:  Under 2b?
     DR. EMANUEL:  Right.  3b.  Yes.  
     DR. GREIDER:  Under 2b.
     DR. EMANUEL:  2a probably.  Right.  Something like that. 
Whatever.  To be or not to be.  Right.  
     DR. GREIDER:  2a.
     DR. EMANUEL:  Which is why--I mean maybe why--we might want
different kinds of standards here.  You know, you might not
weight the objection that much more.
     Can I--  I just want to make an observation, and I think
this is probably my political science training here.
     I mean, consent here is--  I am at fault for using that word
in introducing it.  
     And I think that, you know, there is a model of individual
consent, which is the one we are used to in the medical
community, and then there is a model of political consent, which
is where the word originally started, that has many different
kinds of connotations and implications.
     And I think because, you know, we come from a medical
background, a medical ethics background, every time we say the
word consent, we think individual consent, sign on a form kind of
stuff, whereas, when we talk about communities, I think the much
better analogy is the political consent, where people don't
seriatim go in and sign off their name; where, you know, you are
looking for something like consensus.  You are not looking for
unanimity.  And there is a decision-making process to kind of
integrate all of this stuff.
     And I think--again, I believe that I am probably at fault
for this--at least in the community side, when we are talking
about what the community ought to do, whether we want to call it
consultation or deliberation or input or consent, we need to step
outside the box, and maybe these calls for using a different word
on purpose, the sort of individual consent to a research protocol
type model.
     And I think part of the confusion I hear in the room is
because of those two different kind of paradigms for the word. 
And I think, you know, we really do have to put the individual
aside when we are talking about groups because there is just no
analogy at all there, even though the words are the same.
     DR. LO:  As I understand Jack, what he was saying is that
consent in the political sense is not what he is talking about;
he is really talking about input into a process which many, many
other people also participate in, so that--
     DR. EMANUEL:  It is political consent though, right?
     DR. LO:  Well, let us--  But it seems to me that is
different than a model saying there are leaders in this
community.  We will go to them and they will either agree or
disagree and, if they disagree, we don't do it.   That is very
different than this model where there is a much larger group to
which community members sit at the table, but there will be many
things on which most people at the table agree with.  There may
be some where any one constituency will get out-voted.  So I
think, yes, the right terminology is--
     Tom, and then Bette.
     DR. MURRAY:  Two things I think have become clearer for me
but, after I speak, you will tell me whether that is true or not.
     One is that, thanks to Steve's question, I think I
understand that, in 3b, maybe even 2b, to the extent that people
are identified and it is, therefore, prospective in the sense
that they are asked for their consent to participation, even if
the tissue had been collected before, that they are asked for
consent to participate in it, then it seems to me that the normal
procedures of IRB review for the protection of human subjects are
highly appropriate.
     But probably not necessarily community consultation of the
same kind.  I am not sure.  Because what if people said, "I want
to be in the study," and the IRB says, you know, there is no
particular harm to human subjects, do we want to insist that
there be community consultation?  That is--  To me, I see the
question a bit differently now.
     The second thing that Jack helped me see clearly is that I
don't--speaking personally--I don't want to see an additional
layer of committee work.  You know, you get the IRB approval,
then you get the community approval.  That is probably not a good
model for a variety of reasons.
     A much more compelling model is to say, look, if you are
doing a study that implicates community--and we will have to
spell that out a little bit; what we mean by that--that there
must, in order to even approach the IRB, you must have in place a
process for community consultation, for the community has a place
at the table, prior to submission of the protocol, much like what
I understand you to be describing about the ACTG work.
     That is a model that, at this point, I find very appealing.
     DR. EMANUEL:  I am not sure I understand that.  Could you
just--
     DR. MURRAY:  I will try.
     Suppose a researcher wants to do a study on Gene X, which
may be sensitive--we will put a kitchen sink case--may be very
sensitive in a minority community that has experienced
discrimination, that continues to experience discrimination.  
     Before the researcher goes to the IRB, whatever we recommend
would be that that researcher must consult with the community,
must engage in consultation, bring in the views of that
community, make some, you know, modify the design of the study if
that seems appropriate--whatever--and then go forward with a
report as to how that consultation emerged.  You know, the
results of that consultation.  And that is what goes to the IRB
for approval.
     DR. GREIDER:  But someone has to determine whether a
community is at stake here.
     DR. MURRAY:  Uh-huh.  Yes.
     DR. GREIDER:  So what if the IRB says, "Look, a community is
at stake.  You didn't already do that."  There has to be a way
for them to have their consciousness raised and say, "Ah, right,
there is a community at stake.  I hadn't thought about that." 
And then go forward.
     DR. MURRAY:  Part of that is education and part of that we
are responsible for; to make it clear what we mean by that so
that, you know, a diligent researcher will have a pretty clear
idea of whether they need to take this step or not before they go
to the IRB.  
     Part of it will be the kind of education that most of us
remember; namely, we didn't do it right and we get sent back to
do it again.  That will happen.
     DR. MIIKE:  The same thing will apply to harm or no harm.
     DR. MURRAY:  We have to make that call.  I am not prepared
to make that call right now.
     DR. MIIKE:  No, no, no.  What I mean is that it is the same
thing that--
     DR. MURRAY:  Oh, right.
     DR. MIIKE:  --before you go to the IRB, the researchers must
come to some conclusion whether there is harm or not.
     DR. MURRAY:  Right.
     DR. MIIKE:  So they are going to get second-guessed anyway.
     DR. EMANUEL:  Right.  The suggestion there was--at least my
suggestion--was that the IRB would have administrative decision-making.  Did you stick it into the right box?
     DR. MURRAY:  Yes.  Right.  Is that any clearer now, Zeke?
     DR. EMANUEL:  It is clearer.  I am not sure I agree.  I am
just thinking and cogitating about it.
     MS. KRAMER:  Well, I am just puzzled all together, and I
throw this out as a question.  
     Does your model--does the AIDS model--really hold when it
comes to genetic research?  
     I mean, when you are talking about genetic research, is a
community identifiable or, if you do one piece of research and
that research identifies a community that was never even thought
to be involved--
     I mean, look what happened, for instance, when they used the
Tay-Sachs material and then, all of sudden, they came up with the
BRCA-1, and then they came up with the colon stuff.  You know--
     DR. GREIDER:  But it is the same community.
     MS. KRAMER:  Well, it is.  I know it is the same community. 
But there was no--  There was no way that you would have--that
they could have--anticipated that that would have come forward
so, you know, I mean, to me it is just like a--
     DR. EMANUEL:  But I thought, Bette, we had addressed that in
the following way.  If your research is going to a community. 
Right?
     MS. KRAMER:  Right.
     DR. EMANUEL:  If you are picking a community out because you
suspect they have something--higher representations of whatever
it is--then, you know, your research has already implicated.
     If, on the other hand, you are taking lots of samples from
whatever, you know, Guthrie cards--Guthrie cards isn't a good
example--from a pathology department and you are getting some
clinical data on them, sociodemographics on them, and it arises
from that that, you know, people who seem to be Ashkenazi Jews
pop out.
     MS. KRAMER:  Right.
     DR. EMANUEL:  You know, you didn't anticipate it.  You know,
that is a serendipitous finding.
     I think what we are talking about in--
     MS. KRAMER:  Is where they are at--
     DR. EMANUEL:  --2 and 3 are when the research is specific,
you know, a priori.  It is identifying this community as one it
wants to go after.
     I mean, how could you do consultation in a process where,
you know, you are looking--
     MS. KRAMER:  I guess--
     DR. EMANUEL:  --at random samples and, you know, some
sociodemographic characteristic pops out at you?
     MR. HOLTZMAN:  Yes.  But how do you--  You took that case
and you said it goes in the first box; the one you just said is
that a sociodemographic characterization pops out.  
     But if, and only if, you had, as part of the phenotypic
information, those relevant parameters so, for example, in the
NHANES stuff, the guidelines they have come out with is that,
except under extraordinary circumstances, they won't release to
you those kinds of phenotypic information, such that you could
never have that kind of serendipitous finding.
     So are we really thinking about it the way you just
described, Zeke?
     That is; that whether it will fall into a community box is a
function of you saying, "I am targeting a community," or is a
function of the phenotypic characterization of the group such
that it would allow it to go into a demographic--into a group--bucket?
     DR. EMANUEL:  I don't know all the deliberations at the
NHANES group, but it seems--  I mean, part of the deliberations I
think is because there is not any real clear guideline.
     MR. HOLTZMAN:  Yes.  But--
     DR. EMANUEL:  Well, I understand but--
     MR. HOLTZMAN:  However your thinking is.
     DR. EMANUEL:  --some people may have a tendency to be more
cautious when there aren't the guidelines.
     I was thinking about it just as I stated.  If you are going
to--  I mean, parts of research are to find some such
serendipitous findings.  And I don't want to block that a priori. 
That would seem to me to be a real mistake.
     MR. HOLTZMAN:  No.  I am not saying block it.  Go ahead,
Bette, I am sorry.
     MS. KRAMER:  No, no.  No.  Go on.  Finish your sentence now. 
Finish.
     MR. HOLTZMAN:  No.  I mean, it seems to me that if I go in
to do a study--let us assume it is individually anonymized; all
right?--but I am asking, with respect to the phenotypic
information, that I want to know whether it is women, what is
their religious background, what is their cultural background, et
cetera, et cetera, and then I am going to go in and effectively
do an association study with whatever is my finding against those
parameters.
     DR. EMANUEL:  Right.
     MR. HOLTZMAN:  And it ain't serendipitous.  Right?  I went
in looking for that kind of association.
     DR. EMANUEL:  But you wouldn't--  
     DR. GREIDER:  You didn't know where you were going to
associate it.
     MR. HOLTZMAN:  Okay.
     DR. GREIDER:  Where it associates is random.
     MR. HOLTZMAN:  That is fine.  So--
     DR. EMANUEL:  But how could you have--  Fine, Steve.  Let
us--
     MR. HOLTZMAN:  No.
     DR. EMANUEL:  You couldn't possibly have some kind of
community consultation process there because you have no idea of
what the relative community is going to be.
     MR. HOLTZMAN:  Which community, right.
     DR. EMANUEL:  I mean, you would never get out of the box. 
You would never get the study underway there.  So I don't see how
that possibly could be the process, I guess would be my reaction.
     DR. HOLTZMAN:  Okay.
     MS. KRAMER:  I want to argue--
     DR. LO:  (Inaudible.)
     MS. KRAMER:  I want to shift it a little bit right. 
Exactly.  
     I guess where I am having a problem is that I don't handle
to the whole notion of the discrimination.  All right?  I am an
Ashkenazi Jew.  I don't feel at all threatened by the fact that
they have discovered this increased incidence of breast cancer,
and maybe it is colon cancer as well.  As a matter of fact, I
feel as though I am the beneficiary of that.  
     Now it is true, if my medical insurance company starts
denying me coverage, I am going to be madder than hell, and it
seems to me that that is the problem we have got to fix.
     But I consider that I am way ahead of the game because I
know what risks are out there for me and I can conduct myself in
a manner that hopefully is going to negate the greater risk.  So
I feel, you know, I am the beneficiary.  And I don't understand
the whole concept of why a group is going to be stigmatized by
genetic discovery.
     DR. KILLEN:  I think--I mean from my perspective--you would
be one of the people that I would want to have sitting at the
table--
     (Laughter.)
     DR. KILLEN:  --to have the research go forward to make that
case.
     DR. LO:  But isn't the point that--you know, this article
comes out in The New York Times--for someone in the press to say,
"Wait a minute.  You know, there are some problems here that
maybe we hadn't been aware of," but it could give us pause.
     It seems to me if you start to get that signal then you try
and do a consultation and if most the people say what Bette just
said, "Well, I don't agree with that article at all.  I think
that is a idiosyncratic view.  Let me explain why I disagree with
that."
     Out of that consultation, it seems to me, you either get a
sense that people are really split and there is very strong
feelings on both sides, or you get the feeling that most people
really agree with you and really want this research to proceed
and think it is beneficial rather than stigmatizing, or the other
way around.
     DR. KILLEN:  Or even that the nature of the misgivings that
the people who are against it, even that is extremely useful
information.  You can be against it for reasons, for a lot of
different kinds of reasons, some of which carry more weight than
others.
     DR. MURRAY:  And some of which may affect your design of the
study.
     DR. KILLEN:  Right.  Exactly.  Yes.
     DR. MURRAY:  Maybe that is one of the things that we are
most worried about is the possibility of walking back and getting
identities, so you redouble your efforts to protect privacy and
strip identifiers.
     MS. KRAMER:  I don't think--
     DR. EMANUEL:  Bette, can I just go back to your point?  You
said you would be madder than hell if your insurance were
cancelled.  
     I mean, I think one of the concerns here is, in fact, is
that insurance might be cancelled just on a wholesale group
level, not on--  And that is prima facie--right?--discrimination. 
Okay?  
     So whether you personally feel empowered--  If the--  I
mean, the whole point of I thought of those categories 2 and 3
was--or 3 was--if the group is going to be stigmatized or
discriminated against, or potentially--I mean the word is
potential harm not actual harm--that is exactly what the worry
is.  
     You--  And I think your case actually brings up Steve's
conflict in spades.  Right?  If you individually want to
participate but the community is very fearful of this
discrimination--  Maybe you have a great insurance policy.  Maybe
you are independently wealthy and it is not going to affect you. 
Right?  
     But the other question is, you know, we found this increased
risk for a whole series of cancers which we hadn't seen other
ways and insurance companies are going to use this very
effectively to re-write their underwriting policies.  
     I mean, isn't that discrimination?
     MS. KRAMER:  But, Zeke, is the answer to that then to allow
some community to impede the research, or is the issue to make
public policy such that the insurance companies can't
discriminate?  
     I mean, I just think, you know, by the time the whole
genetic library is devised and divulged, we are all going to be
parts of lots of communities that are going to be vulnerable
probably.
     DR. LO:  Let us go to Larry and Jack then.  I think Tom
wants to say something.
     I think one of the things that has come out of the AIDS
community consultation process is that, when an issue is raised
in just those terms, the solution has not been to stop the
research; it has been to say, "Let us try and do the research and
let us independently try and put pressure on insurers and
employers not to discrimination."       And I think the activist
communities have been very, very helpful in those terms saying,
"We have identified an issue; the way to solve it isn't to turn
off the research, but it is to sort of involve the community in
other ways to call attention to this very real problem of
discrimination that some people are feeling."
     Larry?
     DR. MIIKE:  Yes.  There was a point Bette just made--one of
the points I was going to make--which is that it is an
inappropriate remedy at the wrong place, if you do--
     MS. KRAMER:  What is?  I am sorry.
     DR. MIIKE:  I agree with you in the sense that you don't,
you know, the research end is not the place to try to deal with
the discrimination.
     MS. KRAMER:  Of course not.
     DR. MIIKE:  But I guess the way I would deal with this whole
issue about what are we talking about with community versus
individual, if the individual objects, we don't go and ask them,
"Why are you objecting?"  If they object, we just don't do
anything anymore.
     I mean, you know, like I can say it is because, "My moon is
in the second house on that particular day," and you are not
going to ask, "Is that reasonable?"
     But when we get to the--
     DR. MURRAY:  Well, that is a good reason.  What would be a
bad reason?
     (Laughter.)
     DR. MIIKE:  But when we get to the community side, we are
all sort of saying, "Yes, but we are not going to take any old
reason; we are trying to delve into the reasons for it."  So, to
me, that is why the informed consent stuff on the community side
breaks down.
     And I think we are all agreed that we are not dealing with
informed consent in that particular sense any more--right?--and
we are moving toward a consultation model. 
     But, again, when we get to our final recommendations, I
still am sort of struggling with this issue that we have been
discussing--sometimes tangentially; sometimes direct on--which is
how common is that situation where you have enough time to build
a momentum for the consultation process versus the one-shot
deals?  
     And are we going to be able to come up with some
recommendations again that deal with both, or are we consciously
say, in one area, there is not much concern on that side, and
makes it more an accumulate process that we have to--
     DR. GREIDER:  I personally think that the answers that Jack
gave answered some of my concerns about the one-shot deals; that
there does seem to be a way that you can go out and get at least
some consultation with the community, even on a one-shot deal.
     DR. MIIKE:  But is that--  However imprecisely defined the
AIDS community is, it is a community.  And in these other areas I
have a hard time identifying communities.
     DR. KILLEN:  But it wasn't a community--  But it wasn't a
community when we started.  You know?  We found ways to reach
into it and it is a new community all the time.  
     DR. MIIKE:  But how did you start?  You started up with the
people who came out forward and complained and were activists. 
You didn't go out and look at the ones who were not complaining
and not activists.
     DR. KILLEN:  Yes, we did.  Actually, we did.  Because many
of us were concerned that we were hearing a very biased sample of
community.  So we did, actually, in fact, go out and say, "We
need to broaden.  We need a bigger net," if you will.  How do we--  We did.
     MS. KRAMER:  But, you know, maybe the lesson to be learned
from that is that community arose and identified itself because
of its vulnerability, and they became activists on their own
behalf because of that vulnerability.  And in their activism,
they have certainly advanced.  They have advanced the treatment
of that whole disease.
     I mean, their activism has been very constructive for that
community.  Right?
     DR. KILLEN:  Yes.
     MS. KRAMER:  Tremendously so.
     DR. GREIDER:  But you are thinking about the first community
that started it as--
     MS. KRAMER:  Pardon?
     DR. GREIDER:  The community that got the ball rolling.  But
what I hear Jack saying is that there were a bunch of other
communities that weren't activists to begin with.  That AIDS is
not just gay men.  There are a number of other communities that
are involved that weren't activists.  And he said it is possible
to consult.
     DR. KILLEN:  And I think that the--  You know, we have sort
of two parallel efforts going on.  We have the therapeutics
research program.  We also have a huge vaccine research and
development program, which is a totally different community, if
you will.  It is a community at risk of becoming infected and--
     DR. LO:  Injection drug users in the inner city?
     DR. KILLEN:  Yes.  Yes.  And it is a completely different
set of people.  It is a community where what you are trying to
mobilize is interest around prevention, and traditionally that is
not a thing that our society pays any attention to.
     And we have found ways to reach into that community.  It is
different.  It is a very different dynamic.  It is not an
activist dynamic.  It is not a beating down the door kind of
adversarial relationship at all.  
     On the contrary, it is--  Well, there is a totally different
set of things going on.  So maybe that is actually a better model
for most conditions that you are thinking about than the
therapeutics one.
     But what we have done is take the lessons that we learned in
therapeutics and tried to apply them in this other very different
setting.
     MS. BACKLAR:  Can you describe that in greater detail?
     DR. KILLEN:  Yes.  What we are going to be doing in vaccine
trials is trying to recruit an uninfected population that is at
some risk of infection and studying whether or not a vaccine
protects them from infection.  They will have to be followed over
long periods of time.
     There are all kinds of very interesting and fascinating
discrimination problems that those people face.  Just coming to a
clinic that has AIDS in its name is problematic.  People who
participate in a vaccine study very well might test antibody-positive so that, on a causal screening, they would appear to be
infected with all the ramifications that that might have for them
as individuals.
     And actually, in some of the earlier studies, we had
relationships break up.  We had people lose houses, lose housing. 
We had insurance cancelled for individuals who stuck out their
arm and said, "I want to be a volunteer in this study."
     So that whole dynamic is a completely different population,
a different community that we are trying to reach into to
understand this research process and become partners in it; help
us figure out how to do research in it in ways that are fair and
good and right and ethical.
     MS. BACKLAR:  So do you, when you are designing a study that
this, do you try to put protections in place?
     DR. KILLEN:  Oh, yes.
     MS. BACKLAR:  The kinds of harms--
     DR. KILLEN:  Oh, absolutely.
     MS. BACKLAR:  --you just described to me?
     DR. KILLEN:  Absolutely.  Absolutely.  At least until
recently we had--these people had--cards that they carried that
said, "I am in a research study and contact blank if I have a
blood test that says..."  Yes.  Very definitely.
     MS. BACKLAR:  Yes.  But, for instance, the loss of housing
or the loss of jobs.  You mentioned quite a few.
     DR. KILLEN:  Those are very isolated cases, but I think what
they do is point to the problems that we need to address.  And it
was because we involved the community in the process of designing
the studies that we were able to identify ways that the problems
could be circumvented--
     DR. LO:  Let me just--
     DR. KILLEN:  --in ways that are satisfactory to the
community.
     MS. BACKLAR:  How did you identify this community?  This was
a community of people who were at some risk for the disease?
     DR. KILLEN:  Yes.  That would vary from place to place, from
circumstances to circumstances.  
     In Baltimore, one of the cohorts that we are working with
sort of grew out of a community of injection drug users.  In San
Francisco, one of the groups that we are working with grew out of
the gay community there.  And we were able to identify people in
those communities.  
     We just went to them and said, "What do you think we should
do?  Who are the people we should talk with here?"  And so you do
it from a local level, depending on the local circumstances.
     DR. LO:  I have a historical footnote, which I think is
important; that, at a slightly earlier point in the epidemic, is
that demographics were changing and people realized that
predominant mode of infection was going to be injection drug use
and sexual intercourse leads to that, rather than gay men.
     A lot of people saw that the demographics were shifting. 
You were really talking about people of color in the inner
cities.  And the first attempt to get community input was to say,
"Who are the leaders of that community?  Let us go to them."  
     So people went to the churches, which are very dismal often
in these communities, to elected political leaders, and they were
in denial.  They didn't want to talk about it.  And people had
meetings and the "leaders," in a political sense, weren't
interested.
     And I think the next wave was really much more of a grass
roots level of people trying to identify community-based
organizations who were providing services to people who were
injection drug users, homeless, and whatever.  
     And I think there are some really remarkable stories of
trying to sort of go and find the people who really sort of speak
for those at risk, in a sense that they provide service to them
and, in many cases, actually are former injection drug users
themselves.
     So, back to Larry's point, it isn't easy to naturally find
the people you want to consult with and you may have a lot of
false starts.  And it takes an incredible amount of time and
effort, but even in groups that aren't very well educated--the
use of groups being in the positions of power--with a lot of
effort I think you can really bring them in.  
     In that sense, there may be an analogy to some things we are
talking about.
     We wanted to--
     DR. MURRAY:  Yes.  I am going to--  Thanks.
     DR. LO:  Oh.  I just wanted to thank Jack for coming.  It is
very useful and we may want to come back to you at some point as
our ideas crystallize and say, "How would this work in your
situation and what are the analogies?"  But I think this has been
really helpful to get us thinking.
     DR. KILLEN:  Thank you for the opportunity.
     DR. MURRAY:  Jack, I want to add my gratitude, and to Bernie
for helping to organize this.
     As I recall, Paul Ramsey published The Patient as Person
about a quarter of a century ago.  And in it Ramsey developed the
idea of researcher and subject as co-adventurers.  At that time
he saw the consent process as the key--in fact, probably just
about the only--element of being co-adventurer.  It would be
transforming the subject from being a kind of passive exploited
subject into--his phrase--co-adventurer.
     What I think we are hearing today is that there is another
step that has been taken and that conceivably could be taken even
in our realm here--tissue samples--namely to becoming a much more
genuine co-adventurer in implanting, thinking about, organizing,
et cetera, of research.
     Now that would be not returning to business as usual in
certain realms of research, and I am sure some researchers are
going to be uncomfortable with that.  And if and when we make
such recommendations, we can expect to hear that.
     On the other hand, we understand, from the experience that
Jack related to us, that there are some advantages even to the
very design of the research, but also to the general level of
trust, partnership and co-adventuring that exists between
subjects and researchers.  And those are all things I believe are
proper.
     Let me tell you my proposed plan from here until noon. 
Another brief--real five-minute--break for those who need to take
care of personal needs.  
     We are going to return and take up the discussion of the
framework in the boxes.  I think we can begin filling them in, in
a more informed way, which means we will continue also to talk
about community, since that is a key element in the boxes. 
     So far we have no one registered as wanting to give public
testimony.  During the break, would you please so identify
yourself to Pat Norris, or another member of the commission
staff, if you want to do that?  We will simply allot time before
noon for that to happen.  So we will begin the public testimony
according to how many people want to give public testimony.
     Okay.  We are breaking for five minutes.
     DR. GREIDER:  Can I ask one quick question?
     DR. MURRAY:  Carol?
     DR. GREIDER:  Are you going to be able to stay, Jack, for
this next discussion because I think it would be very valuable
for that.
     DR. KILLEN:  Yes.  Absolutely.
     DR. MURRAY:  Thank you.  Back at 11:15 a.m.
     DR. KILLEN:  I wouldn't miss it.
     (Whereupon, at 11:10 a.m. there was a brief recess.)
     DR. MURRAY:  Here is the game plan.  We have one public
testimony, so we will do that at 11:55 a.m.  
     We have now until 11:55 a.m. to talk substance, to begin
filling in the boxes.  We have a good background now on thinking
about community consultation.  We have some models on that.  And
let us get to work.
     Zeke, do you have any inspirations on where you want us to
begin filling in the boxes?
     DR. EMANUEL:  Well, I mean, if we--(Inaudible.)
     REPORTER:  Give him a microphone.
     DR. EMANUEL:  The immediate thing is to do--
     REPORTER:  A microphone.
     DR. EMANUEL:  --1a and 1b--
     REPORTER:  A microphone.
     DR. EMANUEL:  --because that is the current--
     REPORTER:  You need a microphone.
     DR. MURRAY:  I got it.
     DR. EMANUEL:  I can't yell loud enough?      Because that is
the current--  Those are the only two current boxes that exist
currently.  All boxes are collapsible into 1a and 1b by the
common rule and, as I understand it, 1a says, I mean, if we
assess IRB review, 1a, according to the common rule is, if it is
going to be used in an anonymous manner, no IRB review necessary.
     1b is no individual consent necessary.  It is existing data.
     1b, IRB review necessary and full informed consent of the
individual, and no community linkage being done, so no--  I mean,
they don't even recognize that category in the current standards.
     And I think in these, where there is no community linkage
intended, that it falls outside the purview that we are
interested in.
     The paradigmatic case that Steve had originally raised was
looking for colon cancer genes randomly, not being worried about
a particular grouping or community.
     One of the examples I had circulated was the look for tumor
angiogenesis factors, just going through the Brigham pathological
files, of which would be the sort of 1a kind of category.
     And actually I think I have here--  This is sort of the
current policy outline.  That is my interpretation of what the
current policy is.
     MR. HOLTZMAN:  And the only thing we layered on top of this
is, to the extent that we are going to add additional categories,
that, of all instances, the IRB should make the determination as
to what category the proposed protocol is in.
     So even though there is no IRB involvement, in terms of
approving the protocol in 1a, nevertheless they ought to say that
it is a 1a protocol; therefore we don't need to--
     DR. EMANUEL:  I think we had labeled that previously IRB
administrative review, which is does it fall into this box, or
have you--researcher--made a mistake, and you needed it.  It
really did fall into a different box.  
     Right.  That would be the change from the current.  This is
the--
     MR. HOLTZMAN:  But that is a global change?
     DR. EMANUEL:  Right.
     MR. HOLTZMAN:  We are not going to put it in each box?
     DR. EMANUEL:  Right.
     DR. MURRAY:  Now, should we take them in order?  Are we in
agreement on 1a, which is existing samples, where there will be
no individual linkage to the individual?  Let us run this.  
     We are presuming now that there will be quite adequate
stripping of identifiers, that we will have the appropriate
techniques and procedures, et cetera, for that.  We do have to
speak to those issues.
     But assuming that is all the case, do we agree that this is
a case where the IRB ought to review it administratively in order
to ascertain that it belongs in that category and, if it does,
and if the individual's privacy is appropriately protected and
there is no implication of a particular group, that it ought to
then go through administrative review to be sure it is properly
categorized and, if it meets the other requirements, that that is
all that we need to do.  
     That is too long of a sentence.
     DR. GREIDER:  But I agree.
     (Laughter.)
     DR. MURRAY:  Okay.  Would you explain to me what I just
said?
     DR. GREIDER:  At the coffee break.
     DR. MURRAY:  Is there any discussion or disagreement about
how to treat box 1a?
     (No response.)
     DR. MURRAY:  This is going to encompass a great deal of the
research that actually goes on with tissue samples.
     DR. EMANUEL:  Eric, you had some objection.  No?
     DR. MESLIN:  I will defer until you continue the
conversation.
     DR. EMANUEL:  Well, I think actually this is an important
place to--  I mean, let us--  I think it might be worthwhile
going through all the possibilities.  Could we go back and re-consent people whose samples we want to use anonymously?
     In the Brigham example, they had 104, 110--I don't remember--samples they went to, collected five to 10 years prior to the
date they initiated the study.  They are all to be used
anonymously, in fact were used anonymously.  Gotten some clinical
information with them.
     DR. MESLIN:  The only issue I would remind the commission of
is that the subject of consent, with those samples that were
previously collected, is one that certainly the Genome Institute
wrestled with a year and a half ago when it issued a guidance on
large-scale sequencing in the construction of DNA libraries.  
     And the resulting NIH/DOE guidance on that subject tried to
address this issue in the following ways:    First, it recognized
that, while consent might not be possible from individuals, that,
for purposes of those grantees satisfying their institutional
requirements to either DOE or the Genome Institute, they would
first have to attempt to get consent for continued use of those
previous collected samples;
     That an IRB would have to make a decision as to whether the
protocol for using those samples was appropriate; and,
     That the agency supporting the research--either DOE or NIH--would have to approve it.
     Now that is a very unique case example because it is part of
a set of pilot projects for large-scale sequencing.  It is also a
unique example because of the collaboration between NIH and DOE
on this issue.  
     But it is not unique in the sense that, when you have got a
set of samples that were collected for purposes completely
unrelated to--or potentially unrelated to--the present purpose,
and when many of these libraries were constructed, large-scale
sequencing wasn't an issue.  The Human Genome Project wasn't even
an issue.  So it is not that unusual to make the tough call.
     And what occurred in the guidance was the tough call that
some method of attempting to identify consent process approved by
an IRB would be necessary.
     Now there is one caveat, and the caveat was, for purposes of
the entire program, it was hoped that this situation, where
reliance on existing libraries--and Carol may want to say more
about this--was used, that there was every effort that new
libraries, more detailed with greater depth, greater coverage,
would be created as, in a sense, as quickly as possible.
     So it was hoped that, although the current situation was not
as satisfactory, there were certain risks in simply telling
everyone that we would shut down those libraries because consent
had not been obtained previously.  
     There was a good faith effort to develop a procedural
mechanism for allowing the research to continue in the very
important insertion in the interim, which was an unspecified
length of time, but a hope that that period would be relatively
short and that investigators, both library constructors and
library users, would make every effort to get new libraries on
line and quickly.
     MR. HOLTZMAN:  And therein lies the relevant difference,
right?
     DR. MESLIN:  Right.  Absolutely.
     DR. MURRAY:  Well, I am not sure that is a relevant
difference.
     I guess one of the things I am hearing, Eric--it is quite
interesting--is what distinguishes the cases where you have
existing libraries developed under circumstances of, you know,
somewhat confusing consent?  Minimal consent, no consent, but
supposedly anonymous.
     And I think what we have just--  One interpretation of what
we have just assented to was that, "Well, you don't need
individual consent there."
     Now, I want to make an argument that the libraries we are
talking about are so different in quantity of information
generated about an individual--I mean, we are talking about, you
know, whole genomes here--that it really makes for a qualitative
difference, but I don't know if everybody else would buy that
argument.
     The people that we are talking about, by the way, we are
talking about the basics or the tools, collections of pieces of
chromosomes that will be used in thousands of laboratories.  So
one individual's DNA might, in fact, be, you know, in many, many
different libraries and there is an intensity to that.
     Anyway, I will stop.
     DR. LO:  Can I ask Eric or Tom or somebody to say a little
more about what the ethical objection to that is?  
     I mean, one I think you already addressed is that the
science will be bad science and I think having NIH/DOE approval
sort of, you know, takes away that concern.
     Is another concern that it is really not anonymous; that you
know so much about the genome that de facto you could identify
the person or, you know, I happen to have my own copy of my
genome.  I can look around and say, "My God, at Northwestern
University they are studying me and I didn't know about it."
     Or is it the idea that, even if you don't know people are
doing something to you, it is just creepy to think that so many
people are looking at your genome and I ought to have a chance to
opt out? 
     I mean, because it would help knowing what the ethical
objections were to know whether those same objections hold for
studies where, you know, you are only looking at a very limited
part of my DNA and, you know, you are not going to be able to
identify me.  It is not really me in some sense; the way my whole
genome is.
     DR. MESLIN:  I think there are parts of each of those
concerns.  
     And, again, remember that this discussion began about 18 or
20 months ago, which is really light-years ago, in some ways, for
the way in which many of the ethical discussions about the use of
DNA through the ELSI Program at the Genome Institute have
progressed.
     I think we were especially sensitive to the fact that this
was the first time that this issue had arisen, and it arose
somewhat serendipitiously.  It wasn't as part of an
investigation.  It wasn't as part of a complaint.  
     It was us, in a sense, uncovering this in the course of the
way that science was progressing; that there was an expectation
that, based on already available samples, the Genome Project was
going to be doing human subjects research.  
     And in the paradigm that was operative at the time--if you
are doing research on human subjects, then some effort should be
made to obtain the consent of those individuals--there wasn't an
awful lot of advice that could be gleaned from the common rule.
     So I think it is fair to say that we were erring on the side
of caution and conservatism, and for good reason, and not just
simply because we were concerned about any adverse publicity, but
because I think we felt legitimately concerned that, in the
absence of clear guidance on whether or not these kinds of
procedures could be put in place, we needed to feel comfortable--we being the Genome Institute and our counterpart at DOE--that we
were acting both in the spirit and in the letter of 45 CFR 46.
     Another issue--that, again, maybe Steve or Carol can comment
on more effectively than I--is that we just weren't sure what the
state of the science was with respect to how much information
would be needed to identify individuals.  And in the absence of
clear and unambiguous certainty, that no one could be identified
in any way, at any time.  That infinitesimally small possibility
was enough for us to be cautious.
     Now, one can be concerned or critical or worried about
whether that caution was warranted.  I can say that we are now at
the point where the guidance has been implemented, that the pilot
projects where this large-scale sequencing is occurring are
complying with the guidance, and are giving their plans for how
they will carry them forward.
     So I think, again, you may want to inquire with others at
the Genome Institute and even others, if you think it is
relevant, who have been complying with the guidance as to how
onerous it is, or whether the analogy is relevant to the stored
tissue debate.  You might want to pursue that.
     DR. MURRAY:  Larry?
     DR. MIIKE:  Well, I look at what you have been talking about
as more constrained by what were either old rules or unclear
rules.
     Second of all is that if we go ahead with what we were
leaning toward, there is no prohibition about doing it the way
that you did it anyway.  We are not imposing a ceiling; I think
we are imposing a floor.  Right?
     DR. MESLIN:  I think that is right.  And we also--I didn't
mention it but it is probably appropriate for the record--that
this was all undertaken in consultation with OPRR, so they were
aware of the guidance and, in the course of their deliberations,
they have offered advice to other NIH institutes in this area.
     MR. HOLTZMAN:  Can we get into the facts of this case to see
how relevant or irrelevant they are to stored tissues.  I mean--
     DR. GREIDER:  I just wanted to ask--  I mean, there was one
point that I wanted to make and that, is if we are really talking
about box 1a, and we are talking about putting in place a robust
way to anonymize something, and you believe in that mechanism
that we say we are going to put in place, then this case falls
out because I think this is a case of thinking that it is not
truly anonymous.
     So it is an exception; something that would go through that. 
So if we are talking about making a policy, and we believe that
we can put something in place which is robust to make it
anonymous, then I think that this case does not pertain.
     MS. KRAMER:  Are you saying that would be the IRB
administrative review?
     DR. GREIDER:  No.  That is this double-blind study where the
researcher--  It really is anonymous.  The mechanism by which the
researcher doesn't know the person and can't walk back.
     MS. KRAMER:  No.  But you are saying this case would not be
anonymous.
     DR. GREIDER:  That it would be anonymous.  It would be in
box 1a.
     DR. LO:  That--
     DR. GREIDER:  Oh, I am saying that--
     MS. KRAMER:  Eric's case would be an exception you said?
     DR. GREIDER:  I would say that would be a case where you
wanted it to be anonymous, but you didn't really believe in the
mechanism that anonymized it.
     MS. KRAMER:  So, therefore, the safety net would be that the
IRB administrative review would catch it and say it doesn't
probably belong in 1a.
     DR. GREIDER:  No.  I am saying we should put in place a
robust mechanism to anonymize things, and that we have to believe
in that mechanism.  
     I mean, in our whole--  Everything we do is going to rely on
us believing that we have a mechanism--
     (Simultaneous discussion.)
     MS. KRAMER:  Yes.  I thought you were saying that, even with
such a robust mechanism, that this would be--
     DR. GREIDER:  I am saying that they--
     MS. KRAMER:  We would be able to think that this particular
case would be identifiable.
     DR. GREIDER:  That if I were in their situation, I would say
that, because I don't believe that it could be anonymizable, then
I am going to add this extra protection.  That is how I would
read the case the you just said; an extra added protection.
     MR. HOLTZMAN:  So--  So--
     DR. GREIDER:  But we can't put that as a policy for
everything we are going to do--
     MS. KRAMER:  No.
     DR. GREIDER:  --or we are never going to believe in our own
system of anonymizing things.
     MR. HOLTZMAN:  You can believe in your system.
     DR. GREIDER:  Yes.
     MR. HOLTZMAN:  But it could be the nature of the case of the
information you are ascertaining about the sample; that it is so
deep, so robust, so wide that it can't, by its nature, be
anonymized once that information and, therefore, your IRB would
say--
     DR. EMANUEL:  It is identifiable.
     MR. HOLTZMAN:  --it is identifiable.  Right.
     DR. GREIDER:  Okay.  Do we believe that that is the case
here?  I guess that I what I am saying.
     MR. HOLTZMAN:  Well, in this particular case, it has had
less to do with the fact that I think that you were going to, at
the end of the day, have the whole genome, so much as that they
knew the six grad students who donated their white cells.
     DR. GREIDER:  So in that case it is really is identifiable.
     MR. HOLTZMAN:  Right?  Bottom line.
     DR. MURRAY:  Well, I am told it was on grad students.  
     MR. EMANUEL:  It wasn't that many.
     MR. HOLTZMAN:  Right.  So that is why I think this is, you
know, this case is--
     DR. EMANUEL:  It is relevant.
     MR. HOLTZMAN:  --is off point, right, in that it--
     DR. EMANUEL:  But there is a general point.
     MR. HOLTZMAN:  There is a general point, but it is a
different point--all right?--and so what we have here is a case
where we knew the people who actually contributed the DNA, number
one, and, number two, you could say we are going to go get new
DNA.  All right?  
     It is not the case that you can recreate the whole archive
of samples.  All right?  And we are postulating that we are
anonymizing it.  Okay? 
     So I think the only thing this raises--again, is this point--is, is there research which, for all the anonymization in the
world, will be so deeply revelatory of the subject that it will
lead you back to the subject? And when the day comes that we all
carry our DNA sequence on a diskette--
     DR. GREIDER:  Then the answer is yes.
     MR. HOLTZMAN:  --all right?--and someone publishes a
sequence--right?--with sufficiently long stretching, you know the
answer better that I; that you will be able to say, "That is from
so and so."  Where you plug in your diskette and say, "You know,
that is me."
     DR. GREIDER:  But who else--yes--I mean, who else has that
information?  Right?  Is it--
     MR. HOLTZMAN:  You don't know.
     DR. GREIDER:  If it--
     DR.          :  The government.
     DR. GREIDER:  That is right.
     DR. EMANUEL:  I only--
     DR. GREIDER:  It is only known if you know it.  If you are
carrying your DNA around with you and you know that this person
published it and it is your gene, then it is still anonymous.
     DR. EMANUEL:  Let me--
     DR. GREIDER:  It isn't until other people know that it is--
     DR. MURRAY:  Yes.  But I think this is on the edge here.
     DR. EMANUEL:  Right.  I want to raise three points.  
     The first point is I think we need to remember very
carefully that, while it is the genetic studies that have got us
started, this is by no means restricted to genetic studies.  We
are talking about using stored tissue for immunology.  We are
talking about using stored tissue for lots of other--you know,
cytology--lots of other studies, as well as health records.  
     I mean, I think that a broad interpretation of the correct
cause here is very broad, so I think sometimes the genetics is
relevant; sometimes it leads us astray because I would think, at
least certainly up until 1997, the vast majority of studies are
not genetic studies that we are dealing with.
     DR. GREIDER:  Uhhhhhhh.
     DR. EMANUEL:  Second, I think--  Well, I may be wrong there.
     DR. GREIDER:  1985.
     DR. EMANUEL:  Okay.  All right.
     I think Eric raises an important point for us to think
about.  My own view is it doesn't change the substance of the
decision, and that is how are we going to justify this?  Now, I
think that there are, I would say, three possible justifications.
     One--
     DR. GREIDER:  Justify what?
     DR. LO:  Why we are not going back and consenting.
     DR. EMANUEL:  Right.  Why we are not going back and
consenting.
     One, I think, you know, draws on the I think historical
issue, which is historically we haven't gone back, and we have
not found it necessary to go back.  The interpretation of the
common rule is that you don't go back.
     Second is I think--these are progressively getting better, I
hope--the second is a somewhat practical issue, which is that,
you know, we have discovered that there are in excess of probably
hundreds of millions, a 100 million samples accruing at greater
than five million a year, and there is a practical problem of
going back and, unless we are going to re-write lots of rules for
dead people, et cetera, there is a huge potential cost.
     Third, I think that there are some deep philosophical issues
at stake here.  
     Now are you getting satisfied, Eric?  Your ears pick up?
     One is I think, you know, we shouldn't dismiss or minimize
advancement of scientific knowledge as a valuable item; that we
here, and that the United States people and government, are
constantly supporting; that they want more information and view
it as a valuable good.
     Second is the I think the sense that, if we really do ensure
that the tissue is being used in an anonymous manner, that there
is a sense that this is not, does not remain something of the
individual.  It is not theirs.  And they don't view it as theirs. 
They don't behave as if they view it as theirs.
     That this has entered, in some sense, a realm of a common
good.  People don't go back and reclaim their tissue.  They don't
want their slides unless it is really to check for a second
opinion, and things like that.
     And the third thing I think, if we really do have it
anonymous, the sense of harm that is going to accrue back to the
individual is vanishingly small.  
     And, you know, I think there we get into the balance of what
happens if we get the serendipitous information and want to
reveal it where, ironically to do that, I think we raise the
potential level for harm higher because of potential breaches of
that where it is not appropriate.
     Now I, by no means, want to suggest or imply that that is a
comprehensive delineation of ethical reasons, but I think it is a
list of ethical reasons that we have been talking about.  And
maybe there are more that will sway people different ways.
     Again, my own sense here increasingly is constantly that we
are in this box of you have got to have individual consent until
you can, you know, move out.  And I am not sure it is very
helpful of applicable in this case.
     DR. MURRAY:  So that would--
     DR. EMANUEL:  So that would be some of my reasons for
adopting the policy we have.
     DR. MURRAY:  I think this is--  Thank you.  That was an
excellent discussion, Zeke.  
     And I am assuming all along that you agree with some earlier
stipulations I made about if people objected to these in
research, you would honor that.  Right?
     DR. EMANUEL:  Oh, absolutely.
     DR. MURRAY:  Yes.  And we would expect researchers to
exercise something like due diligence in ascertaining whether or
not people had objected and, if they hadn't objected, then it is
okay if it is used in an anonymous fashion.
     I think we have filled in a box, folks.  Congratulations.  
     And now it is time to hear Mark Sobel give public testimony
for this morning.  Thank you, Mark.
     DR. EMANUEL:  But we have only got one box.