June 25, 2004
Ronald Reagan Building and International Trade Center
1300 Pennsylvania Avenue, NW
Washington, DC 20004
COUNCIL MEMBERS PRESENT
Leon R. Kass, M.D., Ph.D.,
American Enterprise Institute
Benjamin S. Carson,
Johns Hopkins Medical Institutions
Rebecca S. Dresser,
Washington University School of Law
Daniel W. Foster, M.D.
University of Texas, Southwestern Medical School
Francis Fukuyama, Ph.D.
Johns Hopkins University
Michael S. Gazzaniga, Ph.D.
P. George, D.Phil., J.D.
Ann Glendon, J.D., L.LM.
William B. Hurlbut,
Peter A. Lawler, Ph.D.
Gilbert C. Meilaender,
Janet D. Rowley, M.D.,
The University of Chicago
Michael J. Sandel,
Diana J. Schaub, Ph.D.
WELCOME AND ANNNOUNCEMENTS
CHAIRMAN KASS: We have this morning a plan
to return to the subject of neuroscience, brain and behavior,
a topic that we've taken up a couple of times in different
forms in the last two meetings.
And I remind everybody as to why we are at least exploring
this topic in most general terms. There is certainly a sense that
studies and techniques of neuroscience and a study of the brain is very
likely to be of great importance for human self-understanding both
individual and social, and because the brain is so intimately connected
with many of the things that make us human, interventions,
technological interventions based upon this new science will raise
acutely many ethical issues, not necessarily unique ones, but will
raise certain kinds of ethical issues in the most profound way.
The last time, responding to suggestions that before we
probed any ethical questions we ought to learn a little something about
normal brain development and normal psychological development, we had
some very interesting technical presentations on brain development from
Dr. Jessel, and on child development, cognitive and temperamental from
Jerome Kagan and Elizabeth Spelke.
There were some that were wondering about where the ethical issues
were to be found in that discussion, and the truth is that there
weren't any immediately presented. But we promised that we would
develop some for the next meeting, and that the staff has tried
SESSION 5: NEUROSCIENCE,
BRAIN, AND BEHAVIOR IV: BRAIN IMAGING (CASE STUDY)
Today we bring forth two areas, none of them burning
questions at the moment, but things visible already here and on the
horizon, two areas that are fraught with some serious ethical
questions, one having to do with the knowledge gained from
neuroimaging, the other the uses of brain stimulation and the treatment
of psychological and behavioral disorder, and we've divided the
morning sessions exactly along those lines, one having to do with the
ethical questions arising from the acquisition of new information about
the brain and new kinds of knowledge about the brain through
neuroimaging and the other questions having to do with the
possibilities of intervention in relation to behavioral disorder.
I think that we start from — just to speak in a very crude
way, I think a lot of public interest in this topic has to do with the
recognition that working on the brain one is somehow working on the
mind, working on the person, or working on the soul, and that there are
large philosophical questions that surface here from time to time, but
as Dan Foster pointed out, I think, the last time, this is ancient
conundrum, and this Council is not going to settle that kind of
But whatever might be the ultimate truth about the
connection between the brain, its activities, and things called person,
mind or soul, certainly in various practical situations people will
wonder about whether the brain is different and whether approaches to
various human phenomena through the brain raise different kinds of
How would the biological approach to behavioral problems or
questions having to do with moral content differ from biological
approaches to diabetes, which is a non-brain matter, or biological
approaches to those brain matters known as dementia and dyslexia, to
dysfunctions of cognition or Parkinson's disease or epilepsy,
permanent and episodic disorders of motor function?
Are there other kinds of brain disorders or brain
abnormalities that would explain aberrant behavior? And if so, does
that open the way for direct and interventive treatment for aberrant
behavior, not through counseling, moral exhortation, not through
pharmacology even, but through direct actions on the brain?
I think these are the kinds of questions.
To get this conversation going, the staff has prepared by modifying
a case study that was first presented at a conference sponsored
by the Lasker Foundation, a case study that would enable us
to think about the ethical questions raised by gaining new
kinds of knowledge of a particular behavioral disorder.
And here the questions have to do with the use of knowledge
to identify and diagnose the condition, the use of that kind of
knowledge to predict possible future behavior, use of that knowledge to
control the propensity for such behavior by recommending various kinds
of intervention and monitoring its efficacy, and finally, should that
predicted behavior occur, to explain it and perhaps excuse it should it
be brought forth as a ground of moral and legal culpability.
And so keeping in mind, I think, the differences between
interventions and knowledge having to do with cognitive dysfunction,
interventions having to do and knowledge having to do with motor
disorders, we've produced a case that purports to show neurological
correlates of abnormal behavior, in this case anti-social personality
I think all of you have read the case. This is a young
man given to bouts of uncontrollable rage. Psychiatric work-ups
suggest that he might fit the criteria for antisocial personality
disorder, as described in the DSM.
Functional neuroimaging using simulated films reveal — and
the case study assumes that there has been enough study done on this to
show that this kind of correlation is at least reliable; that there is
as expected high activity in the amygdala, unusual and abnormal
activity in the orbital frontal cortex, thought to be an area that has
something to do with the control of anger and other behavior.
There are lots of technical questions that we could raise
about the case and we could raise side ethical questions about
the legitimacy of producing simulated pictures and simulated
cases involving the family pictures and the like, but I think
we should try for our purposes to focus on the questions that
have been posed by the staff in the working paper, and these
questions have something to do with the reliance on this kind
of information in making a kind of diagnosis, questions having
to do with what patients should be told and whether patients
are under an obligation to accept interventive treatment on
the basis of this.
And finally whether such people would be held morally and
legally responsible for acts of violence down the road following the
availability of this kind of knowledge.
Is that okay? I would like to try in the discussion to
keep us talking about one question at a time, and I'll try to move
us through the sequence of questions.
Let me begin with a question on page 5. It's very
clear that the imaging is fairly crude and is nowhere near offering a
causal explanation of these matters, but let's say you do have
these studies showing a kind of high degree of correlation between
these patterns and people who have been given this diagnosis. Just as
a general matter, what do we think about relying on neuroimaging to
assess antisocial personality disorder? Does this strike you as
different from relying on it to assess dyslexia or dementia or is this
simply a similar case?
Mike, that's why you're here.
DR. GAZZANIGA: Finally, I found out.
DR. GAZZANIGA: The problem is that many of
these braining imaging studies are averages of several patients,
and the brains are averaged, ten, 12, 15, 20, 50 patients,
and you get this virtual image of averaged brain areas active
during a particular kind of stimulation, cognitive stimulation.
The problem is if you go back to the individual scans, you
will see wide variation in the part of the brain that's
activated, and moreover, that is a reliable pattern because
you then take a particular subject back into the scanner six
months later and show him the same set of pictures, and a
similar pattern is established.
So I think if you look at a particular patient's image,
you might find a pattern that was consistent with some idealized view
of what structures are involved in a disease, but in any court of law,
any lawyer would be quick to point out that that is a pattern that is
consistent, but certainly you couldn't claim it was causal because
the next patient would have a completely different kind of pattern, and
consistent within the next patient, but not like the first patient.
So you're going to have all of this wide variety of
patterns, and therefore I think to seize upon one and say, "Look.
Those are the pixels that are responsible for this particular kind of
behavior, I just think it's going to be a hard time to establish
that in a court of law.
CHAIRMAN KASS: Well, if we don't talk about the law
first, let's simply ask, and people have done and I think we have
referenced here studies that have done very recently, published studies
on dyslexia in which in individual cases a similar kind of pattern has
been shown compared to a control group, an abnormal neuroimaging
pattern, and that this pattern has been reversed as a result of
successful interventions and an improvement of reading.
The case study assumes that similar kinds of patterns
provoked by patient specific stimulation produces some reliable
difference between the people the psychiatrist say have this disorder
and a normal control group, and the question is, leaving the courts of
it for now, but simply thinking about how we go about diagnosing people
who have various behavioral disorders, are there any issues connected
with just using this as a mode of identifying people with difficulties?
Doesn't the fact that we've got an antisocial
personality disorder rather than, let's say, dyslexia or epilepsy
raise any different kinds of questions here or is this just now
we're getting more sophisticated? Instead of having DSM, we now
can move to some kind of imaging that will give us the behavioral
diagnoses on which we should then start to rely?
That is, I think, the first question. Paul, what would you
DR. McHUGH: Well, first of all, it's important
to know that even the words "antisocial personality disorder"
don't represent, despite the fact that there is lists of category
or criteria you've included here, don't represent a pure
and clear category. Remember DSM-IV and DSM-III should be looked
at like a naturalist field guide, like, for example, Roger Peterson's
Field Guide to the Birds. It's important to have
that because we couldn't ever agree about what's out there.
But just as ornithology doesn't depend on the Field Guide alone
for its progress, but begins to employ concepts of evolutionary
pressures, environmental niches, ultimately responses, and begins
to see which ones of these so-called species are really independent
of one another, and which ones are really fundamentally blurred
into one another, there's an argument, for example, even believe
it or not about the Baltimore oriole, you know, whether it really
exists as something special.
CHAIRMAN KASS: Fifth place.
DR. McHUGH: Yeah. Now, the DSM-IV and DSM-III were very
necessary at a particular stage in psychiatric scientific evolution.
We had to at least know what we were calling — what the words we were
using were going to be across the nation. Once again, you had to tell
the difference between a yellow warbler and a Prothonotary warbler even
though some people might think that those distinctions weren't
Now, when it comes to the so-called Axis II groups in DSM-III
and IV, which include the compulsive personality, the narcissistic
personality, the antisocial personality, those are to be looked
at not as separate categories, such as you'd look at dementia,
as clear, cookie-cutter-like replicas of patterns, from patient
to patient, but should be looked at as tendencies, issues of themes
within the life of the person that they have more or less of, much
in the same way as you look at mental retardation.
So when you come to something like antisocial personality,
what you're saying is this individual has a temperament in which he
or she is more emotionally responsive to the situation at the moment
and less likely to feel for the other person on the other side, but
it's not an absolute, and the decision as to where you say this
person meets the criteria or this person just has antisocial qualities
is always argued.
Should you say somebody has an IQ of 80 has mental
retardation or they have to have two standard deviations from the mean
to have it, like 70?
I'm sorry, gang, to carry you into this long thing, but
to some extent getting to the heart of this, the question you're
asking, really does depend upon what you're trying to explain. If
you have a clear faculty loss, like the inability to read or the
inability to see, then aspects of finding something relatively clear
cut in the brain is probably more likely than when you're saying,
well, this person has a tendency to do this. Maybe he has a strong
tendency, but would you necessarily turn to the brain area to get the
diagnosis rather than continue in the psychological realm?
This is a long way around to say that before we can use the brain
pictures to take the place of the psychological elements, we've
got to be absolutely sure about what psychological elements and
what fixed psychological elements we're trying to describe.
Now, I believe with Steven Rose that the best way to look
at the emerging neuroscience and its linkages to the psychological
realm is to see it like the Rosetta stone, that we have several
languages. One language, you know, we've got the hieroglyphics and
the Demotic Greek and things of that sort, but the same message is in
each of the languages, and we don't know the translation rules from
one language to another.
Although we can perhaps expect that we'll find how to
do them, we'll probably also expect to find the same questions get
asked at this level will get asked at that level.
Now, let me just tell you what the question is about, the
antisocial personality, and even our patient here when you show them
something and they explode with emotion. The emotion may or may not
express itself in behaviors that you and I find reprehensible, like
striking out at somebody or hitting them.
And the psychiatrist again and again at the level of
antisocial personality are faced with people who say, "I
couldn't help it, Doc. I couldn't help it. I
And we always, "Well, we don't know the difference
between whether you couldn't help it or you wouldn't help it.
You punched that guy."
"Well, I couldn't help it. He made me so angry,
and you know, Doc, I'm just that kind of fellow. I have a hair
trigger, and I go off quickly."
And then somebody will say, "Well, you've got to
understand him. That's the way it is."
And I say, "Well, we're happy to try to do what we
can," but the real question is whether the society should have
something to say in this, too, not just us.
Finally, some wise psychiatrist will say to the person or
to us that, "Well, look, if there's a policeman standing at
his side, would he still punch him?"
And then the answer always is, "No, he
Okay. Well, yes, he has intense emotions. Yes, his
emotions explode quickly when he's thwarted, but certain additions
to the situation would change whether we would express it one way or
another. Then the treatment becomes how can we put a figurative
policeman at his side all the time.
And somebody says, "Well, you know, you
Well, then maybe you have to do something with him such
that he begins to see that that's there for him. Now, I don't
think cutting his brain is going to do it, but other forms of
restriction of his freedom and ultimately getting him to see that there
are real consequences that he can lead to control himself.
So ultimately it comes back to the question can you replace
yet the language of brain with the language of psychology. I say we
had better know the language of psychology if you're trying to do
that. I do believe you will find at the level of the brain much the
same things as you will find at the level of psychology, although
probably at psychology you will add more things, more appropriate
things that come from a culture and our understanding of each other.
That's a long way around to answering your question,
Leon. Can we —
CHAIRMAN KASS: You answered them all, actually.
DR. McHUGH: Yeah.
DR. McHUGH: But, you know, I defer to my friend Michael
Gazzaniga here because I might be — or Ben — I may be still at sea as
I'm trying to understand the Rosetta stone, as it were. We have a
richer vocabulary at the level of psychology, even though it's
still problematic in our categorization and our diagnosis than we have
at the level of — at the step-down, the Demotic Greek, if you would,
with neuroscience, but the neuroscience is coming on and bringing
wonderful things to bear.
I don't think it's going to really change our moral
attitude towards people psychologically in the realm of social
personality. It's certainly going to change and let us understand
a lot more perhaps about the dementias, things of that sort, where
faculties are lost.
CHAIRMAN KASS: Michael, to this?
PROF. SANDEL: This is really to put a question to Ben and
Michael and Paul, and to maybe just begin by not asking the big
questions about moral responsibility, but to start at a simpler level
and to clear away the uncertainties about the science just to clarify
Suppose the brain imaging became sophisticated enough so
that for every psychological syndrome that might take someone to
Paul's office, you could put that person in an imaging machine and
maybe show them the video or whatever it would be, and you could find a
certain place where their brain, the pixels lit up, and that you could
identify that with some regularity so that you could get a reliable
correlation between some event in the brain and the tendency to or the
inability to control anger, or whatever the syndrome would be.
Suppose you could do that.
CHAIRMAN KASS: That's the assumption of the case, in
fact, the exact assumption in the case.
PROF. SANDEL: And here's my simple question, even
before we get to moral responsibility and what society should do.
Would that be interesting to you? And if it would be interesting —
put aside even whether we have some intervention that can go in and fix
that thing. Put that even aside.
But would it be interesting? And I think it would be
interesting. And why?
DR. CARSON: Well, it actually gets at the root of a
continuum here because if you go back many years ago, you know, people
may act in an abnormal way. We didn't have all of the imaging
modalities, but sometimes, you know, maybe there's a meningioma
going through their skull and we could see that.
And then later on we got to the point where we had plain
X-rays and we began to see more and we began to make more assumptions,
and then we had CAT scans and we could see even more.
There was a time when people with epilepsy were thought to be
crazy or demon possessed or having some kind of behavioral disorder.
Certain types of epilepsy, then we began to do CT scans and we could
see the medial portion of the temporal lobe was small, was sclerotic,
and we started diagnosing mesial temporal sclerosis, and then we
found out if we went in and we resected that the seizures would
PROF. SANDEL: By the way, could I ask you did that lay to
rest the explanation that they were possessed by a demon or not
DR. CARSON: Yes, it did.
PROF. SANDEL: Why did it? Why did it?
DR. CARSON: Well, unless demons caused mesial
PROF. SANDEL: Well?
DR. CARSON: Well, maybe they do. I don't
know. So it hasn't definitely laid it to rest, but at
least we have an explanation now.
PROF. SANDEL: Well, maybe we have two explanations. Why
do we assume that one displaces the other? That's my puzzle.
DR. CARSON: But let me continue. But let me continue with
PROF. SANDEL: Right.
DR. CARSON: Because then we developed MRIs, and we could
see even more and we began to make even more associations. We began to
look at people's hypothalamus and saying, you know, homosexuals
have different shape and size hypothalami, and things like that.
And then functional MRI. We began to look at things even
at a cellular level and pretty soon at a molecular level and pretty
soon at a subatomic level.
There's no question that we will begin to find more and
more things that are wrong as we become more and more sophisticated,
and I guess the real question becomes what do we do with that
information because as we find these things, as we did with temporal
lobe, medial temporal sclerosis, we were able to accurately correlate
them, and we were able to do accurate intervention, and we are able at
an 80 percent level to cure that disease process.
So I actually believe as we apply science to these
observations and are objective, we will, in fact, be able to change
things. Now, you —
PROF. SANDEL: Could I press my earlier question?
DR. CARSON: Okay.
PROF. SANDEL: Let's say we've got this whole
explanation. The person is possessed by a demon. Then we discover
another explanation. There is this thing that you've described in
the brain. Why do we tend to think and is it right to think that the
new explanation is inconsistent with —
DR. CARSON: supersedes.
PROF. SANDEL: — or supersedes the other
one? Why is that?
DR. CARSON: I'll defer.
DR. GAZZANIGA: It is absolutely prejudiced against demons,
you know. It's pejorative in every sense. But you know, the real
problem with the example is that neuroscientists would flip through
hoops if they actually could find a pixel illuminated in the brain that
caused a set of behaviors in an absolute ironclad way. We're just
And the real fact of the matter is that you take any
clinical group, whether they be schizophrenics, whether they be people
with horrible frontal lesions and what have you, and where because of
their disease state, they are told that they are exculpable for a
particular behavior because they had a violent act or something like
The problem is that their rate of violence with this
disease is no greater than the rate of violence in the normal
population for almost all of these examples you read about time and
time and time again.
Now, you can take the case of schizophrenia. The rate of
violence isn't higher than in the normal population, but the jails
are full of more schizophrenics. How could that be? There must be
Well, they're full of more schizophrenics because of
drug abuse, not because of their violent behavior. And the orbital
frontal lesions are the same. You're supposed to get release from
inhibition and you tend to engage in more violent behavior, but the
wards are full of people with orbital frontal lesions that don't do
that, and so there's this problem that always captures you that
these oversimplified models of cause and effect of the lesion,
therefore the behavior are of interest, and they're certainly
tantalizing, but they're not — it's just not a set piece, and
so to get to this idealized case, there's always other reality in
the way that whole thing —
CHAIRMAN KASS: But I'm sort of puzzled. Paul begins
by saying, "Look. This is just a list of symptoms." It's
kind of an empirical thing to sort of know what the words mean, and you
could say, by the way, dyslexia is just simply a name. It's not a
disease. It simply means trouble reading.
If it turns out that you find, for example, not knowing
causation yet, but certain kinds of unique patterns on imaging that
correlate with difficulty in reading, let's say, in 80 percent of
the dyslexic cases, I would think that you know you now begin to think
you have some kind of organic foundation for these kinds of cognitive
Similarly, if you've got a group of people that
you've been classifying for years on this symptomatological basis
and the neuroscientists now say, look, in 97 percent of these cases —
I'm not talking about causation — but there is an imaging picture
which seems to correlate with this and not with other things, and never
mind that there might be other kinds of violent people who act out for
I would like to think that one would say, "Look. This
helps us. This helps us identify. This helps us diagnose. This helps
us point us in the direction of what the underlying foundation of this,
even if we don't yet know cause."
And we're not talking about exculpation. We're
simply talking about getting a new appreciation that this is something
which is brain related.
PROF. SANDEL: Why do you say, by the way, underlying
foundation? Why don't you just say a description from another
point of view that turns out to be accurate? Why are you privileging
it by that language of underlying foundation?
CHAIRMAN KASS: Because I —
PROF. SANDEL: You're sounding here like Steve Pinker.
CHAIRMAN KASS: Well, this is the question. Don't you
think that the discovery of the presence of scar tissue in the brain at
places or tumors in the brain in the places you'd expect when you
see epileptic seizures is a better explanation than demonic
PROF. SANDEL: Well, I think that's a practical
CHAIRMAN KASS: No, no, no. I think it's .-
PROF. SANDEL: No, I don't think it's — it's
better if it turns out it provides ways of treating the problem that
wouldn't have occurred to us otherwise, but to take the example of
the dyslexia and the inability to read and you find some correlations
in the brain, that suggests two possibilities for treatment. One is it
might be if you could intervene in the brain you could change the
ability to read, or if you teach the person to read, you might find
when you do the next scan that those physical characteristics will have
So it's a practical question whether we, given the two
descriptions can find practical interventions from one direction or
from another direction.
So which explanation is better? I wouldn't say one is
more foundational a priori. I would say the better explanation is the
one that helps us devise a way of intervening that's effective, but
I wouldn't say necessarily that because we find a physical
correlate that the best intervention always will be the physical one.
CHAIRMAN KASS: We're not talking about the
PROF. SANDEL: But that's the only test of better
PROF. MEILAENDER: Could I just ask a question here?
I'm not unsympathetic to the position you're pressing, Michael,
but it seems a little bit less persuasive to me when I think of the
case of dementia.
Would you try to run that argument through in that case?
Do you think it will work as well?
The dyslexia one isn't bad. How about dementia?
PROF. SANDEL: I know nothing whatsoever about it. I meant
that would qualify me to answer, but I would say what I would look for
to try to fit an account that would match the one here we would have to
know more about the reflexive character of the understanding. So the
interesting thing to explore, if you want to work from both ends,
obviously we would look to try to intervene at the purely physical
level, but we would also, I think, want to experiment and see whether
making the person aware of the new description would in some ways open
up possibilities of using that reflexive understanding to find ways of
So I would try from both directions. And I don't know
enough about it to know what would succeed or if either would succeed.
DR. McHUGH: I'd like to jump in there because this is
the key to that argument we had before with Michael or with Bob
Michaels when I said this approach to the brain-mind issue was a fairy
I said, and I'm with Michael Sandel on this, that we
don't know how the brain produces the mind and, therefore, we
don't know how the mind affects the brain. We do know that you
can't have a mind without a brain, but we also know that things
which happen in the mind will affect the brain, just like things which
will happen in the brain will affect the mind.
Now, the brain is an organ like any other. You can expect
it to suffer disease and damage and have that reflected in the mind,
but the mind is also an active agent that can affect the brain in every
kind of way that we know, and our problem always is this one. We
don't want to buy into the fairy tale that as we know the brain, we
are ultimately going to see absolutely new things in the mind.
I think it works both ways, bottom up, top down.
You've got to find out which way is the most effective way to
illuminate the problem, predict the future, and intervene properly.
Sometimes it works one way and the other.
CHAIRMAN KASS: We agreed we were not going to settle the
large philosophical question that .-
PROF. SANDEL: I think we just have.
CHAIRMAN KASS: But as a psychiatrist, are you indifferent
to discovering brain correlations that would give you an increased
sense of confidence that you're dealing with — that you have
somehow correctly identified a certain kind of problem?
In other words, are you indifferent to learning about the
brains of your disturbed patients?
DR. McHUGH: Absolutely not. No, I'm very interested
in learning. I want to learn all I can about it, just like I want to
know the Demotic Greek to understand the hieroglyphics and the
hieroglyphics vise versa. Without that, Champollion wouldn't have
understood this. I'm very interested in the fact that the reading
brain is correlated with the reading mind and vice versa.
But I don't want to privilege one over the other. I
don't want to go so far as to think that I'm going to introduce
demons back in because we've gotten into a lot of trouble. The
reason that we don't do the demons is, you know, we got into witch
burning that way and all kinds of stuff.
But, on the other hand, I don't want to give up the
fact that the human mind, in particular, is a marvelously active agent
that relates to the brain in ways that are totally mysterious to us.
We don't have a clue how it does it. Okay?
And just getting one language doesn't immediately let
you know how it links.
PROF. SANDEL: I agree entirely with what Paul has said,
but take the case we have here in the scenario. If the guy went into
the MRI, saw the video, had the scan, he presumably would be
interested. You or I, suppose we were in that situation, wouldn't
we be interested to know, well, how did it come out? We'd like to
have had that scan. We'd like to see the scan.
It wouldn't be just the doctor reading the scan,
figuring out, well, can I intervene and tweak it, and then if the
doctor explained to us, well, actually this is the event in your brain
that fired, that lit up when you saw that video. Here's a possible
explanation of the link between the two, and you would get into a
discussion, an interpretation with the patient about that. Then that
would be interesting and potentially a source of intervention.
So there might be a continuity between the brain imaging
and Paul's line of work. You would actually use that data as an
ingredient and an interpretation that the patient would share and maybe
you could work something. Maybe it would lead to some deeper
understanding that could liberate him from the grip of this anger
PROF. MEILAENDER: Just a quick comment. As I said, I
agree in large measure with the direction. The two-way movement Paul
is describing makes sense to me.
I have to say though, and again only within the limits of
my own knowledge which are considerable, that in the case of dementia
language like organic foundation makes more sense to me, and it's
harder for me to imagine what the form of intervention at the
behavioral level would be that might actually — you know, so that I
think the dementia case is a harder one for the line that Paul has been
pushing. The dyslexia or the behavioral disorder, I find it actually
pretty persuasive, but I'm less sure that organic foundation
doesn't look to me as if it works in a dementia case.
CHAIRMAN KASS: Alfonso.
DR. GÓMEZ-LOBO: First, with regard to the demons, I had a
sense of de javu because the matter was vigorously discussed in Greece
in the Fifth Century, B.C. In fact, there is a treatise by Hippocrates
on the same disease.
And I won't repeat the arguments, but basically what
happens is that in the naturalistic interpretation, you have a number
of criteria of consistency, prediction, et cetera, that you don't
have with the demons. The demons are very hard to fasten upon, and
actually it's, I would say, that little treatise together with the
treatise on ancient medicine that is the foundation for medicine even
today. Physicians look for natural causes. They don't look for
demons in Western medicine.
But I don't want to discuss that. I would like to add
to some really questions or maybe a slight countersuggestion, and
it's this. When Bob Michaels was here, he said we can read brains,
but we cannot read minds. I don't know if you remember that
And my first reaction was, gee, this is fascinating, but
then when I went home I started thinking, well, is that true. I'm
DR. McHUGH: The answer is no.
DR. GÓMEZ-LOBO: Okay, but that's exactly the point I
want to get to. If that's wrong, then the Rosetta stone analogy is
also wrong, and the reason is this, is that from what I've seen
here, what a neurologist does is to observe and observe phenomena, and
everything that Mike tells us is that, of course, we observe lighting
up and functioning of neurons, et cetera, et cetera.
Now, the process of reading is a symbolic process. To read
you have to take, for instance a physical reality, a sign, and
interpret it as pointing to something else, and any reading is
symbolic. For instance, I cannot read Chinese because I don't
understand the Chinese symbols. I could write, you know, Spanish with
a Greek alphabet, for instance. It's perfectly possible because
then I can understand the symbols.
So the assumption of the Rosetta stone, of course was that
you had the same text in three different sets of symbols, and
that's why it allowed Champollion to decipher.
The problem we're facing here is that when we talk
about correlation, we're talking about correlating things or
phenomena that have drastically different properties. Lighting up is
one thing. Choosing to take revenge on someone is a symbolic action.
You cannot understand it by sheer observation.
Even if you had, which Mike Gazzaniga tells us we
don't, but even if we had a perfect correlation, we would still be
lacking a key understanding of what's going on at the level of the
Now, of course, I wouldn't doubt for a second that the
brain is a I don't know whether you'd call it condition or I
don't want to commit myself on that, but it's certainly the
case that it's an organ that is intimately connected to all of
My only word of caution here is that any effort to
correlate the two has to take into consideration the fact that these
two things have drastically different properties, one, and second,
that, therefore, our observations of those properties have to go on
radically different tracks. We're just not going to understand
choice, for instance, by seeing whether certain regions of the brain
light up or not. I'm very, very doubtful that that is going to
CHAIRMAN KASS: Could I move us and maybe try to refocus
the question again, since Michael has given us the suggestion that the
patient actually might want to know something about this?
And let's keep this case and its assumptions in mind
and also keep the related case of epilepsy in mind, just these two
things. Let's assume that for better or for worse as part of the
standard work-up for suspected antisocial personality disorder brain
scanning, fMRIs, becomes routine and you do this study and you're
now the physician or you're the patient.
What should Jones be told and why? And if you're
Jones, what do you want to know and why?
And keep in mind as a parallel I'm assuming that he had
had a seizure, and we'd had loss of comparable kinds of things.
Is this different or is this the same?
DR. LAWLER: It's amazing you guys separate brain and
mind so clearly and metaphysically. I thought I was the old fashioned
guy on this.
Anyway, but abstracting from that, okay, let's say, and
it's probably so, I suffer from antisocial personality disorder,
which as Paul pointed out is a weasely and vague title for something.
All right. So I go in and I have an fMRI and the doctor says,
"Well, there's a correlation between your brain and your
inability to control your anger very readily."
I as an ordinary guy would say, "Yeah, sure. You mean
you're saying I'm hard-wired to have a quick trigger
In a certain way the doctor is not telling you anything you
did not already know. So when he tells you this, you almost yawn,
although you're glad to know this and go home and tell your wife
that, you know, "It's just the way I am. You know, tough
break," but you already were telling her that. Now you have a
picture that gives you evidence of that, number one.
Okay. Number two, and the interesting question that
Michael was raising: well, what do you do with this information in
terms of leading a better life or whatever?
The old fashioned view, which still is practiced by all
psychologists, is various ways you could be taught self-control, that
you're still responsible for this. We all have strong points and
weak points in our brains, and you're responsible for controlling
those bad things you have a propensity toward, and we all have some
propensity toward some bad things.
So the old fashioned teaching is pretend like there's a
policeman next to you. Go to church. Like Aristotle, develop good
habits or something.
But what if? And this to me is the only interesting
question at this point. It could just be a purely physical fix. We
could then change your brain so that you no longer have this propensity
to have a quick trigger finger or lose your temper too readily.
And it seems to me it would be utterly disastrous if we
could do that, and I admit we can't do that, but if we could do
that, it would be utterly disastrous to start to do that, although we
should cure epilepsy if we could.
Dyslexia is kind of on the border because there are ways
you could cure it short of — you know, people can learn to read
without having their brains changed, and as Michael pointed out,
sometimes the brains change when they learn how to read, right? So the
cause and effect is not so clear here.
But in this particular case, it would seem to me that
except in maybe a very, very extreme case, such as a guy that's
going to go to jail and is going to go out and kill someone, we
shouldn't mess with this, right, because there are certain
advantages to having this kind of personality. We might want this guy
on the front line during battle. We might actually want this guy to be
maybe not a policeman, but maybe a high school teacher.
DR. LAWLER: There are jobs for which this sort of
personality, this sort of temperament is an advantage, right? And so I
react badly to the idea that we —
CHAIRMAN KASS: Uncontrollable anger is an advantage?
DR. LAWLER: No, I don't think it is uncontrollable.
If you read the case, this fellow, you know, took up with Paul, got a
good psychologist probably. It could be controlled, right?
And then it was absolutely uncontrollable. It is an
extreme case, but if you read the antisocial personality disorder
characteristics, they are vague. I think I have two-thirds of them.
So it depends on the intensity with which you have these things,
right? So sometimes it may be direct physical intervention might be
the cause, but that would be the cause of last resort.
I'm in favor of telling the truth except in the case we
talked about yesterday. So you should tell the guy there is this
physical connection, and when you tell him that, you're not telling
him anything he didn't already know truly.
But then you say we're going to do everything we can to
use ordinary, old fashioned, psychological means to bring this under
control, and only as a last resort would we intervene physically.
And there will be a temptation in the future, in the
Utopian future described here, where these direct physical
interventions become easy to homogenize temperaments, and that I think
is the real danger here, right?
So my position would be — and also because of the point
Michael made — what we don't, right, is whether if this guy
responded well to Paul's old fashioned psychological therapy that
his brain would not, in fact, change, that the impulse would diminish,
So I think this is not like epilepsy. Dementia, the
difference obviously with respect to dementia is temporal. There is no
psychological therapy for dementia. You can't make that guy better
through other techniques.
And I'm done because there are so many hands up.
DR. GAZZANIGA: Just as a question in the intervention
notion, do people have a problem with the fact that the intervention
might be surgical versus pharmacological?
So we take this problem and flip a blue pill and everybody
is fine. Is that socially acceptable, whereas the neurosurgeon says,
"I'll go in here and tickle his amygdala and the person will
be fine, too."
I'm just curious to know what the fear or what the
concern of an intervention is. Is it that somehow when you touch the
physical brain through surgery it's quite a different thing kind of
than when .-
DR. GÓMEZ-LOBO: Can I respond to that?
CHAIRMAN KASS: Could I make a procedural comment? The
subject of the actual intervention for behavioral disorders is the
topic of the second session and Dr. Cosgrove is going to present that
issue. We're at this point simply talking about the uses of the
information both to predict and to intervene.
People wanted, I think, to respond either to Peter or Frank
and then Mary Anne.
PROF. FUKUYAMA: Well, and it seems to me one way of
thinking about this that might be useful to distinguish this case from
the epilepsy is just the economist concept of moral hazard because, you
know, moral hazard comes up with insurance. If you insure against a
certain kind of behavior, you get more of it because the consequences
are mitigated, and it's a very common way of understanding, you
know, a lot of behavioral problems.
And it seems to me, you know, what really makes epilepsy
and dementia quite different from this case is that there's no
moral hazard in either of those. I mean, if you knew that you had this
biological diagnosis, I mean, there's nothing in your behavior that
would change that would make it more likely that the behavior will come
Now, it seems to me that what happens in the other cases
where there is moral hazard is that, of course, you know,
scientifically you'd say there's some biological degree of
causation and then there's some, you know, degree of individual
responsibility. But the tendency in our society is to take the
information that there is some degree of biological causation and then
to run with that as far as possible.
And that's what leads to this general phenomenon we
discussed in this Council many times earlier of, you know, this
perpetually expanding domain of the therapeutic. And we saw this
before in ADHD where, you know, that's again a situation where
there are some patients where the behavior is very heavily biologically
caused and, you know, only a small degree of individual responsibility,
but there's a large number of other cases where the two sorts of
causation are much more equal and where people could modify their
behavior if they wanted to or with help or whatever, but once
they're told that there is a biological foundation for it, they
say, "Great. You know, just give me the pill and let me stop
worrying about my own degree of responsibility," and then it gets
into all of the economic incentives with insurance and everything else.
And so it seems to me that's really the problem with
this category of things for which there is moral hazard, is that people
like that actually, and they want to be absolved of, you know, the
individual part of the responsibility, and so they never get accurate
the relative weights of the individual and the biological causation.
CHAIRMAN KASS: Mary Anne.
PROF. GLENDON: Well, this is a question about whether
— I'm really not sure, but I think we may have already taken some
steps along the lines of informing patients and offering to them
surgical and chemical treatments for — I don't know the name of
the disorder, but what I'm thinking of is the violent, predatory
Does it help to think about that case, where we're
pretty sure in some of these cases that there is a biological basis. I
don't know whether it's in the brain or somewhere else, and
here's where I'm a little unsure, but haven't I read that
some of these people are offered surgical and chemical treatments and
do, in fact, accept them as a condition of parole?
DR. CARSON: That has been done, and I think that's
going to be covered in the second section. Actually that's part of
the paper for the second section.
CHAIRMAN KASS: Rebecca and then Bill.
PROF. DRESSER: This point has some overlap with what
Frank said, but the very act of labeling the condition as, all right,
this seems to be related to the brain lesion or whatever, I think we
always worry about consequences when labels are applied, and now I
think in this case one of the main, major areas of concern is social
consequences of getting a label.
But the other is personal consequences, and there's a
famous social psychology study, the Pygmalion effect where children in
first grade were divided into three reading groups, the Bluebirds,
Redbirds and some other birds, and they were told, "Okay.
You're in this group because your reading ability is lower than
average, average, or higher than average," and they were randomly
selected, and at the end of the year, they were tested, and they fell
right into their groups.
So the lesson was that even though it was unconscious, the
teachers, the students, everybody was playing into this classification.
So in this case I think telling the patient that, well,
we think your behavior is related to this lesion would affect
that person's, as Frank said, understanding of the problem,
his roll in the problem, and probably affect how others treat
that person, and it could actually increase the chance that
there would be more behavior just because of getting the label.
Now, you have the same problem if the label comes from a
psychological testing classification, but because of this tendency we
have to put a lot of weight on physical explanations, I think it would
be a special danger here.
CHAIRMAN KASS: Bill Hurlbut.
DR. HURLBUT: That comment seems to me to sum up one of the
major issues here. I don't actually agree with you, Peter. I
think that when you go and somebody tells you something about why
something is happening, people right now at least in the current phase
of our culture are inclined to take a scientific view, which has a
certain element of determinism in it and explain it away.
And I think here's really the crux of the question from
which a lot of practical issues flow, and that is what is moral
behavior. If it were epileptic seizures in today's world, we
wouldn't be so concerned about it. We'd say, oh, a physical
explanation. That's fine.
But when it comes to moral behavior, we feel with our folk
psychology at least, and probably correctly, that there is something
called freedom, and freedom is intrinsically not determined.
That's what makes it free, and that's what may be the
difference between our concepts of brain and mind.
At the most fundamental level, we feel like the mind has an
element of something that you can't describe with a scientific
finding. The interesting here, for example, with dyslexia, I have a
paper in front of me done by one of my colleagues, John Gabrielli at
Stanford, where they did a series of studies on children with dyslexia
before and after some remediation. This is mentioned in the paper, and
it showed a change in neural imaging after the remediation.
And so then you ask yourself, well, what's going on
there. Was the dyslexia just simply a physical cause and what else
would it correlate with besides dyslexia?
It turns out that there's a very high rate of dyslexia
among people on death row. So does dyslexia then also cause criminal
Well, the interesting thing is maybe it correlates, but the
question is what's between that and the criminal behavior, the
dyslexia and the criminal behavior. Of course, there's a whole
process of personal existence, the sense of low self-esteem that comes
with failure in school.
And so it's sort of what you make of the finding. I
think we should face into this. It seems to me that in the future
we're going to see more and more quasi correlative forms of quasi
explanation. I don't think we should avoid this issue. The
mystery of human existence is that there is something called freedom,
and that's what makes us moral creatures, but it's almost
certain that that freedom emerges from the fragile frame of our
And it's much easier to correlate a pathology with a
cause than it is freedom. Freedom emerges from the whole being.
It's the right functioning of the whole being, and therefore, it
correlates with something that's a condition but not a cause in a
Finally, our highest order behaviors emerge not just from
our physical existence, but our process of identity formation, our
memories, our habits, and then, of course, our aspirations, our beliefs
And that's where I think many practical things flow
from that, but it seems to me that what we're really contending
with here is that mystery, that what we think of as our highest order
human capacities, our moral capacities are, in fact, an emergent
property of our whole frame of being, not somehow of one identifiable
locus of cause just like there's really no brain that's a
reification, a convenience of thinking. There is no source of moral
behavior except the whole being.
So is that right, Paul?
CHAIRMAN KASS: Look.
DR. McHUGH: Wow.
DR. LAWLER: Yes or no? Yes or no?
DR. McHUGH: First of all, I believe, I absolutely believe
that we're going to and have to appreciate that freedom is what
we're all working to have for patients, and we're doing that
with physical as well as mental conditions, and freedom gets restricted
in a number of different ways, and ultimately freedom is not a faculty,
but it is a psychological experience itself of understanding the
distinctions and choices and taking responsibility for the outcome.
Now, we're capable of doing that because we have the
kind of brain we have, but it permits us to have the kind of mind we
have, which relates to that brain in a very special way, and it's
unique to humankind as far as we can tell.
And that was all swept under the rug by Steve Pinker and
all of that, and we should obviously salute that view.
I just don't think we can start, Bill, from that
position to understand the questions that have been raised around this
table about moral hazard, about the dementia question. I
remember so well what Rebecca is talking about because my children were
in school at that time, and they were getting various kinds of slips.
So I know all of that.
I don't think though we can answer the questions that
are raised here from that level. We've got to work at another
level to understand what the primitive field of psychiatry is about and
how it will relate to these problems.
CHAIRMAN KASS: Could I? I think we really have to come
down to the more concrete question rather than deal with this thing at
the most global level. You've got a dangerous guy here. This is a
fellow with an explosive temper and lack of self-control. His family
is bothered by it. Even if he doesn't feel remorse, he's at
least willing to go and try to seek some kind of help.
As part of the work-up, they find out that there might, in
fact, be something which it's not epilepsy, but there might be some
kind of organic contribution to his inability to exercise self-control.
And never mind what I think as a philosopher. Here's a patient,
and there is this kind of correlation, and I would be surprised
if this correlation is meaningless. Quite frankly, I would be surprised
if the people who have explosive temperaments and who have no capacities
for self-control have perfectly normal brains. It would surprise
That there would be a lot of abnormality that winds up
eventually in prison I don't think should surprise us, whatever our
philosophical view is, dualists or what.
And here is a question. I mean, here we have this kind of
information. What use should we make of this information? That's
a kind of retail question. It's not the question for the Council
What do we tell him? What should he do on the basis of
this kind of knowledge or is it knowledge?
DR. GAZZANIGA: What's the problem? If Mr. Jones has X
wrong with his brain and we have a pill that fixes it, fix it. Next
CHAIRMAN KASS: There you are.
DR. GAZZANIGA: I mean who's lessened by that?
DR. CARSON: Well, it's not that.
CHAIRMAN KASS: There are all kinds of people
who I think are trying to undermine the force and potential usefulness
of the findings. He (Frank Fukuyama) talks about the moral hazard
of making such a diagnosis. She (Rebecca Dresser) talks about the
trouble of labeling. He's (Paul McHugh) worried about contributing
to some kind of purely reductionist view of the human spirit. Bill
(Hurlbut) is worried about freedom.
I was waiting for Mike to say, "Look. Here is
biological information relevant to the person's well-being, never
mind society's well-being. Here is information that he should be
told about, and insofar as there is effective treatment available, he
should be encouraged to get it fixed.
DR. GAZZANIGA: Sure, why not? I mean, but let's go
back to —
CHAIRMAN KASS: Like epilepsy or other sorts of things.
DR. GAZZANIGA: Well, there are drugs that are active and
help schizophrenics, and they fix the dopaminergic system. You tune it
up and pretty soon people are in fairly good shape.
That solution doesn't ever touch the question of why
did that guy think he was the king of Siam before the medication. No
one has any idea how that works. The same with this.
So you can just fix it. Fix it and worry about all this
other stuff in some other context.
DR. CARSON: Well, one thing we have to recognize even
about the epilepsy case. When people have lesions, we see them. We
don't jump to surgery automatically. If they can be easily
controlled some other way, then they generally are controlled some
other way. Surgery is usually not number one on the list. In some
cases it is, but not in all cases.
The other thing to keep in mind is let's say this guy
— and we have found some abnormality in his amygdala. It doesn't
necessarily mean that because there's an abnormality there we want
to go do something physical to it, but the reason that people have
envisioned a physical response is because there have been numerous
cases of people who have had rage type behavior and have had a tumor in
that area. We have gone and taken the tumor out, and the behavior has
It was the same kind of thing that led to the interventions
for sexual predators. Because people had tumors there, they went in,
took it out, the behavior resolved.
So you know, this is not something that came about just
because somebody saw an abnormality. There really have been
correlations for these things.
DR. McHUGH: Can I just come into this very important
discussion that Ben and Mike have brought out?
The problem for me is not whether you, if you have an
effective pill, whether you shouldn't use it. It is, one, what
you're using it for and what are the consequences as well of having
If you're simply using it in antisocial personality to
reduce the responsiveness of the patient, it is the same thing as
saying to the antisocial personality, "Never take alcohol because
that raises your threshold for anger." So I have no objection to
What I have an objection to is when you demonstrate that
this does lower his short trigger, that you then say, "Well, you
see, because we're able to do it with this, therefore, he
doesn't have any responsibility the other times when we didn't
have the pills and he shot his wife." Okay?
The fact that you can alter the temperament up and down
doesn't change a bit the moral question, which was part of the
things that made this really an interesting question at this point.
CHAIRMAN KASS: Everybody. Let's start Michael, Bill,
PROF. SANDEL: Well, I have no objection if it really will
make him better, all things considered, though what counts as better is
something we would have to investigate from social, moral, as well as
physiological point of view.
So I don't have any problem with Mike's answer if
it really will make this person, all things considered, better, but we
have convened in this session as the President's Council on
Biometaphysics anyhow. I don't think we can avoid that.
PROF. SANDEL: So I just want to respond to the worry.
There is a common worry, and it has been voiced around the table that
freedom is at stake here. Freedom is threatened by scientific
explanation or a fuller picture of the correlations in the brain.
I think that's a mistaken idea of freedom because it
conceives freedom as consisting in and depending on gaps in scientific
explanation, and then the reason it depends on the idea of gaps is
because it assumes that freedom is the capacity of the will to initiate
uncaused action, action that's uncaused in the sense that it
doesn't have some physiological correlate.
And I think that conception of freedom is a mistake, but we
probably don't have time to explore that here, except by way of
going back to some concrete cases.
It was said, perhaps, Leon, well, it wouldn't be
surprising if criminals had some abnormalities in their brains, but
then wouldn't we also say that the same would be true for saints?
If we were to give scans to Mother Theresa and we found that there were
features of her brain that we could identify that were different from
less saintly people, that shouldn't surprise us any more than it
should surprise us that criminals have certain features that are not
true of the general population.
Now, that isn't a threatening finding I would say.
It's not threatening to the idea that certain people are saintly
and others are criminal or sinful. I don't think that those two
descriptions or that scientific discovery in any way undermines the
saintly or the criminal as a mode of moral discourse and judgment and
There was an experiment someone did once. I don't
remember who did it, who wanted to find out how much the soul weighed.
Do you remember reading about this? And so he did experiments by
sitting near terminally ill patients and putting them on a scale before
and after, and at the moment of death figuring our how much the weight
went down when the soul departed.
And it turned out that, you know, the soul weighs, you
know, 2.5 ounces or something like that. Now, that experiment, I
don't think that experiment proves or disproves the existence of
the soul. It's surprising it weighs so little actually.
CHAIRMAN KASS: I'm sorry. I remember this
Do you want to quick to that because Bill was next?
PROF. MEILAENDER: Yeah, interestingly the second question
on page 5 used the language "abnormal." What more would we
need to know before an abnormal neural image?
Is the thrust of your point, Michael, that we shouldn't
actually we talking about an abnormal neural image but just a different
And if that's true, would — and this is really not
just for you, but I'm just thinking with you — if that's true,
would we want to say the same thing in the case of the demented
patient, that there wasn't anything about it that we'd call an
abnormal image, but just a different one?
I mean, I'm trying to figure out whether these cases
really are different sources of cases or not.
PROF. SANDEL: Well, I'm trying to understand
what's your —
PROF. MEILAENDER: Well, we've got saints and we've
got incarcerated people, and we've got the rest of us who float
around somewhere in between.
PROF. SANDEL: And if it turned out that we could find some
pattern between the brain scans are the same of the criminals and the
people in between.
PROF. MEILAENDER: I wouldn't call any of them
abnormal. I would just say here are these different ones, and
they're correlated with people we call by different names.
PROF. SANDEL: Well, it might or might not be useful
information. If that's the question, we might consider the brain
scan of Mother Theresa to be extraordinary and the one of the criminal
to be —
PROF. MEILAENDER: Well, that would just mean it's just
statistically abnormal, which isn't a whole lot different from
PROF. SANDEL: Well, these descriptions, I think, only
matter from the standpoint of possible interventions, but whether the
intervention is (a) desirable and (b) effective is a further question.
PROF. MEILAENDER: But if we said that the image of the
brain of the demented person is abnormal, we would mean characteristic
of a person who cannot really function fully as an adult human being
does when reasonably flourishing.
DR. McHUGH: Can I translate that into physical medicine
for you to make it clear what I think is going on?
PROF. SANDEL: Yes, yes. We try to treat it.
DR. McHUGH: I think that this issue that
you're raising Gil and that you're pressing Michael
on is, in fact, something that doctors are very accustomed
to. You take a baseball player who is at the top of his game,
and he's 33 years old or 34 years old and his batting
average is beginning to fall off, and he tries and practices
and works away to see if he can get his skills back to where
it was before with new weights and new exercises. And it
fails, and he goes to the doctor and the doctor says, "You
have amyotrophic lateral sclerosis. It is a disease of your
And of course, we're talking about Lou Gehrig. If you
look at the general batting averages of baseball players, they fall off
in a very particular way. It's associated with a statistical
change in the muscular structure of men as they age, but in Lou
Gehrig's case, you can see the batting average falls off the cliff
and you have a real pathology in the tissues that have got nothing to
do with the statistical change. You have a new process in action.
These things relate to what you're going to tell Gehrig
what he can do and what his future is, and it's going to generate,
and it's going to generate all of our scientists to want to find a
cause for that amyotrophic lateral sclerosis so that we can prevent it
in the future.
That's what happens, and that's the difference
between somebody who has a dementia that is falling off and a new
process is in action versus somebody who, like me, doesn't have
quite the same capacity that he had when he was 30 to remember the
names of all my friends and some of my acquaintances.
This is a natural process, and the other thing is a
disease. And dementia is that, and that's how we come at this
CHAIRMAN KASS: And what are these behavioral disorders of
DR. McHUGH: In relation to this?
CHAIRMAN KASS: Yeah.
DR. McHUGH: These behavioral disorders, if you want to
call them — I call them temperament disorders or personality issues —
they are the different forms of our constitution in which we have a
Bell shaped relationship in the world, and we're at some place
along these dimensions, and they express themselves not only in our
behavior, but very much more clearly in relationship to our emotional
responsiveness to the situation.
We're extroverts versus introverts. We're more unstable,
unstable. Those things are biologically built in, and they
are responsive to biological measures because nothing happens
in our mind that doesn't have some correlation with something
happening in our brain. It doesn't happen any other way,
and we have to think of them though in quite different terms
than we do in relationship to the diseases that reflect the
organ that generates it. Hence, the difference between dementia
and mental retardation, ordinary physiological mental retardation,
and in relationship to these behavioral disorders and what
we would do about them and imply from them.
CHAIRMAN KASS: Bill.
DR. HURLBUT: That strikes me as the right way to frame
it. Obviously, whatever else we are, we are chemical, and whatever
else we are, we're going to find patterns of brain circuitry for
every behavior that we manifest, but that doesn't make the pattern
of the saint somehow the same as the pattern of the criminal.
Obviously they would be different patterns, but one could manifest its
phenotype or its overt behaviors as a manifestation of a weakness,
whereas the other could manifest the fuller integrated functioning.
That would give them quite a different moral meaning and quite a
different practical meaning with regard to what we do with our emerging
The criminal might be doing what he or she does in a sense
by having a missing link in the chain of freedom, whereas the saint may
be doing something from an extraordinary level of freedom. And that
seems to me very different reality.
And so what I'd like to ask Mike, based on what you
said a few minutes ago, are we going to end up with two categories of
crime eventually? One will be pathological crime and the other will be
freely generated crime. One of them goes to the hospital and the other
goes to jail?
DR. GAZZANIGA: I don't think so, but that's
another story, and I'll send you an article I wrote on it though.
DR. GAZZANIGA: But let me raise maybe an orienting
question or orienting point for all of us to think about. If you are
an evolutionary biologist and you're trying to understand
something, what's the first thing you do? You ask, well, what is
the thing for that I'm trying to understand. So if it's a
kidney or liver or heart, you go find out what it does, and then you
figure out how evolution fits into that picture.
So the question with respect to the nervous system is what
is the brain for. You've got to ask that question.
Does anybody here? Do you all know the answer?
I know the answer. It's there to make decisions.
It's a decision making device. And if we're going to
understand how the brain plays a role in all of these things we're
talking about, we're going to have to understand how the brain
It's making a zillion decisions as we sit here on 100
different levels, from eye movements to breathing, to talking, to
trying to formulate a sentence, all of these things. It's a
decision making device.
What does neuroscience know about how the brain makes
decisions? Basically nothing. We're all kind of working on it.
People are doing elegant experiments, but how it all comes together
into making the final decision, a final decision that is being made, is
just the great unknown in neuroscience.
In these kinds of things we're just discussing,
we're dealing where we have maybe genetic dispositions to
particular temperament. There are biasing decisions. We're
affected by our somatic system in these decisions. We're affected
by our past experience in these decisions. We're affected by a
zillion things, but once you just sort of get out of the mystique and
just ask yourself the question, what is the brain for, it is the
decision making device, and that's how we're trying to
understand its role in all of these issues that we're dealing
with. That's what it is.
PROF. SANDEL: But then the question is one of the best
neuroscientists might turn out to be Dostoyevsky.
DR. KRAUTHAMMER: I think I have stumbled in on a seminar
on metaphysics here. But, Mike, there's a difference between the
organ of the brain and the organ of the heart. You don't go to
jail if you have an arrhythmia, but you do go to jail if you make the
wrong decision. So that's why you have to introduce the
metaphysics, and you can't be ultimately a reductionist.
I think the real question is, you know, is antisocial
behavior just as Gil was implying in this question, you know, one end
of a normal distribution of adaptation to societal requirements or is
it a medical abnormality.
The question, I think, here is medicalizing sin, if you
like, or criminality or bad behavior or bad decisions. I think
it's a critical question, and if you give the guy a pill and you
say you've solved the issue, you haven't. You have to decide
whether or not he's responsible for what he did, and that requires
answering the question. Is this a disease, in which case we would
assume he isn't? If a person is schizophrenic and he kills someone
assuming he is the king of Siam and the other person is a pumpkin,
well, you'd say, "Well, he doesn't go to jail."
But if it's not a medical abnormality he does go to
jail. So I think it may sound abstract, and it isn't metaphysical,
but in the end it's extremely practical as a question.
DR. GAZZANIGA: I think you have to recognize that this
decision making view of the person finds that person able to learn
rules and to follow them. Schizophrenics stop at red lights, right?
They know how to take a rule and follow it, and to call upon most sorts
of disease cases as being exculpatory just doesn't work.
DR. KRAUTHAMMER: What about Hinkley?
DR. GAZZANIGA: I know it has been done. I don't
particularly agree with —
DR. KRAUTHAMMER: Well, and you're saying it
shouldn't have happened.
DR. GAZZANIGA: Yeah, I don't think it should happen.
DR. KRAUTHAMMER: We shouldn't have an insanity
DR. GAZZANIGA: I don't agree with it.
DR. KRAUTHAMMER: It's a fairly practical
DR. GAZZANIGA: It's a very practical position, but
it's also such a teeny part of all court proceedings. Less than a
quarter of one percent is it ever used by —
DR. KRAUTHAMMER: Oh, you don't think it's an
DR. GAZZANIGA: Yeah, yeah.
DR. KRAUTHAMMER: A man assassinates the
President of the United States assuming that he's —
DR. GAZZANIGA: I'm just not particularly in favor of
the insanity defense.
DR. KRAUTHAMMER: I assumed that.
CHAIRMAN KASS: Frank, take the last. We're going to
take a break. Frank, take the last comment.
PROF. FUKUYAMA: I can kind of formulate my answer to this
question that Mike posed a long time about what's wrong with just
fixing this, and I think it was involved in this interchange between
Michael and Gil.
But I think another thing wrong, apart from this responsibility
issue, is in the question of how we define abnormal. Now,
the case takes, you know, this propensity for uncontrolled
violence, which almost anybody would agree is not socially
desirable, and I would say, Peter, it's not good in high
school teachers. It's not good in soldiers. I mean,
it's very hard to imagine a case where it is good.
But there is a kind of precedent and slippery slope issue
involved here because I think what people would worry about is the sort
of One Flew Over the Cuckoo's Nest kind of behavior, you
know. DSM is a book that's got oppositional disorder, you know, in
it as an officially recognized disorder, and if you remember the Ken
Kesey novel, you know, McMurphy goes into this asylum and it turns out
that all of the inmates are in there voluntarily because they're
just afraid of being out in the world, and so he tries to take them out
in the world and, you know, this is regarded by Big Nurse as, you know,
clearly antisocial behavior, and then he is given the lobotomy and, you
know, everybody then ends up conforming.
But it does seem to me that there's a large other
category of behaviors that are not, you know, sexual predation and not
uncontrolled propensities for violence where, you know, the good
aspects of behavior are all tied up with things that are, you know,
much more questionable.
And I guess, you know, you're kind of opening up the
possibility of biologizing that, too, and you know, raising these
questions. Then do we know what, you know, so clearly is abnormal?
And I think the precedent from the discipline of psychiatry
is, you know, a little bit troubling because there are a lot of things
that are considered abnormal which, you know, may not be.
I mean, homosexuality is a good case of that. It's
all very politicized and so forth.
CHAIRMAN KASS: Yes. Look. We did only partial justice to
what's here. I think to —
PROF. SANDEL: I'm not sure if it was partial
or excessive justice.
CHAIRMAN KASS: In a way our conversation will continue in
the next session when we're dealing with specific interventions for
behavioral and psychiatric diagnoses, but just as an observation, it
seems to me — and I'm guilty of this myself — to talk about
biologizing something, to give it that label and, therefore, to let
that label do the sort of work of defeating its desirability, I think,
is going to be insufficient here.
You remember the case of the guy who went up in the tower
at the University of Texas with a machine gun and shot up the place,
and one's attitude about what that was changed dramatically when,
after they shot and killed him, it was disclosed that he had a tumor in
the temporal lobe. One might want him eliminated; one might want him
incarcerated, but one would not have put that guy on trial and held him
morally responsible for what he did. That's a clear case.
These kinds of cases become less clear, and even if Paul is
right that with the policeman standing next to the guy he wouldn't
have beaten his wife, nevertheless, we move from an area where
something is absolutely clear to something where there might, in fact,
be major biological contributions to the lack of self-command.
And to simply name it as biologic in this thing as if that
was somehow going to be sufficient in a climate where this kind of
evidence is going to become increasingly important, I think, is to miss
the force of what's coming even before science can explain fully
how the brain is a decision making instrument.
These cases are beginning to come forward now, and the question
of how this bears on moral and legal responsibility can't
be answered, I think, because we worry about the slippery
slope. We have to, I think, face it directly.
Let's take a break and we'll convene at 20 after.
DR. GAZZANIGA: Just one point though.
CHAIRMAN KASS: Please.
DR. GAZZANIGA: There are plenty of patients with those
same temporal lobe tumors who don't go up and shoot up a campus.
CHAIRMAN KASS: That's true.
DR. KRAUTHAMMER: And there are plenty of schizophrenics
who don't do that either.
(Whereupon, the foregoing matter
went off the record at 10:08 a.m. and went back on the record
at 10:20 a.m.)
SESSION 6: NEUROSCIENCE, BRAIN,
AND BEHAVIOR V: DEEP BRAIN STIMULATION
CHAIRMAN KASS: Some wag in the room at the break indicated
that we need to develop a new kind of disorder for the DSM which is
called change the question and quick to metaphysics disorder.
CHAIRMAN KASS: And we have fMRIs ready for all of you
between now and the next meeting.
I don't want to take any time away from the session. The
change in the weather has led some of our colleagues to have to
leave before this session is over, and on their behalf, I offer
their apologies for the necessity of leaving before we're done.
It's a great pleasure to welcome Dr. Rees Cosgrove to the
Council. He's Associate Professor of surgery and neurosurgery
at Harvard Medical School and the Associate Visiting Surgeon at
the Mass General Hospital. He kindly interrupted his vacation to
come back and offer us a presentation on the just newly emerging
uses of deep brain stimulation not for motor disorder, but for disorders
And, Dr. Cosgrove, thank you very much. Welcome, and we
look forward to the presentation.
DR. COSGROVE: Dr. Kass, thank you very much for inviting
What I would like to do briefly this morning is give a very
short historical perspective because I think that's paramount to
understanding some of the moral and ethical issues that are involved
with surgery for psychiatric illness; briefly describe for you the
current practice of ablative surgery for psychiatric illness; then
discuss the issues of deep brain stimulation and some of the very
vestigial or rudimentary, early experience, and it is tiny, of deep
brain stimulation for psychiatric illness, specifically obsessive
compulsive disorder; and then trying to address some of the ethical
issues which Dr. Kass so kindly directed me to consider; and then leave
plenty of time for questions and discussion.
The modern era of psychosurgery was begun by this man, Egas Moniz,
who is a very celebrated and famous Portuguese neurologist who experimented
by injecting alcohol into the frontal lobes of 20 institutionalized
psychiatric patients and thought that 16 of the 20 were favorably
He subsequently went on to devise a more discrete operation in the frontal
lobe through burr holes, and this was such a major public health
problem in those days with the asylums full of the psychiatrically
impaired and mentally ill that these initial, early experiments
in treating psychiatric illness were very favorably received because,
in fact, they did actually improve behavior, and Dr. Moniz was,
in fact, awarded the Nobel Prize in medicine in 1947 for his work
in this area.
And he was the man who coined the term
At the same time, the champion of this field in this
country was a psychiatrist-neurologist named Walter Freeman, and he, in
conjunction with Washington, D.C. neurosurgeon James Watts, performed
multiple prefrontal lobotomies, which was disconnecting the entire
frontal lobes with the use of a sort of calibrated butter knife
inserted through holes in the coronal temporal region and inserted to
Dr. Freeman himself was an unusual man. There may have
been some psychiatric diagnoses potentially attached to him.
DR. COSGROVE: But his zeal and his sort of
overenthusiastic adoption of this procedure really was difficult for
the neurosurgeon. It's rare that the neurosurgeon is the
responsible character in these teams.
But actually the neurosurgeon showed great responsibility
by actually declining to participate and collaborate with Dr. Freeman
because he thought Dr. Freeman was over extending the applications and
misusing the surgery.
That didn't really stop Dr. Freeman who was a
neurologist remember, who then devised a procedure that he could do
himself, and this was the famous transorbital "icepick"
procedure in which a sharp blade was inserted over the globe, over the
orbit through the very, very thin roof of the orbit into the underside
of the frontal lobes, and he performed thousands of these.
He actually would cross the country in his van, really
advertise his arrival in major metropolitan centers, and actually
perform these at asylums and hospitals throughout this country, and
he'd perform ten or 20 in a morning and then off he'd go.
So Dr. Freeman was probably in large part responsible for some
of the negative feelings toward psychosurgery of this sort of closed,
nonstereotactic methods that were used.
As you might imagine, these procedures were associated with
some significant mortality and morbidity. It's estimated that
there was about a ten percent major mortality and morbidity.
Nevertheless, these procedures were considered actually useful, and
despite the fact that the National Commission on the use of Human
Subjects and behavior in research experiments in the mid-1970s said
that at least half of the patients whom were operated upon sustained
benefit from these procedures.
The psychosurgery had its grand demise slowly throughout
the '70s for many reasons. I think in large part the most
compelling ones were these moral, social, and philosophical aspects in
which I think we heard a little bit this morning about operating on the
brain to heal the mind.
Issues arose probably in large part because of, again, the
morbidity associated with these gross and very crude techniques. There
was a lot of, I think, people harmed by the early times of surgery.
There were a variety of political stances against this kind of surgery
because of the outrage, and there are a variety of medical and legal
But probably most compelling was that in the mid-1950s, the
first psychopharmacological agent, chlorpromazine, was introduced. And
so right at this time alternative psychopharmacological agents became
And as we've heard, it's far easier to give a pill
than do an operation to treat illness. then over the next, you know,
30 years a huge variety of more selective psychopharmological agents
that were very effective in treating schizophrenia, depression, and
even obsessive compulsive disorder arose. And so for a large variety
of reasons, surgical interventions for psychiatric illness basically
declined to just a handful of cases throughout the world.
And if you want to read a great book to describe all of the
somatic therapies that were used in these times of great need, read
Elliot Valenstein's book. It's a wonderful document of this
Currently, however, surgery is still practiced in rare occasions,
and the only two indications that we typically perform the surgery
for are major depression and obsessive compulsive disorder, and
the surgery is only performed in those patients who have severe
and incapacitating psychiatric illness.
The degree of severity is typically estimated or estimated with a Beck's
Depression Inventory score of greater than 30, and the global assessment
and function score of less than 50. These are people who are severely
ill and completely incapacitated.
In terms of obsessive compulsive disorder, we typically only operate
on patients who have a YBOCS — that's called the Yale-Brown
Obsessive Compulsive Score — of 25 to 30, and this is an enduring
illness. This is chronic illness usually of many, many years'
In addition, we only perform the surgery on patients who
are being completely refractory to all forms of conventional therapy.
So you must look at this as a salvage operation or a palliative
procedure, and it's only performed on patients who have actually
exhausted all forms of modern psychopharmacology and
pharmacotherapies. Typically this means that in the obsessive
compulsive disorder group that they've had three trials of modern
SSRIs with up to maximum tolerated doses augmented with either lithium
or Wellbutrin or clonazepam, any of those things.
In addition, one of the major therapies for obsessive
compulsive disorder is behavioral therapy, and they have to have
exhausted all forms of behavioral therapy or at least committed to 20
or 30 hours of behavioral therapy, and they've also had to fail
when appropriate electroconvulsive therapy, which we know is a very
practical and important intervention for major depression.
This procedure is undertaken, and I will review for you our own. We
have all patients who are referred to us undergo evaluation by a
psychiatric neurosurgery committee, and this is a committee that
has been in existence for the past 20 years at our institution,
and it is composed of six members, three psychiatrists, the former
chief of psychiatry in our institution and then a specialist in
obsessive compulsive disorder and a specialist in major depression.
There's one neurologist, myself as the neurosurgeon,
and a recording secretary to document all of the information that
passes through our hands. and it is this expert multi-disciplinary
panel that is charged with the selection and implementation of the
interventions. And this panel, primarily the psychiatrist actually,
are responsible for insuring that the accuracy of the psychiatric
diagnosis, the adequacy of drug and pharmacological therapies, the
adequacy of behavioral therapy and ECT.
One of the psychiatrists is assigned as the primary on the referral
and actually does a review of a detailed psychiatric referral form,
and all of the records are reviewed and summarized for the committee,
and then all of these things are discussed in a committee, and there
has to be unanimous approval by all members of the committee that
the patient meets criteria for surgical intervention, and there's
a whole bunch of other tests, including EEGs, MRIs, PET scans, neuropsychological
And then if they meet these criteria, then they're
brought in person for evaluation by the primary psychiatrist on the
case, the neurologist and the neurosurgeon for final decision making.
One of the important aspects of modern psychosurgery is the
use of appropriate outcome measurements. What we have attempted to do
and what is occurring now in the past decade has been implementation of
these outcome measurement scales. These are the same scales and using
the same thresholds in terms of determining successful treatment as are
used in pharmacological drug therapies.
So one of the important things is if we're going to
promote any sort of surgical intervention for a psychiatric illness, we
have to use terms and outcome scales that are recognized by the
psychiatric community, and so that we can show by comparison how they
rank with appropriate psychopharmacological therapies.
These are very standard and accepted throughout the world.
A Beck's depression inventory or a Hamilton depression
inventory of 50 percent improvement from baseline would be
considered a success in the psychiatrist's eyes.
Obsessive compulsive disorder, which we'll talk about a
little bit more, is much more difficult to treat, and there are fewer
successes. And so in this instance a 35 percent improvement in their
YBOC score is considered a successful pharmacological intervention or
behavioral therapy intervention. A global assessment of function is
sort of a psychosocial level of functioning and the minimum is a 15
point improvement in the GAF.
And then also, although a subjective score, this clinical
global improvement scale is a seven point score with one or two being
either very much improved or much improved.
So these are the scales by which modern psychosurgery is
measured, and in terms of our own institution, we actually put
additional — because we're looking at individual patients and not
groups of patients, we actually characterized our outcomes as a patient
who responds to our intervention as having in the depression scale
either a 50 percent improvement in their Becks and a CGI of very much
improved or much improved, or in the obsessive compulsive patients, a
35 percent improvement in their YBOCS and very much improved or much
And of course, patients have a continuum of response, and
so we considered partial responders as meeting the numerical criteria
for a pharmacological therapy or either that or being considered very
much improved or much improved by the rater.
And then all other patients were considered nonresponders,
even though there might be some improvement overall, but they
didn't reach significance or threshold.
So if we use these very much more stringent criteria, these
are very much more stringent criteria than was ever used in the older
psychosurgical literature, and I think that's in large part
explained by some of the differences in outcomes.
And one also has to consider that, in fact, in the old
psychosurgical literature none of the SSRIs and current modern
pharmacological therapies were available so that the patient on whom
we're performing this surgery on are much sicker, in general, and
have failed a whole host of selective pharmacological agents.
However, these are two of our own studies. This was the
first prospective study ever done to look at cingulotomy, which is one
of the procedures, ablative procedures, that is performed for obsessive
compulsive disorder, and performed prospectively using unbiased,
unrelated observers, and those more stringent clinical outcome
criteria, and in our group of those patients who had failed everything
else, you see about a third of the patients became responders and, you
know, 17 percent were partial responders for an overall response rate
of about 45 percent.
And we subsequently continued this prospective accrual of
data, and so some of these patients are in here obviously, but more
recently with a larger number of patients, with a longer follow-up,
surprisingly almost identical response rates.
So now neurosurgeons typically would look at a response
rate of 30 to 45 percent as being not particularly encouraging. If we
had a 30 percent response rate or success rate in surgeries that we do,
we wouldn't be doing much surgery anymore.
But I think that psychiatrists, if you take that this is
now a complete salvage rate, these are patients who failed all of other
forms of therapy, and I think that if the psychiatrists in the group
said that they did a drug trial in which a new agent was added on to
everything else that was being done and they got a 45 percent response
rate, that would be a powerful new drug in the treatment of obsessive
compulsive disorder, to salvage a completely treatment refractory
So while these numbers are not fabulous, they are, I think,
Now, that's one particular procedure. That's
cingulotomy in modern times. The other typical procedure performed for
obsessive compulsive disorder is capsulotomy, and in this instance,
this is the gamma knife capsulotomy results from the Brown Group.
Unfortunately it's unpublished results, but this is a very
impressive group with a lot of experience in dealing with severe and
intractable obsessive compulsive disorder, and they have a similar
number of patients with a similar degree of follow-up, and the gamma
knife capsulotomy is done with radiosurgical lesions in a slightly
different part of the brain, in the anterior capsule of the brain
And what's interesting is using, again, appropriate
criteria for rating outcome, they have 22 out of the 35 patients
responding, so for a 63 percent response rate.
What is very similar in terms of the two kinds of ablative
surgery performed for this condition is that there's no immediate
benefit from intervention. In fact, it goes six to 12 months before we
begin to see improvement, and in fact, as we follow the patients
further and further, in fact, the success rates go up, and that's
true for gamma knife capsulotomy. That's true for cingulotomy.
So as we follow the patients out further, they improve
more, which is completely in contradiction to the natural history of
obsessive compulsive disorder and argues against any sort of placebo
So if these ablative interventions are so successful, why
would we want to consider deep brain stimulation? Well, there are a
variety of reasons. Deep brain stimulation is now currently widely
applied to the treatment of movement disorders, and so many groups in
the country are very familiar and expert in the technology.
But the real advantage of deep brain stimulation is that
it's reversible. What is done is that using stereotactic
techniques and the same techniques that are used to make these small
lesions in the brain, instead of making a lesion, we implant an
electrode with multiple contacts, usually four contacts, into the
And so because it's reversible and we're not
creating a lesion, any side effects associated with implantation or
stimulation can be dialed down or you can turn the stimulator off, and
the side effects and the benefits are reversible.
So this allows us to explore areas that would not be
previously conceived as possible to place lesions in. The best analogy
is subthalamic nucleus stimulation for Parkinson's disease. No
neurosurgeon with experience would want to place a lesion in there
because the target is so small and the real estate so expensive
surrounding this small, you know, five millimeter nucleus that any
minor error in lesioning could create a devastating and irreversible
Now, by placing an electrode into the area, we all do now
with great regularity and with great safety.
So that is a primary advantage of deep brain stimulation.
The other thing, it's adjustable. So one can adjust in terms of
getting therapeutic benefit, and one can adjust in terms of any
negative side effects, and it also is adjustable potentially over the
course of that patient's illness.
So whereas a lesion is succinct and defined and
irreversible, deep brain stimulation is adjustable, which has very
We've talked about how it allows placement in otherwise
risky targets in the brain. So, in fact, most targets in the brain now
are potentially accessible by deep brain stimulation. It's
familiar technology to us, all neurosurgeons and stereotactic and
And the other important thing — and this is where I think
it creates certain ethical issues for the Council — is that it reduces
psychological barriers to implementation. There's something about
creating a small lesion in the brain that neurologists, psychiatrists
and lay people and patients have a problem with, although it has been
used successfully over the past 50 years.
But if you talk about stimulating the brain, and the fact
that it's reversible, the barrier to considering this kind of
intervention drops significantly. I can tell you that that's true
both in the Vegas nerve stimulation study for depression. That's a
relatively low risk procedure, and patients would volunteer.
They'd come into the office with their neck exposed like this and
say, "Can I be part of this trial?" because it's a
relatively low risk, and it's stimulating.
Similarly, when you stimulate the brain, I think a lot of
negative biases naturally are reduced. I'm not necessarily saying
that's a good thing, but it does actually reduce these barriers to
referral and barriers to implementation.
Deep brain stimulation, as we know, is currently accepted
and has FDA approval for all sorts of treatment of movement
disorders, intractable tremor, Parkinson's disease, and
the dystonias, and certainly in pain. It's widely performed
throughout the world for these indications.
It's under investigation for intractable epilepsy,
cluster headaches, and obsessive compulsive disorder, and soon
depression. So these are still experimental. We don't know the
results of these studies yet.
But there is the potential for a wide variety of behavioral
and other psychiatric conditions: anorexia, morbid obesity, addiction,
self-mutilation, violence and aggressivity, and schizophrenia. All of
these, in all of those indications, ablative surgery has been performed
in the past.
But you realize that here's an interesting moral
question. Anorexia nervosa is a life threatening condition. We've
all seen cases of that. Now, the psychiatric or the psychological
situation is that the patient is uncomfortable with their body image
typically. They can look in the mirror and they can say even though
they are thin and what you and I would say that's a very thin
person; they think of themselves as ugly and fat or their perception of
themselves is fat.
If you did an operation that restored their willingness to
eat and consume, because many of these patients in their worst
conditions are actually so malnourished that even minor physical
activity can actually result in pathological fractures. They die of
And so here's an interesting question. If you take
that patient, to save the patient's life and you do an operation to
make them consume more calories and eat so that now we're happy
with the image of the patient, but now they're looking in a mirror
and saying, "God, I thought I was fat then. Now, I'm" —
it would be pure psychological torture for the patient.
So that's an interesting conundrum. Even though
you're doing the best thing that you think for the patient and you
might save the patient's life, that's a horrible position to
put the patient in. Anyway, something to think about.
Now, there have been approximately greater than 25,000
cases of deep brain stimulation performed worldwide for Parkinson's
disease pain, tremor, dystonia, a variety of things. As of May of this
year, there have only been 23 cases performed for psychiatric
indications. So you're talking about .001 of the experience. So
this is in its absolutely embryonic stages.
And yet so why are we interested in it? We're
interested because of the early results and because of some of the
advantages of deep brain stimulation which I've spoken about. The
first published experience was from Belgium by Nuttin and they operated
and used the anterior capsular target. So instead of making a lesion
placing electrodes into this area, into the exact same area in which we
would perform a capsulotomy.
So we know that capsulotomy empirically has a pretty
favorable track record in refractory OCD patients, but instead of
making a lesion, we say let's stimulate, and in four of his
patients, three of them became responders and meeting criteria of that
same sort of 35 percent improvement in their YBOCS. One patient was a
nonresponder. And this was done using blinded observers and was done
in a very appropriate fashion.
So that was the initial experience that prompted enthusiasm
in this area, and I should say that one of the reasons that it's
important to discuss deep brain simulation is that there's so much
enthusiasm in the area that, in fact, some of it may need to be reigned
in, and the reason I say that is very year I give a seminar on
psychosurgery for neurosurgeons, and you know, typically I tell people
it's not something that you want to do very much of because, first
of all, it's not paid for. It's all gratis. It's
uninsured by Medicare. So all of the professionals and the hospital
institution gets no money for Medicare patients. It's one of the
eight specific procedures that Medicare and CMS denies.
But whenever I ask a group of neurosurgeons, stereotactic
and functional neurosurgeons who do surgery for Parkinson's
disease, do surgery for epilepsy, do deep brain stimulation, I ask, you
know, "Who's considering doing this this year?"
The hands go up, about 75 percent of them, and that to me
is a scary thought because it's a neurosurgical procedure, but
it's based upon an expert multi-disciplinary group of psychiatrists
and neurologists, and the neurosurgeon actually in this instance is the
technician, skilled technician nevertheless.
But in any case, so this was the original paper. There
have been a couple of anecdotal reports, and this initial experience
has prompted a 15 person/patient investigational trial in this country,
the results of which are not yet available.
One of the things that was learned from this early anterior
capsule experience was that although it's nice for us
to think that deep brain stimulation, you can turn it on and
off and, therefore, you can have a control state to this.
Patients and evaluators, both the patients and the evaluators
know when the DBS is on. So you really cannot blind this.
In fact, the Belgian investigators sent in medical students
to try and figure out if they could accurately predict whether they
could tell whether the stimulator was on or off, and they were 97
percent accurate in determining whether the thing was on or off.
So thinking that you can do one of the .- one of the
proposed advantages of deep brain stimulation is that you can do
blinded studies. You can't do blinded studies. Patients and
evaluators know when the stimulators are on or off.
PROF. SANDEL: How does the patient know?
DR. COSGROVE: Perception, feeling, how they're feeling
PROF. SANDEL: No, but independent of the relief of the
symptoms, do they know it's on?
DR. COSGROVE: No, because these thing are turned off and
on with a magnet, and it's simply their perception of how
they're feeling when it's on.
DR. HURLBUT: How does the observer know?
DR. COSGROVE: Well, I think it's actually how in
talking about the patient and looking at their behavior, looking at
their movements, looking at their interaction. It's a behavioral
The other way, of course, you have a monitor which you
check. This stimulator, the electrode is attached via a subcutaneous
lead to a pulse generator here that's placed just under the
clavicle, just like a heart pacemaker is, and you can interrogate this
through the skin, and you can program and change the settings all
through the skin, just like .-
PROF. SANDEL: With a magnet? How do you do it?
DR. COSGROVE: It's a little computer that's
telemetry, via telemetry, the same way you do cardiac pump pacemakers,
the same technology.
And the neurologist or the psychiatrist, as we do for
patients with Parkinson's disease, you can select which contacts,
the current, the pulse duration, the frequency, and you do that all
through the little hand held device that is superimposed over the pulse
PROF. SANDEL: Who holds the clicker? Like where is that,
in the doctor's office?
DR. COSGROVE: The doctor has that, yeah, yeah.
The patient can turn the device on or off with a magnet
that they just pass over the device. So they only have the ability to
turn it on or off. The physician is the one who has the ability to
So what's very clear, and this gets to your question,
is that when the DBS is on, patients were more alert, more spontaneous,
less anxious, and less depressed, very clear.
When the stimulator is on, it does not appear to impair
frontal lobe tasks. So neuropsychological tests looking at frontal
lobe tasks, decision making, all of these things.
The improvement in their Yale-Brown obsessive compulsive
score is sustained if DBS is continued, but when the battery fails or
you turn it off, the YBOCS improvement goes back to where they were
preoperatively. And then you turn it back on again and you can see the
sustained improvement again.
PROF. SANDEL: Is it immediately or over a period of time?
DR. COSGROVE: No, it's over a period of time. What is
immediate is the mood effects, but the obsessive compulsive traits or
disorder symptoms do not improve right away. They take time.
And the other interesting thing is that it requires high
stimulation parameters, and what happens is what or when. So it means
you go through a lot of batteries, maybe every one and a half to two to
three years you have to replace the battery. So not inexpensive.
And the other very interesting thing is that the optimal
effect is contact dependent. So we have four contacts in there, and
Paul Cosyns, who is one of the investigators in Belgium, relates this
very wonderful anecdote that one of the patients who successfully
treated has, you know, their four contacts, and she says, "Well,
Dr. Cosyns, when I'm at home doing my regular things, I'd
prefer to have contact two, but if I'm going out for a party where
I have to be on and, you know, I'm going to do a lot of
socializing, I'd prefer contact four because it makes me revved up
and more articulate and more creative."
So there's an example of contact dependency, and we have our
own patient who is a graphic designer, a very intelligent
woman on whom we performed the surgery for severe Tourettes
disorder and blindness resulting from head tics that cause
retinal detachments, and we did this in order to try and save
her vision. The interesting observation was that clearly
with actually one contact we could make her more creative.
Her employer saw just an improvement in color and layout in
her graphic design at one specific contact, when we were stimulating
a specific contact.
And that raises this very thorny issue of improving
performance with deep brain stimulation, which is not where we're
at obviously, and I don't think it's a place where we should
ever go to, but you can see that different stimulation through
different contacts has different effects.
So one of the things that Dr. Kass asked me to try and
address is are the indications for deep brain stimulation for
neurologic disorders, such as Parkinson's disease or epilepsy; are
they different from psychiatric disorders?
And it's my belief, and it's actually the belief of
all members of our committee that, in fact, trying to differentiate
surgical intervention for Parkinson's disease from psychiatric
disease is artificial. Trying to distinguish those things is
I believe that psychiatric illness is a manifestation of
the mind, the disease of the brain and disease of the mind.
So if we choose to perform surgery to help a patient, it should
be done more based upon the assessment of the risks of your
intervention versus the possible benefits that can be supplied,
and then a critical element obviously is the ability of the
patient to give informed consent.
And I think that one of the important things for this
committee to understand is that the patients on whom we're
operating, patients with severe depression, the patients with severe
obsessive compulsive disorder, these are severely ill psychiatrically,
and yet they are in the vast majority, they are completely aware of
their illness and they are completely able to give informed consent.
And so one has to avoid being paternalistic about our
protection of patients in the sense that if they are aware of the risks
and benefits and if they are able to give informed consent, then we
should allow them the opportunity to explore some of these novel
interventions in the same way that we would allow them to explore
enrollment in a clinical drug trial.
So to me the differentiation between neurologic versus psychiatric
indications is artificial and unnecessary, and I think it
stems in large part from the history of psychosurgery in
the past and some of the hold-over from the early and less
precise interventions, but it's clear that outcomes have
to still be measured using the clinically validated rating
scales that I have told you about.
And is deep brain stimulation different from
pharmacological trials? Many times we're dealing with the same
patient population. Most of our patients who come to surgery have
already failed multiple novel investigational pharmacological agents,
and there clearly is a difference, however, from a pharmacological
add-on agent to a surgical intervention, and it has to do with the
The risk of deep brain stimulation for intracranial
hemorrhage is probably somewhere between one to two percent. The risk
of neurologic deficit associated with that is not insignificant in that
one or two percent. The risk of malfunction of the device, infection,
abscess, all of those things, disconnection, a whole bunch of different
things, is probably in the five to ten percent range now. So it's
There are also risks of adding on pharmacological agents,
of course. You could get an idiosyncratic reaction and have a problem,
but you know, it's much easier to stop a medication than to explant
a surgical device.
So that's a major difference between deep brain
stimulation and pharmacological trials, but the design of these trials
and the selection of the patients, the follow-up, and the usage of
appropriate outcome rating scales should be similar. The only
difference, I guess, is some of the selection criteria. I would
propose that, in fact, for surgical interventions patients should be
refractory to all appropriate therapies, whereas one might consider
drug trials in patients with mild depression and you use a different
agent or, you know, moderate depression or moderate OCD. I think
surgery should be reserved for the most refractory and severe cases.
And then the issue arises. You can certainly do placebo
blinded crossover trials with drugs. There's some intimation that
you could do this with deep brain stimulation, but I think that's
I think that, first of all, you can't really do a
placebo surgical procedure, not a good one. You may have discussed
some of these, but certainly there is some micro lesioning effect of
just placing an electrode onto the target.
As I've said before, you can't really blind the
patients nor the observers. You can certainly do crossover trials
with deep brain stimulation because you can turn it on and off, and I
think that that's a real value.
I'll finish up shortly.
One of the important issues and outstanding issues for deep
brain stimulation is that we are not clear what the optimal
targets are. We don't even know what the optimal stimulation
parameters are, and we don't know what the long-term effects
We don't understand how deep brain stimulation works.
We know that in gray matter it typically inhibits gray matter
structures, and in white matter it typically excites white matter
But any neuroscientist knows that even in gray matter nuclei,
the deep brain nuclei, that yes there's a predominance
of nuclei or neurons, but they're all attached with a
myriad of white matter tracts, and so it's not as simple
as we make it out to be.
It's extremely expensive in terms of time and money.
The hardware, the equipment is expensive, and when you're utilizing
one of these pulse generators every one to two years, that's a very
important annuity to the manufacturer.
Not only that; it's extremely expensive in terms of
time for the treating physicians. Seeing the patients, adjusting the
stimulators, we know this for a fact in the Parkinson's group.
Always trying to get at a little better. There's no "okay.
that's good enough," and accepting it as such.
And you can imagine in the psychiatric population of always
trying to get that little bit better so that it's endless.
One important issue is to realize that currently, you know,
deep brain stimulation is device based, and there's only one
manufacturer in the world. So Medtronic has a monopoly on this.
Medtronic is the sole financial supplier for the investigational
studies. Most of the people who are involved in these studies are
Medtronic consultants in some way or another, or if not directly,
indirectly receiving a lot of research support for their activities
Now, I know many of the people, and they're all
upstanding people who are involved. I know the people involved in the
OCDDBS study, and they're all upstanding and wonderful people, but
one has to be cognizant of this very fact, that there's no
alternative to the supplier.
And one of the other big issues, and it's true for all
psychiatric research, is that there are no good animal models exist.
So we are doing this. We are doing experimentation on humans. In
Parkinson's disease we had great animal models. We understood some
of the basic neurocircuitry, and we had hypotheses in which we directed
our interventions, and we don't have that in deep brain stimulation
for psychiatric illness.
So I'll conclude by saying that deep brain stimulation
for psychiatric illness and indications are currently experimental and
remain so. The preliminary experience appears encouraging and,
therefore, proceeding thoughtfully and cautiously seems appropriate,
but — and this is the big "but" — we must guard against the
indiscriminate and wholesale experimentation and repeating the mistakes
of the past because this is, I think, an important opportunity to do
this right. We won't get a third chance to do this right.
On a very final personal note, I will say that as a neurosurgeon
— and Ben will back me up on this — as neurosurgeons,
we see an incredible amount of death and disability in our
daily life, in our daily work, from a huge variety of different
illnesses. So we're used to seeing death and disability
And in my near 25 years of doing neurosurgery, never in my
professional experience have I ever witnessed the suffering that these
people have, and it's suffering, constant suffering, and such
disability that affects not only the patient, but every member of their
family and friends around them. It is horrible.
So that anything that we can do to alleviate or lessen,
reduce these patients' suffering is important work.
CHAIRMAN KASS: Thank you very much.
There are a couple of our colleagues who are going to have
to promptly leave soon, and I'd like to give them the first shot if
they would like to take it, to ask a question. We're going to
excuse them shortly.
Michael Sandel is one.
PROF. SANDEL: This is just a naive factual question. Is
this different from or the same as what we read about in the popular
press about the use of high powered magnetic treatments for depression?
DR. COSGROVE: No, this is different. What you're
talking about is transcranial magnetic stimulation, and this is quite
different from that. There is a possibility — it does supposedly the
same things internally in the brain, but noninvasively, but it's
not continuous. You go and receive the transcranial stimulation. It
stimulates the train in certain areas and thereby that's how we
think that the improvement might result from. It's electrical
But it's only done episodically, and once these
electrodes are placed, it's internal and continuous.
PROF. SANDEL: And do you have a view about the comparison
between the two, the promise of the two? How would you compare them?
DR. COSGROVE: Well, the great promise of transcranial
magnetic stimulation is that it's completely noninvasive, and I
think that the problem is that I think that without continuous
stimulation, I think that it's less likely to be successful on the
long term, but both areas are investigational, completely
PROF. SANDEL: Right, and there's no data really to
compare them yet. It's still being developed?
DR. COSGROVE: No, there's no data. One synergy that
might come from this is actually predicting which patients might
respond to deep brain stimulation because if you can focus your
stimulation in a certain area, then you might be able to predict which
patients would respond, and then you would go to the risk and effort to
implant an electrode if you could select that.
This person seems to be responsive to transcranial magnetic
stimulation. Therefore, why don't we take the next step and do
deep brain stimulation?
CHAIRMAN KASS: Before Michael goes, it seems to me, just
to try to connect this conversation with the one we have in the
previous session, admittedly this is at a very early stage and there
are obstacles to having this implemented because of the Medicare
restriction and the like, but Dr. Cosgrove listed amongst the potential
applications of these addiction, self-mutilation, violence and
And assuming that one had rather severe instances of those
things that this is not a treatment of first resort, but for refractory
cases, would you be uncomfortable following this as a mode of
treatment? Would this be making us guilty of some kind of wrongful
understanding of the underlying foundations of a disease if in the
retail business you've got a patient with a severe problem of this
sort, and Dr. Cosgrove through deep brain stimulation can rescue them?
PROF. SANDEL: Well, yes to the first question
and no to the second. Yes, I would be uncomfortable, but
only because I'm squeamish about all of this stuff, but
no to the second question. I wouldn't rule it out on
moral grounds without knowing more about what kind of success
it could achieve. I wouldn't say it's some fundamental
violation of our humanity or of our understanding of moral
responsibility, no. I'm squeamish about it, but that
CHAIRMAN KASS: And squeamish about it in a way different
from being — are you equally squeamish about doing this for
PROF. SANDEL: Yes, it's just as squeamish about
planting the thing into the brain, but morally, no. Morally I
don't see a difference, provided it —
CHAIRMAN KASS: So the fact that it's a behavioral
disorder as opposed to a motor disorder is no part of your concern?
PROF. SANDEL: No, for reasons that were partially
developed in the earlier discussion. I don't see the intervention
to deal with behavioral disorders as crowding out or being inconsistent
with other interpretive or therapeutic ways of treating or of
understanding. I don't see the two kinds of description as
incompatible and at odds with freedom in a way that on a certain
picture they would be.
CHAIRMAN KASS: Questions?
DR. McHUGH: But I would be. I would agree completely. I
would say yes and no in the same ways, but I would be squeamish for
another reason than just invading the brain, and that's the reason
that Dr. Cosgrove brought up. Whereas in Parkinsonism we do understand
the mechanisms that we're working on in relationship to these
things; we have no clue as to what the mechanism is. Now, I'd
still do it, but I'm squeamish until we begin to discover whether,
for example, doing these brain stimulations are releasing certain
endorphins or exciting the pathways for self-stimulation and things of
that sort and then I would become less squeamish because I would then
know what we're doing.
Because we don't know what we're doing here, even
though we know that it's effective, I would be squeamish, but I
would be accepting of it.
PROF. SANDEL: Well, I would agree with that. That
doesn't reach the philosophical question that you were asking
though. Yeah, I would accept that.
CHAIRMAN KASS: Dan, do you want to comment? You look like
DR. FOSTER: Well, just one quick question. You've
mentioned over and over again how expensive this is and so forth.
Let's say if it were fundable in some sense. Would you have a
ballpark figure of what, let's say, the first two years of
treatment might be?
DR. COSGROVE: That's a difficult figure to come up
with. The equipment ballpark figure is in the $15,000 range.
That's for the first time. Each time you put in another IPG
Hospital cost for the initial implantation is probably in
the $30,000 range, and again, these are Massachusetts rates. So
they're very low.
But then the real hidden cost is all of the time and
multiple visits required for stimulation adjustment and that. It has
got to be over the space of — I can't really give an accurate
number on that because I haven't been involved in the trial, but
DR. ROWLEY: But doesn't that have to be weighed
against the costs? Otherwise, these are not patients who otherwise
you're spending no money on at all. So it's the differential
that you're asking about that's important.
DR. COSGROVE: Yes, that's absolutely true, but I guess
one has to also remind people that nobody is ever cured with these
operations. I think that's very important. So that nobody ever
gets off medication and nobody is ever cured, especially in the OCD
population. Their function may be improved and restored more back
towards normal, but in the patients on whom I have operated on and what
we have seen, nobody is ever cured and they remain under treatment,
both pharmacological and behavioral and medical.
DR. ROWLEY: But can they go back to work?
DR. COSGROVE: It's very rare because they're so
severely ill and they've had such disabling illness for so long.
We don't know about that in the deep brain stimulation because
we're talking about a tiny experience.
In my experience with ablative surgery, yes, there are some
people who go back to work. There are some people who are working
still. Those are the minority, but, yes, there are a percentage that
will go back to work.
PROF. SANDEL: Why don't you play out a little bit the
objection that underlay your question before?
CHAIRMAN KASS: It wasn't so much an objection.
It's partly what interests us here is whether any kind of initial
disquiet that anybody might have about these kinds of — in fact, Mike
asked before: is there a difference? People would be happy giving
drugs for these things but might be unhappy doing brain surgery. Is
that just because there's surgical risk or is there some kind of
quasi philosophical reason that you don't somehow fix people by
putting your hands on the brain?
And if that's your concern, how do you differentiate
between going to work on Parkinson's disease or removing a tumor
and actually doing this, even if we don't exactly know what
PROF. SANDEL: So we say no, but you may think yes. So
could you say a little bit, or what do you think? What would you say?
CHAIRMAN KASS: I don't have a firm opinion. In other
words, this is a real question. And, indeed, the more one sort of
talks about this, the harder it is for me to make the distinctions
between. That's partly why I was leaning on you in the other
session. I'm not sure it's so easy to make a distinction
between a behavioral disorder. The lines are fuzzy.
DR. KRAUTHAMMER: I'm not quite sure it matters whether
we know the mechanism or not. When we first started using
anti-psychotropic drugs, I'm not sure anybody knew the mechanism,
or lithium. I don't know the entire history, but a lot of these
there's an extremely obscure, but it worked, and if it worked it
I'm not sure that's the salient.
I wanted to ask our presenter. Do you feel personally any
differently, a difference between ablative and stimulative surgery?
DR. COSGROVE: No, because the scientific evidence
isn't there for deep brain stimulation, you know. So there are
theoretical advantages for deep brain stimulation. It's an
important opportunity to learn more about how the brain works in these
disease states and how it may be modulated. So I think it's an
important moment, but I'm not necessarily sure at this point that
deep brain stimulation is better than ablative surgery, and we
won't know that until we actually get many more years of
DR. KRAUTHAMMER: If I could just ask you, you had
expressed some concern about the enhanced creativity by your patient
who used electrode number four. Could you draw you out on that a bit?
Assuming you have a stimulative treatment that helps someone and they
do have enhancement of normal functions by tweaking it on occasion, are
you against the tweaking on principle or how do you feel about it?
DR. COSGROVE: Well, yeah. So now we're treading on
this tricky moral ground. In my opinion our concept is to restore
normal function. In the same way that I would have an aversion to
trying to use deep brain stimulation for social, political, or, you
know, legal issues, I have also a problem with trying to enhance
function artificially because it seems beyond what is normal for that
So I think of these interventions as trying to relieve
suffering. I think we can all agree that that's typically a good
thing and a laudable goal, and then to try and restore function back to
normal for that not beyond because then I think you're treading on
very difficult areas.
DR. KRAUTHAMMER: And just to follow up, do you think
that's scientifically plausible? Aside from the moral issues of
whether you ought to do it or not, do you think it will be doable in
DR. COSGROVE: Could you improve function?
DR. KRAUTHAMMER: Yes.
DR. COSGROVE: I believe it will be, and that's why I
think it's important to have these discussions now when it's
not an option at this point, but that there's a firm ethical
framework upon which we will judge and make decisions going forward
because I do think we will be able to improve certain functions in
DR. HURLBUT: What kind of functions?
DR. COSGROVE: Well, this is just an example of creativity
that was manifest in a single patient. So if you could work harder and
better and faster and do better work, then is that something — well,
that's what we try and encourage our kids to do.
DR. HURLBUT: What do you mention?
DR. COSGROVE: Well, one could be, again, more creative
from a scientific perspective. You may have clarity of thought. You
might have better as we've said artistic endeavors. I mean these
are all scary things. You might be able to analyze a situation more
Whether that's a specific effect or whether it's a
relief of some underlying problem. For example, on many of the
patients in whom you improve with depression, their performance on
neuropsychological tests often increases, improves after even
appropriate medication or even a surgical intervention, and it's
not because they are any really smarter or better. It's that their
mood is improved, which allows them to pursue and attend and function
at a higher level.
So all of these things are very speculative, and I'm
not typically a speculating type.
CHAIRMAN KASS: Peter, Janet, and Gil.
DR. LAWLER: So in your opinion, to summarize, right now
this is for symptom relief in very extreme cases.
DR. COSGROVE: Correct.
DR. LAWLER: But it could be a lot more than that, but
you're against that.
DR. COSGROVE: Yes, at this point in time.
DR. LAWLER: What if I had been a great
neurosurgeon, but I was suffering from mild depression and
I could save many lives if this option were open to me? What
would be wrong with that?
DR. COSGROVE: Because there are other, much better
alternatives for the treatment pharmacologically, and Ben probably is a
little depressed, and he still saves a lot of lives.
DR. COSGROVE: We all get a little depressed when you do
neurosurgery for this long.
So I guess it all comes down to — it all comes down to the
risk-benefit analysis, and you know, surgery always has risks
associated with it.
DR. LAWLER: I agree there's no ethical question if
it's symptom relief in genuinely extreme cases, but what's to
keep your colleagues from disagreeing with you as these procedures
become easier and the cost-benefit analysis starts to shift on you?
DR. COSGROVE: Well, when we have the evidence to
demonstrate that we really understand what the outcomes are, what the
benefits are, and what the risks are, then, of course, one reassesses
the situation, and in the same evolution in epilepsy surgery it used to
only be done for patients who had failed all anti-convulsive
In the past decade or so, we have evolved into the patients
with medial temporal sclerosis as that's a surgically curable
epilepsy, and we know that about 80 percent of those people with
appropriate operation will be cured.
So we've evolved from only doing it for the intractable
patients that failed medications to saying there is a subset that
really looks good and, you know, we know what the outcomes are.
Therefore, the risk-benefit is good.
Similarly, with Parkinson's disease, we used to only do
it for the end stage. Now we do it for younger patients because we
know what the track record is and we feel that there is an advantage to
doing it when you're younger to maintain function for longer.
When we get the information about deep brain stimulation
for psychiatric illness that we can hang our hat on and know, then we
DR. LAWLER: Well, now you're scaring me. Then
Leon's question kicks back in, right? This is a radical stand.
I'm for complete eradication of Parkinson's disease. I know
it's controversial, but the same thing with epilepsy and so forth
and so on. But what you're saying is over time what seems extreme
becomes less extreme because it becomes easier to do.
DR. COSGROVE: No, not because it becomes easier to do.
It's easy to do this now. That's not the difficult part. I
mean, it's easy for any good neurosurgeon to do this now.
That's the dangerous part. It's easy to do right now.
What we don't have is the knowledge and the experience
with it, and that is what's missing.
DR. LAWLER: So it becomes more easy and reliable and
comprehensible and stuff, right?
DR. COSGROVE: It's much more predictable.
DR. LAWLER: Predictable. That's the word I'm
DR. COSGROVE: "Predictable" is what you're
looking for. When we can predict exactly what the outcomes are going
to be, then it makes it easier to make a decision.
DR. LAWLER: Then the analysis for the decision is easier.
CHAIRMAN KASS: And now much a technical point in
follow-up, Janet, if I might intrude myself in the queue. On the one
hand, you seem to be saying that it's much too early to tell, but
it's at least conceivable that once the data were in, that
psychosurgery, precise psychosurgery of the sort we're now talking
about and precise stimulation, might become not a treatment of last
resort, but maybe even for certain kinds of conditions a treatment of
I mean if the trouble with obsessive compulsive disorder is
that these people who have had it for such a long time are now hard to
restore to work because, as you indicated, disease is so severe; there
has been so much damage as a result. Then one could make an argument
if one knew what one was doing that you shouldn't allow them to
have 20 years of this disease and that it would be more efficacious to
go in there early, assuming you could —
DR. COSGROVE: Predict outcome.
CHAIRMAN KASS: Predict outcome.
DR. COSGROVE: In that specific patient.
CHAIRMAN KASS: In that specific case.
DR. COSGROVE: So, yes, we have that same analogy in
epilepsy. We prefer to operate now on children with epilepsy because
we know what the natural history is of that disease.
CHAIRMAN KASS: Right.
DR. COSGROVE: To try and, you know, allow them to have a
40-year history of epilepsy and then operating on them when they're
40 seems a waste of time, but we have intimate knowledge of the natural
history. We have intimate knowledge of what the expected outcome will
be from an intervention, and we can make it even individual specific
because of our characterization, our knowledge of the disease, our
understanding of the pathophysiologic mechanism.
So while we can draw an analogy to that, I think that, you know,
I would not consider it as a first line of resort ever because
there are pharmacological and behavioral therapies that are
really the mainstay of treatment.
And as I've told you before, this surgery, ablative
surgery or this surgery, does not cure these patients. It improves
sometimes just their response to behavioral therapy or their response
to the medicines. So it would not be considered in the same way we
talk about surgical cures. It's a different animal.
CHAIRMAN KASS: Janet.
DR. ROWLEY: Well, actually the question I had has been in
part answered by these conversations. I was reminded of my colleagues
in oncology who started out with new drug therapies on the patients who
have failed everything, partly to get experience with a particular drug
or treatment, the dose, the scheduling, and all of the rest of it, and
for those that appear to be efficacious, and then moving on to using
them in earlier patients.
And so this conversation has said that, in fact, that might
be a possible scenario as you gain more experience both with the type
of patient that could respond to the treatment as well as all of the
down sides of this treatment so that you're more comfortable going
earlier in the patient's disease.
What I take away from this conversation in the last few
minutes is that, in fact, this would be an appropriate, reasonable way
to move, but you do indicate that surgery is not the first line for
virtually any patient, but that there may be a subset of patients in
whom some kind of surgical or deep brain stimulation intervention would
be appropriate much earlier in the disease than you presently feel
comfortable with, but you need more experience to determine that at
CHAIRMAN KASS: That's true.
PROF. MEILAENDER: Just a question. When you were
discussing the surgical procedures and the percentages of people who
are responders and partial responders and so forth, you said that the
improvement is greater over time. It's not immediate. Why is
DR. COSGROVE: That's one of the enduring questions,
isn't it? It speaks to our relative lack of understanding of the
neurobiological basis of these illnesses. We —
PROF. MEILAENDER: Could I just sharpen it? Is it certain
— does it raise questions about whether the basis is entirely
DR. COSGROVE: No, not in my mind. I believe, you know, in
the same way that it takes time for an antidepressant medication, you
know, you have to have it in the patient for two to four weeks at
appropriate levels before you begin to see any change in the
neurochemistry and, you know, before you begin to see change in
symptoms. The making a lesion or stimulating the brain is sort of an
internal neural modulation of some sort, and it's probably because,
you know, it's not a specific nucleus that drives all of these
things; that it's some rebalancing act that is occurring.
We don't understand why it takes that long and why we
tend to see improvement over time, and you know, even some of the
speculative mechanisms that we've used to explain some of these
things are just wrong. You know, we find out 20 years down the road
that, well, it seemed like a good explanation for it, and it seemed to
fit our empiric observations, but it was just totally wrong.
So I don't believe in speculation. I have too much
work to do to spend time speculating, and I am a fairly strong believer
in empiricism if it's valid, but nobody really understands why it
takes time. I think it has to do with interfering with circuitry that
allows the brain to remodel.
CHAIRMAN KASS: Ben Carson.
DR. CARSON: Yeah, Rees. That was a very, very informative
talk. I think it's going to give us a lot of food for thought.
One of the things that I think people need to understand is
that neurosurgeons tend to be extraordinarily conservative people, and
you can see from Dr. Cosgrove's presentation that he fits into that
I have no doubt that as time goes on and as people become
more and more familiar with the techniques and as more less invasive
types of techniques become available, that the degree of conservatism
will slacken and that the number of applications will begin to expand,
and this will become a significant issue.
You look at things like intervention at the level of the
hypothalamus. You know, if you ablate the ventral medial hypothalamic
nuclei, all satiety goes away. A rat will eat until, you know, it
The same thing would happen to a person. You stimulate the
lateral hypothalamic nuclei, they're not going to want to eat.
Now, don't believe for one moment that somebody isn't going to
try to exploit that, you know, when we come to all of this dieting and
ways of getting people to be looking, you know, the way they think they
should be. All of these things are going to happen because we can do
it. We have the ability to do it.
Like Clinton said, "I did it because I could."
You know, it's going to happen, and we're going to need to deal
CHAIRMAN KASS: Could I follow that? Because the
measuredness and sobriety of the presentation I very much appreciate.
In fact, that's one of the reasons why you were recommended to us,
and you didn't disappoint.
But you indicated that, on the one hand, there is a kind of
unfortunate restraint based upon the past history which prevents these
procedures from being reimbursed under Medicare, right? This is by
name specified as a no-no, and that now stands in the way of actually
people doing these procedures as much as they would be indicated to
actually help the people who were in desperate straits.
On the other hand, you say that whenever you get the neurosurgeons
together, you ask them, "How many of you guys are ready
to do deep brain stimulation for psychiatric indications?"
and all of the hands go up, which means that there is an enthusiasm
for doing this already, even in the absence of the kind of
knowledge that we have, and if that financial constraint,
if the reimbursement constraint were removed and you have
also this kind of monopoly, you know, of the device driven
and monopolistic character of the equipment, should we not
be concerned that there is something ready to take off here
in a few years?
I mean, or is this just science fiction and that we should
rely on the good, conservative sense of the Carsons and the Cosgroves?
DR. COSGROVE: No, you shouldn't because neurosurgeons
actually — I'm not sure I agree with Ben entirely that they are a
conservative group. Neurosurgeons often operate first and ask the
questions later, and in this regard neurosurgeons are not well equipped
to assess the accuracy of diagnosis, the adequacy of treatment. I
mean all of those things.
They are equipped to do the surgery, but sometimes it's
frightening to me how even ill equipped some of the people are that
undertake the surgery, where I get phone calls about, well, you know,
"I'd like to do a cingulotomy for such-and-such," you
know, and they're calling about the coordinates, about how you do
And I have repeated, you know, experiences this way, and
then at the end, after I'm thinking, well, are you sure you want to
do this or are you sure you have support of your institution, because
of the lay people's impressions and, you know, all of the trouble
you can get yourself into.
And then, you know, at the end of the conversation where
I've described everything and sort of put up all of the warning
signals and then at the end, you know, the neurosurgeon says,
"Well, are you supposed to do that on both sides?"
DR. COSGROVE: And I think, "Oh, my God," you
know. So I'm not so sure that we're all going to be
responsible practitioners. You see, I'm very sensitized to the
irresponsible practitioners of the past, and I do believe that this
surgery, whether you use ablation or deep brain stimulation, is an
important intervention. Currently it's an intervention of last
resort, and it is a good palliative procedure.
I do not think we will have another opportunity to do this. So
if we do not do this right and carefully and, you know, properly,
I don't think it will come back.
DR. ROWLEY: Can I just ask you a question? Is there a
role for the IRB here? I mean, you would think that somebody
couldn't just go and do an operation willy-nilly particularly in
what is an experimental operation.
So where are the institutional safeguards?
DR. COSGROVE: So one of the things, as I said, if
we're going to move forward with this, it should only be performed
by expert, experienced, multi-disciplinary groups, number one, with all
of the people that I've proposed.
Two, it has to have institutional review or board approval
for the institution. And so, you know, it has to because it is an
investigational, any intervention.
One good thing to say is that the company, Medtronic, which
creates all of this equipment, is actually very responsible in its
behavior. It is not out there trying to get people to do these
In fact, they, you know, don't want these done outside
of the context of a trial because they are also concerned about misuse
and abuse, and again, if it's not done properly, well, their bottom
line will suffer, and that's why they're interested in it.
But you know, we as practitioners and as leaders of
society, we have to concern ourselves with not their bottom line, but
the society's best interest and then the individual patient's
best interest within that society.
CHAIRMAN KASS: Bill. We're coming to the end of this
DR. HURLBUT: One very quick little question. When you
proceed from the costs, the practical and the aesthetic constraints on
this, wouldn't this really be better than pharmacologic treatment?
It's more targeted. It's more specific. You're actually
addressing a local problem instead of the global, systemic delivery of
And secondary to that question is are these techniques
eventually going to be very valuable in explorations as well? I mean,
you wouldn't explore in a well patient, but we'll learn a lot
from patients on this.
Can you combine this with local drug delivery through these
same devices and can you do a micro electrode analysis of what's
going on in the local area while you do it?
DR. COSGROVE: Those are fabulous questions.
Yes, it is conceivable that this would be more locally specific
than a medication taken systemically, although, again, it
reveals our basic lack of understanding of the neurobiological
basis of these illnesses, but we do know there's a lot
of evidence that implicates the frontal orbital cortex, the
ventral striatum, the anterior cingulate. All of these areas
that we've targeted in the past and that we're stimulating
now have broad ramifications primarily in the frontal lobes,
and cortical thalamic connections and striatal connections.
So, yes, it is possible that you could get a better, more
selective, therapeutic effect with deep brain stimulation. It's
possible. No evidence to suggest that that's so at this point in
Can you learn a lot about human behavior with these? Yes,
by implication you can stimulate different contacts, and can you by
stimulating alter behavior and, therefore implicate those areas? Yes.
You have to remember though that just because you're stimulating in
one little area doesn't mean you're not stimulating afferents
and efferents that are going to far reaching neural systems.
And so, you know, it's not as simple as, well, if we
push this button, if we stimulate here, that that is the seat of that
What was the other one? Oh, could you inject through the
catheter stimulator? Yes, it's quite possible. I mean, we do
those kinds of experiments and injections in Parkinson's patients
in whom we're studying. We have an opportunity to study neural
function at the target zone because we are there. We actually use
micro electrode recordings to fine tune our targeting. While we're
doing that, it's a fabulous opportunity to study human
neurophysiology, and we actually undertake those experiments.
And when you're dealing with psychiatric and behavioral
issues, you know, you can train a monkey to move a joy stick and you
can time and you can analyze the motor systems much more easily, and we
know much more about motor systems because we have monkeys that can do
that. We can train them, and we can train animals to do certain
But you can't train a non-human primate to make moral
decisions about a — well, it's much harder to train them about
reward and negative consequences and various things, whereas a human
gets it like that.
So the ability to explore human brain function that is
unique to human beings, yes, it does provide an opportunity. I will
say it's not easy to do that, you know, in an operating room with a
patient. You only have a short period of time and the set-up and the
rig and all of the requirements to do that well is difficult. You can
certainly do it poorly and come up with all sorts of speculative
reasons why this works, but, yes, in my mind it's a unique
opportunity to understand brain function both on a macro level and a
micro anatomical level.
CHAIRMAN KASS: I'm going to wind up. Indulge me one
last question because you've sat through the somewhat chaotic
discussion in the last session, but could I bring you to comment?
If it were the case that neural imaging were able to give
some fairly clear correlations now, without understanding
causation, to identify populations of patients who have difficulty
controlling rage, and that borders on violence and aggresivity
that you spoke about earlier, do you see a possible future
that these things might not be controllable pharmacologically?
Is there a possibility that brain stimulation or ablation
might be able to lend a hand here?
I know this is not what you get paid to do. I mean, you
get paid to deal with the people in the retail business, but as you
were listening to that conversation, did it sound to you like something
that might sooner or later come your way as a result of what brain
imaging is going to disclose?
DR. COSGROVE: So can I give it a little preamble about
braining imaging and neuropsychiatric illness?
CHAIRMAN KASS: Please.
DR. COSGROVE: So it's already there. Helen Mayberg
has shown that with PET studies you can predict almost with 100 percent
accuracy which patients are going to respond to Prozac, one of the
first SSRIs, by a demonstration in the anterior, most rostral cingulate
gyrus of metabolic changes there. If a patient has those changes, then
you know that they're going to respond to the Prozac. If they
don't have the changes, they're not going to respond to the
So there are already several other examples of the same
thing. So functional neuroimaging can predict outcome to drugs. We
have only pilot data both in our depressed patients and in our OCD
patients. We would love to be able to predict which of our patients
are going to be responders because if we can get all of those
nonresponders out of our pool, then all of a sudden our statistics look
great and everybody would say it's a great operation, right?
We do the same thing in epilepsy, of course. We do PET
scans to try and ascertain, you know, the PET scan showing temporal
hypometabolism predict outcome. It's a much better predictor of
We have done this work in about a dozen patients in both
populations, trying to correlate preoperative PET scans with outcome
from surgery, and the remarkable thing is that in both the OCD
population and the depressed population, there's one area that
predicts outcome, and it's linearally correlated with improvement.
In the OCD population it happens to be posterior cingulate, well behind
where we do our lesion. That's the only area. It has broad
connections in that area to some of the areas that we're talking
about, and in the OCD population it happens to be the right thalamus
and the right orbital frontal cortex.
So these predict and, again, in a linear fashion. So if this
holds true, and we're trying to substantiate that with
larger numbers, and this might be just an epiphenomenon.
You can never be sure, but it makes sense with our a priori
knowledge of what systems are involved. If this holds true,
then we have a much better predictor of response to our intervention.
Now, getting back to your more thorny question of if, you
know, somebody was presented to me with aggressive behavior and you
know we had a predictor of response based upon neuroimaging, well, it
would have to be a convincing predictor of response.
Then you would have to correlate that with your response to
outcome or your outcome in response to the treatment, and then it would
also still have to satisfy in my mind the two preeminent criteria that
the patient understands the risks and benefits as we know them, and so,
you know, assuming you have great data on that, and that they wish to
pursue this and they're able to give their own informed consent,
not that the institutional advisor in the penitentiary, you know, says
this guys is bad and you should do it because then I think that
you're revisiting the issues that were addressed in the '60s of
mind control, violence in the brain, all of those thorny issues which
did nothing to help the discussion and debate on the subject matter at
CHAIRMAN KASS: Thank you very much, and thank you really
for a wonderful presentation —
DR. COSGROVE: Thank you.
CHAIRMAN KASS: — and very thoughtful
stuff for discussion.
SESSION 7: PUBLIC COMMENT
CHAIRMAN KASS: We have only one person
who has asked to make comment in the public session. So I'd
ask Council members not to break here. We'll have that
comment, and then we will adjourn.
We welcome Joan Wheeler, who is a member of the
International Adoption Reform Movement and the American Adoption
MS. WHEELER: Hello. I deeply regret not being informed of
your meetings in prior months or years on reproductive technologies.
It is because of March's production, your booklet on reproductive
technologies, that I am here today.
I represent the children created by reproductive
technologies. Those of us who were adopted know the pain of loss. We
were relinquished into secrecy, victims of traditional closed
adoption. We were given new families, and we were told we were
ungrateful if we wanted to know our origins.
As an adoptee reunited with my birth family for 30 years, I strongly
oppose the blind use of donor gametes, and I agree that regulation
Adoptees from traditional closed adoption suffer low
self-esteem and identity confusion from being given away and lied to.
Children of donor parents face similar problems. These children, now
adults, are organizing around the world to seek out their donor
fathers. They suffer long life consequences for the actions of both
sets of parents.
Donors are not fully educated as to the consequences of
their actions. Young men believe masturbate and get paid? Great way
to make money. I'm a medical student. I'm a genius. Someone
can benefit from having my genes. Oh, and I don't even have to pay
Young women believe, sure, I'll help infertile
couples. I want to give the gift of life to a couple waiting for a
child. It's not as if I'm actually handing over a real baby.
Once she's pregnant, it's her kid. Besides, I can use the
Being that gift of life is a psychological burden that no
one should have to bear. I can hear it now. Why do you want to know
your genetic mother? I carried you for nine months. I went through 20
hours of labor for you. I'm your mother. She's just a donor.
Forty years ago adoption was in the best interest of the
child. Now the perceived rights of infertile people take precedence.
Recipient parents of donated gametes desperately want to have a child
of their own. They have no intention of telling their children. They
don't need to. They are safe to raise the child under false
pretenses. This is an extension of closed adoption practices.
Internet adoption agencies boast of total anonymity. This
instills false beliefs in the donor recipient parents. They fiercely
defend their rights and deny the existence of other parents. The
recipient mother gestates and gives birth. So it is assumed she is the
child's only mother.
There is no documentation and no identification of the
donor parents. No legal adoption takes place, and no one need know the
truth, especially not the child. Birth certificates are legal lies.
Couples who claim to be infertile are often very not
infertile at all. Lesbians are leading consumers of the sperm donor
industry. They don't want a man in their life. So they opt for
anonymous sperm. These mothers will some day have to face their
children's questions. Mom, you fought for the right to marry your
same sex partner, but will you honor my right to know my father? Who
is my father? Why don't you know who my father is?
With two sets of parents conspiring against the donor
child, this situation is far, far worse than traditional closed
adoption. Parents are not only not the only conspirators. Fertility
doctors are in control. They determine where a donor's semen is
shipped, and then embryos and eggs are traded like stocks and bonds.
This determines the gene pool to avoid consanguinity, as if biological
relatedness is only science.
They don't want sisters and brothers to interbred. So
they spread donor gametes far and wide with no record keeping. This is
social and genetic manipulation.
It is troubling that the Council buckles to popular demand
to take out the recommendation to track every embryo made because that
could be a political agenda. I ask the Council to reconsider.
Tracking gametes and embryos is not a conservative Republican or
liberal Democratic agenda. It is a human rights issue.
Because of the opposition to openness, the issues I bring
before the Council could be considered radical. Imagine donor children
have the same rights as normal children. Adoptees have the same
rights as non-adoptees. Civil rights for children? These are radical
Regulation, tracking and disclosure of identity of donors
and medical histories should be expected, demanded, and enforced by
federal law. Genetic parents and legal parents should be clearly
identified on unsealed birth certificates.
Parents who use reproductive technologies need to accept
and respect their child's full circle of parentage. When
alternative, nontraditional families are created, honesty is the best
policy. Therefore, I urge the President's Council on Bioethics to
strictly regulate the fertility industry. Tracking every sperm, every
egg, every embryo is not only possible, but it is in the best interest
of the children to do so.
CHAIRMAN KASS: Thank you very much for an eloquent
Anybody have any final business?
CHAIRMAN KASS: Thanks to everybody. We will be in touch
about follow-up on both the topics of discussion yesterday and the
topics we have broached today.
Anybody who has afterthoughts after this meeting both of
substance and of procedure, please let's hear from you, and
we'll be in touch with you shortly.
Thank you all for coming. The meeting is adjourned.
(Whereupon, at 11:57 a.m., the meeting was concluded.)