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Meeting Transcript
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., Chairman
American Enterprise Institute

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

Rebecca S. Dresser, J.D.
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.
Dartmouth College

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

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

Alfonso Gómez-Lobo, Dr. phil.
Georgetown University

William B. Hurlbut, M.D.
Stanford University

Charles Krauthammer, M.D.
Syndicated Columnist

Peter A. Lawler, Ph.D.
Berry College

Gilbert C. Meilaender, Ph.D.
Valparaiso University

Janet D. Rowley, M.D., D.Sc.
The University of Chicago

Michael J. Sandel, D.Phil.
Harvard University

Diana J. Schaub, Ph.D.
Loyola College



INDEX


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 to do.

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 question.

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 questions.

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 disorder.

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.

(Laughter.)

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 say?

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 important.

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 couldn't."

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 wouldn't."

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 can't."

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.

(Laughter.)

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 the question.

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 go away.

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 necessarily?

DR. CARSON:  Yes, it did.

PROF. SANDEL:  Why did it?  Why did it?

DR. CARSON:  Well, unless demons caused mesial temporal sclerosis.

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 the continuum. 

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 not there.

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 that.

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 something.

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 disturbances.

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 different reasons.

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 possession?  Really.

PROF. SANDEL:  Well, I think that's a practical question.

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 changed.

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 intervention yet.

PROF. SANDEL:  But that's the only test of better explanation here.

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 intervening.

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 tale.

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.

(Laughter.)

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 mechanism.

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 remark.

And my first reaction was, gee, this is fascinating, but then when I went home I started thinking, well, is that true.  I'm sorry?

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 mind.

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 these functions.

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 happen.

Thank you.

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?

Peter.

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 finger?"

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.

(Laughter.)

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, right?

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 about.

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 sexual offender.

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 behavior?

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 physical existence.

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 sense. 

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 images.

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.  Okay?

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 me greatly.

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 of Metaphysics.

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 question?

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 resolved.

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 used it.

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 that.

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, Peter.

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.

(Laughter.)

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 understanding.

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.

(Laughter.)

CHAIRMAN KASS:  I'm sorry.  I remember this experiment. 

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 neural image?

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 different.

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 nervous system."

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 issue.

CHAIRMAN KASS:  And what are these behavioral disorders of this sort?

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 science.

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.

(Laughter.)

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 makes decisions.

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 defense.

DR. GAZZANIGA:  I don't agree with it.

DR. KRAUTHAMMER:  It's a fairly practical position.

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 important question?

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.

(Laughter.)

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.

(Laughter.)

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 of behavior.

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 me.

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 improved.

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 "psychosurgery."

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 the midline.

Dr. Freeman himself was an unusual man.  There may have been some psychiatric diagnoses potentially attached to him.

(Laughter.)

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 issues.

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 available.

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 history.

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' duration.

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 testing.

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 improved.

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 group.

So while these numbers are not fabulous, they are, I think, impressive nonetheless.

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 bilaterally.

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 response.

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 target zone.

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 neurological deficit.

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 specific advantages.

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 functional neurosurgeons.

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 starvation.

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 better.

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 thing.

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 generator.

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 program.

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 artificial.

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 surgical risk.

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 not trivial. 

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 fallacious.

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 are.

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 structures.

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 from Medtronic.

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 suffering.

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.

Thank you.

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 stimulation.

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 investigational.

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?

Thank you.

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 aggressivity.

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 may —

CHAIRMAN KASS:  And squeamish about it in a way different from being — are you equally squeamish about doing this for Parkinson's disease?

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 you were.

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 it's $8,000.

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 it's significant.

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 we're doing?

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 works.

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 experience.

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 person.

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 our lifetime?

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 different individuals.

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 clearly.

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.

(Laughter.)

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 medications. 

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 might —

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 looking for.

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 first resort.

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 that point.

CHAIRMAN KASS:  That's true.

Gil.

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 that?

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 neurobiological?

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 category.

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 explodes. 

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 with it.

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 this.

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?"

(Laughter.)

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 procedures.

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 session.

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 a drug.

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 time.

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 function.

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 things.

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 Prozac.

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 outcome.

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 hand.

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 Congress.

Welcome.

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 is needed.

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 child support.

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 money.

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 concepts.

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.

Thank you.

CHAIRMAN KASS:  Thank you very much for an eloquent statement.

Anybody have any final business?

(No response.)

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.)


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