Sheraton National Hotel
900 South Orme Street
Arlington, VA 22204
COUNCIL MEMBERS PRESENT
Leon
R. Kass, M.D., Ph.D., Chairman
American Enterprise Institute
Elizabeth
Blackburn, Ph.D.
University of California, San Francisco
Rebecca
S. Dresser, J.D.
Washington University School of Law
Daniel
W. Foster, M.D.
University of Texas, Southwestern Medical School
Michael S. Gazzaniga, Ph.D.
Dartmouth College
Robert
P. George, D.Phil., J.D.
Princeton University
Alfonso
Gómez-Lobo,Dr.
phil.
Georgetown University
William
B. Hurlbut, M.D.
Stanford University
Charles
Krauthammer, M.D.
Syndicated Columnist
William
F. May, Ph.D.
Southern Methodist University
Paul
McHugh, M.D.
Johns Hopkins University School of Medicine
Gilbert
C. Meilaender, Ph.D.
Valparaiso University
Michael
J. Sandel, D.Phil.
Harvard University
INDEX
Welcome and Opening
Remarks
CHAIRMAN KASS: Could we get
started, please. Greetings, fellow Council Members, Guests, Members
of the Public. Welcome to this the 10th Meeting of
the President's Council on Bioethics, and welcome to Virginia.
I want to acknowledge the presence of our Executive Director,
Dean Clancy, who is also the Designated Federal Officer, in whose
presence this is an official meeting.
In this first session, we will be discussing Pediatric
Psychopharmacology, a topic which comes to our attention first in
keeping with our exploration of the beyond therapeutic uses of
psychotropic drugs in children and in youth, stimulants like Ritalin,
anti-depressants like Prozac, of interest to us for their possible uses
beyond therapy for personal enhancement and social control.
The Council has been on this topic a couple of times in the
past. We certainly recognize that there are clear disorders for which
these drugs are not just indicated, but indispensable. And yet at the
same time, we are concerned about the possible over-use of these
medications, and struggling amongst ourselves to figure out what the
boundaries are between appropriate and inappropriate use.
In the last meeting, a series of possible topics for further
exploration was suggested in the Council discussion, some of them
financial incentives, practices of insurance companies, and the
pharmaceutical companies, but there was also a request that we
pursue questions of some of the deeper diagnostic, cultural, and
conceptual issues that make performance enhancement and behavior
control so tempting, that also might bear upon why depression
and self-discontent is so common, and why both are so liable to
be addressed through medicines, and through drugs.
And to help us in this discussion, we're really very, very
fortunate to have as our guest this morning Dr. Steve Hyman.
He's a Professor of Neurobiology at the Harvard Medical School,
the Provost of Harvard University, and from 1996 to 2001 was the
Director of NIMH. Dr. Hyman is a careful and profound student
in really all aspects of this topic from the nature of mental
illness to the -- its biological substrate and its social and
cultural implications, and also on the uses of drugs, the abuses
of drugs and addiction.
As I learned from conversation with him about a month ago, he
began really in philosophy and philosophy of science, and also
a kind of a philosophical interest in the matters under discussion.
It's really just a great pleasure to welcome you, Dr. Hyman,
to the Council Meeting and look forward to your presentation.
tHURSDAY, MARCH 6, 2003
Session 1: Pediatric Psychopharmacology
DR. HYMAN: Thank you very much for inviting
me. As you and I discussed, we want to have an overview of some
very difficult issues, such as how we set diagnostic boundaries
in psychiatry in general. There are even more difficulties, as
you know, in children where the science is less advanced.
I prepared a Power Point presentation. This has become a necessary
crutch for all of us for about 30 or 35 minutes. I can't
possibly address all of the wide-ranging issues that we need to
think about in order to grapple with these topics, but would be
happy afterwards as we engage in discussion to go very, very far
from what's in the Power Point. Also, I think to be maximally
useful, I'm happy to be interrupted during this Power Point
discussion if something is opaque, or alternatively if you already
have thought about an issue, and feel that time would be better
spent elsewhere.
I note that I wear my intellectual biases on my sleeve. If
you can even judge by the back drop of my title slide, you can
see that there's a brain there, so we have a number of different
questions when it comes to the use of psychotropic drugs in children.
As the absolute medical groundwork, we have to ask whether particular
drugs, Methylphenidate, Prozac-like drugs, anti-psychotic drugs
are safe and effective. And we have to ask it for different age
groups, because brain development means a fortiori that children
are not simply small adults.
Secondly, we have to worry, effective for what? When we're
testing the utility of a drug, are we looking, as we most often
do, for diagnosable disorders, or are we thinking as we do increasingly
in general medicine about early intervention or even prevention?
We have to ask whether we treat risk states for psychiatric disorders
in the same way as we do for heart disease. So, for example,
I wonder if you had planned to have an ethical panel on the early
and widespread use of the statin drugs to lower cholesterol.
And if not, I think it's not a question beneath contempt,
why we consider drugs to treat the diseases of the mind differently
than we treat drugs to prevent general medical disorders.
We have to think about unknown, of course it's a great conundrum
on how we would learn about long term unwanted drug effects.
We'll come back to this. And then we also have to ask a question
that is so often forgotten, which is how does an untreated mental
disorder, or even - and here I think we get to some of the issues
you're grappling with - milder impairment affect the developing
brain, and how does it affect real-life outcomes?
Unfortunately, we do not have adequate empirical data on almost
any of these outstanding questions. There's some things we
-- I just would like to assert. I have a few picture slides afterwards,
and I don't want to get into scientific detail, but I think
it's very important that we not fall into the ordinary trap
of thinking that drugs are about the brain, and lived experience
is about the mind, and they do not mechanistically interact.
In fact, both psychotropic drugs and lived experience affect
behavior, both brain, physical substrate and behavior, both short-term
and long-term. And both psychotropic drugs and lived experience
alter the brain probably by remodeling of synapses, which is something
that I know that those of you who are not scientists don't
think about every day. This is really just a picture to help
me make a few points. This is a picture. It's a drug experiment.
It's from Terry Robinson at the University of Michigan, and
I just thought it would be worth your seeing physically what I
mean by this.
On the screen in front of you are two dendrites, the receptive
processes of nerve cells, and these are a kind of neuron aptly
named medium spiny neurons because they have dendritic spines.
And we think that the communicative connections of different neurons
make these connections or synapses on these spines. And what
you can see is after a certain drug treatment, just comparing
the left and the right, that the architecture of these spines
is different.
Now there's a lot we don't know. Are synaptic connections
really made? Is information processing really changed? Is this
rat thinking and behaving differently in a way that correlates
with these synaptic changes. But I think what's really important
to recognize, again just to grapple with this mind/body distinction,
is that even beginning 20 years ago, Bill Greenough, a psychologist
at the University of Illinois, began comparing rats raised in
the normal laboratory shoebox cage with rats raised in what might
be called a rat park, you know, with interesting toys and interesting
food, not just Purina Rat Chow, but also chocolate chips and so
forth. And when he looked at dendritic complexity and cortical
thickness, they were really quite different in the rats raised
in this enriched versus the shoebox cage environment.
The point is that there is no fundamental mechanistic physical
difference using drugs to affect the brain and lived experience.
In fact, drugs act on mechanisms that are present for normal lived
experience in the brain. Now, of course, the potency of the effects
and precise effects will vary enormously, but there is no categorical
difference. I think that's really quite important to recognize.
Now one of the things I understand you're grappling with
are the boundaries of psychiatric disorders, so if I can switch
from that assertion to the issue of psychiatric diagnosis. This
will be fast. I misspelled the title a bit, but -- and we can
come back to this. Psychiatric diagnosis today, whether it's
for ADHD or depression or anything, is made based on operationalized
criteria derived from symptoms and signs. There are no objective
laboratory tests for any mental disorders that we normally think
about them. There are some appearing, so narcolepsy, which could
be considered a mental disorder, has been discovered to be related
to defective expression of a particular gene, the orexin gene
or its receptor, and there will be tests for this. But in general,
we are talking about the scoring of symptoms and signs by human
observers.
In the DSM-IV, the current American Diagnostic Manual, reliability
is king, not validity. Now let me tell you what this is. Reliability
is the notion that two independent observers will arrive at the
same diagnosis. This is not a trivial feat. Prior to the DSM-III,
published in 1978, psychiatry had the Tower of Babel problem-
different people could not understand each other. People had
idiosyncratic diagnostic criteria. The putative prevalence of
schizophrenia in the United States was said to be twice what it
was in Great Britain. None of this was credible, and we needed
shared diagnostic criteria that would be simple enough, and good
enough to permit two observers to arrive at the same diagnosis.
This is not the same as validity. This is -- I have another
slide later which mentions this, but this is -- validity is about
picking out natural kinds, carving nature at the joints, and the
two are obviously related to each other but are not the same thing.
Now the fact that the DSM has only tenuous claims to validity,
although not zero claim, really reflects the early stages of the
sciences of brain and behavior. And also, the difficulties of
the genetics of behavior. Now at the same time that we have these
difficulties, we still have a need to make treatment decisions
and to communicate with our patients, so we've come up with
what really has to be considered a provisional diagnostic schema.
The problem is that that diagnostic schema has become reified
in a way that isn't warranted by the science, but is all too
predictable.
Now I'm just going to show you two pictures again, because
to say that the science is difficult and that it's early is
just -- it's such an important point to make. And to say
that it's difficult and early doesn't mean we won't
ultimately understand the biological basis of mental disorders.
And again remember, the biological basis means the integration
of genetic experience and lived experience, and other environmental
factors integrated by the functioning of the brain. So this is
a recent paper from Judy Rappaport and colleagues showing over
time the loss of gray matter, of cells in the cerebral cortex
of children who have an early onset of schizophrenia. And what
you can see in these pseudocolor scales -- where always in pseudocolor
red is bad -- comparing a normal adolescent with an individual
with schizophrenia, that there has been loss of gray matter, and
here you can actually, by scanning the same person at intervals,
you can look five years later and actually map the loss of gray
matter.
I'm showing you this because the technology to map, find
differences, small differences with reliability in the brain,
even to parcelate different brain regions is really a technology
of the last years of the 20th Century, and it's
still under development. It is not -- when people who are, you
know, true enemies of psychiatric diagnosis like Thomas Auz, saidwell,
you don't know that the brains are different in his books
in the 60s and 70s. He was mistaking the difficulty of the science
for impossibility.
Now we don't have answers. We can't turn these pictures
of regression of gray matter in the cortex of children with schizophrenia
into clinical diagnostic criteria. Maybe this will never be a
criterion, and if it is, maybe it will take a decade. The point
is that we are really at the birth of the kinds of neuroscience
technologies, and as you'll see, genetic technologies that
can help us get some handle on the underlying biology of mental
disorders.
Okay. Let's turn to genetics, because this is also very,
very important in understanding the boundaries of what are called
psychiatric disorders. And here, the glass is both half-empty
and half-full. Family studies with appropriate designs, meaning
properly designed studies comparing monozygotic and dizygotic
twins, that is twins that share 100 percent of their DNA versus
twins that share about 50 percent of their DNA. Studies that
have been performed of children adopted out of their biological
families early in life and so forth do not fully corroborate the
current DSM-IV diagnosis, which is to say these diagnoses, based
on symptoms and signs, have chosen certain symptoms and signs
that experts felt could be reliably scored, and have decided that
this cluster equals a disease.
We can then go to experiments in nature, to genetics and ask
whether the symptom clusters co-segregate; that is, whether they
are transmitted as a group, as a single entity from generation
to generation. And what we find when we look very carefully is
that there are, you know, again not complete invalidation, but
not complete validation of the way we do things, that symptoms
and signs mix and match in a rather uncomfortably loose way often.
Now there's also reassurance. Despite these problems, despite
the fact that for, for example, many families with manic depressive
illness, you'll find that they have psychotic symptoms, delusions
and hallucinations, and the delusions and hallucinations are not
passed down exactly together with the mood disorder, for example.
Even though we have situations like that, there is reassurance.
If our categories were arbitrary, if they were completely fantastical
chimeras, we wouldn't see any significant passage of these
traits from generation to generation. They would not cohere.
And in fact, what family and genetic studies show us, is that
the categories we have, as problematic as they are, are picking
out something real, so let me make you ersatz geneticists just
for a few moments.
A useful if imperfect measure of heredity, because it doesn't
perfectly separate genes and environment, but it goes something
like this. The likelihood of expressing a trait if something
is genetic should increase as a person shares a higher percentage
of DNA with someone else who expresses that trait. That means
that if you share 100 percent of your DNA with somebody and they
have schizophrenia, you should have a higher likelihood of having
schizophrenia or ADHD, or depression, or diabetes than if you
share about 50 percent of DNA with somebody, if they are your
dizygotic twin, your sibling, your parent. And there should be
correspondingly less association with second degree relatives.
And when we, using this crude but useful measure, when we look
at what are called recurrence risk ratios, what you can see is,
and let me explain this. And I think after this, we're done
with the most technical slides, but I do think some detail, rather
than bald assertion, is important here. What you're seeing
here, this recurrence risk ratio is as follows. Your increased
risk of having a, in this case disorder, given that in the first
column you have a sibling with a disorder, and then in the second
column you have an identical twin with the disorder, where the
ratio is your increased risk over the population base rate. And
the higher the risk ratio given a, in this case a monozygotic
twin or a first degree relative with the disorder, the higher
the ratio, the more genetic the disorder. And this kind of information
is used by people using the tools of genetics, even to pick what
diseases they want to work on.
So let's look at schizophrenia. We've been talking
about it. The population base rate of schizophrenia is 1 percent.
If you have an identical twin with schizophrenia, you have about
a 50-fold increased risk over the population, so in this case
about a 50 percent, 48 percent risk overall of having schizophrenia.
If you have an ordinary sibling, on average you'll share about
half of your DNA, you have a 9-fold increased risk. So I want
to compare this with Type II or Adult Onset Diabetes, which is
widely understood to be a genetic disease, and you can see that
genes have a lot more to say about schizophrenia than they do
about Type II Diabetes. And even with our problematic classification
of ADHD, it has recurrence risk ratios that look very much like
Type II Diabetes. So again, these are not ridiculous chimeras,
as imperfect as they are. They are picking out something that
is transmitted as disease risk across generations.
Now some of you who remember genetics would say ah-ha, but those
ratios - I should actually go back - like 9 and 48 are not what
Gregor Mendel would have taught us; that is, if -- I don't
want to get into the details, but rather say this, and we can
come back to it in discussion. What the studies tell us overall
is that genes play a substantial role in, I've shown you only
pathology on these slides, but also in normal behavioral variation.
And this entails another whole set of debates, but I would like
to forestall them with the second bullet here, which is that behavioral
variation, including psychopathology, is genetically complex.
That is, when we say in common parlance that something is genetic,
what most people have is a deterministic notion that there is
a single gene for Attention Deficit Hyperactivity Disorder, or
schizophrenia, or Diabetes Mellitus, or criminal tendencies, when
in fact, what genetic complexity means is that, as we're going
to see, this idea, this simple idea is really of little which
is relevant to some rare single gene disorders like Huntington's
Disease or Cystic Fibrosis, is of little relevance to behavior,
and actually the most common human illnesses.
Where it is currently thought that many different genes, many
different places in the genome or loci interact to produce risk,
and that they interact equally with, or in some ratio with environmental
factors, and chance. Chance is often forgotten in this. You
can't wire up a hundred trillion synapses in the brain in
a mechanistic and reliable way. There are a lot of stochastic
effects in this, and that these interactions are non-linear.
Genotypes help select the salience of environmental experiences,
and those affect gene expression, so these are extremely complex
interactions.
The other thing which is very important in thinking about disease,
something like depression, depression which affects 15 percent
of the population, these are not likely to be deleterious mutations
in the genome, the truncation of an important protein, something
important not being made. Instead, these are more likely to be
just variants, that in some combinations are neutral, in others
are advantageous, and only in certain infelicitous combinations
and in interaction with environmental factors and chance do they
produce disease.
So let's just think about this again. There's some
evolutionary speculation, and it is speculation about, you know,
Diabetes Mellitus, that the thrifty genes, the metabolically thrifty
genes that would have helped you store fat before the neolithic
revolution are not a good thing to have in the era of McDonald's.
And these are not harmful mutations, these are just particular
variants that are interacting, and give you a particular metabolic
situation. And similarly, for behavioral variants, including
mental disorders.
Now, of course, certain combinations of these variants can give
you the risk of very severe illness. I mean, there's no doubt
that even if Autism is a group of variants, that depending on
which ones you get set you up for being somewhere on a spectrum
of being a little bit aloof, which might help you to be a great
mathematician, versus somebody who can't communicate at all
with other humans, that still doesn't make these things mutations.
It means that these -- again, this is an interaction of genetic
variants. And let me just say again, we think this is right.
I mean, there's a lot of data that this is right, but this
is -- we're right here on the edge of genomics and genetics.
Okay. Now I just also want to point out for our later discussions,
that the boundaries of mental disorders are not the only disorders
that are going to be redefined once we understand better the genetics
and the genomics. So let me show you a picture of a breast cancer
that looked the same to pathologists. So how does one make a diagnosis
of a cancer? Well, a tumor is removed by a surgeon, and still
today in most cases, a pathologist will put an acidic dye, and
a basic dye on the tissue specimen, a 19th Century
technology. And the pathologist is very learned in comparing
patterns of -- seen under a microscope with certain clinical outcomes.
And the pathologist will say this is a certain kind of lymphoma
or breast cancer.
Well, here is a gene chip, and the investigators here basically
arrayed 5,000 different human genes. And they asked whether a
gene was on being expressed in a cell, or not on, not being expressed
in a cell. And then they asked the computer just to array patterns
of gene expression in 98 different breast tumors which are arrayed
on the left to see whether there was any pattern of correlation
between the likelihood of metastasis. And indeed, with this gene
chip you can see that what looked for many years, eons, like one
disease, was actually at least two diseases. There are two different
patterns of gene expression here shown by red and green. Green
is off, red is on, and these are genes that might be very much
involved in invasiveness and metastasis and so on, but the point
is that genomics and genetics are redefining the boundaries of
disease everywhere.
The difference between this and behavior, frankly, is again,
this is an objective test outside the body; whereas, in behavior,
despite the early Judy Rappaport picture of this brain of the
young person with schizophrenia that I showed you, we are still
lacking any objective tests that we can look at outside of the
behaving human being.
Well, just to bring this full circle, and to make sure we don't
get too focused on the genes, and I've already said this,
if genetic complexity were not enough, ultimately it's not
our genes but our brain that regulates our behavior. And that
while genes are very important, neural circuits are shaped by
gene environment interactions over a life time. This is the idea
of synaptic remodeling by lived experience. Thus, behavioral
traits reflect the interaction of multiple genetic, environmental
and stochastic factors.
Okay. So it's very complicated, but we shouldn't despair.
Our genetic studies to date, for example, show us that we have
some coherence. I'm getting pretty close to the end of this.
The other thing, and this makes your job harder as you ponder
the questions that you are, is that depression, ADHD, autism,
and many other conditions appear to be quantitative or dimensional
traits.
Now the current DSM actually says, you know, to have depression
you need to have five out of nine DSM-IV symptoms of depression,
and you have to have those symptoms every day for two weeks.
Well, that's really quite arbitrary. In fact, of course,
the boundaries between -- really getting the boundaries right
between normal and diseased phenotypes have enormous impact on
treatment decisions. And the truth is that even though these
are handled relatively arbitrarily in the DSM-IV, medicine is
very comfortable dealing with quantitative traits like hypertension.
Basically, how did we decide that 120/80 is terrific, and 140/90
is a disease and warrants treatment? Well, we did long-term follow-up
studies, and it turned out that if you had 140/90, there seems
to be a bit of a discontinuity, actually, and you have a clear
increased risk of strokes and myocardial infarctions. And whereas,
the 5 out of 9 DSM-IV criteria for major depression just felt
right to a committee, they haven't been exposed to that kind
of empirical test, to understand what is a risk state and so forth.
The other thing is that we understand that there is early, and
transient, and mild, and moderate, and severe hypertension. And
again, in the DSM we have no capacity to do that.
Okay. Now this is a problem, this issue of not having rational
diagnostic thresholds defining either risk states or actual pathology,
has -- does a disservice, especially to children. It creates
a lot of lack of clarity with respect to when one intervenes in
children, both in the over-treatment domain, and in the under-treatment
domain. In the DSM approach, you know, you only achieve it if
you have 5 of 9 DSM-IV criteria. If that were applied to cardiology,
we might limit our diagnoses to angina and heart attacks, and
not to early coronary disease or even elevated cholesterol.
Okay. The complexity of mental disorders is humbling at the
levels of genetics, neurobiology and behavior. But then again,
many illnesses in general medicine are not so simple. I showed
you a cancer example. It's just true for all common disorders
that these are not unitary disorders, but have very complex boundaries.
The difference is again, that in general medical disorders there
are objective tests that get you within the pathophysiologic family,
and we have to live with this. We can't tell people in distress
to come back when our science is more advanced. We have to do
as well as we can.
Okay. So now in the last five minutes, just to give us a --
put this to work, so Attention Deficit Hyperactivity Disorder,
you already know this. I assumed you've discussed these things.
It's defined as age inappropriate inattention, impulsivity
and hyperactivity. It's critical that the diagnosis requires
symptoms and disability in multiple settings. Ideally, the workup,
therefore, involves looking at the child, interviewing the child,
and also the parent and the teacher. If symptoms only occur in
Mrs. Smith's classroom but not at home or on the playground,
that's not ADHD. It is a clinical diagnosis. There is still
no objective test.
Even with these diagnostic criteria, when they are well applied
by experts with a proper workup, they are associated, it is a
high risk state. It is associated with bad outcomes. It's
associated with academic and occupational under-achievement compared
with abilities otherwise measured. There is an increased risk
for substance abuse which, by the way, is decreased with Ritalin
treatment, even though Ritalin is abusable. And there is an increased
risk for arrest.
Anecdotes, you know, one takes with a big grain of salt, but
when I was NIMH Director, some of our ADHD research was co-funded
by the Justice Department, because there was such an over-representation
of kids with untreated ADHD who are incarcerated.
It is also associated with an increased risk of other disorders,
depression, anxiety and conduct disorder. It's the most common
behavioral disturbance that results in a clinical referral. Thirty
to 50 percent of kids who are referred clinically for a psychiatric
illness have this diagnosis. It has to start before the age of
7. And as you already know, it runs in families and it's
likely that some of the risk is genetic.
Treatment has been very well studied. Stimulant drugs in particular
have been around for a time. We know that behavior therapy is
effective. We know that stimulant medication, Methylphenidate
is effective. We know that from the very extensive MTA trial
which was conducted in 1999 through the NIMH, I have -- it was
initiated before I arrived, so I don't have a sense of ownership,
that careful use of medication is more effective than behavior
therapy.
Behavior therapy is interesting. It doesn't generalize
across different contexts, so behavior therapy in school doesn't
necessarily generalize to home or playground. Behavior therapy
in the home doesn't generalize to school. Combining medications
and behavior therapy is cost effective only for children, not
uncommon, but only for children with co-occurring disorders; that
is, ADHD plus anxiety or ADHD plus depression.
We also know that community treatment of ADHD is not as good
as it should be; that is, there are lots of kids who are on Ritalin
but don't have good outcomes, their doses are wrong, they
don't know about side effects, they're not being monitored.
A certain number of children who are said to have ADHD in our
communities and are being treated with stimulants also do not
meet criteria for ADHD. Adrian Angold in 2000 had a paper that
suggested - he's at Duke - that 50 percent of children carrying
this diagnosis wouldn't really meet standardized criteria.
There's enormous variability with some communities treating
it far less than the epidemiology suggests. The epidemiology
again -- so now you know how, you know, problematic these criteria
are, but if you apply them, and apply them rigorously, the suggestion
is that 3 to 5 percent of boys have ADHD, but we see rates of
treatment often close to zero among non-caucasian minorities and
some inner cities to the best documented. There was a paper looking
at several suburban Virginia counties - it's apt that we're
in Virginia - where 20 percent of the boys in some counties were
getting Ritalin, and anecdotally in some schools, especially among
middle class or upper middle class caucasian males, 30 or 40 percent
of the boys may be on Ritalin. That's not rigorous, but even
rigorous epidemiology shows this disparity between a 3 to 5 percent
incidence, and 20 percent.
There is also an unexplained increase in stimulants and other
psychotropic drug use. I know that the Julie Zito studies have
alarmed many people. I would caution you though, the studies
are very difficult to interpret since drug prescription data is
divorced from good diagnostic workup, so we just really have no
idea what's going on with these kids.
The bottom line, there's a mismatch between children in
need of treatment and children getting a diagnosis, both under-treatment
and over-treatment. We need better diagnostic methods. We need
to understand the best use of existing treatment in all age groups,
and we need better treatments. I'll skip over where we need
to do research. So to conclude, how do we take this -- how do
we think about these things? Why did I give you the first 20
or 25 minutes on genes, and brain, and behavior and the complexity
of diagnosis?
Well, partly we have to remember that while we're worried
about the risks of drugs on the brain, you also have to remember
that for childhood mental disorders there may also be risks of
no treatment. You have to ask how easy is it to recover from
persistent problems, in well diagnosed kids with school, and parents,
and peers, especially if the symptoms persist. There may be a
downward spiral for depression, anxiety, ADHD in which a kid has
symptoms, aggregates with deviant peers, gets in trouble with
the law and so forth, and these may leave their permanent traces
on brain and behavior, and life trajectories.
We live in a world of diagnostic gray zones, as Dr. Kass said
right at the outset. And increasingly in medicine, we have an
ethic of prevention and early intervention. We're told that
the time to treat -- that Osteoporosis is actually a pediatric
disease that expresses itself in old age, you know, you're
building your bone density as a child. Is there a moral difference
between lowering cholesterol levels and altering neurotransmitter
levels? Why might it be okay for everyone to be on a statin but
not an SSRI stimulant or Medaphenil so that we can stay awake
and work all night?
In treatment there's always a balance between risks and
benefits, and the balance is influenced by severity of symptoms
and stage of illness. Difficulties related to children with psychological
symptoms. For most conditions -- see, if we had this answer it
would be easy, but we do not know enough to project trajectories
with or without treatment.
There is abundant evidence that appropriate treatment decisions,
however, are not currently being made with ADHD in particular.
We could also talk about depression, because of outside pressures
to treat coming from family, school, drug advertising and so forth.
Inadequately trained physicians. There are very few child psychiatrists,
and pediatric neurologists, and behavioral pediatricians in our
communities. Almost all prescribing is done by family physicians
who are working in earnest, but don't have the training, and
they don't have adequate time or reimbursement for full work-ups
and follow-up. A full work-up to demonstrate ADHD would take
several hours, or would require talking to several people. And
also, medications are seen in many health plans as cheaper and
easier than behavioral treatments.
And when we go beyond well-defined disorders and high risk states
toward early intervention and prevention, the balance of medical
risk side effects shifts. Right? It shifts against treatment.
There are unknown long term effects of drugs. Now I've talked
about unknown effects of going untreated, but now there are unknown
long term effects of drugs on a child's symptomatic trajectory.
Does giving drugs now mean that a child might need drugs later
that they might not otherwise have needed? Well, we don't
know.
There are symbolic messages to children about self-efficacy.
Behavioral control comes from a bottle. We have the problem of
anabolic steroids for the soul. Can we really separate health
and prevention issues from performance enhancement issues? I
think that's a very, very difficult line to draw. And then
there's the issue of social coercion or unilateral disarmament.
I find it working at the University an anathema that all of our
kids, well many of our kids feel the need to get coaching for
their SATs, and they get their resumes spruced up, and one couldn't
possibly be a serious professional football player, I would imagine,
without the use of some performance enhancing drugs. And one
might take an ethical position, but taking that position puts
one at a competitive disadvantage. And in the case of ADHD in
schools, and maybe one day Prozac in the work place, there might
be a sense that you'll get the message that to do well, you
know, you shouldn't be the only one not being treated.
So let me end there. You can see that you have -- well, actually
as you know, you've gotten yourself into an area of extraordinary
difficulty because of the intrinsic complex nature of psychiatric
disorders, because the science of understanding and diagnosis
is young, because despite that, we've empirically discovered
treatments that have efficacy and a low side-effect burden, because
if I'm right and these disorders really are the left-tail
of a bell curve and not something discontinuous, these effective
treatments will work not only for those severely effected, but
those less severely effected, and those who wouldn't even
receive a diagnosis. And you're addressing this at a time
when we really don't understand fully how sets of behavioral
symptoms portend a certain trajectory for children. Thank you.
CHAIRMAN KASS: Thank you very much for a very
clear, comprehensive presentation. The floor is open for discussion.
Elizabeth Blackburn.
PROF. BLACKBURN: With relation to your table
with the risk ratios, you gave some very precise numbers, and
then you talked about the degrees and the quantitative aspects
of diagnoses. And I was curious about those numbers, did they
come from the extreme very, you know, say 9 out of 9 symptoms
for depression, for example, category?
DR. HYMAN: Yes.
PROF. BLACKBURN: Because I could see --
DR. HYMAN: What we did basically, and it's
interesting. The genesis of this slide was when I was NIMH Director,
and we were about to make an enormous investment in genetics,
we were working out -- that is, which diseases warranted an early
attack on the genetics given the complexity as genomic approaches
were maturing. And it was quite clear that autism, schizophrenia,
and manic depressive illness, because of their very high risk
recurrence ratios, were apt targets for genetic studies, and actually
other things were a lower priority. And the way we went about
it is basically to do a search and find every credible well-designed,
adequate end study that had been done comparing identical twins,
dizygotic twins and siblings. Per force they were done in different
countries using different diagnostic criteria, and if we did this
in a more technical meeting and you saw error bars, you would
be somewhat alarmed, but in the end, I think there's a general
consensus that these numbers are not far off, representing the
heritabilities.
PROF. BLACKBURN: Yes. No, I take the point
about the relative contributions of heritability, but I was curious,
for example, bipolar, you know, 7-fold for sibs, 60-fold risk
ratio for monozygotics. But then if depression, which is only
part --
DR. HYMAN: Yeah.
PROF. BLACKBURN: I mean bipolar is only part
of that, 15 percent so clearly there must have been a subset --
DR. HYMAN: Oh, bipolar --
PROF. BLACKBURN: -- how broadly you define
these things.
DR. HYMAN: I'm sorry. Okay. So depression,
when we -- so if you've ever had a manic episode you're
not in the unipolar depression category, you're in the bipolar
category.
PROF. BLACKBURN: Yes, but from what you're
saying, since you took studies from multiple countries --
DR. HYMAN: Yes.
PROF. BLACKBURN: -- it must have been a fairly
broad set of criteria that were included then in these things.
DR. HYMAN: Yes.
PROF. BLACKBURN: I was curious about whether
this represented, you know, as you say, the right hand side of
the bell curve for these diseases.
DR. HYMAN: Right.
PROF. BLACKBURN: It sounds from what you're
saying as though it's a fairly broad set of definitions.
DR. HYMAN: Yeah. I would have to -- I mean,
for autism it's not so broad. For major depression, it is
broad. We were dependent on the world's existing literature,
but I take your -- your point is -- if your point is that the
input data has certain infirmities, it certainly does.
PROF. BLACKBURN: No, I wasn't --
DR. HYMAN: Yeah.
PROF. BLACKBURN: I think the point is well-taken,
and I certainly think there's every reason to think this.
But I was just curious about how broadly some of these things
were defined. Were they looking at the extreme ones where you
could be very, very clear.
DR. HYMAN: I think, yes.
PROF. BLACKBURN: Or did they segue into them
--
DR. HYMAN: So for autism, bipolar disorder
and schizophrenia, they're very, very clear. I think for
major depression there is no clarity.
PROF. BLACKBURN: Okay. Thank you very much.
CHAIRMAN KASS: Rebecca Dresser.
PROF. DRESSER: You were very balanced and
fair in your presentation, and I wondered if I could get you to
express a point of view on something that's relevant, not
just to this project on "Beyond Therapy", but also another
project we have, which is regulation.
You seem to say that in some situations that diagnostic criteria
are fairly defensible, but there's still this problem of getting
professionals to apply them stringently, or even with reasonable
rigor. And also, dealing with parental demand, I suppose sometimes
patient demand. I wondered if you had any ideas on what might
be done to address that problem?
DR. HYMAN: I have no problem expressing a
direct opinion on this topic. I think that in medicine in general,
in psychiatry in particular, and in pediatric mental disorders
most particularly, there is -- as early as our criteria are, if
they were well-used, and if children were followed-up appropriately
to ensure that the first diagnostic hypotheses and treatment suggestions
were optimal, it would be a much better world.
I think the data suggests, as my slide listed, that most prescriptions,
as far as we can tell, for psychotropic drugs are made by family
physicians, well-meaning to be sure. I do not want to bash family
physicians. They are working at an extreme disadvantage. They
have been untrained. They have no time. I mean, it's fine
for me to say that you should spend several hours on a diagnosis,
and one of the things you want to do is make sure not only that
the child is in trouble in the classroom with the teacher, but
also is being rejected by peers on the playground, so it's
fine for me to say that. The family physician is not trained
to know what questions to ask, very often has 11 minutes to get
from the beginning of the intervention to writing a scrip, and
would not be reimbursed to take the time after the visit to make
those phone calls.
As a result, and in combination with outside pressures that
exist in certain school systems, and through advertising, I think
that what we -- there is a yawning gap between what we know, which
is imperfect but good enough in a rough-and-ready way and what
we do.
I would also say that while I focused on diagnosis, I think
the follow-up issues are as or more problematic; that is, if the
medicine isn't working and has side effects, it may or may
not be stopped. Kids who really need it may not be complying,
and nobody notices, so I think there is an enormous problem of
medical practice.
Let me say one other thing about coercion, and let me give you
a thought experiment, because I think it's -- coercion already
carries with it negative connotations, you know, the evil empire
forcing a child to take the medication. We can certainly imagine
a situation. Why you don't risk a unilateral disarmament
situation, where you have a few symptoms, and you're not performing
so well, and all of your friends are taking this drug, and their
parents and the teachers are happy consumers. That's not
an ideal situation. I don't think anyone could defend that.
On the other hand, there's a case where there's 25 kids
in a classroom or 28, and one teacher, and there are two kids
who have symptoms of severe behavioral disorder, who absorb almost
all of the teacher's time. And any of you who have children
or have been in a classroom know that this is a reality, and so
the 23 kids don't really get much of an education.
Now the issue here is that schools should never be making diagnoses,
and schools should never be saying, as has been rumored, you know,
get Johnny on Ritalin. That's absolutely wrong. But for
schools to demand that somebody be worked-up or treated in a certain
way so that everybody could learn I think is a different issue.
And I think when we think about the roles of schools, you have
to think not only about the dark 1984ish scenario, but also about
the second scenario, and weigh those.
CHAIRMAN KASS: Do you want to follow-up, please?
PROF. DRESSER: This is rather provocative.
I was involved in a group of pediatricians addressing the growth
hormone question, and one idea which didn't really go very
far was that only pediatric endocrinologists should be able to
prescribe because of this desire to do a good work-up, and keep
the boundaries. Has anybody ever proposed something like that
in this area?
DR. HYMAN: It is absolutely infeasible. The
number of -- I mean, in most -- if you think of inner cities or
most of rural America, the number of trained pediatric psychopharmacologists,
behavioral neurologists, or behavioral pediatricians tend towards
zero, and so the burden of doing this correctly must be on the
family physician.
The pediatric growth hormone issue is, as you know, exactly
analysis. Short stature, but my child does have short stature.
He was going to be a center for an NBA team, you know, and I'm
drawing that line.
CHAIRMAN KASS: If I -- Rebecca when she first
started to ask about the -- whether you had some suggestions,
in fact, about the regulation of this practice, you've gone
and indicated why it is in need of such attention, but in effect
said this is a problem for professional practice. And almost
all of the pressures make it almost impossible for it be done.
Is that the best that we can do?
DR. HYMAN: I hope not. On the other hand,
regulation that flies in the face of reality is -- decreases respect
for regulation and fails.
CHAIRMAN KASS: Of course.
DR. HYMAN: You know, I would -- I have long
believed -- so I've told you I believe that family doctors
are going to carry the burden of most of this. I think certainly
that at least in certification requirements, there has to be increased
attention among family physicians to pediatric psychopharmacology.
I mean, if you look at the numbers of young people receiving Ritalin
or an SSRI, this must make up a very substantial part of general
pediatric and family physicians practice, and I think some kind
of training is necessary.
I must say in my years of looking at the gap, as I call it,
between what we know and what we do, and physician behavior, I've
become not quite despondent about the power of education by itself,
and I think that some kind of accountability to make sure that
these -- that what is being taught is being practiced in some
way is very, very important. But that accountability, if it just
accrues to the physician who doesn't have time or resources,
and is not reimbursed, becomes very, very problematic, so I think
it has to be -- it really has to look at health systems in some
sense, and really look at the quality of the overall work-ups
that are being performed and reimbursed within a system.
CHAIRMAN KASS: Dan Foster.
DR. FOSTER: You used the term that on a "rough-and-ready"
basis if the things that we know were followed, we would be in
a much better world, the sense being that although there might
not be a bright line between disease and --
DR. HYMAN: There isn't.
DR. FOSTER: There isn't and so it's
broad.
DR. HYMAN: There is not, yes.
DR. FOSTER: At least there would be some broad
category of defense about prevention and so forth. And you talked
earlier a little bit about a curve that went on into normality,
where there might still be an enhancement from excitatory drugs
and so forth. I just wondered if you -- I think I know what you
would say about this, but merging out of the issue of children
with - as an example here - what is your opinion about the enhancement
virtues that kids in college and so forth, you know, are using
these drugs extensively and so forth? Is that defensible or not
defensible in your view?
DR. HYMAN: I really struggle enormously with
this. It really comes down -- I'm not going to give you a
crisp answer because I'm not done struggling. It comes down
to the anabolic steroids issue in some sense. Athletics has decided
that you are supposed to -- I mean, even though we know that illicit
and problematic use of drugs continues in sports at all levels,
tragically sometimes leading to death, the sports community will
assert that it wants human beings to compete with each other in
athletics, only based on their bodies and the physical training
that they undergo. And that the use of drugs is just not to be
part of an athletic contest. And in some sense, if you -- that
idea, which is so -- always breached, or often breached, that
idea which is so attractive, really doesn't translate very
easily to life as it is truly lived. And here my impulses, my
libertarian impulses, and impulses as a physician begin to take
over.
If somebody feels distressed and doesn't meet any criteria,
and finally a physician says well, I don't really know what's
going on with you, but let's try this thing. It's marketed
as an anti-depressant, but since everything is really probably
on a bell curve, you know, it doesn't stop working if you
don't have 5 out of 9 DSM-IV symptoms. And the person has
no side effects, or model tolerable side effects, and really it
relieves their distress, and they're a better husband or wife,
and they're functioning better at work. It seems very difficult
in America to say that they can't feel better. I think it's
actually impossible to say that. But then that scenario shades
into the dystopic notion that but if everybody in the work place
is -- if these drugs get better and better, and everybody in the
work place is on these drugs, might we not have a coercive situation
where somebody who wanted to engage life without a psychopharmacologic
agent is now being in some sense forced to join the crowd, which
is the situation if you want to an interior lineman in the NFL.
You might have moral questions about anabolic steroids, but you
would be ill-advised if that's your chosen career to avoid
them, so I can't give you a crisp answer.
I think it's really -- if you think about the case, the
first case I gave you -- I mean, I've given you extreme cases,
but in the first case it would be very hard to say that somebody
couldn't have the drug, and in the second case one begins
to really imagine some fairly nightmarish scenarios. And I think
finding -- if there is some way of finding an appropriate middle
ground, I imagine that's what you are all engaged in, and
I can't make it easy.
You might think my interim solution while I struggle is not
strong enough, but my interim solution is really that physicians,
because these are prescription drugs, physicians really have to
be a lot better. They can't say -- somebody can't say
I've read an ad for -- you know, I've been shy all my
life, and I read an ad on a side of a bus, and I want you to prescribe
X. I mean, the physician really has to understand the person's
symptoms, and treat a prescription as an empirical trial, and
not a birthright, and stop it if it's not working, and weigh
risks and benefits. And maybe it doesn't make you happy as
an answer, but we're not even there, we're not nearly
there.
CHAIRMAN KASS: Could I pursue this with you
unless, Dan, you want to follow-up? Are you okay? Yeah. In
the presentation, on the one hand at the very beginning, you make
clear your view that both lived experience and drugs affect the
brain.
DR. HYMAN: That's correct.
CHAIRMAN KASS: And that there is no fundamental
categorical difference.
DR. HYMAN: At the level of the brain.
CHAIRMAN KASS: At the level of the brain.
DR. HYMAN: Right.
CHAIRMAN KASS: Yet toward the end when you
talked about the kinds of problems that might -- and among the
list of problems about the use of these drugs was the concern
that you would be sending symbolic messages about self-efficacy
to children.
DR. HYMAN: Uh-huh.
CHAIRMAN KASS: That somehow drugs were a better
way to deal with their difficulties.
DR. HYMAN: Uh-huh.
CHAIRMAN KASS: And then this question about
the anabolic steroids for the soul which we talked about.
DR. HYMAN: Right.
CHAIRMAN KASS: If you bracket the question
of social coercion that might come if you were dealing with competitive
situations, and simply talked about the fact that look, we don't
know whether there's a diagnosis here. In fact, it's
not clear this is a medical condition, but there's some kind
of self-discontent. And you've already pointed out that in
the absence of certain kinds of treatment, the possible plasticity
of the brain might, in fact, be under-developed and not used.
CHAIRMAN KASS: Why wouldn't you say that
-- why don't these concerns sort of vanish, concerns at the
end if you begin to think about the thought at the beginning;
namely, that we could use pharmacological agents to help lots
of people feel somehow better about themselves, in the wake of
which feeling better, all kinds of other experiences might go
better. The brain might, in fact, develop and become richer.
Isn't this just sort of priggish concerns that you have?
DR. HYMAN: Yes. No, no. No, no. Well, I
think that's why I began with athletics, where society has
made a decision that you're supposed to be competing naked
of pharmacology. And we haven't made that decision when it
comes to the rest of life. WE're uneasy. I mean, we are
generally uneasy. And the whole reason I struggle is because
I can't refute that final position that you took.
Let me also say at the beginning, there are also certain kinds
of experience that can have bad effects on life trajectory presumably
mediated by the brain, by long-term changes in the brain. I mean,
we're worried about pathologic gambling, you know. That's
a lived experience. That's not a pharmacologic experience,
and it can have very profound effect on brain function. I was
really just making the point that we can't -- you shouldn't
rest your deliberations on the idea that there's something
fundamentally categorically different between drugs and experience
and their effect on the organism. There are other issues that
we are struggling with, which has to do with symbolism, with relative
moral weights, and of course, with medical side effects, risks
and benefits.
CHAIRMAN KASS: But bracket the side effects.
DR. HYMAN: Yes. Right.
CHAIRMAN KASS: Why isn't, in a way, the
philosophical teaching about the brain sort of at odds with the
desire to privilege the symbolic meaning of do it for yourself
without drugs?
DR. HYMAN: Yes.
CHAIRMAN KASS: Bracketing your -- no one is
going to ban anything here.
DR. HYMAN: Right.
CHAIRMAN KASS: Bracket libertarian concerns.
DR. HYMAN: Right.
CHAIRMAN KASS: And just talk about the kind
of anthropological question, moral self-understanding.
DR. HYMAN: Well, I think that there is a symbolic
difference that we don't -- that we often don't recognize
that plays itself out, often in irrational ways in other aspects
of medical practice. For example, we are quite well aware that
most people will not control their cholesterol with diet and exercise
over the long run. And yet, every medical textbook tells you
to start with diet and exercise, and force somebody to fail through
this exercise in self-control before you would prescribe a statin,
even though the statins are, you know, they're -- we can bracket
side effects, but they have side effects. And I think what we'r
talking about here is what kind of society -- I think what we're
engaged in is what kind of society we want to have, and whether
we, as a society, want to recognize as valid, unstigmatized, and
in no way diminishing of someone's humanity, that they gain
appropriate treatment even early, or preventive treatment for
identifiable high risk states, but that in general as a society,
we would like people to work with their own native abilities,
with their own struggles.
The alternative view is that if we can find medications which
will enhance our performance, lengthen our life, decrease the
stress, do we really think that Aldous Huxley was right and we'll
end up, you know, in some "Brave New World", or is it
more likely that we will end up in a happier, healthier world
where people can all function well? And I think we don't
know the answer to that, and what you and -- what we are all here
together struggling with is we're worrying about the Huxley
and dystopic, but it would be hard to say that we should not be
aiming for the more utopian version of this. And in fact, if
such drugs were to be developed, no regulation in the world would
keep them from general use.
CHAIRMAN KASS: Michael Sandel.
PROF. SANDEL: I'd like to continue along
Leon's lines. What he's been doing has been -- you gave
us a very balanced and elegant, and terrifically, for me, informative
overview of these issues, and you have an instinct that's
emerged in the discussion for which you call the appropriate middle
ground, but Leon, and now I am trying to drag you into the fray
that we've been occupying.
DR. HYMAN: Uh-huh.
PROF. SANDEL: Which is partly an ethical and
ideological fray, as it intersects with the medical and scientific
account that you've given.
DR. HYMAN: Absolutely right. I mean, medical
practices -- there are a lot of problems in medical practice that
have to be addressed, but we're talking about something very
separate from medical practice now.
PROF. SANDEL: Right.
DR. HYMAN: So you're not letting me hide.
Yes.
PROF. SANDEL: Okay. So if I could continue
along these lines. First, when you gave your general, your opening
account of the mind, calling into question the sharp metaphysical
mind/body distinction, both drugs and experience have effects
on the brain, to some ears, to some people listening to this,
see that finding, if it's true, as threatening to something
they believe about ethics and about freedom, and about moral responsibility.
I don't think that they're correct in seeing this as a
threat --
DR. HYMAN: Correct.
PROF. SANDEL: -- to proper understandings
of freedom and moral responsibility, but there's a powerful
philosophical tradition that supports their worry that this would
be a threat.
DR. HYMAN: Right. I agree.
PROF. SANDEL: But in any case, to come closer
to the surface of these ethical and ideological issues, so you
signalled -- those were fighting words your account, your brief
account about drugs and experience having effects on the brain.
And then you reinforced them, and you posed as a question if statin,
why not stimulants?
DR. HYMAN: Right.
PROF. SANDEL: What's in principle the
difference between the use of the two for prevention and early
intervention?Maybe we stigmatize the second more than the first,
but is that defensible in the light of this earlier thing, so
that gets closer. And then -- so to take one step further along
the lines of Leon's questions, go back to the sports case.
Now you dodged that by saying well, we as a society have decided
that we want sports athletes to play just with their bodies and
physical training.
DR. HYMAN: Right, but you could imagine a
different --
PROF. SANDEL: Well, first of all, it's
not clear that that's true sociologically, and even if it
were, it might be mistaken.
DR. HYMAN: Right. Right.
PROF. SANDEL: And one could raise questions
about improved running shoes, or graphite tennis racquets and
so on, which have nothing to do with bodies or with physical training,
but which are external in just the way that drugs would be external.
DR. HYMAN: Uh-huh.
PROF. SANDEL: You don't object to that,
so at the level of sociology, it's not so clear that we've
accepted that. In the Sports Illustrated expose of the
use of steroids that they pointed out that players now speak to
each other in the language of "playing naked", you're
not going to play naked, are you?
DR. HYMAN: Yes. That was my unilateral disarmament.
PROF. SANDEL: Right.
DR. HYMAN: Right.
PROF. SANDEL: But here's the issue. Suppose
we put aside questions of safety, we find something that doesn't
have bad side effects as steroids do.
DR. HYMAN: Uh-huh.
PROF. SANDEL: And we put aside the question
of fairness, that by making it available to everyone if they want
to, to use it let's say in sports, some drug that will enhance
performance, that doesn't pose medical risk, and that's
equally available on a voluntary basis to anyone who wants to
use it, so you remove the fairness.
Now you may say well, there's some people who want to be
play naked, they'll be effectively coerced, but if it's
safe, then it's no more coercion in that direction than it
would be in the other direction if you said people who want to
use it, can't use it.
DR. HYMAN: Right.
PROF. SANDEL: So it would be a draw. So the
coercion is gone, the fairness is gone, the safety objection is
gone -- something objectionable about enhancing performance through
a drug rather than through, let's say, a more rigorous training
or better genetic luck. That's question one.
The second question is the parallel to that in the case of Ritalin,
in the case of stimulants. And here, there's been a lot of
discussion about over-treatment, and over-treatment reflecting
an ideology of the, you know, the diagnostic manual, this ideological
--
DR. HYMAN: Right.
PROF. SANDEL: It's led, or permitted and
over-treatment.
DR. HYMAN: And there's also under-treatment.
PROF. SANDEL: Well, but you --
DR. HYMAN: As are more problems --
PROF. SANDEL: Well, that's a different
emphasis you brought from the ones we've had in previous discussions.
You said well, we have to look at the risks of not treating, we
have to look at the incidence of under-treatment. And if it's
safe, and let's say even hypothetically to isolate the issue,
if it doesn't have adverse health side effects, then the under-treatment
would be worse than the over-treatment.
DR. HYMAN: Uh-huh.
PROF. SANDEL: So the question then, the first
question is this -- the hypothetical in the sports case, and the
analogy in the Ritalin case. If we do away hypothetically with
the medical risk, is there anything objectionable to letting any
kid whose parents let's say agree to have Ritalin to improve
behavior or concentration on the SAT, provided it's available
to everyone, and assuming for the sake of argument it weren't
risky.
DR. HYMAN: So you'll force me to take
off my medical hat that makes me worry, and to address in very
naked terms where I would come down. I would say that if there
were drugs that could enhance performance, that were perfectly
safe, but I want to define safe on my terms.
The key for me is, and this is very unlike the soma of "Brave
New World", there must be no clouding of consciousness, there
must be no alteration of -- no artificial control of overall moods,
but rather -- in short, we don't want people getting high
all the time. I would include that in a risk. It's very
important for me to segregate, you know, artificial elevation
of moods and change in human judgments into the category of side
effects. But if we had drugs that were free of that, I would
think that it would be -- they would be acceptable. I think that
--
DR. GAZZANIGA: We do. That's Ritalin.
DR. HYMAN: Well, not quite Ritalin. I mean,
Ritalin is not -- well, let me come back to the second point.
The reason that you've found me so worried about this in talking
about the moral symbolism is I also believe that it is better
for humans -- we never want somebody to have to struggle against
difficulties with some rectifiable disorder, defect or disability.
We want to bring everybody up to a certain normal level of function,
with the understanding that that's a very gray zone. But
it's also important -- I would argue that a society which
-- if a society errs in the direction of increased personal responsibility
and sense of moral agency, that's a better society than a
society which errs in the opposite direction. And that while
I said yes ultimately to your first question, the way you set
it up, the way that such drugs would be used, the way Ritalin
can be used, worries me because of the risk of undercutting a
broad societal sense of moral agency and responsibility.
I don't think that -- and the two positions are not really
fully congruent. Right? Because I know that one of the risks
of having risk-free performance enhancers is potentially to undercut
a set of moral agency and responsibility. And yet, it is very
hard for me to find a bright line where if these things were truly
risk-free, didn't make people -- give people artificial emotions
and impair their human judgments, that I could say that we can't
have. We will have. What I'm saying is we have to learn
to manage them, and we have to learn to manage them in a way that
minimizes the loss of a sense of moral agency.
DR. FOSTER: I just want to interrupt for a
second to say, I'm not sure at all about the issue of safety
of Ritalin in young children. I mean, I'm not sure that it's
a safe drug anywhere, but particularly I don't think that
the neurological circuits and everything are completely, you know,
at 7 years of age you're not worried about that. You remember
that -- if you look at something like alcohol and pregnancy,
I mean four hours of alcohol at 200 milligrams percent you've
got a defective brain.
DR. HYMAN: You know, Dr. Foster, I don't
want to cut you off, but time -- I'm going to have to go exactly
at 10:30.
DR. FOSTER: All right.
DR. HYMAN: Let me just say, if you actually
look at the data, imperfect as it is in any clinical trial, the
data would tell you that properly used by any criteria that we
have, Ritalin is a safe drug. Can it be misused? Yes. Can it
be abused? Yes. Do all drugs we have today have side effects?
Yes. But compared with almost actually another drug we have that
we use in psychopharmacology, oddly the data that we have suggests
that Ritalin is the safest. Now you and I might argue about this,
but I don't think that's where these questions are going.
CHAIRMAN KASS: I have Gil, Paul, Bill. You
have how much time?
DR. HYMAN: I have to leave at 10:30, about
five minutes.
CHAIRMAN KASS: Okay. Well, let's try
to -- briefly then.
PROF. MEILAENDER: Yeah. I'm confused.
If I follow what you said to Leon, and then to Michael, it would
seem that you're not prepared to draw a line against enhancing
performance for perfectly normal people.
DR. HYMAN: Right.
PROF. MEILAENDER: Enhancing performance so
long as it doesn't have bad side effects, one of which would
be altering of moods.
DR. HYMAN: Artificial elevation.
PROF. MEILAENDER: Yes. So somehow a person
who just, you know, is not clinically depressed or anything, but
just goes through life a little discontented and would like to
be happier, has less claim to be helped than someone who without
help can get a 1400 SAT and would really like to hit 1550. If
I'm understanding your right, I just don't see why anybody
would draw that line.
DR. HYMAN: Would draw the line.
PROF. MEILAENDER: Yes. Why do you have more
sympathy for the person who wants to notch up the SAT than the
person who would like to be a little happier.
DR. HYMAN: I'm sorry. I don't have
more sympathy. I just --
PROF. MEILAENDER: Well, you're more prepared
to permit them to look with some --
DR. HYMAN: I must not have expressed myself
-- well, I just said I have much more sympathy with the sickest
person, and --
PROF. MEILAENDER: I'm not talking about
a sick person, just a person who'd like to be a little happier.
DR. HYMAN: What I'm saying is, I don't
find a rational way to draw the line to say that at some point
we can't -- I've been trying to take refuge in good medical
practice, and I've been not allowed to do that, and ask whether
in principle I would draw a line in which somebody with no diagnosable
illness - right - with no diagnosable illness would not be allowed
to take a medication. And what I'm saying is that if you
ask me naked of all my protections about medical practice, follow-up,
and this and that, I would have to say I can't find that line
right now, but that I'm worried about the impact of that on
the sense of moral agency and personal responsibility.
CHAIRMAN KASS: Paul.
DR. McHUGH: I'm sorry you have to leave,
Steve, because we could go on for a long time talking about your
presentation, and how thorough it was. But I want to come, if
you would, just briefly to talk about the foundations of your
opinions here today as expressed. I know you have other opinions,
and they turn on this idea that we're dealing with reality
out there, and we have to make accounts of reality. But, Steve,
you know perfectly well that those realities of our making, particularly
from the psychiatric side. And that DSM-III-R, IV, and IV-TR
are based on a particular approach to things that had a reason
25 years ago, to try to get us to talk, but now has its own deep
problems, very deep problems.
DR. HYMAN: Right.
DR. McHUGH: Including the expansion of psychiatric
disorder so that it's now a huge, huge thing.
DR. HYMAN: Right.
DR. McHUGH: The belief in appropriate treatments
now being offered for various forms of conditions that are placed
in there, certain forms of PTSD, social phobia, multiple personality
disorder, and all of that rests upon this idea that a top-down
approach of checking off a checklist is the right way to diagnosis.
With your hope that ultimately we'll find a validation of
that from --
DR. HYMAN: A different set of --
DR. McHUGH: Yeah, entirely different. Now
since that reality is of our making, that's what makes for
the 11 minutes is all you, and that you can't teach people
appropriate approaches to psychiatry, I have two questions. What
are we going to do about getting a psychiatric approach to diagnosis
that approximates medicine? DSM-IV does not approximate anything
like medicine in ICD-9 and 10, as you know that, so that's
the first question.
And the second question is, do we understand development, maturation
and acculturation for it's psychosocial tasks adequately,
and its responsibilities for the development of the child right
now to be able -- for most children to be able to intervene with
medications? You said that drugs and life experience do the same
thing to the brain. And you know I agree with that. They certainly
change the synapses. But we also know that both drugs and live
experiences can do terrible things in the process of building
--
DR. HYMAN: Right.
DR. McHUGH: So question one, where are you
going with DSM-IV to DSM-V? Secondly, do we understand anything
to be able to satisfy the gentlemen on this side, and ladies on
this side, to say that we know how to build a child sufficiently
well to make the gains on your SAT scores adequate to the things
you lose in depriving them of the opportunity to play more, to
have different friends.
DR. HYMAN: Right. Okay. So this is -- right,
these were not exactly yes or no questions.
DR. McHUGH: No.
DR. HYMAN: You know because you've read
my criticisms of current psychiatric diagnostic nomenclature,
that I find enormous problems, and again, in one minute, we have
a difference between trying to coalesce around and name important
conditions that we really see that people have, like manic depressive
illness or schizophrenia, versus the exigencies of a profession
that wants to be reimbursed for its work and is forced by, you
know, the reimbursement system to give a lot of things names,
and we know that there is a lot of -- this is not theoretically
neutral or apolitical, but at the same time, I have a certain
amount of sympathy in my better moments given the -- the real
difficulties of doing better given the state of our science, so
we have to change, but I don't have any easy prescription
for how to change. And I'm very conservative about blowing
up an existing system. I'd like to fight its excesses. You
and I would both like to fights its excesses, but I don't
want to blow it up until I have something really that -- until
our genetics is farther along, our neuro imaging is farther along,
because we'll go back to Babel.
The other issue is exactly my problem, and Professor Sandel
here smoked me out, that I am living -- on the one hand I can't
find, you know, a bright line that if we really had perfect drugs
which didn't create, you know, the 1980 -- I'm sorry,
the "Brave New World" scenario. I could find a bright
line to outlaw them, but at the same time, my -- as I said my
precise concern is the messages that we deliver in terms of human
self-efficacy and moral responsibility. And if you can find a
way to manage the reality that will dawn on us, there is just
no doubt that minimizes the undercutting of a sense of human agency
and moral responsibility, without unfairly stigmatizing those
who are truly in need of treatment. You have my blessing and
best wishes. Unfortunately, I have to be off --
DR. McHUGH: If I could just reply to that
just to say that maybe the thing that we need is not more neuroscience
at some level and better psychiatry at some level, both to develop
a classification and to answer some of these questions about what
maturation itself is doing to individuals, and that's where
my problem.
CHAIRMAN KASS: Dr. Hyman has to return to
teach a class. It's heroic of him to have come on a teaching
day to spend time with us. Thank you enormously for a wonderful
session. We're adjourned for 15 minutes.
(The session then went off the record for a break.)
***
CHAIRMAN KASS: This is a session on the topic
of "Beyond Therapy: Ageless Bodies?" Before we start
into that, at least a couple of the people who had their hands
up when time ran out have spoken to me about a possibility of
at least putting into the record certain kinds of questions or
concern, not so much to interrogate Dr. Hyman, who unfortunately
had to leave, but if people would briefly like to simply put into
the discussion the questions or concerns that they had, since
that was a conversation that was just about to take off, I think
it would be appropriate if we allowed room for that. I had on
my list Bill May, and Bill Hurlbut, and I don't know if there
was anyone else in the queue. Bill, do you want to add something?
DR. MAY: Well, I felt that Dr. Hyman talked
about the gap between what we know and what we do, which tends
to lead to too much over-treatment, and too much under-treatment.
But earlier he really talked about the gap in science really,
it's a young science we're talking about. And also, there's
a second gap between what we know now, and what we would like
to know to feel comfortable about what we do. And both of those
gaps seems to lead in the direction of saying no regulations,
no bans, but it makes you very dependent upon a guardian class
in the interval before you narrow the gap between what we know
now, and what we should know to feel fully confident in what we
do.
But what was quite depressing, it seemed to me, is you depend
upon the guardian class, but it turns out that our guardian class
doesn't have the timing, or the time or the training to do
what it ought to do in order to guard. So no regulations given
the gaps with which we live, real dependency upon the clinicians,
but we discover the clinicians are woefully under-trained in operating
in a system where they have no time, even if they had the training,
to do what needs to be done. Which again leads bioethics out
in the direction of systems, institutions and structures, away
from some of the issues that we've dealt with.
CHAIRMAN KASS: Bill Hurlbut.
DR. HURLBUT: I was going to inquire of Dr.
Hyman whether he thinks that he would see ADHD in a hunter/gatherer
community, and in the same amount. And whether it really is in
some way an artifact of narrowing our definition of normal, because
it seems to me that -- well, if it were a Mendelian trait, we'd
define polymorphism as 1 percent of the population. Here we have
3 to 5 percent. It seems like well, 3 to 5 percent of the population
could have some kind of a deficit, but then the question becomes
well, is this just part of the spectrum of human variation in
a positive aspect of our society which should not necessarily
be treated or narrowed, but given a different educational process
and opportunity to develop in its own trajectory.
I think it's interesting that ADHD is kind of a derivative
diagnosis based on the educational system. Isn't that where
it's first picked up, as inability to sit at a little desk,
read little black symbols off of white pages, and not playing
out with the activity that normally accompanies childhood for
most of human history? What worries me about this is it also
goes deeper than that. I think the idea that this is a genetic
disease, which is -- certainly, there's a strong corollary
between monozygotic twins, but that doesn't necessarily mean
it's even genetic, of course, because it's -- they share
nine months in the womb. And there are some people that believe
that maternal stress during gestation provokes this problem, and
that even if it were correlated through generations doesn't
prove its genetic because there are now evidences that stress
itself is echoed generation after generation. And what worries
me in that is that when you label something genetic, it's
much easier to justify the concept that it has a single unitive
source as maybe a missing enzyme or something like that, and then
justify a medical diagnosis and a pharmacologic intervention,
so I think those are worth saying.
And then just two final points. One is that I disagree with
the statement that was made, if I understood it right, that there
was no difference between treating somebody who seems to fall
below the norm and somebody above. I think there's an intrinsic
difference there, and one case you might argue that it is more
like therapy in the sense that it's normalizing, that it's
bringing somebody into community.
On the other hand, that's when you treat the left side of
the bell curve. But when you treat the right side of the bell
curve, it's intrinsically competitive because it's moving
you away from the norm into a realm of superior performance.
I mean, there's a lot more to be said about that, but I think
if you think of human community as the ground not just of human
strength in sociology, but also human meaning, then there's
an intrinsic difference between the treatment of those two sides
of the bell curve.
And finally, it seems to me that one of the fundamental dangers
in this simplistic notion of a genetic deficit is that the reification
of a very complex human phenomenon where we tend to think of complicated
human realities as treatable by some kind of magic bullet, when
in fact the closer you get to meaningful human existence, the
less easy it will be to intervene, because human beings have evolved,
or have been created, however you want to see it, to be distanced
from determinism, and even simple molecular interventions. The
most meaningful human existence is somehow the comprehensive willed
self-governance of our humanizing activities. And to the degree
that we give over easily to notions that there are simple deficit
disorders, we have to be very cautious about that because that's
a very dangerous assumption in a complicated species like our's.
That's not to say I don't believe there are disorders
like that, and I'm not saying this one isn't, but it just
strikes me as a very, very important point. And actually, let
me add one final point to that. Even if you say this is directly
related to say a genetic cause, there are historical conditions
that suggest that we need to be very, very careful about what
we think that cause is. An example of that would be cleft palate
and the relationship with mental retardation, which was long assumed
to be correlated. And then when it got to the point where our
medical treatments could go in and do surgical interventions early
enough, we realized that that so-called genetic mental retardation
was actually a byproduct of the fact that the cleft palate was
blocking the eustachian tubes, causing earaches and otitis media,
and muffling speech, and therefore, causing the children to not
be able to keep up with their peers because they couldn't
hear and understand what was going on. So what looked like a
genetic cause of mental retardation, turned out to be just a secondary.
CHAIRMAN KASS: Okay. I think there are people
who are also in the midst of developing their own thoughts in
relation to Dr. Hyman's presentation. And Paul and others,
if you'd be so inclined, a couple of paragraphs leading to
some kind of question, we would welcome them at the office, and
we can send them on to him and see if we can elicit from him some
further elaboration on some of the things of concern to us.
Let me turn to --
DR. FOSTER: Leon, let -- could I just --
CHAIRMAN KASS: Please, Dan.
DR. FOSTER: I want to sort of give a reference
for the library that people might have here, because one of the
things we talked about in the last hour was the issue, the moral
issue of one struggling without the help of drugs and so forth
in mental illness, and maybe some of you have seen it, but Leon
Rosenberg, who happens to be a close friend of mine, Leon Rosenberg
has published his experience with manic depressive illness. Leon
was a Dean at Yale Medical School for 10 years, and now works
at Princeton, and Robby probably knows him in molecular biology
and so forth. He published an article called "Brainsick",
and it's in Cerebrum, Vol. IV. I can't remember
the pages, last year. It's one of the most remarkable documents
that I have ever read, a confession about a struggle from youth,
ending up finally in a suicide attempt in which ultimately then
somebody who struggled against this for life, was a great investigator,
became the Dean of Yale, and all these things, trying to fight
this alone, and eventually succumbed and surrendered to a suicide,
requiring ultimately electroconvulsive therapy and Lithium and
so forth. It also is a familial, as he outlines, it's a familial
illness, and it simply emphasizes to me the difference between
a highly moral struggle to try to do it by one's own in an
illness which ultimately requires medical therapy. And so it's
heroic in one sense, and in another sense it's a tragedy.
I mean, not that he didn't achieve everything, but he might
have had a happier life if he could have done that. So I simply
wanted, if you haven't seen it. It's a rather obscure
journal, and so -- but I thought it would be an interesting article
to put into the archives of the library that the Council is putting
together.
CHAIRMAN KASS: Yeah. Thank you, Dan. We'll
find it and actually circulate it to members.
DR. FOSTER: Yeah. Leon Rosenberg is the author.
It's called "Brainsick" in Cerebrum. Okay.
Session
2: Beyond Therapy: Ageless Bodies
CHAIRMAN KASS: Thank you very much. Other
comments before we move forward? Okay. The topic of this session
is "Beyond Therapy: Ageless Bodies?". This is a piece
of the "Beyond Therapy" project in which we are investigating
those uses of biotechnology to intervene in the human body, in
the mind, affecting the life span and the mode of generating new
life. We are working toward writing this up, and I hope by the
next meeting, before the next meeting, there will be things to
read of a more coherent and unified sort.
In the previous sessions when we touched these topics, we had
invited outside experts to tell us where the science is, both
now and prospectively. What we have in two sessions today is
a return to these topics to look at the human and moral significance
of acquiring these new powers, in this case, over the aging process.
And the next case, over some aspect of human memory. And this
is a much more difficult task, where we're engaged in forecasting
the human significance of things which are not yet here, and in
which the meaning of any one of these developments will be connected
with many other things that may or may not happen, either in biology,
or in society, or what have you. And part of the reason for tackling
this project is to allow at least one aspect of that cumulative
meaning to come forward; namely, what human life might look like
if a variety of these powers arrived at once, or arrived in concert.
In this session, we've put together reflections on what
it would mean to intervene either in toto in the process of the
human species, or in part, looking at the possibility of stronger
and longer-lasting skeletal muscles through the intervention of
various biotechnologies, in particular, genetic modification of
muscles. You'll recall that we heard about this from Dr.
Sweeney already last, I want to say July.
The Staff has prepared two papers which are in the briefing books.
I trust you've read them. In this session, rather than go
in the usual form, sort of episodic comments, I would see if I
could try to hold the reins a little more tightly and discuss
some of the, what I think might be the critical issues. Let's
stipulate that these techniques would be widely available, relatively
inexpensive, and for the sake of the discussion, relatively safe.
And that one would either be able to significantly extend the
human life span through intervention in the aging process, or
more modestly, that one would be able significantly to affect
human musculature through interventions. And let's also,
I think probably not as reasonably assume that these things would
be equally available, so that we don't raise, at least for
the moment, the question of unequal access, or the fact that these
would be the gifts only to the rich or to the privileged, just
so that we could look for the moment at the thing itself.
And I guess the two staff papers have, in addition to
reviewing the state of the science, listed a number of possible
implications of this, both for individuals and for the society as a
whole. But I thought I'd like to begin and see if we could discuss
the question. Does it strike us as reasonable to regard biological
aging on the model of a disease which would be at least addressed, if
not remedied or alleviated, at least to some extent by medical
intervention? The conceptual question now of how we sort of think
about the process of aging, whether this is rightly to be thought of as
on the model of disease begging for medical examination, intervention,
and possible remedy?
By the way, I should mention while you're pondering, and
I'm going to stop in a second, the latest issues of Science
magazine, 28 February, has "The Research on Aging: The
End of the Beginning" is the theme of the issue, and it's
linked to a website, "Science of Aging Knowledge Environment",
SAGE KE, which has a whole series of articles which describes
this really as the end of the beginning phase of this research.
And in fact, talks about the conclusion of the editorial, quotes
Charlie Chaplin, "That we are all amateurs. We don't
live long enough to become anything else."
It goes on to say, "If the aging process could be
attenuated, humans would have additional healthy years to bring their
personal goals to fruition. The challenge to society will be to ensure
that those goals are compatible with the needs of humanity",
whatever those might be.
It seems that we -- our discussion has at least got the
imprimatur of the latest issue of Science Magazine, so we're
not too far ahead of the curve. Let's start with this question.
Is it reasonable to think that the biological processes of aging are
rightly regarded as analogous to a model of disease to be studied and
modified? Elizabeth.
PROF. BLACKBURN: I think the problem I'm having in
reading the paper which didn't clarify it, and I think we should
bring up now is, we're going to assume mortality at some point.
Right? We're going to assume that that will happen. And I think
the issue is the rate at which we approach that from some peak state.
Right? And so, if we -- none of these discussions seemed to deal with
the idea that we could imagine a scenario in which we had different
kinetics of the various stages in life, and so you used in the paper
the rubber band analogy where everything is stretched out.
And I'd like to return to this, but the quick question is,
if we assume that these sorts of ideas are based upon the idea of an
extension of the say prime years of life as defined by, you know,
whatever your prime favorite decade is, your 20s, or 30, or 40s,
whatever, 50s, but then -- and then 60, of course, terrific decade.
And then there would be a decline that would be say, to put it
scientifically, a particular slope down to death. Right.
Now you keep that slope the same, but now that slope would
only begin at say 100 years old. Right? What you've done is
simply extended the adult phase. Right. That would be saying that
there is a phase which for the life, contour and so forth is, you know,
a decline which everybody would have, but the delay before its onset
would be different, and that's what I'm not clear about. You
see what I'm saying? Or you could have mortality in two seconds,
you know. Suddenly, you're going from prime to death, and I
don't know if that's the thing that's being specifically
discussed here, that there is no intervening period of what one has
been calling senescence.
Could you clarify, because I could see various trajectories.
If you'll line them up, there's three. The rubber band,
everything is equally stretched. Twenty-four months of gestation, three
decades of teenagerhood. Great. I can see that's not going to
work. Right? So let's say -- and I think developmentally that is
incorrect, so I think we probably will mature at reasonable ages. Then
the question is -- at reasonable speeds. Then we get to adulthood.
Should there be an adulthood of 80 years of undeclined abilities and so
forth. Right. And then a normal rate of decline, i.e., we decline at
some normal rate as a species, and then there's mortality. Or the
other extreme is that you have the extended decades of adulthood, and
then a very rapid decline, because we're going to assume that
there's death at the end.
<
