February 16, 2007
COUNCIL MEMBERS PRESENT
Edmund Pellegrino, M.D., Chairman
Floyd E. Bloom, M.D.
Scripps Research Institute
Rebecca S. Dresser, J.D.
Washington University School of Law
Nicholas N. Eberstadt, Ph.D.
American Enterprise Insitute
Daniel W. Foster, M.D.
University of Texas, Southwestern Medical School
Michael S. Gazzaniga, Ph.D.
University of California, Santa Barbara
Robert P. George, D.Phil., J.D.
Alfonso Gómez-Lobo, Dr.phil.
William B. Hurlbut, M.D.
Leon R. Kass, M.D.
American Enterprise Institute
Peter A. Lawler, Ph.D.
Paul McHugh, M.D.
Johns Hopkins University School of Medicine
Gilbert C. Meilaender, Ph.D.
Janet D. Rowley, M.D., D.Sc.
University of Chicago
Diana J. Schaub, Ph.D.
SESSION 5: THE GENOMIC "REVOLUTION" AND THE PRACTICE OF MEDICINE
DR. PELLEGRINO: Good morning. Our speaker this morning
is Dr. Francis Collins. It's been customary, Dr. Collins, not to
go into a long dissertation on people's accomplishments. In your
particular case, that would be certainly overdoing it.
We don't have to say very much. No one is better known than Dr.
Collins in this field. And so I just want to express our delight
and our pleasure and our honor of having you with us. And you take
off in the direction that you have indicated in your title.
Following Dr. Collins' presentation, the discussion will be open
by two of the members of our Council: Dr. Janet Rowley and Dr. Bill
Dr. Collins, the floor is yours.
DR. COLLINS: Well, thank you very much, Ed.
DR. COLLINS: It's a real pleasure to have a chance
to address this distinguished group. And on this rather cold morning,
nice to see you all here looking so bright and ready for an interesting
discussion. That's what I'm expecting will happen here
because I think the topic is certainly a timely one.
I know that in November at your meeting you heard
presentations from Kathy Hudson and from Bob Nussbaum on this topic of
where genomics is taking us as far as its implications for medicine.
And I will try not to duplicate very much the materials that they went
over, although there will be some unavoidable overlap of a sort. But I
did have a chance to look at their presentations. So I think I know
some of the ground that has already been covered.
So I thought what I would do is particularly this morning
to focus on the science, to tell you about things that are happening.
And they're happening quite quickly in the applications of genomics
to understanding the hereditary factors and somatic factors that play a
role in health and disease that are moving rather quickly in the
direction of application in the practice of medicine, maybe not as
quickly as some of us would like because we're impatient but
certainly more quickly than I think a lot of practitioners are aware.
This is I think, therefore, an appropriate topic for this
Council to consider because it also carries with it a lot of ethical,
legal, and social issues, which I will try to mention a few of those
anyway towards the end of the presentation. And then I hope we can
have a vigorous discussion about all of this.
So we do, after all, have the circumstance now, a rather historic
one, of having our own human sequence accurately determined and
sitting in an internet-accessible database as a consequence of a
Human Genome Project happening.
Interestingly, just about exactly 50 years after Watson and
Crick's description of the structure of DNA, now in April of 2003,
all of the goals of the Human Genome Project were completed, including
this 3.1 billion base pair, human DNA sequence deposited all the way
along by more than 2,000 investigators, who worked together to achieve
this goal in a really remarkably efficient and selfless way.
But, of course, we are just beginning readers in a certain way
when it comes to trying to understand that genome sequence, our
ability to look at those A's, C's, G's, and T's
and figure out what information is encoded there. And how it all
works is moving forward, but we still have a lot to learn to try
to understand how this script gets read and how sometimes glitches
in the script result in disease risk.
I think many people, sort of excited as they were about the
consequences of having our human genome sequence, now in 2007, 4 years
later, are saying, "Where's the beef? Why haven't we
completely transformed everything that we are doing in the medical
arena?" And anybody working in the field would have told you that
wasn't a realistic expectation, that this was a foundation. But
now we have to build on it.
And I think this is a pretty good representation of the
first law of technology, which is we tend to overestimate the effect of
a technology in the short run and underestimate the effect in the long
run. And I think that will turn out to be true for genomics and we can
decide what is the definition of short run and what is the definition
of long run. But this law, which is played out in many other
instances, I think will play out here as well.
So today I am going to talk to you mostly about things that
are present now in the research arena, which I think will find their
way into the clinical application, but some of them are already there.
And clearly, as we try to anticipate the consequences of all of that,
the time is now to pay attention and try to put into place appropriate
considerations to be sure that this is all done in a benevolent way,
that it helps people avoid or deal with disease, as opposed to putting
them at unnecessary risks.
So many of us do have this future dream that medicine will,
in fact, move into a phase where individual information can guide the
process. You wouldn't think of buying shoes in a single size.
I'm quite sure that all of you here when you went to the shoe
store did not just randomly pick a pair of shoes off any old shelf.
You looked for the section that had your particular size. And then
you applied other criteria to what you might want to pick out.
But you certainly if you wear a size seven didn't start in the
size ten section looking for what would fit you.
And, yet, for medicine, we have largely been forced to do
that kind of generic approach because it was what we had. It was the
best information we could go on.
We did some tweaking of that, you know, trying to adjust
drug dosages by body mass index or body surface area and certainly
treating children different than adults most of the time, although not
always. But it has been still very much a one size fits all kind of
approach in terms of the diagnosis, the prevention, and the treatment
And since we know we are all different individuals with
different risks, this is not an ideal circumstance. And one of the
promises of genomics is to try to do a better job of this kind of
individualizing of the approach.
So let me just mention a few notes from the front lines
here for using this metaphor of the genomic revolution, which, you
know, is maybe not the greatest metaphor because it sounds all very
This is certainly not our intention here. But, in fact, it
does seem as if there is a real groundswell of change underway. And so
we may as well call it that. I guess that was the title I was
assigned. So I'll stick to the word "revolution."
Let me just point out a few notes from the front lines of
things that are happening, some of them just in the last year or two,
that may not have necessarily reached the ears of the public to the
degree that perhaps they should have because I thought this group of
distinguished experts might want to consider what some of the
consequences would be.
Some people somehow assumed that DNA sequencing was all
over once we had gotten that reference sequence of a human genome and
some other model organisms, like mouse and rat and dog and horse and so
on, that that would sort of be it.
And that is obviously turning out to be a very narrow
view. In fact, DNA sequencing is emerging as a tool for human medicine
in ways that I think most people had not quite been prepared for. And
the idea of being able to sequence any of our genomes for an affordable
cost, maybe $1,000, could well be no more than 5 or 6 or 7 years away
given the way in which the technology for doing this is moving forward
Two instruments have found their way into our large-scale
sequencing centers in the last year and in many other places as well.
These machines are beginning to be tried out. And at a meeting in
Marco Island, which is one of the gatherings every year where
technology gets trotted out and discussed, the production efforts being
built upon these instruments were truly impressive. And this is just
two weeks ago.
So one of these is a machine called 454, which is a rather odd
name, I suppose, for a company and an odd name for an instrument,
but that's what it is. The idea of both of the two machines
I'll tell you about is to get away from the traditional gel-based
methods, which is basically the method that Fred Sanger invented
back in the late 1970s.
All of the DNA sequencing we have done up until now has
largely been to build better and better efficient steps into that
gel-based dideoxy method of DNA sequencing. And it's served us
very well. And we have driven the cost down by orders of magnitude,
particularly because of the Genome Project and its need to do so.
But we are now seeing a real quantum change in the
approach. And the two methods that are now finding their way into
practice are really built on different principles. This one is done on
beads, where the idea is that you attach DNA to specific beads. You
amplify them on that bead.
And then — and here is the trick — you can then do
sequencing at massively parallel platform arrangements so that, instead
of in a typical current sequencing machine, where you might run 96
reactions at once, here you can run hundreds of thousands or even
millions of reactions at once, simultaneously collecting all the data
in a rapid way.
There are still bugs in these systems. Their quality of
the data is not as good as the tried and true method that has been
optimized now over more than 20 years, but it's coming along very
quickly. And it's clear this is going to make a major impact on
our ability to collect the DNA data.
Perhaps even more of an impact may come from this machine
built by a company called Solexa, which again uses massively parallel
approaches instead of beads. Basically the DNA fragments are attached
to a surface and then amplified in place using a polymerase chain
reaction so that you end up with clusters of molecules that can then be
sequenced. And that's just, in fact, what one can do.
Once those clusters are there, you can actually see them
affixed to the solid surface, as in this picture. And each one of
those clusters can then be sequenced using an enzymatic reaction.
These give you short reads but, as you can imagine, just a very high
volume of them.
And it looks as if we have already reached the point of
having the ability to sequence an individual human genome for something
in the neighborhood of $100,000. And that is two orders of magnitude
cheaper than it would have been if we had stayed on our current cost
curve. And the expectation is that that will continue to drop.
Already individual human genomes are beginning to be sequenced by people
using these instruments for research purposes. And you should anticipate
that this will increasingly find its way into larger-scale research
and ultimately into clinical practice of medicine.
And I think that is where the real growth area for DNA sequencing
is: we're already now applying this kind of very high throughput
in expensive sequencing to try to find the genes that are still
out there unidentified from Mendelian disorders because there are
many rare conditions where we have not been able yet to find the
responsible gene. And to be able to sequence the entire genome or
a segment where you know that the gene must reside, based on linkage
evidence, is undoubtedly going to help a lot finishing out this
work of identifying those conditions.
We know, for instance, there are probably 50 different
types of x-linked mental retardation that have not yet had their genes
identified. And you can imagine a project, in fact, that is now
getting underway where you simply get DNA samples from large numbers of
affected males and you sequence all of the exons of the genes on the
And you can do that, actually, for a very affordable cost.
And undoubtedly you will make a lot of discoveries of genes that are
involved in brain function and that account for these particular
conditions. And, of course, the hope would be that some of those will
lead you in the direction of ideas about treatment.
Common diseases also sequencing can be now applied to
candidate genes and as it gets cheaper and cheaper to just sequencing
the whole thing. But perhaps a particularly attractive approach that
is being undertaken right now with DNA sequencing is for cancer. This
has been unaffordable until now, but now it is becoming so because this
cost curve is coming down so rapidly.
The cancer genome atlas is a joint effort of the Genome
Institute and the Cancer Institute currently being conducted as a pilot
project on just three cancers, the three that you see here. And the
goal is to sequence something in the neighborhood of two or three
thousand genes in four or five hundred individual tumors of each of
these types for which DNA is also available from blood so you can
compare the DNA sequences and figure out what is a new mutation
somatically and what is a hereditary change and not only to do
sequencing but also systematically to look across the genome for
changes in copy number, where you have delegations or amplifications,
as well as to look at gene expression.
And we put all that data set together, together also, I
should say, with epigenetic information. We may finally begin to have
a comprehensive view of what goes on in these three tumor types. If
this goes well, we would hope to expand this after the pilot phase to
look at many more tumor types and apply the same approach.
Obviously the more rapidly the cost comes down, the more
practical that is, especially as NIH is at the present time rather
significantly strapped in terms of budgetary restrictions on what we
And TCGA has several components. I won't dwell upon
this. But basically it is a highly organized effort involving now
dozens of laboratories that are working together to try to apply all of
these new technologies to the same set of tumors and to put all of the
data into a database where any qualified investigator can immediately
see the results and there is technology development as well.
And ultimately, as I have been saying, I think the next
step beyond these more focused efforts will be complete genome
sequencing, initially for research and then as part of mainstream
medical care. And that, of course, is some years away but not as many
as one might think.
So what are we to do in the meantime for those common
diseases like diabetes and asthma and schizophrenia, autism,
hypertension, the common cancers, where we know there are hereditary
factors? Some have been found, but a lot have not. Do we have to wait
until we have the ability to do complete genome sequencing to find
those variations or could we speed up the process now by taking some
sort of shortcut? And, of course, I wouldn't answer the question
if the answer wasn't yes.
So, in fact, there is a very exciting phase getting
underway now about how to find those factors. If there are relatively
common variations, we have the ability now to do that without having to
look through the entire genome.
So here is the next sort of note from the front lines — the
discovery of genes for common disease is happening, particularly
in the last few months. And I think you're going to see in
the next few months a virtually outpouring of discoveries about
variations in the genome that are relatively common in the population
that play a significant role in risks of common diseases.
The idea is to develop methods that can find the ticking
time bombs that are residing there in the DNA. And we all have them,
probably dozens of them. None of them carry a very high risk of going
off. Perhaps if you have one of these, your risk might go up by 10 or
20 percent over the situation if you did not. And it's the
combination of these particular genetic risk factors plus environmental
exposures that generally is responsible for whether disease occurs or
And we need to uncover what both the environmental and the
genetic risk factors are in order to figure out better ways to
intervene. And, frankly, the genetic factors we're not going to be
able to change, but if we understood how they occur, who is at high
risk, and could modify the environment or the medical surveillance
plan, that would be a good strategy for individualized prevention.
So how are we doing this? Well, basically what you would
like to do would be to sample across the entire genome and find
variations, here color-coded to make it somewhat simpler to explain the
strategy, like variant b. So in variant b, our ten affected
individuals have a higher proportion of the orange spelling than do the
unaffected individuals, who have many fewer orange spelling
Most of the genome will not give you that kind of answer.
If you're looking at a disease like diabetes, most of the genome
you would not expect to see a difference between the cases and the
controls. But somewhere out there if you accept the idea that some of
the hereditary risk factors in common disease arise from common
variants, you would expect if you had a systematic way of surveying the
genome, to be able to find examples like this.
Now, my cartoon makes it look easier than it is because
most of the risk factors you find are not going to have this kind of
dramatic skewing between cases and controls. You're looking for a
relatively modest difference because these are not going to be
deterministic findings. They are going to be risk factors.
And so, instead of 10 cases and 10 controls, in general,
you need 1,000 or more if you're going to have sufficient power to
be able to assess the situation. And that has been the daunting
That means you have to identify a large number of
individuals with the disease and carefully characterize their
phenotypes. And you have to have well-matched controls so that you
don't end up chasing down false positive results that have nothing
to do with the disease.
But the most daunting part of this until recently has been
how would you actually survey the whole genome to do this kind of
comparison? And so people have largely been forced to look at
so-called candidate genes, which is to say you've got to have a
hunch and you've got to go and figure out amongst the 20 or 22
thousand human genes what's on your short list that might be
involved in the disease.
And the problem is for most diseases that you would like to
apply this to, we're not smart enough to know what the short list
ought to look like. We're still pretty ignorant about the genetic
factors in a disease like, say, diabetes.
And so most candidate gene studies have been pretty
disappointing. There have been false positives that didn't hold
up. There have been occasional success stories, but mostly it has been
one long story of disappointment and frustration.
And, of course, you would like to get beyond that forced hunch,
sixth sense situation, to be able to scan the whole genome systematically.
And that's what we now can do, and that's why there is this
real dramatic leap forward occurring in discovering these genetic
factors because we finally have the tools to do this.
A big part of that comes out of this project which was an
international project called the HapMap Project. I had the privilege
of serving as the project manager of this effort, as I did for the
Human Genome Project.
This was focused on that .1 percent of the genome where we
differ, not the 99.9 percent where we're all the same. And we
wanted to get a really good catalog of what that variation looks like
in different parts of the world. And we were limited in how many
different parts of the world we could look at.
So we basically looked in a population with northern European background.
We looked at the Yorba tribe in Ibadan, Nigeria. And we looked
at in individuals living in China and Japan. That was our sample.
And it actually turns out that that's a pretty decent representation
of the variation that you might have found in other places as well.
And what HapMap did was to basically tell you where the variation
in the genome is and how it's organized into neighborhoods because
it doesn't turn out that these variations in the genome are
all independent of each other. They're actually traveling in
a bit of lock-step, reflecting our relatively recent descent from
And the good news about that is that means that you
don't have to sample all of the ten million variants that are
common in the genome to find the ones that are associated with disease
because they are associated with each other in local neighborhoods.
If you pick wisely, you can pick a much smaller set of
these variants. And they basically stand in as surrogates for all the
rest. And if you're smart about how you do the picking and
that's what HapMap allows you to do, instead of having to look at
ten million things, you may only have to look at a couple of hundred
That has now become possible with the kind of chips that
are being used to do DNA genotyping. One can look at more than 1,000
cases and more than 1,000 controls with hundreds of thousands of these
genetic variants and afford all of that for something in the
neighborhood of one to two million dollars, which is a lot less than
the cost of having collected all those cases and control in the first
And so there is a huge amount of interest and activity
going on right now to apply those ideas to common disease. And the
success stories are starting to build up.
The first success story and one of the most dramatic one is
this common cause of blindness in the elderly, macular degeneration.
Most people were not that convinced that this was going to be a disease
where genetic factors were all that important. It doesn't come on
until your 70s, 80s, or 90s. There was some familial clustering, but
it wasn't all that impressive.
Applying the HapMap, Josephine Hoh and colleagues were able to
identify a variant in Complement Factor H, which plays a very strong
role in disease risk. And not too long after that, another major
risk locus was identified, HTRA1. And just these two variations
seem to account for about 50 percent of the risk of this disease.
Another significant environmental risk factor is smoking.
So we have gone from knowing very little about the cause of
this illness to having a much more refined picture and one that
actually suggests the possibility of interventions because both of
these genes seem to be involved in the inflammatory pathway. And it
may very well be that prevention could then be mounted by using an
approach that depends on anti-inflammatory agents, including ones that
are already FDA-approved. So this is a pretty exciting story to go
from essential ignorance about a disease to a really nice view of what
is going on in the space of just a few months.
Other early results from HapMap from about a year ago, the identification
of a gene, TCF7L2, in Type II diabetes, now confirmed by almost
a dozen groups as a major player in risk of this particular common
adult-onset disease that causes so much mortality and morbidity;
a variant associated with prostate cancer, which, interestingly,
this variant is more frequent in African populations and might account
for some of the health disparity in prostate cancer between different
groups, although not all; and in Science a few months ago,
an association identifying IL23R as a gene important in Crohn's
disease. And this one also suggests immediately a therapeutic strategy
that I'm sure is being pursued by more than one group at the
And just three days ago — this is from online Nature,
not yet out in print, another study of Type II diabetes, which both
confirmed that TCF7L2 that we already knew about but also identified
three other genes, including this guy, SLC30A8, which is a fascinating
discovery and one which my own lab has already independently found,
which is a zinc transporter that is only expressed in the islet
cells of the pancreas. Insulin in the pancreatic islet cells is
complexed with zinc.
And you can imagine how this kind of transporter, if it's not
quite doing its job, might have an effect on the ability of your
pancreas to make insulin when it's supposed to, also immediately
suggests a dietary form of therapy, which might be a very nice nutrigenomics
kind of outcome for this sort of discovery.
So these things are happening. And I tell you in the next
two to three months I know of at least three or four other major papers
that are coming out on other conditions, such as schizophrenia, that
are going to be quite revealing in terms of finally nailing down some
of the well-validated genetic factors that play out in diseases that
have been so puzzling.
To try to stimulate this to go even faster, NIH has been
engaged in an unprecedented public-private partnership, again trying to
speed up this process at a time where NIH funds are somewhat
We built this public-private partnership using the
foundation for NIH as the moderator of the whole thing and obtaining
funds from the private sector to support what is basically a completely
open access competition for individual investigators who already have
collected samples from cases and controls of particular diseases to get
access to this kind of high throughput genotyping.
The requirement is that all the data has to be put in a
database, where any qualified investigator can see it. And that has
been agreed to. And we had more than 30 applications for this
particular competition. And when the dust all settled, these are the
six studies that are now underway and already well into the pipeline.
Interestingly, four of those six are mental illness
conditions. And we didn't necessarily expect that was going to be
the case. It just reflects the fact that the National Institute of
Mental Health was thinking about this five or six years ago and really
preparing for the moment where this would become possible. And so they
had already collected very well-characterized cases and controls, dealt
with the consent issues in an effective way so that these samples
could, in fact, be put into this pipeline and have the data from the
genotyping accessible to lots of investigators around the world. And
that's a serious issue for some of these studies where the consents
are, in fact, going to be a problem.
So that's one big initiative that's underway. And
then on top of that, just starting in the last couple of months and
strongly supported by Secretary Leavitt, we have an NIH genes and
environment initiative, which really is now trying to pull together
advances in technology to detect environmental exposure in a more
rigorous way than we have been able to do in the past. And by that I
also include diet and physical activity.
There's a lot of opportunity here, particularly using
cell phone technology, to do a better job of actually recording what
people are exposed to, than the questionnaire-based methods, which have
been the mainstay in the past. And this will also support additional
And this is all being done in a coordinated, integrated way
that David Schwartz, who directs NIEHS, and myself are co-leading. And
this will involve the expenditure of $40 million a year for each of the
next 4 years to try to speed up this process of identifying factors and
coming up with strategies for intervention.
So I think it's fair to say we're going to see
these major common variants for common diseases coming out — they
already are — in the next two or three years, that we will go from a
pretty significant level of ignorance to a much better informed
situation about what factors are involved in disease pathogenesis.
And each one of those discoveries provides both an
opportunity to suggest who is at risk by using this diagnostically, but
in the longer term, I think what we're most excited about is that
this points you towards a pathway that could be used to target a
We desperately need new ideas about therapeutics that go
beyond our current hunches about what pathways are involved. And I
think in the longest term, this whole business of discovering, using
the tools of genomics, hereditary factors, and disease is going to have
its biggest impact by revolution in therapeutics.
But we all know how long that takes because that means you
have to come up with a hypothesis. You have to then go down the
pathway of identifying a small molecule, of finding out whether it
works in cell culture, then in animal models. Is it toxic? Does it
have appropriate distribution, metabolism, and excretion patterns? And
ultimately can you run a clinical trial, show benefit, and get it
approved? So one should not expect the therapeutic impact of these
discoveries that are happening right now in less than a decade or even
So let's move, then, to those clinical applications.
Again, as I'm saying, I think the full consequences are going to
take a while. But some of these things are coming along more quickly.
And they will all come sort of helter-skelter. It
won't be every disease is moving through this pathway of gene
discoveries and therapeutics at the same pace. A lot of that will
depend upon how much energy is being put into it, how many resources,
and also serendipity.
You know, you run into a gene, like that zinc transporter
that immediately suggests a simple treatment. Well, you're much
further along than if you encounter a gene than nobody has ever studied
before and you have no clue what it does. First you have to figure out
a lot of basic science about its function before you can begin to apply
your ideas about treatment.
So let's consider, then, this flow of information
that's coming out of this revolution in genomics. And I think
what's basically happening now in a big way is the diseases with a
genetic component, which is virtually all diseases if you look hard
enough, are going to have their genetic defects identified because of
these increasingly available and efficient tools.
Then the clinical implications will kick in. And probably
first of all diagnostics because it is, at least in concept, rather
simple once you have identified a variant that you are quite confident
increases the risk of disease, then you could begin to offer that
prospectively to people who might want to know.
And there are all kinds of interesting issues about why
would people want to know. And a lot of that relates to whether there
is, in fact, a preventive strategy associated with knowing you are at
After all, we have known for quite a long time, about 15
years now, that a major risk factor for Alzheimer's disease is
having the e4 allele at the APOE locus. And, yet, that test is not
very much used and is not all that interesting to most people because
we have nothing to offer the people who are found to carry that allele
other than to say, "Well, you might want to plan your future a
little more carefully." And most people don't find that a
sufficient reason to take the chance of getting information that could
actually be quite distressing.
So I think perhaps what has been underestimated is just how important
and how complicated it is to go from having a hypothetical diagnostic
to being able to demonstrate that you do have an intervention that
only sort of makes good common sense, but it actually works. You
want to have that data, I think, before you begin to advocate for
a change in the practice of medicine.
In some instances, we are there. Perhaps the best example
in my mind is in cancer because familial cancer syndromes have as their
mainstay early detection if you want to try to improve the outcome.
And certainly colon cancer is a wonderful example of this,
families such as this. And this is a real family from Baltimore. Not
too many years ago, if this person marked with the arrow here had come
in asking what her risk is and whether there is something she should be
doing about that risk, she would have gotten sort of a general
recommendation that yes, you're probably at higher risk because of
your family history. But there's not a whole lot more we can say
That's all changed now with the discovery that families
like this are extremely likely to have mutations in one of a couple of
DNA mismatch repair genes, which can be tested for in this family.
That was, in fact, done and showed that the affected individuals had a
mutation in the MLH1 gene, which is a mismatch repair gene. And then
that made it possible for the unaffected individuals who are at 50
And there are in this picture five of them to find out
whether they also carry that mutation. And in this instance, that was
done. And it turns out two of them do have that additional risk and
are at about a 60 percent likelihood of developing colon cancer during
Now, here is a case where we have very good data to say
that if you're in that situation, you should begin colonoscopy
probably at age 30 or 35 and you should do that every year, not every 5
years. And with that kind of rigorously adhered to program, the
likelihood of finding polyps while they're still small and easily
removed before they become invasive cancers is extremely good.
And so here is a case where this kind of family history taking,
which was an important start point — you notice here family
history is not going to go out of date just because we have fancy
ways of assessing DNA sequence. Family history taking followed
by a thoughtful analysis of the potential here of a specific mutation
being tested, followed by careful recommendations and implementation
of those in medical surveillance is life saving and actually saves
money as well.
Now, not all diagnostics are going to be on the germ line
DNA. And, in fact, I think the area of greatest growth in diagnostics
right now is actually in cancer and relates to somatic changes and
particularly the effort to try to predict from what you find in a
tumor, what's the likely future course for that individual.
And perhaps the most widely applied example of this is the oncotype
DX approach, which genomic health has marketed for prediction about
whether a particular breast cancer is likely to recur or whether
it is very unlikely to and, therefore, whether adjuvant chemotherapy
might be passed over.
And this is data from a paper now almost three years old
showing that, in fact, the score, which is basically built upon an
assessment of gene expression for a rather short list of about 17
genes, correlates reasonably well in a prospective way with the
likelihood of distant metastases ten years later.
So this test, in fact, has been adopted by many oncologists in the practice
of taking care of women with breast cancer, although the FDA is
still questioning whether, in fact, this test is appropriate for
them to intervene and try to regulate.
And, interestingly, FDA did approve a competing test just a
couple of weeks ago based on a similar strategy but which requires
frozen tissue, cannot be done on a paraffin-imbedded formalin-fixed
section, which is where most breast tumors currently end up.
So it would be, in fact, unfortunate from the perspective
of applicability of this test if only the frozen sections were
useable. Many women would not be able to have the chance to learn
about this. So that's an interesting debate that is going on in
terms of how much FDA regulation and this kind of test is appropriate.
So that is the diagnostic part. A big area of current
interest, which has grown rather quickly and which is I think coming
closer every day to becoming standard of care but not quite there
except in a few uncommon circumstances, is to apply this information
about genetic variation to predict drug response.
And already now for almost two years on the market has been
a chip that will determine an individual's variations in the p450
genes, which are responsible for metabolizing a very large number of
drugs. And certainly knowing your genotype for p450 does have
predictive value in terms of how you might respond to antidepressants
and anticonvulsants and anticoagulants and a number of other drugs.
Interestingly, while this was marketed two years ago, the
uptake has been very limited. And I think that's because most
physicians are really not quite sure what to do with the information
that comes out of this. There are really no good guidelines about how
to take that information about somebody who is a poor metabolizer or an
ultra rapid metabolizer and change the dose that you're prescribing
of a particular drug. And I think that is an area where we need more
data and certainly more education.
A drug where this particular approach together with other
kinds of pharmacogenomic analyses might very well find its way into
practice relatively soon is the drug warfarin or Coumadin, which is one
of the most commonly prescribed drugs and the one which is used for
anyone who has had atrial fibrillation with a risk of a stroke or a
deep vein thrombosis. So this is an anticoagulant.
Many individuals, including my mother, are on this drug.
It is a very difficult drug to manage. The window between an adequate
dose and an overdose is extremely limited. And many people do, in
fact, suffer consequences, particularly at the initiation of therapy,
because the drug dose turns out to be too high or too low.
And it's very clear in retrospective studies that you can make a
pretty good prediction about what the maintenance and loading dose
ought to be. If you know the individual's genotype at both
p450 and at a gene called VKORC1, something like 55 percent of individual
variation in the dose requirement comes from those 2 sets of genes.
And we can now do that prospectively.
The question is, do we have enough data to begin to make
that recommendation? Should the FDA now put this on the label, saying,
"If you're going to prescribe Coumadin, then you should
determine the genotype first?"
Well, there is an issue here. How do you get the data
quickly enough? You've got somebody with a deep vein thrombosis.
You need to start them on the drug. If it's going to take two
weeks to get the genetic tests back, it's pretty irrelevant.
So we need to figure out how, in fact, logistically to
actually implement this test. And most of us think if this is going to
be the first one that we really try to move into practice and it will
be a real sea change in the mindset of many practitioners, you want to
be darn sure that this is actually going to help.
And so NHLBI and ourselves are organizing a prospective
trial to compare the outcome using the genetic test versus using a
dosing algorithm that incorporates everything else that we know is a
variable, like age and gender, which are also important variables for
predicting the dose. And we'll have to see.
And if, in fact, the genetic test adds only minimally to
that and adds additional cost and logistical challenges, then it
won't be appropriate to do this. If, on the other hand, you can
show that including the genetic information reduces the risk of
somebody getting way out of range or having a bleeding complication,
well, then I think that will be a compelling case.
Maybe the first drug, though, that is ready for
pharmacogenomics is not Coumadin, but it's a drug probably many of
you haven't heard about, Abacavir, which is a very effective drug
against HIV/AIDS. And, yet, about seven or eight percent of people who
are given this drug get a rather severe hypersensitivity reaction,
which can require hospitalization and can even be life-threatening.
We now know a lot about what that is about. And this
particular hypersensitivity reaction comes about because of a variation
in a gene in the HLA complex. If you happen to be one who carries the
HLAB5701 allele, your likelihood of getting a hypersensitivity reaction
to Abacavir is pretty high. And if you don't have that, it's
So this is a very attractive opportunity to try this out.
And the Australians have done this, not just retrospectively but
prospectively, and were able to show that when they introduced this
prospective genetic screen, that they dropped the incidence of Abacavir
hypersensitivity almost to zero. And this looks like, then, a good
poster child for being able to implement a pharmacogenomic approach to
And we're talking intensely right now with FDA and
NIAID about whether there is any need for additional data here or
whether this is one where we already have enough information to take
that step. And there are labs that will do this test and will do it in
the space of 24 to 48 hours. And the need to prescribe this drug
immediately, as opposed to waiting a couple of days, is not as
Ultimately, though, where you really want to get to in our
diagram — and I mentioned this earlier — is the therapeutics. And
that is going to be the longest lead time. And it's, therefore,
going to be frustrating to us.
We have to, I think, take some comfort, however, in the fact that
the strategy is a very appealing one. And in a few instances, it
is beginning to play out quite nicely. And I can't come to
this group and talk about therapeutic advances based on the genome
without referring to the most compelling example, which comes out
of the work of Janet Rowley but, of course, based upon work that
was done a long time ago.
So one of the reasons this is now such a success story is
that the basic work to get us here was started a long time ago. It
wasn't a direct consequence of the Genome Project.
And this is, of course, Gleevec, a drug which turns out to block
the active site of the kinase that is generated by this Philadelphia
chromosome that Janet described, which is a fusion of chromosomes
9 and 22, seen in most patients with chronic myeloid leukemia.
That particular kinase transforms well-behaved white cells into
leukemic cells. And Gleevec, the drug that Brian Drucker and Novartis
collaborated on, ends up blocking that active site.
Just recently, a couple of months ago, a five-year follow-up of
this drug published in the New England Journal showing
that, in fact, the long-term success here is really quite startlingly
wonderful that there are individuals who become resistant to the
drug. But, as you can see from this curve, all told here, the number
of deaths related to CML after initiating therapy is actually quite
small in a five-year period.
So we would love to see that replicated over and over
again. I think that is the dream that we all have as we begin to
discover these genetic factors involved in lots and lots of diseases,
but recognize the pipeline is a long one to get to this kind of
I can't help but point out a couple of other examples
where smart researchers aided by some serendipity may be able to
short-circuit some of those very long steps.
This is the work of Hal Dietz at Hopkins working on Marfan
syndrome. Hal was involved 15 years ago in the discovery of the gene,
which is a gene called fibrillin. And everybody assumed this is a
structural protein and that's why they have the heart disease and
there's probably not much you can do about it because it's a
Well, it turns out fibrillin has another function.
It's also an inhibitor of TGF-beta. And it turns out if you have a
mutation in fibrillin, you don't inhibit TGF-beta well enough and
so you have over-activity of that particular factor. And that
contributes substantially to the phenotype.
And in this paper, Hal was able to show that this drug, losartan, which
is already FDA-approved for the treatment of hypertension, is also
a TGF-beta antagonist and in this mouse model of Marfan syndrome
essentially prevented the aortic dilatation, which is the cause
of death in many patients with this disease.
And I've seen recent data that Hal has presented at meetings,
showing that this drug, now given to children who have particularly
a rapidly advancing course of Marfan syndrome, seems to stop the
dilatation of their aorta as soon as the drug is started.
And there is now a big trial underway to apply this in a
much larger group and compare it to the standard beta blocker
approach. It looks very promising that, in fact, by banging away at
trying to understand the biology of this disease based upon the gene
discovery but not assuming that it is just as obvious as what it
initially seemed, that Hal has happened into something here that might
be an incredibly valuable discovery for the treatment of this disease.
My own lab works on this disease, progeria, the most rapidly progressive
form of premature aging shown here in three pictures over the course
of about 12 years of a young man with this disease, whose hands
you see holding the photo.
We discovered the gene four years ago, found that it's
a sporadic mutation in a single base pair of the Lamin-A gene that
creates a dominant negative protein that results in the premature aging
But, again, because we fell into a pathway that other
people had worked on for 20 or 30 years, Lamin-A has been the subject
of much interest among cell biologists for a long time. And we know a
lot about that protein. We are now about to initiate a clinical trial
using farnesyl transferase inhibitors, which if I had more time I would
explain the logic for.
Here is a girl with progeria on the treadmill getting ready for her to
establish a baseline so that when the treatment is started, one
can see whether it's working.
And, again, this is putting together a number of previous
observations with gene discovery, with the fact that there are a lot of
drugs out there that have been developed for other purposes that may
potentially turn out to have unexpected uses.
And even cystic fibrosis, a disease that had certainly
hoped to see advances now for quite a number of years given that the
gene was published, the discovery was published, in 1989, we are now
seeing because of this new approach of applying gene discovery to drug
development drugs coming into clinical trials. And so the first
gene-based drug has now entered clinical trials.
Just out of curiosity, this is the same person. This is Danny,
who is on the cover of Science. This is a couple of months
ago, when I ran into Danny at a cystic fibrosis event. And he's
obviously doing very well. But we need to come up with a better
strategy as soon as possible for this disease.
This is an interesting cover. This is Drug Discovery World,
one of these magazines that I don't generally read, but somebody
gave it to me. And what are they saying the future of drug discovery
is? GWAS. Well, what is that? Genome-Wide Association Studies.
This is HapMap-based approaches to understanding genetics
of common disease, mapping the future of genetics. They're
concluding it is going to be the best engine for therapeutic discovery
that we have had in a long time. And I certainly agree. And it's
kind of a cool cover, too.
So, finally, to bring this back more perhaps to this
Bioethics Council in terms of the issues to worry about and to think
about, certainly the attention to ethical, legal, and social issues,
which have been part and parcel of the Human Genome Project from the
very beginning, are more important than ever as we see this
accelerating pace. And I'll just mention a few. And I'm sure
others may come up in the discussion.
The number one issue for us at the Genome Institute from
the very beginning from the 14 years I've been there, if you want
to say what is the most important policy issue that we need to attend
to, it's to prevent an outcome where people who find out
information about their DNA have that used against them and
particularly in health insurance and in the workplace.
Here we are, 2007. We still do not have effective federal
legislation, but we are a lot closer than we have ever been. Going
back a couple of Congresses, in the 108th Congress, a good bill that
covered both health insurance and employment passed the Senate
The House failed to act. So we had to go on to the 109th.
In that case, the House did actually have a bill introduced, but,
again, no action was taken upon it. And, as you know, the 109th
Congress came to an end about two months ago. So now we're at the
And I'm happy to say that the momentum is certainly
better than it's ever been. Both the Senate and the House have
bills that were introduced early in the session. Both have now been
marked up, the Senate bill a couple of weeks ago, the House bill just
this week. And there is a growing enthusiasm for the idea that this
might actually come to a vote on the floor of the Senate and the floor
of the House.
I was very gratified when President Bush visited NIH a
month ago and I had a chance to spend 45 minutes with him, he used a
good chunk of his comments at the beginning of this session to talk
about this issue of genetic discrimination and again to underline his
perspective that this is a issue that needs a legislative solution and
that he would hope to see this particular legislation passed.
And he would be prepared to sign it right away. So maybe
we might actually get there this year. After many, many years of false
starts and disappointments, I'm trying not to get excited because
it is such a letdown when something falls through, but considering all
of the tea leaves at the moment, this looks more promising than it has
The opposition here is largely coming from the Chamber of
Commerce, who feel that, in fact, employers may be subjected to
frivolous lawsuits if people who have been fired for good cause then
come back and say, "Well, they did it because of my DNA."
And the bill is actually written rather carefully to try to
discourage those kinds of frivolous lawsuits. And it's also I
think important to note that more than 40 states now have legislation
of this sort and there has not been a single such lawsuit in more than
Oversight. I know when Kathy Hudson came and talked to you
in November, she spent a lot of her time focused on this and
appropriately so. We want to find the right balance, but squashing
an area of genetic testing between not squashing an area of genetic
testing that is potentially growing rapidly and has a lot of promise
but also doing something to put the brakes on tests that are actually
not well-validated. And then it might actually do harm.
The FDA up until now has largely taken a hands-off approach. I
mentioned that they have now started to look at these multiplex
tests for breast cancer. Whether they also begin to look at other
tests is an open question. And what other kind of oversight ought
to be there, especially when you look at the wide, wide work of
direct-to-consumer testing that is going on out there, some of which
is really pretty bizarre.
U.S. News and World Report just a couple of months ago
had a whole discussion about this, pointing out in a pretty good
story that these tests can show you risk, but how good are they?
And many of them are not yet I think at the point where you would
want to fully trust the results because most of the discoveries
upon which such tests would be based are just now happening when
you're talking about common disease.
I am actually concerned that this topic is still not
getting as much attention as it should. It is easy to say, "Well,
the 99.9 percent identity of human DNA ought to be an argument for
saying how much alike we are and ought to be an argument for reducing
bias and prejudice." And I think that has occasionally been an
argument that has gotten attention.
But also as we look more carefully at DNA, it's clear
that if you give me a sample of DNA and ask me, "Did this
person's ancestors come from Japan, West Africa, or northern
Europe?" I could answer your question given a few days in the
laboratory because there are variations that are differentially
distributed around the world, reflecting all kinds of migration
patterns over the last 100,000 years.
It is even clear that there are regions of the genome that
have been under recent selection. And you can see the signature of
that. And for a very small number of those, we understand the reasons
So if you look at the beta globin gene, for instance, in
the malaria belt, you will see evidence for selection. Well, okay.
That's because that has been protective.
If you look at the lactase gene in people from northern
Europe, you'll see evidence of recent selection that allows them to
digest milk as adults; whereas, others in other parts of the world may
not be able to do this.
But there are hundreds of these segments of the gene for
which we do not know what the function is but clearly show differential
selection depending on which part of the world you're looking at.
And it would be hard to imagine that some of these aren't going to
turn out to be controversial in certain ways. And it's not clear
to me that we're fully ready to face up to that.
Again, I think the health disparity question is one of our
most important issues as researchers, but it's a very complicated
one. What really is the relationship between self-identified race and
ethnicity? There are a lot of connections here. And people tend I
think to blur through them rather quickly and maybe oversimplify.
Maybe in my limited view here, it's good to keep in
mind that an awful lot of health disparities have nothing to do with
genetics or heredity, but it related to differential environmental
exposures, including education, access to health care, culture,
socioeconomic status, and even things like stress. And those play a
major role in health and disease.
But it's clear — and I mentioned the example of
prostate cancer — that at least in some instances, there are genetic
connections as well that reflect ancestral geographic origins. And
those, in turn, are reflected in genome variation. And that, in turn,
may then result in variance in specific genes that play a role in
So self-identified race or ethnicity is a proxy for a lot
of other information. The sooner we can get closer to the action and
really identify what the proximate factors are that are involved in
disease risk and stop using race or ethnicity as a surrogate, the
better off we'll be, both in terms of the precision of our
information and the lower likelihood that this is seen as a means of
reidentifying the concept of race in a way that it doesn't
deserve. We have got a lot of hard work to do, I think, to get through
to that outcome.
Access is a big issue. As we contemplate the $1,000
genome, for instance, okay. Who is going to have access to that if it
turns out to be valuable? It probably won't be everybody at once,
at least not in this country.
I would refer you to what I think is a very thoughtful
piece coming from the Secretary's Advisory Committee on Genetics
Health in Society, a group which I'm sure this Council has been
watching closely because they have struggled with many of the same
issues that you all are dealing with in your discussions, particularly
the ones about genetics.
And they, I think, pointed out all kinds of things that potentially
could be done but require a lot of national will and political will
to achieve because at the present time we're clearly not in
a circumstance where coverage and reimbursement of tests and services
based on genetics are on a trajectory to make access even and relatively
When I spoke to this Council five years ago — and I looked
back, it was five years ago — the topic was enhancement.
I think at that point the conclusion, and justifiably so, was that
a lot of the scenarios that were being put forward about enhancement,
like the Gattaca movie, which we watched a clip of that
day, — right, Leon? — were rather fanciful. And we
should spend our time worrying more about things that are realistic
in the sort of ten-year time frame than things that won't happen
during that interval, if at all. And I think probably that was
a wise recommendation. And I wouldn't really stray away from
I think in terms of enhancement, the practical applications
at the present time really fall much more in the direction of PGD,
where you have an increasing ability to apply more and more kinds of
genetic tests to pre-implantation genetic diagnosis. And the question
is, where should those limits be set?
It's one thing to tests for Tay-sachs disease.
It's another to test for gene variant for, say, obesity. And I
know that there is a gene variant for obesity that will be published
soon that is clearly highly validated. So is there going to be an
application there that enterprising marketers to couples who determine
to optimize everything will see as something they want to begin to
And then there is this more philosophical question and one
that I am very interested in and have been from the beginning. Are we
running the risk with all of this excitement about genetics — and,
believe me, I'm excited — that we overemphasize the role that DNA
plays in humanity and undervalue other things, such as the environment,
free will, and the human spirit?
And for me as somebody who very much enjoys the opportunity
to seek the truth, not only scientifically but spiritually, I do worry
that one of the contributors, one of many, to the increasing view of
humans as more machine-like than spirit-like, may be our own field of
genomics. And we really should work very hard to explain what this can
tell us and what it cannot.
And in that regard, I seem to have had the opportunity recently
to get engaged in conversations like this one in Time magazine,
a debate with Richard Dawkins, who obviously is putting forward
the view that what we're learning about genes and evolution
means that we should sort of get over the idea that there is any
need to consider things beyond that. My view is rather different.
And this was an interesting experience, I can assure you.
So let me not go on any longer because I went on a little
longer than I intended to. Basically I do think it is an appropriate
and ethical stance to try to apply the tools of genetics and genomics
to alleviate human suffering.
I think one of the least ethical things we could do would
be to say we should slow this down. I would have a very hard time
explaining that to the parents of a child who has an illness that
desperately needs some new intervention.
At the same time, I think we would have to have our eyes
wide open to the ways in which these kinds of advances may lead to
misuses that society will be comfortable with. And that's why
I'm glad all of you are spending as much time as you are in rooms
like this thinking about those issues and trying to sound some sort of
warning signals when there are things that need more attention than
they are currently getting. And I am glad to be part of your process.
Thank you very much.
DR. COLLINS: Shall I come and sit down over there? Would
that be —
DR. PELLEGRINO: Yes, please. Thank you very much, Dr.
Collins, for an absolutely superb, breathtaking, exciting review of the
field of genetic medicine. You have really taken us from the molecule
to the ethical and the social and even the spiritual. And it's
been a great privilege to hear your presentation.
What we plan is to have two members of our Council open the
discussion of your paper. And I will ask them to make their comments
and then open the discussion to the members of the Council generally.
Our first discussant will be Dr. Janet Rowley.
DR. ROWLEY: Well, firstly, Francis, I want to thank you
very much for your comments related to my own research in Gleevec and
point out to members of the Council that Dr. Collins has been far too
modest himself to point out that he has contributed to many of the
things he described, including helping to clone the gene for cystic
fibrosis. So that he certainly merits the thanks of all of us and also
I think the acclaim that he has received.
I can only echo Dr. Pellegrino in saying that, as always, Francis
has presented a very dramatic and exciting talk. And it has been
wide-ranging. So that when you think of a President's Council
on Bioethics and think of the ethical issues that may be raised
by the discoveries of the Genome Project, that, in fact, you covered
pretty much what the ethical issues are and some of the status of
trying to deal with those.
And I think that the question of trying to make sure that
genetic information is not used against an individual or a family is
certainly one of the major challenges that we face.
And I can remember when Clinton was president and I was
president of the American Society for Human Genetics writing a letter
on behalf of the society urging that individuals not be discriminated
And I think, unfortunately, many members, who are sort of
similar to the pedigree that Francis illustrated of a family with colon
cancer, in this case with the gene MLH1, but women will not get tested
for VRCA1 because they don't want that information available to
insurance companies or to employers, but I think in one sense women or
families are more concerned about insurance and that this country has
not protected those individuals yet, as I think a disgrace and an
ethical, moral disgrace.
So that is an area I would guess with bills in Congress,
that there isn't a whole lot that the Council can do except
possibly to encourage the consideration and passage of that bill.
I think another issue that you raised, Francis, is that as
a society and the physicians in that society are not really prepared to
deal with considering diseases on this kind of genetic basis or
probably more appropriate is how to evaluate information that is coming
And, again, this is not an ethical issue. This is more one
of education in saying that medical schools have got to do a better job
of teaching medical students about the medicine of the future and about
societies and other organizations to which physicians and nurses and
other health professionals, the societies to which they belong have got
to be important.
The question that I had thought of before we started was
for you was going to be what the ethical issues were for the
President's Council. And, yet, you have gone through most of
them. I guess I would still come back to that question.
Are there issues that you didn't in your presentation
have an opportunity to discuss as fully as you might have liked that
the Council could deal with or are there additional issues that for
constraints of time you didn't have an opportunity to speak about?
DR. PELLEGRINO: Thank you, Janet.
Dr. Hurlbut, you are the next commentator.
DR. HURLBUT: Actually, I would like to give as much time
to Francis to answer the last question, but just let me make a couple
of comments to frame this. It's obvious that we're talking
here about a subject, right or wrong, that touches on the very meaning
of origins and ultimate ends when humans think about their genetics.
And that clearly is at the foundation of individual and
social identity and the grounding of morals itself. We tend to think
of this in a very special way with regard to the causal circle of
being, right or wrongly.
But it does strike me that there are some interesting
things we ought to put into the mix of our discussion. You mentioned
the issue of race and the parent exaggeration of determinism and so
You [mentioned the 99.9% similarity between individuals]. I just
want to point out that percentage has relatively little to do with
biology in the sense that we have dynamic systems and we are percentage-wise
very similar to chimpanzees, but there is quite a dramatic leap
between us, at least in some characteristics. [So the basis of our
moral equality must be something other than the percentage of our
shared genetic sequence.]
Also, given the nature of gene-gene interactions and
environmental interactions and so forth, most of our data on cause is
going to be placed in terms of statistical probabilities. And there
will even be stochastic events that trigger certain dramatic changes in
the outcomes of events, even if most things seem very similarly
So that strikes me as important. And, likewise, because of
these confusing questions of determinism and the reductionistic model
that genetics seems to promote in the common mind anyway, there is a
special fear of genetics, both excitement and fear essentially, promise
and peril, as it has been said 1,000 times.
And here is an issue I really appreciate some comment on,
Francis. Apparently people are quite reluctant to go into studies that
involve the use of their genetics. They're more willing to do
studies that involve their RNA than their DNA.
And obviously if we're going to exploit the full
possibilities of this field, we're going to use huge databases with
demographic and epidemiological data. And you might comment on that a
I think, reflecting on what our Council might do, I think I
would like some guidance because this is a subject that has been
thought about a great deal, funded a great deal. And if you look at
what has happened over the last 15 years of discussion, it actually
hasn't moved that far in terms of conclusions.
So I would like your thoughts about what issues remain to
be talked about deeply and what some avenues in to those might be.
And, just to mention a couple that strike me, the issue of
discrimination that you mentioned in the bill, some people have raised
a question about whether that bill and our general social attitude
sufficiently address the question of pre-implantation genetic diagnosed
and whether families might be vulnerable to not having their children
covered by insurance or so forth. Would you address that question for
us, whether that's a subject that's been adequately dealt with?
Also, what I mentioned in the way of DNA records, recently
there was an op ed. by Michael Crichton concerning patenting of
genes. Would you mention something on that?
And, finally, two final things. One, could you say
something about the advances in synthetic DNA synthesis and where that
might lead us? And one thing that you only implicitly touched on that
I would be interested in hearing about is you brought us back down to
the notion of interventions that are preemptive or preventative medical
interventions. If we could only know what was influencing disease
development, we could perhaps go down to the bottom and prevent the
expression of these diseases.
It does strike me that that presents a rather interesting
dilemma for medicine. We don't want to intervene in a way that is
damaging to an individual. A lot of disease expression is secondary
physiological response to unfolding disease conditions. It might be
much more subtle to intervene in these diseases than we think.
Do you get what I'm getting at there?
DR. COLLINS: No.
DR. HURLBUT: Not entirely. Well, quite a lot of disease
symptomatology is actually the result of the body's response to a
disorder. So, for example, tuberculosis is an immune reaction largely,
the body's compensation mechanisms. And we could very easily
target the wrong response.
Well, just go to the bottom of how we might intervene in
genetic disease early in the special challenges in watching how we ramp
up to that.
Do you understand what I'm saying? So those are the
main things that strike me. And what I most of all would like to hear
about is what you think we could do that others have not done.
DR. PELLEGRINO: Dr. Collins?
DR. COLLINS: Well, a very challenging pair of
commentaries. And I'm not sure that I'm well-positioned to
tell this distinguished Council exactly what direction to go in, but I
will reflect a little bit on the number of issues that you all have
raised. And thanks to both of you.
Maybe we'll go straight to this genetic discrimination question
because both of you brought this up. Certainly there's no,
I think, real disagreement from an ethical and moral perspective
on this topic, that this is an issue of justice, that if, in fact,
you don't get to pick your DNA — and we don't —
that that should not be used to deny you access to health care or
to a job that you would otherwise be qualified for.
The recent discussion about the details of the bill that
you mentioned, Bill, in terms of whether, in fact, it's written
appropriately to cover the circumstance of PGD has, in fact,
represented the latest hiccup in trying to actually get this done.
I must say from my perspective, I think the bill is written
in a way that covers those circumstances, but it quickly gets you into
some pretty deep weeds as far as legal language of particular
And the fact that it has been raised — and you probably
saw a letter from a Catholic bishop specifically pointing out the need
to address this. And there was an amendment proposed in the House
markup that would have changed the language in the existing bill, which
did not, I think, pass — in fact, I know it didn't pass — and
which actually worried a lot of the people in the Senate that the whole
process might be falling apart on these grounds.
I would say this is an important issue, but I think those
who are proposing changing the language of the bill to try to
accommodate it really need to sit down very carefully and make sure
that that is necessary because I think the coalition to get this bill
passed still remains somewhat fragile. And there are lots of opposing
forces out there that would love to see an issue raised that would slow
down or stop the momentum.
This is the latest issue that has been raised. And I'm
not sure that it is one that is understood well enough by those who are
suggesting amendments to make those changes. And it could potentially
derail the whole process. So I think we have to be very careful in
making those kinds of proposals.
In terms of a related question, you asked about
people's reluctance to participate in research that involves DNA
testing, as opposed to RNA. We have done actually studies on that
phenomenon by asking people who are otherwise qualified for NIH
research projects and who decide not to participate, "Why was it
you decided not to participate?" And it is this concern about
And that's why they're worried about the DNA part.
They get it that RNA expression is probably less likely to get them in
trouble because it comes and it goes, but they understand that DNA is
with you for life if you're talking about the germline part of it.
And once that information has been determined, you may not
be able to pretend it wasn't. And it could in the current
circumstance come back to haunt you, especially if you have to apply
for an individual health insurance policy down the road, which is the
part that is currently not protected.
Fully one-third of people who were in a situation similar
to that family I showed you with colon cancer, who were given the
chance to participate in a research study at NIH to go through the
process of genetic testing and counseling and particularly to monitor
what do they do with that information, do people actually change their
health behaviors, do they enroll in colonoscopy programs, do they
follow them rigorously, we need to know all the steps here.
A third of the people who were in the same high-risk
situation as the woman I showed you in that pedigree ultimately decided
not to participate because of this concern about discrimination.
So this is a very real and present issue. And the
legislative solution, it seems to me, would have a huge impact on
that. Whether it would reduce that risk completely to zero or whether
people would still have anxieties about what might happen in other
areas, like long-term disability or life insurance, which are not
currently covered, I don't know.
By the way, those are topics which we have essentially
avoided getting into in this country. And that might be an area that
is worth some consideration. I think people have been anxious not to
distract the conversation from the highest priority of discriminatory
circumstances, which is health insurance and the workplace, by raising
these other issues, but they are going to be there.
In the U.K., there has been a pretty productive discussion
about life insurance, for instance, with the conclusion being that also
there needs to be some ability for individuals to be able to at least
get a basic level of life insurance, which you need in many instances
to get a home mortgage, without having questions asked about your DNA.
In this country, we really haven't had that conversation.
Long-term disability will be a very difficult one because I
think you can argue there that adverse selection could come into play
and that if you know you're at high risk for Alzheimer's
disease but the company issuing the disability policy doesn't know
that, you're really going to destabilize the economics of long-term
disability insurance. And that will be an interesting and difficult
area to get into. And, as I say, presently we really haven't had
much progress in that direction.
So, again, I guess maybe because it is the big elephant in
every room that talks about ethical, legal, and social issues coming
out of the Genome Project, genetic discrimination comes immediately to
my mind in a response to both of your questions but other areas.
You mentioned intellectual property in the sense of asking about
Michael Crichton's op ed. I don't know how many of you
read Crichton's book called Next. Well, I have.
DR. COLLINS: It's rather fanciful. It includes
a cloning experiment gone awry that results in a sort of chimeric
chimpanzee human. It includes a parrot who seems to have remarkable
abilities to speak and think. And they all get mixed together in
this sort of "biotechnology gone wild" soup and a great
deal of additional sort of political commentary as folded in there
by Crichton about how intellectual property is really the evil that
has resulted in all of this. And biotechnology doesn't look
good in Michael Crichton's book, as you might imagine.
In the appendix, he sort of goes on a bit of a tear about
what he has learned about this and what should be done. I think there
are a number of aspects that he has got right and a number of aspects
that I don't think are quite properly presented in terms of the
facts of the matter in that op ed.
I am certainly one who has for the last 14 years, since I
have been at NIH, tried in every way to discourage the idea of
patenting information that in the past would have been considered
foundational and pre-competitive and ought to be in the public domain.
You have seen NIH move successively in the direction of not
only saying that but enforcing that by issuing guidances about
intellectual property claims in genomics and by putting as conditions
of grant awards those kinds of statements that "If you're
going to do this, your data has to go into the public domain
I think we have had a pretty positive impact there. And I
think the landscape really has changed. Crichton's complaints in
the op ed. would have resounded more ten years ago than they do now.
But we do have this legacy of a big mess that got created
during the 1990s, when there was, frankly, a bit of a gold rush going
on by people claiming intellectual property on snippets of DNA sequence
whose function was really not known and getting in some instances the
Patent Office to issue very broad coverage of those claims in a way
that now ties things a bit in knots for people who are trying to do
follow-on experiments that might actually help the public. So I think
the big problem we really have to deal with is more what, the mistakes
we made in the past than quite so much the present.
We are still pushing that envelope as hard as we can, not
just for DNA sequences. We have a new program at NIH to make it
possible for academic investigators to get access to this high
throughput screening process to find small organic compounds that have
activity in interesting biological essays and that might ultimately
lead to the development of a therapeutic.
And we have insisted that all of the participants in that project
put all of their screening results up on the database called PubChem
immediately without claiming intellectual property.
There was a big squawk about that, particularly from
universities, who I think kind of overvalued what it is that you get
out of a very early stage screen of this sort and thought that they
ought to be able to hang on to this information and patent it and maybe
not publish it for a while.
I, frankly, think that is not the way you are going to lead
to the kind of public benefit that the program was set up to do. So we
have held the line on that and insisted that if you are part of that
program, all the data has got to go into PubChem and no IP can be
filed. I think people are now getting used to it. Every time you come
into a new domain here, there is one of those issues.
With all of these genetic association studies that NIH is
funding, there is a discussion going on right now and lots of public
input has been sought about whether, in fact, the discoveries that come
out of that ought to be placed in the public domain or whether if you
have found a variation in a gene like that zinc transporter I told you
about that's associated with diabetes, that you ought to be able to
patent that as a therapeutic.
Our arguments are that the patenting really ought to apply
to further downstream efforts once you actually have shown something
that's on the pathway towards public benefit. And so our
insistence is that all that data also goes into a public database
immediately. And, therefore, patents cannot be applied to it.
We are encountering some resistance on that point, but I do
think just looking at the landscape over the last 15 years this
pendulum has really swung from where it was in a real land grab
environment to a much more sanguine realization that if our goal here
is to advance science and to benefit the public, you don't want to
put a lot of toll booths in the way early in this road towards
discovery. You want to let people travel on it freely and quickly.
You asked about DNA synthesis and the ethical issues there. And
I am glad you brought that up. I didn't have time to mention
it, the abilities to basically make any DNA sequence at will. While
they are not moving forward orders of magnitudes every year, they
are certainly improving substantially.
For instance, in a program we had been leading for the last
four or five years to try to get all of the human full-length coding
regions of the genes into a public database that everybody could have
access to and other means of sort of spurring research, we realized
about a year ago that, instead of trying to identify those coding
sequences from some library, that it's cheaper now to just make
And so we are now synthesizing those genes from, you know,
organic chemicals at a more affordable cost. And that tells you we
really crossed a line somewhere. And I don't think it's out of
the range of possibilities that many laboratories in five or six years
won't bother to store all of these clones that we keep around and
fill up our freezers with stuff we can't even quite remember what
it was. You'll just, instead, make it and say, "Oh, well, I
need that vector with that sequence with that particular
mutation," punch it in the computer. Tomorrow morning there it
will be because the synthesis will be just that good.
But, of course, that raises the specter of how this might
play out if falling into the wrong hands and people begin to make
pathogens that are really horrible.
And I think the group at NIH that is considering all of the
consequences that may come out of advances in biotechnology that could
be used for bioterrorist purposes are quite concerned about this issue
of DNA synthesis and is there any way to try to keep track of that.
So that, for instance, companies that are providing that
service monitor what it is that people are asking them to make.
Instead of just saying, "Oh, it's just all A, C, G, and T. It
doesn't matter," we need to have some kind of system of
keeping track of that.
That will work for a while as long as most of the synthesis
can only be done in a large facility, but it won't work forever if
it becomes increasingly portable. And that's an area to keep track
I need to quickly sort of get to the meat of your question,
Janet and Bill, what other issues and where do you think that the focus
might be for this Council.
I have to say I come back again to this concern about
genetics and the study of genetics and how that impacts our concepts of
race and ethnicity and what it means to be human.
All men and women are created equal, endowed by their
creator with certain inalienable rights. How is that affected by our
increasing ability to discover that where your particular ancestors
came from is going to be reflected by certain things that have been
selected for in your genome that might not be there were it not for
Those hundreds of places in the genome that show those
fingerprints or those footprints of that kind of selection are
ultimately going to bit by bit get figured out.
And some of them will be simply understood and
noncontroversial, like your ability to drink milk as an adult, but
others of them will be more controversial in terms of your abilities in
certain intellectual ways. It's possible. It's going to play
Behavior traits. We don't know what is going on there,
what kind of influences down through the last 100,000 years have shaped
the genome in different ways depending on where you are.
As we apply the tools of HapMap and the ability to scan
across the genome to find subtle variations that play a role in disease
risk, people are also applying those to look for things that aren't
Intelligence is clearly going to in the next couple of
years have variations discovered that are associated with how you
perform on an IQ test. That's inevitable.
Similarly, behavioral traits that you measure on a
personality test, some of which have already been discovered, although
some of them haven't held up very well, we're going to have a
big outpouring of that as well. And if those are differentially
distributed across different geographic groups, people are going to
draw conclusions about that.
And people will use that for demagogic political purposes
in certain ways that we will all find offensive. But are we prepared
to come up with an appropriate counter response or are we kind of
headed into a future and a not terribly distant future where the
wonderful idea that genetics is going to bring us all together will,
instead, be used to drive us apart? I am deeply concerned about that.
And I don't think at the present time we have a
particularly well-coordinated strategy. It's one of the things
when I meet with my staff that works on ethical, legal, and social
issues that's always at the top of the agenda.
There are many perspectives about this that are I think not
fully cognizant of what is happening in the field of genetics yet
because it's come along so quickly. We need to have a strategy
here. And it needs to be a strategy that reflects our shared
principles of equity and justice. And I think there's a lot of
work to be done there.
DR. PELLEGRINO: Thank you very much, Dr. Collins.
I would like to now throw the discussion open to the
Council members. We are close in time. So I will take the
Chairman's privilege of extending this discussion to 10:15, rather
than 10:00 o'clock. So if you indicate your desire to speak, I
will recognize you in some sort of order. Dr. George and Dr.
Meilaender in that order.
PROF. GEORGE:Thank you, Dr. Pellegrino. And thank you, Dr.
Collins, for that wonderful presentation.
I would like to explore with you for a few minutes those
philosophical questions that you touched on at the end and then again
at the end of your responses to Janet and Bill.
As a way in, I would like to just quote to you from a paper
that was included in our materials, though not for this session, for
our next session, in which an eminent philosopher, Daniel Dennett, says
the following, "Science has vanished the soul as firmly as it has
vanished mermaids, unicorns, and perpetual motion machines. There are
no such things. There is no more scientific justification for
believing in an immaterial and immortal soul than there is for
believing that each of your kidneys has a tap dancing poltergeist
living in it." Is that so?
DR. COLLINS: That's quite an interesting way to phrase
the question. So I know Dan Dennett.
DR. PELLEGRINO: Yes or no?
DR. COLLINS: He and I have occasionally debated
this issue about science and faith. And, of course, his book Breaking
the Spell got a lot of attention about a year ago when it came
out and expressed many of the same perspectives that are included
in that quote, which is really quite a zinger.
I think the problem with what he is saying there is that it
basically applies a scientific approach to a nonscientific issue. And
so it's guaranteed to get you nowhere.
If there is such a thing as a soul, science is not going to
discover it. If there is such a thing as God who is outside of nature,
science is the wrong way to discover him or her as well.
And so in the same way that I think this argument coming
from the sort of extreme atheistic wing of the scientific community
doesn't get you very far, it basically takes the tools of science
and applies them in a place where they don't work.
So obviously science is the way, the tried and true, the
dependable way to find out the truth about nature and how it works.
And one should not settle for anything less than scientific proof if
you're trying to ask a how question about how something in nature
But if you're trying to ask questions like "Why
are we all here or is there a soul or is there a God? And if so, does
God care about me?" it's immediately apparent, I think, as
soon as you step back for just a minute from that question to say,
"Science is the wrong way to try to approach that answer."
From my perspective — and I wrote much more extensively about
this in this book called The Language of God that came
out last summer — it is truly unfortunate that we have arrived
at this point in our culture, where there seems to be a battle going
on between the extreme views, where we have atheists, some of them
from my scientific community, arguing that we ought to just get
over this idea of faith, that it's a throwback to the past.
On the other hand, we have people of strong fundamental
faith who say that science can't be trusted because it contradicts
certain views that they hold about the origins of the Earth and human
Most of us live in the middle. Most of us are pretty happy
there. Forty percent of scientists are believers in a personal God.
It really is unfortunate that there is so much noise coming from the
extreme perspectives that people are beginning to wonder if that is all
I find that particularly difficult for young people,
particularly young scientists, who are being told that you have to make
a choice between these world views. That choice is both unnecessary
PROF. GEORGE:If 40 percent are believers, that would
suggest that 60 percent are either nonbelievers or agnostic on the
question. Would it be fair to infer from that or perhaps just from
other information that you have available that a substantial percentage
of scientists, perhaps not a majority, agree that science has vanished
DR. COLLINS: I think that is a very strong statement. And
I don't think most scientists would probably acknowledge the truth
of that statement. A few would.
I think most of that 60 percent, although the data is not
particularly strong here, are not scientists who are in the strict
atheist community in the way that Dan Dennett and Richard Dawkins and
Sam Harris are. I think they are mostly people who are agnostic who
basically say there is no way to know. They are not particularly
hostile to religion, but they are just not themselves participants in
that world view.
Frankly, I think many of them haven't given it much
thought. And I say this because I used to be one of those.
PROF. GEORGE:So you would say that most scientists
don't believe science establishes what these philosophers claim
science — that these scientists have, in fact, shown?
DR. COLLINS: I think in the phrasing that Dennett puts in
there about science having disproved the soul, most scientists would
have trouble agreeing with that.
PROF. GEORGE:My way of framing it would be that science is
concerned with understanding material and efficient causes if I can use
those old categories. And then the effort to suppose that since
science is concerned with studying efficient and material causes, there
can't be any other cause. In other words, there can't be
formal and final causes.
DR. COLLINS: Sure. If you imagine a circle that contains
all the truth that could possibly exist now or forever and then you ask
what is the scientific part of that circle, it's not the whole
thing. And so if an answer to a question you're looking for
happens to be outside the scientific circle, that doesn't mean
it's an inappropriate question. It just means you need another way
to approach it.
PROF. GEORGE:Now, the question that you raised at the very
end of the response to Janet and Bill about how they relate to each
other, does that mean that the answer to the important question about
how we will, whether we should, sustain the belief in the fundamental
equality and dignity of human beings is something, a challenge that has
to be met, not with the resources of science itself since efficient and
material causes are not going to even in a deep understanding at the
moment explain the basis of human equality and dignity, that science
itself will have to be subject to judgments brought from beyond
science, where we can explore realms of knowledge that would enable us
to judge, in fact, that all human beings are created equal, endowed by
their creator with unalienable rights.
DR. COLLINS: I certainly would agree with that. In my
view, morality is not sufficiently explainable by scientific or even
evolutionary arguments. Otherwise you're forced into the
conclusion that right and wrong are simply an evolutionary contrivance
and artifactual sort of representation of something that has no
absolute truth associated with it.
And when it comes to the principles of justice and equity,
I think those are principles where science needs to be brought into the
conversation so that we know what the facts of the matter are about how
humans are similar or how they're different, but I don't think
we're going to resolve the issue about equality and justice based
upon purely scientific arguments.
DR. PELLEGRINO: Thank you. We have four members of the
Council who wish to speak. The time is short. And I would like to
please ask that you be as direct as possible out of deference to your
colleagues, who would like to also participate. Dr. Meilaender?
PROF. MEILAENDER: This is very brief, actually, but you
puzzled me near the end, when you were talking through the various
ethical questions that you saw arising. And you came to enhancement.
And you recalled being here five years ago and you said when you were
here five years ago and talked about it, sort of general agreement that
certain things which were interesting to think about were not really
likely to happen in the near future.
And the way that sentence was moving, it sounded as if what
it was about to say was "But it's a little different now. It
looks a little different now than it did five years ago, but it sort of
just petered out at that point and didn't conclude anything."
Do you hold the same view? Do you hold a different view?
What is your view on that question?
DR. COLLINS: Well, Janet will remember this because we
certainly tried to struggle in that discussion about differentiating
between the designer baby scenarios that make good Hollywood movies but
really don't have much scientific legitimacy to them and to things
that might actually happen.
I think some of the things we talked about that might
happen in a ten-year horizon, things such as using human artificial
chromosomes, for instance, to introduce a new set of genes that
weren't already there haven't actually moved very quickly over
the course of those five years.
The one thing — and I was at that point aware that I was
running out of time. So I probably did hurdle forward rather quickly
at this point in the presentation.
The one thing that we did identify, which I do think has
moved forward, will continue to move forward, and is deserving of a lot
of attention, is the use of pre-implantation genetic diagnosis, not
that you're going to use that as a circumstance to insert a new
gene, not that kind of gene intervention, not that kind of enhancement,
but that you're going to try to skew the odds basically by having a
number of embryos and picking the ones that you're going to
re-implant based upon a DNA test that you perform, a biopsy, if you
will, on those embryos.
And, again, there is increasing availability of that
technology over the last five years. And there is certainly increasing
knowledge about genetic factors in conditions that are increasingly
more like traits than there was five years ago.
And I mentioned obesity in my remarks as an example that
might be seen as appealing to some enterprising provider of IVF
services. I don't know whether that will happen, but that is the
sort of scenario I think to think about, which five years ago we could
think about, but now it's getting a little closer to reality.
So I guess if I had to focus on an area of enhancement that
deserves another look, that would be it.
DR. PELLEGRINO: Dr. Kass?
DR. KASS: Thank you.
I could listen to you all day. Thank you for this
presentation and for your absolutely spectacular leadership, not just
in terms of science but in bringing this conversation to the public.
You've done it here. You've done it everywhere. And everybody
should acknowledge with gratitude your service.
I want to leave these large philosophical questions alone.
I want to come to the practical questions of the translation of this
genomic knowledge into clinical medicine.
In the paper that you submitted, there is a nice paragraph
which says, "Health professionals will need to become genomically
literate. New curricula of educational models must be developed.
Behavioral science research will need to establish how best to use
genomic information to affect health behaviors and outcomes," all
that sort of stuff.
There's a lot packed in there. And there's a
certain irony to me in the little slide which was shown twice,
"Personalized Medicine: A Future Dream." I mean, there are
some of us who would say leaving genomics out of it, personal medicine
of the sort you and I were trained to practice seems to be a vanishing
I guess there are two issues. One is given the
doctor-patient relationship and its dwindling character, given the
amount of education that would actually be required to discuss risk
management when you're dealing with statistical evidence here,
statistical factors at best, doesn't that particular part of this
— it's not just a matter of information. It's a matter of the
institutions that could act on that knowledge and do the kind of
education with stuff which is really not intuitive for the average
patient. That would be one.
And yesterday we had long discussions, several discussions, about
the efficacy of preventive medicine, which involves people's
changing behavior for things for which we have 100 percent correlations,
not 100 but very, very high correlations, of behavior and misery.
And Dan Foster took the very dour view that we just can't do
very much about making people change, even when the evidence is
staring them in the face.
So, I mean, the slides are marvelous. Some of the
innovations are marvelous when it comes to these targeted things. But
in terms of risk management, the first side, shouldn't we be much
more modest about our ability to use this knowledge efficaciously until
we have either a different way of doctors relating to patients and the
other matter about actually affecting people's behavior based upon
this knowledge, which is, at best, merely statistical and from the
patient's point of view like astrology?
DR. COLLINS: Those are great questions, Leon, as usual. I
think you have cut very much to the heart of the question about the
applicability of all of these discoveries, when it comes particularly
to the prevention arena.
You could argue that the therapeutic arena is more likely
in the long run to have a bigger impact because basically what
you're talking about there is a discovery engine for new approaches
to developing therapies. As long as we at least have a medical care
system that's capable of diagnosing and treating, having treatments
that work better would be a good thing and would probably advance
How realistic is this individualized prevention strategy
going to be? There are a lot of roadblocks. And you have mentioned
most of them. Certainly this circumstance, where at the very time you
would hope physicians would have the opportunity to learn about this
and to spend the time necessary interacting with the patient to walk
through this complicated information is the very time where they're
being taken increasingly to task for spending more than four minutes
per patient. It doesn't look like a very promising scenario.
Actually, ten years ago we founded with the AMA and the
American Nurses Association an organization called the National
Coalition for Health Professional Education in Genetics, NCHPEG, which
now has more than 100 member societies.
And it's increasingly clear to me it's not the
physicians that are probably going to carry the load of this. If we do
see this kind of genetic information finding its way into a discussion
with an individual about their own prevention strategies, it's
probably going to be someone like a nurse or a nurse practitioner or a
physician assistant who is able in our current cost system to spend a
little bit more time.
And we will also have to use heavily teaching aids that are
based upon computer learning approaches, as opposed to having
everything done in a one-on-one fashion by a busy and expensive health
Let me also address, though, your question about will
people actually use the information or it will just be like
"Okay. That was nice. Let me go back to doing exactly what I was
doing." We don't have good data on that.
A lot of the intervention about health care behaviors is
pretty discouraging when presented with information that ought to be
motivating. People don't always get motivated.
Now, a lot of that comes out of cigarettes. And we have to
acknowledge there is an addiction issue there, which makes that a lot
more complicated potentially than some of the things that we will be
able to offer up that come out of genetics. But one shouldn't
minimize the fact that we really don't have a lot of data.
We just started a project at NIH where we're going to
offer people, hundreds of them, the chance to come and be tested for
all of the things that we know currently are validated as predicting
future risk of illness.
We'll let them decide whether they want all of the
information or just the ones where an intervention is available. We
will then give them the kind of counseling about what kind of change in
health care behavior or medical surveillance would be appropriate for
their circumstance. And we'll watch and see what happens.
We need data because right now it's really hard to know
what the answer is going to be. You can look at a little bit of
encouragement perhaps from our cholesterol experience. I mean, the
idea that we should all sort of know what our cholesterol is and if
it's too high, we should do something, that has found its way into
many people's attitude towards their medical management.
And the evidence is pretty good it's actually doing
some substantial good in terms of the long run. Not everybody will
agree with that I would judge by your raised eyebrows, but it does seem
DR. KASS: Dan thinks it's statins.
DR. COLLINS: Right. Well, why do we have so many people
taking statin? Some of them because they have their cholesterol
measured and so they figured that they needed to do this. So if we had
a statin equivalent for a lot of the genetic risks that are coming out
of current discoveries, you can imagine an improved outcome.
But you are so right to point out all of the uncertainties
here. And I didn't mean by putting this diagram forward to say
that we're confident exactly what the consequences will be.
The pharmacogenomics part maybe is going to be a more clear
success story, but we don't even know that yet. The therapeutics
I'm sure will be, but it's a long lead time.
The individualized preventive medicine strategy, where we
alter our health behaviors based on genetic information, it will be
interesting to see what happens.
There will certainly be people who are sort of information
seekers who embrace this and run with it, but is that going to be one
percent or is that going to be 50 percent of the people who have the
chance to get the information? I don't know. I just wanted them
to have a chance to get the information without being fearful of it.
DR. PELLEGRINO: Dr. Dresser?
PROF. DRESSER: Thank you.
I have a general question and a specific question. The
general one is you haven't said anything about proteomics. And
after the Genome Project was done, everyone said that is the next big
So are there any ethical implications, developments we
should know about? And the specific question is — I'll try to get
it right — a critique of the anti-discrimination approach to health
insurance and genetics, genetic exceptionalism Mark Rothstein has
So if it's unfair to use underwriting, to use a genetic
predisposition in insurance understanding, then why is it fair to use
an actual genetic disease, like breast cancer related to the bracketing
in underwriting as a preexisting condition?
And if that's unfair, why is it unfair to use another
kind of breast, somebody who has another kind of breast cancer that we
haven't found the gene that it's related to, to exclude them in
underwriting? And if that's unfair, why is it unfair to exclude
someone who was injured in a car accident?
That is, if you consider the unfairness in this narrow
genetic predisposition area, that's a drop in the bucket and
doesn't address the larger unfairnesses in individual underwriting.
DR. COLLINS: Another set of good questions. Proteomics
quickly I think is moving forward. I was one of those who was
considering that the buzz about proteomics might be a little
premature. It's very difficult to do this. You have to deal with
five or six or seven orders of magnitude in abundance if you really
want to sample all the proteins in a particular body fluid or in a
And we don't have the technologies yet to do that
reliably and effectively and reproducibly. So a lot of this has just
been technology development. We're not there yet.
There have been some advances in terms of the ability to
look at proteins that are in circulating plasma or serum and make a
guess about what's going on internally in the rest of the body, but
those have been hard won and not always well validated. So I think the
promise of proteomics mostly still lies ahead.
In terms of the discriminatory or ethical issues, I think
the fact that proteins are, after all, synthesized as a result of
instructions provided in DNA. That means the connection is pretty
tight. And most of the same issues apply. But certainly if you're
talking about individual variations that pose a risk of future illness,
yes, it's the same kind of story.
Now, in terms of exceptionalism, — and I know this has
been an area of considerable discussion and rightfully so — it is
probably the case that the fact that there is so much public concern
about the use of predictive genetic information in health insurance is
in a certain way an indictment of our whole health care plan and the
fact that we in this country have more than 40 million people who
don't have health insurance and that we are able to somehow live
with that and not find that already to be a violation of certain
principles of justice. It does, I think, point you to the — the
fundamental problem may be much deeper than whether or not genetics is
covered or not covered.
But genetics does in the public mind and with a certain
legitimacy occupy a special place. It does, after all, carry
predictive information. It is permanent. It is not like a blood test
that's here today and gone tomorrow. Once it's there, it's
It is family-relevant. So the test you have has
implications for your relatives, and other tests don't carry that.
And it's personal. People feel somehow that this is private
information in a fundamental way that may not apply to other kinds of
laboratory tests that are conducted upon them.
So I do think there is a legitimacy towards carving this
out, but in a certain way maybe it is also a way of saying we have a
fundamental problem. We're going to try to fix this one now, but
let's pay attention to the fact that this is not the only problem
that we have.
Again, your examples about why genetic information should
be given a special place here and not used in a discriminatory way;
whereas, others can, again, it's not being argued that if you have
the diagnosis of a disease that happens to be a genetic disease, that
you no longer can be subject to underwriting.
It's the predictive information in a currently
undiagnosed healthy person that is off the table. So that's
different than the person who already has cancer or the person who
already has a broken ankle. It's this predictive stuff.
So you might say then, "Well, you shouldn't be
able to use your cholesterol either for underwriting in a health
insurance plan." And there is some argument about how much of
cholesterol is genetic anyway and where the boundary is there.
But I think the line that is trying to be drawn is saying
genetics is special for the reasons I outlined and we're just
talking about the predictive part. And it is a serious problem now in
research, and it will be soon in terms of clinical practice.
DR. PELLEGRINO: Professor Gómez-Lobo and Dr. Hurlbut? And
then I'm afraid that will have to be the last question since
we'll be extending the period until 10:30.
DR. GÓMEZ-LOBO: Just a brief information question. Could
you explain to us the contents of that amendment in the bill that has
been submitted to Congress with regard to the discrimination issue?
DR. COLLINS: I don't have the language in front of me,
but it basically extends the definition of a covered individual to
include an unborn child. And, again, the arguments are that the way in
which the legislation is written, DNA information obtained on the
unborn child in the medical system effectively are considered relevant
to the mother. And as soon as that child is born, then the legislation
would apply already. So that the argument is that there is no window
of non-coverage given the way that the bill is already written.
And this addition is unnecessary. And, of course, it
raises all kinds of other issues immediately because it seems to bring
another very controversial and difficult public discussion into the
middle of this bill that was never intended to be a place for that
debate to occur.
DR. PELLEGRINO: Dr. Hurlbut?
DR. HURLBUT: My last comment was inarticulate. So I just
want to return to what I think is the heart of the question.
DR. COLLINS: All of mine were. So go ahead.
DR. HURLBUT: And I actually would like one more thing,
too, and that is for you to sum up what you think we should do. But
first I was trying to make a distinction between interventions very
early, when we have a genetic proclivity and the later kinds of things
we are used to, therapeutic interventions for existing disease.
What strikes me is that personalized medicine, so conceived
as you have laid it out, could end up bordering on enhancement
conceptually. In other words, sure, if you're going to intervene
in something that's clearly leading linearally to a disease, that
might be uncontroversial.
But then there will be other things where there will be
genetic proclivities towards certain behaviors or certain dispositions
of being certain combinations of your possible genomic expression. And
that borders on precluding or promoting certain possibilities within
And this would come down to small molecule interventions.
You know, that is where this will all go. The revolution of biology is
likely to be a revolution in pharmaceuticals, not gene therapies,
And so what I guess I am asking you is in the broad sense,
are you worried about where this kind of knowledge is taking us and how
we might use it to intervene in human lives to "educate" the
genome to do certain things versus others?
DR. COLLINS: That would be a very interesting discussion
to pursue if we had more time to dig into it. I think we already do
this in a less high tech way.
I think parents routinely are assessing the characteristics
of their children and trying to figure out, oh, does this child have a
particular musical ability? And if so, should we nurture that?
So they're observing the consequences of some genetic
inheritance and trying to adjust what they do in terms of enhancing
that child's ability to carry out certain valuable life activities.
Is it categorically different if those kinds of judgments
are assisted by some kind of DNA analysis? I'm not sure it's
categorically different. I'd worry that it might be seen as more
reliable and that you might get into the self-fulfilling prophecy kind
of outcome, where kids got early on slotted into a particular pathway
of what kind of training and experiences they're going to get based
upon DNA information that was actually pretty shaky. That would be
I mean, I guess the thing to fear here is limitation on
opportunity based upon predeterministic kinds of conclusions based upon
DNA analyses that should have never been taken with that much weight
but somebody might try to do.
I do think that there is a risk there that we ought to
think about in the longer term in terms of society, but I think
we're a ways off from getting to it. And it would not be one of
those where you could draw a bright line. And those are sometimes the
most interesting and the most difficult.
DR. PELLEGRINO: Dr. Collins, I think I expressed the
feelings of all the members of the Council, expressed our gratitude to
you for being so generous in your time, responding to all of the
questions in a very definitive way, and especially for opening up the
whole field to us and particularly also for some of the suggestions you
have made about the ideas this Council might deal with in the ethical
realm. Thank you very, very much.
DR. PELLEGRINO: We will now break to 10:45.
(Whereupon, the foregoing matter went off the record at
10:27 a.m. and went back on the record at 10:46 a.m.)
SESSION 6: HUMAN DIGNITY AND BIOETHICS - A PREVIEW OF COUNCIL'S UPCOMING DIGNITY VOLUME
DR. PELLEGRINO: Council members, welcome back. Council
members, are we all here? It doesn't look like it. I know some
are gone. Very good. Thank you very much.
This last session is devoted to the upcoming volume or anthology
being put together on the subject of human dignity. Those of you
who have followed the publications of the Council over the years
I'm sure have seen the concept of dignity in a sense hovering
over a lot of the discussion, what it is to be human, how do we
preserve human dignity in the face of a variety of assaults on it
Council members have received papers that have been
elicited from a variety of authors, some on the Council, others not on
the Council. And the subject of today's discussion is to get
comments from the Council members on the volume, which is being edited
by Adam Schulman and is coming close to completion and ready for
We have asked two of the Council members to open the
discussion: Dr. Floyd Bloom and Dr. Peter Lawler. And while
they're making their comments and throughout the rest of the
discussion, I want to urge other Council members if they wish to take
the invitations being extended to write a comment on one of the
existing papers, which you have read, or submit a paper of your own.
We would like as much as possible to have Council participation as well
as the participation of invited authors.
Let's begin, if I may. Dr. Floyd Bloom, would you lead
DR. BLOOM: I hadn't been appointed
to the Council when you decided to do this compilation of essays
on dignity. So when Dan asked me to start the discussion of the
essays by Gil and by Dan Dennett, I looked at it as a great learning
Reading Gil's essay gave me the chance — in fact it required
— that I go back and read parts of Human Cloning and Human
Dignity, Being Human, and Beyond Therapy.
A skeptical Council member might wonder whether getting new
Council members to read old Council reports is not a major part of how
you get picked to lead discussions.
DR. BLOOM: If that were the case, thank you because
I learned a lot. And I thought these were both thought-provoking
When I moved from the NIH to the Salk Institute in 1975, I
was given the study of Jacob Bronowski, who had just died. And
it's Bronowski's writings that come to mind, especially The
Sense of Human Dignity, when I ponder the phrase "human
But the Council's early report, as Gil so clearly notes
in his essay, Bronowski used the term "human dignity," but,
as far as I can tell, he never defined it except by examples of respect
within the community of scientists for each other's findings and
interpretations, whether or not one agreed with them, and the
scientific spirit to dissent and explore while searching for truth as
human values, which in his phrase he said were "ratified by the
great religions of the world."
He said the outcomes of science and technology are mere
tools and artifacts, it's the spirit and creative energy behind
them that form the basis for human values and ideals, which is as close
as I think I could find that he came to talking about human dignity
explicitly. And it's that spirit that I think of when I ponder the
meaning of dignity in the sense of this volume and these two particular
Gil's essay refers to the three definitions of dignity described
by Beyleveld and Brownsword and more recently by Caulfield and Brownsword
in their considerations of policy-making for the era of biotechnology.
Those three definitions are: number one, empowerment, which is
very similar to what Mike said yesterday, the right of individuals
to make autonomous choices; secondly, as a means of constraint;
and, thirdly, as dignified conduct.
So since Gil is here and I can pose the query to him, it
seems to me that you use dignity as constraint in a fashion somewhat
differently than do Beyleveld and Brownsword. You used it in the sense
of constraint in a legal or ethical issue to control activity to which
one freely consents and which seems to harm no one. But Beyleveld and
Brownsword used the sense of scientific constraint in the terms of
barring activities, such as cloning humans or selling organs for
transplant, as a social position that these forms of scientific
activity are against human dignity because they are contrary to the
public good. And that seems to me much closer to the way I read
Leon's essays to have defined or used the phrase "human
Dr. Dennett's essay that we already engaged in a little
bit of discussion earlier this morning is much closer to neuroscience.
And so I feel more akin to it. And it uses the recent findings with
non-invasive imaging on which to build the case that human dignity
arises — and this is his list — from the capacities of the human
brain that allow for language, art, music, religion, humor, recording
and reviewing history, and planning projects that go well into the
future, and that humans are the only animals that can conceive of the
project of leading a good life.
Studies that begin to disclose the parts of the brain that
work together when we make decisions that attribute trust and emotional
status to others ground for me in real substance these brain-based
human abilities that lie at the heart of human dignity.
One might also expand on his concepts of dolphins and great apes as having
a protomorality, a capacity to cooperate and express altruistic
behaviors. Elephants, for example, have recently been shown to
be capable of mirror self-recognition and altruism, not only for
their own species but for other species. And recent news stories
again substantiate the idea that dogs will willingly rescue human
beings, even if they don't know who those human beings are.
For the most part these two essays, both very thoughtful,
taking their own levels of resolution do not directly contradict each
other except for the one exception that Robbie pointed out in his
questions to Francis Collins.
On page 6 of his essay, Dennett asks whether the very
meaning of our lives depends on the reality of our immortal soul. And
he answers no. Well, Gil on page 11 takes the view that society's
commitment to equal dignity is best and most safely grounded in
So if Dr. Dennett had been here this morning, what I would have
liked to have asked him is this. I know or I can imagine how the
human brain does language and music, remembering and planning.
And when I queried PubMed about brain imaging and religion, much
to my surprise, there were more than two dozen papers that use positron
emission tomography, functional MRI, EEG, even SPECT., to look at
phenomena from the mystical experiences of Carmelite nuns to buddhists
contemplating a remembered meditation.
So, not surprisingly for those who understand that
interpretation, there are certain parts of the brain, particularly on
the right side of right-handed people, that show enhanced activity
during religious experiences, but what Dr. Dennett doesn't tell us
is what brain systems or networks he thinks underlie religious
contemplation and what in our evolutionary history has given rise to a
system that would mediate such functions.
That's mostly what I have to say, but I would like to offer
this for the Council's amusement after this lengthy discussion.
This is the final version of Bob Dylan's song "Dignity"
from 1991, "So many roads, so much at stake, so many dead ends,
I'm at the edge of the lake. Sometimes I wonder what it's
gonna take to find dignity," 1991.
DR. PELLEGRINO: Thank you very much, Floyd.
For the benefit of those who have not seen these papers, we
asked our discussants to look at two of the papers, particularly that
will be appearing in the volume. One is Dr. Gil Meilaender's
"Human Dignity: Exploring and Explicating the Council's
Vision" and another by Daniel C. Dennett, "How to Protect
Human Dignity From Science."
Now for our second discussant.
DR. LAWLER: Well, thank you. And I will try to be
brief, given the lateness of the hour.
So my job is to introduce these two papers by Meilaender
and Dennett. And I will use the last names because I don't know
From one point of view, they defend two extreme and incompatible
positions. They're both extremists.
DR. LAWLER: As was pointed out in the last session,
Dennett is surely an extreme atheist. And Meilaender we might say
is an extreme theist; that is, an Augustinian. But extremism in
defense of dignity is surely no vice.
DR. LAWLER: And they are both, as they say, nice guy
extremists, although you can find a sentence or two in both articles
like the one Robbie quoted last session, which are overly assertive and
a little bit mean.
In general, these dignity extremists lack the
self-righteousness that often accompanies dignity extremism. So they
agree. And they agree. As extremists often do, they agree on many
things, more things that it appears at first. They both agree that
dignity is not a useless concept. And this is not a small point of
And they both agree that dignity has to be saved from modern science
or at least misunderstandings of what modern science actually teaches.
Not only that. They seem to agree that our understanding of dignity,
at least our traditional understanding of dignity, is Christian.
So Meilaender says that the dignity of each unique and
irreplaceable human person is real. And the only explanation for that
observed phenomenon of human dignity that makes sense is the Christian
one. So our belief in the equal dignity of all human persons is part
of our Christian inheritance.
Dennett agrees that our understanding of dignity or at least the
traditional understanding of dignity, the given understanding of
dignity is Christian. But he adds that the Christian claims about
the soul or some immaterial dimension of personal existence have
been refuted by modern science.
So dignity has now the same status as the mermaid, although I would add:
sensible people never believed in mermaids, although sensible people
in the past I think believed in the soul.
Dennett adds — and this is very important — that our need
to believe in dignity is real and characteristic of the type of social
being human beings alone are.
We social beings, who conceive a project for the good life
to live good purposeful lives, good lives, can't live together well
without believing in some useful illusions, like free will, love, and
dignity, but free will, love, and dignity, strictly speaking, have no
real basis in what we can actually know about our accidental
evolutionary and wholly material existences.
So Dennett's ingenious solution that solves the problem of the
incompatibility perhaps of dignity and modern science is to say
today we should candidly admit our need to believe, that we're
hard-wired to need to believe. And then our allegiance to the belief
in human dignity will be supported by the good life it makes possible
We can see that if we give our allegiance to dignity, our
lives will be better. So we can suppress the thought about whether our
belief in dignity actually makes any natural sense because we can't
see. According to nature, we do believe. And when we do believe,
we're better off as a certain singular kind of social animal.
So a difference, a major difference, between the two great
thinkers we're talking about is that for Gil Meilaender, it would
make all the difference in the world. We really are unique and
irreplaceable beings. Dennis suggests we can suppress that thought
about the reality of the situation and regard that thought as a useful
So for Meilaender, our dignity is mysteriously given to us
by a personal god. And the human situation is fundamentally mysterious
in certain respects without a religious explanation at least.
For Dennett, nothing human is mysterious. Everything can
or will be explained in a wholly material way. That's good,
though, because then we can understand scientifically why we have to
attribute dignity to ourselves. Insofar as we believe our dignity is
mysterious, we can't consciously and rationally employ it for the
purposes of flourishing social life. So modern science, properly
understood, makes dignity more effective.
There are other points of agreement between these two extremes. Meilaender
and Dennett don't agree with those who connect dignity with
autonomy, with our freedom from our natural limitations for laws
or choices we impose on ourselves.
Autonomy is based on the denial of the truth about our
embodied existence. And dignity, properly understood, should be
compatible with what we really know about our limited social and
Even Dennett's fictional dignity depends on our understanding
of our real material situation. So for both Meilaender and Dennett,
dignity is a characteristic of embodied beings who know the truth
about their situation. Not only that.
These two extremists both have an egalitarian view of
dignity, separating themselves from, say, certain members of this
Council, who have a more aristocratic understanding of dignity.
They deny that our dignity is dependent on the excellence
or virtue we display in social context. It's easy for Dennett to
do that because there's nothing I can do that will really make me
more dignified given that I am not really dignified anyway. And
Meilaender says there is nothing I can do that can really make me
undignified. So Meilaender says it's true, and Dennett says
it's useful to regard all human beings as equally dignified.
We have to wonder whether either Meilaender or Dennett
really disconnect dignity from real human achievements in thought and
action. Meilaender criticizes Leon Kass for saying patients because
they lack agency lack the capacity to be dignified. And to support his
case, he gives us the example of a dignified patient who acts with
patience in light of the truth about his dependent human condition.
So in a very Christian way, he explains how patients can be more dignified
and more truthful than great leaders or manly or magnanimous men
who have forgotten about the limitations of their embodiment.
But Kass responds that in describing the patient, the
dignity he displays depends upon action and thought appropriate to a
situation. So the patient, Meilaender describes, is not really a
patient. He's just part patient and part not because a pure
patient would be perfectly passive.
So a pure patient would be someone with advanced stage
Alzheimer's, lacking any capacity for thought and action. But an
advantage of Meilaender's and Dennett's position over, say, the
position of Kass is they can explain quite clearly why patients with
advanced stage Alzheimer's, late stage Alzheimer's, have
Meilaender says they have dignity because of the type of being
they are and cannot change. Dennett might say, at least, it's
just socially useful to regard people with late stage Alzheimer's
as having equal dignity; we'll have a better life as a result.
Kass actually has to think about this. And it's hard because
he doesn't regard dignity as given in either of those two ways.
Now, I would make one more point. Meilaender and Dennett connect dignity
with degradation, Dennett almost in spite of himself. Indignant
behavior is or anti-dignity behavior is reducing human beings to
less than they really are.
So Meilaender has told us that a human being who alienates
his body or alienates himself from his body through the sale of his
kidneys is acting in an undignified way. And even Dennett worries that
a misinterpretation of modern science will erode our indispensable
faith in human dignity.
So they both really want to preserve the qualities that
really distinguish human beings from their attack by modern science in
some way or another. So surely even Dennett wants to preserve the real
existence of human beings capable of acting in a dignified way from,
say, biotechnology that would suppress those parts of the brain that
make dignity indispensable.
So they both show us why we should use the word
"dignity" because that's not self-evident because
Americans in most of our history have spoken not so much of dignity but
of rights. Because we can speak so clearly of rights, why go down the
murky road toward dignity, which is controversial and causes us to be
self-righteous. Here's why.
The Twentieth Century and the Twenty-First Century. The
word "dignity" made a comeback in the Twentieth Century
because what the totalitarian regimes did in the war against the
reality of human nature was a lot worse than a violation of rights. So
you can't say Hitler just violated rights. You can't say
Stalin just violated rights because they were at war against the being
capable of experiencing dignity, human individuality.
So the great dissident opponents of totalitarian regimes,
like Solzhenitsyn and Havel and Pope John Paul II, were big on bringing
back the word "dignity" because the word "rights"
just wasn't enough.
And in the Twentieth-First Century, great men like Leon
Kass bring back the word "dignity." By replacing "life,
liberty, and the pursuit of happiness" in a crafty way with life,
liberty, and the defense of dignity because what biotechnology could
conceivably do to us, misapplied, would be at war with the very aspects
of our nature that allow us to be dignified beings because
biotechnology opens the opportunity of actually changing our natures in
an undignified way.
So I think even Dennett in his own way agrees with that. We have
to have the use of the fiction of dignity to fend off biotechnology
that might do that. But I would add to everything these great experts
say another piece of evidence of our dignity is that both totalitarian
efforts and biotechnological efforts to eradicate those aspects
of our nature that make us dignified beings will inevitably fail.
DR. PELLEGRINO: Thank you very much, Peter.
Gil, would you like to respond?
PROF. MEILAENDER: Let me just say a couple of things. Judy
Crawford was already nailing me at breakfast with some questions about
my essay. And I told her I was just going to refer all questions to
her. That would be my preferred strategy, actually.
And also I don't myself think it would be a fruitful
discussion for sort of me just to respond to questions. I think the
Council should have its own discussion.
Let me say a couple of things. Floyd directed a specific
question. But I wasn't sure I understood it, Floyd. Let me say a
word. And you'll just have to see whether I got you or not.
I took the second notion of dignity from B&B, as I like
to call them since their names are not easy, the side constraint
notion, to be at least somewhat similar to the notion I had developed
in the last part of my paper about dignity as a kind of anthropological
position or dignity as serving as a placeholder, as I called it, for a
richer anthropological view but only somewhat similar to that in the
sense that theirs is largely a negative notion.
The language you quoted I thought was less mine than their
view in a way, just autonomous action that harms no one and so forth;
whereas, it seems to me that the anthropological vision that I had
tried to show the Council at least attempts to develop, though it will
have some of those negative functions that serving as a side constraint
is an attempt, actually, to say something more positive about what
really makes human beings human beings. So that would be sort of what
I would say to that.
Then just a word, drawing on Peter's various comments.
If I had this to do over again, I think I would reverse the parts of
the paper in a way because I think it might make more sense.
See, I tried to sort out what I think are several different
things the Council does with the language of dignity in those reports.
And then I worry about certain issues that they raise.
The second general thing that I sort out, what I was just
referring to, what I call sort of a placeholder for a richer
understanding that comes out at certain places; in Beyond Therapy in
one way; certain places in the cloning report in another way; certain
places, actually, in the little introductory comments in Being Human,
the reader, as I noticed.
I wouldn't have said — now, I'm subject to being
corrected. I wouldn't have said there was anything necessarily
Christian about that claim of mine. I would think there might be
various ways to get to that anthropological view. I probably get to it
in certain theological ways, although there certainly have been
Christians over the centuries who have sort of fallen short of that
view, at least by my lights.
So I don't know. You know, if you had reason to prove
to me that it was necessarily Christian, that would be okay with me.
That wouldn't bother me, actually. But I don't think it is.
And I don't think I developed it that way.
The first kind of issue I worry about, which is where the
equality issue really comes out, that is where I argue that I think, in
fact, we have been dependent on the religious tradition in a certain
way to be able to affirm the equal dignity.
So I think that the development of those two aspects, the
second one is more kind of the dignity of human nature, the nature that
we all share. The first is the dignity of the person, the individual
person, who, though belonging to the species, may have some of the
characteristics of our nature and not others of them. And I think if I
had it to do over again, I might have reversed the order of them in
order to try to make that clearer.
But that much I would say at least by way of trying to
clarify the sense in which there are or are not specifically religious
or theological claims at work. And I think I'll stop there.
DR. PELLEGRINO: Thank you very much, Gil.
I'll open the subject to general discussion now. It
need not be limited to these two papers, any of the papers that you
have read in the anthology that Adam has put together for you up to
this point. Dr. Schaub?
PROF. SCHAUB: Yes. I do have questions for Gil, even though
he doesn't want questions. It will take a while before the
questions emerge, and I want to ask your forbearance. I started
jotting down some notes on Gil's essay, and I got a little carried
Since I am usually pretty brief, I hope that I have some
accumulated minutes and that you will bear with me as I sort of deliver
myself of this. Well, I don't know how to characterize it.
I'll just launch into it.
Gil tells us in his fine essay that there are some realms
in which comparative judgments of excellence are permissible, indeed
required. Assuming that our consideration of these two papers is one
such venue, I feel at liberty to direct my remarks to the more worthy
of these papers and to ignore the other.
Gil argues that Christianity has transformed the Greek emphasis
on comparative dignity. Christianity, he says, marks 'a great rupture in Western culture.' He further argues that this Christian egalitarianism
is the inspiration behind the American assertion of man's equality
in the Declaration of Independence. He suggests that one needs
belief in the fatherhood of God for the brotherhood of men to be
seen as self-evident.
And he worries that with the decline in religious belief
and maybe even more especially the unwillingness to acknowledge the
connection between religion and politics, we're increasingly in a
situation where our commitment to equal human dignity is ungrounded
and, hence, unsustainable.
So Gil wants us back on firm ground. And, in particular, he argues
that there are two places where differences in excellence or dignity
must not matter. The first is at the threshold of death when the
continuance of life itself is at stake. And the other that he mentions
is the opportunity to live within human society and participate
in its common life.
Now, while Gil makes plain his discomfort with the Hellenistic,
aristocratic take on dignity— he even calls it a temptation
that ought to be resisted — I felt that there were many instances
in which Gil was more of a Hellenizer than he admits. And let me
cite just one of those.
Early in the paper Gil presents us with a character from a
Galsworthy novel. I think Gil is probably the only person in the
nation still reading Galsworthy.
PROF. SCHAUB: I mentioned this to a literary critic friend
of mine. And she said, "Galsworthy. How stodgy."
PROF. MEILAENDER: I read it many years ago.
PROF. SCHAUB: In the Galsworthy novel, Gil offers us Old
Betty Purdy as an individual who confounds our aristocratic assumptions
about greatness and dignity. And the passage that he cites does indeed
show the falsity of status and wealth as markers of human dignity, but
I think it does not at all argue for equal human dignity.
The greatness of this little old lady came from the moral
virtue she displayed in the midst of the ordinariness of her life. Her
greatness depended on her comparative excellence, not her equal human
We're told of the meagerness of her material existence
and her limited range of action, but her back had been straight, her
ways straight, her eyes quiet, and her manners gentle.
I take it that we're to admire her fortitude and her
probity and her kindness. Those are not qualities equally possessed.
If the woman had, instead, lived in Buckingham Palace and had the world
as her stage, real greatness would still have depended on her moral
I think that's one of the points made by the wonderful
movie The Queen starring Helen Mirren. Of The Queen also, it could be
said that her back had been straight, her ways straight, her eyes
quiet, and her manners gentle.
Now, although Gil reiterates that he finds something offensive
about the aristocratic view of human dignity, it seems to me that
he himself regularly recurs to a version of it and that he can't
help but do so. After all, in Christianity, the message to respect
basic humanity came from the fullest humanity. The bearer of the
message was not just a godly man but God become man. We are to
imitate his perfection. Christian virtues may be different from
classical virtues, but the standard is — if anything —
Gil appeals to Lincoln for evidence of what he calls the
problem we have with an inegalitarian concept of dignity. I, too,
accept Lincoln as an authority. However, I don't think that Gil
reads him quite right.
Lincoln is not at all offended by the aristocratic view. In fact,
Lincoln always starts his explications of the meaning of the Declaration
by acknowledging the fact of human inequality. Men are not equal
in all sorts of features and capacities. And Lincoln lists a number
But for Lincoln, admitting the existence of those various politically
and socially significant inequalities should not in any way imperil
the real truth of the Declaration, namely that men are equal in
their natural rights to life and liberty.
And note, as I think others have already mentioned, Lincoln
speaks of equal rights, not equal dignity. I suspect that we may have
gone awry when we confounded the language of dignity with the language
Dignity was not a word that either the founders or Lincoln
employed much. And when they did, it was in a, frankly, meritocratic
Moreover, in the passage that Gil cites, I think it is
worth noting that Lincoln illustrates the equality of rights by saying
that human beings are equal in their right to eat the bread that their
own hands have earned.
In other words, even this equal right hinges on earning.
Labor is the title to property. And men will labor unequally. Now,
Lincoln doesn't tell us here what those who are unable to labor are
And I surely don't mean to suggest that Lincoln would
have denied sustenance to the young or the elderly or the sick.
Lincoln was attacking the injustice of slave labor. And his arguments
are marshaled accordingly.
And we certainly have evidence of Lincoln's capacious humanity
in the closing lines of the Second Inaugural, when he calls on Americans
to care for him who shall have borne the battle and for his widow
and for his orphan.
But the example of Lincoln leads me to think that we have a
model for how to combine and celebrate both the respects in which human
beings are equal and the respects in which they are unequal. And one
need not imperil the other.
Indeed, the life of Lincoln, a superior man, who devotes
and sacrifices his life to the teaching of equality, reminds us that we
can't have one without the other. So we shouldn't lose sight
of the success of the American founders, among whom I include Lincoln,
in combining the egalitarian and the inegalitarian. They just
didn't seem to struggle with it as we are.
I was a bit taken aback by Gil's assertion that there
are two places where comparative judgment should not be given any
scope: at the threshold of death and participation in human society.
Gil seems to say that these are absolutes, but I wonder whether he
really means it.
The quote from Kierkegaard says, "If you save a person's life
in the dark thinking that it's a friend but it was the neighbor,
this is no mistake." Well, it seems to me it might have been
a very big mistake if your neighbor also happened to be your enemy
and you happen to have been on a nighttime reconnaissance mission.
In other words, Kierkegaard's statement is radically apolitical.
It abstracts entirely from the distinction between friend and foe.
Gil, do you mean that one is never justified in taking human life,
not even the life of an enemy in combat? If comparative judgments
have no place at the threshold of death, does that commit you to
not only oppose the death penalty, which I take it that you do,
but commit you also to a thorough-going passivism?
If, on the other hand, you allow for individual and
societal self-defense, then it seems to me that you have admitted the
validity of comparative judgments of worth, even at the threshold of
death. So in this case, it seems to me that the language of equal
rights is preferable to the language of equal dignity.
Rights are inalienable, but they also imply reciprocity and
responsibility. Those who violate the rights of others have rendered
some of their own rights forfeited. So that a rights-based approach
protects the innocent and the weak, about whom Gil and all of us are
concerned. But it doesn't require us to abandon human judgments
about virtue and vice.
As to Gil's claim that our founding doctrine is
grounded in Christianity, it's true that the Declaration refers to
man is created equal and endowed by their creator with certain
It's also true that Jefferson shared Gil's worry that once
religious belief falters, the commitment to equality will be hard
to sustain. Here's how Jefferson put it, "And can the
liberties of a nation be thought secure when we have removed their
only firm basis, a conviction in the minds of the people that these
liberties are of the gift of God, that they are not to be violated
but with His wrath?"
Having granted that much, I would just point out that the Declaration
refers to the Laws of Nature and Nature's God. And I suspect
that nature's God is not quite the same as the biblical God.
Gil says that the truth of human equality is a theological
proposition or theological assertion, but how strong a theology is
required? Is natural theology sufficient? Jefferson I think thought
that it was.
And in other writings, Jefferson argued that it was not
religion at all but, rather, reason and science that will reveal the
truth of the Declaration. In a letter written just days before his
death, Jefferson said, "All eyes are opened or opening to the
rights of men. The general spread of the light of science has already
laid open to every view the palpable true that the mass of mankind has
not been born with saddles on their backs, nor a favored few booted and
spurred, ready to ride them legitimately by the grace of God."
Now, as we know, even if equal rights are self-evident,
they're not self-establishing. The paradox of rights is that you
have to hazard your life and liberty in order to vindicate your right
to life and liberty.
As Frederick Douglass never tired of telling his enslaved
brothers, "Hereditary bondmen, know ye not who would be free
themselves must strike the blow."
This was a heartening message for blacks and for women, who
had the wherewithal to strike the blow and secure the dignified
treatment to which they were by nature entitled.
It may not be such a tearing message for the young or the drastically
impaired, although perhaps the answer that Locke gives about the
young is sufficient. He says, "Children I confess are not
born in this full state of equality, though they are born to it.
Consequently, our handling of them must always be aware of their
directedness toward rational liberty." Children are rights
bearers, too. Accordingly, the power of parents and guardians is
Locke insists it does not extend to life and death. Immature human beings,
embryos included arguably, have the same bodily immunity as adults.
There's a fundamental human right not to have one's body
captured or controlled by others for their ends and purposes.
In the case of the weak and immature, respect for this basic right
to life will continue to depend on the deference of the strong.
In his speeches, Lincoln deployed his relentless logic to get those
who had the upper hand to realize the momentary and fragile character
of their strength. He stressed that the only guarantee of one's
one rights lies in the recognition of the rights of others:"As
I would not be a slave, so I would not be a master."
And, again, in giving freedom to the slave, we ensure
freedom to the free, honorable alike in what we give and what we
preserve. This is a version of neighbor love and brotherhood that is
reasonable and republican in character. It doesn't deny the
fatherhood of God, but it doesn't draw attention to it either.
And, in closing, at the risk of impiety, I will suggest
that brothers can get along pretty well when the father, whether human
or divine, remains further in the background. After all, the first
story of brothers in the Bible is a story of fratricide in response to
God's favoring the gift of one brother over the other. I'm not
so certain that it helps our sense of human equality to view matters
under the aspect of eternity.
As I read the Bible, some of us will be eternally damned
and others saved. We are not equidistant from God, either here on
Earth or later. I'm quite certain that Gil is nearer my God to
Thee than I am, but I think that we can still be equal citizens,
mutually acknowledging our individual rights and brotherly
DR. PELLEGRINO: Thank you very much, Dr. Schaub.
Gil, do you want to comment?
PROF. MEILAENDER: Sure. I'll comment on a few things,
not by any means everything that Diana has taken up. Just a comment on
what I drew from my stodgy reading habits, I read all nine volumes at
one time in my life.
Although, Diana, you are always a very careful reader, I didn't
think you did quite justice to the way I used the Galsworthy passage
there. That paragraph where I used it begins, "Suppose, however,
that our understanding of comparative excellence were reshaped somewhat
by a sense of equal human dignity."
And having quoted, I say, "And suddenly what seems almost
a given in the Council's discussion who are the great and who
are the ordinary human beings may be far less obvious." I wasn't
trying to rest the entire argument for equal human dignity on that
but simply to begin to reflect on the significance of a kind of
democratizing of that concept that takes place.
I mean, the argument moves on from there. It doesn't
stop there. So that I think you, careful reader though you are,
abstracted that a bit from the flow of the argument and just let it
stand on its own.
A second point, I don't know if you really want to
argue theology or not, but if you would like a discussion of the
concept of incarnation, we can have it.
Jesus is not thought to have the fullest humanity in any
sense, whatever that might mean. He's thought simply to have
assumed our nature into God's own nature, the nature that we all
share but not a fuller sense of it in any way. So that, I mean, I
don't think that's right.
The Kierkegaard stuff, the neighbor for Kierkegaard is
anyone whom you may encounter. And, therefore, if you rush into the
burning house next door thinking to save someone whom you really like
who is, of course, your neighbor most fundamentally because the most
fundamental category is neither friend nor foe but neighbor, you rush
in, save someone whom you really like, drag the person out to safety,
only to discover that it's someone you have never met or someone
you hate, Kierkegaard says in the most basic sense you have made no
mistake. You ran in there to save your neighbor. You saved him. And
I think that's true.
That doesn't mean that friend or foe distinctions make
no difference at all in life. It doesn't mean — I mean, you
raised the issue of combat, for instance. We may, alas, find ourselves
in circumstances where the needs and the claims of several neighbors
seem to stand in conflict with each other and we have to decide whether
there is any way to serve the needs of any of those neighbors at all
Many people, myself included, have been drawn to some form
of just war thinking in those circumstances. I mean, even the neighbor
against whom you turn has certain claims on you. There are certain
things you can't do at that point. But it's an attempt to find
a way through that sort of conflict between the claims of neighbors.
There have been some people, of course, who have thought
that you just shouldn't do anything. I don't myself think
that, but I think that what one seeks there is — I mean, when the
claims of several neighbors conflict, justice is what one tries as best
one can to do in sort of defending not oneself but some other neighbor
who is in need.
And then, finally, on the kind of, really, I think larger
— the issue that is really at the heart of what you say, well, you
know, I like to honor the founders, too, but I do not bend the knee
The American tradition is larger than what the founders alone had
to say. There was a tradition here before 1776. And that larger
tradition, which has continued to be mined, as you surely know,
by political theorists since then — I mean, think of Cary
McWilliams' idea for eternity in America, for instance —
would suggest that there's a whole lot more to our tradition
than simply that language of rights that in the context of struggle
for independence came to the fore.
But the larger issue here for me would be that, I mean,
I'm not sure what the thrust of your appeal to confine ourselves to
the language of rights is. For better or worse, we happen to have used
dignity, as I think — I mean, whatever you think of my particular
claims, I mean, I tried to sort through the material we used in order
to say things we wanted to say about the nature of human action and how
it relates to enhancement and about human procreation and so forth. We
didn't find the language of rights sufficient to do that.
I point to some examples of this along the way. And I
guess before I took that back, I would need to see an argument that
suggested that the language of rights could accomplish what we tried to
accomplish and what I would still think is important to accomplish.
So that, you know, as I say, the things that we did in
Beyond Therapy and The Cloning Report seemed to me to at certain places
make use of that language in important ways that probably can't
just be duplicated by rights language. And it's, therefore,
language we need to say if we want to say everything that we need to
say. That would be what I would say.
PROF. SCHAUB: Yes. Just very quickly to that, I don't
think I was arguing for a return exclusively to rights language but,
rather, a combination of equal rights and earned dignity so that when
it comes to these issues sort of at the beginning of life and at the
end of life, I really do think that the rights language may be
And it was revealing to me that where the dignity language
really becomes more appropriate is in the Beyond Therapy report and
especially in the section on performance when you're talking about,
you know, the essential dignity of human action. That's why I had
no quarrel with the section of the paper that dealt with the
anthropology. That all seemed to me very fine.
PROF. MEILAENDER: I would just note that it is not the only
place where we — I mean, the Taking Care volume uses it also. And
it's not that kind of anthropological principle at work there.
PROF. SCHAUB: I am just saying I think it is more
appropriate in that one context than in the other context.
DR. PELLEGRINO: Thank you both.
We will now open the discussion to other members of the
Council, not necessarily on these papers, on any of the papers in the
anthology. Dr. George, I saw your hand first.
PROF. GEORGE:Thank you, Dr. Pellegrino.
Gil, I think that there are two beliefs that are the
glories of our civilization and central to our political
self-understanding, our national political self-understanding: the
belief in the inherent dignity of the human person and the belief in
the equal dignity of all human beings.
Now, as I say, those are glories of our civilization, but
they are also problematic and puzzling and difficult to explain because
we know of the profound differences between persons. And we know that
there are some persons who are in severely debilitated conditions with
respect to those very features of our humanity, which seem so central
to its dignity and its specialness. And so we struggle to make the
argument in defense of inherent and equal dignity.
Now, it seems to me that there are two ways of making the
argument. I don't think they are incompatible. And at the end of
this, I'm going to ask you the question whether they're
incompatible and we have to choose.
One way is to make it the way I think you are making it,
drawing on the great moral theologian Oliver O'Donovan, among
others, where one is arguing from the theological proposition that
there is a God and that man is made in his image and likeness to the
conclusion that man, therefore, bears an inherent dignity and all men
have an equal dignity, equal share.
The other way goes in the opposite direction. It is to
observe that human beings as possessors of the God-like powers of
reason and freedom, literally awesome powers, that are traditionally
associated with divinity have a basic dignity, an inherent dignity, and
that since all human beings possess, in at least radical root form from
the beginning to the end, this basic natural capacity, — it may be
blocked in the case of a severely debilitated, congenitally
debilitated, person or something like that, it might be locked, but,
nevertheless, at least in radical form, it's there — we
acknowledge that people have inherent dignity, we're all equal.
And then we raise the question, well, how can it be that we material
creatures possess these powers that are not even reducible to material
causes or so it's supposed?
Dennett would disagree with this, but many of us would
think that they're not reducible and a complete account can't
be given in purely materialistic, reductive terms. How can that be?
And then we ask whether it might be in virtue of a more than merely
human ground or source of these realities in the whole of the intelligible
order, which has given us some share, limited to be sure, and fallible,
but some share, in those powers of reason and freedom, those divine,
awesome powers, the powers that are at the heart of our dignity.
And so in the second way of arguing, the argument is not
from God but, rather, to God. You might put it this way. And I'll
conclude. What does it mean to say, as the Bible says, that man is
made in the image and likeness of God? It obviously doesn't mean
that God has two hands and five fingers on each hand and so forth.
Doesn't it mean that man possesses in limited form but,
nevertheless, really these God-like powers, that God has made man in
his image and likeness by giving him a sharing in these divine powers
of reason and freedom, so that you can say it in theological terms and
quote Genesis or say the same thing in philosophical terms that
don't divert to the theological question but are not incompatible
with it or are they?
PROF. MEILAENDER: I'm moved to reflect again what an
unusual government body this is.
PROF. MEILAENDER: And I apologize for whatever
responsibility I bear for that fact.
PROF. MEILAENDER: Let me ask you one question before I try
to answer. Would I be right in assuming that you are more drawn to the
second of those two styles of argument?
PROF. GEORGE:Only by temperament.
PROF. MEILAENDER: Okay.
PROF. GEORGE:So that I would say I'm not saying that
one is more legitimate than the other or more compelling than the
other. Floyd is a scientist. Janet is a scientist. I do legal
philosophy. I am more inclined toward philosophical things.
I think theologians are wonderful people and so forth and
so on. And I am happy to see them do business their way the way I am
happy to see Floyd and Janet practice their crafts. But by
temperament, I do it the other way.
What I am really interested in asserting unless I'm
wrong, in which case I want to be corrected, is that they're not
PROF. MEILAENDER: Okay. No. That's fine.
Well, you know me. I let 1,000 flowers bloom. And I have no objection
to working in either direction. And I do think that they are in
principle compatible, though I probably have less confidence in
how well the second route will work than you may have.
And I think, just as a matter of fact, that the concept of
the image of God is a really muddy concept, both biblically and in the
sort of history of theological reflection on it. I mean, it's just
not clear anybody knows for sure what it means. So that in terms of
the steps by which you have proceeded there, I mean, I think they would
I probably in this paper proceed a little bit in the other
way because there is a certain point where it seems to me it's
useful, rather than thinking of religious folk as always on the
defensive and having to make the case for saying anything about what
they believe in public discussions about matters like biotechnological
concerns, it seemed to me useful to say, "Well, for better or
worse, these religious folk have got a reason to affirm something that
most of us claim we want to affirm, the equal dignity of human beings.
And, you know, if you want to affirm that and you don't share that
reason, well, then, you know, come up with another one."
It's not that I object to somebody coming up with other
ones, though I'm inclined to doubt that there are just a lot of
them floating around that will be successful.
But, I mean, I was concerned to make the point that this
has functioned as a kind of ground for that view and has a certain kind
of legitimacy to function that way in our discussions.
But certainly I don't expect everybody to want to start
with theological premises. I understand that. And if one can provide
a kind of reasoned argument that gets to the same place, I am happy.
You know, I take my friends wherever I can find them in
life. It's not easy. And, you know, I am happy to get support
from wherever it comes.
DR. PELLEGRINO: Thank you, Gil.
DR. KASS: Thank you.
I am really in a way reluctant to enter after these really very
eloquent and carefully prepared responses, you know, two by assignment
and then this stunning and I think very powerful critique, Gil.
But let me say something about your paper.
I think it has done an enormous service by going through the work of
the Council's previous reports and shining your bright light
on acknowledging the conceptual difficulties and even confusions
that sometimes emerge if you sort of took the various places where
these placeholders sit for certain notions and to call attention
to the central difficulties of the concepts and the not always fully
clear use that we have made of them in those reports while at the
same time defending the necessity of using such notions in those
particular places where nothing else would seem to do.
Second, I think it's a great contribution to call
attention to the insufficiency of simply laying down along side by side
some notion of the dignity of full flourishing and some notion of the
equal dignity independent of flourishing.
You can say you were in favor of both, but if you simply
are doing that, you haven't really articulated their relation. And
it is I think an ongoing challenge for those of us who I think without
self-contradiction — and Diana has given a wonderful example in the
person of Lincoln and the kind of sympathies that we can have for
that. It's not a contradiction.
And, nevertheless, I think that it's incumbent upon us
to try to give an account of how the first and the second are related,
the second is related to the first. And I took that to be, really, my
assignment in struggling with this for the paper, which belatedly came
to all of you only recently.
I can't resist. This is as an aside and not for
comment. The title of the paper is "Explicating the Council's
Vision." And, for the record, I would simply say it's one
man's explication of the vision insofar as it's there.
And to the extent to which my own personal views are
analyzed in this particular paper, every author complains that he or
she has been misunderstood. And I concede that one contributes to such
misunderstanding. I'll simply say on the personal side let my own
essay be an attempt to deal with what I take to be the not quite
On the substance, you talk about in a certain mood we feel a certain
inclination to think this way, that there are certain temptations
that we might feel to make judgments about the lives that people
live or whether they are degrading themselves or are somehow demonstrating
certain qualities that we admire.
I don't think that you would want to say of Thomas
Aquinas that his argument about dignity was based upon his being in a
certain mood or he yielded to a temptation to which he should not have
yielded when he made that comment that you quote.
There are philosophical reasons. Diana has done a really
nice job. Peter has done a nice job, I think, for talking about the
virtue component. And that leads me to the second argument, and I have
done something of this in my current paper.
I think you're mistaken to say the essence of the
notion of the dignity of a virtue, let us say, or of good deeds — and
they are good deeds in the small — is that they are comparative.
It's only accidentally that these are comparative.
If every single human being behaved courageously, it would still
be dignified, even if there were no inequalities. And I think that
you do not have to embrace inequality in order to recognize the
excellence. What you're measuring are the deeds of human beings
against the standard of worthiness, not compared to one another.
The sports example is comparative necessarily because there are
winners and losers. The virtue example is only accidentally comparative,
would that there were less grounds for making that comparisons and
people lived up to the standard, but I don't think that you
have to somehow fear that because unavoidably we will wind up saying
certain people are vicious, that the judgment of virtue depends
upon one person being better than another.
I guess I don't want to go on much longer. Well, two
more comments. I do think that there is a real fear that if you begin
down the road of acknowledging the dignity of a virtue of flourishing,
that you might be put in a position of making invidious judgments at
the edges of life, when nobody wants to do them or at least decent
people shouldn't do them. And if your concern is about the death
and dispatching question, then the equality principle is absolutely
On the other hand, if your major worry is about degradation, dehumanization
of the sort that several people have spoken about, it will not do
simply to make a plug for the principle of equality because one
could be equally debased and not know it.
So I think depending upon which part of this bioethical
discussion you're most worried about or which is most on the table,
these two different notions deserve a place.
And then, finally, — and I don't endorse either of the
two alternatives that Robby has given us. It seems to me that I
don't think there's a word that has been written in any
of the documents that this Council has produced that depend for
their arguments on human dignity on any particular theological view.
It might be that as individuals, that we come to these
things, but we have tried to have these discussions in terms of
arguments and persuade one another on the basis of a kind of public
reason, nor do I think that there is any notion about the dignity that
has been discussed here that rests upon a metaphysics of the immortal
You might want to suspect some people of believing that.
For the record, I am not one of them. So I don't think that — we
have tried to sort of start with human phenomena. We don't
necessarily care whether it reaches to metaphysics or theology.
We're trying to appeal on the plane of the moral
concerns that we now face in our practical decisions and as our life is
unfolding under the new developments in biotechnology.
And it seems to me it's very important. I mean, I
don't mind. In fact, I welcome the fact that the Christian
thinkers don't hide their lights under a bushel. I think
that's very important.
On the other hand, if you want to say, "Look, the
arguments for the equal dignity of human beings depends upon that
teaching," we're, in effect, saying to other kinds of people,
"Either you join the church or you can't defend yourself on
this point." And that it seems to me is not either the wise or
sensible or I would say even the true way.
Part of the reasons we have rights language, there is a much older
tradition in the West, but certain schisms in that tradition led
the Thirty Years' War, in which people bloodied one another over
who had the better account of the immortality of the soul.
DR. PELLEGRINO: Thank you.
We have time for one or two more comments. Janet?
DR. ROWLEY: Well, I generally sit these discussions
out because I feel so ill-prepared and then so shallow in any kind
of comments that I might make or so. "Untutored," I suppose,
is a better word.
And following up on what Leon just said, I have always been impressed
with what I consider the violations of human dignity that are committed
in the name of religion. So, you know, I think that religion, Christian,
Muslim, Buddhist, whatever, has a lot to answer for in terms of
violations of human dignity.
I think also that this Council has done — I'm not sure
whether we have done some damage to what I would consider human
dignity. And I come back, and it's really too bad that Mike
isn't here because I think his book The Ethical Brain and the
discussion of ethics or altruism, as I can recall, — and it's a
while since I read the book — being somewhat near to some of the
aspects toward the end that Peter was getting at, that we really found
as a society that we're a lot better if we behaved ethically and
morally toward one another, however that is defined, than if we
And the things that Floyd was talking about as to
understanding where in the brain some of these impulses might actually
be located makes it, if you will, a scientific, rather than a
philosophical or a religious, question.
And so I'm concerned that we have often overridden
reason and freedom in the name of dignity and said that my reason and
freedom are defective or you have a right as an individual based on
what you think human dignity requires to overrule what I might think
because you're more right and my reason leads me in the wrong
And I think that there is a certain hubris in your saying
that your view of dignity requires certain action and my view of
dignity leads to trampling some of these. Your view of dignity
can't trample my rights, my reason, my freedom, my autonomy because
you're right and I'm wrong. And I think that this is a real
concern that this view can in itself lead to a trampling of human
DR. PELLEGRINO: Thank you very much, Janet.
Just one more. Paul?
DR. MCHUGH: Well, I, like Janet, often find myself
overwhelmed by my ignorance in these areas, but I do think that
it's important to say some things from that interesting interface
between science and art, namely medicine and its practice and what
I'm going to turn back, actually, to Dr. Rowley in a
minute to make my point. And that point comes in a number of different
ways. But one of the things that I found great about our Council which
has happened over this time has been this combination of our interest
in what is basic and then what is expressed.
It's unique, I think, in Council work, that we both talked
about the science and then published this book on what fundamentally
were the expressions of the poets.
Our Council has worked in both of those arenas remarkably
effectively and had very interesting conversations. Leon's recent
article on this speaks to that as he talks about the distinctions that
he wants to draw between human beings and being human and then
ingeniously brings them together in this wonderful circle of the circle
of being, as it were and, therefore, evokes for me that wonderful
phrase from a great poet, the Irish poet, William Butler Yeats, in that
poem "Among the Schoolchildren," where he ends up with
saying, "How do we know the dancer from the dance?" And that
speaks to what the dignity really is.
We hear about the material, and then we hear about what happens.
We don't find inspiration of Cal Ripken in the orthopedic clinic.
We find it on the field. But we can help him if he gets into trouble.
Now, I want to come back to this issue that Professor Meilaender
wants to dismiss, namely this image and likeness of God, because,
in point of fact, I find that both as an Augustinian and as a contemporary
person, a very important issue for us and for me.
I want to come back to Janet in this way because, first of all,
Janet, although I agree with you that in religion we have caused
lots of trouble, I wish it were only religious people that had caused
a lot of trouble.
The real problems we get are what we believe. Okay? And
in the Twentieth Century, did we stop believing in God and we caused
100 million deaths? And we couldn't come close to that when we
believed in God. So it's what we believe and how we use our
Now, I just want to tell you what I believe about what gives human
beings their dignity because it's in their image and likeness
to God. And where do I get that? How do I find it? I find it
in the Trinitarian conception of God. I guess that's Christian.
I guess it's Christian.
DR. MCHUGH: And how do I see it expressed, especially
expressed, on a day I spent in a lecture hall at Hopkins listening to
Janet? Janet came and talked about her work and showed us what came of
it and inspired our lecturer this morning.
The Trinitarian idea is that there are three things about
human beings and three things that are in God. One is the capacity,
the executive capacity, for conceiving of something, conceiving
something could be the father, if you will; the work of working it
through and articulating one thing after another, the word, the Son, if
you would; and, finally, the inspiration given to others and inspiring
us by seeing it. All of these were done by Janet.
DR. MCHUGH: She conceived of this problem of the leukemia
of these children. She worked not just from finding the chromosome but
then worked out the molecular details. And it was a hell of a lot of
work. And she showed us all the various people that had contributed to
But then at the end, we realized together what this journey
meant for us, what it did in dignity to give us cures for these
children but not simply that practical and, as our friend showed us
today, the loss of death, but simply the sense that this experience,
this expression of a human being in action, you know, for me, it just
filled my heart and filled the room in my opinion with everything.
So I am interested in expressing what I mean by human
dignity in this Trinitarian expression, where we can see it, where we
can see it in action, where we can — I don't want to say worship
it at this level but certainly celebrate it. I mean, I celebrated that
day. And I still remember it, of course. And I could tell the dancer
from the dance.
And it's in that arena that our Council has spoken
about dignity in action. Leon speaks about it today. We have heard
about it from Gil and everything. And I come down to thinking it's
DR. PELLEGRINO: Thank you very much, Paul.
Let me again say to Council members I hope relative to this
discussion and looking at the papers, that you will be inspired to
write your own comments. I know that Adam Schulman will welcome them.
Indeed, Adam, would you like to say a word or two about
where the volume is? And I think that that will bring us to the
conclusion of our meeting.
DR. SCHULMAN: Yes. I would just like to reiterate what
Dr. Pellegrino said, that we still would welcome any submissions you
would like to give in the form of comments to the essays that you have
We haven't received too many to date, but I do think
that as the volume gets closer to completion and publication, it will
be a much stronger and much more interesting product if it's not
just a stand-alone collection of essays but includes as well your
considered reactions and comments on these papers. I think it will be
a much more interesting thing for the public to read when it shows what
the Council members made of these essays.
So as we are working on editing these essays and we're
really fairly flexible about when you can submit these things; that is
to say, even until fairly late in the editing process, there would be
room for member comments on these essays.
So I encourage you if you haven't done so to think over
the essays that you have ready. And if there is one that particularly
interests you, we would be delighted to receive commentary on it.
DR. PELLEGRINO: Thank you very much, Adam. Thank you for
undertaking the task of putting the papers together into an anthology.
SESSION 7: PUBLIC COMMENTS
DR. PELLEGRINO: Let the record show that no one has signed
up for public comments. And, therefore, we will not have the section
on comments from those in the audience. No one has requested.
Thank you all very much for attendance at the meeting. And
thank you for your participation.
(Whereupon, the foregoing matter was concluded at 12:05