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Eric Green: Okay. Now the fun begins. By the way, I told
you we were going to have some individuals who are both articulate and actually have
some opinions, and you can start to get that sense. They're certainly not shy, but I thought
they were both terrific presentations to set the stage. We are going to just -- I'm going
to throw a couple things out for a little bit of discussion, but then we're going to
take a break, probably within about five or 10 minutes, because we want to hear from you.
And in addition, I would also say that during the break -- one thing I recognize is there
was some science that got covered along the way, some terms that maybe didn't get defined.
If anybody in the audience has a question, especially a fundamental question, "What does
this mean and what do they mean by that?" feel free to come up and find us at the break,
and we'll happily answer that question, especially around these -- some fundamental concepts.
So, I want to just -- actually there were lots of things I could ask to get this going,
but it was interesting, sitting next to each of them during the other presentation, and
they're feverishly taking notes.
[laughter]
I mean, they're borrowing paper from me, a lot of ink was going. So I guess I want to
start -- and I'm going to ask Robert to start since Susan's talk went first -- what -- name
the one thing, just sort of at a core, that you disagreed with most in what she had to
say. And some of it you covered, but if you were going to crystallize it in sort of one
sentence, what was the thing you had the greatest disagreement in what Susan had to say?
Robert Green: I think the greatest disagreement is somehow
tying the abuses in history to the -- to the medical use of genomics. I mean, yes, that's
true, but I just feel like those are selective examples, and we could dig around for examples
in a lot of other domains that represent pure evil in the world that have nothing to with
genetics and genomics.
Eric Green: And reciprocally, what, fundamentally, you
disagree with the most in what he had to say?
Susan Wolf: That we're dealing with frightened patients
and lazy doctors, and we got to shape these doctors up, get them in their hunting these
incidental findings, performing all these analyses, and somehow, doctor knows best.
When I think, boy, I may trust patients and doctors more than you do, Robert, which is
astonishing to me, because I do trust them to make good decisions with patients, thinking
not in a fog of fear, but really thinking about what results they are prepared to deal
with.
Eric Green: Okay, so I want to start unpacking some of
this because I like both of those things that I heard, and it was some of the things I was
thinking as well. So let's actually start with the latter one. So I want to know -- I
want to know, Robert, you know, how do you react to that because I'm not sure, maybe
part of it I will -- as a physician, my disclosure would be, I didn't hear him saying that, so
I'm just curious how you would respond.
Robert Green: Well, I agree. I don't think I said that.
[laughter]
I -- so --
Susan Wolf: Play the tape.
[laughter]
Eric Green: And there is a tape. There is a tape. And
you can all watch it afterwards on the GenomeTV channel on YouTube, but we'll get there later.
Go ahead.
[laughter]
Robert Green: The framework here I think is that professional
societies have, for decades, made professional guidelines or recommendations to try to improve
the practice of medicine. So this is one of 10,000 such guidelines that gradually try
to nudge doctors. They're not lazy or stupid but they need to be guided by the professional
societies -- that's the fiduciary duty of the societies -- to improve their practice
parameters. So, really, it's rather ordinary what we did. We created a practice parameter
and made a set of recommendations that laboratories search for this information and deliver them
to the physician. Then the physician can contextualize them, and I'll say more about that in further
exchanges, I'm sure.
Eric Green: Susan, I'm curious to hear from you what -- how
you would respond to this issue of -- that some of your arguments were in the past, you're
digging up sort of historical legacy issues, and the world has changed a bit, and yet you
want to go back to sort of these historical figure -- historical -- I want to --
Susan Wolf: I -- So I hereby summon the spirit of George
Santayana, that those who forget the past are doomed to repeat it; that's my first response.
My second is a lot of what I said isn't at all in the past. The fact that NIH was -- really
stepped up to the plate just last year and convened a special panel to control the Lacks
genome is enormously important and a recognition that there is something special about genetics
and whole genomes, and they do need to protected, they do need to be handled sensitively, and
that's really dealing with the legacy of the past. That's just one of many examples. It's
not all in the past. We still have issues going on in Native American populations including
the Navajo -- I could give you a long list -- the Havasupai. As you know, there is ongoing
concern, difficulty even conducting genetic and genomic research because there still is
a problem in getting that true partnership and respectful collaboration to happen.
Eric Green: You buy that?
Robert Green: Oh, yeah, I agree with her completely, but
I don't think that there's more discrimination or insensitivity in genetics than there is
in, let's say, mental health world, where there's tremendous insensitivity. There's
tremendous discrimination. There's historical mini and *** atrocities based on people with
mental health problems. The difference is that there isn't millions of dollars for ethicists
to write about and study the historical or current abuses of mental health ethics. And
there is in genetics; it's an incentive. So, is it wrong? Absolutely. Is it spectacularly
different? No, not so much.
Susan Wolf: I need to intervene, that you noticed, Robert,
I did something different. I did not say that genetics and genomics was the only sensitive
type of medical information. And I was the one who said mental health, substance abuse;
there are even laws that give that extra protection. So I didn't exceptionalize genetics all alone
on Mount Olympus. It's one of a category of things, though it has a special history.
Robert Green: So genetics is different but not so different,
something like that.
Eric Green: And I think actually that's one of the themes
that we were going to -- it's almost what you just said, because that's what I sort
of -- I think it's hard to argue that genetics is different. I mean everything is different
from something else; the question is whether it's spectacularly different from other medical
information.
One of the things I want to get clarity on is, picking up on something that Robert also
took exception with, where you were talking about the error rate, or the errors -- and
I'm particularly curious to unpack this a little because I'm trained as a -- as a laboratory
medicine doc, a clinical pathologist where clearly we -- you know, getting it right when
you do a blood test or you do a chemistry test is critically important. But I also know
that better and better technologies get you better and better and more accurate information.
So is it your contention, Susan, that we will never get it right in terms of genomic information,
or are you simply saying that in here, circa 2014, it's not quite accurate enough to totally
rely on. And I think that's an important point. Because I would agree with you that today,
you know, everything's not perfect yet, but I don't think we should paint a brush of negativity
across genomic information because it'll never be accurate enough because I think if you
follow any medical technology, it evolves with time, it gets better and better. So I
need to get clarity on that.
Susan Wolf: Yes, and I would say two things. Number one,
I was virtually quoting you from the 2011 Nature piece where you said, "Before genomics
really moves full scale into the clinic, we've really got to get it more accurate." We do
have an error transition to get through, so that's agreeing with your second statement.
But the other thing I'm pointing out is, in the world of incidental findings, you know,
and they're not just genetic and genomic. If you look, for example, at studies imaging
the brain or imaging other parts of the body, they too encounter incidental findings, "Oh,
we were looking for this, but, oh, my gosh, this looks like potential pathology. What
should we do?" And what we have found in that domain, too, is sometimes it's a false positive,
and we have to be very cautious about inflicting that on people.
You know, when Robert's committee, the ACMG, came out with the incidental findings guidelines
there was, I think, a very important paper. I mean, I was on it, but I wasn't the lead
author, Wylie Burke was the lead author, basically saying, you know, one thing that the committee
did right was they were upfront. They said, "We really don't quite have an adequate evidence
base to recommend all these 56 genes for what is, in effect, opportunistic screening," which
is a fancy way of saying, "Well, while we're sequencing your genome, your cancer, we're
going to just take that opportunity to look at some other stuff." But there was some difficulties
in doing that, because a lot of what we know about the penetrance of certain genes, for
example, we've discovered by looking at symptomatic populations or populations where we knew it
was problem in the family not just the general public. So we do have some evidence gaps and
we need to pay attention to that, be cautious.
Eric Green: Yeah. So, this is setting the stage. Let me
make one point, especially since you quoted me, I feel have to at least make the point.
I completely agree that there's evidence gaps. I completely agree that we have to worry about
accuracy. And I think it's interesting because some of the studies that Robert showed, MedSeq
and the -- and I forgot the other name off the top of my head, these are exactly studies
that are trying to examine this and to close that evidence gap and to improve those errors
and to figure out what we're doing.
So I don't think, certainly any of us, and I'll let Robert speak for himself, but I don't
think the field of genomics believes that everything is here and now for full-scale
clinical deployment, but what we're trying to do is develop a set of studies that will
refine them, so that down the road, to be defined how many years, it will be in a position
to be deployed. So I think we should also separate, in this discussion, the here and
now versus where we're going to be five, 10, 20 years from now.
Okay, so we've set the stage. You can see lots of issues we can unpack further, and
we're going to want you guys to get involved. So we're going to take a break now; there's
refreshments outside. I think there's index cards outside or something to write on, and
please write down your questions, and then I'm going to pick some of them, and we're
going to come back in how long, about 20 minutes? Fifteen minutes we're going to come back and
we're going to start to ask some of your questions of these two speakers.