Will Precision Medicine Improve Public Health?

Will Precision Medicine Improve Public Health?


>>This meeting is being recorded. If you
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live in the room. You may join in the conversation on twitter using hashtag NCI PMPH. And with
that it is my pleasure to turn today’s session over to Dr. Debbie Winn.>>Welcome. We’re delighted that you are here
to listen to our webinar on Precision Medicine and “Will Precision Medicine Improve Population
Health?” This webinar is sponsored by NCI’s Precision Medicine and Population Sciences
Interest Group. This is our inaugural webinar, so we hope you’ll stay tuned and listen to
learn more in upcoming months about future events. We’re extremely delighted to have
two fantastic speakers today. Dr. Galea will be speaking first; he’s a physician and an
epidemiologist who is currently the Dean at the Boston University School of Public Health.
He also has been the Chair of the Department of Epidemiology at Columbia University, and
has held other academic and leadership positions at University of Michigan and New York Academy
of Medicine. He’s particularly interested in the social production of health of urban
populations, and he’s focused on causes of brain disorders, especially mood/anxiety disorders
and substance use. He’s particularly interested in issues related to mass trauma and conflict.
Our second speaker is Dr. Muin Khoury; he’s the Director of the CDC Office of Public Health
Genomics. He has split his time here with us here at the National Cancer Institute for
many years, divided his — he’s been a busy man working both at CDC and NCI. He’s formally
the Associate Director of our Extramural Epidemiology and Genomics Research Program. And currently
he’s been very actively involved in promoting a dialogue on precision medicine in public
health. He has a PhD in human genetics and genetic epidemiology, and an MD degree. He
has published extensively in genetic epidemiology and public health. And he’s very interested
in the translation of science and research into public health settings. So both speakers
have been extensively published in the scientific literature. And their work is widely read
and cited. They’re both considered to be very influential thinkers and speakers, so we’re
very, very pleased to have them here today. We expect a lively presentation and an exposition
of alternative viewpoints. So to remind you again, our topic today is “Will Precision
Medicine Improve Population Health?” And with that we will just get started. Thank you very
much to Dr. Galea for starting us off today. All yours.>>It’s a pleasure to be here and to discuss
this with Muin and with the audience. So I was asked to tackle this question, and I suppose
I come at this from the point of view of, actually I don’t know how to advance slide;
can I just say advance slide? Will somebody do that? Can we advance the slide? Hmm. I’m
hoping that somebody will be advancing the slide on the other end. I’m just going to
pause until somebody tells me.>>Yes, we’re working on the technical details
of advancing the slides. Just –>>Okay, let me just pause, then. Ah, here
we go. So I can just say “Advance slide,” will that work?>>That’s fine.>>Okay. So I was asked to take a position
as a — what I’m calling the loyal opposition. I am coming from a point of view of someone
who’s going to answer these questions as, I’m not so sure that precision medicine will
improve population health. Next slide. I have been loyal because I’m actually loyal to the
aspirations of science. I actually am excited about the potential of precision medicine.
I think there is a fair bit of mechanistic insight that will emerge from this exercise.
Next slide. But I’m opposed to compelling ideas that I am not convinced will advance
population health, at least in their current formulation. Next slide. So as far as I’m
concerned, there’s only one question that matters. Will precision medicine approaches
improve population health? And the answer I’m going to suggest is, next slide. No, unless.
And I’ll explain about the “unless” in a second. So let me start with trying to answer my no.
And offer three reasons why not. Next slide. So first of all, the first of the reasons
is the challenges of complexity in biology. That a lot of precision medicine efforts are
predicated on the assumption that we shall be able to determine the pathogenesis of disease
so that we can intervene on particular genes, particular molecules which will make a tremendous
difference for individuals. The reality is that the biology is much more complex than
that. Next slide. This is from a paper that just came out recently showing the population
attributable fraction to genes for a wide variety of disorders. And this is really a
best estimate summary I can share. Everybody can see in any number of disorders, really,
the proportion of pathogenesis that is attributable to genes is in the 20 to 30% range for the
most part. That’s just one simple illustration of why genetic factors matter relatively little.
Next. Next slide shows a — from the International Consortium for Blood Pressure a summary of
GWAS, genome-wide associational study, showing that there are a large number of variants
that have been identified that are linked to systolic blood pressure. And to that systolic
blood pressure, all of them showing an effect of about 1 mmHg. Showing an enormous number
of variants which we don’t understand how they work, all of which contributing to a
fairly minor increase in blood pressure, which is our target of interest. Next slide. And
at the level of trials that have looked at this — this is from the SHIVA trial, showing
that when there was an attempt to use molecular-targeted agents versus treatment of physician’s choice,
what you actually see here is the progression-free survival is roughly the same between molecular-targeted
agents and treatment at physician’s choice. Which really gets at the heart of the matter
that at core, despite their efforts to molecularly target or genetically target, it’s unclear
we’re going to have much more gain over the choice of physicians. Next slide. A lot of
this has been discussed on the topic of cancer. And there’s no question that for some somatic
cell tumors, precision medicine approaches are probably the most promising, and it’s
probably more promising pathology. But even cancers of multi mechanism disease with a
fair bit of [INAUDIBLE] resistance that’s predictable. Next slide. And at core, the
— a lot of this argument about the challenge of complexibility rests on the fact that while
we are making all this effort to target molecularly or target genetically, there is this overwhelming
role of behavior. This is for men and women. And this looks at the association with cancer
and BMI. And showing this extraordinarily high relative risk of death with BMI among
men for liver cancer. Among women for uterine cancer; also women around breast cancer. Men,
colon-rectal cancer. Showing that much more easily detectable phenotypes like BMI and
behaviors ultimately are directly associated with pathology in a way that we both understand.
And that gives us much more certitude that we will be able to do something about it.
So that’s point one. Number one is that we have enormous challenges and complexity in
biology. And I think many of our precision medicine approaches are making claims that
are enliving [phonetic] some of the challenges we are going to have in getting to a place
where these molecular-targeted or genetically-targeted approaches will make a real difference. Next
slide. The next point is that many precision medicine approaches conflate individual and
population. And that observations that have utility at the population level do not necessarily
have utility at the individual level. Next slide. This is a fairly standard and typical
dose-response relationship showing a genotype score. This was show, I think from a group
of subjects here at Boston University. And the likelihood of type 2 diabetes. And I show
this slide because it’s a fairly compelling slide that in some respects gets at the very
heart of the argument for precision medicine. If you look at this you’ll say, wow, look
at this genotype score. If I had the genotype score, would I have a higher cumulative incidence
of diabetes? That is the type of compelling narrative that emerges from precision medicine
approaches. The problem is that this is true at the population level. When you get at the
individual level — next slide — What you see is that when you take the exact same data
and map it out, genotype score still on the X axis, and you look at the percent of subjects
with and without diabetes, which are the black and the gray lines, the two curves are fairly
indistinguishable. Meaning that having a genotype score tells you very little about what the
likelihood is of you the individual having disease. Which means that a lot of the observations
from population level — which ultimately is what we’re doing from large sample studies
that get at the molecular and genetic targeting — have relatively little utility at the individual
level. And in case you’re wondering, when do these findings have utility at the individual
level? Next slide. As this slide shows, you need to be at the bottom right of this figure.
This is a mathematical simulation from [Inaudible] California. Here we need an alteration of
about 350 to have the kind of individual predictive utility that we frequently assume is going
to emerge from precision medicine approaches. Now, here’s the good news — or the bad news.
The good new or the bad news is that there is nothing much new in fact about this argument.
In that we have much experience with individual medical approaches that we think make a difference
for population health. Remember, the question I’m asking is, will these approaches improve
population health; that is the question I am most interested in. And that in fact they
do not really improve population health. And to take one very simple example, is the extraordinary
drop in infectious diseases over the course of the 20th Century. And everybody knows that
the drop in infectious diseases over 20th Century is one of the principal reasons for
the prolongation of life expectancy. And as this slide shows, you see the drop in infectious
diseases, you see the spike for the influence of pandemic. But you also see where penicillin
was introduced. And the introduction of penicillin, as you can see there, had made barely a dent
in the drop in infectious disease mortality. That does not mean that penicillin doesn’t
matter. Doesn’t mean that antibiotics are not very important and they’re not very important
for the clinical care of patients who have infections. What it does mean, however, is
that at the population level there was many other factors that mattered to improve health
in the context of infectious diseases. And one last point on this. Next slide. This is
a clinical prediction model, looking at prediction of diabetes. And what you see here is a variety
of lines on this. The red line is clinical prediction model. And the orange, blue, and
purple lines are clinical prediction models adding multiple genetic loci. And what you
see is exactly the same curve for all along. Suggesting that what we know clinically, what
we can tell phenotypically, looking symptomatically, ultimately gets us results that are as useful
as molecularly-targeted or genetically-targeted approaches. Point three, next slide. Which
is that much of the precision medicine discussion also embeds within it the assumption that
if we understand precision medicine, if we understand precisely what our risk is, that
we would behave differently, that populations would behave differently. Unfortunately, data
does not really bear this out. There are several papers on this, but — next slide. A recent
review that just came out about the impact of communicating genetic risks on diseases
— risks of disease on risk-producing health behavior. Next slide. Such that expectations
communicating DNA based risk estimates changes behavior is not supported by existing evidence.
So those are three reasons why I am actually skeptical, why I call myself the opposition
on what I think is a very compelling idea that has utility but I’m not so sure has direct
utility in the short term for population health. But now, moving onto the next slide — Let
me tell you why I think this matters. I think this discussion is not simply an academic
discussion; it’s not an academic discussion between Professor Khoury and myself. I actually
think this matters for three important reasons. Number one — next slide — Number one is
that this kind of discussion, the fact that we are investing a fair bit of our federal
research eggs into this particular basket is distracting us from issues that matter
more. And those issues that matter more are all issues of population health. Everybody
here knows in the United States health indicators in the United States are nowhere near as good
as many of our peer countries. Next slide. What is frequently not known, though — this
is from a National Academy of Medicine report — is that it wasn’t always like this. The
red dot is the U.S., the gray dots are other high-income countries. And what you see is
that while everybody has gone up, the U.S. has over the past 35 years drifted inexorably
and slowly towards the very bottom of the pile. This is what’s important. And this is
what I worry, that distractions like precision medicine will take away our eye off the prize.
And the prize is improved population health. Another illustration is life expectancy, and
there’s enormous widening of life expectancy we’re seeing in the U.S. Next slide. This
looks at life expectancy in the U.S. for women and men looks roughly the same, dividing people
by quintiles. And what you see is that life expectancy has only increases for women for
the richest 20%. In fact, it stayed the same for the middle 60%, and has decreased for
the lowest 20%. This is something which most people, when we first asked them what percent
of people have not had an increase in life expectancy, we tended to not to guess it’s
actually as high as 80%. And despite the fact that we as a country have spent an extraordinary
amount of time in the past seven years discussing the Affordable Care Act and focusing on other
efforts to improve clinical medical care in this country. Next slide. You see that the
percent of adults 65 years and older who have problems accessing health-care services remains
substantially higher than it is in other peer countries. So point one is that an effort
on precision medicine to the exclusion of all else misses the important questions in
population health. Point two, next slide, is that it also makes for missed resource
allocation. And it unfortunately sets us in poor step in terms of investing in the future.
Next slide. I right now happen to live in the State of Massachusetts. Which considers
itself fairly forward-looking on issues of health. I live in Boston where the health
industry is the largest industry in town. But when you look even at Massachusetts state
spending, you see that healthcare spending — or medical care spending, more accurately
— has gone up in the past 14 years. While spending in everything else — primary/secondary
education, law and public safety, mental health, public health, higher education, early childhood
education, environment and recreation — has consistently gone down. And this is the danger
of focusing our attention too much on efforts that are implicitly medical in their approach
about molecular targeting and genetic targeting, that they distract us from investing in the
areas that are ultimately going to improve the health of populations. And our federal
funders nationally are helping, the most important single health fund in the world, is not immune
to this. Because — next slide — If you look at — this is something you can do yourself
from NIH reporter — proportion of NIH funding awarded to projects with the terms “genetic”
or “genetics” in the title, abstract or terms over the past ten years. The blue line is
actual, the red line is just a fitted line. You see that that’s gone up. Next slide. And
conversely, proportion of NIGH funding awarded to projects with the terms “population” or
“public” in the title, abstract, or terms has gone down in the past ten years. So — by
the way, I will point out that the first Y axis was about 30% to 37%, while this Y axis
is 4% to about 0.4%, just to give you sense of the scope. So the second challenge, the
second reason why I think this matters is because of research allocation. Number three,
and I think the third reason why this matters is that we are investing so much of our health
capital in the broader public discussion that the precision medicine approach is leading
to hype over hope. And let me just show you a couple of examples of where hype over hope
and how we are repeating mistakes of the past. This slide says, “The time has come in America
when the same kind of concentrated effort that split the atom and took man to the moon
should be turned toward conquering the dread disease. Let us make a total national commitment
to achieve this goal.” This was of course President Richard Nixon declaring the war
on cancer in 1970 — well, the National Cancer Act was 1971; he made the statement in December
of 1970. Well, how has the war on cancer done? The next slide looks about and shows that
the war on cancer in and of itself has really made nary a dent on cancer. So what you actually
see is the decrease in cancers largely due to stopping on smoking, having very little
to do with the medical approaches that were advocated. And in much of the approach we’re
seeing our precision medicine and many of its ancillary offshoots are doing much the
same thing. If you look at the next slide, this is President Obama saying, “Last year,
Vice President Biden said that with a new moonshot, America can cure cancer. Let’s make
America the country that cures cancer once and for all.” These are very much repeating
the same types of efforts. But we are investing extraordinary resources in medical, clinical
approaches. While turning a blind eye to what is important, which is improving population
health. And this has consequences. It has consequences for how the health enterprise
is seen in the broader public. Leading us to one of my favorite cartoons, which is next
slide. Which has the news reporter reading today’s random medical news saying that coffee
can cause depression in twins. But equally well he could have said that the computer
terminals can cause hypothermia in overweight smokers. And this is the type of roulette
that we find ourselves on as we focus ever more on molecular and genetic targeting at
the expense of broader efforts to improve population health. Next slide. So I said,
“No, unless.” So let me just talk about “unless,” what do I mean by unless? Well, I mean unless
a precision medicine approach or a precision population health approach — which I will
talk about shortly — ultimately focuses on populations. Unless we take a real hard look
about how this fits in with an agenda that is relentlessly pushing the question of how
we improve the health of many. Next slide. This is a population. Population is messy;
it’s interconnected; has spatial interdependencies. People interact with one another and have
behavior changes that are reflected by context and by inter-individual relationships. Next
slide. What we are doing with precision medicine approaches is ultimately taking these populations
and focusing ever more on smaller and smaller subsets. Next slide. What we instead should
be doing is we should be looking at whole populations. We should be saying, these are
diseases in populations. Next slide. And we should be doing whatever we can to improve
the social/economic/cultural context that takes these individuals with pathology in
whole populations. Next slide. And reduces the number of people with pathology. So let
me wrap up; I have two minutes left. I realize that in speaking as a loyal position on the
context of precision medicine population health, I run the risk a little bit of painting myself
into a corner; as being sort of the guy who doesn’t like technology, who doesn’t like
innovation, doesn’t like advance. And I want to be clear that that’s far from the truth.
I actually, I think there is a lot that can be learned, a lot that can be gained from
the type of molecular genetic targeting that is going to emerge from precision medicine.
My argument is not with the utility of these approaches for mechanistic, biological, and
medical work. My argument is with the substitution of an intellectual and a funding agenda towards
the improvement of population health which ultimately is a medical agenda that will help
the few. And, but just to end on a quote and this is again, the counter to my argument
will be well, but look; give this a chance. This is something that we should put our shoulders
to the heavy rock and push it and together. “I know this is a formidable technical task,
one that may not be accomplished before the end of this century. Yet, current technology
has attained a level of sophistication where it is reasonable for us to begin this effort.
It will take years, probably decades, of efforts on many fronts. There will be failures and
setbacks just as there will be successes and breakthroughs. And as we proceed we must remain
constant. Isn’t it worth every investment necessary? We know it is.” And that’s the
kind of inspirational talk that I think is reasonable to affix to something that is,
you know, a little bit futuristic. Like, surely we should do this, surely we should invest
our money in it. Well — this quote is, by the way, President Ronald Reagan when he announced
the launch of Star Wars as the national defense missile shield. And I just put it up there
because I think it’s got the kind of inspirational language and an untested approach that ultimately
ended up not doing anybody any good. So, just to end. Next slide. I started out by calling
myself the loyal opposition. This is the two kings walking by, one of them saying, “My
local opposition wasn’t loyal enough.” I do — to go back to my point at the beginning
— I do think that I am loyal to the aspirations of science. I’m excited by the mechanistic
and medical potential of genetic molecular targeting. And much less excited about its
potential to improve population health. And I’ll end with a medical — next slide. This
is my goldfish — and I’d say it’s a goldfish that I care very much about. I would like
the goldfish to be healthier, to be happier. And I can do two things to make my goldfish
happier and healthier. I can make sure that my goldfish always eats the little food I
put in a measured way and doesn’t eat too much, make sure that my goldfish swims around
in his bowl ten times clockwise, ten times counterclockwise on a regular basis. I can
make sure that my goldfish has safe goldfish sex. I can also make sure that I genify my
goldfish and understand fully the mechanisms of its cancer so I can fix it when it develops
cancer. Or I could yes, do all that, but I could centrally and importantly recognize
that everything about my goldfish’s health is determined by the water the goldfish swims
in. And unless I actually clean its water and create the social, cultural, and economic
environments that promote its health, everything else I do is futile. Next slide. And that’s
it; I will stop there. Thank you.>>Thank you very much, Dr. Galea. I’ll now
turn the mike over to Dr. Muin Khoury. Thank you.>>Thank you very much, Debbie. And Sandro,
you’re a hard act to follow. My answer to the question, “Will precision medicine improve
population health?” You’ve answered the “but” in my “yes.” But I do not think it’s a distraction.
There are a lot of challenges you’ve raised around the complexity in the biology, the
individual versus population focus, the behavioral change issues, the hype and the hope. And
I personally spending relatively a long time between shuttling between NIH and CDC trying
to kind of bridge the worlds of medicine and public health. I have four themes I’d like
to elaborate on. And some of you who are following this discussion would see a lot of similarities
and overlap between Sandro’s ideas and mine. So the first theme is that in order to improve
population health, we have always needed medicine and public health. When you get sick, you
want to have the best available drugs and medications and interventions. And when you’re
not sick, you want to keep, you want to prevent disease and promote health. And this easy/uneasy
relationship between medicine and public health has been going on for decades. And I know
usually medicine gets all the glory. But there is a lot of accomplishments that public health
have made over the years. And as we move from medicine to precision medicine, I think that
same tenet applies. That as we begin to have molecularly targeted treatments of cancer
— and we have a few examples of those; there are some success stories — we still need
public health. So this sort of dichotomy or a distraction saying that, you know, doing
one at the expense of the other is because we always need both. And we can never forget
that point. And the thing that I wanted to impress on the group here is sort of the evolving
definition of precision medicine. I’d like to end up with it at the end. Precision medicine
is not just about genes. It’s a new emerging approach that includes both prevention and
treatment. That also includes environment and lifestyle. So if we subscribe to the idea
that precision medicine is only about genetics, then Sandro’s notion is very much fulfilled.
So just to highlight the need for both population and individual approaches, this is a paper
from Jonathan Fielding from a few years ago. That highlights the need for both approaches
as you go from well to being sick in bed. And, you know, there are activities you do
at the individual level and the societal level. And all of these things need to be done. And
they should not be done at the expense of one another. A leader at CDC [Inaudible] has
put up his own version of this, sort of the health impact pyramid. The five levels of
interventions at the population level. Of course, if you work at the base of the pyramid,
provide opportunities to wipe out poverty and improve socioeconomic status, you’re going
to improve health. Of course, that would have the largest impact at the population level.
At the top of the pyramid, going one-on-one talking to people and clinical interventions
will achieve lesser of an impact. So what am I saying here, am I agreeing with Sandro?
Yes, of course I’m agreeing with Sandro. But we cannot have this discussion and say precision
medicine versus public health. To me it’s a false dichotomy — we need both. We need
both in an era where medicine can become more precise, as well as public health can do its
work. And I think my ending argument is at the end that public health will become more
precise, as medicine will become more precise. So the second theme of my talk is that there
is a lot we can do now to implement what we already know. This is not a pie-in-the-sky.
There is course a lot of hype. But there is a lot of hope. And I reflected that on the
paper I wrote last year with Jim Evans about balancing long-term knowledge generation,
which is now geared up with a one-million person cohort. With early health benefit.
If you take a look at a cohort of a million people, there are thousands of people that
can benefit from interventions at the molecular or other level that they may not currently
be benefiting from. So melding intervention and implementation science with discovery
science is very important at this point. The CDC has been maintaining this simple tiered
classification of genomic tests — and let’s stick with genomics for a little while. The
tier ones are those that are applications that are ready to be put in play. A few of
the cancers, newborn screening which affects all newborns in the United States. And all
the way ranging to tier three, which is not ready for prime time, as Sandro mentioned
about personal genomic tests and direct-to-consumer. But there is a whole shades in between of
the tier two. And if you think about some of the tier one, there are already many examples
and millions of people that can be affected by these things. Two examples, hereditary
breast and ovarian cancer and Lynch syndrome. Yes, do affect a small fraction of all cancers.
But that translates to thousands of preventable cancers every year in the United States. And
there are actions that public health can do now to prevent certain cancers associated
with these hereditary conditions. And a public health/healthcare partnership will be needed.
Because healthcare alone does not seem to be ascertaining those people who need the
services, genetic counseling, and some of the interventions that currently work. And
there are disparities. And of course if you are in public health, we have to worry about
disparities. Not only in the [Inaudible] research, but implementation. And this is data from
a very large data set of 15 million insured people that shows the disparities of utilization
of BRCA testing in young women with breast cancer by race and ethnicity. So the third
theme what I want to continue on this journey is that public health is a partner in the
development of precision medicine. And what we call public health sciences — I’ll tell
you a few of them as we go along — are essential in ensuring the success of precision medicine.
Let me elaborate on that. So a few years ago, Francis Collins put out this vision for the
future of medicine in which he portrayed this 23-year-old man named John who goes for his
primary healthcare checkup. And he gets this fictitious printout of genes, and then a personalized
intervention strategy to mitigate the risk of these various diseases. But let me ask
the question here, where do you get these numbers to begin with? These numbers can be
only gotten from large-scale population studies. And as Sandro showed us, some of these current
kits are not that predictive. And I’ll elaborate on that a little bit more. But the question
is, what do you do with these numbers when you get them? Because there is a whole lot
of things that can be done. So a case in point is this discussion about mammography, which
is sort of a population-wide screening effort that’s been discussed at the forefront. And
all these changing strategies in how often do we need them, at what age. And the various
recommendations by different groups and different countries. And if you think about these sort
of not very predictive genetic factors that Sandro showed us a bit earlier, they don’t
have to be too predictive. But you can think about whether or not they can be used in crossing
a certain threshold for utilization. This is data from last year from JNCI that shows
on the basis of 80 snips, and now probably there’s about 200 of them, the ten-year absolute
risk of developing breast cancer for women with and without family history by this polygenic
risks score that was mentioned earlier. And depending on your cutoff and screening, you
might decide to use the risk score. Or at least in the informed shared decision-making.
Because if you see a certain cutoff, sometimes people cross that threshold at a younger age
group if they have a higher genetic load. And it doesn’t have to be as predictive of
the phenotype that we have in mind. So the question is, the public health sciences are
eminently needed to translate this activity of what’s going on with precision medicine
discoveries. And Sandro showed us a slide that showed that we don’t have enough of these
population sciences here in the division of cancer control and population sciences, about
30% of our portfolio is in population sciences and precision medicine. Much of it is in epidemiology,
but some of the other areas are growing. The literature actually shows a deficit of this
public health genomic science beyond bench to bedside. About 1% of published genomic
research is beyond the initial discoveries. And half of it obviously is in cancer because
it’s a hot area of discovery right now. So I want to close with Theme number four, which
if you remember how we defined precision medicine at the beginning. I want to posit to the group
here and have some maybe dialog and discussion afterwards, as medicine moves into a precision
medicine territory, I submit to you that public health is moving in that same space towards
an era of precision public health. And let me explain that a bit more. Yes, we know that
there is complexity in biology. But there is more than biology involved. Health and
health outcomes are determined by multiple levels, ranging from the molecules all the
way to environmental and socioeconomic factors, the exosome in big ways, and all this technology
is going to allow us to measure these things a little bit more than we’ve had before. So
it’s not just about genes. I’ve showed you examples of a few single gene disorders earlier
that account for about 5 to 10% of the human disease. But our complexities which are major
killers — heart disease, cancer, and diabetes, that account for the majority of human diseases
— hopefully can be approached with this melding of all the exposures that come together. So
it’s not about our susceptibility any more, it’s about various types of exposures and
the genomes that we come across, including the microbiome that there is more of them
than us in our own body, if you will. There is that complex interactions that we’re just
beginning to skim the surface. And there are a few success stories, but tremendous challenges.
A promising area is epigenetics. Which is more than just about the gene sequence. It
really, it’s the ultimate gene-environment interaction. Because it uses the life course
approach to look at the impact of environmental factors on gene expression across multiple
generations. And the promise for that is yet to be explored. But cannot be over — sort
of overruled, in a way. So I wanted just to end with a couple of these slides. Because
we get stuck on words. And we have been using a lot of words. And sometimes the words have
a purpose of their own. Precision medicine has had its roots in the words “personalized
medicine.” Which means that we apply things at the individual level. If you look at this
Google term search, the blue shows how the trends and utilization of “precision medicine”
has taken off after the announcement of a precision medicine initiative in 2015. But
there is more to that. Because the 2011 Precision Medicine National Research Council actually
outlined a case for precision medicine beyond utilization of these technologies at the individual
or personal level. We know that there are lots of individual information that are very
imprecise, like some of the data that Sandro showed us. That the active genetic testing
movement is a very imprecise movement. And while it’s really highly personal, it doesn’t
advance the cause of public health. Whereas sometimes you have precision medicine discoveries
that combine biological and environmental insight, where the applications are not necessarily
for the people with a rare disease condition. For instance, the use of statins. It was discovered
because of a rare genetic disease of cholesterol, familial hypercholesterolemia. But a lot of
people are benefiting from statins at the population level regardless or not whether
they have familial hypercholesterolemia. Our challenge ahead, really, is using and measuring
all determinants of health. From the macro to the micro. To develop analytical approaches
to population health. It’s a question. And I think the technology is moving in that direction.
So last year I published this paper about big data meeting public health. And asked
the question, can our public health functions become more precise? We do a lot of surveillance,
where we practice these at the population level. We do develop policies, and then we
deliver interventions. Can we use the tools of analytical data science and big data to
do public health better? And as a matter of fact there are three upcoming areas that we
have initial success in using these tools at the population level — modernizing surveillance,
pathogen genomics, and then the targeting. Pathogen genomics is really the early frontrunner
of precision medicine for public health, whose applications are not necessarily at the patient
care level. But more at the population health and outbreak detection and response, effective
antibiotic use guidelines, and reducing the burden of these conditions. And this is just
one example from data from CDC showing that after the use of whole genome sequencing in
surveillance for Listeria outbreaks, we are now more able to link more of these outbreaks
because of the sequence with the source of the food from which the outbreak is derived
as a result of whole genome sequencing of Listeria samples. Ultimately at the population
level, we want to use tracking in order to solve public health problems. So this quote
from WGS to GPS is reminding us, all of us in public health know about John Snow. And
the Broad Street pump. And this is sort of a quote from Harvard that essentially posits
that if John Snow was alive today he would have solved the outbreak much more precisely
and more quickly than he had at his disposal in 1859, or whenever he had to painstakingly
try to map where people drank the water that was infected with Vibrio, and correlating
it with the outcomes of interest. And that’s what at least I would like to mention Sue
Desmond-Hellman, CEO of the Gates Foundation, has been thinking along the same lines. Of
trying to come up with a new era of precision public health. For those of you who don’t
know, Sue Desmond-Hellman was at UCSF. She was one of the architects of the National
Resource Council Report of 2011. And is now leading the Gates Foundation global health
effort to think about how we can bring the analytical tools of data science and others
to do tracking and understanding disease at the population level. So that we can improve
health not only for rich people, but across the globe. So in conclusion, the four themes
that I have presented to you are as follows. That as we move into these new tools and technologies,
we still need both medicine and public health to improve population health. That was true
before precision approaches, will always be true even after precision approaches. Partnerships
are needed to implement what we already know. And what we will know even ten years from
now. Because there are opportunities to save lives now that we are not capitalizing on
in that precision medicine space. Then public health sciences are needed to generate and
implement the new knowledge that’s coming from the bench. And finally, we are entering
a new era of precision public health that’s not just about genes, drugs, and diseases.
And with that, I conclude my talk. And turn it back to Debbie. Thank you very much.>>Thank you to Sandro and Muin for their
presentations. We will now open the floor for questions. As mentioned, questions can
be submitted using the Q&A feature on the right-hand side of your screen via WebEx.
Please type your question in the provided field and hit Submit. For those in the room
at NCI, we ask that you approach and activate a microphone before asking your question.
With that, I’ll turn it over to NCI’s Dr. Amy Kennedy to moderate the Q&A. Amy?>>Okay, as we wait for questions coming in,
is anyone in the room here at NCI just speak up, come up to a microphone, or –>>Hi, Sandro; it’s Ann Geiger. How are you?>>Hi, Ann. How are you? Good to hear from
you.>>You too. So I’m going to pose to both of
you this question. Which is, it seems to me that there’s an important matter of economics
— [ Silence ]>>Yes, my light isn’t lighting up. But anyway
–>>Ann, all I heard was “economics,” then
you cut out.>>Okay, we’re going to move microphones;
here we go. So for me, this, you know, Sandro, these issues of funding basic science over
population science have existed for decades. You know, they’re a legacy I think we’re all
aware of. I think my question for both of you is, we have limited budget. And so, you
know, I wonder if the two of you have a different perspective on where is bang for the buck?
Because I think I heard implicit, difference in the two of you. Sandro, you referred to
things like antibiotics and I would say public works. That are actually pretty cost-effective
for what we got from them. And for me the question is, is precision medicine screening
public health going to be similarly cost effective? So I’m curious to know what you two think.>>Well, I can take the first crack. I actually
think economics is at the very heart of my argument. That if we have limitless resources,
I actually probably would take a lot of my argument off the table. Because then I would
say, God bless, let us invest in molecular genic targeting, and let’s also invest in
efforts that improve the health of populations. So we can actually create a better world.
But the challenge, of course, is as everybody know, that we are in this country — just
focusing on the U.S. for a second — we spend roughly 6% more in GDP in health than any
other country. We have the worst indicators of any of our peer high-income countries.
And a lot of that is ultimately misallocation of resources. So my — at the heart of my
argument is a concern with resource allocation. Now I’m well aware of the fact that the resources
come from different buckets and different pools. And it’s not a simple matter of saying,
well let’s take the money that’s being spent on precision medicine and shift it into more
population-based approaches. It doesn’t work that way. But at the end of the day it’s the
broader national conversation that determines where we put our — which basket we put our
eggs in. And my worry is that we have a momentum behind an individualistic approach that has
reached its apotheosis in a precision medicine approach. and my worry if would crowd [Inaudible].
Again, just to be very clear about my argument, I think there is a lot of utility at the level
of science that can emerge from these precision medicine approaches. My worry is that it crowds
out everything else. So really it comes down to politics and resource allocation.>>This is Muin here. So I do not disagree
with you, Sandro. And I think the question is well posed. And the economics is always
an issue. And as someone who has spent most of his career in a public health agency, I
can attest to that. The question is right now is whether or not investments in both
the population sciences and basic science — I mean, the case that I made is that a
more holistic investment is first likely to make precision medicine success. And second,
it would lead to a new era of precision public health. So that’s the sort of the argument
I’m putting forward. I’m not trying to pit one agency versus another. I’m saying that,
you know, that the investment — the return on investment if we are to take on precision
medicine moving forward would be much better and much faster if we, as we learn new knowledge
we implement what we already know. And we use the same technology at the population
level to track and measure population health problems. And then target the interventions
where they are needed the most. Based on any number of factors. And they don’t have to
be genetics; they could be based on geography, on the resource allocation. And so economics
is always at the heart of it. But I’m hoping that moving forward this would not be a competition
but a collaboration between the various sectors of public health, medicine, and the basic
sciences. [ Silence ]>>Okay, this is Debbie Winn. Question for
both of you. Sometimes fundamentally I think, well, precision medicine really all that means
is risk stratification. Or prognosis stratification. Or stratification on the basis of treatment.
And I’m trying to reconcile that with equity access. To some extent if we really are going
to achieve some level of equity and reduced disparities, that there has to be some level
of detailed and precise stratification of groups of people into subgroups. And that
by doing that we could perhaps in appropriately targeting those subgroups, we could have better
health than we could at some measure that might be more cost-effective and reach a larger
community, but maybe not have quite the impact. Do you want to talk about that issue of equity
and access disparities? Thanks. Muin will go first.>>I mean, equity, access and disparities
are at the heart of the public health, I guess the public health mandate. And if — just
to repeat some of the same arguments that I just elaborated on, that for precision medicine
to succeed and succeed widely across the population it’s not enough to do the discovery. Even
if the discovery includes a wide cross section of the population. Because I know the current
precision medicine initiative is trying very hard to be inclusive across the population.
But also dealing with the equities of implementation of the new discoveries. And as I said earlier
— I mean, I showed some data that shows even with the things that we know what to do, like
with any new technologies, they’re not well implemented across the population. So could
we use — if we put genetics aside for a minute, some of the new analytics and data science
and visualization, could we be able to show more robustly and more persuasively some of
these disparities that are rampant across the population for which resource allocation
needs to occur? So I think I’m not too far from Sandro on that point. Because it’s at
the heart of the argument that there is disparities that need to be dealt with.>>Dr. Galea?>>Yes, I don’t disagree. I think the only
thing I would add is that the question underlines a tension that I don’t think we have been
fully honest in grappling with about the society. Which is a tension between advancing efficient,
targeted efforts that improve the health of a few and the inevitable trade-off that results
in terms of widening health equity gaps. And will high-end medical therapies based on genetic
and molecular targeting result in potentially better clinical care for a small subset of
people who get really sick? Probably. Will that also widen health gaps? Almost certainly.
Is that a price we’re willing to pay? I don’t know that we have discussed that as a society.
And I also don’t think — the discussion playing field is not level. And for obvious reasons.
And that there are many special interests that push such discussions in a very particular
way. So it strikes me as almost canonical that these approaches, as with any other high-end
technological approaches, will result in widening health gaps in the short- and medium-term.
Whether or not they have success in improving health in the long term and eventually in
narrowing of health gaps remains a subject of debate.>>Okay, taking a question from online. Would
you say that familial hypercholesterolemia, a common genetic disorder affecting one in
250 people would be a good example of what precision health could mean for heart disease
prevention at the population level?>>Can I take that one, Sandro? Because –>>All yours.>>Yes, our office at CDC has been — has
promoted and put familial hypercholesterolemia as one of these tier one green applications.
It didn’t show up on my slides today because I’m at the NCI and the focus is mostly on
cancer. So let’s take FH. FH is an interesting story by itself. It’s the genetic disease
that’s not rare; it’s actually the most common genetic disease. We have data that shows from
[Inaudible] that it’s about one in 200, 250 people in the U.S. have it. Very high, early
premature heart disease risk. But that accounts for less than 5% of all heart attacks. So
in terms of the magnitude of the burden, it’s not that big in terms of a population attributable
fraction. But there are thousands of patients who have FH. And the relatives, who could
benefit from early detection and treatment with statins that are not being cared for
right now. And I think using these precision tools to find them and, you know, registering
them. And there are different studies that have been shown recently to be able to track
FH at the population level is, yes, an example of a precision approach at the population
level. Similarly to what you can call newborn screening as a program. Newborn screening,
I mean, we screen four million babies every year to find 10,000 or so who have one or
more genetic conditions like PKU. That’s truly a population-wide effort that benefits the
few that otherwise would not have benefited from health care by themselves. Or they could
have had mental retardation. So it is an example of precision public health. [ Silence ]>>Another question from online. Muin, I think
it’s directed towards you. “Can you elaborate on the potential of epigenetics to bridge
the approaches of social, environmental, behavioral, and genetic factors’ influence in population
health?”>>Well, I mean like with all technologies,
there is both hope and hype about epigenetics. And I’m here at NCI where there are many more
epigenetics experts than I am but I don’t see anyone here. But I want to refer people
to a blog I wrote a couple of years ago after I gave a talk at a public health, the Association
for Tape and Editorial Health Officials annual meeting on why epigenetics is so appealing
to public health. You know, when you talk about genes, you can’t change your genes and
their effects are small. But epigenetics is one of those areas where truly the environmental,
social determinants of health really come face-to-face with the biology. And, you know,
both from the experimental studies and even some of the human studies, we know that genes
can be turned on and off, especially at the right time in growth and development. Now,
are the applications here? I mean, there are a few applications. It’s mostly the promise
of using epigenetics and epigenetic markers as a union between nature and nurture. Well,
I’ll stop there and if people want to know more info, I’m happy to correspond to them.>>Sandro, I don’t know if you have anything
else to add?>>No, that’s fine. [ Silence ]>>I think in the absence of any additional
questions, we should give both of our speakers a few moments for a couple of last words.>>This was a good discussion today, Sandro.
I appreciated your willingness to engage in this discussion. I’m hoping that this dialogue
will continue and some of the challenges that you raised will be looked at very seriously.
Both from a funding perspective as well as societal perspectives and so on and so forth.
Because at the end of the day, all the new tools and technologies with all their promises
are not going to lead to improved population health unless we use them and we use them
judiciously at the right time. And do not forget about some of the other things that
we have to do as well. Thank you.>>Yes, thank you for having me; I enjoyed
the discussion. My feeling about this is that there are a lot of very good scientists. And
health thinkers who are engaged in this. And perhaps this is why I started my presentation
by casting myself in [Inaudible] position. I’m deeply committed to the goals and aspirations
of science towards improving health. And my commitment and beliefs is that we need to
have this kind of conversation to try to not just end where we should be, and figure out
what that space is. So I’ve enjoyed this conversation. Thank you.>>In these last moments, I’d like to take
time to thank Drs. Winn, Galea, Khoury, and Kennedy for their time. Thank you to all of
us who joined today in person via the web. This session has concluded. You may disconnect
at this time. [ Applause ]


One thought on “Will Precision Medicine Improve Public Health?

  1. This webinar series is a great initiative. With whatever I am seeing and learning, Precision Medicine will surely improve Public Health. But it won't happen overnight. We are talking about complex diseases like cancer, diabetes, etc. It will take several decades before we can expect significant impact from genomics on public health.

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