Information and a lot of activity that you
have been personally responsible for in just remarkable ways. So it’s a real privilege for all of us to
have you here at the American Society of Human Genetics and for me to be able to be your
inquisitor for the next half hour or so, after which two other inquisitors will turn up. No, actually it’s a friendly group, don’t
worry. And I think we have also now started broadcasting
this live on Facebook, so whatever happens here will be kept in posterity, so try not
to flub it too badly. There are a few people who have once suggested
to me that perhaps because of our physical resemblance that you and I are the same person,
but I hope all of you who are here today can put pay to that rumour because unless one
of us is a hologram we are clearly not the same person, but it’s an honour to be considered
in such a way. So I guess let’s start with HIV because
here we have this incredible pandemic which we’ve known about now for 37 years or thereabouts
and which clearly has been in the human population longer than that and which we have made first
of all significant strides. Today someone who is born in a country that
has access to antiretroviral vaccines and turns out to be HIV positive let’s say age
21 has almost a normal life expectancy and some of the younger folks in the audience
who were not here in the late 80s and early 90s may think that it’s always been that
way, but it was certainly at that time a death sentence. So great progress there and we’ve learnt
other things that have been particularly encouraging in terms of how we can by driving viral loads
down to very low levels essentially reduce the transmission as well. But as Tony Fauci wrote about in a JAMA article
just a week or so ago, the idea that we could actually end the HIV pandemic, that we could
in fact usher in an Aids free generation seems very difficult to achieve, maybe even impossible
without a vaccine. I think the challenges of trying to achieve
that in resource poor countries or in other countries for that matter without the vaccine
seem almost insurmountable. So first of all do you agree with that and
second of all, how are we doing on the HIV vaccine strategy, because there’s a lot
of activity here? Are you optimistic that we are on a glide
path towards success? Well the HIV story is as you say definitely
a glass half full. We don’t yet have the magical tools that
we want and yet in rich countries the ARV treatments are amazing. You know, the innovation there has given us
a lot of really good solutions and the drugs are priced at less than $100 a year, so that
access although it started out not being great, now it’s gotten to a really great place. And this is an area where US generosity is
pretty amazing. The PEPFAR programme plus the US portion of
global fund has… The US government spend over six billion a
year keeping over 10 million people alive because of access to these ARV drugs and the
challenge is that until we get a very good preventative tool which a vaccine is likely
the only thing that’ll really fulfil that, the disease is just being held in status,
that is the population growth in the 16 to 24 year old age group in the African countries
where unfortunately most of the epidemic is, you have so much population growth that we’re
not really cutting the infection rate with all these interventions that we’ve had and
so it’s just staying the same. If the money is cut unfortunately we will
go back up to the peak which was back in 2006. And so we’ve got to keep doing a better
job with the tools we have today and there’s a lot of innovative things that PEPFAR is
doing around that about getting out to young women and getting them to protect… Change their behaviour so that they’re less
likely to get the disease. But without a vaccine the numbers won’t
change dramatically and there’s many vaccine leads. I mean the amount we learned about the immune
system because this is a disease of the immune system I think is pretty phenomenal, you know,
learning about antibodies. There are many paths that look promising. I mentioned one called CMB. There’s an Ad26 vector based approach that
looks very promising and there’s three or four others and so I’m optimistic that there’s
a good chance that in the next decade we could have such a tool. There’s no guarantee and it certainly won’t
be in the next six or seven years. How good does it have to be? Right now we have the 702 trial that’s underway
in South Africa which is trying to take what was the first actual signal of some response,
which is a lot different than having no signal of response from the RV144 trial, and now
bring that forward with the new Ativan [?] and some other boosts and all that, do you think
it’s going to work? We won’t know for a couple of years. Well, you know, you and your organisation
NNH and my Gates Foundation are two of the big funders. Yes, we’re you’re bank. There’s two potential benefits of that work;
one is if it got to like a 50% effect then it would be a tool that we would want to deploy. That’s the best case. The second case is that it really confirms
the hints about the biology that were in that earlier trial and so that we really lane a
roadmap out for okay what should the antigen look like, you know, the end- antigen done
a certain way that is way better than other antigens and so it’s a very important trial. Like all these things it always takes a little
bit longer than I wish it would to get it going, to get people enrolled in those things. So it’s fantastic that now we have that
underway. The other candidates are, you know, maybe
three years behind that at best. And what about broadly neutralising antibodies? This seems like it’s such an exciting opportunity
to discover there are people who spontaneously produce these, a little too late for it to
be helpful to them in terms of fighting off the disease, but clearly they’re making
antibodies that look as if they would neutralise a vast percentage of HIV genomes that are
around there and why can’t we just come up with a vaccine that causes all of us to
make one of those and get it one with and then we’d be all where we need to be. Yes, the quality of these antibodies, both
the ones that have been isolated in humans and now in things like cows, these are incredible
antibodies, so that insight you can think of three ways that could get out and have
an impact. One is that the antibodies could be cheap
enough and have a long enough half-life that you could do passive immunisation. That looks to be tough but there are people
looking at that. A second is some incredible people that include
Scripps and many other groups including NNH is to actually figure out how you elicit those
antibodies and because they’re highly hyper mutated antibodies getting the immune system
to go down the right path independent of your immune type it’s a wonderful scientific
problem and they are making progress. But you can’t do it in one step. No, it’s a multi-step thing and so… Take the immune system to graduate school
here. Is that kind of what you’re doing? You’re right. And the third approach which, you know, may
be the wildest of all is an antibody factory where you would, you know, give somebody AAV
in the muscle and then it would be generating the antibody, but understanding all the safety
issues about that how you’d get that pushed through. That’s probably why the genetic editing,
you know, whether it’s the rare diseases or sickle cell disease, the fact that the
genetic editing tools have been worked on and, you know, still lots of tough, tough
problems, but that has a lot of promise. In fact as we were talking to the sickle cell
disease people about what the profile for gene editing they would need, it was interesting
that there’s a lot in common of what you would need to do an HIV type cure using those
tools. So, you know, it’s not imminent but you
know the work that’s been driven has that potential. What do you see right now as the greatest
biological threat to our world? Is it something we’ve already talked about? Well if you model pandemics, the fact that
people move around so much more today than they did in 1918 means that, you know, a flu
which you know call that 30% of the pandemic risk is a specific pathogen that we actually
know pretty well, the rate at which it would spread would be phenomenal and society is
very dependent on supply chains, you know, highways, communication systems aren’t designed
for the type of panic and desire to move that would result. And so I’m not saying it’s very likely,
but I do feel the world is quite underprepared for that and I’m hopeful that some of these
tools will eventually give us the ability to have the kind of quick response that you’d
want against that. Or a universal flu vaccine where you don’t
have to have a quick response because everybody’s already immune. That would be ideal. In fact a number of studies we’ve done have
shown that flu… A mother getting flu during pregnancy has
a significant effect on birth weight and therefore on what happens with that child. Now these are in equatorial regions, so until
we get a… Using the flu vaccine doesn’t really work
that well in the equatorial regions because you don’t get this lead time like we do
in the northern hemisphere. But a universal flu vaccine I think would
be brilliant because it would reduce pandemic risk, I also think the human health benefit
would be larger particularly in developing countries than we’d expect. So many people looking at the epidemiology
would point out that the fastest growing area of morbidity and mortality in low and middle
income countries is now the non-communicable diseases, things which maybe you could say
were adopted by Western lifestyles become more prominent – diabetes, heart disease,
obesity and cancer. That seems in many ways to be a surprise to
some people and it certainly doesn’t seem that we have at the moment a worldwide sort
of organised idea about how to approach those issues the way that we have at least to some
degree with infectious disease. Obviously Bill and Melinda Gates Foundation
thinking about global health and about every life having equal value must also be thinking
about where to go with those, even though that’s not been the area of main focus. What are your thoughts on NCDs? Yes, I’d say that I’d encourage everybody
to go to this IHME, International Health Metrics and Evaluation. It’s a institute that’s under the University
of Washington where Chris Murray and the team he’s built track a global burden of disease
and it’s got great interactive tools where you can sit and see by country, by time period,
you know by gender not only the direct causes of death, but the disability. And this idea that chronic diseases are the
biggest growing problem is super evident in rich countries, but it’s absolutely true
that in India they have as much chronic disease burden as infection. They’re right at that kind of cross over
point where unfortunately they have serious issues still in infectious but already very
serious issues in chronic disease, including diabetes. And so the world is going to have to be very
innovative. The unique role that we think of our foundation
having is health equity, so when the rich world comes up say with an HPV vaccine which,
you know, for cervical cancer works very well or Hep B for a type of liver cancer then it’s
really our role to make sure it gets cost reduced and made available worldwide. And, you know, so we need great breakthroughs
for Alzheimer’s and diabetes. Heart disease is a fascinating one where Tom
Frieden who was the head of the CDC came to us when he finished that job and said he wanted
to take on somewhat are now low cost blood pressure control tools and other things related
to heart disease. Salt for instance. And get those things out into the developing
world. And so Michael Bloomberg, Chan Zuckerberg
and our Foundation funded Tom who’s been a great partner in all sorts of things to
go really now take heart disease and show us how we can get total health equity there. Likewise tobacco cessation is one that we’ve
been very involved in, you know now trying to figure out where e-cigarettes and warm
tobacco should fit into that effort. So this is an audience obviously that’s
particularly focussed on the science of genetics which has made remarkable advances technologically
and in terms of applications to medicine, maybe particularly one could say in cancer
and also in birth defects. And this is also a very international audience. Many of the people here are not from the United
States. And I think all of us who have a sense of
the importance of global health, which you of all people I think have been such a beacon
for the importance of, would like to make sure that our science of genetics and genomics
is also finding its way into those places where it could be clearly providing a benefit. We talked about that this afternoon about
sickle cell disease since the vast majority of people with that condition do not live
in developed countries but they live in Africa and India, but there are other areas as well. Cancer where clearly the opportunity to have
cancer genomics to tools associated with some choice about therapeutics could begin to be
pretty valuable as well and yet the barriers can be quite substantial, I don’t have to
tell you, in terms of that kind of technology being exported to circumstances where there’s
not a lot of infrastructure. Many of us dream though about that changing
and we could look at many of these countries and say well they’re still struggling, at
least they are on some sort of a positive trajectory. Many of them are, not all, in terms of their
GDP beginning to take an upwards swing. If we could sort of look forward over a decade
or two, what’s the path that we ought to try to get on so that if we were having this
discussion in 2037 it would look different and there would be more empowerment of the
places where such benefits could be achieved but which at the present time we’re not
really situated to be able to embrace them? Yes, when we think about different countries
it’s probably best nowadays to put them into three buckets. In the 1960s it really was the developed world
and what was nicely called the developing world which meant the poor world. Today the good news is that most of humanity
lives in the middle income countries, so you know China, Brazil, India is kind of on the
boundary, and then we still have some very poor countries. Those middle income countries are in some
ways for health the most interesting places because they can’t afford to do help like
we’ve done. As we’ve discussed their disease burdens
are every bit as challenging in a few cases like obesity and diabetes it, you know, looks
like there’s even some genetic predilection that will make it even tougher for them. And so they are going to be looking for effective
solutions and in some ways they’ll be less conservative and that could lead to some mistakes,
but they really need with ageing populations and that chronic disease burden, they will
need to adopt innovative technologies. So I’m hopeful we don’t get off down the
path we got with genetically modified organisms where there’s a backlash and a fear and
a lack of understanding because the potential human health benefit for those middle income
countries if these tools can be made fairly low cost is just, you know, really mind-blowing. And, you know, I’m personally very optimistic
about those things, but how we tailor these solutions, eventually see approaches that
are not 300,000 per year type things that even the US is going to have a heck of a time
affording, you know, that type of cost. It’s just. It’s great and, you know, I’m a huge believer
that the US does the world an incredible favour by having its medical market fund well between
the taxpayer generosity for funding the research which is phenomenal and the market funding
the private companies, we do an amazing job for the world. But it means that the particular profile they’re
going to need including that cost profile, that’s a huge challenge for us. Indeed. I want to ask you a little bit about education. It was a lot of fun this afternoon being part
of these sessions that were put together by ASHG to talk about topics that you’ve mentioned,
epigenomics and sickle cell disease and something about population genetics and clearly you
are somebody who is focussed in about as intense a way as I’ve seen in anybody about learning
new things, about trying to fill out all kinds of areas of science and medicine and public
policy and public health that are relevant to your mission. And at the end of the epigenomics session,
I think you said it again here, it was clearly really complicated and you got a good sense
of what the complications are but you thought I need to go and find out more about this
and I’ll go and find an online course you said. So everybody in this audience needs to be
doing that same kind of thing on all kinds of topics that we don’t necessarily know
enough about. So how do you do that? Teach this group here about how you do your
continuing education. How do you find the good stuff in the time
you’ve got available to fill your brain with all the information that you seem so
familiar with? Well this is the best time to be alive in
terms of learning new things, whether it’s, you know, reminding myself how to compute
correlation so I can help my son with his statistics class or, you know, learning enough
meteorology so I understand hurricane severity and what… Why that’s going up with climate change. The number of great lectures that are out
on the internet is unbelievable. I would say that the most straightforward
thing is going to the courses from the Learning Company because they’re of uniformly high
quality. The economics courses, the history courses,
the science courses like the astronomy course, they have the best geology courses, the best
meteorology courses and they’re taking the best university professors. And, you know, you kind of fall in love with
these people because they’re so good at explaining their things and they love the
topic that they’re working on. And then you can supplement that with other
online materials. It is a time where, you know, like in physics
the explanation there that’s a case where the web stuff is really quite phenomenal. And how about public education? You have put a lot of resources into trying
to improve the state of K through 12 education and I can gather from some of the things I’ve
seen that that’s not been an easy task and we still have I think lots of circumstances
that are not that different than what turned you off about biology where people spend their
time dissecting worms instead of talking about really interesting principles of life. By the way that’s what turned me off to
biology and sent me into chemistry and physics for a few years before I came back and realised
that I’d missed out on the really good stuff. But I think the really good stuff is still
maybe a little hard to find in an awful lot of curricula and as a result we still have
serious problems in this country just in terms of literacy about science and particularly
about biology and… How are we doing in terms of trying out creative
ideas which I know your Foundation has put forward to try to see if we could turn this
around? What do we need to do to get our country,
which ought to be you know really performing well here, out of the basement from where
we currently are if you assess what 15 year olds know about science? Yes, the US is a paradox. We still have by far the leading universities
and, you know, the scientific knowledge that’s coming out of that to benefit the world is
just incredible. And yes, you know, the UK, the rest of Europe,
China see that, they’re doing some of those things but the US lead whether it’s in biology
or computer science or many other fields although those two in particular is an incredible thing. But if you look at how we’re educating the
population, high school drop outs, math scores, reading and writing scores, we’re actually
getting a little bit worse even as we spend a higher percentage of GDP on education and
a lot of that is the contrast between the inner city schools and the suburban schools. The suburban schools just took those by themselves
or the best charter schools or the private schools. The US is every bit as good as the other exemplars,
which are mostly Asian; South Korea, Singapore and China are numbers 1, 2 and 3 and if you
just take the trends of some of these Asian countries, you know, they’re still going
up. Now that’s not to say that their system
is perfect. There’s a lot of rope learning, there’s
a lot of pressure and so and culturally we’re unlikely to mimic all those things that they’ve
done, but particularly in math and science making sure high school teachers make those
things interesting, using the new personalised approaches that show a great deal of promise
and so I don’t think the benefit of technology has yet had an impact on schools. Yes everybody can go look at Wikipedia, that’s
super nice, but the idea of tracking which students are falling behind, giving them personalised
learning that’s interactive enough so that they can still feel a sense of progress and
get the special attention they need, that’s still in front of us and so I’m optimistic
about that. But it is fair to say that in global health
our Foundation working with others conceived dramatic impact, even beyond what we would’ve
expected, whereas in our US education work those overall country wide numbers have not
moved. So although you can go see a few public schools
and a few charter schools doing some of these new things that makes me hopeful that if we
can scale that up we will see dramatic improvement. You know, it’s still hard to know. Are you worried about anti-science sentiments
in this country and whether they’re getting worse instead of better? Yes, I generally think things get better,
so whenever people give me counter examples I think let me go study that. So I hope not because if you look at the jobs
that the economy’s generating, you know, we’re a high cost economy and so some understanding
of science, even to be, you know, a high level nurse or, you know, to work in a technology
type job you’re probably going to have to not only have some understanding, but you
have to have some fascination. You have to find it fairly interesting. And our high schools are currently making
math and science sort of forbidding subjects that a lot of people shy away from. And so the very way that math is taught or
people are drawn into science, I do think there’s room for creativity in that. And it is important because the gap between
where the jobs are going to be and how we’re training people is a very big gap and so you
get this disappointment that can create even in the political realm sort of this sense
of okay you let us down, but it’s very predictable unless we improve education that there is
going to be that mismatch. So in a minute we’re going to bring Nancy
Cox and Pete Scuderi [?] up here. Before we do so I guess Bill, I just ask from
your perspective with your very broad ability to survey across a whole landscape of what’s
happening in biological science and medicine and global health, two things; what are you
most excited about and what are you most worried about? Well the progress is amazing. I mean just take the microbiome. Oh my. Okay, maybe it won’t cure everything, but
if it does a 10th of the things that various start-ups are working towards, curing… Alzheimer’s, diabetes… Alone, yes, depression, I mean why not. Heart disease, depression, nutrition. You know we have a result that the risk per
act of acquiring HIV varies by a factor of 10 depending on your vaginal microbiome and
so if we can intervene in… And it turns out Western women have more of
the protective type over 70% whereas in Africa less than 20% have the protective type, and
so if there is an intervention that can make a big difference. It won’t end the disease, but it will really
knock the numbers down pretty incredible. And that’s just one, you know, microbiome
insight which without you know sort of massive genetic information, you know, what were we
going to do, just stick the bacteria under the microscope and watch them swivel around. I mean, this… The numbers involved and, you know, thank
God the digital world is sort of giving us infinite storage and computation because geneticists
are one of the few people who can fill up those discs. And we’re doing it. So thank you for all of your data that will
allow these Cloud computing facilities to grow with no end in sight. I have a great future ahead, man. And so I’m… You know, I think we’re getting fundamental
insights and if you put the brain aside where it’s hard to predict the timing for a lot
of key diseases the next 15 years I think will be pretty amazing. I hope the brain, Alzheimer’s and other
things get into that, but I think that one’s a little harder to predict even though it’s
very important. I’d say my biggest concern is that a lot
of these things whether it’s policies about genetic editing or policies about climate
change or, you know, having open dataset so that we can advance science as fast as possible,
they really require a global perspective. Even though the US on its own preeminent and
amazing the global cooperation, including with the poorer countries developing their
scientists, having them on site where they can see what needs to be done, and so anything
that kind of threatens that sense of, you know, humanity working as a whole, you know,
doing things like the PEPFAR programme to jump in, anything that threatens that I think
is very damaging to what can be done. And, you know, it runs counter to my general
optimism so it puzzles me greatly. I’m glad you’re puzzled because I have
a feeling when you’re puzzled something happens, so. So let me invite Nancy Cox and Pete Scuderi
to come up and join this conversation because they are bringing with them questions that
you all have submitted over the web in the course of the last few days and I’m sure… Because I don’t know what they’re going
to ask us about, we’ll have an interesting next chapter in this hour and a half conversation
with Bill. Okay, alright so I’m going to lead this
off. Okay, Pete. You seem to have managed to capture a lot
of the questions that the audience already posed to Bill, so we’ll see how this goes. So the first question came from Barcu Darce
[? ]from the University of Wisconsin. The field of genetics has seen huge changes
over the past 20 years especially due to whole genome sequencing technologies. So now that we’re all trying to become data
scientists, what do you foresee as being the next big thing to change this field? So I’ll pose this to either one of you,
Francis if you want to take this first. Well I’ll start but I’m sure Bill would
have things to add to this. So I think we have to recognise, as was just
said, that we have become a major producer of large datasets that are going to be of
incredible value for understanding how life works and how disease occurs and we should
not limit our perspective about that just to germline genome sequences, although that
is obviously an area of great interest, but also all the other kinds of omics that are
going to be coming along. We heard the microbiome and you can make a
big dataset with microbiome without hardly trying and all of the things that one can
do now with circulating RNA, but whether it’s free RNA or whether it’s RNA sic done on
peripheral blood mononuclear cells and certainly exosomes that carry around nucleic acids. All of these things which not only you would
want to sample once, you’d want to sample those repeatedly and follow over the course
of time what’s happening to an individual as a window into their biology and perhaps
into whether they’re at risk for something or even starting to develop an illness, all
of these omics opportunities, and I should certainly say that’s not just nucleic acids,
that’s metabolomics, that’s proteomics, those are going to be phenomenal opportunities. And we need to be sure that we are not missing
the chance as those datasets are collected to put them in a place where lots of researchers
can learn from them, compute on them and those are going to be datasets that are much too
big to sit in anybody’s server, so it’s not going to be on your server or mine. It’s going to have to be in a place where
it can be accessed and that’s going to have to be in the Cloud and that means we’re
going to really have to re-tool ourselves in terms of how we do those analyses because
not just the data but the analytics will have to be in the Cloud as well. You’re not going to be able to download
all those petabytes to your machine and work on it. It’s not going to work that way. So it’s a transformative opportunity but
it is also a responsibility that all of us who are generating those kinds of datasets
think about how to make sure that they’re sustainable and they’re accessible and they’re
fair for everybody who has something they might want to learn from them. That’s going to be true in human genetics. It’s going to be true in any area that uses
human genetics, certainly including infectious disease. And the era where it is okay to basically
sit on your own dataset for many years trying to mine it and then re-mine, then re-mine
it again, that era is over and I’m certainly speaking as the NIH director here, we now
have quite a lot of ways to encourage good behaviour in this regard, some of which are
in fact less pleasant, some of which are just that we try to provide appropriate incentives. I’ve often said that trying to manage the
research community many people have concluded is really like herding cats and it is like
herding cats, but guess what, I’ve got a big bag of cat food, it’s called the NIH
budget and if it’s appropriately applied it can actually encourage some pretty good
things to happen, so anyway. But Bill, data access. Well I’d say the next frontier, and this
will show my bias as a software person, is to think of DNA as much more of a programme
than as a set of constants. You know, as I sit and listen to people talking
about, you know, this enhancer talks to this promoter that, you know, loops around to touch
this other thing, you know that is software. And so whether we could build these software
models by hand or whether we have to just gather massive data and machine learn into
this more symbolic software type approach, you know, the dynamics of what are going on
to drive expression will need rich symbolic models. And so, you know, once again the fields of
computer science and modelling and the field of genetics will have to have these polymathic
people who know both of them take this to the next frontier. Yes, I mean just to follow up on that, I mean
Francis you were talking about just generating these massive datasets and that’s showing
no signs of slowing, right. We keep generating more and more data and
we use, you know, computers vigorously [?] to find transient meaning in that data and analyse
that genetic variation. But I think all of us are still struggling
at that, right. It’s a huge amount of data and, you know,
we’re constantly looking for I think new advances in computing that enable us to really
find meaning in the data. Is there anything coming down the pipe that’s
kind of going to help us out and help us to advance human health and disease with respect
to technology advancements? I mean is there AI come in, is there other
things that we can look forward to? I think this is where I’m supposed to say
machine learning and then Bill will say no way man, that doesn’t answer any questions
unless you already have a lot of data. Do we have enough data to say that that’s
going to be the solution? I do think we’ll get there. I mean the idea of being able to look for
patterns without having to know ahead of time even what you’re looking for is enormously
appealing. It’s not so appealing when you get the answer
but you don’t know why and that’s a bit of a challenge about it. But I’m sitting next to somebody who really
knows about this stuff. So yes what about it, is AI going to solve
all the problems in biology? Well it’s a tool. You know, did mathematics solve all the problems
in physics? Sort of. Sort of. It’s a pretty good framework. We couldn’t solve the equation. Yes, solving the equation is a form of truth,
so you know thank God for mathematics. And so yes the tools of machine learning will
be helpful to us. Right now in machine learning the idea of
taking symbolic understandable things and how those combine with these pure sort of
data driven opaque, you know, 41 level vision system type system, the ability to explain
and diagnose what’s going on in those things, that’s a very state of the art problem. You know, for example if the machine is recognising
cats to say okay what do you think a cat is, what characterises a cat, that’s a symbolic
inquiry back into the machine learn thing. So there’s a lot of progress that has to
be made in that. It is stunning how quick the progress has
been in the last six years versus the 20 years before that, that we reached a threshold of
computing and understanding with the Cloud techniques that will be very, very key but
there’s a lot to be done. I mean the paradigmatic problem that I like
is give the computer a biology textbook and then give it a biology test. We don’t know how to do that today. You can ask what the words in the book were
but in the sense of how you represent knowledge we’re nowhere. Vision and speech which were viewed as paradigmatic
problems, those are solved problems. We are better than humans and we’ll continue
to get better, but those are kind of low level compared to true reading and understanding. This is like a touring test but a different
kind of touring test. Right. Can the computer actually understand at the
level of knowledge not just symbols. And that should be tractable. I mean one of the paradigms Microsoft developed
what’s called the alter ego where it reads things and helps you get things done, but
the idea of, you know, reading all the medical articles and trying to find information that’s
one a lot of people are working on, which would be great. It would be but we’re still waiting. Yes, no in the next decade I predict we’ll
make progress on that. Okay, well this is a synthesis of a question
from a number of people. Both of you in different ways have moved outside
the traditional comfort zones of scientists to engage with broader communities. So Francis, you’ve had to learn to work
with presidents and politicians, you engage with businesses in your work. Mr Gates, you have worked with businesses,
you’ve worked on global health, you’ve worked in education. Do you think that there’s a need for scientists
to be more engaged in public discourse and, if so, what is the best way for human geneticists
to engage in that discourse and do you have any advice for us all on how to get outside
the science bubble? Go ahead Bill. Well I think there’s always this concern
that people jump like whenever you talk about AI people jump to the control problem and
don’t look at the incredible benefits. I mean I’m not saying we shouldn’t talk
about the control problem, but that is, you know, probably lifetimes away and you know
there’s a lot of issues and benefits that come before that. But genetics people often jump to the designer
baby type question so quickly and, you know, they don’t think about hey sickle cell disease
and, you know, what an incredible human tragedy that is or even as I mentioned getting plants
and livestock that make the healthiness and nutrition of everybody in Africa even with
the challenges there dramatically better. You know I’ve been… A big part of my work at the Foundation is
meeting with government leaders in Africa and talking to them about their health systems,
which isn’t often a priority and, you know, saying hey here’s how you compare, there
are other countries at your level of wealth who do it far better than you do and I’ve
been amazed at the reception that I’ve had. You know, they’re definitely interested. So scientists with credibility can… And people bringing science or measurements
of credibility can have a very positive effect on things. And I actually think that’s not something
for a scientist to fear as oh my gosh they’re going to make me talk to this particular constituency. It’s actually quite satisfying if you kind
of approach it with a clear idea of what you’re trying to accomplish. I certainly never would’ve expected to spend
as much of my time as I do in those kinds of conversations with politicians and other
constituents, certainly also working now a lot trying to build partnerships with advocacy
organisations, with philanthropy like this guy, with industry, with the congress for
instance. I mean if you want to see the success of American
biomedical research, the US Congress is basically the place that’s going to decide what the
resources that the Federal Government is going to put into this are going to look like and
I can’t tell you how important it is when those decisions are made that the members
of congress actually have some sense about what’s being done and that it’s being
done not just in Bethesda Maryland but it’s being done in every state, in every district
around this whole country including places that they drive by when they go home on leave
from congress. Getting that message across and getting them
to have a chance to actually talk to a scientist maybe in their own district who’s doing
an experiment they’re excited about makes all the difference. So I hope all of you who have not had the
opportunity to invite your elected representatives to come to your institution and tell them
what you’re doing will do so. It’s the most important thing we can do
I think to try to encourage support for all this. Obviously that’s not the only audience. It is an important one. I probably met with more than 400 members
of the United States Congress in the last four or five years one-on-one talking about
an area of science that’s interesting to them. I can’t think of a single one of those that
I walked out of thinking oh that went badly. It always goes well because the story is so
compelling. What you all do, what we all do is the most
amazing story that they’ve heard that day because mostly what they’ve heard is a lot
of special interests and a lot of political things that aren’t going well and to walk
in and say let me tell you about discoveries that are happening right now that are going
to potentially transform our understanding of life and have this potential to do something
about diseases that we currently don’t have answers to, they want to know about that. And then you can tell them about how this
is also going to stimulate the economy in their state. There’s some good statistics about that. And also how it’s going to maybe bend the
healthcare cost curve that they’re really worried about and encourage the continued
success of American biomedicine because we’re such an important part of this ecosystem that
involves not just public support but also private support and philanthropy. That’s such a winning story, you can’t
lose if you sort of package that right and if you do a little homework to find out what
are the interests of the person you’re talking to. So as you can tell I get a bang out of this. I am not a regretful person at all when I
have a chance to have those kinds of conversations and I would encourage all of you, figure out
who your best audience is. Now maybe it’s not the member of congress. Maybe it’s a high school that’s struggling
and trying to figure out how to get the right kind of life science into place. Many of you are part of DNA day, this effort
that brings people together on April 25th but has reverberations that go throughout
the year, sort of figure out that it’s worth putting a few percent of your time into that. You’ll get more out of it than the people
you speak to, but they’ll get a lot out of it too. That was my speech. Thank you for asking. Do you have another one? So, yes, this is a question from a combination
of [inaudible] and Dechal Geldman [?], synthesis of a question. So we’re kind of playing catch up to have
sufficient genome interrogation of diverse human populations so that we can avoid creating
new kinds of health disparities around genetics but also recognising issues around health
literacy and science literacy and financial access to precision medicine. How would you prioritise the activities needed
to move as rapidly as possible towards what Mr Gates described as really achieving the
larger goal of high quality precision medicine for all and what parts of those activities
do you think our society can be most helpful in in achieving those goals? Both of you. Well I think the term precision medicine sometimes
is taken to the point of saying okay we’re going to have personalised medicine and, you
know, individual drugs for individual diseases and, you know, I don’t think in, you know,
the next 30 or 40 years that’s the right direction to go. We still have major diseases, diabetes, Alzheimer’s,
you know, HIV, malaria, that we need to make sure the resources are going into those. And in terms of how you create products that
you can assure safety on, it would be… It will be a challenging problem to get to
that. So, you know, I still feel like there’s
big, big things that we need to keep our attention on and, you know, I’m often looking at the
incentive system and saying okay is cancer about the share it should be, are orphan diseases
which got almost nothing now are getting a lot, you know, is that at that right share. So making sure the incentive system is still
making it attractive to go after these big things, that’s super important. And so the US Congress not only sets the NIH
budget which is sort of the world’s health research budget. I wish I could say it was a third of the world’s
health research budget, but it’s way over half particularly if weighted by effectiveness. They also set the drug pricing policies that
determine where those scientific discoveries are taken by both biotech and pharma, you
know, what things they go after and what they do. And although it’s, you know, great to talk
about tuning either of those things, it is important to acknowledge the system is in
a large part working extremely well today, that the number of great companies that are
being started up, the potential solutions that are coming along, and so I hope people
are careful as they think about toying with either of these things. And perhaps drawing the rest of the world
in to do more of its share, particularly these rising middle income countries, you know I
hope we maintain the positive elements we have. Yes, I think precision medicine for me does
not imply that you have to sort of develop one drug for one person, but rather that if
you have a menu of interventions that you try to figure out which one is going to work
best for which of the many thousands of people who need that particular intervention. I was heartened by the recent publication
on Warfarin in pharmacogenomics showing that actually there is a compelling story here,
that using genotyping improves outcomes in the administration of this commonly prescribed
drug and there are many others I suspect where that would be true if we had the data. So the question though I think is also asking
about health disparities and what about the people in the rest of the world but also here
at home who have not been the beneficiaries of some of these advances and are not the
beneficiaries of the way our healthcare system works. I think one of the things that we as researchers,
and that’s I guess the hat that I’m pretty much required to wear, I can’t fix some
of the other aspects of what’s wrong with our healthcare, but as far as research we
really should be in everything we’re doing paying attention to this issue about underrepresented
groups and have we in fact reached out and been welcoming to them, both in terms of being
participants in research and being part of our workforce. When I come to this meeting I’m always reminded
that we have a ways to go in terms of the diversity of people that we have made it seem
attractive to come and work in the field of human genetics. We’re still way short of where we need to
be if we were going to be taking full advantage of the power that a diverse workforce in terms
of its team effort has been clearly shown to demonstrate. And likewise in our participation we are a
lot better than we used to be in terms of research participation by groups that are
not the majority but we could do better and in this regard I have to give a quick commercial
then for all of us, this unprecedented programme that is underway right now in a beta test
mode to enrol a million Americans in longitudinal prospective cohort study that will involve
collection of bio specimens as well as electronic health records, lots of personal information
that they will record, wearable sensors that they will walk around with. This is going to be a massively interesting
dataset and it’s going to be set up so that qualified researchers can have a look at it,
coming back to Pete’s question about how do we make sure we’ve set this up in a way
that it empowers everybody. This is going to be done that way and the
participants are going to be at the table. But importantly, we have made a commitment
that at least 50% of the participants in that study are going to be from underrepresented
groups and that means not just race and ethnicity, but also socio-economic status, also people
from rural communities who tend not to get invited to these studies. So watch this space. When this launches which is expected to happen
right now in about April there will be an opportunity to bring all kinds of folks into
this tent which we think is a pretty exciting one and a lot of people that you maybe haven’t
seen before because we haven’t engaged with them and now we think it’s time. And maybe out of that we will fill in some
of the missing pieces about health disparities. But if we really want to get there in terms
of precision medicine and having inequities taken care of it’s going to have to deal
with reimbursement and right now the pathway between knowing that something can improve
outcomes and getting agreement that it’s going to be paid for is not as direct as it
might be. And for genomics we still don’t even have
that for some cases you would think for instance cancer where the evidence is pretty compelling
and yet in many instances third parties are not paying for it. One more question. So this is a question specifically for you,
Bill. So infectious disease and preterm birth, these
are things you mentioned that are obviously a big priority for the Gates Foundation. But what else is on the priority list? I mean what’s… You know, what’s really on your mind as
sort of the next big thing that needs to be addressed in addition to these? We’re driven by the health equity and so,
you know, still that means our biggest areas are HIV, TB, malaria in those first 30 days. And I’m very hopeful that as we make progress
on those things that we can find the places where the US health system and other wealthy
countries have come up with really great interventions and then it’s a challenge to us to say okay
how… What is the marginal cost, how would you have
to change that. With the vaccine manufacturers or the HIV
drug manufacturers it’s worked out super well that they literally make it available
to the poorest countries at the marginal price and then we go in and provide the fixed cost
to develop the processes, we go in and make volume guarantees and that in the vaccine
market has changed it from being one where the vaccines usually take 30 years between
when they’re available in the US to when they’re getting to Africa to now literally
pneumococcus was only a few years’ difference. HPV we have one country now that’s actually
ahead of the US in terms of using HPV vaccine. Rwanda. Exactly. They’re good at a lot of things. So it’s scaling that up will be a challenge,
but it’s interesting that, you know, that’s one where the US hasn’t totally cracked
the code of high usage rates. And so, you know, I’m very much hoping that
there will be interventions for take diabetes and Alzheimer’s which are so wide spread
and will be such a problem for these health systems. If the middle income countries can innovate
that’s great, then we see our role as taking it from the middle income down to the poor
countries. So we’re going to be scanning. You know, there are things like how eye surgery
is done where India actually created a very high volume low cost model. Even for heart surgery, you know, it looks
like they’ve maintained very high quality through using these high volume operations. So I think we’ll find inspirations from
all over the world and it’ll always be good news when we can take something like polio
and say okay we had a $400 million a year budget for polio and now that budget is the
same as our smallpox budget which we never had to spend any money on that because people
before us got rid of the disease. So that, you know, we’ll celebrate all those
things that we can move beyond and then, you know, we’ll find the next thing that really
makes sense in health equity. I wonder, you mentioned TB but we didn’t
really get into it. If I sort of look across the landscape here
of things where we’re making progress and things where we’re really struggling, TB
worries me with the advent of additional sort of examples of multi-drug resistant strains
coming out and an occasional sort of introduction of a new therapeutic, a lot of struggling
with vaccines and yet here is a disease which is clearly far from being vanquished in any
part of the world although we don’t think about it so much. What should we be doing with TB that we’re
not doing? What are we missing? Well there’s… In TB I’m very optimistic about good TB
diagnostic, either a blood or urine test which makes a huge difference because if you can
catch somebody early then you can put them under treatment and their infection… They’re infecting a lot less people, so
you’re really bringing that R zero down. Also with TB we have latent disease and if
you have a huge amount of latent disease eventually you’re going to have a lot of people with
TB. China is an exemplar on TB. They ten years ago did not do a good job,
they put resources into it and they’re bringing the TB rate down pretty substantially, but
it won’t go away completely because they’ll have people… The latent disease that’s there unless we
come away with treatment that will come out. The drug pipeline, the second piece, also
looks very good and that’s in partnership with pharma companies, new compounds. The goal is to have a regime that is so novel
that no existing TB is resistant to it. So it’s a new three drug regime that I absolutely
think in the next decade that we’ll get that. The dream would be to have a vaccine but… And the genetic tools are going to help us
a lot with this one because we’re always so confused with TB; do we want the immune
system to do more or do we want the immune system to do less. This is a pathogen that has evolved together
with the immune system, that’s the most preserved part of the TB is the way it interacts
with macrophages and, you know, so it gets this privileged compartment and the heterogeneity
of the disease, the improvement of the disease models I can’t say whether we’ll have
a vaccine but I do think even compared to say HIV we’re in much better shape because
the drug pipeline looks promising and it’s not a lifelong disease. In fact the regiment if we can get the right
measurement tools the regiments could go down to two or three months. That’s grand. Well I want to thank all of you for your attention
and the questions that you sent to us. I want to thank the Gates Foundation, the
NIH and the Society staff who helped coordinate and organise all of the activity around this. I had a blast working with this. I want to thank Francis for taking time to
attend your own meeting. Yes, it’s great to be back with my peeps. It’s always a pleasure to have you and to
get to talk science with Francis. And it was a pleasure to have you, Mr Gates,
we thank you for your activities in science and on behalf of global health and also for
the many of us who were nerds and science geeks way before it was cool, thank you for
helping to make it a lot more cool for all of us. Thanks. Good job. Thank you. Thanks a lot. Thanks Francis, so much.
