So the question is,
whether we could use genomic information to predict disease.
This is a difficult question and answer is actually yes and no.
So we could think of two extreme scenarios,
and one scenario is of monogenic disease,
and there we can predict the risk of development of
such disease very well using genomic information.
And on the other side of the spectrum,
you could think of some trait with negligible heritability.
So it's almost entirely on the control of environment,
and it's quite clear that for such trait or disease,
use of genomic information is well,
almost of no use.
However, all the real situations are somewhere in between.
And it depends on the heritability of the trait how well we could in theory,
after years and years of research and studying all these finding out,
all these genes which are controlling this trait.
But the heritability is putting the upper limit of your predictive power.
Well, one thing this is interesting,
and this is something very unique for genetics,
is that genetics provides you with very long term prediction.
So you can take a baby which is just born and
try to predict the risk of development of certain disease by the age of 50.
And in a way this will be a right prediction,
but it will be also very inaccurate prediction for most of the situations.
But interesting thing is that,
it's very long term prediction.
And then you can think that, so now,
we developed all of this mixed techniques and we can assess the levels
of thousands of different molecular species in organisms.
And you can think of constructing biomarkers
which would be predictive of the short term risk.
And we already have a good examples of that, classical examples,
like fasting glucose level is providing
very good prediction for the development of diabetes in the next five years,
or also, very well-known example,
cholesterol levels for the risk of cardiovascular disease.
So you can think that actually,
you would like to smartly combine the knowledge of
genetic predisposition with the system which would
assess the levels of current risk using some panels of biomarkers.
Right? And smartly combine it in a way to predict the risk of development of disease.
However, I think that actually,
the main value of genetics for human disease is not in the risk prediction.
At least in the long term,
I think way more benefit to humankind if you wish,
is from use of genetics as a tool to understand
biology of this disease because this can really dramatically change the picture.
We can come up with new strategies
for treatment of this disease and prevention of this disease.
I would instantly think about cancer in this case.
Because even if a cancer occurs in the same tissue,
it may have a different genetic cause.
So some cancers will have mutations in,
aka rest or unrest,
other mutations have other cancers type mutations in p53.
And depending on the mutation,
we can now direct specific therapies.
So it's very important to sequence cancers,
to know which therapy,
which track will work.
And also, if you then repeats the sequencing after some time of treatment,
you can see whether the cancer is escaping the therapy
and you would be allowed to redirect to another drug.
So from a therapeutic standpoint in cancer,
that genomic information is huge and important.
So the future of genetics.
While this is a very broad topic and of course,
if I try to answer it,
if I try to play a prophet,
I'm going to be biased towards the position I'm standing in.
But if you think of this,
then like two major classes of problems in genetics are,
so the first problem is,
you can call it a problem of ontogenesis,
a problem of development,
or a problem how the genetic information translates into an organism.
Right? And this organism has developmental trajectory,
it grows, and then at certain point,
it start aging, right?
So how the genetic information on the individual level
translates in all these traits and some of these traits are diseases.
So this is one from the mount of think.
And then other fundamental thing is of course, is about evolution.
Right? So how does the genetic information now,
not in the context of specific individual,
how does it change with time?
How does it evolve?
Now, I'm trying to be a little bit more specific.
I'm thinking of this area of genetic analysis where we study how
genetic information is translated into phenotypic diversity, into phenotypes.
I think that is one very important step which we are going to make,
I hope in the future years,
because if you think of this in the area of
complex disease genetics and complex trait genetics,
quantitative trait genetics, may have accumulated a lot of knowledge.
We performed a lot of Genome-Wide Association
Scans and we have all these regions of associations.
However, for most of these regions,
we have very little idea how these statistical results,
all these peaks and P-values,
how do they translate into biology?
So we really need to understand better the function,
we need to understand better how it works.
So this I see as major next step in
the development of human genetics for the future years.
I have a very specific view about this.
Maybe not specific in the sense that it's mine.
It's shared by many people.
But I think genetic will become the basis of medicine.
There will be genetics in all different specialties of medicine,
be it cardiology or fertility.
I think we will sequence a lot of patients,
try to explain why they have this disease,
and then respond accordingly.
This will be called genomic medicine.
The term already exists.
What we are waiting for is to see this kind
of introduction of genetics in all the different specialties.
I strongly believe that this is the future of genetics.
It will become genomics as we call it now.
And I also see that increasingly,
we are sequencing patients.
We can now sequence entire genomes with
the novel technologies of massive parallel sequencing.
So eventually, I believe that everybody will be sick as a bird.
You may say this will not happen.
People will say, "What are you talking about?"
It's not my opinion,
it's what I anticipate that will happen.
I think society will want us to sequence everybody at birth,
to try and predict disease,
to try and prevent disease, and so forth.
So let's say that in 10 years from now,
genetics will be in every house not just in medicine.
So it seems to me that resequencing our genomes,
that's certainly imminent revolution.
And it's primarily, I think we can say that because the cost of sequencing has already
gone down spectacularly and because there is
no reason to believe that this tendency is going to stop.
So the cost of sequencing a genome will be of the same order of magnitude if not
cheaper than many of the medical tests that
clinicians are relying on a daily basis today.
And I'm confident that there is sufficient information hidden, if I may say,
in our genome or genomes that it will justify a nearly systematic use of this technology.
So I think we can say with near certainty that our children will
all have their genome sequenced on multiple occasions during their lifetime.
So this will primarily be used,
I think, to address problems with newborns,
so severe problems with newborns that are possibly due to inherited,
to mutations with major effects.
It will be used extensively,
I imagine, in the context of cancer.
So I think we are rapidly approaching a time where the DNA of
every tumor will be sequenced because in a number of instances,
it may suggest therapeutic approaches which are personalized,
which target the genetic defects that characterize that mutation.
Where it's more difficult to know where things will go,
is for multifactorial complex traits and complex diseases.
So, I think that in a second wave of GWAS,
the phenotypes will not be the diseases per se,
but things like response to treatment.
So a former pharmacogenomics,
evolution of the disease,
and that kind of information may help the doctor to make choices,
make decisions about how to approach a given patient,
what treatment to choose,
whether to go for surgery or not,
for instance, in the case of inflammatory bowel disease.
So I think there will be a number of
clinical decisions that will gain from the genomic information.
With regards to prevention of disease and management of disease, there in fact,
my view at the present time,
is that the information from the individual is very,
very difficult to use.
I think that if we were to look at our individual genomes,
we would all see that we are a bit at
higher risk for disease A and a bit at lower risk for disease B.
And so if you go through all the diseases,
we'll all be somewhere equal with few exceptions,
where all of us will have some risk that
is increased compared to the mean and some that is decreased,
and I doubt that it will easily affect our behavior.
I know that I should eat less and do more sports to live longer,
and I don't do it and I don't believe that reading in
my DNA is going to affect my decision.
So from the individual,
it is something where I think the information is,
for most of us, of limited value.
The difficulty is that for the group, for society,
it could be an information that can potentially be used in a way, for instance,
to be more cost-effective in the way we handle our dollars,
I want to say, or the rubles that we spend on our health as a community.
So, if we could stratify the population by the risk to different diseases,
we may if we have economic strains on the system,
decides that we reserve some diagnostic screening,
preventive diagnostic screening, to the people that
are at the highest risk of developing the disease.
And I think mathematically,
one can show that this may ultimately save quite a bit of money for
the society even if it is with methods that have low sensitivity,
which means that you will miss a lot of people who you should have given this option,
and that you will actually force the tests
or allow a large proportion of people to do the test,
which in fact didn't need it.
So despite the fact that this test will not be perfect,
when you average it over a large population,
you are going to save money.
So I think that the difficulty will be to balance
the interests of the individual versus the interest of the group.
And it is likely that different societies will actually approach that in different ways.
And we can just hope that it will be done in the most ethical way possible.