Towards a genomics revolution India has the scientic resources for genetic research — all it needs is the vision at the national level to leverage them

in #medical7 years ago

In 1865, Gregor Mendel disco-
vered the two laws of inheri-
tance that are now named after
him. Almost 90 years later in 1953,
the work of James Watson, Francis
Crick, Maurice Wilkins and Rosa-
lind Franklin, deciphered the
structure of the molecule — DNA —
that stores our hereditary informa-
tion and gets transmitted from pa-
rents to children over generations.
Personalised medicine
At this point, in principle, the
prospect of building individual-
ised medicine based on the pre-
cise information stored in each hu-
man’s DNA (their genome) had
come into view. But the human ge-
nome has around 3 billion base
pairs and in 1953 it wasn’t possible
to imagine extracting genetic in-
formation on the molecular scale
and of this collective size.
Technological advances in se-
quencing methods have made the
possibility glimpsed 60 years ago a
reality today. Already by 2001 the
human genome project and its
private competitor, Celera Genom-
ics, showed that an entire genome
could be sequenced.
Since then the cost of doing so
has plummeted — currently it is so-
mething like $1000 per person
and becoming cheaper — and the
age of genomics­informed medi-
cine is now within sight. Perhaps
this will also make interventional
treatments feasible, in the not too
distant future, thanks to the revo-
lutionary advances brought about
by the discovery of new gene­edit-
ing techniques, such as CRISPR.
Surveying Indian variation
What implications do these deve-
lopments have for India and are
there deliberate choices that
would shape this coming future
more advantageously for the coun-
try and its people? Are there
strengths that India can bring to
this task? To gain fully from the ge-
nomics revolution, India needs to
collect information about the ge-
netics of its population and train
manpower capable of interpreting
it. The information that is needed
has to come from a large and sus-
tained collection of data — fully se-
quenced individual genomes
along with medical histories for
the individuals who volunteer for
this eort.
This kind of longitudinal study
is what would allow actual physi-
cal manifestations relevant to
health, e.g. specic illnesses, to be
related to features in the genome.
To pick an ambitious but not im-
possible number, a data bank that
collects this kind of information
on one million Indians over the
coming decade would be a feasible
eort of the right magnitude. We
note that the China Kadoorie Bio-
bank has been studying half a mil-
lion people since their recruit-
ment in 2004­2008. As India is
much more genetically diverse —
with something like 5,000 ethno-
linguistic and religious groups
(castes and others), all of which
probably have some degree of ge-
netic distinctiveness — it needs a
larger survey to do justice to all In-
dians.
The genetic distinctiveness of
dierent Indian groups is in part
the result of endogamy. While we
cannot know the full impact of en-
dogamy in advance of a proper
survey, some recent research has
shown that endogamy is very like-
ly to be medically signicant.
Castes are not just “of the mind”.
The genetic implication of this is
that there are likely to be many re-
cessive diseases stemming from
single genes specic to individual
groups that can be identied.
Decreasing disease burden
This knowledge could then also be
quickly applied to the task of ma-
naging diseases in these groups as
well as be used for genetic coun-
selling that could reduce their inci-
dence in future generations. As an
example elsewhere, the founder
group of Ashkenazi Jews have al-
most eliminated Tay­Sachs disease
from their population by such
means. Looking ahead a bit more,
with large samples the technique
of “genome­wide association stu-
dies” that compare genomes of
cases and controls could be used
to identify genetic risk factors re-
lated to common diseases (such as
heart disease that stem from many
genes) that aect the health of ma-
ny more individuals. We would
like to emphasise that much of this
is simply a question of applying ex-
isting methods and could all be
done fairly quickly.
This is a good point at which to
note that such a survey of Indian
genetic diversity will be an impor-
tant asset, beyond disease genet-
ics. The data collected as part of
these eorts will also help to un-
cover the basic biological function
of genes and their interactions,
which are not yet fully under-
stood. This knowledge will be use-
ful to humanity worldwide and al-
so oer India a chance to claim a
piece of the global medical and
scientic frontier.
As a large part of the enterprise
would be the application of infor-
mation technology or “bio­infor-
matics”, the prospects of esta-
blishing viable commercial
enterprises with synergies to exist-
ing IT champions are also
promising.
What then is to be done?
As things stand there is certainly
progress under way. There has
been path­breaking work in using
genomics to shed light on Indian
history, a small number of hospi-
tals are using genetic information
to help patients, and there is at
least one private sequencing com-
pany in India. But all of this activi-
ty is on a much smaller scale than
needed and is currently not gener-
ating the manpower required to
equip the next generation of med-
ical and research activities in the
area. What is needed is a coherent
push at the national level that in-
volves government, academic in-
stitutions, the existing health­care
industry, the IT industry and the
nascent biotechnology industry.
This coherent push should aim to
set an ambitious but realistic ob-
jective of creating an Indian genet-
ic data bank, to promote academic
programmes that train scientists,
technicians and doctors in this
area and to create a regulatory fra-
mework that promotes broad ob-
jectives for both public and private
sectors without being self­defeat-
ing.
The fact is that both genetic da-
ta and biological samples are easi-
ly transported across borders and
if Indian regulation is shortsight-
ed, it will simply cause Indian ge-
nomics to move abroad to places
such as Singapore. In this context
it is worth mentioning that the Ge-
nomeAsia 100K Initiative based in
Singapore plans to sequence
100,000 Asian genomes, includ-
ing some from South Asia. While
this is eminently worthwhile as it
will provide a broader pan­Asian
set of data, it would be important
to make similar investments at a
national scale quickly to avoid the
situation that this is one of the on-
ly enterprises to which Indians
can turn to.
All in all, the time is ripe for In-
dia to begin its own genomics re-
volution. The technical under-
standing and will needed to
launch this is present in India’s
scientic leadership, in medicine
and in industry. What is needed is
a vision and leadership at the na-
tional level to leverage this and
seize the day. Nothing less than the
very health of the nation is at
stake.