DECEMBER 2010 Volume 9ii

Letter from the Country Director

There could scarcely be a better time to be involved in AIDS
vaccine research. Over the past couple of years, HIV researchers
have witnessed the rst demonstration in humans that a vaccine
can prevent HIV infection and the discovery and analysis of a
slew of unusually potent antibodies against a broad spectrum
of HIV variants. These breakthroughs have revitalised the eld
and renewed optimism about its prospects. So we are happy to
report in this issue of Sankalp that the agenda of HIV prevention
is winning growing support from lawmakers at both the state and
national levels. The government has, meanwhile, taken concrete
steps to cultivate an atmosphere conducive to the development of
new tools to prevent HIV infection. Further, the Prime Minister has
announced plans for a Decade of Innovation that will re-focus the
governments attention on this area and the National Innovation
Council set up under the PMs ofce will amongst other sectoral
areas, also focus on science and technology as well as innovations
related to public health.
This issue of Sankalp explores how all this has changed the
prospects of scientists contemplating a career in India: one story
looks at the phenomenon of young, expatriate Indian scientists
returning to India, and asks what drives this migration. Another
delves into the intricacies of systems biologyits power and
promise for infectious disease preventionand explains why India
is enviably positioned to take the lead in this powerful but edgling
eld. Finally, we examine the relationship between innovation in
science and technology and economic development.
We hope you will have as much fun reading this issue of Sankalp
as we had producing it. Wishing you a very happy new year.

Rajat Goyal

in this issue

02
World AIDS Day 05

Indo-vation for health

Im coming home,
Ive done my time

06

A systems approach

09

insight

Indo-vation

for health

Exploring the role of science and technology in the Indian public health space

India often seems to occupy two different

worlds. It boasts on the one hand, an economy
growing at a torrid rate. On the other, many
of its public health problems reect those of
far less economically advanced nations. This
strange dichotomy has serious long-term
implications. Economists have long pointed out
that poor public health can be a heavy drag on
an economy. Conversely, a healthy population
is both more productive and less costly to the
public purseand the cost-savings are like
kindling for blazing growth1. Indias staying
power as an economic leader will hinge on
its ability to bring its numerous preventable
diseases to heel.
Chief among these are infectious diseases.
These ailments are primarily the bane of the
impoverished. And if India hopes to close
the vast disparities that have characterised its
emergence as an economic power, it will have
to deal with them. But to do so, it will have to
learn to help itself: the global pharmaceutical
industry has little motive to invest in drugs and
vaccines that are unlikely to yield signicant
nancial returns. In this, it needs to cultivate a
capacity to research and develop home-grown
biomedical products to address its own public
health problems.

The question is, how should it go about

doing that?
In short, by nurturing innovation in
the applied biomedical sciences, and by
investing in the translational research that
converts ideas forged in the laboratory into
products that can be manufactured by the
biopharmaceutical industry. We have many of
the elements of this scheme in place. We have
a small but rapidly expanding pharmaceutical
industry that can help translate ideas into
viable products. And we certainly have the
generators of those ideas: an enviable pool of
highly educated scientists who are looking
for opportunities to turn their lab-bench
discoveries into useful products. According to
a World Economic Forum report published in
20082, India has more scientists and engineers
available in its population than all but two
other nations; by comparison, China ranked
a mere 57th. Yet, strangely enough, India came
in at 35th in the overall ranking of innovative
output, 10 spots behind China. So, it appears,
we have all the human and institutional
resources we need to forge a highly
innovative economy, yet were strangely
reluctant to use them. Whats missing is the
smart management of those resources.

The smallpox vaccine eradicated smallpox in 1979 and resulted in an estimated savings of US $1.35 billion in global control
expenditures and eliminated an estimated 10-15 million annual infections primarily in the developing world. Additionally,
10-15 percent of economic growth in developing countries between 1960 and 1990 can be attributed to reductions in mortality.
2
Source: Global Competitiveness: Innovation Capacity Components Index. World Economic Forum, 2008
1

With a little focus on applied research and a lot

more investment, India could become a leading
innovator. Certainly, India will need to invest
in the quality of its educational institutions,
and do more to encourage people to pursue
the highest scientic degrees: despite Indias
high ranking in the availability of engineers
and scientists, it produces fewer than 7000
PhDs each year in these elds from its reserve
of 1.3 billion people. Fortunately, we already
have sufcient numbers of them to boost our
home-grown biomedical innovation. And
we undoubtedly have the entrepreneurial
experience to harness their ideas. Consider
how Indias early investment in training
physicians and surgeons has contributed to its
blossoming medical tourism industry. People
today travel to India from all over the world
to access affordable and high quality surgical
care at Indias expanding private hospitals. Our
surgeons have not only mastered their craft,
but have gured out how to do it better and for
a lot less moneythey have innovated. Theres
no reason Indias redoubtable pharmaceutical
manufacturers should fail to do the same for its
armies of scientists and engineersprovided
they have some ideas to offer.
And those ideas, in the arena of public health,
will need government funding. A lot of
innovative projects are by denition highrisk from an investors perspective, so private
enterprise is often reluctant to support such
efforts, especially if they promise no great rate
of return. This is why, in India, 75-80 percent of
funding for R&D comes from the public sector,
while only 20-25 percent comes from private
enterprises, and a paltry three percent from
universities. Contrast this with average R&D
expenditures in Organisation for Economic
Cooperation and Development (OECD)
countries69 percent by enterprises, 18 percent
by universities, 10 percent by government R&D
labs, and three percent by private non-prot

institutions3. The Indian government invests

less than one percent of its GDP on R&Das
opposed to 2.5 percent invested by enormous
economies such as that of the US. It could do
much better.

According to a World Economic Forum

report published in 2008, India has more
scientists and engineers available in its
population than all but two other nations;
by comparison, China ranked a mere 57th.
Yet, strangely enough, India came in at 35th
in the overall ranking of innovative output,
10 spots behind China. So, it appears,
we have all the human and institutional
resources we need to forge a highly
innovative economy, yet were strangely
reluctant to use them. Whats missing is
the smart management of those resources
Linking scientists with drug
manufacturers
Generating scientic ideas from applied research
is critical, but how does one translate them into
biomedical products? Translational research
describes that art, and it has historically been
the bailiwick of the pharmaceutical industry.
But a non-prot model for linking the worlds
of research to the translational expertise of
drug manufacturers already exists and has
much to offer India. It is known as the Product
Development Partnership (PDP). PDPs essentially
link scientists working on a particular problem
with drug manufacturers who have translational
research expertise, and invite their participation
by assuming the nancial risk that accompanies
such projects. In return, the commercial
enterprises agree to sell the products that
emerge from the partnership at rates affordable

Unleashing Indias Innovation Toward Sustainable and Inclusive Growth Ed. Mark Dutz; Published by the World Bank.

to developing countries and their people. The

Global Alliance for TB Drug Development, which
is collaborating with AstraZenecaa global
biopharmaceutical companyat its TB research
centre in Bengaluru on TB drug discovery
project4 is one such organisation.
IAVI, with its mission to develop an AIDS
vaccine that is both accessible and of relevance
to the developing world, is another. The model
appears to be effective. In 2009, PDPs had nearly
150 biopharma, diagnostic and vector control
candidates in various stages of development,
including 32 in late-stage clinical trials. So
far, PDPs have developed and licensed at
least a dozen products to combat sleeping
sickness, cholera, Japanese encephalitis, visceral
leishmaniasis, TB and meningitis5.
By conducting research in developing countries
and in partnership with their scientists, PDPs
like IAVI also help build capacity for scientic
research and applied science, and help local
institutions build partnerships with industry.
These facets of the PDP model have certain longterm benets for scientic innovation, laying
the groundwork for training young scientists
and establishing the mechanisms by which
innovations in research can be translated
into products.
PDPs, in other words, provide a model that can
be adapted by governments to systematically
harness innovation in service of their public
health needsand, at the same time, lay the
foundations of future economic growth.
One thing is certain. Fostering innovation is
an imperative. Consider the economic case:
investments in R&D provide a 78 percent or
higher return on investment in developing
countries6. The rapid economic growth of

Dealing with the challenge of public

health issues of a large population requires
out of the box thinking all through the
discussion, development and delivery chain
Dr R A Mashelkar
several countries, including South Korea, Japan
and Singapore has been driven by their R&D
investments7. More recently, the nancial clout of
the knowledge-based economy and the growth
of high-technology industries, have made
investment in R&D a development imperative8.
With the Indian government declaring 20102020 as the Decade of Innovation and the
establishment of the National Innovation
Council in 2010, India is certainly receiving a
strong top down impetus for innovation. Now
we need to, as a nation, make the commitments
and the investments needed to translate that
general directive into tangible benets for the
countrys public and economic health.
The nal word should rightly go to a visionary,
who has been advocating investments in R&D
with almost missionary zeal much before terms
like 'pharmerging' were coined. Commenting
on the relative importance of innovation
in the Indian health space today, Dr R A
Mashelkar, Council for Scientic and Industrial
Research Bhatnagar Fellow and President,
Global Research Alliance, National Chemical
Laboratory, Pune sums up the journey ahead
saying, Dealing with the challenge of public
health issues of a large population requires
out of the box thinking all through the
discussion, development and delivery chain.
Isn't it time we seriously started strategising on
our own brand of innovation: Indo-vation?

Source: http://www.tballiance.org/newscenter/view-brief.php?id=919. Retrieved on 30/12/10 at 13:12 IST.

Boston Consulting Group (BCG). 2009. PDP Support Project. (Presentation, funded by the Bill and Melinda Gates Foundation).
6
D. Lederman, W. Maloney, R&D and Development (World Bank Policy Research Working Paper 3024, 2003).
7
Lederman, 2003
8
Juma, 2005

World

AIDS Day
IAVI addresses the Forum of
Parliamentarians on HIV/AIDS

The Forum of Parliamentarians on HIV/AIDS (FPA)

observed the 22nd World AIDS Day on December
1, 2010. Seventy-ve MPs from both houses of
parliament, members of state legislative assemblies,
representatives from UNAIDS, 25 people living
with HIV (PLHIV) and eminent sports personalities
gathered at the Forum ofce in New Delhi. Dr Rajat
Goyal, Country Director, IAVI India and Mr Dana
Ward, Managing Director, Population Services
International (PSI) were special invitees.
With a diverse membership base, FPA provides
leadership to the HIV/AIDS response in India,
and works towards raising awareness with elected
representatives. It inuences stakeholders and policy
makers towards balanced legislation and policies
aimed at effective prevention of HIV infection and
empower those affected and infected with HIV/
AIDS to become full partners in development.
Addressing the meeting, the President of the
Forum, Mr Oscar Fernandes, Rajya Sabha MP
assured the Forums support for an early passage
of the HIV/AIDS Bill. He underscored the need
for access to information and services whilst
referring approvingly to the National AIDS Control
Organisations (NACO) Red Ribbon Express a
cross-country train that reached an estimated 80 lakh
people with HIV/AIDS awareness and prevention
messages. Appealing for everyones support,
Mr Fernandes pointed out that HIV is a common
enemy and beyond party politics.
Prof B L Mungekar, Former Member, Planning
Commission, Government of India pointed out that
together with poverty and unemployment, HIV/AIDS
is a key concern. Reinforcing the need for legislative
support towards HIV control, he added that effective
implementation of these laws was key and this
would only be possible through joint efforts of the
government and national and international agencies.
Dr Goyal stressed the need to integrate a range
of prevention tools as part of a comprehensive
approach to end the epidemic in India. Various HIV
prevention methods and tools (such as microbicides,
vaccines, PrEP, PEP) in development globally have
the potential to reduce the scale of HIV epidemic in a
comprehensive manner. Recent ndings from the Thai
trial and the discovery of the neutralising antibodies

by the Neutralising Antibody Consortium of IAVI and

other researchers around the world have injected fresh
hope for the development of an AIDS vaccine. Though
the journey towards a successful AIDS vaccine may
be long, support from forum leadership in India was
essential to ensure long-term sustainable commitment
for the scientic endeavour. He added that initiatives by
the government, some in collaboration with IAVI and
other key stakeholders from academic institutions and
Indian industry were contributing to the global effort.
If these are enhanced in numbers and scope and ably
supported by the country leadership, India could be a
leading voice in the global arena.
PLHIV advocated for provision of second line drugs
to all those in need of them, free treatment of TB
and other opportunistic diseases, provision of free
travel for the poor who lose their daily wages when
they have to repeatedly report to a health facility for
medication, and institutional support to HIV infected
pregnant mothers. They also raised signicant
concerns about access to medicines and the India-EU
Free Trade Agreement (FTA).
Some of the leadership from individual states
highlighted the efforts made at their level towards
initiatives in spreading HIV/AIDS awareness. As the
meeting drew to a close, Mr Rajesh Lilothia, MLA
from Delhi and others present lauded the efforts of the
forum under the leadership of Mr Oscar Fernandes
in raising awareness in the country for the infection;
mobilising effective support for Indias campaign
against HIV/AIDS; and addressing critical issues
and policies in order to ensure a balanced strategic
approach for prevention of HIV infection.

L to R: Dr Rajat Goyal, Dr B L Mungekar, Dr Thokchom Meinya

and President FPA, Mr Oscar Fernandes

trends

Im coming home,
Ive done my time
This line from an old song (Tie a Yellow Ribbon by Tony Orlando) resonates with the trend of
young scientists returning home to India. What are the challenges, opportunities and changes in
the Indian scientic community today?
1990: A young scientist returns home to India
from the US. Anjan Ray, a graduate from the
Indian Institute of Technology (IIT), Delhi,
who has earned a PhD in Inorganic Chemistry
from the University of Pennsylvania under
the guidance of the Nobel Laureate Alan
MacDiarmid, moves back not just because hes
missing home, or to tend to his aging parents,
but because he sees that his homeland is poised
to become an engine of scientic research.
Already, he had noticed, a growing number
of international patents and frequently cited
papers were coming out of India, especially
from the nations leading labs at Council for
Scientic and Industrial Research (CSIR) and
out of the investigative engines of the IITs. Ray
also noticed that the number of science PhDs
from India (though still lagging) was beginning

Courtesy: Jitender Gupta/Outlook

to show a perceptible increase, suggesting that

the quality of undergraduate science education
in India had improved.
Today Anjan feels vindicated. As Business
Development Director (Specialty Materials)
at Honeywell India, in the National Capital
Region, he is creating products for a market
newly vibrant in India, and stagnant in the
US. And he nds himself in a position to serve
the future generations through his work in
sustainability and alternate energy.
2010: Akshay Pandey, a young biotechnology
researcher at the University of Illinois, Chicago,
wants to come back to India after completing
his doctoral programme. Akshay is working on
a protein that determines the fate of a cancerous

cell. He isnt being driven home by the deep

recession that has aficted the West, and he
isnt only coming home because he wants to
contribute to his country. Rather, Akshay is
coming home because he smells opportunity. He
believes, too, that India will offer him a better
perspective of the kinds of problems he wants to
address in his research.
Anjan and Akshay, two decades removed from
each other, are the harbingers of a migration that is
changing the professional terrainand, perhaps,
the technological prospectsof modern India.
There was a time when most Indian scientists
studying or working in the West would
only have come back to India after they had
achieved all they wanted professionally. But
that is increasingly not the case. Young Indian
scientists today see opportunity blossoming
at home and are coming back to put their
careers on the fast-track in the newly vibrant
and intellectually fertile atmosphere of Indian
science and technology. This is not to say things
are perfect. But theyre getting there.
One big problem is bureaucracy. But
policymakers are paying attention to that
problem. The Prime Minister, Dr Manmohan
Singh (who also holds the distinction of being
among the most erudite of Prime Ministers)
acknowledged, at the 97th Indian Science
Congress in January 2010, that a major cause for
Indias lack of scientic progress is simply red
tape, political interference and lack of proper
recognition of good work1. He also said that his
government is considering boosting doctoral
and post-doctoral fellowships, and formulating
schemes to support all research scholars.
Have things improved since the prime ministers
admission? Dr M K Bhan, Secretary, Department

A recent report indicates that the only

signicant percentage increase in spending
on science and engineering research and
development between 1996 and 2007
has come from the Asia Pacic region,
led by India, China and other developing
countries. The prime driver for this has
been increased capacity for research
of Biotechnology, Government of India, Ministry
of Science and Technology, believes they have,
particularly in the area of resource allocation.
Today, he says, no meritorious scientist will be
denied money for the work he wants to do. He
also notes that Indian scientists are increasingly
collaborating with the private sector in India
and in other countries. India is reaching
outside, Dr Bhan observes. There is a lot of
global collaboration, a variety of new institutions
and new methods of funding. The work
environment has changed as well, he notes. The
newer institutions foster a more autonomous
approach. And though he admits that the
leadership of scientic research institutions could
be stronger, he says the issue is on the radar
of policymakers.
It bears noting that Indian scientists are
increasingly working in interdisciplinary
teams, and doing so with collaborators here
and abroad. In 1981, more than 95 percent of
Thomson Reuters-indexed papers from India
named authors exclusively at India-based
institutions. By 2007, however, the percentage of
such papers had fallen to 80 percent, indicating
that the nation is gradually participating more
in internationally collaborative research2.
Further, between 1985 and 20073, publications
co-authored by scientists in India have more

http://pmindia.nic.in/lspeech.asp?id=872 Retrieved on November 23. 2010 09:31 IST

http://sciencewatch.com/ana/fea/08sepoctFea/ Retrieved on November 23. 2010 09:42 IST
3
This refers to the number of papers indexed by Thomson Reuters for each year between 1985 and 2007 that listed at least one Indiabased institution among the author addresses. In 1985, the number was approximately 12,500, and for the next 15 years the total never
much exceeded 14,000. Around the year 2000, however, the number began to tick upwards, rising to nearly 17,000 in 2001, reaching
20,000-plus in 2003, and winding up at more than 27,000 in 2007. http://sciencewatch.com/ana/fea/08sepoctFea/ Retrieved on
November 23. 2010 09:46 IST
1
2

India is well-positioned today to play a key

role in scientic development in its region
and can assume leadership in collaborations
between developing countries
than doubled in volumeand those papers
were in general more heavily cited than in
previous years. Not only has the volume of
Indias scientic output risen, so has its quality.
In fact, a recent media report4 indicated that
placement of Indias top universities on the
H-index, which measures citation impact, has
gone up signicantly in the past two years.
Better funding has certainly helped. A recent
report5 indicates that the only signicant
percentage increase in spending on Science
and Engineering Research and Development
between 1996 and 2007 has come from the Asia
Pacic region, led by India, China and other
developing countries. The prime driver for this
has been increased capacity for research.
India is well-positioned today to play a key role
in scientic development in its region and can
assume leadership in collaborations between
developing countries. The young scientists who
return to India, with extensive exposure to
international practice, will be well-equipped to
drive this endeavour.
Beyond new organisations like THSTI6 (also
see box) offer opportunities that are difcult
to match outside India. India is on the verge
of several dramatic transitionsdemographic,
economic, medical, environmentalthat
will unfold inexorably over the next 20 years.
Science will play a central part in harnessing
the good and mitigating the bad aspects of
these transformations. And being a part of
that change promises to be quite a ride. Young

The Times of India - Mumbai | Date: 23/11/2010 Page: 15 Top

univs improve scores on R&D front
5
http://www.nsf.gov/statistics/nsb1003/
6
http://www.thsti.org/documents/Capacity%20building%20wh
ite%20paper.pdf
4

researchers returning to India have much to

look forward to professionally.
As the vice president of R&D at Jubilant
Technologies, one of Indias largest custom
research and manufacturing services rms,
Dr Robin Santra is looking forward to
their return. A growing economy and the
corporatisation of research has enabled access to
high-end technology, he says. An abundance
of scientic and technical workers should be our
greatest advantage.

The good news

1.

Between 1980 and 2004, 42 of 75 major nonagricultural Science and Technology World Bank
loans went to only 7 countries (Korea, China,
Brazil, India, Indonesia, Chile, Mexico).
Source: http://www.igfagcr.org/Sara%20Farley2.pdf
Retrieved on November 23 2010 11:34 IST

2.

The establishment of the IISERs (Indian Institute

of Science Education and Research) in 2006 has
introduced exible, borderless and integrated
Masters and Doctoral programmes that
allow students to engage with research more
meaningfully and at an earlier stage.
Additionally, several new initiatives in the
biological science sphere have begun or reached the
planning stage in the past two years. These include
the Translational Health Science Technology
Institute (THSTI), as well as UNESCO Center for
Biotechnology Research and Education.
Source: http://jcb.rupress.org/content/184/3/342.
full#F15 Retrieved on November 23 2010 12:02 IST

3.

The Ramalingaswami Fellowships announced

by the Department of Biotechnology in
2006-07 are ve-year fellowships which are
re-entry grants for scientists of Indian origin
currently working outside the country in
various elds of biotechnology and life sciences,
and who are interested in taking up scientic
research positions in India.
Source: http://dbtindia.nic.in/annualreports/
Biotechnology%20English.pdf Pg. 27. Retrieved on
November 23 2010 14:24 IST

new frontiers

A systems

approach

Dr Dhiraj Kumar explains how the edgling eld of systems biology has deep implications for
research into infectious diseases of the developing world
Our understanding of fundamental biological
processes has undergone something of a
revolution over the past century. Building
on the 19th century foundations of classical
genetics, biologists harnessed increasingly
sophisticated analytical tools made available by
huge advances in biochemistry and later, the
founding of molecular biology and genomics
as elds in their own right, to probe ever
deeper into the biology of the cell. But our
understanding of how these processes interact
and unfold within the human bodyand
even within the cellhas remained relatively
reductionistic. That is set to change in the
21st century, thanks in large measure to systems
biology. This edgling eld seeks to draw
together the major disciplines of cell biology
and apply new tools and technologies, most
notably computational analysis, to generate
a more holistic picture of the dynamic,
interdependent biochemical processes that
culminate in life and disease.
Systems biology has deep implications
for research into infectious diseases of
the developing world. HIV infection and
tuberculosis (TB) are a case in point. Physicians
and researchers have fought a pitched battle
against TB for more than a century, yet made
few inroads into the effective treatment of this
chronic and often lethal disease. There have,
indeed, been some breakthroughs: the discovery
of BCG (the only successful vaccine against TB)
in the early 20th century, and the introduction of
chemotherapeutic agents, including antibiotics

like Isoniazid and Rifampicin in the latter half

of the 20th century, would certainly qualify. But
these agents of prevention and cure have their
limitations. BCG provides a relatively inefcient
and inconsistent barrier to infection, and other
drugs have been compromised by the rise of
multiple drug-resistant strains of the bacillus
that causes TB.
By comparison, both the HIV pandemic and the
battle against it are relatively recent; scarcely
three decades have passed since the virus was
found to be the cause of AIDS. And researchers
have in that time made remarkable headway
in treating the disease: there are more drugs
available today to treat AIDS than there are for
all other viral ailments put together. But HIV
frequently becomes resistant to their assault,
and the development of an effective HIV
vaccine remains among the most challenging
problems facing modern science today.
What accounts for these failures? Consider HIV
drugs. Most of them target enzymes essential
to the ability of the virus to multiply. They
work by disabling virally encoded enzymes
that are essential to the cycle of replication
and infection central to the HIV life-cycle. But
their very effectiveness drives the evolution of
HIV into variants that can escape targeting.
TB treatments fall short for the same reasons:
the antibiotics used to treat it act as selective
forces that inadvertently promote the evolution
of bacterial strains that can escape them. To
circumvent this challenge, physicians target
9

This edgling eld seeks to draw together

the major disciplines of cell biology and
apply new tools and technologies, most
notably computational analysis, to generate
a more holistic picture of the dynamic,
interdependent biochemical processes that
culminate in life and disease
both pathogens with multiple drug regimens,
assuming that while each pathogen can adapt
to evade a single line of attack, neither is likely
to develop the means to evade several at once.
That calculus has proved remarkably accurate,
but it is now leading to the evolution of several
multi-drug resistant strains of both HIV and TB
bacillus. Clearly, new ideas are needed.

Systems biology for drug target

discovery
Systems biology could help us nd a few.
This approach stems from a deceptively
simple insight: for any intracellular pathogen,
bacterial or viral, to survive and multiply
inside its host cell, it must establish a dynamic
relationship between the biochemical factors
it produces and those that are produced by
the cell. This suggests that the obstruction of
such interactions might render the pathogen
vulnerable to the hosts existing machinery of
self-defence. Several studies have been done
recently testing this hypothesis, and they have
given researchers a rst look at the various
host factors that seem to be important for the
survival of intracellular pathogens.
Though this concept is potentially invaluable to
medicine, it remains far from clear how it might
be applied to the treatment and prevention
of disease. In a healthy cell, proteins encoded
by some 30,000 genes and a host of other vital
molecules are in a state of equilibrium known
as homeostasis. Infection by an intracellular

10

pathogen like Mycobacterium tuberculosis

(MTB) or HIV results in the disruption of this
equilibrium, as the pathogen establishes its
own set of relationships with host molecules.
The challenge is to identify how many of
these newly established relationships are
indispensable to the pathogen. Several
previous studies on MTB and HIV have
identied such host factors, but have failed
to identify host targets for therapies or a
granular understanding of the host-pathogen
relationship. Systems biologists today are
trying to ll those gaps. Rather than analysing
such systems piecemeal, they have tapped
sophisticated microscopy and novel highthroughput genomics and biochemical
technologies for the large-scale proling
of proteins to take panoptic snapshots of
what goes on inside cells under a variety
of circumstances.
These techniques are now widely used to better
understand a number of infections. Several
genome-wide siRNA screens (siRNA is a family
of molecules that, among other things, silence
gene expression) have been done to identify
host factors important for HIV propagation.
These have resulted in the identication of
many molecules that are now targets of choice
for a new generation of drugs. A similar
study on MTB identied at least 74 genes that
may be harnessed to kill the intracellular
mycobacterium, irrespective of its drug
resistance pattern.
It should be noted that these approaches,
and the technologies involved, are very
expensive and can be afforded by few
laboratories not located in wealthy nations.
They also require considerable computational
expertise and powerthe vast amounts of
data generated by large-scale analyses of
biological systems can be a nightmare to
organise and analyse. Laboratories involved
in systems biology have thus become hotbeds
of interdisciplinary collaboration.

Systems biology for vaccine research

If systems biology has so far been employed
only sparingly in vaccinology, it is increasingly
clear that the strategy has much to contribute.
Our scant understanding of the basic, molecular
interplay that underlies vaccine-induced
immunity has hindered development of
vaccines against malaria, TB and AIDSall
pathogens that have mastered the art of evading
the adaptive immune response. Systems biology
can illuminate this dark corner of vaccinology.
Vaccines essentially mimic an infection to teach
the body how to avoid it in the future. In other
words, they perturb the homeostasis of the host,
albeit to the hosts long-term benet. Because we
already have in hand several proven vaccines
smallpox, polio and tetanus, to name a few
we can ask what kinds of initial perturbations
of immune system homeostasis are required to
induce protection. This is a complex business:
the mammalian immune system has two major
armsthe innate system, whose many cellular
components target pathogens in general, and
the adaptive response, which includes cells that
learn to recognise specic antigens found on
specic pathogensand they are intimately
linked to each other. A systems approach would
tell us a great deal about which connections
within and between those systems are most
important to protection from a given pathogen
(and indeed, initial studies along these lines
have proved quite revealing). Such proles
could help guide not just the design but the
evaluation of candidate vaccines.

Systems biology in India

India is poised to emerge as a leader in the
design of drugs and vaccines against infectious
diseases like TB, malaria and HIV. We not only
have the need, but the scientists as well. Until
recently, however, high-throughput studies
were not often encouraged by funders due to
their high cost. But lately, India has developed

If systems biology has so far been

employed only sparingly in vaccinology,
it is increasingly clear that the strategy
has much to contribute. Our scant
understanding of the basic, molecular
interplay that underlies vaccine-induced
immunity has hindered development of
vaccines against malaria, TB and
AIDSall pathogens that have mastered
the art of evading the adaptive immune
response. Systems biology can illuminate
this dark corner of vaccinology
enviable computational capabilities, and vast
reserves of computational theorists who have
much to contribute to the design, analysis and
interpretation of high-throughput experiments.
The group at ICGEB, for example, performed
the rst high-throughput genome-wide
siRNA screens for identication of host factors
important for the survival of intracellular MTB.
The targets identied through these studies
hold great potential for the design of drugs
against resistant strains of TB. We now have a
proven experimental system in place in which
we can perform our follow-up high-throughput
studies, assessing a variety of small molecule
inhibitors of the targets we have identied.
And we have laid the groundwork for such
research to begin in our country. It is now up to
the government and other funding agencies to
support that vital enterprise.
Dr Dhiraj Kumar is a research scientist in the
Immunology group at the International Centre for
Genetic Engineering and Biology. His research groups
focus is Understanding host-pathogen interactions in
case of Mycobacterium tuberculosis infection using highthroughput experimentation and integrative (global)
analytical approaches.

11

Editorial Board: Dr Rajat Goyal, Neeta Vinay, Rohan Mishra

Editorial Advisor: Unmesh Kher
Editorial Consultants: Sumita Mehta, Richa Dubey
Contributors: Dr Rajat Goyal, Dr Dhiraj Kumar, Unmesh Kher, Richa Dubey
Contact: Rohan Mishra,

E-mail: rmishra@iavi.org

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