The grand impact of the Gates Foundation

Abstract

In an ideal world, scientific research would be free from constraints; the professional interests of the scientific community and individual scientists would determine research topics and directions, and funding would be limitless. In the real world, however, factors such as the economy, health and social interests also have an influence and eventually limited financial resources must be prioritized. Public agencies and private benefactors support research with the expectation that the results will translate into tangible benefits such as economic growth, health products, or solutions to social problems. Given that much of academic research is predominantly funded by public money, funding agencies frequently determine the direction of research.

> The foundation frequently stated that the goal was not only to solve global health challenges, but also to attract new scientists to the field

In the USA, the National Institutes of Health (NIH; Bethesda, MD, USA) has an annual budget of approximately US$30 billion and influences biomedical research extensively by setting funding priorities. Given that the NIH distributes taxpayers' money, it predominantly supports research that targets health problems affecting US citizens. However, more recently, the US Federal Government's funding allocations through the NIH have been influenced by private foundations, shifting their focus and resources towards addressing the problems of global health. Most notable of these foundations has been the Bill & Melinda Gates Foundation (BMGF; Seattle, WA, USA; www.gatesfoundation.org), which was set up by the couple in 2000.

Here, we review the impact of the Grand Challenges for Global Health (GCGH) initiative that was started by the BMGF in 2003 and that managed to influence the NIH's funding priorities. We found that the NIH supplemented the GCGH with increased funding of approximately US$1 billion for global health issues at a time when the overall NIH budget experienced little growth. Interestingly, this redirection of …

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The grand impact of the Gates
Foundation
Sixty billion dollars and one famous person can affect the spending and research focus of public agencies
Kirstin R.W. Matthews & Vivian Ho
I
n an ideal world, scientific research would
be free from constraints; the professional
interests of the scientific community
and individual scientists would determine
research topics and directions, and funding
would be limitless. In the real world, how
-
ever, factors such as the economy, health
and social interests also have an influence
and eventually limited financial resources
must be prioritized. Public agencies and pri
-
vate benefactors support research with the
expectation that the results will translate into
tangible benefits such as economic growth,
health products, or solutions to social prob-
lems. Given that much of academic research
is predominantly funded by public money,
funding agencies frequently determine the
direction of research.
In the USA, the National Institutes of
Health (NIH; Bethesda, MD, USA) has an
annual budget of approximately US$30 bil
-
lion and influences biomedical research
extensively by setting funding priorities.
Given that the NIH distributes taxpayers’
money, it predominantly supports research
that targets health problems affecting US
citizens. However, more recently, the
US Federal Government’s funding alloca
-
tions through the NIH have been influenced
by private foundations, shifting their focus
and resources towards addressing the prob-
lems of global health. Most notable of these
foundations has been the Bill & Melinda
Gates Foundation (BMGF; Seattle, WA,
USA;
www.gatesfoundation.org), which was
set up by the couple in 2000.
Here, we review the impact of the Grand
Challenges for Global Health (GCGH) ini
-
tiative that was started by the BMGF in 2003
and that managed to influence the NIH’s
funding priorities. We found that the NIH
supplemented the GCGH with increased
funding of approximately US$1 billion for
global health issues at a time when the over-
all NIH budget experienced little growth.
Interestingly, this redirection of resources
towards global health by the NIH and the
BMGF contradicted the traditional wisdom:
that increases in funding from one agency in
a particular area of research will lead other
agencies to reduce their financial support
for the same field.
T
he BMGF is the largest charitable foun-
dation in the USA. It came into exist
-
ence in 2000 when the William H.
Gates Foundation, founded in 1994, merged
with the Gates Learning Foundation, founded
in 1997. As of March 2007, the BMGF’s
endowment was estimated to be US$33
billion, of which it awards approximately
US$1.6 billion in grants (BMGF, 2006). The
endowment and number of grants will con-
tinue to increase steadily after US investor
Warren Buffet announced in June 2006 that
he would contribute another US$30 billion
over the next decades (BMGF, 2006).
According to its website, the goal of the
BMGF is to “reduce inequities and improve
lives around the world.” To achieve this, the
Foundation concentrates on three main areas:
global health, global development, and the US
program that includes education and access
to technology for low-income communities in
the USA. The Foundation’s global programmes
focus on: “improving health, reducing extreme
poverty, and increasing access to technol-
ogy in public libraries.” These priorities were
greatly influenced by the year 2000 United
Nations’ Millennium Development Goals
(Sidebar A), which identified eight action
items to be completed by 2015. Over the past
13 years, the BMGF—and its predecessor, the
William H. Gates Foundation—distributed
more than US$7.8 billion, including more
than US$2 billion for work combating HIV/
AIDS, tuberculosis (TB) and malaria; approxi
-
mately US$1.9 billion for immunizations;
and US$448 million for the GCGH projects
(www.gatesfoundation.org).
Bill and Melinda Gates envisioned the
GCGH as a way “to identify research areas
with the greatest promise for saving and
improving lives in the developing world;
to fund novel, interdisciplinary approaches
The foundation frequently stated
that the goal was not only to solve
global health challenges, but also
to attract new scientists to the field
Sidebar A | The UN millennium
development goals
Goal 1: Eradicate extreme poverty and hunger
Goal 2: Achieve universal primary education
Goal 3: Promote gender equality and empower
women
Goal 4: Reduce child mortality
Goal 5: Improve maternal health
Goal 6: Combat HIV/AIDS, malaria and other
diseases
Goal 7: Ensure environmental sustainability
Goal 8: Develop a global partnership for
development
(Source: www.un.org/millenniumgoals)

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among researchers seeking solutions; and
to get the ‘rich-world’ scientific commu-
nity to apply its experience to pivotal health
questions of the developing world” (Gates,
2003). The initiative aims to challenge and
encourage researchers in the biomedical
field to apply their knowledge and exper-
tize to diseases and conditions that dispro-
portionately affect the developing world.
In doing so, the initiative aims to alleviate
the so-called 90–10 gap in biomedical
research; each year, US$70 billion are spent
on research worldwide, but only 10% of
this money is used for research on diseases
that affect 90% of the world’s population.
T
he Grand Challenges were inspired
by the German mathematician David
Hilbert (1862–1943), who, at the
International Congress of Mathematics in
Paris, France, in 1900, presented 23 unsolved
problems in mathematics (Hilbert, 1902).
Hilbert’s challenge ultimately guided math-
ematical research for the following century
and many of the problems were eventually
solved, although a few remain unanswered.
Unlike Hilbert, Gates did not propose a list
of specific challenges himself, but asked a
group of experts to compile a list of 10 main
issues for global health that his foundation
would attempt to solve by targeting its funds.
The objective of the initiative was to sup
-
port high-risk research with a high potential
impact on public health.
The BMGF donates the GCGH funds to
the Foundation at the National Institutes of
Health (FNIH; Bethesda, MD, USA), which
manages the research projects. The FNIH is a
non-profit organization established by the US
Congress in 1996 to promote collaboration
between non-profit charities, industry and
academia, “to support the NIH mission of
improving health through scientific discov-
ery” (www.fnih.org). Other partners include
the Wellcome Trust (London, UK) and the
Canadian Institutes of Health Research
(Ottawa, ON, Canada). Although the FNIH
manages and administers the grants, the
GCGH scientific board oversees and selects
the projects to be funded. The board is led by
Nobel laureate Harold Varmus—President
of the Sloan–Kettering Cancer Center (New
York, NY, USA) and former director of the
NIH—and consists of 20 leading scientists
from industry, academia, philanthropic
organizations and government with exper-
tize in biomedical research (Varmus et al,
2003; www.gcgh.org).
O
n the basis of solicitations to bio-
medical researchers, which resulted
in 1,048 submissions from scientists
and institutions in 75 countries, the GCGH
board agreed on seven long-range goals with
14 grand challenges (Sidebar B). These chal
-
lenges or goals do not address individual dis-
eases; instead, they concentrate on crucial
research problems that affect multiple disor-
ders. However, the goals are heavily slanted
towards infectious diseases, which the board
believe have the greatest impact on health
conditions in the developing world. “These
are all very significant and difficult scientific
problems,” commented Varmus in a Science
article, which published the challenges
(Varmus et al, 2003). “If we could solve any
one of these grand challenges, the impact
on health in the developing world could be
dramatic, and we hope to solve several in the
course of this new initiative.”
Following the announcement of the
GCGH, the FNIH issued a request for pro
-
posals, and reviewed more than 1,500
letters of intention and 445 project pro-
posals. The BMGF first proposed to spend
US$200 million on the project, but even
-
tually decided to inject an additional
US$250 million after receiving and review
-
ing the large number of grant applications.
In July 2005, the FNIH awarded grants
to 43 projects totalling US$437 million.
These ongoing five-year grants range from
US$579,000 to US$20 million, and the grant
recipients come from 33 countries, although
more than half of the grants are to research-
ers in the USA (Cohen, 2005). The last grant
was awarded in September 2005, making a
total of 44 projects funded with US$448 mil
-
lion (www.gatesfoundation.org). The BMGF
acknowledged that this would not be a one-
shot deal, and that they expect successful
projects to request and receive additional
funding in the future.
Unlike traditional grants from the NIH
or many other funding agencies, GCGH
grants also require researchers to define spe-
cific milestones, and scientists could poten-
tially lose funding if they do not accomplish
them. Applicants must also submit a plan
that explains how their product, once it has
been developed, will be made available and
affordable to people in developing countries.
The foundation frequently stated that the
goal was not only to solve global health chal-
lenges, but also to attract new scientists to the
field (Gates, 2003). The BMGF realized that,
in order to do so, the field needed new invest-
ment. Ultimately and interestingly, this came
not only from the BMGF and other private
donors but also from the NIH.
T
he 2006 fiscal year budget for the
NIH was US$28.5 billion. After
several decades of steady growth—
Sidebar B | The Grand Challenges
in Global Health
Goal 1: Improve childhood vaccines
Grand Challenge 1: Create effective single-dose
vaccines
Grand Challenge 2: Prepare vaccines that do not
require refrigeration
Grand Challenge 3: Develop needle-free vaccine
delivery systems
Goal 2: Create new vaccines
Grand Challenge 4: Devise testing systems for
new vaccines
Grand Challenge 5: Design antigens for
protective immunity
Grand Challenge 6: Learn about immunological
responses
Goal 3: Control insects that transmit agents
of disease
Grand Challenge 7: Develop genetic strategy
to control insects
Grand Challenge 8: Develop chemical strategy
to control insects
Goal 4: Improve nutrition to promote health
Grand Challenge 9: Create a nutrient-rich staple
plant species
Goal 5: Improve drug treatment of infectious
diseases
Grand Challenge 10: Find drugs and delivery
systems to limit drug resistance
Goal 6: Cure latent and chronic infection
Grand Challenge 11: Create therapies that can
cure latent infection
Grand Challenge 12: Create immunological
methods to cure chronic infections
Goal 7: Measure health status accurately and
economically in developing countries
Grand Challenge 13: Develop technologies
to assess population health
Grand Challenge 14: Develop versatile
diagnostic tools
(Source: www.gcgh.org)
…this sudden interest and
financial support for global health
research at the NIH was largely
due to the BMGF, and its strong
outreach to both the scientific
community and the public

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including a doubling of the budget between
1998 and 2003—the figures have been
relatively constant since 2003 (Fig 1) with
only small increases each year. The NIH
itself consists of various institutes at the
Bethesda campus, and the one that has the
most responsibility for research into infec-
tious diseases and funding such projects
is the National Institute for Allergies and
Infectious Diseases (NIAID). Of the main
institutes at the NIH—the National Cancer
Institute (NCI), the National Institute for
Heart, Lung and Blood (NHLBI), and the
NIAID—it was the NIAID that was least
affected by the stagnating budget. In fact,
its budget has increased by 23% since
2003, whereas the NCI and NHLBI each
saw increases of only 4.7% (Intersociety
Working Group, 2007).
Some of this increased funding since
2003 can be explained by new initia-
tives—such as a focus on bioterrorism
and preparedness in light of a possible flu
pandemic—but other diseases that are
addressed by the GCGH have also expe
-
rienced remarkable increases in funding.
Research in infectious diseases increased
by 26%: research on malaria and tuber-
culosis in particular increased by 40%
and 22%, respectively. The biggest win
-
ners were vaccines (Fig 2): the funds for
general vaccine-related research increased
by 41%, and research on vaccines against
malaria and tuberculosis increased by
96% and 62%, respectively. These changes
are even more remarkable when com-
pared with other disease-related research:
anthrax-related research saw a reduction
in funding of 49%; asthma increased by
only 15%; and heart disease—the leading
cause of death in the USA, which is funded
by NHLBI—saw only a 3% increase during
this time.
I
n our view, this sudden interest and
financial support for global health
research at the NIH was largely due to
the BMGF, and its strong outreach to both
the scientific community and the public.
First, the Foundation encouraged scien-
tists to get involved in the whole process
to address challenges in global health
research; this is in stark contrast to the NIH
Roadmap, in which only a select 300 scien
-
tists were asked for input. Although Gates
had a few preconceived ideas about what
the GCGH should fund—such as finding
new approaches to preventing and treat-
ing HIV—it was the Foundation’s scientific
board that chose the specific challenges
and projects to be awarded.
The strong response from the scientific
community confirmed their interest in the
project: more than 1,000 responses and
more than 1,500 letters of inquiry were
submitted. “The overwhelming response
demonstrates that when scientists are given
a chance to study questions that could
save millions of lives, they eagerly rise to
the challenge,” Gates commented in 2005
when he announced the additional US$250
million for the project (Cohen, 2005).
Second, the BMGF engaged the media.
At the World Economics Forum Annual
Meeting in Davos, Switzerland, in January
2003—a gathering of leaders from busi-
ness, government, international institutions,
non-governmental organizations, universi-
ties and other communities to discuss global
Fig 1 | National Institutes of Health funding: percentage change from previous year, financial years 1999–2008.
Source: American Association for the Advancement of Science; NIH budgets by institute and funding
mechanism, financial years 1998–2008 (www.aaas.org/spp/rd). Estimated budgets are given for 2007 and 2008.
Fig 2 | Estimates of funding for specific diseases and research: percentage change between 2003 and 2008,
by research area. Source: National Institutes of Health (NIH); estimates of funding for various diseases,
conditions, research areas (www.nih.gov). Estimated budgets are given for 2007 and 2008. NIAID, National
Institute for Allergies and Infectious Diseases.
Year
NIH funding
(percentage change from previous year)
Estim. 2008
–5% 0% 5% 10 % 15 % 20%
Estim. 2007
2006
2005
2004
2003
2002
2001
2000
1999
NIH funding
(percentage change 2003–2008)
0%
NIH NIAID Vaccine
related
Vaccine
related
(AIDS)
Malaria
vaccine
Tuberculosis
vaccine
20%
8%
23%
41%
96%
62%
41%
40%
60%
80%
100%
120%

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issues—Bill Gates announced that the BMGF
intended to create and sponsor the GCGH,
and his appearance at the meeting guar-
anteed worldwide press coverage (Butler,
2003). The following day, Gates published a
commentary in the Wall Street Journal out-
lining the concept and the reasoning behind
it (Gates, 2003).
Third, the BMGF used and continues
to use the GCGH to “advocate—vigor
-
ously but responsibly—in [its] areas of
focus”: research focused on diseases that
predominately affect developing countries.
In addition, the Foundation supports other
advocate groups with similar aims such as
the ONE Campaign (
www.one.org), which
actively lobbies for increased US federal
funding to combat global poverty and
global health challenges.
By reaching out to the press and creating
enthusiasm among the scientific community,
the BMGF has been able to translate their
own contribution into a significant increase
in federal research in this area. The BMGF’s
fund of US$450 million over five years for
research related to global health issues was
eventually supplemented by approximately
US$1 billion from the NIH for the period
2004–2008. By encouraging an increase in
NIH funding, the BMGF also succeeded in
recruiting additional researchers into the field
who would be hesitant to rely on Foundation
support alone for biomedical research.
T
he BMGF prides itself on making
bold choices and pushing research-
ers to find ways around impedi-
ments—whether a lack of collaboration
between AIDS vaccine researchers or the
lack of researchers in global health research.
By aggressively promoting their aims and
research, and by making the GCGH grants
prestigious as well as generous, the BMGF
was able to raise the profile of global health
research in the USA, which encouraged
legislators in Congress to notice global
health as a priority and helped to increase
similar research at the NIH.
Furthermore, the BMGF gained a dispro
-
portionate influence on public health policy
(Wadman, 2007). One example is the require
-
ment that all GCGH grantees must draft a
plan of how to make health products result-
ing from their research affordable to people in
developing countries. Furthermore, in 2006,
the BMGF dictated that all AIDS-vaccine
grantees share their results in order to help the
field move forward (Chase, 2006).
T
he experience of the BMGF and its
GCGH illustrates how strong advocacy
can influence public research policies
and budgets (Brower, 2005). Of course, the
NIH does not directly change its funding
priorities based on pressure from advocacy
groups. However, politicians—members of
Congress—are more receptive to campaigns
from patient groups. Congress then directs
the NIH, through the appropriation process,
to target specific areas for increased fund-
ing. Such was the case for HIV/AIDS in the
1990s, in which advocacy groups managed
to increase HIV/AIDS funding at the NIH to
approximately US$3 billion by 2006, as well
as breast cancer research, which obtained
more than US$700 million from NIH in the
same year.
Many health advocates believe that the
push for global health and research on dis-
eases affecting developing countries was
long overdue. In fact, the BMGF has found
a niche that was not previously supported:
high-risk, high-impact projects in the
context of infectious diseases. One of the
BMGF principles is to “take risks, make big
bets, and move with urgency.” To this end,
the BMGF announced a new US$100 mil
-
lion programme in October 2007 to fund
1,000 new high-risk research projects under
the title “Grand Challenges Explorations”.
This new programme will complement the
GCGH projects with US$100,000 awards
that enable scientists to test new ideas by
using a faster approval process than a trad-
itional NIH grant (Cohen, 2007). “The sci
-
entific community has shown tremendous
interest in the Grand Challenges initiative,
and the projects funded so far are begin-
ning to show important progress,” com-
mented Varmus. “The new Explorations
initiative will help to further increase
innovation in global health research”
(www.gatesfoundation.org).
Although the BMGF should be com
-
mended for their role in raising the profile
of research into infectious diseases that pre-
dominantly affect the developing world, the
true impact of the GCGH will only be rea-
lized after the initial grants run out. Is five
years enough time to expect projects to yield
conclusive results? Will they lead to new
products that benefit people in developing
countries? Will promising projects find new
funding if the BMGF does not continue to
support them through its GCGH? Are the
GCGH projects focused on the right priori
-
ties? Only time will tell if the GCGH initia
-
tive and its goals are an efficient strategy to
improve global health. In the meantime, they
serve to focus the attention of policy-makers,
scientists, the media and the general public
on the particular health problems that still
affect the majority of people on this planet—
a worthwhile goal indeed.
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BMGF (2006) Annual Report. Seattle, WA, USA:
Bill and Melinda Gates Foundation.
www.gatesfoundation.org
Brower V (2005) The squeaky wheel gets the
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assault on killer diseases. Nature 421: 461–462
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researchers unless they pool data. The Wall
Street Journal 20 July
Cohen J (2005) Gates Foundation picks winners
in Grand Challenges in Global Health.
Science
309: 33–35
Cohen J (2007) Bill and Melinda play risk.
Science
318: 183
Gates W (2003) Humane research: the West’s
best scientists should turn their attention to the
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Journal 26 Jan
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delivered before the International Congress
of Mathematicians at Paris in 1900.
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Math Soc 8: 437–479
Intersociety Working Group (2007)
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(www.aaas.org/spp/rd/)
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Daar AS, Singer PA (2003) Grand Challenges in
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of the donation. Nature 447: 248–250
Many health advocates believe
that the push for global health
and research on diseases
affecting developing countries
was long overdue
Kirstin R.W. Matthews (left) and Vivian Ho (right)
are at the James A. Baker III Institute of Public
Policy, Rice University, Houston, TX, USA;
Vivian Ho is also at the Department of Medicine,
Baylor College of Medicine, Houston, TX, USA.
E-mail: krwm@rice.edu
doi:10.1038/embor.2008.52