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Leading Edge

Commentary

Roots, Not Parachutes:


Research Collaborations Combat Outbreaks
Nathan L. Yozwiak,1,2,* Christian T. Happi,3,4 Donald S. Grant,5 John S. Schieffelin,6 Robert F. Garry,6 Pardis C. Sabeti,1,2,7
and Kristian G. Andersen2,8,9,*
1Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA
2Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
3Department of Biological Sciences, Redeemers University, Ede, Osun State, Nigeria
4African Center of Excellence for Genomics of Infectious Disease, Redeemers University, Ede, Osun State, Nigeria
5Kenema Government Hospital, Kenema, Sierra Leone
6Tulane University Medical Center, New Orleans, LA 70112, USA
7Howard Hughes Medical Institute, Chevy Chase, MD, USA
8The Scripps Research Institute, Department of Immunology and Microbial Science, La Jolla, CA 92037, USA
9Scripps Translational Science Institute, La Jolla, CA 92037, USA

*Correspondence: nyozwiak@broadinstitute.org (N.L.Y.), kristian@andersen-lab.com (K.G.A.)


http://dx.doi.org/10.1016/j.cell.2016.06.029

Recent infectious disease epidemics illustrate how health systems failures anywhere can create
disease vulnerabilities everywhere. We must therefore prioritize investments in health care infra-
structure in outbreak-prone regions of the world. We describe how rooted research collabora-
tions can establish capacity for pathogen surveillance and facilitate rapid outbreak responses.

International research collaborations are and MERS. Additionally, endemic human vaccines and therapeutics make early
essential in combating major public pathogens, such as dengue and West detection, isolation, and contact tracing
health emergencies. Failure to collabo- Nile virus, have expanded to new regions critical. However, even when effective
rate can delay critical findings, hamper due to changing demographics and vaccines are availablesuch as in the
outbreak response, and erode trust be- increased urbanization. recent outbreaks of yellow fever in Africa
tween institutions and nations. In this Due in part to underinvestment in and measles in the USbreakdown of
commentary, we expand on recent dis- health care infrastructure and scientific health care infrastructure and/or low
cussions on the lack of openness during research, Africa harbors a dispropor- vaccination rates allow preventable infec-
public health emergencies and perceived tionate infectious disease burden and tious diseases to spread. Combined with
exploitation of disease-stricken countries vulnerability to acute outbreaks. Though an ever expanding human population
by parachute researchers (Heymann more than a billion people call Africa and an increase in the ease of travel, in-
et al., 2016). We draw on our experience home, the continent produces only 5% fectious disease outbreaks can therefore
establishing the Viral Hemorrhagic Fever of the worlds gross domestic product no longer be considered local threats,
Consortium and the African Center of (UNESCO, 2015). Total investments in Af- but rather represent international emer-
Excellence for Genomics of Infectious rican research and development (R&D) gencies. With these factors in mind, we
Disease in West Africa and show how rose more than 50% between 2007 and anticipate recurring interactions with se-
rooted collaborations can assist during 2013, but still comprise less than 1.5% vere pathogens, with unpredictable con-
public health emergencies. Recognizing of the worlds total R&D expenditure sequences to human health.
that many successful infectious disease (Marsh, 2016). This increase in invest-
research collaborations exist, we highlight ment, however, translated into an imme- Rooted Research
their critical and often unheralded role diate expansion of scientific output, with The recent Ebola and Zika epidemics illus-
in mitigating and preventing infectious a rise in publications of 60% from 2007 trate how vulnerable the world can be to
disease outbreaks. to 2013, compared to less than 15% in the threat from severe viruses. To effec-
Infectious disease outbreaks continue Europe over the same period (Marsh, tively combat such pathogens, the global
to pose challenges to global health and 2016). community must prioritize investments
security, prompting reactive counter- Health care and disease surveillance in health care infrastructure in regions of
measures. Recently, severe outbreaks of disparities can exacerbate local out- the world most susceptible to outbreaks,
Ebola and Zika virus were designated by breaks into global infectious threats. The and establish local capacity for pathogen
the World Health Organization as Public large imbalance between health care ca- detection and containment before they
Health Emergencies of International pacity in Africa and most western nations occur. This capacity building should not
Concern. Other emerging viral patho- means that serious infectious disease only focus on the potential danger from
gens have warranted similar attention, outbreaks in Africa should be shared con- emerging pathogens, but rather should
including virus outbreaks from Lassa, Chi- cerns in the US, Europe, and elsewhere. address ongoing matters of local pub-
kungunya, avian influenza, Nipah, SARS, Controlling pathogens that lack effective lic health importance. Well-established

Cell 166, June 30, 2016 2016 Elsevier Inc. 5


research collaborations are at commonly built on four pillars:
the center of creating such (1) co-creation, (2) capacity
capacity and can serve as a building, (3) sustainability,
major source of knowledge and (4) openness. Co-crea-
transfer and preparedness tion, through the mutual
before, during, and after an agreement on research goals,
outbreak. This is a much outcomes, and scientific pub-
more powerful and cost ef- lications among partners.
fective strategy than reacting Capacity building, through
once the outbreak has begun, frequent training and estab-
as in the 2013-2016 Ebola vi- lishment of scientific infra-
rus disease (EVD) epidemic. structure. Sustainability, by
What would become the providing short-term and
largest recorded EVD out- long-term research goals,
break began in December and continued technology
2013 in Guinea, yet was not transfer among partners. And
detected until March 2014 finally, openness, by immedi-
(Baize et al., 2014). Local ate public sharing of data,
outbreak responders contrib- analyses, findings, and, if
uted vital efforts during the feasible, resources and sam-
epidemictragically result- ples (Figure 1).
ing in more than 500 deaths We are not advocating sim-
of West African healthcare ply for the creation of addi-
workers (Currie et al., 2016). tional research consortia or
Ultimately, more than USD recognition of the general ben-
$7 billion were raised for the efits of scientific collaboration.
response, but despite this Research collaborations have
Figure 1. Pillars Underlying Rooted Infectious Disease Research
large injection of foreign become standard practice
Collaborations
capital, only once the local Rooted partnerships operating during public health emergencies are across all sciences; address-
response was sufficiently commonly built on four pillarsco-creation, capacity building, sustainability, ing big scientific challenges,
strengthened did the region and opennessthat enable immediate and long-term approaches for such as emerging infectious
outbreak response. Artwork by Sigrid Knemeyer.
control the outbreak. Collabo- disease surveillance and con-
rative clinical research played trol, unquestionably requires
a key role in facilitating this, by ensuring In several cases, international scientists large, multi-disciplinary teams. We also
comprehensive training of West African with no established collaborations in recognize that one size does not fit all for
outbreak responders. In addition, some West Africa allegedly transported sam- research collaborations and that there
of the diagnostic and surveillance labora- ples back to their home countries for exist many successful approaches to
tories established during the epidemic further research, in many cases without forming lasting and mutually beneficial
remain in place and continue to support permission or knowledge of the affected research partnerships. Rather, we seek
case investigations by local researchers nations (Heymann et al., 2016). Parachute to highlight the critical and often unher-
(Ariasa et al., 2016; Blackley et al., research can be detrimental to emer- alded role of rooted research collabora-
2016). These operations added critical gency response by preventing sharing tions in mitigating and preventing infec-
capacity to detect and investigate the of resources critical to public health and tious disease outbreaks. Sustainable
multiple flare-ups of EVD observed over fails to enhance the capacity of affected partnerships build trust and capacity
the last year and continue to be instru- regions to combat future outbreaks (Hey- upon which outbreak responses can be
mental in determining likely transmission mann et al., 2016). quickly mobilized.
chains originating from EVD survivors A more successful and sustainable
(Ariasa et al., 2016; Blackley et al., 2016). approach to outbreak response is built Collaboration, Education, and
Despite the ultimate containment of on collaborations that incorporate both Capacity Building in West Africa
EVD, however, collaborations during the immediate and long-term solutions for Our collective experience establishing
20132016 EVD epidemiclike many outbreak prevention into their infec- research consortia in West Africaone
other public health emergencies before tious disease research programs. We among many infectious disease collabo-
itwere often sub-optimal (Heymann term this rooted research to reflect rationsprovides insights into the value
et al., 2016). In some instances, re- the need for securing the research of rooted research partnerships. We
searchers parachuted into the affected with a firm foundation in the affected have tried to build and guide these collab-
countries, conducted research in isola- countries. As opposed to parachute orations adhering to the four pillars of co-
tion, and departed without creating sus- research, rooted partnerships operating creation, capacity building, sustainability,
tainable infrastructure or a lasting impact. during public health emergencies are and openness.

6 Cell 166, June 30, 2016


Building on decades of research expe- education to create a critical mass of Sierra Leonean and American partners.
rience in West Africa, weresearchers well-trained African scientists to carry A similar assay had previously been
from West Africa and the USco-created out genomic infectious disease surveil- developed for Lassa virus; both tests
the Viral Hemorrhagic Fever Consortium lance in West Africa. were used in Sierra Leone during the
(VHFC; www.vhfc.org) in 2010 with the The establishment of VHFC and epidemic, and via new collaborations are
goal of enabling research leading to better ACEGID facilitated rooted collaborations now expanding their reach into other
diagnostics and treatments for Lassa that not only allowed us to perform West African countries. Notably, much of
fevera virus that causes hemorrhagic research on Lassa fever directly in the the research was performed and directed
fever in thousands of people annually. communities most affected by them, but by West African researchers with shared
The VHFC unites the worlds only two to be better prepared for the emergence co-first and co-senior authorships on
Lassa fever wards, at Kenema Govern- of another viral hemorrhagic fever virus. the resulting scientific publications. We
ment Hospital (KGH), Sierra Leone, and As the EVD epidemic spread to Sierra believe these advances would have
Irrua Specialist Teaching Hospital (ISTH), Leone and then Nigeria, the research been delayed or impossible were it not
Nigeria, with academic, government, and capacity and partnerships developed for existing commitments to long-term
industry partners. Investment by local in-country enabled early and critical rooted scientific projects in Sierra Leone
ministries of health and US governmental response and insights into the outbreak. and Nigeria.
agencies has supported clinical centers Within a week after Ebola virus was
capable of reliable diagnosis, clinical confirmed in Guinea, together with the Future Responses
care, and investigation of category-A level Sierra Leone Ministry of Health and Nurturing rooted research requires
pathogens in otherwise austere circum- Sanitation, we implemented PCR-based long-term investment and planning. The
stances. Together, in 2014 we also diagnostic tests for Ebola virus at KGH to benefits of collaboration may take many
founded the African Center of Excellence supplement already available diagnostic years of commitment and cooperation
for Genomics of Infectious Disease assays for other severe pathogens. This to appear, which requires dedicated
(ACEGID; acegid.org), centered at Re- enabled local staff to rapidly detect and funding, even when wealthy countries
deemers University, Nigeria with support respond to the first Sierra Leonean EVD face no immediate outbreak threats.
from the World Bank and H3Africa. patient who presented at KGH at the end Increasingly, global health funders are
ACEGID expands infectious disease of May 2014 (Gire et al., 2014). The same facilitating rooted South-South (i.e.,
research and training among West African tests were introduced at Redeemers intra-African) research partnerships such
researchers and has established genomic University, which allowed Nigerian re- that low and middle income country re-
sequencing capabilities for the study and searchers to quickly diagnose the first searchers independently set research
surveillance of human pathogens. case of EVD in Nigeria in July 2014. Over agendas and program direction. Pro-
Capacity building and long-term sus- the ensuing months, Sierra Leonean and grams supported by the US. National In-
tainability have both been central tenets Nigerian researchers continued to play a stitutes of Health (H3Africa), World Bank
of ACEGID and VHFC. In addition to critical role in diagnosing EVD cases and (African Centers of Excellence), the US.
investment in clinical, diagnostic, and other febrile patients. Centers for Disease Control and Preven-
research infrastructure, both consortia In addition to these diagnostic efforts, tion, Institut Pasteur, the Fogarty Founda-
also have a significant focus on training our collaborations also made possible tion, the UK Medical Research Council,
African researchers, combined with several scientific studies that could be and the Wellcome Trust (DELTAS), seek
frequent technology transfer to West Af- shared rapidly and openly to ensure to establish long-term and equitable
rica. By creating ACEGID we sought to maximum utility from the research. Open science partnerships between African
expand the training part of our collabora- sharing of data and analyses encourages nations and international partners. For
tions, by creating long-term graduate- close collaborations, enables broad in- example, the H3Africa program advo-
level (M.S. and Ph.D.) programs for African vestigations, and can help correct or cates access to funding, samples, and
university students, as well as short-term corroborate analyses that the original in- data for African researchers and sets
foundational training programs for African vestigators had posited. Our efforts al- a new standard for international collabo-
educators and laboratory technicians. In lowed us to investigate clinical features rative health research that involves Afri-
addition to training at host institutions of EVD (Schieffelin et al., 2014) and can research participants. An important
in West Africa, we have established two- dissect the molecular evolution and aspect of H3Africa research is that it is
month training programs for African edu- spread of Ebola virus during the epidemic under the leadership of scientists on the
cators and researchers hosted each year (Gire et al., 2014; Park et al., 2015). We African continent, with grants awarded
in the US. Now entering its third year, this immediately released all the generated to, and managed by, African institutions.
annual program has educated over two data into the public domain - a practice North-South (i.e., international-African)
dozen students in a training-of-trainers many other groups also followed during collaborations can continue to flourish
model, covering molecular diagnostics, the epidemic. The rooted collaborations under such programs, perhaps even
microbiology, evolutionary genetics, and in Sierra Leone and Nigeria also led to more strongly, as collaborators prioritize
teaching pedagogy. Ultimately, we aim the development and manufacturing of professional interests and research ques-
to modularize and extend this approach, an Ebola virus rapid bedside diagnostic tions while encouraging long-term finan-
pairing laboratory enhancements and test (Corgenix ReEBOV), co-created by cial health and independence.

Cell 166, June 30, 2016 7


Ultimately, rooted research consortia this manuscript. C.H. is supported by the World Coulter, S., Mate, S., et al. (2016). Science
can enable robust detection systems Bank project ACE019 and NIH H3Africa Award Advances 2, e1600378.
1U01HG007480-03. R.F.G. is supported by NIH
to rapidly respond as outbreaks first Currie, J., Grenfell, B., and Farrar, J. (2016). Sci-
grants and contracts including 1R01AI104621,
emerge. We envision networks of partner ence 351, 815816.
U19AI115589, and U19AI109762. P.C.S. is an
laboratories equipped with diagnostic Howard Hughes Medical Institute Investigator, Gire, S.K., Goba, A., Andersen, K.G., Sealfon, R.S.,
and genome sequencing capacity and and her work is supported in part by NIH Park, D.J., Kanneh, L., Jalloh, S., Momoh, M.,
know-how to characterize the range of 1R01AI114855-01 and U19AI110818. K.G.A. is a Fullah, M., Dudas, G., et al. (2014). Science 345,
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Translational Studies Clinical and Translational
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ACKNOWLEDGMENTS
Rapid outbreak sequencing of Ebola virus in Sierra Schieffelin, J.S., Shaffer, J.G., Goba, A., Gbakie,
Leone identifies transmission chains linked to spo- M., Gire, S.K., Colubri, A., Sealfon, R.S., Kanneh,
We honor and thank all the African outbreak re-
radic cases (Virus Evolution). L., Moigboi, A., Momoh, M., et al.; KGH Lassa
sponders who worked to control the 2013-2016
Baize, S., Pannetier, D., Oestereich, L., Rieger, T., Fever Program; Viral Hemorrhagic Fever Con-
EVD epidemic, many of whom tragically died in
Koivogui, L., Magassouba, N., Soropogui, B., Sow, sortium; WHO Clinical Response Team (2014).
the process. We also thank all the members of the
M.S., Keta, S., De Clerck, H., et al. (2014). N. Engl. N. Engl. J. Med. 371, 20922100.
Viral Hemorrhagic Fever Consortium and the Afri-
can Center of Excellence for Genomics of Infec- J. Med. 371, 14181425. UNESCO (2015). UNESCO Science Report: To-
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Jasmine Hanifi for helpful suggestions in preparing Lo, T., Gilbert, M.L., Gregory, C., Dambrozio, J., report.

8 Cell 166, June 30, 2016

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