The human, societal, and scientific legacy of cholera William B. Greenough III J Clin Invest. 2004;113(3):334-339. https://doi.org/10.1172/JCI20982. Science and Society The recent history of research on cholera illustrates the importance of establishing research and care facilities equipped with advanced technologies at locations where specific health problems exist. It is in such settings, where scientific research is often considered difficult due to poverty and the lack of essential infrastructure, that investigators from many countries are able to make important advances. On this, the 25th anniversary of the founding of the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), this article seeks to recount the Centre’s demonstration of how high-quality research on important global health issues, including cholera, can be accomplished in conditions that may be considered by many as unsuitable for scientific research. Find the latest version: https://jci.me/20982/pdf SCIENCE AND SOCIETY The human, societal, and scientific legacy idly exchanging fluids and electrolytes with net secretion preeminent. The of cholera accurate measurement of the compo- sition of intestinal secretions and the William B. Greenough III clear demonstration that net fluid and electrolyte absorption could be Division of Geriatric Medicine, Department of Medicine, and Division of International achieved in cholera patients when glu- Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, cose was added to perfusing electrolyte Maryland, USA solutions formed the foundation not only for highly effective intravenous The recent history of research on cholera illustrates the importance of rehydration but also for oral rehydra- establishing research and care facilities equipped with advanced tech- tion therapy (ORT). The beauty of nologies at locations where specific health problems exist. It is in such ORT is that it does not require medical settings, where scientific research is often considered difficult due to skills to administer and it is inexpen- poverty and the lack of essential infrastructure, that investigators from sive. Both of these features make it many countries are able to make important advances. On this, the 25th accessible to nearly everyone, regard- anniversary of the founding of the International Centre for Diarrhoeal less of location or financial resources Disease Research, Bangladesh (ICDDR,B), this article seeks to recount (3). Today, over 100 countries have the Centre’s demonstration of how high-quality research on important programs to deliver this life-saving global health issues, including cholera, can be accomplished in conditions treatment, and ORT is used in over that may be considered by many as unsuitable for scientific research. 50% of all cases of diarrhea. The devel- opment and global application of J. Clin. Invest. 113:334–339 (2004). doi:10.1172/JCI200420982. ORT has decreased the death rates from diarrheal diseases by more than Cholera kills by swiftly draining away technologies, undertook clinical stud- half in the last 30 years. body fluids. It is an ancient scourge, ies in South and Southeast Asia where yet research on this disease has yielded cholera was endemic. This “bringing In the beginning insights into fundamental biological science to where the diarrhea is” (1) It was the agricultural sciences that processes and established effective dissipated the dogma of Rudolph Vir- first broke ground in establishing treatment that is within reach of every- chow — often considered the father of facilities where scientists from many one, even those who live in resource- modern pathology — which insisted different countries could do research poor, underserved areas of the planet. that Vibrio cholerae irreversibly dam- with advanced technologies on crops A more complete understanding of aged intestinal epithelium, causing the in their natural settings. In 1958, the cholera began when physician-scien- loss of protein-rich body fluids, just as International Rice Research Institute tists, versed in basic science and its one sees when the epithelium of other (IRRI) was established in Los Baños, tissues is destroyed. This theory was Philippines. Dedicated to aiding farm- Address correspondence to: William B. based on poorly collected clinical spec- ers in developing countries in produc- Greenough III, The John R. Burton Pavilion, imens from patients in India suffering ing more food on limited land while Johns Hopkins Bayview Care Center, cholera-induced shock for prolonged using less labor and water and fewer 5505 Hopkins Bayview Circle, Baltimore, Maryland 21224, USA. Phone: (410) 550-0782 periods with resulting ischemia and chemical additives, this institute was or (410) 550-0247; Fax: (410) 550-2513; mucosal autolysis. Virchow’s ideas the first step in what is now called “the E-mail: [email protected] or took nearly a century to disprove (2). Green Revolution” (4), which has [email protected]. His method, which depended on sam- allowed the rapid and increased pro- Conflict of interest: The author is a shareholder in and scientific advisor to Cera ple collection by poorly informed and duction of specific foodstuffs in order Products Inc., Jessup, Maryland, USA, which supervised workers in Calcutta, who to meet the needs of a rapidly expand- manufactures the rice-based oral electrolyte then shipped them to his home labo- ing world population. The IRRI and its solution CeraLyte. ratory in Europe, proved to be serious- successors have taken science and Nonstandard abbreviations used: oral rehydration therapy (ORT); International ly flawed. From 1960 to 1970, research advanced technologies to centers in Rice Research Institute (IRRI); Cholera by clinician-scientists on site in Dhaka, remote areas and staffed them with Research Laboratory (CRL); International Bangladesh (previously East Pakistan) top researchers, and through exten- Centre for Diarrhoeal Disease Research, and Calcutta, India demonstrated that sion activities have put their laborato- Bangladesh (ICDDR,B); International Centers for Medical Research and Training (ICMRT); the digestive system was not damaged ry findings into practice, first locally, oral rehydration solution (ORS). during cholera infection and was rap- then globally. This network of agricul- 334 The Journal of Clinical Investigation | February 2004 | Volume 113 | Number 3 Figure 1 Chronological landmarks during the development of current cholera therapies, including important achievements of the ICDDR,B. tural research centers has been coordi- developing countries, which ensured standing interactions between humans nated and supported by the Consulta- that scientists from all countries and the agents that cause specific dis- tive Group for Agricultural Research (developed and developing) could be eases requires sustained research at sites under the auspices of the World Bank. recruited to work without lengthy or where disease is prevalent. Only years of The adaptation of the agricultural obstructive visa processing and that sustained observation and hypothesis sciences model to basic health science supplies and technologies could be testing have clarified the mechanisms practice in developing countries has imported without duties or customs by which cholera is maintained in the been partially realized. In 1960, Fred delays. The sovereignty of the host surface waters of rural and urban areas Soper used the charter of the Institute country was protected by the ex officio of Bangladesh and how it causes sea- of Nutrition of Central America and presence on the governing boards of sonal epidemics in human populations. Panama as a model for establishing trustees by positions designated by the A precise model of the interaction of V. the Cholera Research Laboratory host country, which included the Sec- cholerae with phytoplankton could only (CRL) in Dhaka, and in doing so retary of Health, the Secretary of the have been determined at a location became the first CRL Director. In External Resources Department, and a where cholera was endemic (5). In order 1978, the CRL became the Interna- third respected member from the local to effectively study the epidemiology tional Centre for Diarrhoeal Disease scientific and/or public health fields. and pathophysiology of cholera in Research, Bangladesh (ICDDR,B). Its Thus, the charter of the ICDDR,B is a countries with limited or low resources, charter was negotiated with the gov- conceptual blend of the charters of the a stable institution in situ with excel- ernment of Bangladesh and was agricultural and health sciences. In lent advanced laboratories and a dedi- accepted by the United Nations Devel- December 2003, the ICDDR,B cele- cated staff of high-quality scientists and opment Program at a meeting hosted brated its 25th anniversary, marking technicians was necessary. The rapid, by the WHO in Geneva in 1979. It its contributions to science and global efficient sharing of patient cultures and incorporated features of the Interna- health (Figure 1). serum samples with collaborating lab- tional Agricultural Research Centers, Many diseases have highly specific oratories throughout the world has as well as features from previous inter- relationships with a particular geo- been of critical importance. Such spec- national health research efforts in graphic location and ecology. Under- imens were usually hand carried by the The Journal of Clinical Investigation | February 2004 | Volume 113 | Number 3 335 Figure 2 A three-month-old