Opinion
SCIENTIFIC DISCOVERY AND THE FUTURE OF MEDICINE VIEWPOINT
Jeremy Farrar, FRS, FRCP, FMedSci, OBE The Wellcome Trust, London, United Kingdom.
Corresponding Author: Jeremy Farrar, FRCP, FMedSci, OBE, The Wellcome Trust, Gibbs Bldg, 215 Euston Rd, London NW1 2BE, United Kingdom (j.farrar @wellcome.ac.uk).
Science, Medicine, and Society A View From the Wellcome Trust tions between medicine, life, and art. Last year saw the culmination of Art in Global Health, a project and exhibition involving artist residencies in Trust-funded research centers in the United Kingdom, South Africa, Malawi, Kenya, Thailand, and Vietnam. Such a range of activities provides a unique perspective on health and medicine, incorporating culture and society with science and innovation. Being independent, the Trust can work with national governments, health care systems, and pharmaceutical companies anywhere in the world, as well as with academia, whether funding basic cell biology, population health research, commercial applications, or capacity building and engagement. As part of the Affordable Healthcare in India scheme, for example, the Trust recently supported OneBreath, a Silicon Valley start-up, and Vaatsalya, a health care company in India, to develop a new ventilator that could substantially increase access to mechanical ventilation in Indian community hospitals and help prevent deaths from respiratory illnesses. In the United Kingdom, a different perspective is being explored in a project called As ever, translating new knowledge Life of Breath: pulmonologists, philosointo better health will require the phers of medicine, cultural scholars, and people with chronic obstructive pulmoseamless integration of science, nary disease are working together to unmedicine, and society. derstand the subjective experience of breathing and breathlessness. sowed the seeds for modern medical progress. But The Trust can take a very long-term view. For many their stories reveal that scientific evidence is not decades, the Trust has invested in programs to enough to improve medicine: social and cultural fac- strengthen health research in low- and middle-income tors are vital as well. countries, including Human Heredity and Health in Africa The Wellcome Trust was established in London in (H3Africa, in partnership with multiple collaborators in 1936, under the will of Sir Henry Wellcome, to Africa and with the US National Institutes of Health). advance medical research and the understanding of Building on this experience, the Trust launched a new its history. The Trust continues to pursue that vision scheme last year to support African-led development of today, supported by investments currently worth world-class researchers. In time, the Developing Excelabout $27 billion, of which more than $1 billion is lence in Leadership, Training and Science (DELTAS) Africa spent each year around the world.3 The Trust funds initiative will give a new generation of African scientists research across the biomedical sciences and biotech- a major role in deciding, shaping, and driving a locally relnology, interrogating the fundamental processes of evant health research agenda and contributing to betlife in health and in sickness and using that knowledge ter health for the continent. to develop ways to promote well-being and to diagBut the Trust can also tackle urgent problems. Faced nose, treat, or prevent disease. with the Ebola epidemic in West Africa last year, the reBecause the Trust appreciates the importance of sponse of the Trust was fast, effective, and coordithe history and social contexts of medicine, it also nated with other agencies. In a matter of weeks, more supports research across the medical humanities, than $15 million was committed to projects aimed at unsocial sciences, and bioethics, as well as funding for derstanding, controlling, and ending the outbreak, inartists and educators to engage the public with cluding contributions to vaccine and therapeutic trials, research. Wellcome Collection, a free public venue, epidemiology, anthropology, and the ethics of conductoffers exhibitions and events exploring the connec- ing research during an epidemic. In 1847, Ignaz Semmelweis introduced a policy of handwashing at the Vienna Maternity Hospital to prevent medical students transferring disease from bodies in the morgue to patients on the wards. Although this policy considerably reduced mortality, it was not adopted in other hospitals. Semmelweis was an uncharismatic champion of progress, but there was also resistance from physicians who rejected the idea that diseases could be transmitted in such a way and concluded—in the face of the evidence—that handwashing could not possibly have any effect.1 Similarly, John Snow had the handle of London’s Broad Street pump removed in 1854 to stop transmission of cholera through the water supply, but as soon as the outbreak was over the pump handle was replaced and the authorities rejected Snow’s theories.2 Semmelweis and Snow—and other pioneers such as Pasteur, Koch, and Gorgas—helped develop understanding of the causes of infectious diseases and
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(Reprinted) JAMA June 16, 2015 Volume 313, Number 23
Copyright 2015 American Medical Association. All rights reserved.
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Opinion Viewpoint
The Ebola epidemic shows how scientific modern medicine can be in creating a pathway from identification of a pathogen to drugs, vaccines, and public health measures to treat or prevent the disease. However, additional work and progress are needed. The world was underprepared for this epidemic: treatments had been in development, but work had all but halted until the severity of the outbreak was realized. However, even for diseases that have sustained funding and interest, such as human immunodeficiency virus/AIDS, essential vaccines have not yet been developed. With infectious diseases, the path is never straight: each success creates further challenges. The Wellcome Trust was deeply involved in the introduction of artemisinin-based therapies for malaria. Scientists in the Southeast Asia research program chanced on a Chinese study detailing the antimalarial properties of an herb from the sweet wormwood tree. Years of Trust-funded research and clinical trials followed to prove that a derivative of this herb—artemisinin— was better than quinine for treating malaria.4 Eventually, international treatment guidelines were changed to recommend artemisinin. As a consequence, and along with the use of insecticidetreated bed nets, millions of lives have been saved. Less than a decade later, however, societies face the emergence of malarial parasites resistant to artemisinin. Increased resistance is not confined to malaria. Antibiotics are generally at risk of becoming ineffective as drug-resistant bacteria spread. The Trust has funded research into new antibiotics— including the discovery of plazomicin, which was taken into earlystage clinical trials by the US biopharmaceutical company Achaogen with Trust funding and is now in phase 3 trials to assess its effectiveness in treating carbapenem-resistant Enterobacteriaceae. But the Trust also supports new approaches in scientific discovery. The trust has supported the British company Oxitec to develop and breed “sterile” males of mosquito species that carry diseases such as dengue. Field trials of these mosquitoes, and other mosquito-control approaches developed by Eliminate Dengue and supported by the Trust and the Bill & Melinda Gates Foundation, are under way or soon to start in Brazil, Panama, Vietnam, and Indonesia. These are innovative ideas based on outstanding science, but they will also need outstanding communicaARTICLE INFORMATION Conflict of Interest Disclosures: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and reported receiving grants from the Wellcome Trust from 1996 to 2013 and serving as director of the Wellcome Trust since 2013. REFERENCES 1. Loudon I. Ignaz Phillip Semmelweis’ studies of death in childbirth. J R Soc Med. 2013;106(11):461-
2316
tion and engagement between researchers and the public before they can be implemented widely. Although there have been great strides in many areas of medicine in the last century, in some areas it has proved much more difficult to see the way forward. For instance, current understanding of mental health, and of diseases such as schizophrenia and depression, arguably remains prescientific, even though mental and substance use disorders are the leading cause of years lived with disability worldwide and are associated with 8.6 million years of life lost to premature mortality each year.5 A solid theoretical understanding is lacking to explain how the mind works within the brain, and until a mechanistic framework is established, research will continue to proceed by trial and error. There are rigorous studies testing mental health interventions, but without an underlying mechanistic framework, scientists will continue to look for pathways in uncharted territory. Here, too, the Trust can be a catalyst. The Trust supported the Human Genome Project through the Wellcome Trust Sanger Institute. At a time when competition between several centers threatened to allow access to the human genome to be controlled by commercial interests, the independence of the Trust facilitated open publication of the data. This helped to drive advances in sequencing and create opportunities for commercial applications, laying the foundation for the full potential of genomic medicine to be realizable within a lifetime. Can a similar transformation be catalyzed in neuroscience and mental health? Taking a long-term view, the Trust is collaborating with the Gatsby Foundation to establish the Sainsbury Wellcome Centre for Neural Circuits and Behavior in London. The field of neural circuits is barely a decade old, but as new technologies come together, this field of discovery will grow to provide a real understanding of the mechanisms of the mind. With that understanding, bolstered by research in ethics and the humanities, will come the possibility of truly rationally designed interventions in mental health, where the need is so great and knowledge so thin. As ever, translating new knowledge into better health will require the seamless integration of science, medicine, and society. If anything, it is even more important today than in the time of Semmelweis, Snow, or Gorgas.
463http://jrs.sagepub.com/content/106/11/461 .extract. Accessed February 19, 2015. 2. Cameron D, Jones IG. John Snow, the broad street pump and modern epidemiology. Int J Epidemiol. 1983;12(4):393-396. 3. Wellcome Trust. The Wellcome Trust Annual Report and Financial Statements 2014. London, United Kingdom: Wellcome Trust; 2014.
treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial. Lancet. 2010;376(9753):1647-1657. 5. Whiteford HA, Degenhardt L, Rehm J, et al. Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010. Lancet. 2013;382 (9904):1575-1586.
4. Dondorp AM, Fanello CI, Hendriksen IC, et al; AQUAMAT Group. Artesunate versus quinine in the
JAMA June 16, 2015 Volume 313, Number 23 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a University of Georgia User on 06/16/2015
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SCIENTIFIC DISCOVERY AND THE FUTURE OF MEDICINE VIEWPOINT
Jeremy Farrar, FRS, FRCP, FMedSci, OBE The Wellcome Trust, London, United Kingdom.
Corresponding Author: Jeremy Farrar, FRCP, FMedSci, OBE, The Wellcome Trust, Gibbs Bldg, 215 Euston Rd, London NW1 2BE, United Kingdom (j.farrar @wellcome.ac.uk).
Science, Medicine, and Society A View From the Wellcome Trust tions between medicine, life, and art. Last year saw the culmination of Art in Global Health, a project and exhibition involving artist residencies in Trust-funded research centers in the United Kingdom, South Africa, Malawi, Kenya, Thailand, and Vietnam. Such a range of activities provides a unique perspective on health and medicine, incorporating culture and society with science and innovation. Being independent, the Trust can work with national governments, health care systems, and pharmaceutical companies anywhere in the world, as well as with academia, whether funding basic cell biology, population health research, commercial applications, or capacity building and engagement. As part of the Affordable Healthcare in India scheme, for example, the Trust recently supported OneBreath, a Silicon Valley start-up, and Vaatsalya, a health care company in India, to develop a new ventilator that could substantially increase access to mechanical ventilation in Indian community hospitals and help prevent deaths from respiratory illnesses. In the United Kingdom, a different perspective is being explored in a project called As ever, translating new knowledge Life of Breath: pulmonologists, philosointo better health will require the phers of medicine, cultural scholars, and people with chronic obstructive pulmoseamless integration of science, nary disease are working together to unmedicine, and society. derstand the subjective experience of breathing and breathlessness. sowed the seeds for modern medical progress. But The Trust can take a very long-term view. For many their stories reveal that scientific evidence is not decades, the Trust has invested in programs to enough to improve medicine: social and cultural fac- strengthen health research in low- and middle-income tors are vital as well. countries, including Human Heredity and Health in Africa The Wellcome Trust was established in London in (H3Africa, in partnership with multiple collaborators in 1936, under the will of Sir Henry Wellcome, to Africa and with the US National Institutes of Health). advance medical research and the understanding of Building on this experience, the Trust launched a new its history. The Trust continues to pursue that vision scheme last year to support African-led development of today, supported by investments currently worth world-class researchers. In time, the Developing Excelabout $27 billion, of which more than $1 billion is lence in Leadership, Training and Science (DELTAS) Africa spent each year around the world.3 The Trust funds initiative will give a new generation of African scientists research across the biomedical sciences and biotech- a major role in deciding, shaping, and driving a locally relnology, interrogating the fundamental processes of evant health research agenda and contributing to betlife in health and in sickness and using that knowledge ter health for the continent. to develop ways to promote well-being and to diagBut the Trust can also tackle urgent problems. Faced nose, treat, or prevent disease. with the Ebola epidemic in West Africa last year, the reBecause the Trust appreciates the importance of sponse of the Trust was fast, effective, and coordithe history and social contexts of medicine, it also nated with other agencies. In a matter of weeks, more supports research across the medical humanities, than $15 million was committed to projects aimed at unsocial sciences, and bioethics, as well as funding for derstanding, controlling, and ending the outbreak, inartists and educators to engage the public with cluding contributions to vaccine and therapeutic trials, research. Wellcome Collection, a free public venue, epidemiology, anthropology, and the ethics of conductoffers exhibitions and events exploring the connec- ing research during an epidemic. In 1847, Ignaz Semmelweis introduced a policy of handwashing at the Vienna Maternity Hospital to prevent medical students transferring disease from bodies in the morgue to patients on the wards. Although this policy considerably reduced mortality, it was not adopted in other hospitals. Semmelweis was an uncharismatic champion of progress, but there was also resistance from physicians who rejected the idea that diseases could be transmitted in such a way and concluded—in the face of the evidence—that handwashing could not possibly have any effect.1 Similarly, John Snow had the handle of London’s Broad Street pump removed in 1854 to stop transmission of cholera through the water supply, but as soon as the outbreak was over the pump handle was replaced and the authorities rejected Snow’s theories.2 Semmelweis and Snow—and other pioneers such as Pasteur, Koch, and Gorgas—helped develop understanding of the causes of infectious diseases and
jama.com
(Reprinted) JAMA June 16, 2015 Volume 313, Number 23
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a University of Georgia User on 06/16/2015
2315
Opinion Viewpoint
The Ebola epidemic shows how scientific modern medicine can be in creating a pathway from identification of a pathogen to drugs, vaccines, and public health measures to treat or prevent the disease. However, additional work and progress are needed. The world was underprepared for this epidemic: treatments had been in development, but work had all but halted until the severity of the outbreak was realized. However, even for diseases that have sustained funding and interest, such as human immunodeficiency virus/AIDS, essential vaccines have not yet been developed. With infectious diseases, the path is never straight: each success creates further challenges. The Wellcome Trust was deeply involved in the introduction of artemisinin-based therapies for malaria. Scientists in the Southeast Asia research program chanced on a Chinese study detailing the antimalarial properties of an herb from the sweet wormwood tree. Years of Trust-funded research and clinical trials followed to prove that a derivative of this herb—artemisinin— was better than quinine for treating malaria.4 Eventually, international treatment guidelines were changed to recommend artemisinin. As a consequence, and along with the use of insecticidetreated bed nets, millions of lives have been saved. Less than a decade later, however, societies face the emergence of malarial parasites resistant to artemisinin. Increased resistance is not confined to malaria. Antibiotics are generally at risk of becoming ineffective as drug-resistant bacteria spread. The Trust has funded research into new antibiotics— including the discovery of plazomicin, which was taken into earlystage clinical trials by the US biopharmaceutical company Achaogen with Trust funding and is now in phase 3 trials to assess its effectiveness in treating carbapenem-resistant Enterobacteriaceae. But the Trust also supports new approaches in scientific discovery. The trust has supported the British company Oxitec to develop and breed “sterile” males of mosquito species that carry diseases such as dengue. Field trials of these mosquitoes, and other mosquito-control approaches developed by Eliminate Dengue and supported by the Trust and the Bill & Melinda Gates Foundation, are under way or soon to start in Brazil, Panama, Vietnam, and Indonesia. These are innovative ideas based on outstanding science, but they will also need outstanding communicaARTICLE INFORMATION Conflict of Interest Disclosures: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and reported receiving grants from the Wellcome Trust from 1996 to 2013 and serving as director of the Wellcome Trust since 2013. REFERENCES 1. Loudon I. Ignaz Phillip Semmelweis’ studies of death in childbirth. J R Soc Med. 2013;106(11):461-
2316
tion and engagement between researchers and the public before they can be implemented widely. Although there have been great strides in many areas of medicine in the last century, in some areas it has proved much more difficult to see the way forward. For instance, current understanding of mental health, and of diseases such as schizophrenia and depression, arguably remains prescientific, even though mental and substance use disorders are the leading cause of years lived with disability worldwide and are associated with 8.6 million years of life lost to premature mortality each year.5 A solid theoretical understanding is lacking to explain how the mind works within the brain, and until a mechanistic framework is established, research will continue to proceed by trial and error. There are rigorous studies testing mental health interventions, but without an underlying mechanistic framework, scientists will continue to look for pathways in uncharted territory. Here, too, the Trust can be a catalyst. The Trust supported the Human Genome Project through the Wellcome Trust Sanger Institute. At a time when competition between several centers threatened to allow access to the human genome to be controlled by commercial interests, the independence of the Trust facilitated open publication of the data. This helped to drive advances in sequencing and create opportunities for commercial applications, laying the foundation for the full potential of genomic medicine to be realizable within a lifetime. Can a similar transformation be catalyzed in neuroscience and mental health? Taking a long-term view, the Trust is collaborating with the Gatsby Foundation to establish the Sainsbury Wellcome Centre for Neural Circuits and Behavior in London. The field of neural circuits is barely a decade old, but as new technologies come together, this field of discovery will grow to provide a real understanding of the mechanisms of the mind. With that understanding, bolstered by research in ethics and the humanities, will come the possibility of truly rationally designed interventions in mental health, where the need is so great and knowledge so thin. As ever, translating new knowledge into better health will require the seamless integration of science, medicine, and society. If anything, it is even more important today than in the time of Semmelweis, Snow, or Gorgas.
463http://jrs.sagepub.com/content/106/11/461 .extract. Accessed February 19, 2015. 2. Cameron D, Jones IG. John Snow, the broad street pump and modern epidemiology. Int J Epidemiol. 1983;12(4):393-396. 3. Wellcome Trust. The Wellcome Trust Annual Report and Financial Statements 2014. London, United Kingdom: Wellcome Trust; 2014.
treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial. Lancet. 2010;376(9753):1647-1657. 5. Whiteford HA, Degenhardt L, Rehm J, et al. Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010. Lancet. 2013;382 (9904):1575-1586.
4. Dondorp AM, Fanello CI, Hendriksen IC, et al; AQUAMAT Group. Artesunate versus quinine in the
JAMA June 16, 2015 Volume 313, Number 23 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a University of Georgia User on 06/16/2015
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