Nigel Lane, Louise Powter, and Sam Patel (eds)
- Published in print:
- 2016
- Published Online:
- November 2020
- ISBN:
- 9780199680269
- eISBN:
- 9780191918360
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/oso/9780199680269.003.0016
- Subject:
- Clinical Medicine and Allied Health, Professional Development in Medicine
Eugene H. Cordes
- Published in print:
- 2014
- Published Online:
- November 2020
- ISBN:
- 9780199337149
- eISBN:
- 9780197562864
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/oso/9780199337149.003.0013
- Subject:
- Chemistry, Medicinal Chemistry
The Perils of Pauline is a 1914 film serial in 20 episodes. In each episode, a villain, perhaps a pirate, menaces Pauline, played by Pearl White. In each episode, ...
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The Perils of Pauline is a 1914 film serial in 20 episodes. In each episode, a villain, perhaps a pirate, menaces Pauline, played by Pearl White. In each episode, Pauline seems certain to meet her demise, only to escape or be rescued at the last possible moment. Outdoing the proverbial cat of nine lives, Pauline had 20. The Perils of Pauline bears more than a passing resemblance to drug discovery and development in which some villain, perhaps an issue of safety or efficacy, threatens the life of a project. I know of no better example of this than the course of getting the antibiotic Primaxin from the laboratory to the bedside. The perils of Primaxin plays out in a scientific serial of five episodes in which the project is rescued from impending disaster in each episode. The Primaxin story is one of the great tales of drug discovery in the world of antibiotics—the molecules that have power to prevent or cure bacterial infections. Primaxin is a triumph of the pharmaceutical industry in general and of Merck specifically. Victory did not come easily. The road from a drug discovery start to a marketable human health product is often rough, occasionally very rough, and sometimes impassable. The Primaxin story stands out for the number and nature of bumps and ruts that impeded passage. That Primaxin made it to the market for the benefit of countless patients with infectious diseases is a tribute to the wit and determination of the many scientists who saw it through. That story comes later. Let’s get started with some general background on the field of antibiotics. The next time you have the occasion to explore a cemetery, have a look at the tombstones for people born around 1900. A significant fraction of those tombstones will reveal that the date of death is within 10 years of the date of birth. Simply put, many people born around 1900 or earlier did not live to be 10 years old.
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The Perils of Pauline is a 1914 film serial in 20 episodes. In each episode, a villain, perhaps a pirate, menaces Pauline, played by Pearl White. In each episode, Pauline seems certain to meet her demise, only to escape or be rescued at the last possible moment. Outdoing the proverbial cat of nine lives, Pauline had 20. The Perils of Pauline bears more than a passing resemblance to drug discovery and development in which some villain, perhaps an issue of safety or efficacy, threatens the life of a project. I know of no better example of this than the course of getting the antibiotic Primaxin from the laboratory to the bedside. The perils of Primaxin plays out in a scientific serial of five episodes in which the project is rescued from impending disaster in each episode. The Primaxin story is one of the great tales of drug discovery in the world of antibiotics—the molecules that have power to prevent or cure bacterial infections. Primaxin is a triumph of the pharmaceutical industry in general and of Merck specifically. Victory did not come easily. The road from a drug discovery start to a marketable human health product is often rough, occasionally very rough, and sometimes impassable. The Primaxin story stands out for the number and nature of bumps and ruts that impeded passage. That Primaxin made it to the market for the benefit of countless patients with infectious diseases is a tribute to the wit and determination of the many scientists who saw it through. That story comes later. Let’s get started with some general background on the field of antibiotics. The next time you have the occasion to explore a cemetery, have a look at the tombstones for people born around 1900. A significant fraction of those tombstones will reveal that the date of death is within 10 years of the date of birth. Simply put, many people born around 1900 or earlier did not live to be 10 years old.
Eugene H. Cordes
- Published in print:
- 2014
- Published Online:
- November 2020
- ISBN:
- 9780199337149
- eISBN:
- 9780197562864
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/oso/9780199337149.003.0014
- Subject:
- Chemistry, Medicinal Chemistry
These are the words of Dr. William C. Campbell, hereinafter known as Bill. Bill was Merck’s leading authority on parasitic diseases. He played the leading role in the ...
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These are the words of Dr. William C. Campbell, hereinafter known as Bill. Bill was Merck’s leading authority on parasitic diseases. He played the leading role in the discovery of the greatest antiparasitic drugs in history—ivermectin and abamectin. Having said this, and as Bill has pointed out, this drug discovery story, like all of them, was the result of a team effort involving hundreds of people. When you start giving credit by naming scientists who contributed, it is tough to know when to stop. If you try to name them all, you get a telephone book for a small village and you will still miss somebody. The other extreme is to name nobody, but I have already violated that alternative. So I will mention four scientists at Merck who, in addition to Bill, were the authors of the publication in the prestigious journal Science of the article announcing the discovery of ivermectin. They are Mike Fisher, the chemist who led the chemistry effort at Merck focused on the avermectins; Ed Stapley, who led Merck’s natural product screening effort; Georg Albers-Schönberg, who headed the group that elucidated the structure of the avermectins; and Ted Jacob, Merck’s leader of animal drug metabolism. Before getting into the story, a word about names—this time about molecules, not scientists. As I relate in this chapter, avermectins are a small family of related molecules. Ivermectin is a chemically modified derivative of one of the avermectins, and abamectin is one of the avermectins. Bill Campbell is an Irishman and native of Donegal. He took himself to Trinity College in Dublin for his undergraduate work where he did research under the direction of J. Desmond Smyth, a noted parasitologist. Near the end of Bill’s undergraduate days at Trinity College, Dr. Arlie Todd of the University of Wisconsin wrote Smyth to ask whether he had any promising students to recommend for graduate study. Smyth recommended Bill to Todd, along with two others.
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These are the words of Dr. William C. Campbell, hereinafter known as Bill. Bill was Merck’s leading authority on parasitic diseases. He played the leading role in the discovery of the greatest antiparasitic drugs in history—ivermectin and abamectin. Having said this, and as Bill has pointed out, this drug discovery story, like all of them, was the result of a team effort involving hundreds of people. When you start giving credit by naming scientists who contributed, it is tough to know when to stop. If you try to name them all, you get a telephone book for a small village and you will still miss somebody. The other extreme is to name nobody, but I have already violated that alternative. So I will mention four scientists at Merck who, in addition to Bill, were the authors of the publication in the prestigious journal Science of the article announcing the discovery of ivermectin. They are Mike Fisher, the chemist who led the chemistry effort at Merck focused on the avermectins; Ed Stapley, who led Merck’s natural product screening effort; Georg Albers-Schönberg, who headed the group that elucidated the structure of the avermectins; and Ted Jacob, Merck’s leader of animal drug metabolism. Before getting into the story, a word about names—this time about molecules, not scientists. As I relate in this chapter, avermectins are a small family of related molecules. Ivermectin is a chemically modified derivative of one of the avermectins, and abamectin is one of the avermectins. Bill Campbell is an Irishman and native of Donegal. He took himself to Trinity College in Dublin for his undergraduate work where he did research under the direction of J. Desmond Smyth, a noted parasitologist. Near the end of Bill’s undergraduate days at Trinity College, Dr. Arlie Todd of the University of Wisconsin wrote Smyth to ask whether he had any promising students to recommend for graduate study. Smyth recommended Bill to Todd, along with two others.
Dickson D. Despommier and William C. Campbell
- Published in print:
- 2013
- Published Online:
- November 2015
- ISBN:
- 9780231161947
- eISBN:
- 9780231535267
- Item type:
- chapter
- Publisher:
- Columbia University Press
- DOI:
- 10.7312/columbia/9780231161947.003.0008
- Subject:
- Public Health and Epidemiology, Public Health
This chapter examines the life cycle of Onchocerca volvulus. Onchocerca volvulus is a nematode that causes onchocerciasis or “river blindness.” The life cycle of this parasite begins when an infected ...
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This chapter examines the life cycle of Onchocerca volvulus. Onchocerca volvulus is a nematode that causes onchocerciasis or “river blindness.” The life cycle of this parasite begins when an infected female black fly of the genus Simulium bites its host. The worms then mature inside the subcutaneous tissues, just underneath the skin. They induce the host to produce a nodule of tissue, often reaching the size of a walnut, where the worms will dwell and lay eggs. The adult parasites also coax the host to supply extension of their body blood circulation to obtain nutrients. The larvae of the worm, called microfilariae, would then irritate the subcutaneous tissues, causing the corneal stroma to thicken, until the host becomes blind.Less
This chapter examines the life cycle of Onchocerca volvulus. Onchocerca volvulus is a nematode that causes onchocerciasis or “river blindness.” The life cycle of this parasite begins when an infected female black fly of the genus Simulium bites its host. The worms then mature inside the subcutaneous tissues, just underneath the skin. They induce the host to produce a nodule of tissue, often reaching the size of a walnut, where the worms will dwell and lay eggs. The adult parasites also coax the host to supply extension of their body blood circulation to obtain nutrients. The larvae of the worm, called microfilariae, would then irritate the subcutaneous tissues, causing the corneal stroma to thicken, until the host becomes blind.
Stephen L. Cochi and Walter R. Dowdle (eds)
- Published in print:
- 2011
- Published Online:
- August 2013
- ISBN:
- 9780262016735
- eISBN:
- 9780262304207
- Item type:
- book
- Publisher:
- The MIT Press
- DOI:
- 10.7551/mitpress/9780262016735.001.0001
- Subject:
- Biology, Disease Ecology / Epidemiology
Disease eradication represents the ultimate in global equity and the definitive outcome of good public health practice. Thirty years ago, the elimination of smallpox defined disease eradication as a ...
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Disease eradication represents the ultimate in global equity and the definitive outcome of good public health practice. Thirty years ago, the elimination of smallpox defined disease eradication as a monumental global achievement with lasting benefits for society. Today, the global commitment to eradicate polio and guinea worm, and heightened interest in the potential eradication of other infectious diseases, including measles/rubella, lymphatic filariasis, onchocerciasis, and malaria, dominate public health concerns. But what does it take to eradicate a disease? This book takes a look at the evolving concepts of disease eradication, influenced by scientific advances, field experience, societal issues, and economic realities. A diverse group of experts from around the world, representing a range of disciplines, examines the biological, social, political, and economic complexities of eradicating a disease. The book details lessons learned from the initiatives against polio, measles/rubella, and onchocerciasis. Further chapters examine ethical issues, the investment case, governance models, organizational and institutional arrangements, political and social factors, the feasibility of eradication goals, priority setting, and the integration of disease eradication programs with existing health systems.Less
Disease eradication represents the ultimate in global equity and the definitive outcome of good public health practice. Thirty years ago, the elimination of smallpox defined disease eradication as a monumental global achievement with lasting benefits for society. Today, the global commitment to eradicate polio and guinea worm, and heightened interest in the potential eradication of other infectious diseases, including measles/rubella, lymphatic filariasis, onchocerciasis, and malaria, dominate public health concerns. But what does it take to eradicate a disease? This book takes a look at the evolving concepts of disease eradication, influenced by scientific advances, field experience, societal issues, and economic realities. A diverse group of experts from around the world, representing a range of disciplines, examines the biological, social, political, and economic complexities of eradicating a disease. The book details lessons learned from the initiatives against polio, measles/rubella, and onchocerciasis. Further chapters examine ethical issues, the investment case, governance models, organizational and institutional arrangements, political and social factors, the feasibility of eradication goals, priority setting, and the integration of disease eradication programs with existing health systems.
Adrian Hopkins
- Published in print:
- 2011
- Published Online:
- August 2013
- ISBN:
- 9780262016735
- eISBN:
- 9780262304207
- Item type:
- chapter
- Publisher:
- The MIT Press
- DOI:
- 10.7551/mitpress/9780262016735.003.0004
- Subject:
- Biology, Disease Ecology / Epidemiology
Onchocerciasis is a skin disease characterized by intense itching and the presence of filaria in the skin of those infected, and which is also associated with blindness. This chapter discusses the ...
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Onchocerciasis is a skin disease characterized by intense itching and the presence of filaria in the skin of those infected, and which is also associated with blindness. This chapter discusses the evolution of the onchocerciasis program and the lessons learned along the way. It describes the two major onchocerciasis programs—the Onchocerciasis Elimination Program for the Americas (OEPA) and the African Program for Onchocerciasis Control (APOC), and the strategies developed by these initiatives. The emphasis for onchocerciasis eradication has been the “elimination of transmission.” There is also a need to develop surveillance, monitoring, and diagnostic tools to certify that the disease has been eradicated.Less
Onchocerciasis is a skin disease characterized by intense itching and the presence of filaria in the skin of those infected, and which is also associated with blindness. This chapter discusses the evolution of the onchocerciasis program and the lessons learned along the way. It describes the two major onchocerciasis programs—the Onchocerciasis Elimination Program for the Americas (OEPA) and the African Program for Onchocerciasis Control (APOC), and the strategies developed by these initiatives. The emphasis for onchocerciasis eradication has been the “elimination of transmission.” There is also a need to develop surveillance, monitoring, and diagnostic tools to certify that the disease has been eradicated.
Margaret S. McMillan, William A. Masters, and Harounan Kazianga
- Published in print:
- 2016
- Published Online:
- May 2017
- ISBN:
- 9780226316222
- eISBN:
- 9780226316369
- Item type:
- chapter
- Publisher:
- University of Chicago Press
- DOI:
- 10.7208/chicago/9780226316369.003.0006
- Subject:
- Economics and Finance, Development, Growth, and Environmental
This paper uses historical census data from Burkina Faso to characterize local demographic pressures, including population shocks associated with internal migration after disease eradication in river ...
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This paper uses historical census data from Burkina Faso to characterize local demographic pressures, including population shocks associated with internal migration after disease eradication in river valleys, and forced repatriation of migrants from Cote d’Ivoire. We combine those data with a new survey of village elders that was designed to document change over time and differences across villages in local public goods provision, market infrastructure, and property rights. We hypothesize that higher local population densities are associated with more collective services and a transition from open-access to regulated land use, offering a village-level test of fundamental hypotheses about social and political change in Africa. Controlling for year and province fixed effects, we find that villages’ variance in population associated with proximity to river valleys and to Cote d’Ivoire is closely correlated with higher levels of public services, infrastructure, religious facilities, and markets; in addition, villagers’ land is more often governed through individual as opposed to familial rights, with more land-market transactions and stronger regulation of villagers’ forest use. Responding to population growth with improved public services and more private property rights is consistent with both scale effects in public good provision, and changes in the scarcity of land.Less
This paper uses historical census data from Burkina Faso to characterize local demographic pressures, including population shocks associated with internal migration after disease eradication in river valleys, and forced repatriation of migrants from Cote d’Ivoire. We combine those data with a new survey of village elders that was designed to document change over time and differences across villages in local public goods provision, market infrastructure, and property rights. We hypothesize that higher local population densities are associated with more collective services and a transition from open-access to regulated land use, offering a village-level test of fundamental hypotheses about social and political change in Africa. Controlling for year and province fixed effects, we find that villages’ variance in population associated with proximity to river valleys and to Cote d’Ivoire is closely correlated with higher levels of public services, infrastructure, religious facilities, and markets; in addition, villagers’ land is more often governed through individual as opposed to familial rights, with more land-market transactions and stronger regulation of villagers’ forest use. Responding to population growth with improved public services and more private property rights is consistent with both scale effects in public good provision, and changes in the scarcity of land.
