Interferon: The Science and Selling of a Miracle Drug
http://www.100md.com
《新英格兰医药杂志》
In 1957, the discovery of an antiviral agent that could rival the bactericidal power of penicillin generated excitement in government, industry, the media, and the general public. Nearly 50 years later, this class of biologic agents collectively called interferons generates a $5 billion global drug market.
In Interferon: The Science and Selling of a Miracle Drug, Toine Pieters charts the culture of medical research in the mid-to-late 20th century, the blossoming of biotechnology, the politics of scientific research, the influence of the media, and the pressure of lobbies for patients.
What is particularly effective (and accurate) in Pieters's book is the detailed story of the early years of interferon research — a story of a dedicated band of believers who kept faith in the face of conflicting data and impure preparations of variable potency. Pieters captures the pioneering atmosphere of those days very well. In this era of biologicals — when hundreds of molecularly defined, pure recombinant cytokines can be ordered for next-day delivery — it is easy to forget that at one time the best interferon source in the world had only 0.1 percent purity and was made from Sendai virus–stimulated human leukocytes. For many years, scientists doubted the very existence of interferon and its antiviral activity. Indeed, as late as 1977, when I started a postdoctoral fellowship with the interferon researcher Joyce Taylor, the immunologist Peter Alexander said to me, "But Fran, you cannot work with interferon — it doesn't exist!" Just three years later, the first (of many) human interferon genes was cloned by Biogen and Schering-Plough.
The interferons (there are 4 main types and more than 20 subtypes with the shared ability to induce an antiviral state in cells) blazed the biotechnology trail. Their story illustrates the challenge of developing therapeutic proteins. Interferon research also laid the foundation of cytokine biology, defining the unexpected hallmarks of this important group of intercellular communicators: families of proteins with pleiotropic effects on homeostasis and disease, species specificity, byzantine regulatory mechanisms, activity in picomolar or femtomolar amounts, and key roles in both innate and adaptive immunity.
In the 1970s, interferon was a magic bullet, a wonder drug that could cure all ills, especially cancer. Pieters writes, "The picture conveyed . . . interferon as a somewhat mysterious, clinically unharnessed, non-toxic natural body substance that was claimed to be the hottest, though long ignored, line of medical research currently being followed." The media gave the impression that if only there was enough of this extremely scarce and expensive natural protein, everything from chickenpox to cancer would be cured. Virologist Mathilde Krim and oncologist Jordan Gutterman lobbied Congress so effectively that 3 percent of the annual National Cancer Institute budget was earmarked for the Biological Response Modifier Program on the condition that the focus would be on interferon. The interferon message was one of promise and hope, and the media coverage in the 1970s and 1980s mirrored the expectations and opinions of those in the biomedical realm.
The history of interferon, which must be considered to be recent, is full of surprises. For instance, in 2005, when it takes months and mountains of paper before permission is granted by an ethics review board to conduct the simplest clinical trial, it seems amazing that the first clinical studies with interferon alpha used historical controls and very small numbers of patients. But this protocol was not particularly unusual for that time. We learn in Pieters's book that in the 1970s, many oncologists claimed that randomization in clinical trials was neither ethical nor necessary.
When there was enough interferon to go around for properly conducted clinical trials, however, the results were disappointing and the interferons were consigned for many years to the status of orphan drugs for rare terminal diseases. Their slow and continuing transformation into approved and effective drugs for more than 10 diseases is another interesting story but one that is not covered in detail in this book. I found this omission disappointing. However, Pieters focuses on answering one intriguing question: Why does interferon enjoy a public reputation similar to penicillin's even though it remains a treatment confined almost entirely to specialty diseases? In its answer, the book succeeds admirably.
Fran Balkwill, Ph.D.
Barts and the London Queen Mary's Medical School
London EC1Y 2AN, United Kingdom
frances.balkwill@cancer.org.uk((Routledge Studies in the)
In Interferon: The Science and Selling of a Miracle Drug, Toine Pieters charts the culture of medical research in the mid-to-late 20th century, the blossoming of biotechnology, the politics of scientific research, the influence of the media, and the pressure of lobbies for patients.
What is particularly effective (and accurate) in Pieters's book is the detailed story of the early years of interferon research — a story of a dedicated band of believers who kept faith in the face of conflicting data and impure preparations of variable potency. Pieters captures the pioneering atmosphere of those days very well. In this era of biologicals — when hundreds of molecularly defined, pure recombinant cytokines can be ordered for next-day delivery — it is easy to forget that at one time the best interferon source in the world had only 0.1 percent purity and was made from Sendai virus–stimulated human leukocytes. For many years, scientists doubted the very existence of interferon and its antiviral activity. Indeed, as late as 1977, when I started a postdoctoral fellowship with the interferon researcher Joyce Taylor, the immunologist Peter Alexander said to me, "But Fran, you cannot work with interferon — it doesn't exist!" Just three years later, the first (of many) human interferon genes was cloned by Biogen and Schering-Plough.
The interferons (there are 4 main types and more than 20 subtypes with the shared ability to induce an antiviral state in cells) blazed the biotechnology trail. Their story illustrates the challenge of developing therapeutic proteins. Interferon research also laid the foundation of cytokine biology, defining the unexpected hallmarks of this important group of intercellular communicators: families of proteins with pleiotropic effects on homeostasis and disease, species specificity, byzantine regulatory mechanisms, activity in picomolar or femtomolar amounts, and key roles in both innate and adaptive immunity.
In the 1970s, interferon was a magic bullet, a wonder drug that could cure all ills, especially cancer. Pieters writes, "The picture conveyed . . . interferon as a somewhat mysterious, clinically unharnessed, non-toxic natural body substance that was claimed to be the hottest, though long ignored, line of medical research currently being followed." The media gave the impression that if only there was enough of this extremely scarce and expensive natural protein, everything from chickenpox to cancer would be cured. Virologist Mathilde Krim and oncologist Jordan Gutterman lobbied Congress so effectively that 3 percent of the annual National Cancer Institute budget was earmarked for the Biological Response Modifier Program on the condition that the focus would be on interferon. The interferon message was one of promise and hope, and the media coverage in the 1970s and 1980s mirrored the expectations and opinions of those in the biomedical realm.
The history of interferon, which must be considered to be recent, is full of surprises. For instance, in 2005, when it takes months and mountains of paper before permission is granted by an ethics review board to conduct the simplest clinical trial, it seems amazing that the first clinical studies with interferon alpha used historical controls and very small numbers of patients. But this protocol was not particularly unusual for that time. We learn in Pieters's book that in the 1970s, many oncologists claimed that randomization in clinical trials was neither ethical nor necessary.
When there was enough interferon to go around for properly conducted clinical trials, however, the results were disappointing and the interferons were consigned for many years to the status of orphan drugs for rare terminal diseases. Their slow and continuing transformation into approved and effective drugs for more than 10 diseases is another interesting story but one that is not covered in detail in this book. I found this omission disappointing. However, Pieters focuses on answering one intriguing question: Why does interferon enjoy a public reputation similar to penicillin's even though it remains a treatment confined almost entirely to specialty diseases? In its answer, the book succeeds admirably.
Fran Balkwill, Ph.D.
Barts and the London Queen Mary's Medical School
London EC1Y 2AN, United Kingdom
frances.balkwill@cancer.org.uk((Routledge Studies in the)