The Cutter Incident, 50 Years Later
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《新英格兰医药杂志》
On April 12, 1955, Jonas Salk's polio vaccine — made by inactivating poliovirus with formaldehyde — was declared to be safe and effective. The trial of Salk's vaccine had included 1.8 million children who were inoculated with either vaccine (made by either Eli Lilly or Parke-Davis) or placebo or were not inoculated but only observed. That afternoon, an advisory committee to the Laboratory of Biologics Control (the federal agency that was responsible for licensing biologic products in the United States) recommended that licenses to produce the vaccine be granted to five pharmaceutical companies: Eli Lilly, Parke-Davis, Wyeth, Pitman-Moore, and Cutter. The licensing process took only two and a half hours.
Technician at Cutter Laboratories Inspecting Filters during the Manufacture of Polio Vaccine, 1955.
Courtesy of Bayer Corp.
Two weeks after the release of the vaccine, on April 26, the director of the Laboratory of Biologics Control, William Workman, received a series of telephone calls about five children in California who had become paralyzed after receiving polio vaccine. In each case, paralysis occurred in the arm that was inoculated, and in each case, the vaccine had been made by Cutter Laboratories. Cutter's vaccine was immediately recalled, but 380,000 doses had already been administered — mostly to healthy first- and second-graders.
The Epidemic Intelligence Service of the Communicable Diseases Center (a precursor of the Centers for Disease Control and Prevention) was asked to determine whether polio vaccine was causing the paralysis. The agency's scientists found that two production pools made by Cutter Laboratories (accounting for 120,000 doses) contained live poliovirus. Among the children who had received vaccine from these pools, abortive polio (characterized by headache, stiff neck, fever, and muscle weakness) developed in 40,000; 51 were permanently paralyzed; and 5 died.1 Cutter's vaccine also started a polio epidemic: 113 people in the children's families or communities were paralyzed, and 5 died.1 It was one of the worst pharmaceutical disasters in U.S. history.
Subsequent studies found that cell debris contained in Cutter's vaccine had prevented adequate exposure of virus particles to formaldehyde. The federal requirements for vaccine manufacture were revised, and between 1955 and 1962, a total of 400 million doses of safe, inactivated polio vaccine were distributed in the United States; the incidence of polio decreased dramatically.
Two years after the tragedy, the first lawsuit was filed on behalf of Anne Gottsdanker, a five-year-old girl whose right leg was paralyzed as a result of Cutter's vaccine. Cutter was sued on two counts: negligence (that the company failed to exercise ordinary care in the production of its vaccine) and breach of implied warranty (that it was implied that a vaccine labeled "inactivated" polio vaccine did not contain live poliovirus).2
The jury was shown two pieces of evidence that determined the verdict: all five companies had difficulties in completely inactivating poliovirus, and Wyeth Laboratories also produced one lot of vaccine that paralyzed and killed several children in the Northeast.3 The jury found that Cutter Laboratories was not negligent but was guilty of breaching an implied warranty.
The ruling in Gottsdanker v. Cutter Laboratories meant that juries could find companies financially responsible (liable) for their products without finding them negligent in the production or design of those products (i.e., liability without fault). In reference to the Cutter tragedy, an article in the Yale Law Journal stated that "manufacturers of products for human consumption are liable for personal injuries caused by their products, not because they are at `fault' for the injuries, nor because they would have prevented them, but because they can best distribute this unavoidable cost to all persons who benefit from the enterprise."4
Since proof of negligence was no longer required, it was easier for juries to find pharmaceutical companies liable. Decisions could now be made solely on the basis of the harmfulness of the product — and therefore relied on the jury's capacity to understand the science of cause and effect. Unfortunately, jurors have been imperfect arbiters of scientific truth, as they have shown, for example, in deciding that silicone-filled breast implants caused connective-tissue diseases and that Bendectin (a combination of vitamin B6 and doxylamine) and spermicidal jellies caused birth defects.
Initially, vaccines were unaffected by the Gottsdanker verdict. But in the early 1980s, lawyers in the United States successfully sued vaccine makers, claiming that the pertussis vaccine caused permanent harm, despite a series of studies whose results were at variance with such claims. To raise enough money to pay for increased liability insurance, the companies hiked the cost of the diphtheria–tetanus–pertussis vaccine from $0.17 per dose to $11 per dose, and the number of companies that made the vaccine dropped from eight to one.
In 1986, to ensure the continued participation of pharmaceutical companies in the manufacture of vaccines, the National Vaccine Injury Compensation Program (VICP) was born. Funded by a federal excise tax on each dose of vaccine, the VICP remains a model method for ensuring that all persons harmed by vaccines are compensated quickly and generously, while also protecting companies that make lifesaving products from abuses of the tort system.
Unfortunately, as plaintiff lawyers begin to find weaknesses in the VICP, the viability of vaccines is again threatened. For example, when the program rejects claims that are not supported by medical or scientific studies, lawyers can easily opt out of the program. Hundreds of lawsuits have been filed claiming that the preservative thimerosal, which was added to many vaccines before 2001, caused autism. Although this contention is not supported by a recent study by the Institute of Medicine,5 vaccine makers have spent tens of millions of dollars defending against these lawsuits and are bracing for settlements or awards that could threaten their desire to remain in the vaccine business.
What's more, the VICP does not cover some vaccines. Plaintiffs have sued makers of the vaccine against Lyme disease on the grounds that the vaccine caused chronic arthritis, even though these claims were unsupported by large prelicensure studies. In part because of media attention to these lawsuits — and resultant fears that the vaccine was unsafe — the manufacturer stopped making Lyme vaccine. In addition, because coverage by the VICP does not extend to the fetus, vaccine makers have been hesitant to pursue strategies that include immunizing pregnant women to prevent diseases such as those caused by respiratory syncytial virus or group B streptococcus.
The Cutter incident resulted in the first coordinated national response to a medical emergency and in the creation of a better system of regulating vaccines. But the incident's final ironic legacy may lie in a court ruling that, although designed to protect children from harm, has greatly reduced the willingness of pharmaceutical companies to make lifesaving vaccines.(Paul A. Offit, M.D.)
Technician at Cutter Laboratories Inspecting Filters during the Manufacture of Polio Vaccine, 1955.
Courtesy of Bayer Corp.
Two weeks after the release of the vaccine, on April 26, the director of the Laboratory of Biologics Control, William Workman, received a series of telephone calls about five children in California who had become paralyzed after receiving polio vaccine. In each case, paralysis occurred in the arm that was inoculated, and in each case, the vaccine had been made by Cutter Laboratories. Cutter's vaccine was immediately recalled, but 380,000 doses had already been administered — mostly to healthy first- and second-graders.
The Epidemic Intelligence Service of the Communicable Diseases Center (a precursor of the Centers for Disease Control and Prevention) was asked to determine whether polio vaccine was causing the paralysis. The agency's scientists found that two production pools made by Cutter Laboratories (accounting for 120,000 doses) contained live poliovirus. Among the children who had received vaccine from these pools, abortive polio (characterized by headache, stiff neck, fever, and muscle weakness) developed in 40,000; 51 were permanently paralyzed; and 5 died.1 Cutter's vaccine also started a polio epidemic: 113 people in the children's families or communities were paralyzed, and 5 died.1 It was one of the worst pharmaceutical disasters in U.S. history.
Subsequent studies found that cell debris contained in Cutter's vaccine had prevented adequate exposure of virus particles to formaldehyde. The federal requirements for vaccine manufacture were revised, and between 1955 and 1962, a total of 400 million doses of safe, inactivated polio vaccine were distributed in the United States; the incidence of polio decreased dramatically.
Two years after the tragedy, the first lawsuit was filed on behalf of Anne Gottsdanker, a five-year-old girl whose right leg was paralyzed as a result of Cutter's vaccine. Cutter was sued on two counts: negligence (that the company failed to exercise ordinary care in the production of its vaccine) and breach of implied warranty (that it was implied that a vaccine labeled "inactivated" polio vaccine did not contain live poliovirus).2
The jury was shown two pieces of evidence that determined the verdict: all five companies had difficulties in completely inactivating poliovirus, and Wyeth Laboratories also produced one lot of vaccine that paralyzed and killed several children in the Northeast.3 The jury found that Cutter Laboratories was not negligent but was guilty of breaching an implied warranty.
The ruling in Gottsdanker v. Cutter Laboratories meant that juries could find companies financially responsible (liable) for their products without finding them negligent in the production or design of those products (i.e., liability without fault). In reference to the Cutter tragedy, an article in the Yale Law Journal stated that "manufacturers of products for human consumption are liable for personal injuries caused by their products, not because they are at `fault' for the injuries, nor because they would have prevented them, but because they can best distribute this unavoidable cost to all persons who benefit from the enterprise."4
Since proof of negligence was no longer required, it was easier for juries to find pharmaceutical companies liable. Decisions could now be made solely on the basis of the harmfulness of the product — and therefore relied on the jury's capacity to understand the science of cause and effect. Unfortunately, jurors have been imperfect arbiters of scientific truth, as they have shown, for example, in deciding that silicone-filled breast implants caused connective-tissue diseases and that Bendectin (a combination of vitamin B6 and doxylamine) and spermicidal jellies caused birth defects.
Initially, vaccines were unaffected by the Gottsdanker verdict. But in the early 1980s, lawyers in the United States successfully sued vaccine makers, claiming that the pertussis vaccine caused permanent harm, despite a series of studies whose results were at variance with such claims. To raise enough money to pay for increased liability insurance, the companies hiked the cost of the diphtheria–tetanus–pertussis vaccine from $0.17 per dose to $11 per dose, and the number of companies that made the vaccine dropped from eight to one.
In 1986, to ensure the continued participation of pharmaceutical companies in the manufacture of vaccines, the National Vaccine Injury Compensation Program (VICP) was born. Funded by a federal excise tax on each dose of vaccine, the VICP remains a model method for ensuring that all persons harmed by vaccines are compensated quickly and generously, while also protecting companies that make lifesaving products from abuses of the tort system.
Unfortunately, as plaintiff lawyers begin to find weaknesses in the VICP, the viability of vaccines is again threatened. For example, when the program rejects claims that are not supported by medical or scientific studies, lawyers can easily opt out of the program. Hundreds of lawsuits have been filed claiming that the preservative thimerosal, which was added to many vaccines before 2001, caused autism. Although this contention is not supported by a recent study by the Institute of Medicine,5 vaccine makers have spent tens of millions of dollars defending against these lawsuits and are bracing for settlements or awards that could threaten their desire to remain in the vaccine business.
What's more, the VICP does not cover some vaccines. Plaintiffs have sued makers of the vaccine against Lyme disease on the grounds that the vaccine caused chronic arthritis, even though these claims were unsupported by large prelicensure studies. In part because of media attention to these lawsuits — and resultant fears that the vaccine was unsafe — the manufacturer stopped making Lyme vaccine. In addition, because coverage by the VICP does not extend to the fetus, vaccine makers have been hesitant to pursue strategies that include immunizing pregnant women to prevent diseases such as those caused by respiratory syncytial virus or group B streptococcus.
The Cutter incident resulted in the first coordinated national response to a medical emergency and in the creation of a better system of regulating vaccines. But the incident's final ironic legacy may lie in a court ruling that, although designed to protect children from harm, has greatly reduced the willingness of pharmaceutical companies to make lifesaving vaccines.(Paul A. Offit, M.D.)