Full text of DOI:10.1093/jhmas/57.3.249

The True Story of Pertussis Vaccination:
A Sordid Legacy?
DAVID GEIER and MARK GEIER
URING the last half of the twentieth century, pertus-
sis vaccine has been at the center of controversies
over the evaluation and marketing of vaccines for
children. This controversy has transcended the sim-
ple confines of scientific research to redefine rela-
tionships among industry, government, law, and
consumer advocacy. The dangerous side effects of whole-cell pertussis
vaccine have been known for at least the last five decades, and for
the last four a safer alternative has been available. But not untilthe
late s has that safer alternative become routine for American
children. This paper explains why and how this transformation in
care took place. We were part of the transformation, supporting the
advocates for the new, acellular vaccine with scientific testimony.
Although our appearance in this story takes place in the s, the
history of the vaccine began much earlier in the twentieth century.
Even though there was incidentalmedicalevidence as earyl as the
s and clear-cut evidence by the s that whole-cell pertussis
vaccine caused neurological sequelae, American pharmaceuticalcom-
panies by and large persisted in marketing whole-cell vaccines until
the end of  because the acellular versions, in their opinion, were
too costly to produce, test, and sell. Nevertheless, U.S. manufacturers
were granted at least one patent in every decade since the s
to produce acellular pertussis vaccines, and severalcountries either
legislated the use of the acellular form only or stopped using pertussis
vaccination altogether. Change finally began in the United States in
We thank Dr. Margaret Humphreys of the Journal of the History of Medicine and Allied Sciences
for her patience and help in significantly revising and improving our paper.

2002 oxford university press
issn 0022-5045
volume 57
pages 249 to 284
[  ]

 Journal of the History of Medicine : Vol. , July 
the s and was completed by , largely because of the combined
pressures of litigation and political action on the part of groups of
parents whose children were damaged by the whole-cell vaccines.
These groups pressured the federalgovernment to study and ameilo-
rate the adverse effects of the vaccine, but the federalgovernment
was also pressured by vaccine producers for protection from the
potentially large numbers of highly expensive civil lawsuits brought
by parents. These pressures culminated in the passage of a compensa-
tion act and the charging of the U.S. Institute of Medicine (IOM)
of the NationalAcademy of Sciences to make recommendations
for solving the problem. This ultimately led to the licensing and
recommendation of acellular pertussis vaccine for booster shots begin-
ning in  and for all shots given beginning in . By the end
of , U.S. manufacturers had stopped making whole-cell pertussis
vaccine for use in the United States.
In this detailed history of the topic, we first describe the infectious
disease pertussis and the story of the vaccines produced to prevent
it. We then consider the history of scientific knowledge about the
myriad adverse reactions that have been observed following vaccina-
tionfrom mild fevers to seizures, encephalopathy, permanent brain
damage, and even death. We review the history of the scientific
advances that allowed production of a far safer and more effective
vaccine. Finally, we explore the history of the industrial, monetary,
political, legal, and consumer factors that finally led to the use of the
safer vaccine for all U.S. children as well as the work that still needs
to be done to provide it to children around the world.
the scourge of pertussis
Pertussis, commonly called whooping cough, is a bacterialinfection
that usually strikes its victims with initially mild symptoms, resulting
in an incubation time for the disease that is hard to determine but
is usually estimated to be from six to twenty days, with a mean of
seven days. As the disease progresses the symptoms become more
pronounced, with coughing episodes occurring ten to twenty-five
times a day as a means to expel accumulated mucus blocking the
airway. After the mucus is expelled, the victim’s breathing is labored
due to swollen and irritated air passages, which results in the produc-
tion of a whooping sound with every inhalation. The disease severely
affects the nutrition and hydration of its victims. The cough causes

Geier & Geier : Pertussis Vaccination

hemorrhages on various portions of the body, herniae, emphysema,
and pneumothorax. Additionally, the disease in its most severe forms
can cause seizures, encephalopathy, and even death. Recovery from
the disease is characterized by a decreasing frequency of coughing
episodes and a general increase in wellness. However, this usually
requires many weeksa characteristic reflected in the Japanese and
Chinese name for pertussis: the -day cough.1
Pertussis is an epidemic disease, occurring every  to  years in
endemic areas, with an average intervalof . years. It is highly
infectious; attack rates in nonimmunized populations have been re-
ported to range from  to  percent in schools and from  to 
percent in susceptible household contacts. Based on data from a large
series of children hospitalized for pertussis, it has been estimated that
. to  percent or more of its victims will develop central nervous
system complications. The incidence rates of encephalopathy ranged
from an estimated . per , cases from  to  in Brooklyn,
New York, to . per , cases in the NationalEncephaolpathy
Study.2
Our earliest recorded description of pertussis comes from a 
record by Guillanne de Baillon:
The lung is so irritated by every attempt to expel that which is causing
the trouble it neither admits the air nor again easily expels it. The patient
is seen to well up and as if strangled holds his breath tightly in the middle
of the throat . . . For they are without the troublesome coughing for the
space of four or five hours at a time, then this paroxysm of coughing returns,
now so severe that blood is expelled with force through the nose and
through the mouth. Most frequently an upset stomach follows . . . For we
have seen so many coughing in such a manner, in whom after a vain attempt
semi-putrid matter in an incredible quantity was ejected.3
Unlike many bacterial diseases, in whooping cough the organism
does not invade the entire body but is localized in the lining of the
lungs. The most severe symptoms are caused by the poison the bacteria
. J. H. Lapin, Whooping Cough (Springfield, Ill.: Thomas Publishing, ); A. T. Wilson,
I. R. Henderson, E. J. H. Moore, and S. N. Heywood, “Whooping-cough: Difficulties in
Diagnosis and Ineffectiveness of Immunization,” Br. Med. J., , , –; L. C. Olson,
“Pertussis,” Medicine, , , –; F. F. Cartwright, Disease and History (New York:
Dorset Press, ).
. U.S. Institute of Medicine, Adverse Events Associated with Pertussis and Rubella Vaccines
(Washington, D.C.: NationalAcademy Press , ).
. Quoted in W. H. Holmes, Bacillary and Rickettsial Infections (New York: The Macmillan
Co., ).

 Journal of the History of Medicine : Vol. , July 
secrete, called pertussis toxin, which has a wide variety of effects in
patients. It sensitizes them to the effects of histamine through a
biological marker called histamine-sensitizing factor (HSF). Another
component, islet-activating factor (IAF), causes a rise in insulin secre-
tion and a consequent fall in blood sugar. This can cause brain damage
if it is too extreme because the brain is solely dependent on sugar
for its energy. Pertussis toxin includes leukocyte-promoting factor
(LPF), which raises white blood cell counts. The toxin lowers the
blood–brain barrier, allowing various other toxins and viruses to enter
the brain. And pertussis toxin itself is a known neurotoxin. Finally,
pertussis bacteria make an exotoxin called adenyl cyclase, which
adversely affects neurotransmitters.
Because the symptoms of whooping cough are caused primarily
by pertussis toxin, one of the main mechanisms by which pertussis
vaccines protect against whooping cough is by causing the body to
produce antibodies that inactivate the toxin. Because some exposure
to the toxin is required to achieve this effect, the toxin itself is included
in most pertussis vaccines. This can cause problems if it is included
in active form, as it is in whole-cell pertussis vaccine. The problems
that result are similar to the clinical symptoms of pertussis infection,
though they occur to a lesser degree. There is, however, a way to
neutralize this potentially dangerous toxin chemically or by genetic
engineering so as to render it inactive while maintaining its antigenic
properties. The currently used acellular vaccine accomplishes this by
mildly damaging the pertussis toxin with formaldehyde.4
early vaccine work
The development of a vaccine against pertussis first became possible
when the bacterium Bordetella pertussis was grown in the laboratory.
Jules Bordet and Octave Gengou of the Pasteur Institute of Brussels
developed the initial technique in  after more than twenty years
of work by a considerable number of investigators.5 The development
of this technique led to a wave of empirical research attempting to
produce a pertussis vaccine by culturing the bacteria on BG agar
. R. D. Sekura, J. Moss, and M. Vaughan, Pertussis Toxin (New York: Academic Press,
).
. J. Bordet and O. Gengou, “Le Microbe de la Coqueluche,” Annales de l’Institut Pasteur,
, , –; Bordet and Gengou, “Note Complementaire sur le Microbe de la Coque-
luche,” Ann. de l’Institut Pasteur, , , –; Bordet and Gengou, “L’endotoxine
Coquelucheux,” Ann. de l’Institut Pasteur, , , –.

Geier & Geier : Pertussis Vaccination

plates (named for Bordet and Gengou) and then inactivating the
bacteria and toxicity by physicaland chemicalprocedures . The indi-
viduals associated with this research included Bordet and Gengou in
, Charles Nicolle of the Pasteur Institute of Tunis in , and
Thorvald Madsen of the Danish State Serum Institute in Copenhagen
in , among others.6
The first challenge these researchers faced was to establish the
efficacy of the vaccines produced, a task that was complicated by the
facts that much of the older population was already immune to
pertussis infection, that there were no laboratory or animal tests in
existence at that time to measure how well the new vaccines were
working, and that toxicity was difficult to measure because there was
no agreement among the scientific community as to the nature of
the toxicity. This resulted in all the vaccines produced from the early
research falling into one of several groups. There were vaccines that
appeared to prevent the disease, but there were questions about their
toxicity. There were other vaccines that were so toxic that they could
not be used for clinical studies. Finally, there were vaccines that were
not toxic but whose disease-fighting ability could not be established.7
Despite the difficulties, by  there were six U.S. manufacturers
of pertussis vaccine, and pertussis vaccine was listed in “New and
NonofficialRemedies ,” published by the American Medical Associa-
tion (AMA). This document was a listing by the AMA of treatments
that had possible efficacy but were not fully proven to work. Pertussis
vaccine was removed from this list in  because of equivocal
efficacy results, but was readmitted in .8 In practice, various
presumptive pertussis vaccines were used sporadically with no formal
testing between  and . Madsen, in  and later in ,
was the first to report the results of clinical trials using whole-cell
pertussis vaccine during the – whooping cough epidemic
in the Faroe Islands of the North Sea. A carefulexamination was
made between vaccinated and unvaccinated individuals who had been
exposed to the disease. For the first time, the results were encouraging,
. A. Chase, Magic Shots: A Human and Scientific Account of the Long and Continuing Struggle
to Eradicate Infectious Diseases by Vaccination (New York: William and Morrow Co., Inc.,
).
. E. M. Sill, “The Vaccine Treatment of Whooping-cough,” Am. J. Dis. Child., ,
, –.
. H. M. Felton and C. Y. Willard, “The Current Status of Prophylaxis by Haemophilus
pertussis vaccine,” J. Am. Med. Assoc., , , –.

 Journal of the History of Medicine : Vol. , July 
establishing the usefulness of pertussis vaccine as a protective instru-
ment against infection. But there was also evidence that additional
work would be needed to develop a more effective vaccine. The
study specifically showed that individuals in both the vaccinated and
the unvaccinated group developed the disease at the same rate, but
among those vaccinated the manifestations of the disease were much
milder and hence fewer died.9
In a  outbreak of pertussis again in the Faroe Islands, Madsen
showed for the first time that the vaccine could be used to help
prevent the disease. In his study, pertussis bacteria grown on BG
plates with horse blood and killed by mild heat produced a decrease of
more than  percent in the occurrence of pertussis among vaccinated
individuals when compared to those who were unvaccinated. Addi-
tionally, as with the previous study, the symptoms that vaccinated
individuals developed were much milder, if they did come down
with the disease.10 Although these early vaccine trials successfully
helped to control two outbreaks of pertussis, Madsen’s  paper
also reported two instances of lethal adverse reactions within forty-
eight hours of vaccination. Additionally, in that same year, Louis Sauer
of Northwestern University MedicalSchoolin Chicago described a
clinical study in Evanston, Illinois using a pertussis vaccine similar to
that of Madsen’s trialthat showed minor reactions to the vaccine .11
In , Dr. PearlKendrick and her associate Dr . Grace Eldering,
both of the Michigan Department of Health in Grand Rapids, began
working on producing a more effective vaccine against childhood
pertussis by growing the bacteria on BG medium plates that contained
sheep’s blood. The bacteria were then treated with thimerosaland
stored at refrigerator temperatures as a means to inactivate them.
When the vaccine was subjected to clinical efficacy trials in ,
Kendrick and Eldering reported positive results.12 However, a similar
study conducted in Cleveland, Ohio, by J. A. Doull (a prominent
. T. Madsen, “Whooping-cough: Its Bacteriology, Diagnosis, Prevention, and Treat-
ment,” Boston Med. Surg. J., , , –.
. T. Madsen, “Vaccination against Whooping-cough,” J. Am. Med. Assoc., , ,
–.
. L. Sauer, “Whooping-cough: A Study in Immunization,” J. Am. Med. Assoc., ,
, –; L. Sauer, “Immunization with Bacillus pertussis Vaccine, ” J. Am. Med. Assoc.,
, , –.
. P. Kendrick and G. Eldering, “Progress Report on Pertussis Immunization,” Am. J.
Public Health, , , –.

Geier & Geier : Pertussis Vaccination

epidemiologist) and his colleagues in  showed that the vaccination
provided no increased protection over those who remained unvacci-
nated.13 Analyzing these conflicting results, Kendrick, Eldering, and
Dr. Margaret Pittman decided that varying numbers of bacteria might
be contained in the vaccines, so they developed an optical method
known as opacity unitage to test bacterialcontent . This method
correlated the cloudiness of a bacterial suspension with the amount
of bacteria the suspension contained.14
The idea of quantifying the concentration of bacteria was later
used to develop another test, this one performed in mice. Known as
the mouse potency test, it measured the ability of pertussis vaccine
to protect mice from being killed by pertussis infection. All clinical
trials conducted in the late s and s used this test as a means
of determining the efficacy of new whole-cell pertussis vaccines. On
 January  the NationalInstitutes of Heatlh (NIH) sent the
mouse potency testing method to the fourteen U.S. manufacturers
of whole-cell pertussis vaccine, and it became part of the First NIH
Minimum Requirements for Pertussis Vaccination in . Three of
the manufacturers met the specified potency levels, three manufactur-
ers had products with no demonstrable potency, and there was lot-
to-lot variation among the remaining eight manufacturers.15 Use of
the test led to the eventual acceptance by the s of whole-cell
pertussis vaccines as the most effective means to prevent the wide-
spread occurrence of the wild-type disease.16 Meanwhile, trials of
pertussis vaccine efficacy in human populations were done over the
years, but they were sporadic and the results were highly variable.
The scientific community generally accepted, at the time, that whole-
cell pertussis vaccines that had passed the mouse potency test were
. J. A. Doull, G. S. Shibley, and J. S. McClelland, “Active Immunization against Whoop-
ing Cough. Interim Report of the Cleveland Experience,” Am. J. Public Health, , ,
–.
. M. Pittman, “History, Benefits and Limitations of Pyrex Glass Particle Opacity Refer-
ences,” J. Biol. Stand., , , –.
. The following memoranda were referenced in M. Pittman, “History, Benefits and
Limitations of Pyrex Glass Particle Opacity References,” J. Biol. Stand., , , –:
NationalInstitutes of Heatlh , Memorandum to Manufacturers of Pertussis Vaccine, ;
NationalInstitutes of Heatlh , Minimum Requirements: A Tentative Mouse Protection Test for
Determining the Antigenicity of Pertussis Vaccine, ; NationalInstitutes of Heatlh , Minimum
Requirements: Pertussis Vaccine, .
. MedicalResearch Council , “The Prevention of Whooping-cough by Vaccination,”
Br. Med. J., , , –; MedicalResearch Council , “Vaccination against Whooping-
cough,” Br. Med. J., , , –.

 Journal of the History of Medicine : Vol. , July 
the best way to controlpertussis and that any disadvantages were far
outweighed by their positive effects.
The effectiveness of the new vaccines was not the only issue that
needed to be addressed, however. It was also necessary to measure
the toxicity of the vaccines in those who were injected with them.
This was done, again using mice as models, in what became known
as the mouse toxicity test. This test assesses endotoxin, LPF, and heat
labile toxin (HLT). Early mouse deaths in the mouse toxicity test
would indicate the presence of biologically active HLT. The degree
of weight loss at twenty-four hours is probably an indication of the
endotoxin content of the vaccine. A reduced rate of late weight gain
is taken to be a measure of the LPF content. At the time that a
product license was approved, evidence was presented to show that
the method of inactivation used by the manufacturer detoxified the
HLT component of pertussis vaccine.17
Since the s, all whole-cell pertussis vaccines licensed and re-
leased in the United States have been required to pass the mouse
toxicity test. It was hoped that the introduction of the test would
serve to limit the toxicity of whole-cell pertussis vaccine by identifying
highly toxic production lots early on and thus preventing their use
in humans. Unfortunately, field observations of the toxicity of the
vaccines have shown that there is little correlation between the toxicity
of a whole-cell pertussis vaccine in humans and the mouse toxicity
test.18 In , Dr. C. N. Christensen, a physician from Eli Lilly and
Company, then a whole-cell pertussis producer, was commissioned
to study whether the mouse toxicity test had been serving its purpose.
The results of his study were conveyed to all manufacturers of whole-
cell pertussis vaccine and were presented at the  International
Symposium on Pertussis. He concluded: “It is obvious that severe
neurologic reactions have occurred in children after immunization
with pertussis vaccines which have passed the toxicity and potency
tests currently in use . . . It was clear that there was no correlation
between the mouse toxicity test and the reaction rates in children.”19
. U.S. Institute of Medicine, Adverse Events.
. R. M. Barkin and M. E. Pichichero, “Diphtheria-Pertussis-Tetanus Vaccine: Reacto-
genicity of CommercialProducts ,” Pediatrics, , , –.
. C. N. Christensen, “Pertussis Vaccine Encephalopathy,” Eli Lilly Report, , –,
p. . This article is in the authors’ possession.

Geier & Geier : Pertussis Vaccination

whole-cell pertussis vaccines
The first modern whole-cell pertussis vaccine was put in its currently
known form by Kendrick in , combining whole-cell pertussis
with toxoided diphtheria and tetanus to form DTP or DPT vaccine.
In producing the pertussis component, the toxins were deactivated
by exposure to mild heat and then stored in a cold environment with
either thimerosalor formailn as preservatives . Thimerosal, which is
a mercury derivative, gained precedence over all other preservatives
and eventually was used as the preservative of choice in most vaccines
(except polio vaccines, since mercury is deleterious to the polio
virus).20 The pertussis vaccine produced in this way could be used
by itself, but it was often mixed with diphtheria and tetanus toxoids
to create the DTP vaccine once commonly given to all American
children. The DTP vaccine produced in this way was considered to
represent an acceptable compromise between a certain level of toxicity
and an effective level of functionality.
However, the toxicity of pertussis vaccine is primarily due to the
levels of two poisons: endotoxin and pertussis toxin. The production
of whole-cell pertussis vaccine does not inactivate these substances.
Therefore, the vaccine has some of the toxic biological activities of
the disease itself. Geier and colleagues demonstrated in  that
whole-cell pertussis vaccine contained enough endotoxin to be de-
tected by the Limulus endotoxin assay even when diluted ,
to .21 Endotoxin is a highly toxic substance. Doctors and scientists
take great care to ensure its absence from most medicines, intravenous
tubing, syringes, and other medicalinstruments before using them .
Given the high levels of endotoxin in whole-cell DTP vaccines, it
is not surprising that virtually all children who receive the vaccine
develop a fever. It is also not surprising that a smaller percentage of
children get more severe reactions which may include seizures, shock,
collapse, and even death.22 Nevertheless, the dangers posed by the
. P. Kendrick, G. Eldering, and A. A. Borowski, “A Study of Active Immunization
against Pertussis,” Am. J. Hyg., , , –; R. A. Gardner and M. Pittman, “Relative
Stability of Pertussis Vaccine Preserved with Methiolate, Benzethonium Chloride, or the
Parabens,” Appl. Microbiol., , , –.
. M. R. Geier, H. Stanboro, and C. R. Merril, “Endotoxin in CommercialVaccine ,”
Appl. Environ. Microbiol., , , –.
. Ibid.

 Journal of the History of Medicine : Vol. , July 
high levels of endotoxin in whole-cell pertussis were overlooked or
tolerated due to two factors. First, from the late s untilthe earyl
s, physicians had no choice but to use whole-cell pertussis vaccine
because there was no other type on the market. Second, the vaccine
manufacturers hid the fact that their whole-cell pertussis vaccine
contained high levels of endotoxin and in fact failed to even mention
endotoxin anywhere in their product information.
Despite these inherent difficulties with the whole-cell pertussis
component of the DTP vaccine, by the late s every manufacturer
had begun using the Kendrick process for producing it. The predeces-
sor of the Food and Drug Administration (FDA), operating without
today’s rigorous requirements of testing for safety and effectiveness,
approved the manufacture and use of whole-cell pertussis vaccine.
This officialposition on whoel -cell pertussis vaccine, coupled with
the ease of its production and the relative cheapness of the product,
caused all of the manufacturers to make the switch to the whole-cell
product. Because of all these factors, more and more children began
to receive voluntary vaccination for the disease. Additionally, the
vaccine manufacturers started lobbying the pediatric societies and the
states to require children to be vaccinated against pertussis. By the
mid-s they had succeeded. Most states had passed laws requiring
all children to be vaccinated with the combination DTP vaccine
prior to entering school.23
With this widespread administration of whole-cell DTP vaccina-
tion came the first published reports of irreversible brain damage after
its administration.24 These reports generated the first warnings that
whole-cell pertussis vaccination should not be administered to anyone
with a neurological disorder. Clinicians also began reporting on a
small number of children each year who were killed by the toxins
in the whole-cell pertussis vaccine. In fact, in virtually every year
from the early s through the present, at least one article has
been published describing similar adverse effects. For example, H. W.
Felton and W. F. Verwey reported in  that “virtually every child
. H. L. Coulter and B. L. Fisher, DPT: A Shot in the Dark (San Diego, Calif.: Harcourt
Brace Jovanovich, ).
. M. Brody and R. G. Sorley, “Neurological Complications following Administration
of Pertussis Vaccine,” N. Y. State J. Med., , , –; R. K. Byers and F. C. Moll,
“Encephalopathies following Prophylactic Pertussis Vaccination,” Pediatrics, , , –.

Geier & Geier : Pertussis Vaccination

who receives pertussis immunization demonstrates some form of
systemic toxicity within the  hours following injection. . . . If the
child survives the typical sequellae of severe generalized episodes,
CNS damage often remains.”25 Justus Strom similarly warned in :
In Sweden, as in severalother countries , neurological complications after
pertussis (triple) vaccinations have been observed. A nationwide investiga-
tion showed that  cases of such complications had occurred in about
, vaccinated children (one in ,) during –. Most of these
consisted of convulsions, coma, or collapse, and the children were restored
to health; but there were four deaths, of which two were sudden, and nine
cases indicative of encephalopathies with severe lesions (one in ,).26
Dr. H. D. Piersma of Wyeth Laboratories, who for many years
manufactured whole-cell DPT, admitted during the Proceedings of
the th InternationalSymposium on Pertussis hedl at the NIH in
 that there was generalagreement among cilnicians that use
of pertussis vaccine was occasionally accompanied by unfavorable
reactions. Certain of these reactions were severe and resulted in per-
manent damage to the CNS.27 Margaret Haire and colleagues in 
likewise concluded, “it is well known that they [whole-cell DTP
vaccinations] cause reactions in many of the infants who receive
them. These reactions, which are largely attributed to the pertussis
component, vary from slight pyrexia and fretfulness, which are ex-
tremely common, to serious and sometimes fatalencephaolpathy ,
which is fortunately exceedingly rare.”28 Criticism of whole-cell per-
tussis vaccine continued during the s.29 In , O. T. S. Bajc
persisted in observing that “since there is a significant difference
between the incidence of spontaneous fits in children of the same
age group and the incidence after DPT, a causalreal tionship between
the DPT and the seizures appears to be confirmed. . . . the severe
. H. M. Felton and W. F. Verwey, “The Epidemiological Value of a Non-cellular
Pertussis Antigen,” Pediatrics, , , –, p. .
. J. Strom, “Is UniversalVaccination against Pertussis Awl ays Justi fied?” Br. Med. J.,
, , –, p. –.
. Proceedings of the th InternationalSymposium on Pertussis , held at NIH,  October
. This article is in the authors’ possession.
. M. Haire, D. S. Dane, and G. Dick, “Reactions to Combined Vaccines Containing
Killed Bordetella pertussis,” The Medical Officer, , , –, p. .
. M. Kulenkampff, J. S. Schwartzman, and J. Wilson, “Neurological Complications of
Pertussis Inoculation,” Arch. Dis. Child., , , –.

 Journal of the History of Medicine : Vol. , July 
damages are particularly tragic as they are iatrogenic and in most cases
affect primarily completely healthy children.”30
A chorus of criticism pounded the vaccine during the s. By
 some physicians questioned whether the vaccine might be a
generally unrecognized major cause of sudden infant and early child-
hood death and wondered if the risk of immunization might outweigh
its potentialbene fits. In Britain parents were urged to seek compensa-
tion for children damaged by pertussis vaccine.31 In , an FDA
researcher reported that reactions from a single lot may vary from
nilto severe and may inculde fever , shock, convulsions, persistent
screaming, and encephalopathy. Neurological symptoms can occur
early or be delayed for several days after injection.32 R. M. Barkin
and colleagues in  agreed that DPT has a high rate of adverse
reactions, citing impressive incidence rates. As many as  percent
of patients experience adverse reactions, including fever, acute behav-
ioralchange , and local reactions. Encephalopathy and permanent
neurological sequellae occur in approximately  in every ,
immunizations. Other researchers agreed that the pertussin toxin
caused cellular dysfunction in the central nervous system, with conse-
quences ranging from irritability to coma.33
In  the U.S. IOM issued a report on the efficacy and safety
of vaccines. About pertussis it concluded:
Low grade fever and local tenderness appear frequently after injection.
Severe disturbing untoward reactions, including shock, convulsions, enceph-
alopathy, and persistent high-pitched screaming, are rare complications.
. . . The frequency of fatalreactions has been estimated to be one to two
cases per ten million injections, and the frequency of serious neurological
disorders such as encephalopathy to be one case per , injections with
persistent neurological dysfunction after one year later.34
. O. T. S. Bajc, “Convulsions after Pertussis Vaccination,” Schweiz. Med. Wschr., ,
, –, p. .
. W. C. To rc h , “Diphtheria-Pertussis-Tetanus (DPT) Immunization: A PotentialCause
of the Sudden Infant Death Ssyndrome (SIDS),” Neurology, , , A–A; A. C.
Wardlaw and R. Parton, Medical Microbiology (London: Academic Press, ), pp. –.
. M. Pittman, “The Concept of Pertussis as a Toxin-mediated Disease,” Pediatr. Infec.
Dis., , , –.
. R. M. Barkin, J. S. Samuelson, and L. P. Gotlin, “DTP Reactions and Serologic Response
with a Reduced Dose Schedule,” J. Pediatr., , , –; L. E. Davis, D. G. Burstyn,
and C. R. Manclark, “Pertussis Encephalopathy with a Normal Brain Biopsy and Elevated
Lymphocytosis-Promoting Factor Antibodies,” Pediatr. Infec. Dis., , , –.
. U.S. Institute of Medicine, New Vaccine Development: Establishing Priorities (Washington,
D.C.: NationalAcademy Press , ), p. .

Geier & Geier : Pertussis Vaccination

The report went on to state that the United States could save millions
of dollars if acellular pertussis replaced whole-cell pertussis as the
form of vaccination in children. Many other researchers echoed these
conclusions.35
Our own work in the late s on adverse reactions following
whole-cell DTP vaccination has been based on the Vaccine Adverse
Events Reporting System (VAERS) database. VAERS is a passive
epidemiological database that has been maintained by the Centers
for Disease Controland Prevention (CDC) in Atlanta , Georgia, since
. All vaccine-associated adverse reactions are to be reported to
this database as mandated by U.S. law. We have analyzed the incidence
of neurological adverse reactions reported to the VAERS database
following whole-cell DTP administration since  and have calcu-
lated the incidence rates of various types of adverse reactions to the
vaccine based on the estimates of the CDC on the number of doses
administered. Our studies were based on the administration of tens
of millions of doses to American children and show that whole-cell
DTP was statistically significantly linked with fevers, convulsions, and
deaths beyond the childhood background rates.36
acellular pertussis vaccine
Because of the effectiveness of the vaccine program, pertussis had
become only a minor infectious disease problem in the United States.
. P. Ibsen, S. Moller, and I. Heron, “Lipopolysaccharides in a Traditional Pertussis
Vaccine,” J. Biol. Stand., , , –; R. D. Sekura, Y. Zhang, R. Roberson, B.
Acton, B. Trollfors, N. Tolson, J. Shiloach, D. Bryla, J. Muir-Nash, D. Koeller, R. Schnerrson,
and J. B. Robbins, “Clinical, Metabolic, and Antibody Response of Adult Volunteers to
an InvestigationalVaccine Composed of Pertussis Toxin Inactivated by Hydrogen Peroxide ,”
J. Pediatr., , , –; J. H. Menkes, “Pertussis Vaccine Encephalopathy,” J. Am. Med.
Assoc., , , ; J. H. Menkes and M. Kinsbourne, “Workshop on Neurologic
Complications of Pertussis and Pertussis Vaccination,” Neuropediatrics, , , –.
. D. A. Geier and M. R. Geier, “An Analysis of the Occurrence of Convulsions and
Death after Childhood Vaccination,” Toxicol. Mech. Methods, , , –. The purpose
of this analysis was to review the VAERS database for attributed adverse events reported
following the actual clinical immunization of American children with whole-cell DTP,
acellular DTaP and DT vaccinations. This paper establishes that the chance association
between serious adverse reactions, neurological adverse reactions and death cannot be
accounted for by coincidence alone. The data clearly established that whole-cell DTP is
far more reactogenic than acellular DTaP or DT vaccines; D. A. Geier and M. R. Geier,
“Clinical Implications of Endotoxin Concentrations in Vaccines,” Ann. Pharmacother., ,
, –. The purpose of this study was to extend and expand previous studies to
determine the endotoxin levels in commercially manufactured whole-cell DTP, acellular
DTaP and DT vaccines and determine the clinical effects of each vaccine’s use in children
in the US. The results of the endotoxin assay showed that whole-cell DTP vaccines contained
considerably more endotoxin than either acellular DTaP or DT vaccines. The VAERS

 Journal of the History of Medicine : Vol. , July 
Therefore, the high level of toxicity of the whole-cell pertussis vaccine
was rapidly becoming unacceptable to the general population. The
scientific community’s awareness of the dangers associated with
whole-cell pertussis vaccine led to many different techniques and
procedures to produce a less harmful variety. The first was developed
by Parke-Davis and Company in the s and consisted of just the
bacterial cell wall and virtually no toxins.37 Despite being a highly
impure form of acellular vaccine, it was associated with markedly
fewer adverse reactions than the whole-cell vaccine because it was
free of the toxic components of pertussis bacterialcutlures .
In , Lederle Laboratories patented an acellular pertussis vaccine
that used soluble pertussis toxin.38 The cells were removed and the
pertussis toxin was toxoided with formaldehyde. This vaccine was
widely and successfully used in the United States in the s and
had some similarities to the acellular form widely used today. It was
shown to be  percent protective in children with definite exposures
to pertussis bacteria, which surpassed the protection offered by a
whole-cell vaccine and roughly equates to the protection of the
Japanese form of acellular vaccine currently used today. According
to Lederle Laboratories head Dr. H. D. Piersma, the company actively
marketed its  acellular vaccine from  to , but ceased
the marketing in  when Lederle began production of Tri-Immu-
nolDTP using a whoel -cell pertussis component.39 The whole-cell
variety was used to avoid the need for laborious and expensive efficacy
testing on an acellular version of the vaccine, which would have been
required under new federalalws .
Another early acellular pertussis vaccine was the stromata-protective
antigen (SPA) vaccine of Pillemer and colleagues in . It was
protective in the mouse potency assay and showed clinical efficacy
showed that statistically significantly more instances of fever, seizures, death, and permanent
brain damage were associated with whole-cell DTP vaccine than acellular DTaP or DT
vaccines.
. W. A. Puckner, “Gonococcus Immunogen, Gonococcus Immunogen Combined,
Streptococcus Immunogen Combined, Pertussis Immunogen Combined, and Pneumococ-
cus Immunogen Combined Not Acceptable for New and NonofficialRemedies ,” J. Am.
Med. Assoc., , .
. C. L. Joslin and T. A. Christensen, “Prophylaxis and Treatment of Whooping Cough
with a Pertussis Antigen,” Am. J. Dis. Child., , –.
. H. D. Piersma (deposition), Corbine vs. Lederle Laboratories (American Cynanamid
Co.),  March ; H. D. Piersma (deposition), Nelson vs. American Cyanamid Company,
Case No. C- A, U.S. District Court for the Northern District of Ohio, Eastern
Division, , –. This deposition is in the authors’ possession.

Geier & Geier : Pertussis Vaccination

in British MedicalResearch Counciltriasl in  and  but was
never licensed for clinical use nor brought to market, primarily be-
cause of its higher cost of production and the cost of additional
efficacy trials that would have been required to gain full licensure.40
Since by the mid-s it was agreed that the mouse toxicity test
was incapable of predicting and thus eliminating potential adverse
reactions to whole-cell pertussis vaccine, the Eli Lilly Company de-
cided to patent, license, and produce an acellular pertussis vaccine
prepared from a trisodium phosphate extract of pertussis cells. This
type of vaccine was described by Weihl and colleagues in their 
publication.41 This vaccine was widely sold from  to  under
the name of Tri-Solgen as a component of their DTP Adsorbed
vaccine. Lilly’s vaccine cost more, but was well received by the medical
community because it caused approximately  percent fewer reac-
tions in children.42 In fact, Lilly’s Tri-Solgen was so well received
that between  and  the company captured  percent of the
market, increasing to  percent of the market between  and
.43
Another commercially available acellular vaccine had been brought
to market in . This vaccine was studied in a number of field
trials and reported to be both safer and more efficacious than whole-
cell pertussis vaccine.44 It was marketed for approximately two years
in  and  by Merck Sharp and Dohme, but by  the
company had gone back to the use of its whole-cell vaccine, presum-
ably because of cost pressures. However, in  Merck withdrew
all products with whole-cell pertussis vaccine from the market, citing
a fear of lawsuits.45 The rationale was that since bad reactions were
. L. Pillemer, L. Blum, and I. H. Lepow, “Protective Antigen of Haemophilus pertussis,”
Lancet, , , –; MedicalResearch Council , “Prevention of Whooping-cough”;
“Vaccination against Whooping-cough.”
. C. Weihl, H. D. Riley, and J. H. Lapin, “Extracted Pertussis Antigen,” Am. J. Dis.
Child., , , –.
. Eli Lilly Laboratories,  Symposium: Lilly Tri-Solgen Vaccine, . This article
is in the authors’ possession.
. R. Meschke (letter), “Toxoid Consolidation Data,” American Cyanamid, Sales Fore-
casting,  April . This article is in the authors’ possession.
. R. Underwood (affidavit), “Whooping Cough Immunization Antigen,” The United
States Patent Office, SerialNumber : ,, January ; H. M. Felton and W. F. Verwey,
“The Epidemiological Evaluation of a Non-cellular Pertussis Antigen,” Pediatrics, , ,
–.
. M. V. Querry (letter), Merck Laboratories InternalCorrespondence ,  April .
This letter is in the authors’ possession.

 Journal of the History of Medicine : Vol. , July 
occurring with its whole-cell pertussis vaccine, Merck could be held
legally liable if it had a safer, more effective product that it did not
sell. Under a U.S. Army grant, a practicalmethod for pertussis toxin
purification was developed and published in .46 This method
subsequently became the basis for the currently used Japanese-type
acellular pertussis vaccines. Similar experimental vaccines were devel-
oped by Wyeth, Parke-Davis, and Lederle and were shown to be
potent in the mouse potency assay, but these companies never mar-
keted these products for generaluse . The main reason for failure to
market these acellular vaccines was their cost. In the early s,
Millman and colleagues developed a soluble pertussis vaccine that
was potent in the mouse potency assay, but was not tested in clinical
trials to determine human efficacy due to cost considerations. In
, Merrell-National developed an acellular vaccine that passed
the FDA potency and toxicity tests, but because the yield was low
in the production process, the company decided not to seek FDA
approval to commercially sell the safer vaccine.47 This product was
later purchased by Connaught Laboratories.
It is interesting that many of the manufacturers who produced
experimental acellular vaccines but were unwilling to pay for the cost
of their production have attempted to discredit Lilly’s Tri-Solgen
acellular vaccine. For instance, Connaught stated in  there were
serious doubts about Tri-Solgen’s efficacy because it had never been
subject to controlled field testing. In reality, Tri-Solgen underwent
extensive trials in the s. Additionally, during the many years that
Tri-Solgen was the vaccine used by the majority of the millions of
children in the United States, no significant increase in the rate of
pertussis in the U.S. population was observed. However, Connaught
claimed that in , as a result of this lack of testing, the FDA had
refused to grant a split cell license to Wyeth Laboratories, which had
purchased Lilly’s rights to the vaccine. In actuality, the Panelon
Review of Bacterial Vaccines and Bacterial Toxoids reviewed Lilly’s
acellular Tri-Solgen in , found it to be both safe and effective,
and recommended that the product be placed in category I (the
. Round Table Conference of Pertussis Immunization , presented by I. Millman,
L. F. Schuchardt, and A. Gray; Y. Juwajima, “Purification of Histamine Sensitizing Factor
of Bordetella pertussis,” U.S. Army Grant, , –. These articles are in the authors’
possession.
. L. Colio (deposition), Terry Lynn Hall vs. Connaught, , –. This deposition is
in the authors’ possession.

Geier & Geier : Pertussis Vaccination

highest rating possible with regard to efficacy). It was a reformulation
of the product by Wyeth after purchasing the patent from Lilly that
caused the FDA to determine that Wyeth was attempting to produce
a “misbranded” product and to reject its licensing.48
During the s and s, pertussis manufacturing companies
developed acellular pertussis vaccines, briefly used them, decided
based on economic factors not to make them, and then were forced
to withdraw from making any pertussis vaccine because of their
knowledge of how to make a better vaccine and the legal ramifications
of persisting in making and marketing an inferior product. Thus, the
pertussis vaccine market contracted so much that out of the multitude
of manufacturers making DPT in the s and s, only four
were left by the s. These were Wyeth, Lilly, Lederle, and Con-
naught. The only one of the four manufacturers actively making the
safer and more effective acellular pertussis vaccine was Lilly. The rest
deemed it too costly to have their experimental new acellular pertussis
vaccines approved and produced on a massive scale. The result, as
stated before, was that Lilly captured a lion’s share of the market with
its much safer and more effective acellular product.
In , however, Lilly stopped the manufacture of all of its biologi-
calproducts . Shortly thereafter, it offered its Tri-Solgen license to
other manufacturers and Wyeth contracted to acquire the rights.
When Wyeth reproduced Lilly’s Tri-Solgen in its laboratory, however,
it immediately realized that the yield was only  percent. Faced
with an unexpectedly large increase in the cost of production, Wyeth
set about to change the formula to get more bang for the buck. By
doing so, the company was able to get five times the yield that Lilly
had achieved with its originalformual . When Wyeth approached the
government for approvalof the reformualted Tri -Solgen, however,
the government balked and threatened the company with “misbrand-
ing.”49 Before the government would approve Wyeth’s reformulation,
the manufacturer would have had to perform safety and efficacy trials.
Wyeth contemplated doing a double-blind safety study comparing
the reactogenicity of Lilly’s formulation of Tri-Solgen to its own
. H. M. Meyer (letter), Director, Bureau of Biologicals,  March  to A. Bernstein,
Wyeth Laboratories. This letter is in the authors’ possession.
. Rubin, “BacterialVaccine Studies ,” Second Quarterly Report Wyeth Laboratories,
, ; F. J. McCarthy (letter), Wyeth Laboratories InternalCorrespondence ,  February
 to A. Bernstein, Wyeth Laboratories; both in the authors’ possession; Meyer, letter to
Director, Bureau of Biologicals.

 Journal of the History of Medicine : Vol. , July 
whole-cell pertussis vaccine, but chose not to do so. The reason was
best expressed by Wyeth scientist Dr. Howard Tint in his cryptic
message on the proposed study, “A reply is needed to N. W. Fleisch-
man (location ) who suggests that possibly we might not want
to see the basic study carried out at all at this time.”50 Dr. Tint knew
that a study would show Wyeth’s whole-cell pertussis vaccine was far
more reactive than Lilly’s acellular product, which would open the
door to potential legal liability against Wyeth for its past failure to
market its acellular pertussis vaccine.
After years of embattled discussion within Wyeth, the decision was
eventually made to produce only whole-cell pertussis vaccine, but
by  Wyeth had completely dropped out of the pertussis vaccine
market. The result was that only two manufacturers, Lederle and
Connaught, remained, each of which was only producing whole-
cell pertussis vaccine in the United States.
pertussis vaccination in other countries
Incidents with pertussis vaccination in Japan, England, and Sweden
began to have profound effects on American perceptions of the safety
and efficacy of whole-cell pertussis vaccination. In , two babies
in Japan died as a result of DPT vaccinations. The Japanese govern-
ment, fed up with the continued use of the reactive whole-cell
pertussis vaccine given to it by the United States after World War II,
sent one of its scientists, Dr. Yugi Sato, to the NationalInstitutes of
Health in the United States to study purification of the product.
After less than one year of investigationusing American technology
developed in the s and sSato developed an acellular pertus-
sis product. The production lots of Japanese acellular pertussis vaccine
contain less than one-twentieth of the endotoxin of a comparable
whole-cell pertussis vaccine and less than  percent of the amount
of active pertussis toxin. Yet Sato and his colleagues reported near
 percent vaccine efficacy.51 The Japanese conducted trials of Sato’s
acellular vaccine between  and . As a result of the positive
findings of the trials, Japan made the decision on  October 
to use only acellular pertussis vaccine.
. H. Tint (letter), Wyeth Laboratories InternalCorrespondence ,  June , p. –.
This letter is in the authors’ possession.
. Y. Sato, H. Sato, K. Izumiya, J. L. Cowell, and C. R. Manclark, “Role of Antibody
to Filamentous Hemagglutinin and to Leukocytosis Promoting Factor-Hemagglutinin in

Geier & Geier : Pertussis Vaccination

In response to the controversy surrounding whole-cell pertussis
vaccination in the United Kingdom, the NationalChidlhood En-
cephalopathy Study (NCES) was begun in  to determine whether
whole-cell pertussis vaccine caused brain damage in children and, if
it did, to establish how often such damage occurred. This was a
prospective case-controlstudy, which reported on the first , cases
for the three years ending  June .52 A case was defined as an
acute neurological illness in a two- to thirty-six-month-old child
who required hospitalization. Permanent brain damage was defined
as a case with residuale ffects after one year. For previously normal
children, the estimated risk of permanent neurological illness attrib-
uted to immunization with DTP vaccine was one in , immuni-
zations.53 The conclusions of the National Childhood Encephalopathy
Study were as follows:
. Most cases of acute and potentially damaging neurological illness in
early childhood are attributable to causes other than immunization.
. Neurological illnesses occur more frequently within seventy-two
hours after DTP vaccination than would be expected by chance.
. Most, but not all, children who manifest neurological illness make
a complete recovery.
. Considering possible alternative explanations of the clinical findings
in cases associated with the DTP vaccine and considering the fact
that similar cases occur after DT vaccine but at a much lower
rate, it seems likely that permanent damage as a result of pertussis
immunization is a realbut rare event .54
An evaluation of the results of the National Childhood Encepha-
lopathy Study by the United Kingdom’s Committee on Safety of
Medicines and the Joint Committee on Vaccination and Immuniza-
tion noted that no causal relationship had been established between
Immunity to Pertussis,” Semin. Infect. Dis., , , –; Y. Sato, M. Kimura, and H.
Fukumi, “Development of a pertussis component vaccine in Japan,” Lancet, , , –.
. R. Alderslade, M. H. Bellman, N. S. B. Rawson, E. M. Ross, and D. L. Miller,
Whooping Cough (London: H.M. Stationary Office, ), pp. –.
. It should be noted that in the United States most children get five doses. Thus, based
on these figures, the best estimate is that  in , American children has suffered major
permanent brain damage from the whole-cell vaccine. In addition to this rare rate of major
brain damage, there is the possibility that the highly neurotoxic whole-cell pertussis vaccine
may cause minor brain damage in a much higher percentage of vaccine recipients. This
damage might manifest itself in loss of intelligence quotient points, reading problems,
language difficulties, or autism. Since these types of brain damage show up years after
vaccination, we may never know who was truly damaged by whole-cell pertussis vaccination.
. Alderslade et al., Whooping Cough, pp. –.

 Journal of the History of Medicine : Vol. , July 
DTP immunization and serious neurological illness, but there was
strong evidence that a link might exist for some children. Advisory
panels in the United Kingdom and the United States reaffirmed
their respective positions that whole-cell pertussis vaccine effectively
protects against pertussis, a disease that also causes severe brain damage,
and that the advantages of vaccination in preventing pertussis out-
weighed the risks associated with its use.55
In the s, however, Sweden banned the use of whole-cell
pertussis vaccine. After severalstudies were pubilshed there , the gov-
ernment concluded that the benefit did not outweigh the risk. The
chief Swedish authority in this finding was Dr. Wolfgang Ehrengut.
He pointed out in  that there had not been a single death from
pertussis, even without vaccination, since . He also stated that
a causalconnection between whoel -cell DPT and encephalopathies
had clearly been shown. Therefore, he felt that parents had a right
to know the pros and cons of pertussis vaccination for their children
and that there should be generalized immunization against pertussis
with a less dangerous vaccine.56
Because of its stance on vaccination, Sweden became a good place
to test the safety and efficacy of the Japanese acellular vaccine in
human populations against the incidence and associated risks of the
actualinfectious disease pertussis . Unfortunately, when the test proce-
dures were formulated, no whole-cell pertussis vaccine could be
administered in Sweden because it had been banned. An idealstudy
would have had two control groups, one receiving whole-cell DTP
vaccine and one receiving acellular DTaP vaccine so that comparative
figures could be analyzed. Instead, the researchers assumed that the
whole-cell pertussis vaccine was approximately  percent effective
at preventing infection by pertussis in human populations. When the
study figures of acellular efficacy came in at  percent and  percent,
it initially looked like the Japanese acellular pertussis vaccine was not
as effective as the whole-cell pertussis vaccination was originally
believed to be. It was only afterward that scientists went back to
question the assumed  percent efficacy rate of whole-cell DTP
vaccine. As it turned out, according to some studies whole-cell pertus-
sis vaccine is only – percent effective in preventing pertussis
. Immunization Practices Advisory Committee, Mortal. Morbid. Weekly Rep., , ,
–.
. W. Ehrengut (letter),  November . This letter is in the authors’ possession.

Geier & Geier : Pertussis Vaccination

infection in humans.57 Another problem the researchers encountered
in determining efficacy was how to define the disease pertussis. Was
culture confirmation necessary? An extended cough for several
months with the characteristic “whoop”? For example, a person
might have a culture of confirmed pertussis but only have a mild
cough for a week. Did that mean the person had pertussis or did
that mean the vaccine had been effective? After the originalpubilca-
tion, the Swedish scientists did a reanalysis. They determined that
Japanese acellular pertussis vaccines were more effective than whole-
cell pertussis vaccines, even though only two doses of acellular pertus-
sis vaccine were required, whereas the whole-cell pertussis vaccine
is usually given in a five-dose schedule.58
the american response to
whole-cell pertussis vaccination
The decline in the incidence of whooping cough by the late s
led the American public to become concerned that the vaccine might
pose greater risks than the disease. The concern was generated by
emotionally effective presentations in newspapers and television that
questioned the need for continued vaccination in the virtualabsence
of the disease, especially considering the potentially harmful side
effects associated with vaccination. Additionally, it was argued, mod-
ern medical treatments including antibiotics could easily treat those
infected with the disease.59 The American public became even more
aware of the potentialfor di fficulties resulting from whole-cell pertus-
sis vaccination in  when all public health clinics using federally
purchased vaccines were required by the FDA to have parents sign an
“important information statement” about the risks of immunization
before their children could be vaccinated.60 It was deemed necessary
to obtain informed consent for this required procedure because of
the overwhelming data that indicated whole-cell pertussis vaccine
could result in severe adverse reactions. Also in that year the Centers
for Disease Control created the Monitoring System for Illness Follow-
. S. A. Halperin, R. Bortolussi, D. MacLean, and N. Chisholm, “Persistence of Pertussis
in an Immunized Population: Results of the Nova Scotia Enhanced Pertussis Surveillance
Program,” J. Pediatr., , , –.
. L. Seachrist, “New Pertussis Vaccines Safer, More Effective,” Science, , , .
. W. G. Rothstein, Readings in American Healthcare: Current Issues in a Socio-Historical
Perspective (Madison: The University of Wisconsin Press, ), pp. –.
. Coulter and Fisher, A Shot in the Dark.

 Journal of the History of Medicine : Vol. , July 
ing Immunization (MSIFI) as a direct result of the difficulties encoun-
tered in the United States with the swine flu vaccine.
Growing concern prompted more study on the reactogenicity of
whole-cell pertussis vaccine. Clinical studies of the more common
adverse reactions were compiled by Barkin and Pichero in  and
by Hopkins in .61 In a prospective study reported by Cody and
colleagues in , reaction rates were recorded after the injection
of DTP and DT vaccines to determine what influence the whole-
cell pertussis component had on adverse reaction rates. The reaction
DTP/DT rates were as follows: “local redness, ./. percent; local
swelling, ./. percent; pain, ./. percent; fever, ./.
percent; drowsiness, ./. percent; fretfulness, ./. percent;
vomiting, ./. percent; anorexia, ./. percent and persistent
crying, ./. percent. Nine of , DTP immunizations resulted
in convulsions, and nine other children had hypotonic hyporesponsive
episodes.”62
A landmark event in the evolution of vaccine toxicity awareness
occurred in  when the CDC held meetings to discuss the relation-
ship between sudden infant death syndrome (SIDS) and pertussis
vaccine after a lot of DPT administered in Tennessee was believed
to be responsible for several deaths. Four infants, all aged two to three
months, died within twenty-four hours of receiving Wyeth lot .
There were , doses of this lot given in Tennessee before the
state withdrew the lot from use on  March . An article in
Morbidity and Mortality Weekly Report later showed that the DPT
vaccine was statistically significantly linked to these deaths.63 As news
of the tragedy spread, Dr. Ted Cannon, the second-in-command of
the FDA in charge of vaccines, ordered the recall of the entire lot
from the shelves in several states. The FDA head of vaccines, Dr.
John Petricciani, was away at the time. Upon returning, however, he
issued a memo stating that the potentialharmfulolts of pertussis
vaccine had to be put back on the shelf for use, and he apologized
. R. M. Barkin and M. E. Pichichero, “Diphtheria-Pertussis-Tetanus Vaccine: Reacto-
genicity of CommercialProducts ,” Pediatrics, , , –; R.S. Hopkins, International
Symposium on Pertussis (Washington, D.C.: U.S. Government Printing Office, ).
. C. L. Cody, L. J. Baraff, J. D. Cherry, S. M. Marcy, and C. R. Manclark, “Nature
and Rates of Adverse Reactions Associated with DTP and DT Immunizations in Infants
and Children,” Pediatrics, , , –.
. R. Hutchinson, “DTP Vaccination and SIDSTennessee,” Mortal. Morbid. Weekly
Rept., , –.

Geier & Geier : Pertussis Vaccination

to the drug companies for the actions taken by the FDA, assuring
them it would never happen again.64 Petricciani’s apology came after
strong pressure was applied by the vaccine manufacturers, who were
unwilling to lose revenue due to an informal recall of their vaccine.
They took measures of their own to ensure against future recalls.
After the Tennessee incident, pertussis manufacturers arranged that
entire lots would never again be sent to single areas of the country.
Specifically, a memo from Wyeth Laboratories stated that since the
SIDS episode, there had been only a limited number of vials of each
lot of DTP shipped to municipal clinics, not exceeding more than
, vials.65 This small lot plan meant that no one region of the
country would have enough adverse reactions to a single lot of whole-
cell pertussis vaccine to alert the clinicians in that region to the fact
that they were using a highly reactogenic lot.
The first legal difficulties over whole-cell pertussis vaccine came
almost two decades before the Tennessee deaths. They were generated
by the Parke-Davis Quadrigen vaccine in the s. In this vaccine,
a whole-cell DTP was combined with a Salk killed polio vaccine
component. It was licensed for use in , and immediately adverse
reactions began to be reported. The result was several successful
lawsuits in which it was alleged that the preservative used in the
pertussis component was extremely reactogenic. Quadrigen was sub-
sequently withdrawn from the market; however, the reports of severe
adverse reactions to whole-cell DTP continued.66
The next major suit came in  from Ken Pederson of an
Idaho law firm that sued and won a large judgment from Lederle
Laboratories on the grounds that their whole-cell pertussis vaccine
was a defective product. This verdict was appealed and upheld all the
way to the U.S. Supreme Court, which refused to hear the case.
Another landmark case was tried by Ted Worshofsky and Victor
Harding in Wichita, Kansas. These successfulcases had signi ficant
implications for the future of whole-cell pertussis vaccination use in
that they were brought on the grounds that the product was defective
and that the vaccine manufacturers had known for many years how
. G. M. Irwin (letter), Wyeth Laboratories InternalCorrespondence ,  January 
to M. Z. Bierly. This letter is in the authors’ possession.
. A. Bernstein (letter), Wyeth Laboratories InternalCorrespondence ,  August 
to L. Hewlett. This letter is in the authors’ possession.
. Coulter and Fisher, DPT: A Shot in the Dark.

 Journal of the History of Medicine : Vol. , July 
to produce a more effective and far safer pertussis vaccine, but had
failed to bring these products to market due to financialconsidera-
tions.67
In , the television program “DPT: Vaccine Roulette” was first
broadcast by NBC affiliate WRC-TV in Washington, D.C., and was
widely publicized. The program depicted children with severe injuries
reported to be associated with whole-cell pertussis vaccine, along
with attorneys Alan McDowell and Toni Colantoni. This television
program raised parents’ awareness so much that soon McDowell and
Colantoni had literally hundreds of lawsuits to file against the vaccine
manufacturers. MichaelHugo , an attorney from Massachusetts, con-
tributed to the effort by compiling a library of information for use
by other plaintiff attorneys concerning whole-cell DPT and its manu-
facture. At first these attorneys had great difficulties in finding expert
witnesses not attached to the vaccine manufacturers or the U.S.
government, yet who were knowledgeable enough and willing to
testify in these cases. The first major expert witness to testify against
the vaccine manufacturers was Kevin Geraghty, M.D., a California
pediatrician. In attempt to prevent Geraghty from testifying, he and
his family were harassed by the vaccine manufactures to such an
extent that he filed a suit against them. It is at this point that Mark
Geier, M.D., Ph.D., became involved in the pertussis cases. A Mary-
land geneticist who had previously studied vaccine problems at the
NIH, Geier was approached by the law firm of McDowell and Colan-
toni, who eventually convinced him that he also needed to testify
against the vaccine manufacturers. These two experts were soon
joined by Arthur C. Zahalsky, Ph.D., an immunologist from Southern
Illinois University. Once the ice was broken, other expert witnesses
came forward to testify against the vaccine manufacturers, making it
virtually impossible for the manufacturers to stop everyone from
testifying. By ,  lawsuits had been filed in U.S. courts alleging
harm to children from whole-cell pertussis vaccination.68
In addition to the dramatic legal actions taken against whole-cell
pertussis vaccine producers, American parents began to band together.
The first and most powerfulgroup was and still isthe advocacy
group Dissatisfied Parents Together (DPT), which was formed in
. U.S. Institute of Medicine, Adverse Events.
. Ibid.

Geier & Geier : Pertussis Vaccination

 by Barbara Loe Fisher. Its members called for research toward
a safer pertussis vaccine and mandatory reporting of all adverse reac-
tions to vaccines. Additionally, in  Fisher and Dr. Harris Coulter
published the book A Shot in the Dark, which educated parents about
the potentially harmful effects of childhood immunizations. Within
a year of the formation of DPT, the group’s messages became so
strong that the American Academy of Pediatrics was forced to conduct
more than eight months of hearings to discuss recommendations for
a federalcompensation program for chidlren with vaccine -related
illnesses and injuries.69 The result of these discussions, along with the
large-scale civil litigation against the manufacturers, helped spur the
introduction of the NationalCompensation Act (S -) in  by
Senators Paula Hawkins and Orrin Hatch. The goalof this act was
to set limits on liability for vaccine-related disabilities. In order to
encourage its passage, a vaccine manufacturer agreed to settle one of
the cases against it for a totalof  million dollars.70 The manufacturer
then cited this large settlement as an example of why it needed
protection against litigation if it was going to continue to manufacture
vaccines.
By the mid-s it seemed that litigation and political action
groups were being more effective in bringing about change in vaccine
policy than the government agencies regulating the vaccines. But in
, Public Law -, the NationalVaccine Injury Act , was passed
by the United States Congress. The law called for the establishment
of the NationalVaccine Program (NVP) to achieve optimalpreven-
tion of human infectious diseases through immunization and to
achieve optimalprevention against adverse reactions to vaccines . Ad-
ditionally, the law called for the establishment of the National Vaccine
Advisory Committee (NVAC) to advise the director of the NVP, the
NationalVaccine Injury Compensation Program (VICP) to evaul ate
claims of injury from vaccines and to provide compensation where
justified, and the Advisory Commission on Childhood Vaccines
(ACCV) to advise the Secretary of the Department of Health and
Human Services and the VICP on vaccine policy. This law also
mandated a scientific review of possible adverse effects of whole-cell
. Coulter and Fisher, A Shot in the Dark.
. J. P. Koplan and A. H. Hinnman, “Decision Analysis, Public Policy, and Pertussis:
Are They Compatible?” Med. Decision Making, , , –.

 Journal of the History of Medicine : Vol. , July 
pertussis vaccine by the Institute of Medicine of the NationalAcademy
of Sciences.71
The NationalVaccine Compensation Act requires that persons
damaged by a vaccine seek compensation under the VICP before
filing a civil claim against the vaccine manufacturers. Although this
act did benefit victims by providing them with another mechanism
by which to receive compensation, it also protected the vaccine
manufacturers from most civililtigation and , in fact, muted litigation
then pending against the manufacturers, which helped to remove the
pressure on them to move from whole-cell pertussis to acellular
pertussis vaccination. Congress foresaw that the act might slow down
progress in converting from a whole-cell to an acellular pertussis
vaccine, so to help ameliorate this problem, it also appropriated funds
and charged the IOM to hold hearings and make recommendations
for vaccine improvement.72
But additionaldi fficulty with the whole-cell pertussis vaccines used
in the United States erupted again in  when the FDA recalled
Connaught Laboratories DPT lot M because of possible con-
tamination of the vaccine with equine influenza vaccine. The poten-
tialcontamination occurred because Connaught was using the same
equipment on successive days to make and fill veterinary products
that it used for making and filling human vaccines. The company
agreed that some children might well have been injected with the
vaccine that was intended solely for use in horses, but it also felt it
was unlikely that the children were damaged by the veterinary-grade
product.73
the vaccine compensation act
The National Vaccine Program established under Public Law -
first began to operate in  under the directorship of the assistant
secretary of health of the Department of Health and Human Services.
The first meeting of its advisory committee was not held until June
, however, and the actualoperation of the injury compensation
program, the VICP, did not begin until . It was administered by
. U.S. Public Law –.
. Ibid.
. M. R. Geier (letter), Medical/Legal Consultant,  August  sent to Dr. M. C.
Hardegree, Director, FDA Office of Biological Research. This letter is in the authors’
possession.

Geier & Geier : Pertussis Vaccination

the secretary of the Department of Health and Human Services
(HHS) through the staff of the Health Resources and Services Admin-
istration. By the end of its first year of operation, the VICP had
received  petitions for compensation, of which  were related
to DPT vaccine.74
The act was originally passed to provide rapid and generous justice
to those American citizens who were damaged by a vaccine that they
were taking for the public good. It was initially funded by the U.S.
Congress for $ million and was to be funded in the future by a
small tax to be charged on each vaccine dose given. Implementation
of the act was to be no-fault and nonlitigious, and in all claims, HHS
was to be the respondent. A person or his or her guardian who
believed that a vaccine had caused damage could file a petition for
compensation. The act also required that HHS advertise and make
known that anyone who believed they were damaged by a vaccine
prior to the passage of the Act could petition for damages, no matter
how long ago the adverse reaction occurred. HHS was to have the
petition read by a neutralexpert physician , who was to recommend
for or against paying the claim. If the decision was unfavorable, the
petitioners could request a hearing on the matter before a special
master working for the U.S. Court of Claims. Since the act’s inception,
the chief specialmaster has been Gary Gokl iewicz . Petitioners could
be represented by counseland coudl bring experts to testify on their
behalf. Petitioners’ attorneys and experts were to be paid by the
VCA, win or lose, so long as the action was brought in good faith.
When Congress passed the act, it included a Vaccine Compensation
Table and Aids of Interpretation to the Table that described in detail
the timeframe and symptoms expected in patients damaged by a
vaccine. If a petitioner could demonstrate that his or her case fit the
table, he or she would receive an award for damages unless HHS
could prove an alternative cause. If a petitioner’s case did not fit the
table, the burden of proof shifted to the petitioner to prove that the
vaccine had caused the damage claimed.75
Despite this congressionalmandate , for approximately one year
after the passage of the VCA, HHS refused to defend the cases,
maintaining that it lacked the staff to adequately act as respondent.
. U.S. Institute of Medicine, Adverse Events.
. U.S. Public Law -.

 Journal of the History of Medicine : Vol. , July 
Since the act stated that anyone who filed a claim would have that
claim adjudicated within six months or they would win by default,
most of the early claims were won by default or through virtually
unopposed hearings. Then things began to get more difficult for the
petitioners based upon the experience of Dr. Geier, who made close
to  appearances as an expert witness before the VCA. HHS asked
for and finally got permission to have U.S. Justice Department lawyers
defend the cases on its behalf. Then HHS, as the respondent, claimed
the right to begin to change the rules of the act by administrative
means. Among the changes made, one involved the dropping of the
six-month time guarantee of adjudication. As a result, some cases
have dragged on for nearly a decade, despite the fact that Congress’s
originalintent was to grant rapid justice to vaccine victims . During
these years, HHS began to shrink the table described in the original
act. As the table got smaller, more and more of the burden of proof
was shifted from the respondent to the petitioners. The VCA also
started to adjust the amount of legal fees paid to the petitioners’
lawyers and experts, making it more and more difficult for petitioners
to find qualified help in bringing cases under the VCA. Since it often
took years for cases to be heard, it also took years for lawyers and
experts to be paid, even if the cases were won and even after the
judgments were entered.
In a finalassautl on the act , HHS did not use neutralmedical
reviewers, but rather experts trained in how to help defend cases.
Despite the fact that Congress had thought most cases would be
settled administratively, HHS basically chose to oppose payment in
virtually all cases, thus making bringing petitions under the VCA a
litigious process. This process was not a predictable one, either, be-
cause the specialmasters of the VCA were not bound by their own
previous rulings. Thus, no precedents were ever set, and it was difficult
to know in advance which cases were most likely to be deemed
compensable by looking at previous rulings in similar cases. The usual
position of HHS’s experts was that whatever happened following a
vaccine was not caused by the vaccine, but rather was only coinciden-
tally associated in time with it. Their argument was that almost all
children receive multiple vaccines, mostly in the first year of life.
Many of these same children are first discovered to have neurological
conditions in that first year of life. Therefore, it follows as a matter
of coincidence that many children will be discovered to have a neuro-

Geier & Geier : Pertussis Vaccination

logical problem shortly following vaccination. Most of the petitioners’
experts, on the other hand, maintained that if an apparently neurologi-
cally intact child has his or her first neurologically significant symptom
closely following a vaccine, and if no provable alternative cause could
be found despite a good medicalanayl sis , then more likely than not
the vaccine caused the neurological problem.
The VCA has resulted in a dramatic reduction in the number of
civilcourt cases filed against vaccine manufacturers. Unfortunately,
it has not resulted in rapid, generous, and nonlitigious justice. The
bureaucracy of the Health and Human Services has defeated the
originalintent of Congress in passing the act .
the counterresponse to difficulties
with whole-cell pertussis vaccine
Because vaccine manufacturing companies are among the most inter-
ested in studying vaccines, they often provide large sums of money
to researchers willing to do so. Such researchers, because they are
well-funded and clinically knowledgeable, often develop reputations
for their expertise, and thus they are often invited to serve on commit-
tees that make recommendations about vaccine policy. Such a system
often results in conflicts of interest because researchers whose liveli-
hoods strongly depend on financialties to vaccine manufacturers are
often the ones making the policy decisions that impact the financial
future of the vaccines. In the pertussis vaccine field, one of the most
egregious examples of such a conflict of interest is Dr. James Cherry,
a professor at the University of California, Los Angeles, who spear-
headed an attempt to change the philosophy of the scientific commu-
nity regarding the whole-cell pertussis vaccine.
Cherry was and continues to be one of the most prolific writers
on the topic of pertussis and pertussis vaccines. His published articles
number in the hundreds and are cited at least once in virtually every
article written by an author in this field. He also has written chapters
on infectious disease in the leading textbooks, such as Nelson’s Textbook
of Pediatrics.76 In a  lecture at a symposium sponsored by Con-
naught, Cherry stated that all physicians are aware that whole-cell
pertussis vaccine occasionally produces severe reactions and that these
. J. D. Cherry, “Encephalitis,” in R. E. Behrman and V. C. Vaughn, eds., Nelson’s
Textbook of Pediatrics, th ed. (Philadelphia: W. B. Saunders Company, ) pp. –.

 Journal of the History of Medicine : Vol. , July 
may be associated with permanent sequellae or even death.77 But
during the s Cherry became a regular consultant and expert
witness on the side of the pharmaceuticalindustry, consistently testify-
ing and publishing that there was no proof that whole-cell DPT
caused permanent brain damage.78 In , Cherry headed a select
committee purportedly appointed to review the data on pertussis
vaccine and its ability to cause permanent brain damage and to publish
findings which would become the officialposition of the American
Academy of Pediatrics. The academy’s own records not only showed
that it had accepted large gifts from the various whole-cell pertussis
manufacturers, but also that the letters of appointment to the members
of the select committee told them that they were to find that the
vaccine did not cause permanent brain damage.79 Not surprisingly,
the committee did an extensive review of the literature on adverse
reactions to pertussis vaccine, the vast majority of which showed a
link between the vaccine and permanent damage in children, but for
one reason or another it found fault with all of the old studies
establishing causation. In , the American Academy of Neurology
published a similar position statement.80 The announcement of the
Academy of Pediatrics position was followed shortly thereafter by a
paper reporting on a vote taken by the Pediatric Neurology Society:
The majority of its members voted in support of the proposition that
pertussis vaccine was not proven to cause permanent brain damage.
The information in the paper was based on the vote and reflected
little scientific research; only twenty-one scientific references were
cited. However, Dr. John Menkes, the author of a leading pediatric
neurology textbook and one of the very few pediatric neurologists
. J. D. Cherry and E. A. Mortimer, “An Old Bacterial Vaccine with New Problems:
Pertussis VaccineRecent Experiences,” Pediatric Immunization Today, Connaught Labora-
tories Symposium, , –. This article is in the authors’ possession.
. J. D. Cherry (deposition), Bobby Hardaway and Wife, Shirley Hardaway, etc., vs. The
Metropolitan Government of Nashville, etc., et al., U.S. FederalCourt , Middle District of
Tennessee, Nashville Division, CivilAction Number : --,  June , –. This
deposition is in the authors’ possession.
. J. D. Lockhart (letter), Director, Department of Maternal, Child and Adolescent
Health, American Academy of Pediatrics,  December  to D. T. Karzon, Department
of Pediatrics, Vanderbilt University School of Medicine. This letter is in the authors’
possession.
. J. D. Cherry, P. A. Brunell, G. S. Golden, and D. T. Karzon, “Report of the Task
Force on Pertussis and Pertussis Immunization-,” Pediatrics, , , –; American
Academy of Neurology, “Assessment: DTP Vaccination,” Neurology, , , –.