Patterns of Infection and Patterns of Evolution: How a Malaria Parasite Brought “Monkeys and Man” Closer Together in the 1960s
Journal of the History of Biology
Patterns of Infection and Patterns of Evolution: How a Malaria Parasite Brought ''Monkeys and Man'' Closer Together in the 1960s
RACHEL MASON DENTINGER 0
0 Department of History King's College London Room 8.05 Strand , London WC2R 2LS UK
In 1960, American parasitologist Don Eyles was unexpectedly infected with a malariaparasite isolated from a macaque. He and his supervisor, G. Robert Coatney of the National Institutes of Health, had started this series of experiments with the assumption that humans were not susceptible to ''monkey malaria.'' The revelation that a mosquito carrying a macaque parasite could infect a human raised a whole range of public health and biological questions. This paper follows Coatney's team of parasitologists and their subjects: from the human to the nonhuman; from the American laboratory to the forests of Malaysia; and between the domains of medical research and natural history. In the course of this research, Coatney and his colleagues inverted Koch's postulate, by which animal subjects are used to identify and understand human parasites. In contrast, Coatney's experimental protocol used human subjects to identify and understand monkey parasites. In so doing, the team repeatedly followed malaria parasites across the purported boundary separating monkeys and humans, a practical experience that created a sense of biological symmetry between these separate species. Ultimately, this led Coatney and his colleagues make evolutionary inferences, concluding ''that monkeys and man are more closely related than some of us wish to admit.'' In following monkeys, men, and malaria across biological, geographical, and disciplinary boundaries, this paper offers a new historical narrative, demonstrating that the pursuit of public health agendas can fuel the expansion of evolutionary knowledge. In 1960, parasitologist Don Eyles was in the midst of a series of malaria experiments on rhesus macaques. Under the auspices of the National
Parasitology; Malaria; Evolution; Public health; Primates; Ecology; Zoonosis; Experimental medicine; Lab-field border; National Institutes of Health
Institutes of Health (NIH), his Memphis laboratory aimed to understand
human malaria infection. Previous work had convinced malariologists
that macaques could not host the human malaria parasite Plasmodium
vivax (Hegner, 1928). Fortunately, however, a monkey-specific parasite,
Plasmodium cynomolgi, was considered similar enough to P. vivax to
effectively model human malaria infection (Eyles, 1960). Eyles and his
team later admitted that they had treated their malarious mosquitoes
casually, considering their itching bites a mere nuisance (Eyles et al.,
1960). As his supervisor G. Robert Coatney explained it, ‘‘erroneously we
thought malaria in the monkey was for monkeys and malaria in man was
for people’’ (Coatney, 1985, p. 10). Eyles was duly surprised when he fell ill
with fever soon after the experiment, and several days passed before he
seriously entertained the possibility that he had contracted malaria. When
he finally examined his own blood films, he was perplexed to see that he
had been infected with ‘‘monkey malaria.’’
A regimen of chloroquine handily cleared Eyles’ malaria – but not
before he had drawn 20 milliliters of his own blood, the first component
in a new series of experiments that would transform the identity of
‘‘monkey malaria’’ for this team of malariologists. One inadvertent
laboratory infection did not necessarily imply a public health threat, but
it did present a string of perturbing questions to Coatney, Eyles, and
their colleagues: Could mosquito vectors reliably transmit monkey
malaria to human subjects? Could they perhaps even transmit the
parasite between human subjects? Did human infection with monkey
malaria actually happen in Malaysia, where the monkey parasite P.
cynomolgi was first isolated? Pursuing these questions would require the
efforts of multiple teams of parasitologists, working in the United States
and Malaysia, conducting human experimentation, opportunistic
collection, and ecological field trials.
However, this inquiry into monkey malaria did not stop with the
medically relevant questions listed above. Coatney and his colleagues
also extended their inquiry into the domain of biology, asking what a
shared malaria parasite implied about ecological and evolutionary
relationships between monkeys and humans. Host animal relationships
had assumed practical importance for parasitologists since the inception
of their field in the late nineteenth century. As in other medical fields,
like bacteriology, they sought experimental animals that could act as
‘proxies,’ ‘surrogates,’ and ‘stand-ins’ for human medical conditions.1
This search was not a straightforward one, though. The extrapolation of
findings from nonhuman to human bodies was based upon an
assumption of evolutionary relatedness, the basis for a posited
biological symmetry; but at the same time, many parasitic organisms had
evolved the ability to infect only very specific host animals, undermining
scientists’ efforts to find nonhuman models for human diseases.2 The
resulting struggle to find suitable, effective experimental animals became
central to the practice of parasitology and it represented an intersection
of medical and evolutionary questions ripe for exploration. Most
critically, it was at this intersection that parasitologists came to engage with
animals of many different species, in many different contexts, and to ask
questions about the biological relationships between them.
While scholars have previously documented the application of
evolutionary concepts to medicine (Bynum, 1983, 2002; M e´thot, 2011;
Buklijas and Gluckman, 2012), and recognized parasitology as a field
that bridged medicine and natural history (Harden, 1985; Li, 2002;
Anderson, 2004), they have almost entirely overlooked the ways that the
study of animal disease has itself generated evolutionary insights.3 Most
importantly, these historical narratives portray medical researchers and
evolutionary researchers as inhabitants of distinct disciplinary silos, with
separate agendas. The case of parasitology offers a new historical
narrative, demonstrating that medical research and evolutionary reasoning
may be pursued in tandem. More specifically, it shows that public health
agendas can fuel the expansion of evolutionary knowledge.
Central to parasitological practice was the examination of a broad
range of animal species, which were tracked or acquired in forests, zoos,
and human households, to name only a few contexts. The diversity of
species employed was necessitated by the demands of host specificity:
Parasitologists worked in the laboratory and in the field to determine how
and why different parasites could be transferred (or not transferred)
between two different animal species. This practical experience induced them
to ask questions about the biology of these animals, hypothesizing about
their ecological and evolutionary proximity to each other in order to
explain the results of their medical experimentation. Thus they began to
use patterns of infection to infer patterns of evolution, a practice identified
2 As Ilana Lo¨ wy writes, ‘‘[n]o simple correlations were found between the suscepti
bility or resistance to a pathogenic germ and proximity on the phylogenetic
[evolutionary] ladder’’ (Lo¨ wy, 2003, p. 437). Even heavily standardized model organisms, bred
specifically for the purposes of hosting human diseases, remain ‘‘largely mysterious
products of millennia of evolution,’’ with the capacity to ‘‘surprise’’ researchers in the
laboratory and beyond (Leonelli and Ankeny, 2011, pp. 315–316).
3 For an exception, see Me´ thot (2012).
as the ‘‘host–parasite method’’ in the 1920s (Metcalf, 1929). Reciprocally,
evolutionary relationships could also be used to predict potential parasitic
infections or disease threats (von Ihering, 1891; Kellogg, 1913; Darling,
1921; Ward, 1926; Metcalf, 1929; Baer, 1940, 1952, 1957; Cameron, 1952).
Essential to both of these modes of the ‘‘host–parasite method,’’
working in either direction of inference, was a direct engagement with the
lives of animals. The history of monkey malaria offers an especially
opportune example of this parasitological practice. Malariologists believed
that cross-infection between monkeys and humans was nearly impossible.
Thus, the jarring reality of Eyles’ accidental infection with monkey malaria
in 1960 had a host of ramifications directly relevant to both public health
agendas and assumptions about primate evolutionary relationships,
bringing the biological reality of the experimental animals into stark relief.
The malariologists who performed this research scrutinized all the
organisms involved, from the protozoan parasites to their mammalian hosts, and
they followed them over geographical, biological, and disciplinary
boundaries. Coming at a time when strategies for malaria control and ideas
about primate evolution were both in flux, the history of this project
demonstrates how evolutionary relationships could be worked out as part
of a public-health agenda.
In the first section of this paper, I explore the selection of research
subjects for the experimental program that took shape in the wake of
Eyles’ accidental infection in 1960. I place these subjects in the broader
context of the early-twentieth century search for appropriate malaria
models and malariologists’ struggle with host specificity in their parasite.
During this time, a transition away from avian models began, as it
became possible to employ primate and other mammalian models. One
especially apposite element of this history was Coatney’s use of human
subjects as models for monkey malaria. Through this reversal of a typical
medical research protocol, an equivalency was wrought between monkeys
and humans; and this equivalency turned the conundrum of the malaria
parasite’s host specificity into a larger complex of questions about
ecological relationships and evolutionary distance between humans and
other species of primates. Unlike typical laboratory experimental models,
which scholars have described as having ‘‘no ‘objective’ counterparts in
nature’’ (Logan, 2002, p. 355), for Coatney and his group, understanding
their experimental organisms – including humans, monkeys, and malaria
parasites – in a natural context became paramount. The naturalness of
cross-infection between monkeys and men was medically significant,
thanks to its potential implications for disease transmission, and
biologically intriguing, thanks to its implications for primate evolution.
In the second section of my paper, I will follow Eyles and his
colleagues as they exited the lab and entered the field in Malaysia,4
reconstructing the ecological reality of both monkey malaria and its hosts, and
collecting data that would demonstrate that human infection with the
monkey parasite was more than a ‘‘laboratory curiosity’’ (Contacos and
Coatney, 1963, p. 914), and was in fact a ‘‘true zoonosis,’’ contractible by
natural means. This history of monkey malaria is one more instantiation
of the ‘‘lab-field border,’’ as Robert Kohler has called it (Kohler, 2002).
As in Kohler’s account, the definition of what is ‘‘natural’’ shifted,
relative to the context and goals of the research project as it developed. As
the apparent naturalness of malaria cross-infection between rhesus
monkeys and humans gained credibility, it brought these two primate
species into closer proximity in the minds of Coatney and his colleagues.
Thus, as they enriched the ecological picture of primate malaria in
nature, malariologists also came to appreciate that ‘‘natural’’ infection
had as much to do with the evolutionary history of hosts as with the
supposed naturalness of an experiment’s context or mode of infection.
In the final section of the paper, I show how the parasitologists involved
in this research transmuted the medical characteristics of malaria
infections, including susceptibility and transmissibility, into
evolutionary characters. Eyles’ accidental infection occurred in a climate where it
was assumed that humans were not susceptible to monkey malaria. In
throwing this assumption into question and following a simian parasite
across the species boundary, parasitologists also formulated an
evolutionary argument that ‘‘monkeys and man’’ were, in Coatney’s words,
‘‘more closely related than some of us wish to admit’’ (Coatney, 1963,
p. 877). My account demonstrates that Coatney’s striking conclusion
was wrought from the most pressing questions and central practices of
parasitology, in which evolutionary insights have long been drawn from
medical practices and medical insights from evolutionary practices.
Modeling Parasitic Disease: Monkeys, Malaria, and Men in the Lab
Coatney’s post-war malaria research coincided with a newfound
capacity to use mammalian experimental models in malariology,
including rodents and nonhuman primates, thus marking a shift away
4 Eyles and his team worked in peninsular Malaysia, which was known as Malaya
until 1963, when it was incorporated into the newly formed country of Malaysia (which
also includes Singapore and Sarawak, on the island of Borneo). As the research
discussed here spans the period of transition from Malaya to Malaysia, I will refer to the
country as Malaysia, for simplicity’s sake.
from traditional bird malaria models (Slater, 2009, pp. 39–42; Cox,
2010). Since Darwin, the extrapolation of knowledge from nonhuman
to human bodies has often been rooted in a notion of evolutionary
relatedness (Bernard, 1865; Guerrini, 2003; Bresalier et al., 2015). Thus
another primate might seem the ideal experimental model for human
malaria, based upon the assumption that close familial relationships
result in easy cross-infection between species. However, parasitic
crossinfection has never followed such straightforward phylogenetic rules,
and even closely related organisms might prove immune to each other’s
parasites. This has been especially true in malaria research, thanks to
the parasite’s relatively high level of host specificity. In other words,
most early attempts to infect monkeys with human malaria failed
(Hegner, 1928, p. 238). To make matters worse, the challenges of
procuring and maintaining healthy populations of nonhuman primates
for experimental use were nearly insurmountable until the
mid-twentieth century, when breeding colonies in the United States were
established (Carpenter, 1940; Schmidt, 1979; Rawlins and Kessler, 1986;
Dukelow and Whitehair, 1995; Montgomery, 2005).
By contrast, birds were easily obtained and reared, and their malaria
parasites were readily isolated. (Slater, 2005a, 2009). For malariologists,
an exact correspondence between avian and human parasites was
unnecessary. In fact, ‘‘the avian malarias were distinct [from the human
malarias] in morphological and phylogenetic detail,’’ Slater writes, and
‘‘they could be viewed as congruent only if viewed over the course of the
whole life cycle of the [parasitic] organism, in its many stages and forms,
and in many locations and transformations, including at times
consideration of the role of vectors and the response to drugs’’ (Slater, 2005a,
p. 291). In other words, the apparent impossibility of finding a closer
evolutionary correlate to human malaria infection required a special
mode of argumentation, a formulation of ‘‘congruence’’ that would
emphasize the parallels between human and avian parasites and
trivialize the divergences. The lack of better options, the ease of maintaining
birds in the laboratory, and the perception of symmetry between the
avian and human parasite life cycles all contributed to making bird
malaria fundamental to the biomedical understanding of malaria
through the 1930s (Slater, 2009, pp. 39–58). However, it left open the
question of how the evolutionary relationships of hosts were related to
their susceptibility to malarial infection – a problem that was
simultaneously practical, experimental, and theoretical, and to which
parasitologists would turn afresh after Eyles’ unanticipated infection with
G. Robert Coatney was one malariologist who was well aware of the
complex association between the evolutionary proximity of hosts and the
chances of experimental cross-infection amongst them. In the 1950s and
1960s, Coatney would take advantage of the growing availability of
primate experimental models, as in the laboratory where Eyles was
infected; but three decades earlier, he had launched his early career with an
avian experimental model. Trained in the traditions of parasitology, with
an emphasis on both zoology and medicine, Coatney worked as a
biology professor at Nebraska State Teachers College in the 1930s. When he
wasn’t teaching, he was combing the Nebraska landscape, seeking a new
model for malaria research amongst wild bird populations. After years
of collecting and screening birds for malaria, he finally identified a
malaria infection from a mourning dove. First he attempted to transfer the
parasite to the canary (a typical malaria laboratory model) but he found
that the infection dropped off rapidly. So he changed tack, shifting to a
pigeon host, and was rewarded: The parasite flourished in his new model
and, thanks to his success, the Public Health Service subsequently offered
him a job (Coatney, 1985).5 As he reported in a 1938 paper in the
American Journal of Epidemiology, the ‘‘close zoological relationship
existing between doves and pigeons’’ had suggested to him that pigeons
might serve as a better laboratory host for a strain of malaria isolated
from doves (Coatney, 1938, p. 382). In other words, early in his career,
long before he had begun working with primate malaria models,
Coatney was already considering how evolutionary distance between different
host species was related to parasitic cross-infection, and could be
employed to make more effective experimental choices.
Soon after Coatney joined the Public Health Service, patterns in malaria
experimental models began to shift. Work in the 1940s revealed that
mammalian malaria life cycles include a stage that is quite different from
avian malaria life cycles – a dormant form that lodges in the mammalian
liver, a finding that undermined the acceptability of birds as proxies for
humans.6 British parasitologists Percy Cyril Claude (P.C.C.) Garnham and
Henry E. Shortt, of the London School of Hygiene and Tropical Medicine,
had uncovered this ‘‘exoerythrocytic cycle’’ while studying a rhesus
macaque infected by Plasmodium cynomolgi (Shortt and Garnham, 1948).
5 In 1935, only a few years after Coatney isolated a plasmodium from a pigeon,
chicken malaria, P. gallinceum, was isolated and identified and it soon became an
extremely common model (Slater, 2009, p. 53), although, according to Coatney, the
USDA would not allow the importation of this parasite until the advent of World War
II made it imperative (Schmidt, 1979, at 13:52).
6 As opposed to the avian malaria parasites, where this stage takes place in a variety
of other tissues (Lainson and Killick-Kendrick, 1997, p. 179).
Immediately after infecting a new mammalian host, malaria becomes
temporarily dormant and enters the host’s liver. From a clinical standpoint,
the parasite is concealed, since blood drawn at this time will show no sign of
infection. Shortt and Garnham confirmed the generality of their finding
with a biopsy of the liver of human mental patient, whose advanced syphilis
was being treated with malarial fever, which was a common treatment at the
time, developed during the interwar period, prior to the advent of
antibiotics (Wagner-Jauregg, 1927; Coatney et al., 1971).
Avian malaria researchers were dismayed by this clear demonstration
that a major stage in the life cycle of human malaria was so distinct
from that of avian malaria, thus challenging the perception of
congruence upon which the avian malaria model rested. In fact, some initially
questioned the validity of these new observations and suggested that
Shortt and Garnham had observed an artifact peculiar to their method
of experimental malaria inoculation or a product of previous biopsies
performed on the monkey’s liver (Eyles, 1960, pp. 553–554). While most
malariologists accepted Shortt and Garnham’s claims, it was at least a
decade before the question was completely laid to rest and Shortt and
Garnham vindicated. Nonetheless, the notion that birds could
effectively model human malaria had been undermined. Even disregarding
the claims of Shortt and Garnham, the avian model could not be used to
accurately test the toxicity of anti-malarial drugs for human subjects –
in this respect, the physiology of a bird was understood to be too far
removed from that of a human (Slater, 2005a, p. 289).
To make matters worse, fear that quinine supplies might be cut off
during World War II meant that the turnaround time from drug
development to implementation in the field seemed desperately short.
Thousands of potential antimalarial drugs awaited testing, and the
safety of these compounds could not be adequately gauged through
avian models. Slater refers to this need as one motivation for the
development of primate malaria research models during this period
(Slater, 2005a, p. 289), but it is clear that there were still very few
reliable sources of monkeys for toxicity trials in 1944. Most large-scale
primate trials required researchers to travel to Asia and make direct
contact with monkey-trappers and then personally supervise their
transport across the globe. The necessity of a lengthy sea voyage during
the war made this prospect seem even less reasonable.7 Coatney, who
was in charge of the federal effort to test antimalarials at this time, knew
7 The acquisition of macaques and other primates for research in 1944 was not much
different from Carpenter’s description of sourcing macaques to stock his colony on
Cayo Santiago (Puerto Rico) in 1938 (see Rawlins and Kessler, 1986, pp. 16–19).
that he needed a reliable source of human research subjects who could
trial the drugs that had proven most promising in nonhuman models.
Fortunately for Coatney, the common use of malarial fever against the
dementia and paralysis of advanced syphilis provided a source of human
subjects, circumventing doubts about the use of nonhuman experimental
subjects. Early in the war, he began antimalarial trials with the patients of
St. Elizabeths Hospital in Washington, D.C., who were already
undergoing treatment with P. vivax, the human malaria parasite. As the war
progressed, however, the demand for human subjects increased. In 1943, a
colleague mentioned the possibility of using prison inmates in this
research, and Coatney was immediately interested in the prospect. Using his
medical and political connections, he was soon able to secure the
cooperation of a federal prison in Atlanta, where he began infecting prisoners
in March 1944 (Schmidt, 1979; Coatney, 1985). Describing the project in
1966 for a New York Times Magazine cover article, science journalist C.P.
Gilmore wrote, ‘‘In the more than two decades since [the project began],
the units have been responsible for much of the progress, both in
antimalarial drugs and in fundamental knowledge of the disease itself’’
(Gilmore, 1966, p. 47). Quoting Coatney, Gilmore reported that 3000
inmate volunteers had participated in the project at the Atlanta
penitentiary during that period. Most prominently, it was this location that
demonstrated the safety of Chloroquine, a successful antimalarial for
more than fifteen years, until the parasite evolved resistance to the drug
(Gilmore, 1966, p. 52). After the war, alternate models for malaria
research proliferated, thanks to the discovery of several rodent malarias and
the increasing supply of nonhuman primates for biomedical research
(Slater, 2005a).8 But the success of Coatney’s prison research scheme
allowed him to continue his human experimentation, in tandem with
primate and other nonhuman malaria research.
The initiation of the World Health Organization (WHO)’s global
malaria eradication program in 1955 further secured Coatney’s access to
multiple experimental populations for his malaria research. The history of
this program and its ultimate failure and cessation in 1969, fourteen years
after it was initiated, has already been told.9 For my purposes, the global
drive toward malaria eradication provides an important context for the
monkey malaria story, providing a powerful justification for the funding
8 Slater (2005a, pp. 270, 289, 293) on the increasing use – and necessity – of non
avian models for malaria. Guerrini (2003, pp. 117–120) describes the general increase in
the use of primates, especially rhesus macaques, in the first half of twentieth century.
Also, see again, on the topic of breeding colonies of primates: Carpenter (1940), Rawlins
and Kessler (1986), Dukelow and Whitehair (1995) and Montgomery (2005).
9 See, for example, Packard (2010, pp. 150–176).
that made this extended project possible. From its inception, the program
had been plagued by challenges and doubts. However, Eyles’ infection
presented the possibility that malaria eradicated from a human
population might return later, thanks to a hidden and inaccessible animal
reservoir. Thus, the breaking down of the species barrier between
macaques and humans within Coatney’s NIH lab had repercussions far beyond
its walls: If simian species of malaria could easily pass from monkeys to
humans via mosquito vectors, this alone could prove fatal to the WHO’s
plans for malaria eradication. As malariologist McWilson Warren
recalled in a 2005 interview with Slater, ‘‘On a worldwide basis, at this time,
the commitment to malaria eradication had become a major issue,’’ and
threats to this goal had to be taken seriously. ‘‘Geneva [the headquarters
of the WHO], London, and Washington were really, very spooked about
the whole business [of Eyles’ infection with monkey malaria,] because
suddenly if there was a significant level of malaria in non-human primates
infectious to man, then the concept of eradication had biologically gone
down the tubes: Under the circumstances, there seemed to be no
possibility that human malaria could be eradicated’’ (Slater, 2005b, p. 9).
Thus, when Eyles was unexpectedly infected with monkey malaria in
1960, a reliable experimental protocol and a pool of human subjects were
immediately available, and Coatney’s team began testing the transmission
of malaria from monkeys to humans. While previous attempts to
crossinfect between monkeys and humans had been performed in the first decades
of the twentieth-century, mostly without success, never had such a
largescale cross-infection project, with hundreds of human subjects, been
attempted.10 From the 20 mL of blood he had drawn from himself, Eyles first
inoculated a macaque in his own lab. The remainder of the blood was sent to
Atlanta, to be immediately administered to volunteers from the inmate
population. And within days, all of the experimental organisms – macaques
and inmates alike – showed signs of malaria infection (Eyles et al., 1960).
Prominent in this project from the beginning was an emphasis upon the
natural status of the team’s laboratory experimentation. Only two years
earlier, in 1958, the Joint WHO/FAO Expert Group on Zoonoses had
assembled to assess the risks to human health posed by nonhuman animal
disease, generating an official definition of ‘‘zoonoses,’’ as those diseases
that were ‘‘naturally transmitted’’ between animals and humans (WHO,
1959, p. 6).11 Embedded as he was in the Public Health Service, funded by
10 For a representative example of past such experiments, see Clark and Dunn (1931).
11 It should be noted that this report makes no mention of the possiblity that malaria
might be a zoonosis, and despite the work of Coatney’s group, malaria continues to be
left out of subsequent reports.
the NIH, and overseeing the WHO Expert Committee on Malaria in both
1958 and 1960,12 it fell to Coatney to create the most ‘‘natural’’ conditions
possible in his experiments, in order to directly address the urgent public
health concern with zoonotic malaria.
Coatney felt this pressure acutely. In his mind, P. cynomolgi, monkey
malaria, had already ‘‘qualified experimentally as a zoonosis’’ (Beye
et al., 1961, p. 315),13 by means of the experimental prison infections
that immediately followed Eyles’ infection. But Coatney also expressed
concern about critics who ‘‘implied that the establishment of a
cynomolgi parasite in man was nothing more than a laboratory curiosity’’
(Contacos and Coatney, 1963, p. 914). In other words, unlike a typical
laboratory experimental model, which scholars have described as having
‘‘no ‘objective’ counterparts in nature’’ (Logan, 2002, p. 355)
establishing the natural complement of this experimental model became
absolutely essential to Coatney’s group.
One method of attempting to recreate ‘‘natural conditions’’ in the
laboratory was to import organisms directly from their original
environment. In general, the experimental animals used in American and
English malariology were not heavily standardized. Of the malaria
research in the first decades of the twentieth century, Slater writes, ‘‘the
birds, parasites, and insects that made up these complex, multiorganism
malaria models were not highly inbred, and often were creatures of the
wild or the market’’ (Slater, 2005a, p. 264). This was also true of most of
the monkeys used in the experiments overseen by Coatney. Indeed,
throughout the first half of the century, most primates for biomedical
research were imported directly from India or other locations in Asia.
Malariologists and their family members recall collecting primates for
research, accompanying trappers on expeditions or seeking them in
public marketplaces (Slater, 2005b, pp. 13–16 and 20; Eyles, n.d., p. 93).
After all, it was not until 1962 that the first Regional Primate Research
Center opened in the United States, ushering in an era of locally bred
primates for research.14 Until that time, the rhesus macaques of malaria
laboratories were typically only one degree removed from their natural
Even the malaria strain used by Coatney’s group appears to have
been a step closer to ‘‘nature’’ than the strain used in other labs in the
12 In 1958, Coatney represented the NIH as a WHO consultant (WHO, 1959) and in
1960 he was a member of the committee (WHO, 1961a, b).
13 My italics.
14 Eventually there was would be seven of these centers, scattered throughout the U.S.
(Dukelow and Whitehair, 1995, pp. 1–2).
United States. While most American malariologists in the late 1950s
shared a strain of the monkey parasite P. cynomolgi that had been
isolated from an infected macaque seventeen years earlier, Eyles had a new
strain, which P.C.C. Garnham had taken from a macaque in Malaysia in
1957 (Eyles et al., 1960, p. 1812). After 1960, Coatney and others
hypothesized that the newer strain of the parasite was able to jump hosts,
from monkeys to humans, because of its more recent wild origin. In other
words, the older strain had been used as a laboratory model for too long
– it was domesticated and no longer held many of the properties that tied
it to its natural ecological existence. While not engineered in the same
sense as a standardized organism, the strain’s long perpetuation in the
contrived environs of the laboratory had separated it from its natural
origin and converted it into a tool of the laboratory.15 By contrast, the
newer strain of monkey malaria challenged the assumptions and artificial
strictures that scientists had attempted to place upon it; it retained a wild
quality even within the laboratory, a fact that the malariologists involved
in subsequent experimentation appeared to appreciate.
Soon enough, Coatney’s group made the conscious decision to
import a naturally infected simian host as well: After the initial set of trials
with Eyles’ infected blood, an infected macaque was trapped in
Malaysia and shipped to the U.S., where its parasite was transferred to six
new human inmate volunteers. Three inmates received the malaria
parasite by mosquito bite while the remaining three all received it via an
injection of the infected monkey’s blood – and all of these were also
infected (Contacos and Coatney, 1963). After this set of experiments,
Coatney and his colleagues were increasingly confident that their strain
of malaria was no mere ‘‘laboratory curiosity.’’
While monkeys and malaria could both be physically imported from
Malaysia, defining a ‘‘natural infection’’ in a human prison inmate
population had much to do with the experimental protocol put in place.
Images from the 1966 New York Times Magazine article give a sense of
how human subjects in the prison were viewed and employed. A photo
on the first page shows the project’s mosquito breeding facilities, with a
caption reading, ‘‘Rabbits and monkeys, as well as human volunteers,
are used in the search for drugs to combat the disease’’ (Gilmore, 1966,
p. 44). While humans are set apart in this phrasing, the clinical gaze of
the camera lens in the series of photos that follows seems to equate the
15 The ‘‘domestication’’ of malaria in this case is reminiscent of the first stages of the
process described by Robert Kohler in his earlier work, when wild Drosophila
melanogaster entered the laboratory, was domesticated, and was subsequently transformed
into an iconic standardized experimental model (Kohler, 1994).
rabbit with the faceless body parts of the inmate volunteers – most
notably their bared forearms, against which white-coated laboratory
technicians hold vials containing malarious mosquitoes.
These vials held the key to mimicking nature: that is, via the natural
route of malaria infection. Previously, many such transmission
experiments had taken place using blood inoculation. After all, as of 1960,
virtually nothing was known of the natural vectors of monkey malaria;
these would not begin to be elucidated until Coatney himself sent a team
of scientists into the field in Malaysia. Blood inoculation was, in the first
place, apparently less effective than infection by mosquito vector. More
importantly for Coatney’s purposes, though, blood inoculation did not
represent what happened in nature.
Thus, as experimentation proceeded in the Atlanta Federal
Penitentiary, efforts were directed in particular at demonstrating mosquito
transmission of the monkey malaria parasites. Figure 1 is an example of
a diagram the team produced to trace the passage of malaria parasites
between hosts. While some transmissions were achieved via blood
inoculation, many more infections were transmitted by mosquito vector.
The complex chain of infection reveals how freely the ‘‘monkey
malaria’’ parasite could be passed between both monkeys to humans.
Coatney’s team quickly demonstrated that every permutation of this
cross-infection was possible – at least in the laboratory. And indeed, it’s
clear that the prison trials were run as a very strict laboratory. As
Collins recalled from his time working at the prison, it ‘‘was a totally
controlled environment,’’ which essentially converted the human
inmates into experimental laboratory animals (Slater, 2005c, p. 9).16 An
argument for the congruence of malaria infection between monkeys and
humans, and the concomitant conversion of human subjects into
laboratory animals, was only advanced when the aforementioned
wild16 I would suggest that it was possibly a better-controlled environment than Eyles’
lab, where infected mosquitoes were able to escape experimental protocols and infect
experimenters. This experimental picture reflects Nathaniel Comfort’s analysis of the
related research program at Stateville Penitentiary in Illinois, which was launched
shortly after the Atlanta program. Indeed, he discusses the transformation of inmates
into objects for research, a process aided by the fact of their incarceration, which had
already removed a degree of agency and individuation (Comfort, 2009). Even outside
the prison context, researchers have been known to equate human clinical research
subjects with laboratory animals, as Susan Lederer has described (Lederer, 1997,
p. 123). But the prison offered a level of standardization and control that would have
been virtually impossible in any other population of human research subjects. Thus, it’s
no surprise that experimental volunteers in prison might be even more thoroughly
converted into ‘‘analytic objects’’ than other humans participating in clinical research
(on ‘‘analytic objects,’’ see Lynch, 1988, pp. 265–266).
infected macaque was imported into the laboratory and the inmate
population was used to study the parasite it carried (Coatney, 1963).
This trial entailed the reversal of the standard method of identifying the
specific causal agent of a human infection: Instead of isolating a parasite
from a human and transmitting it to an experimental laboratory animal
for verification, Coatney’s team transferred a parasite from a monkey to
a human for precisely the same reason. This striking inversion of Koch’s
postulate clarifies the status of the human inmate volunteers, who had
become subjects of experiments designed to study the disease of a
The deeper evolutionary implications of this inversion were also
apparent. Coatney would claim decades later that that the ‘‘greater
question’’ apparent at the time had direct bearing upon the evolutionary
relationships between primates, asking, ‘‘is monkey malaria a true
zoonosis, an anthroponosis, or both?’’ (Coatney, 1985, p. 10). In other
words, not only were humans susceptible to ‘‘monkey malaria,’’ but the
possibility now existed that the disease had actually originated with
humans. This perspective represented a new fluidity in perceived
biological and disease relationships between humans and monkeys, a chink
in the boundary separating us from other primates, and the
advancement of an argument for our proximity to and symmetry with them.
More specifically, however, it indicated a more nuanced definition of
‘‘natural’’ infection, hinging not only upon where infection took place,
but also when, in evolutionary time, the infection had become possible.
This was the critical question of host specificity, in which the
susceptibility to infection was used to understand evolutionary relationships. In
the next two sections of the paper, I show that understanding the
malaria infections of primates was not just about public health and
understanding the mechanism of malaria infection; it was equally about
inferring evolutionary relationships and distance between hosts and
understanding the ecological requirements of the malarial parasite.
Following Monkey Malaria Back into ‘‘Nature’’
As the transfer of parasites between monkeys and men continued apace
in the prison and laboratory in the U.S., ecological questions about
monkeys, malaria, and humans became more pressing. The only way to
pursue these questions was to follow the erstwhile-decontextualized
experimental organisms back into their natural context: the forests of
Malaysia. Within the year following his recuperation from malaria,
Eyles, his family, and a number of NIH colleagues relocated to Kuala
Lumpur. The city proved an ideal setting for this research, thanks to its
ease of access to the forests where monkey malaria, P. cynomolgi, would
most likely be found. McWilson Warren, a parasitologist heavily
involved in this phase of the research, recalled that one ‘‘could travel 15
miles out of the city and it was pure jungle at that time’’ (Slater, 2005b,
p. 19). The city was also home to the Institute for Medical Research
(IMR), a renowned British institution dating back to 1900, which gave
Coatney’s NIH team a chance to collaborate with expert tropical
disease researchers (Slater, 2005b, pp. 9–10). Moreover, the US Army
Medical Research Unit also had an ‘‘arrangement with [the] Malaysian
government for bringing in funds from the outside’’ to support research
at the IMR. According to Warren, this ‘‘was the means by which funds
for the special program in which Don Eyles was going to be working
were brought into Kuala Lumpur,’’ and the NIH Far East Research
Unity (FERU) was established (Slater, 2005b, p. 10).
The team began immediately to look for links between local
populations of humans and monkeys, asking if they might serve jointly as
hosts of the same species of malaria parasite. Public health concerns
motivated the research, but in practice, the ensuing scientific
interrogation took the form of natural history. Eyles had an M.S. in Biology
from Emory University and a Sc.D. (Doctor of Science) from Johns
Hopkins School of Hygiene and Public Health (Bruce-Chwatt, 1963).
The latter was known for its medical zoology, developed by
parasitologist Robert Hegner, who considered the field to be a ‘‘subdivision of
zoology,’’ with equally important ‘‘scientific and practical phases’’
(Hegner, 1924, p. 551). This foundation enhanced Eyles’ standing as a
naturalist, and it was this impression that he gave to his colleagues, who
remember most strongly the breadth of his biological interests. Warren
refers to Eyles as ‘‘the most accomplished, the most brilliant
scientist/thinker that I ever had the opportunity to be around’’ (Slater,
2005b, p. 8).17 Eyles’ wife Mary was also trained as a biologist and
worked with the team, helping to mist-net bats, in order to collect their
malaria parasites (Slater, 2005b, p. 13). Her self-published memoir
offers an invaluable window into the diversity of Eyles’ interests, and she
describes many happy years of botanizing and bird watching with her
husband, before his untimely death in 1963, just as they were about to
leave Malaysia (Eyles, n.d.).18 Thanks to the broadly biological
approach of Eyles and his colleagues, their work exemplified a dual
medical and naturalistic approach, which can be seen in the research
questions that they asked: What undiscovered species of monkey
malaria parasites thrive in Malaysia? Can these parasites infect humans?
Which species of mosquito serve as the natural vectors of Plasmodium
cynomolgi and other Malaysian species of malaria? What types of
habitat do these vectors prefer? And, finally, in their native habitat, will
these vectors bite both monkeys and humans?
During the first three years of their research in Malaysia, Eyles and his
team uncovered five new species of simian malaria and ‘‘some two dozen
natural vectors of monkey malaria’’ (Coatney, 1968, p. 147), the first such
vectors to be identified anywhere in the world (Eyles, 1963; Warren and
Wharton, 1963). But their ecological mandate required more than simply
the collection of indigenous mosquitoes; they needed to know if these
simian malaria vectors were both able and likely to feed on humans.
Instead of bringing these mosquitoes into the lab and forcing them to
conform to experimental conditions, Eyles and his team wanted to
observe them in their natural context. To do this, they had to develop
17 Warren describes, for example, how Eyles led him on an expedition to collect
microscopic snails, from which they later wrote a paper on divergence in shell patterns
of different local snail populations (Slater, 2005b, p. 13).
18 Sadly, Eyles died of a heart attack just after he and his family boarded a boat in
Penang that was to take them back to the United States (Bruce-Chwatt, 1963; Eyles,
n.d., p. 131).
original experimental field methods. Mosquito collection took place at
night, from sunset to sunrise, using nets stitched together into traps by a
seamstress they found working just down the street from the IMR. Asked
where they had acquired their mosquito trapping methods, Warren
replied, ‘‘All these technologies were new with us’’ (Slater, 2005b, p. 18). The
traps were erected both at ground level and in the canopy of the forest,
and baited with both live humans and monkeys. In other words, monkeys
in cages and human volunteers on platforms would spend long nights in
the forest, simply waiting for hungry mosquitoes to home in on their bare
skin (Warren et al., 1970). In each case, trapped mosquitoes were
identified and dissected. Where crossover occurred between the species of
mosquito captured in monkey-baited and human-baited trips, it was
assumed that the species was attracted to both monkeys and humans. Thus,
the malaria carried by these species of mosquito could plausibly be passed
between monkeys and human. This combination of opportunistic
collecting and experimentation was an explicit attempt to follow host animals
and their parasites: first across geographical boundaries, from the United
States to Malaysia, tracking both monkeys and humans; then across
ecological boundaries, crossing zones of the forest to track the movements
of both mosquitoes and malaria parasites; and finally across the
boundaries that separate the bodies of different animal species, in order to
understand what conditions could make cross-infection possible.
In these attempts to follow both human and nonhuman primates,
Eyles, Warren, and their colleagues also had a good deal of direct
contact with local populations of both species. In his interview with
Slater, Warren recalled his experiences collecting primates for research
with Eyles and with regional animal trappers (Slater, 2005b, p. 18).
Local villagers also kept monkeys and gibbons as pets, and these could
be adopted into the experimental program if they were discovered to
carry a malaria infection (Slater, 2005b, p. 20). The sense of proximity
between humans and nonhuman primates is only heightened by the
accounts that Warren and Mary Eyles gave of the connection between
the Eyles family and their pet gibbon, Watu (pictured with Don Eyles in
Figure 2).19 The NIH researchers were immersed in local nature, which
included insects and plants, nonhuman primates and a great variety of
human ones from both local towns and far-flung forest villages,
including hunters, trappers, pet-owners, and tradespeople.
19 Mary Stipe Eyles writes in her memoir that in Eyles’ initial visit to Malaysia in
1963, he also traveled to Bangkok to purchase monkeys for their experiments, ‘‘and a
little gibbon clung to the edge of the cage and kept calling to him. So Don bought him’’
(Eyles, n.d., p. 93). See the caption of Figure 4 for Warren’s account.
Through their work in the field, following mosquitoes and malaria
parasites, the researchers quickly realized that the vectors that regularly
carried the monkey malaria parasite, P. cynomolgi, were attracted to both
humans and monkeys, and would readily bite either one. Nevertheless,
screen as they might, Eyles, Warren, and their colleagues could detect very
few active monkey malaria infections in the local human population. In
one trial, Warren collected the blood of over 1100 people from the
surrounding populations and, pooling the samples into groups of 10, he
inoculated over 100 malaria-free rhesus macaques. Not a single monkey
malaria infection was recovered in this experiment (Warren et al., 1970).
Because monkey-malaria vectors seemed equally likely to bite both
monkeys and humans, the research team left the laboratory behind and
headed to an environment where mosquitoes were most likely to encounter
both species of potential host animal, travelling on foot to make contact with
forest-dwelling human populations. Mary Eyles accompanied them on one
such trip, describing the hike, in which scientists lugging microscopes created
a ‘‘human rope’’ to ford a river. ‘‘The purpose of the trip was to take blood
smears,’’ she wrote, noting, ‘‘By letting the aborigines look in the microscope,
they became interested and friendly. The scientists also took cigarettes and
candy in for good will’’ (Eyles, n.d., pp. 109–110). In his New York Times
Magazine piece, Gilmore would refer to these forest-dwelling populations of
humans as reservoirs – a term usually applied to nonhuman animal
populations harboring human disease – writing that ‘‘such untreated populations
[of humans] continue to be reservoirs of infection that can break out into
neighboring regions at any time’’ (Gilmore, 1966, p. 59). In other words, like
the inversion of Koch’s postulate that Coatney’s team enacted in the
laboratory, the hypotheses of Eyles and his team in the field were based on a
similar inversion, testing whether humans could serve as ‘‘reservoirs’’ for a
monkey parasite. Nevertheless, despite the researchers’ efforts to reach deep
into the forest, where monkey and human populations were in close
proximity, these human blood samples still did not produce a single infection in
any of the inoculated monkeys back in Kuala Lumpur (Warren et al., 1970).
The team proposed a plausible explanation for this apparent lack of
human exposure. While their collection experiments demonstrated that
simian malaria vectors happily bit human hosts, these mosquito species
also tended to spend most of their time high in the forest canopy, a niche
in the forest not visited by the typical human. In other words, Warren,
Eyles, and their colleagues were finding that the habitats of humans and
indigenous simian malaria vectors did not overlap to a significant extent,
even in the deep forest (Warren et al., 1970). This was an important
ecological conclusion, with public health ramifications. While it did not
eliminate the danger of malaria reservoirs in forest populations of
primates, it did suggest that cross-infection between monkeys and humans
was unlikely under existing social and ecological conditions.
A second plausible explanation, not mutually exclusive with the first,
was that humans could develop some degree of immunity to the malaria
parasite (Coatney, 1968). In other words, local human and monkey
populations had become true joint hosts of the same parasite. And, as
scattered evidence of cross-infection accumulated within Malaysia, it
mostly came from the incursions of travelers into the deeper recesses of
the jungle. These travelers were almost invariably foreign visitors, not
indigenous people – providing some support for this immunological
explanation. To understand the dynamics of how this malaria parasite
was shared and communicated across the ‘‘species boundary,’’ the
researchers would have to focus on following humans who had themselves
crossed geographical boundaries, into new ecological zones, where they
would be exposed to unfamiliar parasites.
In an attempt to do just this, one collaborator on the project, a Dr.
Bennet, volunteered to act as an immunologically ‘‘clean’’ human
subject, allowing an infected simian malaria vector to bite him
(Coatney, 1968). While this experiment was much like those carried out
already in the U.S., there was a critical difference that reflected the
group’s desire to understand infection in nature: The vectors used in
Memphis and Atlanta were typical experimental vectors, not the
mosquito species found in the ecological context where the malaria strain
had originated. Thus, when Bennet was successfully infected, it was the
first time an indigenous Malaysian mosquito had been shown to
transmit simian malaria to a human. And yet – it was still an experiment
and Coatney felt he had to qualify his results, writing, ‘‘Even with this
demonstration, the original question remain[s]; namely, does it happen
in nature?’’ (Coatney, 1968, p. 148). The ideal demonstration in
Coatney’s eyes would be an infection resulting from ‘‘natural’’ human
movement, a geographical shift completely unrelated to the
experimental conditions that his team had established in Malaysia.
Coatney did not have to wait long to find just such a human, with
just such a ‘‘natural’’ infection. In 1965, the same year that the report of
Bennet’s infection was published, a 37-year-old surveyor for the U.S.
Army Map Service took a short visit to peninsular Malaysia. He
travelled on to Thailand, where he started to feel ill. It was not until he
returned to the U.S. that his doctor suggested he might have malaria –
the most severe form of human malaria parasite, in fact, P. falciparum.
Fortunately, the surveyor was referred to the Clinical Center of the NIH
for a confirmation of the diagnosis. The NIH doctor who examined him
knew of Coatney’s simian malaria research project and referred his
patient onward. Examining the surveyor’s blood microscopically,
Coatney more capably discerned the species of the malaria parasite:
Rather than a human parasite, the culprit was P. knowlesi, another
parasite of macaques. The surveyor’s case was the first report of a
human infection with monkey malaria in nature. In reporting the case,
Coatney and his colleagues were unambiguous about the status of the
infection: ‘‘This report of a naturally acquired malaria infection in man
transferable to monkeys represents the first proof that simian malaria is
a true zoonosis’’ (Chin et al., 1965, p. 865).20 For them, both practically
and theoretically, this monkey malaria parasite had breached a critical
medical and biological separation between humans and nonhuman
Throughout this account of monkey malaria research, the gold
standard of natural zoonotic infections shifted gradually. First, the wild
nature of the malaria strain lent Coatney’s team’s experiments the
authenticity of nature. Next, a naturally infected animal was imported
to an NIH lab. In the prison research setting, the natural mode of
infection was paramount. Like many twentieth-century scientists
addressing biological questions, Coatney was attempting to meet the
ideals of the laboratory – striving for results that could be generalized,
even universalized – while also attempting to mimic natural conditions
(Kohler, 2002). Finally, bowing to the strictures of the WHO’s
definition of zoonosis, it became necessary to see how infection happened ‘‘in
nature’’ itself. But even then, nature proved elusive, when the local
populations of humans were not demonstrably infected with monkey
parasites. The notion that these populations were regularly exposed to
monkey malaria and were, in effect, joint hosts of the parasite along
with local monkey populations, was supported by the easy infections of
nonimmune outsiders like Dr. Bennet. Still, it was not until an
unsuspecting traveler met a mosquito infected with monkey malaria that the
principle was finally demonstrated in Coatney’s mind. Perhaps most
importantly, that unsuspecting traveler had his infection diagnosed by a
malariologist expert enough to discern between virtually
indistinguishable human and monkey malaria parasites. Only after all of this was
Coatney ready to declare that monkey malaria was a ‘‘true zoonosis.’’
This redefinition of simian malaria had serious ramifications, not
only for the future of malaria eradication, but also for the researchers’
understanding of relationships between humans and nonhuman
primates. Practically speaking, it is easy to see this effect in the
experimental record. Prior to commencing the surveyor’s treatment, Coatney
had samples of the man’s blood sent to Atlanta, where it was inoculated
into both human prison inmate volunteers and monkeys, just as they
had done with Eyles’ blood five years earlier. And, just as in 1960, the
infections were successful. Again, human subjects were placed in the
role of laboratory animals, using humans and nonhumans in parallel.
In retracing the parasite’s path, from his lab in the United States
back to peninsular Malaysia, Eyles and his team were fleshing out the
ecological and evolutionary landscape of these organisms. Where once
they had been circumscribed by the experiments into which they were
slotted, now primates and their parasites were again seen as meaningful
biological entities, embedded in their own biological reality and history,
linked by the reconfiguration of the host specificity of the malaria
parasite. This revivification of malarial macaques as ecological entities,
along with the continued reversal of human and monkey roles in both
the lab (where humans served as laboratory animals) and field (where
human populations could be reservoirs for nonhuman disease), wrought
an increasing degree of symmetry between human and nonhuman
primates. In the final section of this paper, I will draw out the ramifications
of this process, examining how the altered conception of malaria host
specificity changed parasitologists’ ideas about primate evolution and
brought ‘‘monkeys and man’’ into closer proximity.
Using Parasitic Infection to Reconstruct Evolutionary Relationships
When Eyles was infected with ‘‘monkey malaria’’ in 1960, his research
program was already based upon a basic assumption of symmetry
between humans and other primates. At the same time, a biological
boundary was perceived between monkey malaria and human malaria,
firmly grounded in the belief that ‘‘malaria in the monkey was for
monkeys and malaria in man was for people’’ (Coatney, 1985, p. 10).
This apparent paradox was an outgrowth of the parasitological
practices of the preceding decades, in particular the ‘‘host–parasite method’’
(Metcalf, 1929), which placed importance both on inferred evolutionary
relationships between species and on empirical evidence of infection. In
other words, parasitology was a domain where the traditions of natural
history and taxonomy converged (and sometimes conflicted) with
laboratory- and field-based medical research. Following primates and their
malaria parasites as they move across this historical domain provides an
opportunity to analyze how these different modes of science were
pursued in concert and how their interaction shifted the taxonomic and
disease identities and evolutionary relationships of the organisms that
G. Robert Coatney had already applied the logic of the
‘‘host–parasite method’’ in the 1930s, when he chose the pigeon as an experimental
host for his unique dove-derived avian malaria strain and explained the
choice using the birds’ evolutionary proximity (Coatney, 1938). Three
decades later, he perpetuated it still, writing that ‘‘the great evolutionary
gap’’ between monkeys and humans explained the challenges
parasitologists faced passing malaria parasites between the species (Coatney
1968, p. 148). Yet, such sizeable gaps were repeatedly spanned by
malaria parasites in the 1960s, creating points of tension between
taxonomic designations and phylogenetic inference, on the one hand, and
empirical medical evidence, on the other.
For Coatney and his colleagues, these points of tension were
opportunities for parasitological evidence to shed light on primate phylogenies.
The precedent for using parasitic infection to understand primate
evolution had been set as early as 1928, when Johns Hopkins protozoologist
and proponent of the host–parasite method Robert Hegner wrote, ‘‘If the
proposition that close relationships of parasites indicate a common
ancestry of their hosts is valid, then the facts available regarding the
protozoan parasites of monkeys and man furnish evidence of importance
in favor of the hypothesis that monkeys and man are of common descent’’
(Hegner, 1928, p. 242; Mason Dentinger, 2013, 2014). Work on a variety
of other parasites was also brought to bear on the descent of primates,21
and by the time Solly Zuckerman published Functional Affinities of Man,
Monkeys, and Apes in 1933, ‘‘The Diseases and Parasites of the Primates’’
merited its own chapter, alongside those comparing the reproduction,
blood, behavior, and sensory organs of primate species. Zuckerman
expressed concerns about ‘‘phylogenetic speculations based on comparative
host–parasite studies,’’ but admitted that the ‘‘fame of this phylogenetic
method has grown to such proportions that it cannot be passed over’’
(Zuckerman, 1933, p. 80).
Throughout the 1950s and 1960s, primate phylogenies were in dispute,
and the newer laboratory methods seemed to complement and challenge
traditional phylogenetic methods in equal measure. The application of
serological techniques to primate kinship had already suggested that
humans might have closer ties to chimpanzees and gorillas than previously
imagined (Proctor, 2004; Hagen, 2009, 2010; Strasser, 2010; Delisle,
2012). As such, it’s unsurprising that Coatney and his colleagues might see
parasitic cross-infection between humans and monkeys in a new light: Did
the restructuring of evolutionary relationships in the primate lineage
mean that monkey malaria was indeed more of threat to humans? And,
conversely, could these infections provide corroboration for other
innovative phylogenetic techniques? While these parasitologists believed that
21 E.g., Darling (1921) on hookworm.
their field had contributions to make to evolutionary thinking on a
broader scale, there is little evidence – outside of Zuckerman’s inclusion of
the method in his volume – that their ideas about host animal evolution
directly influenced evolutionary thought beyond the domain of
parasitology.22 Thus, the importance of this historical case does not rest upon
the impact parasitology had upon evolutionary biology, but upon the
hybridization between medical and evolutionary research practices that
was integral to the field of parasitology itself.
As such, host specificity is historically interesting not only as a
defining concept in parasitology, but also as a crucial point where
medical and evolutionary research goals were fruitfully linked together.
P.C.C. Garnham, who had been associated with Coatney’s project since
he contributed his freshly isolated strain of Plasmodium cynomolgi for
Eyles’ laboratory experiments in 1960, was instrumental in this regard,
greatly expanding the evolutionary relevance of primate malaria
crossinfection.23 When Coatney convened a special symposium on simian
malaria in 1963, in conjunction with a meeting of the International
Congress of Zoology, Garnham numbered amongst the contributors,
which also included Warren and Eyles.24 Having begun his career in the
1920s studying medicine at St. Bartholomew’s in London and at the
London School of Hygiene and Tropical Medicine (LSHTM), Garnham
then worked as a colonial medical officer in Kenya for more than two
decades, pursuing the malaria parasites of African monkeys. His interest
in nonhuman malaria parasites and his additional knowledge of
entomology exemplified the breadth and depth of his interest in parasite
natural history, which was further borne out in the second phase of his
career, when he returned to London as a Reader in Medical
Protozoology at LSHTM, and later Head of the Department of Parasitology
(Lainson and Killick-Kendrick, 1997). Three years after the 1963
symposium on simian malaria, Garnham would publish Malaria Parasites
22 However, even an evolutionary biologist of the caliber of Ernst Mayr saw that
parasitic infection might yield insights into host evolution (Mayr, 1952, pp. 139–140),
and he collaborated with Swiss parasitologist Jean Baer to convene on conference on the
topic, bringing together parasitologists and other zoologists (Baer, 1957; Mayr, 1957).
23 As Coatney’s malaria project expanded in the early 1960 s, Garnham continued his
association with various members of the team, corresponding extensively with Eyles and
contributing to the group’s effort to understand the relationships between different
species of malaria and different species of hosts. For example, see letters in folder PP/
PCG/D/59, Papers of P.C.C. Garnham, Wellcome Collection.
24 Eyles had passed away earlier in the year, but his paper, ‘‘The Species of Simian
Malaria: Taxonomy, Morphology, Life Cycle, and Geographical Distribution of the
Monkey Species,’’ was included posthumously in the publication of this special session
and other Haemosporidia, which was considered the definitive volume on
plasmodium biology and taxonomy. However, his expertise and
interests ranged far beyond malaria, and he studied a vast array of parasites
and wrote on many different aspect of parasitology throughout his long
career, with a particular interest in the evolution of parasites and
parasitism.25 Garnham’s work represented precisely the sort of synthetic
analysis that could address points of intersection between infectious
disease and evolutionary history.
In his contribution to the symposium, Garnham took the subject of
simian malaria as a launching point from which he could address the
taxonomic and phylogenetic instability of all primates. In the style of the
host–parasite method established by a previous generation of
parasitologists, Garnham transmuted the medical qualities of infectivity and
susceptibility into characters useful for other types of zoological inference.
He provided a graphic representation (Figure 3) of how medical research
might be used to mutually inform evolutionary research, correlating
infectivity/susceptibility with a posited primate evolutionary tree. Instead
of setting humans and their associated parasites apart from all nonhuman
primates and their parasites, Garnham’s tree drew the malaria parasites of
apes and humans into close proximity, while placing those of monkeys at a
greater evolutionary distance. He drew on contemporary
paleoanthropological research, including serological methods, when he wrote: ‘‘There
is evidence today that the chimpanzee and gorilla are closer to man than
the other so-called higher apes,’’ arguing that the clustering apparent in
patterns of malaria infection could be used to bolster this hypothesis
(Garnham, 1963, p. 905). Finally, he went on to propose points in the
shared evolutionary history of primates and their malaria parasites where
both lineages jointly diverged, establishing an evolutionary narrative that
accounted for both hosts and parasites (see Figure 4).
Before the end of the decade, Coatney would follow Garnham’s lead in
making strong zoological claims based upon disease transmission
between host species. Where Garnham used evidence of parasitic
crossinfection to infer a closer relationship between humans and apes, Coatney
argued that humans and chimpanzees shared identical parasites, where
previously parasitologists had recognized separate ‘‘counterpart’’ malaria
species. Like other protozoan parasites of primates, the malaria parasites
that infect humans and chimpanzees often appeared morphologically and
functionally indistinguishable (Bray, 1963).26 Despite this appearance,
25 See, for example, Garnham (1959, 1971).
26 On the generality of shared morphology between monkey and human protozoan
parasites, see Hegner (1928) and Dobell (1933).
however, malariologists, like other protozoologists, assigned different
species identities to these parasites, by virtue of their discovery in the
bodies of human or chimpanzee hosts. In some cases, this division seemed
justified, as the apparently indistinguishable parasites proved to resist
cross-infection between the different species of primate host.27 But in
other cases, counterpart parasite species were morphologically identical
and they could infect humans and chimpanzees with equal facility.
P. malariae of humans and P. rodhaini of chimpanzees represented
just such a pair of counterpart species. ‘‘When P. rodhaini is given to
man via inoculation of parasitized blood it produces a clinical picture
typical of P. malariae,’’ Coatney wrote in 1968. ‘‘It is clear, then, that
the quartan parasite of man [P. malariae] and of the chimpanzee [P.
rodhaini] are actually the same parasite,28 as suggested by Rodhain as
early as 1940, and should [both] be considered as P. malariae’’ (Coatney,
1968, p. 149). Coatney had taken the results of medical experimentation
on cross-infection and used them to make a taxonomic argument for
collapsing the two counterpart parasite species into one. But why had
these parasites been given separate species designations in the first
place? And if Rodhain had suggested they were identical in 1940, why
did Coatney have to argue for their similarity again in 1968? The
apparent resistance to Rodhain’s hypotheses provides evidence that
previous to the 1960s, parasitologists had seen a definite species
boundary between chimpanzees and humans. Moreover, Coatney could
not let the argument rest even in 1968, asserting again, only three years
later, that ‘‘P. rodhaini most likely does not exist but P. malariae does,
and it infects man and apes…It apparently goes from man to ape and
from ape to man with no detectable alteration in morphology or life
pattern’’(Coatney, 1971, p. 798).29 In this, Coatney was making an
29 Even today P. rodhaini is often described as a parasite of apes, even when its
synonym with P. malariae of humans is subsequently acknowledged (Abee et al., 2012).
argument that joined together his medical understanding of malaria
infection with evolutionary inference, arguing simultaneously that
chimps and humans were closely related and that their malaria
parasites, once thought distinct, were actually the same species.
For Coatney, linking taxonomic identity to the history of host–
parasite associations had repercussions in the realm of public health and
beyond. If P. malariae of humans and P. rodhaini of chimpanzees are
one and the same, he wrote in 1968, ‘‘either this simian parasite became
adapted to early man, or the exchange of this parasite between
chimpanzee and man has been taking place for thousands of years. In the
same vein, once the parasite was acclimated to man, it was available for
transfer back to the chimpanzee. In other words, this simian malaria is a
zoonosis of long standing and, more recently, under favorable
conditions, an anthroponosis as well’’ (Coatney 1968, p. 149). The easy
communication of disease that Coatney described would surely present
a challenge to anyone still championing the failing project of worldwide
malaria eradication. Yet, Coatney’s account asserted something more
than his notion that malaria was a historical breaker of species
boundaries. It also conveyed what he saw as the ecological and
evolutionary proximity of humans and chimpanzees. Coatney, like Garnham,
believed that shared parasitic infections between humans and
chimpanzees contained evidence for their shared evolutionary descent.
Unlike Garnham, however, Coatney did not attempt to provide a graphic
phylogenetic representation in support of his position. Instead, he
concluded his paper poetically, quoting century-old verse, originally
published in Punch in 1861 (Coatney, 1968, p. 152):
For Coatney, then, recognizing the surprising lack of host specificity in
primate malaria parasites was a watershed in two interconnected ways:
First, it constituted an unrecognized public health threat; and second, it
prompted a realization of his own proximity to other primates. While the
versification of this dual insight added a personal note to Coatney’s case,
it was, at the same time, just an extension of the decades of research that
had preceded his own, which had linked together medical and
evolutionary questions and research agendas in the pursuit of parasitology.
In 1971, the NIH published The Primate Malarias, a 300-plus-page
volume summarizing the current state of knowledge, coauthored by
Coatney and his colleagues from the primate malaria research project of
the past decade. For each species treated in this volume, the life cycle,
course of infection, host specificity, and immunological reactions of the
host were compiled – an amalgam of zoological and medical data. In the
first chapter, ‘‘Evolution of the Primate Malarias,’’ the authors wrote of
the challenges inherent in the parasitology, ‘‘since not only must the
evolution of the protozoan be accounted for but the concomitant
evolutionary development of both the vertebrate and invertebrate hosts as
well’’ (Coatney et al., 1971, p. 1). This pronouncement captured the
complexity of the parasitological perspective, grounded in decades of
comparative thinking and the host–parasite method, in which
understanding evolution was considered ‘‘more than an academic exercise.’’
‘‘There are some very practical considerations to the evolutionary trends
in the primate malarias’’ (Coatney et al., 1971, p. 1), they wrote, thus
closing the circle: Evolutionary insights could be drawn from medical
practices and medical insights could be drawn from evolutionary
For Coatney, linking ‘‘practical considerations’’ and ‘‘evolutionary
trends’’ had been an integral part of his early parasitological training
and practice in the 1930s, when he employed ‘‘close zoological
relationships’’ between bird species to select his experimental model
(Coatney, 1938, p. 382). After his move from avian malaria to primate
malaria, he observed parasitologists’ conviction that malaria
cross-infection between humans and monkeys was impossible, and he surmised
that it was based on the ‘‘great evolutionary gap’’ between these
primates (Coatney 1968, p. 148). Finally, once it was clear that malaria
parasites could easily cross this boundary, Coatney concluded ‘‘that
monkeys and man are more closely related than some of us wish to
admit’’ (Coatney, 1963, p. 877), indelibly linking disease susceptibility to
Similarly, Coatney’s dogged pursuit of zoonotic malaria also
reflected the notion of human and nonhuman proximity, ending time
and again with the possibility of anthroponosis – that is, humans
transmitting their own malaria parasites to their primate relatives.
Repeatedly, it seems, parasites traversed the species boundary, as in
the case of the chimpanzee parasite P. rodhaini, passing ‘‘from man to
ape and from ape to man’’(Coatney, 1971, p. 798). For Coatney, the
implications of this boundary-crossing were clear: Where once
malariologists had perceived two separate species of parasite, by virtue
of their isolation from different species of hosts, now there was only
one species of parasite and a closer relationship between its joint host
species, chimps and humans.
The notion of a single species of parasite, jointly hosted by different
species of primates, suggested that a narrow focus on eradicating
‘‘human malaria’’ might not suffice to control the disease. Ultimately,
however, the broader public health community seems to have paid
little attention to the hard-won conclusions of Coatney and his
colleagues. The WHO plan to eradicate malaria, initiated in 1955, faced
doubts almost immediately, as resistance to antimalarials and DDT
were quickly registered. But they continued to push this agenda for
another decade, and it was not until 1969 that malaria eradication was
called off. That is to say, the demise of malaria eradication was played
out at precisely the same time that Coatney and his group were
increasingly convinced that simian malaria presented a zoonotic threat
to human health. Yet their work seems to have had little direct impact
on WHO policy, even though Coatney himself served on the WHO
committee in the years just before and after Eyles’ infection (WHO,
1959, 1961a, b). Looking back on the malaria eradication program
from the vantage point of 1971, Coatney recalled, ‘‘The record was
clear. Three simian malarias would grow in man, and one…could
produce grave disease. Even so, no one considered their zoonotic
potential’’ (Coatney, 1971, p. 796).
In recent years, however, the public health community has come to
reconsider simian malaria. Take, for example, Plasmodium knowlesi, the
macaque parasite that infected a U.S. army surveyor traveling in
Malaysia in 1965, and the case that Coatney and his colleagues had
declared ‘‘the first proof that simian malaria is a true zoonosis’’ (Chin
et al., 1965, p. 865). A 2008 editorial in the pages of Clinical Infectious
Disease describes how ‘‘the zoonotic potential of P. knowlesi has, until
recently, seemed limited, with only sporadic case reports of human
infection.’’ However, upon closer inspection of ‘‘what appeared initially
to be an unusually high incidence of [the human parasite] Plasmodium
malariae’’ in Borneo, a research team recognized that, in fact, a large
proportion of these infections were actually P. knowlesi of monkeys
(White, 2008, p. 172). In other words, monkeys and humans in Borneo
already share this parasite to a great extent. The morphological
differences between the human parasite P. malariae and the monkey parasite
P. knowlesi might easily go unnoticed to the eye of a researcher who
assumes that a ‘‘monkey malaria’’ cannot breach what is often called the
‘‘species barrier.’’30 By contrast, Coatney and his colleagues followed
the trails of monkeys, men, mosquitoes, and malaria, and by working as
both medical researchers and natural historians, they were able to
observe how easily border-crossing could occur.
Once the boundary between ‘‘monkeys and man’’ was breached for
Coatney, Eyles, and their colleagues, moving back and forth between
the two species became an ordinary component of their experimental
protocol, reflecting the typical parasitological practice of cross-infection
between myriad species of animal host. Koch’s postulate relied upon the
use of nonhuman animal models to detect the identity of an infectious
agent isolated from an ill human. But for these parasitologists, a human
model could just as easily be used to detect the identity of an infectious
agent taken from an animal. Their key practice was that of following
organisms – parasites and hosts alike – and engaging directly with the
circumstances of their lives. Thus a parasite’s taxonomic identity and its
constitution as a public health threat could simultaneously shift as a
result of their practical investigation. Which mosquito species naturally
host monkey malaria parasites and where do they live? What happens
when humans enter the deep forest and encounter mosquitoes that
readily bite both monkeys and humans? What direction does a parasite
move in crossing supposed ‘‘species boundaries’’ between different
primate species? And at what point in evolutionary history did a species of
malaria parasite first make a leap between primate species? Taken
together, these questions represent the duality of parasitology and its
‘‘host–parasite method,’’ which advanced medical and evolutionary
This historical narrative is distinct from previous accounts, which
seek to understand the effect of evolutionary thinking upon medicine.31
In contrast, this paper demonstrates that the intellectual and
methodological traffic can also move in the opposite direction, enabling medical
concepts to shape evolutionary practices. Malariologists were
particularly well positioned for this form of scientific practice, as they had
struggled for decades to find effective experimental models and were
accustomed to considering the biological symmetry of human and
nonhuman animals. Thus, like parasitologists of previous decades,
30 The American Society of Tropical Medicine and Hygiene construes this discovery as a
vindication of Coatney’s work, writing in their newsletter that ‘‘It has taken over 45 years to
fulfill the goal that Bob Coatney originally sent his people out to prove – that monkey
malaria is a true zoonosis.’’ (https://www.astmh.org/source/newsletter/index.cfm?fuseac
tion=Newsletter.showThisIssue&Issue_ID=11&Article_ID=367, accessed 6 July 2015).
31 See especially Me´ thot (2011, 2012).
Coatney and his colleagues moved fluidly between practical challenges
and evolutionary conceptions, and their medical mission, to fight
malaria, manifestly shaped their ideas about the evolutionary
relationships of hosts. Where Coatney and other malariologists had seen
‘‘monkey malaria’’ threatening human health, they came to see a
parasite that could be jointly hosted by two different species of primate; and
where they had seen separation, they came to see a continuity that
reflected a shared evolutionary history.
This research was funded by the Wellcome Trust (grant 092719/Z/10/A),
on the grant ‘‘One Medicine? Investigating human and animal disease.’’
The insights and suggestions of my colleagues on this grant, including
Abigail Woods, Michael Bresalier, and Angela Cassidy, have been
invaluable. Many thanks also to Julie Hipperson, Gina Rumore, and
Kim Mason, who all commented on drafts along the way, and to
Georgina Montgomery and Rob Kirk, who both shared information about the
use of primates in research in the early twentieth century. Thanks to the
participants of the History of Science Society session (Boston, 2013)
from which this paper originated, in particular Susan Jones, who
provided useful commentary after the session, and Pierre-Olivier M e´thot
(with whom I organized the session) and Glady Kostyrka, both of whom
have generously commented upon this paper. I thank Leo Slater for his
advice when I was originally seeking more information about NIH
malariologists and for his interviews with these scientists, which I could
not have read without the help of NIH archivist Barbara Faye Harkins.
Don Eyles’ son, Don Eyles, Jr., kindly provided me with a copy of his
mother’s memoir, photographs of his family, and his own recollections of
the time his father fell ill with malaria – not to mention meeting with me
in Boston and attending my talk during the HSS meeting! My thanks to
two anonymous reviewers, who provided a thoughtful critique of this
paper. Finally, thanks always to my husband, Bryn Mason Dentinger, ever
the sounding board for my ideas and arbiter of my work.
Compliance with Ethical Standards
The authors declare that they have no conflict of
This article is distributed under the terms of the Creative Commons
Attribution 4.0 International License (http://creativecommons.org/
licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to
the original author(s) and the source, provide a link to the Creative
Commons license, and indicate if changes were made.
Abee , Christian R. , Mansfield, Keith, Tardif, Suzette D. , and Morris, Timothy (eds.). 2012 . Nonhuman Primates in Biomedical Research: Diseases . London: Academic Press.
Anderson , Warwick. 2004 . ''Natural Histories of Infectious Disease: Ecological Vision in Twentieth-Century Biomedical Science .'' Osiris 19 : 39 - 61 .
Asdal , Kristin. 2008 . ''Subjected to Parliament: The Laboratory of Experimental Medicine and the Animal Body .'' Social Studies of Science 38 : 899 - 917 .
Baer , Jean G. 1940 . ' 'The Origin of Human Tapeworms .' ' The Journal of Parasitology 26 : 127 - 134 .
-- 1952 . Ecology of Animal Parasites . Urbana: University of Illinois Press.
- - (ed.). 1957 . First Symposium on Host Specificity Among Parasites of Vertebrates . Neuchatel: Imprimerie Paul Attinger S.A.
Bernard , Claude. 1865 . An Introduction to the Study of Experimental Medicine . Paris: Builliere.
Beye , Henry K. , Getz , Morton E. , Robert Coatney , G. , Elder, Harvey A. , and Eyles, Don E. 1961 . ''Simian Malaria in Man.'' American Journal of Tropical Medicine and Hygiene 10 : 311 - 316 .
Birke , Lynda. 2012 . ''Animal bodies in the production of scientific knowledge: Modelling medicine . '' Body & Society 18 : 156 - 178 .
Bray , R.S. 1963 . ' 'The Malaria Parasites of Anthropoid Apes .' ' The Journal of Parasitology 49 : 888 - 891 .
Bresalier , Michael, Cassidy, Angela, and Woods, Abigail. 2015 . ''One health in history .'' Jacob Zinsstag, Esther Schelling , Maxine Whittaker , Marcel Tanner , and David Waltner -Toews (eds.), ' One Health': The Theory and Practice of Integrated Health Approaches . Wallingford: CABI.
Bruce-Chwatt , Leonard J. 1963 . ''Don E. Eyles Sc.D.'' British Medical Journal 5368 : 1344 .
Buklijas , Tatjana and Gluckman, Peter. 2012 . ''From Evolution and Medicine to Evolutionary Medicine .'' Michael Ruse (ed.), The Cambridge Encyclopedia of Darwin and Evolutionary Thoought . Cambridge : Cambridge University Press , pp. 505 - 513 .
Bynum , William F. 1983 . ''Darwin and the Doctors: Evolution, Diathesis, and Germs in 19th-Century Britain .'' Gesnerus 40 : 43 - 53 .
-- 2002 . ' 'The Evolution of Germs and the Evolution of Disease: Some British Debates , 1870 - 1900 .'' History and Philosophy of the Life Sciences 24 : 53 - 68 .
Cameron , T.W.M. 1952 . ''Parasitism, Evolution, and Phylogeny .'' Endeavour 11 ( 44 ): 193 - 199 .
Canning , Elizabeth U. (ed.). 1981 . Parasitological Topics: A Presentation Volume to P.C.C. Garnham , F. R .S., on the Occasion of His 80th Birthday. Lawrence, KS: Society of Protozoologists .
Carpenter , Clarence R . 1940 . ''Rhesus Monkeys (Macaca mulatta) for American Laboratories .'' Science 92 : 284 - 286 .
Chin , William, Contacos, Peter G. , Robert Coatney , G. , and Kimball, Harry R . 1965 . ' 'A Naturally Acquired Quotidian-Type Malaria in Man Transferable to Monkeys .'' Science 149 : 865 .
Clark , Herbert C. and Dunn , Lawrence H. 1931 . ''Experimental Efforts to Transfer Monkey Malaria to Man.'' The American Journal of Tropical Medicine 11 : 1 - 10 .
Coatney , G. Robert . 1938 . ' 'A Strain of Plasmodium relictum from Doves and Pigeons Infective to Canaries and the Common Fowl .'' American Journal of Epidemiology 27 : 380 - 389 .
-- 1963 . ' 'Simian Malaria: Its Importance to World-Wide Eradication of Malaria .'' Journal of the American Medical Association 184 : 876 - 877 .
-- 1968 . ''Simian Malarias in Man: Facts, Implications, and Predictions.' ' The American Journal of Tropical Medicine and Hygiene 17 : 147 - 155 .
-- 1971 . ''The Simian Malarias: Zoonoses, Anthroponoses, or Both?' The American Journal of Tropical Medicine and Hygiene 20 : 795 - 803 .
-- 1985 . Reminiscences: My Forty-Year Romance with Malaria . Transactions of the Nebraska Academy of Sciences and Affiliated Societies XIII : 5 - 11 .
Coatney , G. Robert , Collins, William E. , Warren , McWilson, and Contacos , Peter G. 1971 . The Primate Malarias . Bethesda: U.S. Department of Health, Education, and Welfare .
Comfort , Nathaniel. 2009 . ' 'The Prisoner as Model Organism: Malaria Research at Stateville Penitentiary .'' Studies in the History and Philosophy of Biological and Biomedical Science 40 : 190 - 203 .
Contacos , Peter G. , Elder, Harvey A. , and Robert Coatney , G. 1962 . ''Man to Man Transfer of Two Strains of Plasmodium cynomolgi by Mosquito Bite .' ' The American Journal of Tropical Medicine and Hygiene 11 : 186 - 193 .
Contacos , Peter G. and Robert Coatney , G. 1963 . ''Experimental Adaptation of Simian Malarias to Abnormal Hosts.'' The Journal of Parasitology 49 : 912 - 918 .
Cox , Francis E.G. 2010 . '' History of the Discovery of the Malaria Parasites and Their Vectors.'' Parasites & Vectors 3 : 5 .
Darling , Samuel T. 1921 . ' 'The Distribution of Hookworms in the Zoological Regions .'' Science 53 : 323 - 324 .
Delisle , Richard G. 2012 . ' 'The Disciplinary and Epistemological Structure of Paleoanthropology: One Hundred and Fifty Years of Development.'' History and Philosophy of the Life Sciences 34 : 283 - 329 .
Dobell , Clifford. 1933 . '' Researches on the Intestinal Protozoa of Monkeys and Man.'' Parasitology 25 : 436 - 467 .
Dukelow , W. Richard and Whitehair, Leo A. 1995 . '' A Brief History of the Regional Primate Research Centers.'' Comparative Pathology Bulletin 27 : 1 - 2 .
Eyles , Don E. 1960 . ' 'The Exoerythrocytic Cycle of Plasmodium cynomolgi and P. cynomolgi bastianellii in the Rhesus Monkey .'' American Journal of Tropical Medicine and Hygiene 9 : 543 - 555 .
-- 1963 . ' 'The Species of Simian Malaria: Taxonomy , Morphology, Life Cycle , and Geographical Distribution of the Monkey Species.'' The Journal of Parasitology 49 : 863 - 887 .
Eyles , Don E. , Robert Coatney , G. , and Getz, Morton E. 1960 . ''Vivax-Type Malaria Parasite of Macaques Transmissible to Man .'' Science 132 : 1812 - 1813 .
-- 1959 . ' 'The Evolution of the Zoonoses .'' Medical Press 241 : 251 - 256 .
-- 1963 . '' Distribution of Simian Malaria Parasites in Various Hosts.'' The Journal of Parasitology 49 : 905 - 911 .
-- 1966. Malaria Parasites and Other Haemosporidia. Oxford: Blackwell.
-- 1971 . Progress in Parasitology. University of London, Heath Clark Lectures 1968 . London: The Athlone Press.
Gilmore , C.P. 1966 . Malaria Wins Round 2: For Every Problem Solved Two New Ones Come Along . New York Times Magazine , 25 September 1966 , p. 47 .
Guerrini , Anita. 2003 . Experimenting with Humans and Animals: From Galen to Animal Rights . Baltimore: Johns Hopkins University Press.
Hagen , Joel. 2009 . ''Descended from Darwin? George Gaylord Simpson , Morris Goodman , and Primate Systematics .'' Joe Cain and Michael Ruse (eds.), Descended from Darwin: Insights into American Evolutionary Studies. Philadelphia: American Philosophical Society.
-- 2010 . ''Waiting for Sequences: Morris Goodman, Immunodiffusion Experiments, and the Origins of Molecular Anthropology.'' Journal of the History of Biology 43 : 697 - 725 .
Harden , Victoria A. 1985 . '' Rocky Mountain Spotted Fever Research and the Development of the Insect Vector Theory , 1900 - 1930 .'' Bulletin of the History of Medicine 59 : 449 - 466 .
Hegner , Robert. 1924 . ''Medical Zoology and Human Welfare .'' Science 60 : 551 - 558 .
-- 1928. ''The Evolutionary Significance of the Protozoan Parasites of Monkeys and Man.'' The Quarterly Review of Biology 3 : 225 - 244 .
Kellogg , Vernon L. 1913 . ''Ecto-Parasites of the Monkeys , Apes and Man.'' Science 38 : 601 - 602 .
Kohler , Robert. 1994 . Lords of the Fly: Drosophila Genetics and the Experimental Life . Chicago: The University of Chicago Press.
-- 2002 . Landscapes and Labscapes: Exploring the Lab-Field Border in Biology . Chicago: University of Chicago Press.
Lainson , R. and Killick-Kendrick , R. 1997 . Percy Cyril Claude Garnham, C.M.G. 15 January 1901 -25 December 1994 : Elected F.R.S. 1964 . Biographical Memoirs of the Fellows of the Royal Society 43 : 173 - 192 .
Lederer , Susan E. 1997 . Subjected to Science: Human Experimentation in America Before the Second World War . Henry E. Sigerist Series in the History of Medicine . Baltimore: Johns Hopkins University Press.
Leonelli , Sabina and Ankeny, Rachel. 2011 . ''What's so Special About Model Organisms?' Studies in History and Philosophy of Science 42 : 313 - 323 .
Li , Shang-Jen. 2002 . '' Natural History of Parasitic Disease: Patrick Manson's Philosophical Method.'' Isis 93 : 206 - 228 .
Logan , Cheryl A. 2002 . ''Before There were Standards: The Role of Test Animals in the Production of Empirical Generality in Physiology .'' Journal of the History of Biology 35 ( 329 - 363 ): 355 .
Lo¨ wy, Ilana. 1992 . ''From Guinea Pigs to Man: The Development of Haffkine's Anticholera Vaccine .'' Journal of the History of Medicine and Allied Sciences 47 : 270 - 309 .
-- 2003 . ' 'The Experimental Body .'' Roger Cooter, John V. Pickstone (ed.), Companion to Medicine in the Twentieth Century . London: Routledge, pp. 435 - 449 .
Lynch , Michael E. 1988 . ''Sacrifice and the Transformation of the Animal Body into a Scientific Object: Laboratory Culture and Ritual Practice in the Neurosciences .'' Social Studies of Science 18 : 265 - 289 .
Mason Dentinger , Rachel. 2009 . The Nature of Defense: Coevolutionary Studies, Ecological Interaction, and the Evolution of 'Natural Insecticides , 1959 - 1983 . Ph . D. Dissertation , University of Minnesota.
-- 2013 . '' Natural'' Infection or Not? Host-Specificity in Early-20th-Century Parasitology and Its Implications for Evolutionary and Disease Biolog. Unpublished Paper Given at the 2013 Meeting of the International Society for the History , Philosophy, and Social Studies of Biology , Montpellier, France.
-- 2014. Partners Through Evolution: Linking Humans , Animals, and Parasites in the Early 20th Century. Unpublished Paper Given at the 2014 Meeting of the American Association of the History of Medicine , Chicago, IL.
Mayr , Ernst. 1952 . ''Notes on Evolutionary Literature.'' Evolution 6 : 138 - 144 .
-- 1957 . ' 'Evolutionary Aspects of Host Specificity Among Parasites of Vertebrates .'' Jean G. Baer (ed.), First Symposium on Host Specificity Among Parasites of Vertebrates. Neuchatel: Imprimerie Paul Attinger S.A. , pp. 7 - 14 .
Metcalf , Maynard M. 1929 . ''Parasites and the Aid They Give in Problems of Taxonomy , Geographical Distribution, and Paleogeography.'' Smithsonian Miscellaneous Collections 81 : 1 - 36 .
Me´ thot, Pierre-Olivier . 2011 . '' Research Traditions and Evolutionary Explanations in Medicine.'' Theoretical Medicine and Bioethics 32 : 75 - 90 .
-- 2012 . ' 'Why do Parasites Harm Their Host? On the Origin and Legacy of Theobald Smith's ''Law of Declining Virulence' ' - 1900 - 1980 .'' History and Philosophy of the Life Sciences 34 : 561 - 601 .
Mode , Charles J. 1958 . '' A Mathematical Model for the Co-Evolution of Obligate Parasites and Their Hosts.'' Evolution 12 : 158 - 165 .
Montgomery , Georgina M. 2005 . ''Place, Practice and Primatology: Clarence Ray Carpenter, Primate Communication and the Development of Field Methodology , 1931 - 1945 .'' Journal of the History of Biology 38 : 495 - 533 .
Packard , Randall M. 2010 . The Making of a Tropical Disease: A Short History of Malaria . Baltimore: Johns Hopkins University Press.
Proctor , Robert N. 2004 . ''Three Roots of Human Recency: Molecular Anthropology, the Refigured Acheulean, and the UNESCO Response to Auschwitz .' ' L. Daston and F. Vidal (eds.), The Moral Authority of Nature . Chicago: University of Chicago Press.
Rawlins , Richard G. and Kessler , Matt J . (eds.). 1986 . The Cayo Santiago Macaques: History, Behavior and Biology . Albany: State University of New York Press.
Schmidt , Leon H. 1979 . Interview with G. Robert Coatney . G. Robert Coatney Ph. D. , Sc . D. , Workers in Tropical Medicine. Bethesda: Department of Health, Education, and Welfare , Public Health Service, National Institutes of Health, National Library of Medicine. Accessed 29 January 2013 , at: http://collections.nlm.nih.gov/catalog/ nlm:nlmuid- 7901256A -vid.
Shortt , Henry E. and Garnham , P.C.C. 1948 . ''Pre-erythrocytic Stages in Mammalian Malaria Parasites .'' Nature 161 : 126 .
Slater , Leo. 2005a . '' Malarial Birds: Modeling Infectious Human Disease in Animals .'' Bulletin of the History of Medicine 79 : 261 - 294 .
-- 2005b. Dr. McWilson Warren Interview , Transcript. Office of NIH History , Oral History Program.
-- 2005c. Dr . William E. Collins Interview , Transcript. Office of NIH History , Oral History Program.
-- 2009. War and Disease: Biomedical Research on Malaria in the Twentieth Century . Princeton: Rutgers University Press.
Strasser , Bruno. 2010 . ''Laboratories, Museum, and the Comparative Perspective: Alan A. Boyden 's Quest for Objectivity in Serological Taxonomy, 1924 - 1962 .'' Historical Studies in the Natural Sciences 40 : 149 - 182 .
von Ihering , H. 1891 . '' On the Ancient Relations Between New Zealand and South America.'' Transactions & Proceedings of the Royal Society of New Zealand 24 : 431 - 445 .
Wagner-Jauregg , Julius. 1927 . The Nobel Prize in Physiology or Medicine , Nobel Lecture , The Treatment of Dementia Paralytica by Malaria Inoculation . Nobelprize.org. Nobel Media AB 2013 . Web, 7 April 2014 . http://www.nobelprize. org/ nobel_prizes/medicine/laureates/1927/wagner-jauregg-lecture.html.
Ward , Henry B. 1926 . ' 'The Needs and Opportunities in Parasitology.'' Science 64 : 231 - 236 .
Warren, McWilson and Wharton , R.H. 1963 . ''The Vectors of Simian Malaria: Identity, Biology, and Geographical Distribution.'' The Journal of Parasitology 49 : 892 - 904 .
Warren, McWilson, Cehong , W.H. , Fredericks , H.K. , and Robert Coatney , G. 1970 . ''Cycles of Jungle Malaria in West Malaysia .'' American Journal of Tropical Medicine and Hygiene 19 : 383 - 393 .
White , N.J. 2008 . '' Plasmodium knowlesi: The Fifth Human Malaria Parasite.'' Clinical Infectious Disease 46 : 172 - 173 .
World Health Organization . 1959 . Expert Committee on Malaria, Seventh Report. WHO/Mal/210.
-- 1961. Expert Committee on Malaria, Eighth Report , World Health Organization Technical Report Series , No. 205. Geneva: World Health Organization.
-- 1961. Joint WHO/FAO Expert Committee on Zoonoses, Second Report , World Health Organization Technical Report Series , No. 169 , Geneva: World Health Organization.
Zuckerman , Solly. 1933 . Functional Affinities of Man, Monkeys, and Apes. London: Kegan Paul, Trench, Trubner.