The Germ Theory, Beriberi & The Deficiency Theory of Disease  
                                             By: K. Codell Carter, 1977

By the beginning of the twentieth century, many diseases could causally be
explained by the germ theory.  However, other important diseases defied
every attempted explanation.  

One such disease was beriberi, which, in some groups, was responsible for
more deaths than were all the infectious illnesses combined.  

To explain how beriberi was caused, a new theory of disease was
developed, the deficiency theory.  

Historical accounts consistently treat the germ theory as an obstacle that
delayed progress on the deficiency theory of disease.  Ihde and Becker claim
that:

"The germ concept proved a major barrier to the recognition and study of
deficiency diseases."  

C. P. Stewart writes:

"One factor which undoubtedly held up the development of the concept of
deficiency diseases was the discovery of bacteria in the nineteenth century
and the consequent preoccupation of scientists and doctors with positive
infecting agents in disease."  

Numerous writers assert that the deficiency concept was difficult to accept
because the germ theory suggested that only a positive agent (such as a
micro-organism or a toxin) could cause something.  

In his excellent history of nutrition, E. V. McCollum notes that:

"Improved microscopes and the staining and other techniques applicable to
the study of the problems of pathology so monopolized the attention of
investigators that they had little incentive to consider any aspect of
malnutrition as a cause of disease."  

In Toward the Conquest of Beriberi, Robert R. Williams treats the germ theory
only as the source of one false explanation for the etiology of beriberi.  

These accounts overemphasize the extent to which the germ theory
obstructed development of the deficiency concept, and they entirely ignore
important ways in which the germ theory contributed positively to the
deficiency theory of disease.  

By taking account of these contributions we can better understand the
relation between the two theories.  

In the early nineteenth century, scurvy and rickets were generally believed to
be diet-related.  In 1830 the
Lancet contained a series of 'Clinical lectures' by
John Elliotson, Professor of Medicine in University College, London.  

In discussing scurvy, Elliotson noted that:

"The cause ... is always, I believe, a want of fresh animal and fresh vegetable
food."  

About seven years later, in a similar lecture, Marshall Hall observed:

"Scorbutus is generally induced by a deficiency of fresh vegetable food.  It is
also occasionally referred to other errors in diet, to the respiration of a
crowded or otherwise impure atmosphere, to excessive fatigue, anxiety, etc.  
The prevention and cure of scorbutus consists in the administration of fresh
[animal?] and vegetable food, and, above all, of citric acid."
 

Both men refer to Gilbert Blane and to James Lind whose works were, by
that time, the recognized sources on scurvy.  Neither Elliotson nor Hall
suggests that his views are new or atypical; indeed, both men
acknowledged that lemon juice had been the standard cure for scurvy for
more than 200 years.  

In 1840 George Budd summarized clinical knowledge of scurvy in an article
in Alexander Tweedie's
A System of Practical Medicine.  Budd discussed
various fruits and vegetables that were generally known to cure scurvy.  

Knowing of Franqois Magendie's experiments demonstrating the
inadequacy of certain macronutrients, Budd speculated that:

"The study of organic chemistry and the experiments of physiologists" would
ultimately shed light on the essential element common to the antiscorbutic
plants.  

Two years later, a series of Budd's lectures was published in which he
clearly and explicitly classified scurvy, rickets, and certain eye disorders as
diseases resulting from dietary deficiencies.  

Budd's 1840 article on scurvy was frequently cited by English physicians
through the turn of the century.  

One reason for his continued influence was that he was among the last
practicing physicians to be particularly interested in the disease.  

By the beginning of the nineteenth century, scurvy had been virtually
eliminated from the British navy.  Except for uncontrollable situations, such
as famine and war, where the known therapies could not be applied, scurvy
gradually declined in other areas and populations.  

Moreover, the prevailing conception in medical circles was that a given
disease was identical with a particular collection of symptoms.  Given this
conception, and given that the symptoms of scurvy were more readily
controlled than were those of most other diseases, scurvy must have been
commonly regarded as completely understood.  

This attitude is typified in an editorial written in 1858 wherein the conquest of
scurvy is spoken of as a leaf in the laurel wreath on the brow of medical
science.  

One can gauge the attitude of nineteenth-century British physicians toward
scurvy by examining references to the disease in the articles, editorials, and
letters in the
Lancet.  

After Budd's articles there are few references to scurvy until 1848 when
failure of the potato crop resulted in numerous cases of the disease in
England and Ireland.  

Work carried out at this time by John Aldridge and (independently) by Alfred
B. Garrod suggested that scurvy may have been caused by a deficiency of
potash.  

Through the next decade there are few references to the disease.  Beginning
in the late 1850s and continuing for about twenty years there are numerous
letters and editorials decrying the continued appearance of scurvy in the
British merchant fleet.  

In these notices, scurvy is consistently treated as a disease entirely
understood and completely preventable-ship owners who allow the disease
to appear are regarded as criminal and, in one editorial, compared with
murderers.  

In one of the few original articles on scurvy to appear in this period, the
disease is attributed to deficiency of protein.  Fifteen years later, in another
original article, we read that:

"No fact in medicine is more clearly established than that the exclusive cause
of scurvy is the prolonged and complete withdrawal of succulent plants and
fruits."  

By the 1880s scurvy is treated as a medical curiosity of which very few
practicing physicians have had immediate experience.  

In that period, however, letters and editorials begin to take account of the
experiences of certain arctic explorers who had survived for months on
fresh uncooked meat with no sign of scurvy.  

The chief question in these writings is whether the dietary deficiency that
results in scurvy could be corrected by fresh meat as well as fresh
vegetables.  

By 1883 some microbiologists were arguing that scurvy was caused by
microorganisms, but the first hint of these arguments to appear in the Lancet
was in 1886.  

In that year, a brief editorial mentions research by the Russian pathologist, T.
Stazevich, who argued that scurvy was a
"form of septic poisoning".  

Until that time the Lancet contains no suggestion whatsoever that scurvy is
anything other than a nutritional deficiency disorder.  

In 1889 Wilhelm Koch published an ambitious study of blood diseases in
which he argued that scurvy, hemophilia, and various other disorders were
variant forms of an infectious blood disease, and that the obvious correlation
between scurvy and the lack of fresh food (like the hereditary pattern of
haemophilia) could be explained on this interpretation.  

Koch's book seems not to have had much impact, but it was given a serious
review in the
Lancet.  

Through the end of the century, there are scattered references to toxic and
micro-organistic explanations for scurvy; these are generally skeptical and
often rebutted.  

In the first decade of the twentieth century opinion was clearly shifting
toward such an explanation, but as late as December 1904, an editor of the
Lancet could still write that:

"The general disposition is to regard scurvy as due to the absence of certain
elements in the food which is taken, but the exact nature of those elements
has not been conclusively demonstrated."  

The preceding quotation is part of a continuous tradition that, as we have
seen, extends back beyond the time of George Budd.  This quotation was
published less than three years before the classic paper on scurvy by Holst
and Frolich that was fundamental to the development of the deficiency
theory, and less than eight years before that theory was given its first full
articulation by Casimir Funk.  

Yet in 1911, seven years after the editorial quoted above, a report on vitamins
published by the British Medical Research Committee stressed the difficulty
of implanting:

"The idea of disease as due to deficiency".  

Ironically, this report contains a reference to Budd's work on scurvy and
commends his treatment of the history of the disease.  

In 1932 a second report by the Medical Research Council retained the
language about the difficulty of thinking of negative causes, dropped the
reference to Budd, and added a note indicating that:

"It is now difficult to understand how scurvy failed in practical medicine to
obtain recognition as a disease due to a deficiency in food."  

The greatest difficulty is in understanding how these false traditions could
have gained influence so quickly.  

There can be no doubt that development of the germ theory captivated the
interests of medical researchers during the latter part of the nineteenth
century.  

With the work of Pasteur and Koch, there penetrated rapidly into all fields of
medicine the idea that infinitely small beings, endowed with special
pathogenic qualities, played a pre-eminent role in producing many diseases.  

The new concept made such a great impression that for a while it was
believed that the cause of all diseases could be ascribed to microbes alone.  
Almost completely dominant, bacteriology at this period became the center
and goal of medical investigations.

However, serious original work on scurvy had ceased decades earlier.  
Through the nineteenth century, practicing physicians saw fewer and fewer
cases of scurvy; medical interest in the disease declined accordingly.  

In this period, the few organic chemists and physiologists who investigated
human nutrition showed almost no interest in the disease.  

By 1880 common medical opinion was that microbiology was the most
promising new field for medical research, but at least in England, physicians
also believed that scurvy was a well-understood nutritional disorder that
held little practical or theoretical interest.  

Under these circumstances it seems misleading (if not false) to speak of the
germ theory as a serious obstacle to the recognition and study of scurvy as
a nutritional disease.  

Indeed, the germ theory provided the incentive to reopen investigation of the
disease as researchers sought to explain scurvy as yet another
manifestation of parasitic infection.  

It was in this context in which medical research was dominated by the germ
theory that beriberi rapidly achieved prominence.  

Beriberi seems to have been known to oriental writers as early as the second
century; the earliest descriptions in western literature are from the
seventeenth century.  

Prior to the nineteenth century, the disease was relatively unimportant even
in the orient.  This is evident, first, from the treatment the disease received in
pre-nineteenth-century medical literature, and second, from the fact that
modern steam-milling procedures, which we now recognize to have been
substantially responsible for the rise of beriberi, did not become common in
Asia until then.  

By the last quarter of the nineteenth century the disease was widespread
and growing at an extraordinary rate.  It is difficult to gauge accurately the
growth of beriberi; we must be content with a few scattered hints.  

In the Japanese Army in 1876 there were 3,868 cases of beriberi among
35,300 men (11 per cent), in 1877 there were 2,687 cases among 19,600 men
(14 per cent), and in 1878 there were 13,629 cases among 36,100 men (38 per
cent).  

This percentage remained roughly constant through 1884 and then it
declined because of dietary reforms, but during the war between Japan and
Russia (1904-1905) there were nearly 200,000 cases of beriberi.  

In thirty-one specific district hospitals in the Malay peninsula, Chinese
patients admitted for beriberi increased from 1,206 in 1881 to 3,175 in 1891,
and to 6,767 in 1901.  

In that period, beriberi accounted for more than 100,000 deaths among
Chinese laborers in the Malay States over half the total death rate for that
population.  

In 1883 August Hirsch reported that within the preceding twenty years,
beriberi had appeared in many areas for the first time (e.g. lower Bengal,
Ceylon, Africa, and Brazil), and that it was epidemic in coastal areas of Japan
and of other Asian countries.  

Ten years later, B. Scheube reported that the disease had recently appeared
for the first time in Siam and in the Philippines, that it was spreading in Africa
and in South America, and that it was now endemic throughout Japan.  

In 1907, Patrick Manson gave the disease a more extensive distribution (e.g.
he states that it is common in southern China where, according to Hirsch
and Scheube, it was formerly rare), and in most areas incidence of the
disease seems to have increased.  

Finally, one can gain some appreciation for the remarkable rise in the
disease by surveying the professional literature of the period.  

Scheube's nearly complete bibliography includes two publications on
beriberi between 1800 and 1809; in subsequent decades the publications
numbered eight, ten, eleven, thirty, sixty-four, eighty, and between 1880 and
1889, one hundred and eighty-one.  

W. Leonard Braddon's incomplete bibliography lists nearly two hundred
articles and books for the decade from 1890 to 1899; another incomplete
bibliography lists two hundred and fifty publications for the period from 1900
to 1910.  

A complete bibliography for this period alone would certainly approach five
hundred items.  Writers in the late 1870s still regarded beriberi as an exotic
and unfamiliar topic.  

About thirty years later, an editorial in the Lancet begins with the observation
that:

"There is probably no disease concerning which so much discussion as to its
etiology has taken place as beriberi."  

We can, somewhat arbitrarily, take 1880 as the beginning of serious
occidental interest in beriberi.  By that time there was a strong and broadly
based opinion that the disease was diet-related.  

It was obvious to everyone that the disease was predominant only in areas
where rice was the staple diet.  Several medical observers between 1850 and
1880 attributed the disease to an:

"Insufficient diet or a diet not corresponding to the metabolisms and blood
making, or to the needs of the body".  

Of those who ascribed beriberi to an insufficient diet, some seem to have
believed that it was simply a quantitative failure-people who got beriberi were
those who had too little to eat.  

However, others believed that the problem was a qualitative failure-those
who contracted the disease had too little of certain essential foods.  

Van Leent, for example, held that beriberi was always due to consumption of
too small a proportion of albuminous substance and of fat.  

Among the most important early observers to espouse a dietary explanation
for beriberi was Kamehiro Takaki.  Takaki was the first person to collect
systematic evidence on a large scale that supported the deficiency concept.  

He first heard of beriberi from his father who was a guard at the Japanese
Imperial Palace.  Many of the guards suffered from beriberi:

"They attributed the cause to food and called a provision box the 'beriberi
box'."  

Takaki became a naval doctor, spent five years studying medicine in
London, and was appointed director of the Tokyo Naval Hospital.  

By 1882 Takaki's own observations led him to attribute beriberi to poor diet.  
His view was that:

"A wide departure of nitrogen and carbon from the standard proportion (1 to
15) essential to the maintenance of health, resulting from a great deficiency of
nitrogenous substances and a great excess of carbohydrates in food, is the
cause of kakke (beriberi)."  

Takaki persuaded the skeptical Japanese Admiralty to initiate massive
dietary reforms-crews were given more meat (especially fresh meat), more
vegetables, and at some meals they were given barley instead of rice.  

The effects were incredible: in 1882 there were over 400 cases of beriberi for
each 1,000 men, in five years the disease had been completely eliminated.  

Takaki's observations were reported in major European medical periodicals,
he himself was honored at home and abroad, and his evidence was
ultimately important for the solution of beriberi.  

Unfortunately, Takaki's own ideas about the etiology of beriberi were false
and he seems to have persuaded almost no one.  

Takaki's theory was conclusively refuted by a large, if unsystematic body of
epidemiological facts that were widely known years before his studies were
even begun.  

In 1835, John G. Malcolmson observed that:

"The comparative cheapness of all kinds of grain in the Circars, and the easy
circumstances of many of the native soldiers who suffered, are fatal to any
supposition of the disease depending on deficient and unhealthy diet."  

By 1880 it was common knowledge that those who contracted beriberi often
ate more and a better range of foods than those who did not.  

Moreover, populations that seemed especially vulnerable to beriberi were
often living amid a larger population that remained healthy, and the only
apparent dietary difference between the two groups was that the larger and
immune population regularly consumed less protein.  

Finally, specific cases were known in which beriberi appeared among
persons who were living almost entirely on protein.  

It was impossible to reconcile these facts with Takaki's theory.  These and
similar facts continued to count as evidence against dietary theories of
beriberi until after the turn of the century.  

Unfortunately, the argument based on these observations regularly seemed
stronger than it really was.  

Notice how Braddon summarized the argument in his own extensive study
of the disease: against those who hold that a deficiency of nitrogen or fat
causes beriberi one can cite:

"Several instances in which outbreaks of beriberi happened, and yet there
was no deficiency of nitrogen or of fat, or of any other proper component of
diet".  

Braddon was obviously assuming that all proper components of diet were
known; only under this assumption could he conclude that beriberi
sometimes appeared where there were no deficiencies of any kind.  

By challenging this unwarranted assumption, it ultimately became possible
to reconcile Takaki's observations with the well-established epidemiological
facts.  One needed only to realize that there were unknown but essential
nutrients which, when lacking, resulted in beriberi.  

Because the deficiency theory seemed incompatible with the facts, most
early observers favored other explanations for beriberi.  Perhaps the most
popular of the alternative theories was that it was
"miasmatic" or "malarial".  

Early observers noted important epidemiological similarities between
beriberi and malaria.  These similarities were emphasized even by persons
who did not espouse the miasmatic concept.  

William Anderson, among the earliest western writers to investigate beriberi
in Japan, noted that most Japanese doctors
"believe that the complaint is
caused by some poisonous emanation from the soil."  

He went on to list similarities between beriberi and malaria, and he
concluded that the disease is most likely due to
"the existence of an
atmospheric poison".  

The Lancet review of Takaki's work emphasized that:

"The majority of observers have been inclined to attribute [beriberi] to a
specific poison which is generated in the soil under certain insanitary
conditions of local origin, and finds its way into the human body by means of
the atmosphere, and perhaps of the food and drinking water also."  

The review continues by observing that, Takaki's work notwithstanding, "the
weight of evidence is still in favor of the miasmatic hypothesis".  

As microbiology became more prominent, hope grew that beriberi would join
the list of diseases that had been explained by this science.  

Various researchers sought (and generally found) the responsible
microorganism, and numerous theories were developed linking specific
organisms with beriberi.  

Hamilton Wright attributed the disease to an organism that enters the body
by the mouth, and produces a toxin in the pyloric end of the stomach.  

Herbert Durham concluded that the disease is similar to diphtheria and that it
is communicated from person to person by fomites.  

Patrick Manson proposed that beriberi is a form of intoxication, not unlike
alcoholism, in which a toxin, manufactured outside the body (probably by
micro-organisms) is introduced into the body (probably through air).  

Researchers could seldom agree which microorganism was the cause of
beriberi, but few seriously doubted that there was one.  In 1897 M. H.
Spencer wrote:

"Little doubt remains that [beriberi] is a germ-borne disease and that the
micro-organism which is the cause of it has a specially toxic influence upon
the peripheral nerves."  

In 1883 C. A. Pekelharing and A. Winkler were sent to Java by the Dutch
government to study beriberi.  They took with them, as an assistant,
Christiaan Eijkman, a microbiologist who had studied in Berlin under Robert
Koch.  

Eijkman's specific instructions in traveling to Java were to find the organism
responsible for beriberi.  

When Pekeiharing and Winkler returned to Europe, they reported that the
disease was definitely parasitic in origin, but that they had not yet
conclusively identified the agent.  

Eijkman, however, remained in Java as director of a microbiological
laboratory that was connected with a military hospital.  While there he made
two important discoveries that led to much of the empirical foundation for
the deficiency theory of disease.  

For years, dogs, rabbits, guinea pigs, and monkeys had been used by
microbiologists in beriberi research.  Eijkman was using chickens in his
laboratory and, while he does not make this explicit, it seems likely that they
were intended for beriberi research.  

Eijkman's first important discovery was that under certain conditions,
chickens spontaneously contracted a disease whose symptoms and
histological features were very like those traditionally connected with
beriberi.  

Eijkman reported that he made this discovery, quite by accident, when the
chickens began to show signs of polyneuritis.  The chickens were examined
carefully and no pathological organisms were found; Eijkman was unable to
infect healthy chickens by exposure to those suffering from polyneuritis.  

In investigating, Eijkman discovered that whereas the chickens at the
laboratory were generally fed a low-grade uncooked rice, it happened that
for some weeks they had been fed surplus cooked rice from the hospital
kitchen.  

His second important discovery was that while the ordinary chicken feed
was unpolished rice, the kitchen rice was polished.  In a few trials Eijkman
convinced himself that consumption of polished rice was responsible for the
inception of polyneuritis gallinarum, as he called the chicken disease.  

Without assuming that polyneuritis gallinarum was etiologically identical to
beriberi, Eijkman sought to discover whether beriberi was also correlated
with the consumption of polished rice.  

There were three ways in which rice was commonly prepared for human
consumption.  

(1) From harvesting, the rice could be milled immediately. In this case, both
outside and inner husks were generally removed, leaving only the white
grain.  This rice was called uncured, polished, or decorticated rice.  

(2) In some areas newly harvested rice was soaked, steamed, and dried
before milling.  In this case the milling process usually left some of the inner
layers of husk, called pericarp, and certain light brown inner coverings of the
grain.  This rice was called cured or unpolished rice.  

In some primitive areas, the rice was not machine milled at all, but was stored
unhusked and then pounded and winnowed just prior to eating.  Local
custom, ethnic origin, and economic status were among the factors
determining which kind of rice an individual ate.  

In Java, prison inmates were usually fed whichever form of rice was
commonly consumed by the local population; in twenty-seven prisons,
inmates ate unpolished rice, in seventy-four others the rice was decorticated
to some extent.  

This provided an ideal opportunity for determining whether beriberi was
correlated with the consumption of decorticated rice.  Eijkman's colleague,
A. G. Voderman, who was then a Civil Medical Inspector, conducted surveys
of the prisons throughout Java.  

The preliminary results were astonishing;
Of nearly 300,000 prisoners, only one in 10,000 of those who ate unpolished
rice had beriberi, while one in thirty-nine of those who ate polished rice had
the disease.  

These results exhibited dramatically the correlation between the incidence of
beriberi and the consumption of a particular kind of rice.  Within a few years,
studies of other populations confirmed these results.  

Braddon noted that in the Malay States, the Chinese, who ate polished rice,
were seriously afflicted with beriberi; Tamils, who ate unpolished rice, and
native Malays, who ate rice that was not mechanically milled, were almost
free from the disease.  

Both Voderman and Braddon's evidence was demographic and it was,
therefore, subject to no strict controls.  Eijkman's studies on fowl could yield
only analogical arguments that many found unconvincing.  

Toward the end of the decade, however, William Fletcher (1907) and Henry
Fraser and Thomas Stanton (1909) published important studies on small and
carefully controlled groups.  These controlled studies probably did more
than anything else to persuade medical opinion that decorticated rice was
connected with beriberi.  

By 1910 the evidence was clear enough for a meeting of the Far Eastern
Association of Tropical Medicine to adopt a motion stating:

"That in the opinion of this association sufficient evidence has now been
produced in support of the view that beriberi is associated with the
continuous consumption of white (polished) rice as the staple article of diet."  

There are unmistakable similarities between the prevailing medical opinion
of scurvy in 1830 and the motion regarding beriberi that was adopted by the
Far Eastern Association of Tropical Medicine in 1910.  

Both focus on an empirical correlation between the respective disease and
particular dietary patterns.  In both cases there was clear evidence that the
disease could be effectively controlled by specific changes in those
patterns.  

The remarkable difference is that, whereas the empirical understanding of
scurvy effectively ended all new study, everyone seems to have regarded
the empirical correlation between beriberi and polished rice as interesting
only insofar as it pointed the way toward a deeper theoretical understanding
of the disease.  

Why was there this difference?  The answer must be found in the germ
theory.  The germ theory provided a causal explanation for many diseases,
but it did much more.  

First, it explained a wide range of facts (facts about the spread of disease,
about certain kinds of immunity, etc.) in terms of the natural behaviour of
microorganisms.  

In many cases, these facts had been known long before the germ theory was
promulgated, but they remained unexplained and unconnected.  

Second, whereas particular diseases had been regarded as collections of
symptoms, the germ theory treated each set of symptoms only as the clinical
manifestation of a disease.  This led to new classifications of diseases and it
made diagnosis much more definitive.  

In these ways, the germ theory systematized certain areas of medical
knowledge.  Consequently, knowledge of these diseases explained by the
germ theory was more fundamental, more coherent, more scientific.  

Thus, the germ theory provided a new standard for judging the
understanding of any disease.  Against this standard, disorganized
collections of facts were no longer adequate.  This was no less true when
those facts included as they did for scurvy, for example-completely reliable
and correct methods for preventing and curing the disease.  

Before the germ theory, the understanding of scurvy constituted a paradigm
and an ideal to be emulated by medical observers seeking to control other
diseases; after the germ theory, that understanding was recognized as
partial and fragmentary.  

Thus, Wilhelm Koch did not controvert what was known of the relation
between scurvy and the lack of fresh vegetables, but he sought an
explanation for that relation and for other disconnected empirical facts about
the disease.  

Shall we say that Koch's investigation (or the theory that motivated it)
obstructed the understanding of scurvy?  Eijkman was a microbiologist.  

Fletcher, Fraser, and Stanton were medical doctors who specialized in
pathology; all did significant original work in microbiology.  These men
subscribed to the standard for theoretical comprehension that had been
established by the germ theory.  

Given that standard, the empirical relation between beriberi and the
consumption of polished rice could not constitute an adequate
understanding of the disease.  No matter how well documented it may be
and regardless of whether it enabled doctors to control beriberi, the
correlation required a theoretical explanation.  

Prior to the germ theory when control of symptoms still constituted the
paradigm for understanding any disease-researchers could not have
recognized the inadequacy of their understanding of beriberi.  

Thus, far from constituting an obstacle to the understanding of deficiency
diseases, the germ theory provided the most important incentive for
studying them.  

Numerous theories were proposed to explain the etiology of beriberi and, of
course, most of these were derived in one-way or another from the germ
theory.  

Braddon proposed that polished rice was the locus within which a toxin was
created by microorganisms and by which it was transferred into the potential
victim.  

Eijkman's original hypothesis was also a version of the toxic theory:

"Under assumption that all polyneuritis ultimately seems to be intoxication,
we must assume that the starch in these cases carries a poison or that from
it-either in the alimentary canal (possibly under the influence of a
micro-organism) or in the nerves-a poison is produced through the chemical
process of metabolism.  

In the pericarp of the grain, then, the material(s) would be present, through
which the poison is, in some way, made harmless or, perhaps, its creation is
prevented."  

An essentially correct theoretical understanding of the situation was
suggested by Gerrit Grijns, a microbiologist who succeeded Eijkman as
director of the pathology laboratory in Batavia.  

In an article published in 1901 Grijns proposed that there may be some
unknown ingredient in the pericarp whose absence resulted in beriberi.  

In the article he asserted that recent developments were leading away from
the idea that beriberi was infectious.  

Moreover, in his own experiments he had induced polyneuritis in chickens
by feeding them concentrated protein (cooked horse meat) and this, he felt,
counted heavily against Eijkman's hypothesis.  

The most likely conclusion seemed to be:

"That there are various natural foodstuffs that cannot be missed without
particular damage in the peripheral nerves".  

Grijns' hypothesis, which did not appear in a readily accessible source,
seems not to have received prompt attention; for the next few years most
researchers continued to favor a toxic or infectious explanation.  

However, it is misleading to attribute this to
"preoccupation of scientists and
doctors with positive infecting agents".  

In the first place, there were persuasive arguments against dietary
explanations of beriberi.  In spite of these arguments, beriberi researchers
remained open to alternative considerations.  

Pekelharing, who was a particularly influential early advocate of an
infectious explanation for beriberi, subsequently performed pioneering
studies proving the inadequacy of the known macronutrients.  

Fletcher emphasized that his findings were compatible with a variety of
causal explanations.  Fraser and Stanton carefully avoided explicit
commitment to any particular theory in their original publications.  

Even Eijkman, who has been said to have been victimized by the
preconceptions of the germ theory, abandoned his toxin hypothesis by
1906.  

Second, through the first decade of the twentieth century, explanations of
beriberi that were based on the germ theory continued to provide important
experimental results.  

Fletcher and Braddon both conducted their demographic studies in
connection with infectious theories of the disease.  

In testing Eijkman's toxin hypothesis, Grijns obtained important results from
animal experiments.  Because he believed that- the pericarp contained a
natural antitoxin that neutralized the harmful influence of the starchy rice
grain, Eijkman began an active chemical investigation in the effort to isolate
the antitoxin.  

He was able to show that an aqueous extract from the rice polishings would
cure polyneuritis gallinarum; he also showed that when foods were heated
above 120 degrees centigrade they lost their effectiveness in preventing and
curing the disease.  These were significant results that profited later
researchers.  

Science advances as hypotheses-both true and false-are tested
experimentally.  A given hypothesis becomes a barrier to progress only
when it ceases to suggest profitable new experiments or when those who
espouse it do not remain open to alternative hypotheses.  

Admittedly Eijkman was somewhat slow in recognizing the truth, but surely it
is an exaggeration to claim that Eijkman's hypothesis, based on the germ
theory:

"Proved a major barrier to the recognition and study of deficiency diseases".  

The success achieved by Eijkman and Grijns suggested profitable avenues
of investigation for researchers working on a different disease.  

Beginning in 1894, crews on Norwegian ships began to suffer from a disease
some of whose symptoms were similar to those of beriberi; the disease was
called ship-beriberi.  

In 1902 a Norwegian research commission reported that ship-beriberi was a
non-infectious intoxication from tainted foods.  

In the same year, Alex Holst visited Grijns in Batavia; Grijns showed him the
experiments he was performing on fowls.  Holst was much impressed with
the work of Eijkman and Grijns; he decided to adopt similar techniques in his
own study of ship-beriberi.  

He tried to induce the disease in pigeons and chickens and later, after
having been joined by Theodor Frolich, in guinea pigs.  The results of
carefully controlled feeding experiments were curious: while Holst and
Frolich were trying to study ship-beriberi, the guinea pigs regularly
contracted a disease that bore every similarity to scurvy.  

Holst and Frolich did not verify that similar diets would induce scurvy in
humans, but they did mention that earlier evidence connected scurvy with
deficient diet, and that scurvy and beriberi often appeared together.  

They also cite B. Nocht, a German observer, who had argued that it would be
helpful to treat ship-beriberi as a form of scurvy.  In their original publication,
Holst and Frolich did not endorse any specific theories about the cause of
beriberi or of ship-beriberi.  

Subsequent developments revealed clearly, however, that they regarded
these diseases (like scurvy) as deficiency diseases.  

For example, at a discussion of the Society of Tropical Medicine and
Hygiene, Holst noted that on identical diets, chickens contracted beriberi,
guinea pigs contracted scurvy, and pigs contracted both diseases.  

As a result of their publications, beriberi, scurvy, and ship-beriberi were all
seen as causally linked to deficient diets and, therefore, as theoretically
linked to one another.  

In 1910 Fraser and Stanton showed that the substance that prevented
beriberi was soluble in strong alcohol, and that the effectiveness of a given
grain in combating beriberi was correlated with the amount of phosphorus it
contained.  

This led Schaumann, who was associated with Nocht, to propose that a wide
range of diseases may be due to deficiency of phosphorus.  

"According to all appearances there is a series of diseases that are similar in
etiology to beriberi.  For scurvy this is, through numerous observations, well
founded.  

To this group of diseases with similar etiology also belong, apparently,
Barlow's disease, rickets, osteomalacia, and possibly also pellagra.  For all
these diseases the opinion is clearly suggested that they are the result of a
shortage of phosphorus."
 

Schaumann's hypothesis was a step backwards insofar as he believed that
all these diseases resulted from deficiency of the same nutrient.  

By obtaining a purer specimen of the crucial ingredient in rice husks,
Casimir Funk was soon able to show that beriberi, at least, was not due to
phosphorus deficiency.  

However, Schaumann did advance matters by classifying pellagra and
rickets with scurvy and beriberi.  Unfortunately, his 397-page treatment of
beriberi, the source of the preceding quotation, contains no discussion
either of pellagra or of rickets, and in his previous and subsequent
publications there is no mention of either disease.  

For Schaumann, classifying pellagra and rickets as deficiency diseases
seems to have been as much a lucky guess as a rational inference.  

By 1910 several lines of work were converging rapidly on the deficiency
theory of disease.  

First, epidemiological studies (Takaki, Voderman, Braddon, Fletcher, Stanton
and Fraser) and animal experiments (Eijkman, Grijns, Holst and Frolich) had
exhibited a connection between certain diets of milled grain and various
distinctive disorders.  

Second, chemical studies (Eijkman, Fraser and Stanton, Funk) had isolated
and characterized with fair precision the particular ingredient in rice
polishings that would prevent and cure some of these disorders.  

Third, an important negative result was that after thirty years of searching,
microbiologists could not agree in identifying a particular microorganism
that was causally responsible for any of the diseases in question.  

Given the importance of the germ theory at this time, it would have been
difficult for any deficiency hypothesis to have been accepted as the ultimate
explanation for beriberi without this negative result.  

Fourth, theoretical developments (Grijns, Holst and Frolich, Nocht,
Schaumann) had generated the elements of a perfect conceptual framework
within which most of the observations could be explained.  

Finally, we must consider one line of research, which, although of relatively
minor importance in the original formulation of the deficiency theory, proved
to be of great significance in its subsequent elaboration.  

Through the nineteenth century, various experiments were performed to test
the influence on animals of simplified diets-often diets consisting of one
isolated food substance.  

For the most part these experiments were not connected with the study of
any particular disease, and often they had relatively little impact on
subsequent medical thought.  

By the beginning of the twentieth century, numerous more systematic
experiments of this kind were performed in examining the processes of
protein synthesis.  Various experimenters discovered that the
macronutrients alone would not support normal growth and development of
animals.  

In 1906 F. Gowland Hopkins, who was a leader in these experiments,
concluded that:

"There are many minor factors in all diets of which the body takes account.  In
diseases such as rickets, and particularly in scurvy, we have had for long
years knowledge of a dietetic factor; but though we know how to benefit
these conditions empirically, the real errors in the diet are to this day quite
obscure."  

Such conclusions provided collateral support for the deficiency concept as
an explanation for beriberi.  Taken together all of these relatively
independent lines of work constituted the basis for the deficiency theory of
disease-it was necessary only that they be assembled correctly.  

The first publication in which all these strands were finally assembled was
Casimir Funk's The Etiology of the Deficiency Diseases published in 1912.  
Funk announced somewhat prematurely the isolation of a highly
concentrated form of the protective substance for beriberi; he proposed that
it be called vitamine.  

Funk identified beriberi, polyneuritis in birds, epidemic dropsy, scurvy,
experimental scurvy in animals, infantile scurvy, ship-beriberi, pellagra, and
(toward the end of his article) rickets, as deficiency diseases.  

He stated clearly that these different diseases are due to different
deficiencies.  Funk, in contrast to Schaumann, provided some justification
for including pellagra and rickets in this classification.  

Funk noted that about twenty years of experimental work had been
necessary to establish that these various diseases were caused by a
deficiency of essential nutrients.  

He admitted that this view was still not generally accepted, but he claimed
that there was enough evidence:

"To convince everybody of its truth, if the trouble be taken to follow step by
step the development of our knowledge on this subject."  

Subsequent research has confirmed most of Funk's opinions and vindicated
most of the arguments he provided in their support.  

After his paper, additional work on the deficiency diseases can be thought of
as the elaboration of an existing theory rather than as the creation of a new
one.  
                                 SUMMARY AND CONCLUSIONS

We began by citing numerous writers who treat the germ theory only as an
obstacle that delayed recognition and study of the deficiency diseases.  

But our investigation has revealed that this point of view does not give due
consideration to important facts.  

Deficiency diseases were recognized as such for half a century before the
germ theory was promulgated.  

In British practical medicine, scurvy was continuously thought of as a
deficiency disease at least from the beginning of the nineteenth century.  

However, early in that century, work on scurvy stagnated, there was little
interest in a more fundamental understanding of the disease until the dietary
explanation was challenged (but never surmounted) by explanations based
on the germ theory.  

During this period, beriberi became prominent.  Its etiology was first
understood by microbiologists and orthodox pathologists who, in the
relatively short period of about thirty years, developed a new theory of
disease that explained not only beriberi but also scurvy, rickets, pellagra,
and various other illnesses.  

There is no doubt that the germ theory misled many of those who
investigated beriberi, but it also suggested demographic studies and animal
and chemical experiments that were crucial for a full understanding of the
disease.  

Moreover, the germ theory provided a new standard for theoretical
understanding of disease.  Against this standard, the understanding of
scurvy was recognized as inadequate, and new studies were undertaken.  

Thus, the germ theory revived interest in scurvy and it motivated researchers
to seek a theoretical understanding of beriberi.  

Without this motivation, work on beriberi might have stagnated once the
disease could be controlled, just as work on scurvy had stagnated about a
century earlier.  

In this sense, the germ theory contributed directly to the development of the
deficiency theory of disease.  In view of these facts, treating the germ theory
only as a barrier to the study of deficiency diseases seems, at the very least,
to reflect a serious lack of historical perspective.  

By: K. Codell Carter

Article: The Germ Theory, Beriberi, and The Deficiency Theory of Disease.  
1977
www.ncbi.nlmnihgov/pmc/articles/PMC1081945/pdf/medhist00107-0005.pdf