Bacteria, Ulcers, and Ostracism?
H. Pylori and the Making of a Myth
Medicine's purported ostracism of the discovery
of H. pylori has achieved a mythological quality.
But it isn't true. After appropriate initial scientific
skepticism, the hypothesis was accepted right on schedule.
In the September/October 2003 Skeptical Inquirer,
I wrote an article critical of the research agenda of the
National Center for Complementary and Alternative Medicine
(NCCAM) (Atwood 2003). Subsequently, reader Myra Jones argued
in a letter to the editor that "we as skeptics should not
throw the baby out with the bath water. Just because the
NCCAM has funded bad science doesn't mean that . . . some
alternative medicine might not have valid claims. Many practices
now accepted were once thought crazy by the medical mainstream"
(Jones 2004). Part of my reply to her was this: "For example,
which practices? Initial skepticism of any new claim is
an appropriate part of the scientific approach. . . . Other
than that, I challenge Ms. Jones to name a single example,
since the era of scientific medicine began in the second
half of the nineteenth century, of a correct claim that
faced dogmatic, closed-minded rejection by the 'medical
mainstream' for any significant amount of time" (Atwood
Be careful what you ask for. A few weeks later, the editors
received this letter from Dr. Tess Gerritsen:
As a physician, a long-time skeptic, and a member of
CSICOP, I'm happy to agree with most of Dr. Atwood's points
about alternative medicine. However, when he challenged
letter writer Myra Jones to come up with a "a single example,
since the era of scientific medicine began in the second
half of the nineteenth century, of a correct claim that
faced dogmatic, closed-minded rejection by the 'medical
mainstream' for any significant amount of time," I must
respond in Ms. Jones's defense.
When I was first starting out in medical practice, back
in the early 1980s, the accepted treatment for peptic
ulcer disease was a bland diet plus antacids and more
antacids. Later, histamine H2-receptor antagonists were
added to the treatment. But that was it, case closed.
Then, in 1984, physicians Warren and Marshall from Australia
claimed that peptic ulcer disease was not caused merely
by overproduction of gastric acid, but rather by a specific
bacterium: Helicobacter pylori, to be specific.
They recommended antibiotic therapy. Believe me, they
were ridiculed by the medical establishment. I recall
my colleagues, and even my own physician-husband, scoffing
at the idea of peptic ulcers being an infectious disease.
For the next thirteen years, most of the "medical mainstream"
refused to let go of their calcified notion that the only
treatment for ulcers was to combat gastric acid secretion.
After all, that was what we all learned in medical school.
Therefore, it had to be the truth!
It wasn't until 1997 that the CDC finally put out the
word to the nation's doctors: Drs. Warren and Marshall
had been correct all along. Helicobacter pylori
was, indeed, the cause of most cases of peptic ulcer disease.
The treatment, at long last accepted by mainstream medicine,
is now antibiotics.
This is only one example; I'm sure my physician colleagues
can think of others. This is a case where skepticism (my
own and that of others) delayed the use of effective ulcer
treatment for over a decade. I think Ms. Jones's warning
that we "not throw out the baby with the bath water" is
indeed a good one. Skepticism is good and healthy, but
at its extreme, it can turn into rigid closed-mindedness.
This is an oft-heard argument. Ms. Jones, in response to
my challenge, offered the same example in a private e-mail
to SI editor Kendrick Frazier. "CAM" supporters brought
it up a couple of years ago at a meeting of the Massachusetts
Special Commission on Complementary and Alternative Medical
Practitioners, of which I was a member. At least one recent
article in a mainstream medical journal has made the same
claim, without attribution (Kaptchuk 2003). Medicine's purported
ostracism of the discovery of H. pylori-to some
extent, as we shall see, fostered by one of its discoverers-has
achieved a mythical quality.
But it isn't true. I have no reason to doubt that many
physicians scoffed when first faced with the notion of a
bacterial basis for peptic ulcer disease (PUD). It is not
the case, however, that the medical mainstream dogmatically
rejected the proposal for an undue period of time. A brief
history shows that the hypothesis was accepted right on
schedule, but only after "appropriate initial skepticism"-the
premise of my challenge-was satisfactorily answered. Some
of the other particulars of the mythical version of the
story are also incorrect.
Before proceeding, I would like to reiterate another point
made in the context of the challenge: all biomedical proposals,
"CAM" or otherwise, can only be judged according to what
is known about nature. The warning that by refusing to commit
scarce resources to the investigation of implausible claims,
we risk "throwing the baby out with the bath water," implies
that we have little basis for deciding which claims merit
further investigation. But that isn't true, either.
Medical researchers Robin Warren and Barry Marshall first
reported the curious finding of "unidentified curved bacilli
on gastric epithelium in active chronic gastritis" (not
ulcer) in two letters to the British journal Lancet,
published on June 4, 1983. They noted that similar bacteria
had been described intermittently, possibly as early as
the nineteenth century and certainly since 1938, but that
these had never been cultured and their significance was
unknown. They explained that the bacteria cannot be seen
with usual staining methods and surmised that this is why
they had typically been overlooked. They reported that the
bacteria are found beneath gastric mucus, thus possibly
explaining how they might be protected from gastric acid.
They noted that similar bacteria had been described in other
mammals and were thought to be "commensals"-harmless inhabitants
of the gastric mucosa (stomach epithelium). Nevertheless,
because Dr. Warren had found the bacteria in biopsy specimens
of inflamed gastric mucosa but not in normal ones, Dr. Marshall
cautiously suggested, "If these bacteria are truly associated
with gastritis . . . they may have a part to play in other
poorly understood, gastritis associated diseases (i.e.,
peptic ulcer and gastric cancer)" (Warren and Marshall 1983).
One year later, in the June 16, 1984, Lancet,
Marshall and Warren published their first full paper on
the topic. They further characterized the bacterium, reported
its first successful culture, and established that it was
a new species of unclear relation to any previously characterized.
At that time, they and others were still referring to it
as a form of campylobacter-variously called C. pyloridis
or C. pylori-because of morphologic similarities
with other campylobacter species, but Marshall and Warren
recognized that there were important differences. These
differences eventually led to it being renamed Helicobacter
The authors reaffirmed the association of the bacterium
with gastritis, but they now also reported it in association
with both gastric and duodenal ulcers. Nevertheless, they
remained cautious: "Although cause and effect cannot be
proved in a study of this kind, we believe that pyloric
campylobacter is etiologically related to chronic antral
gastritis and, probably, to peptic ulceration also" (Marshall
and Warren 1984). They did not recommend antibiotic treatment
but reported that bismuth-an established treatment for PUD
when coupled with acid suppression, that seemed to be associated
with reduced relapse rates compared to acid suppression
alone-was bactericidal to the new "pyloric campylobacter."
A bacterial cause of PUD, they suggested, could thus explain
the finding of a reduced incidence of relapse in patients
treated with bismuth. All of this was plausible but, of
course, still new and unproved.
Search performed at PubMed using
the search terms campylobacter pylori or campylobacter
pyloridis or campylobacter pyloric or campylobacter-like
or helicobacter pylori or curved bacilli gastric.
The 1982 and one of the 1983 citations had to do with animal
The Initial Response of Investigative Medicine
For Marshall and Warren's proposal to gain scientific and
clinical momentum, several requirements had to be met: others
had to confirm both the bacteriologic and clinical findings;
stronger evidence than mere "bystander" status for an etiologic
(causative) role of the bacteria in PUD had to be offered
and replicated; diagnostic methods less cumbersome and expensive
than endoscopy, biopsy, and culture-the methods used by
Warren and Marshall-had to be developed; and antibacterial
treatment had to be shown to be more useful-i.e., as safe
as but more effective than-standard treatments. The last
requirement was not trivial, as I will discuss. All these
steps would take time.
One might expect that if scientific medicine had dogmatically
rejected Warren and Marshall's hypothesis, there would be
scant references to their reports for the several years
after the initial publications. The opposite is the case:
the biomedical world was abuzz with Campylobacter pylori
from the start, as is demonstrated in the figure. It shows
the number of papers listed on PubMed, the online database
of the National Library of Medicine, as a function of the
calendar year throughout the 1980s and early 1990s. The
rate of increase after 1983 is nearly exponential. Anyone
who doubts the infatuation that medicine had with C.
pylori at the time can surf to PubMed and, using the
same search criteria that I used to generate the data for
the figure, peruse thousands of abstracts.
Within a couple of years of the original report, numerous
groups searched for, and most found, the same organism.
Bacteriologists were giddy over the discovery of a new species.
By 1987-virtually overnight, on the timescale of medical
science-reports from all over the world, including Africa,
the Soviet Union, China, Peru, and elsewhere, had confirmed
the finding of this bacterium in association with gastritis
and, to a lesser extent, ulcers. Simpler and less invasive
diagnostic methods were devised (Graham et al. 1987; Evans
et al. 1989). The possibility of pyloric campylobacter being
the cause of gastritis or ulcers was exciting and vigorously
discussed, even as it was acknowledged by all, including
Marshall and Warren, to require more evidence. Here is a
typical opinion, in this instance from the Netherlands:
"There is an explosion of interest in the role of Campylobacter
pylori as a cause of active chronic gastritis. . .
. To what extent this intriguing microorganism is causally
related to peptic ulcer disease remains to be elucidated,
but all the evidence which is available so far supports
a pathogenetically important role" (Tytgat and Rauws 1987).
The New England Journal of Medicine, the most
widely read medical journal in the world, offered this editorial:
"Further unfolding of the details [of the possible etiologic
role of C. pylori in peptic ulcer disease] will
be enhanced by the development of an animal model, by epidemiologic
studies, and by identification of the source and the virulence
properties of specific serotypes of C. pylori.
The prospects are exciting, intriguing, and promising" (Hornick
The Quest for Proof of Cause
Establishing that a microbe is the cause of a specific
disease is not a simple task. The mere presence of microorganisms,
even if reliably found in association with diseased tissue,
does not prove that the organism causes the disease. Myriad
species of bacteria and fungi are always present in the
human large intestine, for example, but most never cause
diseases. Thus, there must be specific evidence of cause
The accepted standard for establishing such a causal relation
was offered by Robert Koch in 1882, during the flowering
of the Germ Theory of disease. As described in his classic
lecture "Die Aetiologie der Tuberkulose," Koch established
the bacterial cause of tuberculosis by the following steps:
He harvested, from post-mortem specimens of human lung
and brain tissues taken from patients who had died of
tuberculosis, a characteristic bacterium with identical
microscopic features in every case.
He grew these bacteria by placing specimens of diseased
tissue onto appropriate solid-culture media. Solid-culture
media, one of Koch's most important innovations, allowed
him to discern discrete colonies of bacteria, for the
first time providing a method of isolating pure cultures.
By serially reintroducing bacteria from these colonies
onto new media, he achieved pure cultures of bacteria
identical to those originally found but without any
possibility of contamination from the original sample.
The bacterial progeny manifested the same microscopic
features as those he had originally found.
When he introduced these offspring into guinea pigs,
the result was the characteristic disease of tuberculosis
(the guinea-pig variety).
He then recovered the identical organism from the diseased
guinea-pig tissues (Koch 1882).
These steps became known as "Koch's postulates" and resulted,
over the next twenty years, in the elucidation of most bacterial
and parasitic diseases that had afflicted humankind during
historical memory. It would have been more certain for investigators
to reintroduce the pure cultures into humans instead of
nonhuman animals, because one could not know that all infectious
diseases in humans have susceptible hosts in the animal
world; and as subsequently has become clear, they don't.
For obvious reasons, this has not usually been done.
Part of the problem for C. pylori was that for
several years after Marshall and Warren had first cultured
it, there was no good animal model. Thus efforts to satisfy
Koch's postulates were hampered. Fortunately, much had changed
since Koch's time, such that a presumption of a microbial
cause of a disease could now be based on additional evidence:
specific immune responses to the organism, an elucidation
of microbial pathogenesis at the tissue and molecular levels,
response to specific treatment, and more. An important difference
between the H. pylori story and what Koch faced
is that there were now effective treatments for bacterial
diseases, unavailable in Koch's time. Thus a "proof in the
pudding" was possible. That eventually became the clincher
for H. pylori.
Another difference is that unlike anthrax, TB, pneumococcal
pneumonia, bubonic plague, malaria, cholera, and other dreaded
microbial diseases investigated by Koch and others near
the end of the nineteenth century, presumptive H. pylori
gastritis or even peptic-ulcer disease is not particularly
dangerous. It was also eminently treatable in the 1980s
even without antibiotics and prior to any knowledge of H.
pylori-a point that belies any argument that a delay
in accepting the bacterial hypothesis caused widespread,
The relatively indolent nature of presumptive H. pylori
disease led some investigators to attempt to demonstrate
cause by the most direct of means. In the 1985 article "Attempt
to fulfill Koch's postulates for pyloric Campylobacter,"
Marshall and colleagues reported that a normal volunteer
had swallowed a pure culture of the organism. The result
was " . . . a mild illness . . . which lasted fourteen days.
Histologically proven gastritis was present on the tenth
day after the ingestion of bacteria, but this had largely
resolved by the fourteenth day. The syndrome of acute pyloric
campylobacter gastritis is described" (Marshall et al. 1985).
This constituted highly suggestive evidence that the organism
caused gastritis. But it was far from conclusive, because
it involved a single subject and was reported by the very
author most wedded to the hypothesis. Thus, replication
by others would have been required. Perhaps more important
was that the subject, who was none other than Marshall himself,
failed to develop an ulcer. Note also that the disease resolved
As unlikely as it may seem, such a human demonstration
was twice repeated with similar results. As late as 1995,
Marshall himself reviewed these studies and conceded that
Koch's postulates, still the "gold standard" for demonstrating
a microbial cause of a disease, had not been fulfilled for
H. pylori and peptic-ulcer disease (Marshall 1995).
Persuasive Evidence for Etiology and Treatment
What ultimately convinced the medical world was not this
sort of experiment but one that took advantage of the existence
of effective antibacterial agents. To introduce the history
of this effort, it is necessary to consider the setting
in which it was done. As mentioned, there were already highly
effective treatments for PUD by the early 1980s. The rate
of complete healing of endoscopy-proven duodenal ulcers,
after several weeks of treatment with potent inhibitors
of acid production, is about 95 percent (Straus 1996). Symptomatic
relief occurs within a couple of weeks (McFarland et al.
1990). Such treatment, moreover, is remarkably safe and
free of side effects. The same cannot be said for metronidazole,
the first widely used antibiotic for H. pylori.
This and other proposed antibiotic treatments for H.
pylori have unquestioned side effects, some of which
mimic the symptoms of the very disease for which they are
prescribed. These can pose significant disincentives for
patients who would like to feel better. The selection of
strains of H. pylori that are resistant to antibiotics,
moreover, was reported in the very first large trial of
their use. Does any of this sound promising for such a treatment?
I'm playing the devil's advocate. I am a firm believer
in the H. pylori hypothesis, and if I had a duodenal
ulcer, I would take metronidazole in a heartbeat. This was
far from obvious throughout the 1980s, however, not because
of dogmatic rejection, but for legitimate scientific and
medical reasons. To summarize: Even by the end of the decade,
it was not clear either that H. pylori caused PUD
or, if it did, that specific antibacterial treatment would
be preferable to existing treatments.
What finally convinced doubters of both cause and treatment
was something that by its very nature took several years
to establish. The initial treatment of peptic-ulcer disease
was not the problem. The problem was relapse. In
patients whose ulcers have completely healed after treatment
with acid-suppression only, 50-95 percent will recur within
two years, although the percentage is much lower if acid
suppression is continued indefinitely (Gough et al. 1984).
We now know that if temporary acid suppression is coupled
with eradication of H. pylori, the recurrence rate
drops to 5-10 percent.
But consider the time required to complete a trial that
could establish this fact. The trial alone requires following
about 100 patients for many months (twelve to twenty-four,
typically), because ulcer recurrence is the issue. Patient
accrual in any clinical trial is not instantaneous but usually
occurs over several months or more, and the trial is not
complete until the last patient entered has been followed
for the planned period. This time is in addition to the
usual time required for planning, applying for and receiving
grant money, applying for and obtaining human-studies approval,
overcoming unforeseen technical obstacles, writing the paper,
waiting for a response after submitting it to a journal,
revising it based on reviewers' recommendations, revising
it again based on copy editors' recommendations, and waiting
for ultimate publication. Thus, the least amount of time
for such a project to proceed from inception to publication
is about four years.
The first trial that was both large enough and rigorous
enough to be noticed was conceived by Marshall and Warren
in 1984 and published in Lancet at the very end
of 1988 (Marshall et al. 1988). It had followed 100 patients
for twelve months. The authors reported that the recurrence
rate of duodenal ulcer was much lower in patients whose
H. pylori were eradicated than in those whose bacteria
were not, but there were problems. Such eradication occurred
only when the antibiotic tinidazole was combined with bismuth.
When tinidazole was given alone, resistant H. pylori
strains invariably thrived. The authors also reported more
unpleasant side effects, including diarrhea, in the groups
that took the antibiotic. Thus the results were highly suggestive
that eradicating H. pylori could prevent ulcer
recurrence, but somewhat less suggestive that this could
be done effectively in the long run with minimal side effects.
Since the authors were the original proponents of the bacterial
hypothesis, moreover, any firm conclusions would first require
confirmation by others. This was not ostracism; it was appropriate
By early 1992, at least three more studies had been published
that, in the aggregate, convinced the academic medical world
of the causative nature of H. pylori in PUD. The
trial portion of the last and most influential of these
was already underway by September 1988, well before Marshall
and Warren's paper was published-further demonstrating the
commitment of medical scientists to investigate the hypothesis.
This study followed 109 patients for two years, using a
triple-antibacterial regimen that was far more effective
than that reported by Marshall and Warren. It found, unequivocally,
that the recurrence rate of both gastric and duodenal ulcer
was far lower in patients whose H. pylori had been
eradicated. Antibiotic resistance was not apparent because
of the triple-drug regimen, and side effects were tolerable
(Graham et al. 1992).
This study, according to Lawrence S. Friedman, chair of
the American Board of Internal Medicine Subspecialty Board
on Gastroenterology, opened the floodgates in the United
States. "After that everyone accepted the causative role
of H. pylori, and everyone, at least among gastroenterologists,
treated PUD with antibacterials." According to Dr. Friedman,
this was done for duodenal ulcer [DU] even in the absence
of specific proof that the patient harbored the organism:
"Early on (early 1990s) all patients with duodenal ulcer
were assumed to have H. pylori; the presence of
a DU was justification for treatment of HP, though in practice
many physicians still tested for the organism (at endoscopy
and to some extent by serology)" (Lawrence Friedman, personal
In case there were still pockets of resistance to the H.
pylori argument, the National Institutes of Health
(NIH) convened a Consensus Conference in February 1994.
Marshall was a member of the planning committee. The proceedings
were published the following July in the Journal of
the American Medical Association (NIH Consensus Conference
1994). The report strongly supported the causative role
of H. pylori in peptic ulcer disease, and unequivocally
recommended triple antibacterial treatment for patients
with ulcers and H. pylori. It also enthusiastically
supported further research on the organism and its potential
role in cancer of the stomach.
How to Explain the Myth?
That, then, is the history of the H. pylori hypothesis
and its acceptance by the medical mainstream. Its journey
from proposal to acceptance was quite ordinary. The first
reports were surprising but intriguing and entirely plausible.
The potential implications didn't require a "new paradigm,"
just a little work. Other investigators quickly jumped on
the research bandwagon, and in a matter of a few years,
the basic story and its therapeutic ramifications were established.
The profession, as represented by its literature and institutions,
readily accepted it. The entire process took about eight
years-ten, if one insists on including the NIH coming-out
party (I don't), but not the thirteen that has been claimed.
This amount of time was entirely appropriate, given the
nature of the task.
So why the myth? I don't know how it started, but there
are a couple of clues. Dr. Gerritsen refers to the Centers
for Disease Control and Prevention (CDC) "putting out the
word" in 1997. Is it possible that she is remembering the
NIH Consensus Conference but got the date wrong? Probably
not, because the CDC is not the NIH, and the CDC did publish
a report on the topic in 1997. The word that it put out,
however, was not "to the nation's doctors that . . . Helicobacter
pylori was, indeed, the cause of most cases of peptic
ulcer disease." On the contrary, it reported that national
surveys in 1994 and 1996 had found that 90 percent of primary-care
physicians and gastroenterologists in the U.S. already "identified
H. pylori as the primary cause of PUD." The actual
point of the article was to show that "only 27 percent of
the general public [emphasis added] is aware of
the association between H. pylori infection and
PUD" (CDC 1997). Ironically, 60 percent of the general public
still thought that the cause was "stress," a vague, whimsical,
and mildly insulting "mind-body" hypothesis that medicine
hadn't taken seriously for at least a generation.
To be fair, I will add that the CDC report also mentioned
that although most physicians were aware of the H. pylori
association, many of them (50 percent of primary care
docs and 30 percent of gastroenterologists) were still not
testing for H. pylori in patients with first-time
ulcer symptoms. Rather, they were simply treating these
patients with acid-suppressors. Ulcer symptoms, however,
do not ulcers make. Such symptoms are frequently vague and
nonspecific to ulcers per se and are similar to
the far-more-common symptom complex known as "dyspepsia."
Since the NIH consensus panel had specifically recommended
not treating H. pylori in patients with dyspepsia
but no ulcer, even when H. pylori was known to
be present, it could be argued that these physicians were
merely practicing cost-effective medicine: treating first-timers
with a safe and inexpensive agent known to both heal ulcers
and relieve symptoms promptly in the vast majority of cases
while reserving the more invasive and expensive tasks of
diagnosing both ulcer and H. pylori only for patients
whose symptoms recurred after treatment was complete. While
this does not refute my thesis, it may explain Dr. Gerritsen's
memory of the report.
A bit of digging reveals that Marshall himself has had
a hand in nurturing, if not creating, the myth. I tried
to contact him to comment for this article, but he has not
replied. Most of what I can glean from his Web page makes
me think that he and I agree on important issues. For example,
he lists Quackwatch, the most useful "CAM" information site
on the Web, as one of his favored links (Barry Marshall
2004). (Disclosure: I have several pieces on Quackwatch
and collaborate with its creator, Dr. Stephen Barrett, as
co-host of the subsidiary NaturoWatch.) Marshall also links
to a great debunking of "stress," which I hadn't previously
seen (Spencer 2002). And he has, quite evidently, a good
sense of humor.
Nevertheless, there seems to be a bit of the self-promoter
about him. I say this good-naturedly and with an affectionate
nudge, imagining that someday we may meet and chuckle together.
But also linked to his Web site is a 1997 article in The
Sydney Morning Herald that sets the stage of his humble
Western Australian beginnings on a dirt floor in a mining
town and then bursts with suggestions of eventual Galileo-like
ostracism by the vested interests of the drug industry and
the "conservative world of medicine": "Everyone knew that
bacteria couldn't survive in the stomach's acid environment.
They'd been taught so at medical school" (Sweet 1997).
Huh? Everyone who has taken a microbiology course in the
past few decades is aware that there are bacteria adapted
to conditions far harsher than inside the stomach, including
some that live at near-boiling temperatures and others that
use ether-usually a powerful disinfectant-as a food source.
Everyone who has studied histology and physiology knows
that changes in the body's microenvironment, including acidity,
can be dramatic over very small distances (measured in microns).
The means by which H. pylori withstands the stomach's
acid environment have been largely elucidated. The organism
has a membrane that is particularly impermeable to acid.
The membrane also contains acid-dependent urea channels
that begin to admit urea from the stomach juices when the
pH is a mere 6 (10,000 times less acidic than the normal
stomach pH of 2). The urea is then rapidly transformed to
ammonia via the enzyme urease, which the bacterium produces
in abundance. Because ammonia is a base, this produces a
tiny region of non-acidic space within which the bacterium
dwells (Sachs et al. 2003).
Although these mechanisms were not known at the time that
H. pylori was discovered, the plausibility of such
mechanisms existing was never an issue. To argue otherwise
is to conjure a "straw man." After all, similar organisms
had already been described in the equally acidic stomachs
of other mammals. The only questions that investigators
in 1983 asked were: Are the bacteria really there, and if
so, what do they do?
Marshall, who was interviewed for the Morning Herald
article, offers no clarification when the reporter
writes, "Marshall took at least a decade longer than he
expected to persuade colleagues that ulcer patients with
H. pylori should be treated with antibiotics" (Sweet
1997). That may be, but it wasn't because of ostracism.
Marshall had previously written, in a technical monograph,
"In my na´vetÚ I expected H. pylori to be immediately
accepted as the cause of duodenal ulcer," [but] "the presence
of H. pylori in many apparently healthy persons
has made its pathogenic role harder to understand and has
delayed wide acceptance of the new bacterium as an important
pathogen" (Marshall 1991).
Another link from Marshall's Web site is to a radio interview
in which he and others discuss the history of H. pylori,
particularly with regard to its several near-discoveries
prior to Warren's finding in 1979 (four years before the
letters in the Lancet). In that interview is this
telling exchange among three people: Sharon Carleton (the
moderator), Irvin Modlin (a gastroenterologist from Yale),
Sharon Carleton: One component you don't mention
is finance, money. How much influence do you think the
drug companies have had in the past in trying to keep
the truth at bay, or was it really primarily the medical
Irvin Modlin: I think those two components are
almost inseparable; there's little doubt in my mind that
in a world where ulcers had been declared to be acid-related,
corporations that were involved in the manufacture of
acid-suppressive agents didn't want to even conceive that
there would be any other possibility for the pathogenesis
of peptic ulceration. And of course, many of the people
who were in a position to evaluate any other possibilities
were heavily indebted to corporate support for their own
research work and were, I think, not necessarily overtly
but in a sort of covert or subtle way influenced to almost
look the other way.
Sharon Carleton: In his own chapter in the book,
Barry Marshall asks rhetorically, was there a conspiracy
to keep the H. pylori story under wraps? His
answer-yes. But this was fired more by inertia and bad
advice than by the drug companies' malice.
Barry Marshall: Well, you have to take pity
on them because one particular company who's now in the
H. pylori business with everybody else was Glaxo,
and after the helicobacter meeting that we had in Chicago
one year, their stock dropped from $20 down to $18 which
represented about a billion dollars off the value of their
company (ABC Science 2003).
What's missing from this pharmaceutical conspiracy theory
is evidence that drug companies were successful in suppressing
H. pylori research, even if this was their intent.
The effectiveness of the "covert or subtle" means suggested
by Dr. Modlin is simply not supported by the historical
record, a fact that Dr. Marshall appears to have acknowledged.
But it seems that even as Marshall equivocates when his
champions trumpet conspiracy theories, he coyly encourages
them. And yet, to paraphrase Galileo, medical science does
move. It is my hope that Marshall the Quackwatch fan will
read this article and recognize that his nurturing of the
myth has given unintended succor to quackery.
Thus, the basis for the challenge remains untainted. The
legend of H. pylori and peptic ulcer disease was
a good try, because it is so widely believed, but it fails
to stand up to scrutiny. In this case, as in modern medicine
in general, progress resulted from the vigorous investigation
of a plausible hypothesis-even if there was early skepticism
and even if certain "vested interests" may have preferred
otherwise. That said, I respectfully urge any remaining
doubters to conduct their own research prior to submitting
further nominees for exceptions to this rule.
An interesting article appeared in New Scientist a
couple of years ago. It turns out that H. pylori lives
in "around half the world's population" and "in parts of
the developing world as many as 90 percent of the population
carries the bug," but "only a fraction of these people ever
get sick" (Hamilton 2001). Thus it may be a commensal after
all. Of more concern is that it may protect against esophageal
cancer, a disease that is recently on the rise even as rates
of H. pylori carriage are falling. The question
of whether it is wise to eradicate H. pylori thus
remains open. Such is the nature of science: to march on.
To Marshall's credit, I found the article linked from his
own H. pylori laboratory Web site (Helicobacter
pylori Research Laboratory 2004).
I am indebted to Ed Leadbetter, Professor of Molecular
and Cell Biology at the University of Connecticut. As a
student in his microbiology course at Amherst College in
1973, I learned to expect the marvelous adaptive mechanisms
to be found among the prokaryotes.
Kimball C. Atwood IV, M.D., is an anesthesiologist at the
Newton-Wellesley Hospital in Newton, Massachusetts. He is
Assistant Clinical Professor at the Tufts University School
of Medicine and Associate Editor of The Scientific Review
of Alternative Medicine. E-mail: email@example.com.