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Larry Altman reports on closed minds in medicine and science

Larry Altman, the New York Times senior medical correspondent, has followed the saga of the two Australians who fathomed the real cause of ulcers since 1984, when he interviewed “American medical leaders about the Australian findings”. He recalls in an article this morning (Tues Oct 11) how some of those leaders dismissed the news then as unimportant “because a bacterial cause of ulcers had not been discussed at recent national scientific meetings”.

In The Doctor’s World column, “Nobel Came After Years of Battling the System”, Larry catches up the rest of the press in commenting on the total vindication of the two ulcer heretics after their long battle against entrenched thinking in their field.

The article is a good analysis of why their contribution was scorned for so long, which mentions several fresh reasons that show how much there is to the issue, although it overlooks some reasons why some object even today to the theory, such as the bacteria occur to such a high extent in the general population that they seem neither necessary nor sufficient for ulcers.

All those who naturally wonder how the global science of HIV/AIDS can possibly be misguided when nearly all the world’s authorities endorse it, and powerfully oppose any review, should study this piece, though. It gives all the reasons why the seemingly outlandish (to those not in the know) claim of the fallibility of global AIDS consensus can not be dismissed a priori, simply because the paradigm is so widely endorsed.

All the factors created a type of rigidity that many doctors say still exists for better or worse.

Altman’s thorough understanding of medical myopia makes it all the more mysterious why he has gone along so easily and so faithfully with the current HIV paradigm in AIDS, especially when he has written articles on some of the more outlandish aspects of a theoretical scheme which makes little sense according to standard medical ideas and practice.

Many put it down to Altman suffering from many of the same social and psychological effects mentioned in his piece, since he is a graduate of the unpublicised CDC training course for journalists and others who need to be briefed on the field of epidemiological medicine and its politics.

Among the important reasons he collects to account for the uphill fight waged for what in retrospect looks like a pretty clear avenue of discovery and adoption, apart from the resistance of his profession to enlightenment, are these:

*Profit: A medical-industrial complex was entrenched in the belief that psychological stress was the cause. Doctors had vested interests in treating ulcers and other stomach disorders, and drug companies had come up with Tagamet, which blocked production of gastric acid and was becoming the first drug with $1 billion annual sales. Ulcers often recurred, requiring repeated courses of the drugs, providing a steady stream of profits. Ulcer surgery was lucrative for surgeons who removed large portions of the stomach from patients with life-threatening bleeding and chronic symptoms. Psychiatrists and psychologists treated ulcer patients for stress.

*Theory and mental framework: The concept of curing ulcers with antibiotics seemed preposterous to doctors who had long been taught that the stomach was sterile and that no microbes could grow in the corrosive gastric juices. A bacterial cause “was just too wild a theory for most people” to accept, and something so ingrained as stress causing ulcers was too difficult to dismiss. Blame focused on psychological stress in part because many patients had stressful lives and scientists lacked another explanation.

*Practical evidence: Tagamet and similar drugs, known as H2 blockers, safely made ulcers and their symptoms disappear.

*Funding bias: The makers of H2 blockers funded much of the ulcer research at the time, and they ignored the discovery.

*Political strategy: All the drug companies had to do was ignore the Helicobacter discovery. “The fact that the big drug companies who were supporting the journal articles ignored H. pylori was far more effective than actually saying that a bacterial cause was not true because if they had said it was false, or not important, they would have created a controversy and maybe media interest.”

“If the drug companies were truly into discovery, they would have gone straight after the Helicobacter,” Dr. Marshall said, but they did not because of the success with H2 blockers. “Had these drugs not existed, the drug companies would have jumped on our findings,” he added.

*Not invented here: the fresh thinking was coming from what many doctors regarded as a medical outpost, Perth.

*Closed minds: All the factors created a type of rigidity that many doctors say still exists for better or worse. There was skepticism from colleagues who mostly did not want to know, or believe, what Dr Warren was describing. “Anyone could see the bacteria through a microscope, but the clinicians did not want to see them.” Skeptics asked Why was he the only one seeing the bacteria? Why had others not described them earlier? and Dr Warren did not know the answer. “Once I started looking for them, they were obvious,” he said, “but convincing other people was another matter.”

*Counterarguments and difficulty of proof: Even doctors who peered down the barrel of a microscope and did agree bacteria were present said they must be opportunists, not the cause of stomach ailments. Dr. Warren pointed out that the bacteria were all the same, not the variety that would be expected of secondary invaders. But, he said, “It was hard for me to prove them wrong.”

*Ignoring the literature: Dr. Marshall painstakingly searched for papers published decades earlier than those listed in the United States National Library of Medicine’s electronic data base that starts about 1965. Although a few doctors had described the curved bacteria in the late 19th century, the findings were passed over in the hundreds of peer-reviewed articles published thereafter.

*General caution about novelty: “In the 1970’s and 1980’s there was a bit of a mind-set that all the important stuff in medicine had been discovered”…. “The medical world wanted convincing proof and there was a lot of urgency to publish data” but many American researchers, Marshall said, “seemed more interested in carefully studying the mechanism of how H. pylori produced stomach damage rather than driving straight in to treat people”….. “The medical profession is brought up to be very careful with new findings, and that is probably a good thing for most patients because you have to be fairly careful with new findings or otherwise you may do something stupid.” Experience has taught that rushing to use a new therapy without the backing of findings from controlled trials can have serious, if not lethal, outcomes. One example was that freezing the stomach cured ulcers, when it sometimes resulted in dead tissue.

*Need to retain authority: It can be hard for doctors, like others, to admit error. Sometimes the caution is excessive and it, too, can cost lives.

*Infatuation with current idea: Dr. Alfred Sommer, the former dean of the Johns Hopkins Bloomberg School of Public Health, recalled how medical leaders in the 1980’s rejected evidence that inexpensive vitamin A pills could prevent death from infections as well as blindness. Now it is standard therapy. Dr. Samuel Hellman, a former dean of the University of Chicago’s Pritzker School of Medicine, said that doctors “often fall in love with a hypothesis, and that holds in my field, cancer.” Medicine’s peer-review system for deciding what articles to publish and which grants taxpayers should support “discriminate against the truly inventive, exciting, far-out ideas,” Dr. Hellman said. Peer review “tends to adhere to things that are consistent with prevailing beliefs and models,” he said, and “really new ideas usually just get thought of as crazy.

So why did the two Australians prevail after ten or fifteen years, when the dissidents in HIV?AIDS, for example, have not in twenty?

*Persuasive demonstration: Dr. Marshall performed a famous self-experiment in which he swallowed a culture of H. pylori, got sick, documented that he developed an inflamed stomach and was cured of the gastritis with an antibiotic.

*Reading earlier literature: Dr. Marshall painstakingly searched for papers published decades earlier than those listed in the United States National Library of Medicine’s electronic data base that starts about 1965. Although a few doctors had described the curved bacteria in the late 19th century, the findings were passed over in the hundreds of peer-reviewed articles published thereafter.

The article mentions two suggested solutions to such difficulties:

*Funding should be assigned to novelty: Medicine’s peer-review system for deciding what articles to publish and which grants taxpayers should support not “discriminate against the truly inventive, exciting, far-out ideas, Dr. Hellman said.

The National Institutes of Health, a federal agency, supports biomedical research at its campus in Bethesda, Md., and in medical schools and centers throughout the country and abroad. But, Dr. Hellman said, “innovation does not get funded at the N.I.H. right now because it can pay for only a very low percentage of approved grants.”

*Open minds: Helicobacter has opened people’s minds to the possibility of an infectious cause of all those other diseases whose cause is unknown.”

Needless to say anyone who studies the HIV?AIDS situation finds many of the same negative factors at work in spades:

*Profits are high for the drug companies involved, and some of the money is distributed to doctors and even to activist orgnaizations.

*The theory and mental framework has become as rigid and entrenched, both medically and politically correct and any review treated with hostility.

*Practical evidence: The practical evidence is freely available but the interpretation is political and escapes peer review, and within the scientific literature the theory has been rejected without refutation but the rejection ignored.

*Funding bias: There have been no funds for reexamining the standard theory of HIV?AIDS since the federal level press conference announcing HIV as the culprit before the science was published, let alone confirmed.

*Political strategy: The politics of HIV?AIDS has been very similar in that the strategy of dispensing with review and dissent by ignoring it has been very successful.

Is it too much to hope that Altman, who notes that “all these factors created a type of rigidity that many doctors say still exists for better or worse” might be prompted to review his own reporting on AIDS in this light?

(show)

The New York Times

October 11, 2005

Nobel Came After Years of Battling the System

By LAWRENCE K. ALTMAN, M.D.

When two Australian scientists set out in the early 1980’s to prove that a bacterium, Helicobacter pylori, caused stomach inflammation and ulcers, they met opposition from a medical-industrial complex entrenched in the belief that psychological stress was the cause.

Opposition to their radical thesis came from doctors with vested interests in treating ulcers and other stomach disorders as well as from drug companies that had come up with Tagamet, which blocked production of gastric acid and was becoming the first drug with $1 billion annual sales.

Ulcer surgery was lucrative for surgeons who removed large portions of the stomach from patients with life-threatening bleeding and chronic symptoms. Psychiatrists and psychologists treated ulcer patients for stress.

The concept of curing ulcers with antibiotics seemed preposterous to doctors who had long been taught that the stomach was sterile and that no microbes could grow in the corrosive gastric juices.

A bacterial cause “was just too wild a theory for most people” to accept, and something so ingrained as stress causing ulcers was too difficult to dismiss, Dr. J. Robin Warren, one of two who won the 2005 Nobel Prize for Physiology or Medicine on Oct. 3, said in a telephone interview.

Blame focused on psychological stress in part because many patients had stressful lives and scientists lacked another explanation.

Also, Tagamet and similar drugs, known as H2 blockers, safely made ulcers and their symptoms disappear. But the H2 blockers were not one-shot cures. Ulcers often recurred, requiring repeated courses of the drugs, providing a steady stream of profits.

“The opposition we got from the drug industry was basically inertia,” said Dr. Barry J. Marshall of the University of Western Australia, the other Nobel winner, and “because the makers of H2 blockers funded much of the ulcer research at the time, all they had to do was ignore the Helicobacter discovery.”

“If the drug companies were truly into discovery, they would have gone straight after the Helicobacter,” Dr. Marshall said, but they did not because of the success with H2 blockers.

“Had these drugs not existed, the drug companies would have jumped on our findings,” he added.

Then, too, the fresh thinking was coming from what many doctors regarded as a medical outpost, Perth.

All the factors created a type of rigidity that many doctors say still exists for better or worse.

Further, Dr. Marshall said, “The fact that the big drug companies who were supporting the journal articles ignored H. pylori was far more effective than actually saying that a bacterial cause was not true because if they had said it was false, or not important, they would have created a controversy and maybe media interest.”

Right from the moment in 1979 when Dr. Warren, a pathologist, first saw bacteria in stomach biopsies at the Royal Perth Hospital, he said: “I met skepticism from my colleagues who mostly did not want to know, or believe, what I was describing. Anyone could see the bacteria through a microscope, but the clinicians did not want to see them.”

Why was he the only one seeing the bacteria? Why had others not described them earlier? He did not know, Dr. Warren said in answer to the skeptics who asked. “Once I started looking for them, they were obvious,” he said, “but convincing other people was another matter.”

Even doctors who peered down the barrel of a microscope and did agree bacteria were present said they must be opportunists, not the cause of stomach ailments.

Dr. Warren pointed out that the bacteria were all the same, not the variety that would be expected of secondary invaders. But, he said, “It was hard for me to prove them wrong.”

Proof took years.

Early support came from Dr. Marshall’s efforts in the library and laboratory. Aided by a librarian in Perth, Dr. Marshall painstakingly searched for papers published decades earlier than those listed in the United States National Library of Medicine’s electronic data base that starts about 1965.

Although a few doctors had described the curved bacteria in the late 19th century, the findings were passed over in the hundreds of peer-reviewed articles published thereafter. Then Dr. Marshall performed a famous self-experiment in which he swallowed a culture of H. pylori, got sick, documented that he developed an inflamed stomach and was cured of the gastritis with an antibiotic.

Many critics took notice of the bacterium’s dangers, Dr. Warren said.

As a practicing gastroenterologist, Dr. Marshall saw many patients go to surgery for ulcers and some die from internal bleeding.

His top priority was to determine which combinations of antibiotics cured ulcers. “There was a lot of urgency to publish data because” the medical world wanted convincing proof, Dr. Marshall said.

But many American researchers, he said, “seemed more interested in carefully studying the mechanism of how H. pylori produced stomach damage rather than driving straight in to treat people.”

There were many reasons for the different tacks.

Dr. Warren said that “the medical profession is brought up to be very careful with new findings, and that is probably a good thing for most patients because you have to be fairly careful with new findings or otherwise you may do something stupid.”

A cardinal rule of medicine is: First, do no harm. Experience has taught that rushing to use a new therapy without the backing of findings from controlled trials can have serious, if not lethal, outcomes. One example was that freezing the stomach cured ulcers, when it sometimes resulted in dead tissue.

It can be hard for doctors, like others, to admit error. Sometimes the caution is excessive and it, too, can cost lives.

Dr. Alfred Sommer, the former dean of the Johns Hopkins Bloomberg School of Public Health, recalled how medical leaders in the 1980’s rejected evidence that inexpensive vitamin A pills could prevent death from infections as well as blindness.

Now it is standard therapy.

Dr. Samuel Hellman, a former dean of the University of Chicago’s Pritzker School of Medicine, said that doctors “often fall in love with a hypothesis, and that holds in my field, cancer.”

Medicine’s peer-review system for deciding what articles to publish and which grants taxpayers should support “discriminate against the truly inventive, exciting, far-out ideas, Dr. Hellman said.

Peer review “tends to adhere to things that are consistent with prevailing beliefs and models,” he said, and “really new ideas usually just get thought of as crazy.”

The National Institutes of Health, a federal agency, supports biomedical research at its campus in Bethesda, Md., and in medical schools and centers throughout the country and abroad. But, Dr. Hellman said, “innovation does not get funded at the N.I.H. right now because it can pay for only a very low percentage of approved grants.”

When this reporter interviewed American medical leaders about the Australian findings in 1984, some dismissed them as unimportant because a bacterial cause of ulcers had not been discussed at recent national scientific meetings.

Reflecting on his road to the Nobel Prize, Dr. Marshall said: “In the 1970’s and 1980’s there was a bit of a mind-set that all the important stuff in medicine had been discovered.

“So maybe we started something that was more important than we thought because Helicobacter has opened people’s minds to the possibility of an infectious cause of all those other diseases whose cause is unknown.”

2 Responses to “Larry Altman reports on closed minds in medicine and science”

  1. Robert Houston Says:

    This analysis of resistance in science, which Truthseeker has presented so well in examining Dr. Altman’s article, reminds one of an extraordinary paper by a distinguished critic of science. I wonder if Truthseeker or Altman may have read it; anyone interested in the subject or in AIDS really should do so. It’s called “The Scorn of Heretics” (Click HERE to see it.)As Truthseeker notes, the same factors are operative in the field of “HIV?AIDS” (great new term!), and one of them was a factor called “Not Invented Here” (NIH). Altman wrote, “Then, too, the fresh thinking was coming from what many doctors regarded as a medical outpost, Perth.” Indeed, the two new Nobel laureates are affiliated with the University of Western Australia (Dr. Barry Marshall) and its teaching hospital, the Royal Perth Hospital (Dr. Robin Warren), where they developed their ulcer theory in the early 1980s. Outside of Berkeley, the main international locus of scientific dissent on AIDS is the Perth Group, also centered at the Royal Perth Hospital, where its leaders, Eleni Papadopulos, Ph.D. and Valendar Turner, M.D. are based. If the dawn of enlightenment ever illumines the benighted science of AIDS, then Dr. Papadopulos and her colleagues should be recognized as early pioneers in demolishing the fallacious HIV theory. Her first paper on the subject, Reappraisal of AIDS, was written in 1986, rejected twice by Nature, but finally published in Medical Hypotheses (25:151-162, 1988), a year after Dr. Peter Duesberg’s first AIDS paper. In it, she identified abuse of recreational drugs, expecially nitrites, as a cause of AIDS a year before Duesberg first did so in his 1989 Proceedings paper. Should they share the Nobel prize?

  2. Robert Houston Says:

    Though based in Perth, Australia, the Perth Group also includes medical scientists in the USA, Austria, and South Africa. Their latest broadside against the HIV fallacy is “A critique of the Montagnier evidence for the HIV/AIDS hypothesis,” which appeared in Medical Hypotheses 63(4):597-601, 2004. (Click HERE to read it.)

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Larry Altman reports on closed minds in medicine and science

Larry Altman, the New York Times senior medical correspondent, has followed the saga of the two Australians who fathomed the real cause of ulcers since 1984, when he interviewed “American medical leaders about the Australian findings”. He recalls in an article this morning (Tues Oct 11) how some of those leaders dismissed the news then as unimportant “because a bacterial cause of ulcers had not been discussed at recent national scientific meetings”.

In The Doctor’s World column, “Nobel Came After Years of Battling the System”, Larry catches up the rest of the press in commenting on the total vindication of the two ulcer heretics after their long battle against entrenched thinking in their field.

The article is a good analysis of why their contribution was scorned for so long, which mentions several fresh reasons that show how much there is to the issue, although it overlooks some reasons why some object even today to the theory, such as the bacteria occur to such a high extent in the general population that they seem neither necessary nor sufficient for ulcers.

All those who naturally wonder how the global science of HIV/AIDS can possibly be misguided when nearly all the world’s authorities endorse it, and powerfully oppose any review, should study this piece, though. It gives all the reasons why the seemingly outlandish (to those not in the know) claim of the fallibility of global AIDS consensus can not be dismissed a priori, simply because the paradigm is so widely endorsed.

All the factors created a type of rigidity that many doctors say still exists for better or worse.

Altman’s thorough understanding of medical myopia makes it all the more mysterious why he has gone along so easily and so faithfully with the current HIV paradigm in AIDS, especially when he has written articles on some of the more outlandish aspects of a theoretical scheme which makes little sense according to standard medical ideas and practice.

Many put it down to Altman suffering from many of the same social and psychological effects mentioned in his piece, since he is a graduate of the unpublicised CDC training course for journalists and others who need to be briefed on the field of epidemiological medicine and its politics.

Among the important reasons he collects to account for the uphill fight waged for what in retrospect looks like a pretty clear avenue of discovery and adoption, apart from the resistance of his profession to enlightenment, are these:

*Profit: A medical-industrial complex was entrenched in the belief that psychological stress was the cause. Doctors had vested interests in treating ulcers and other stomach disorders, and drug companies had come up with Tagamet, which blocked production of gastric acid and was becoming the first drug with $1 billion annual sales. Ulcers often recurred, requiring repeated courses of the drugs, providing a steady stream of profits. Ulcer surgery was lucrative for surgeons who removed large portions of the stomach from patients with life-threatening bleeding and chronic symptoms. Psychiatrists and psychologists treated ulcer patients for stress.

*Theory and mental framework: The concept of curing ulcers with antibiotics seemed preposterous to doctors who had long been taught that the stomach was sterile and that no microbes could grow in the corrosive gastric juices. A bacterial cause “was just too wild a theory for most people” to accept, and something so ingrained as stress causing ulcers was too difficult to dismiss. Blame focused on psychological stress in part because many patients had stressful lives and scientists lacked another explanation.

*Practical evidence: Tagamet and similar drugs, known as H2 blockers, safely made ulcers and their symptoms disappear.

*Funding bias: The makers of H2 blockers funded much of the ulcer research at the time, and they ignored the discovery.

*Political strategy: All the drug companies had to do was ignore the Helicobacter discovery. “The fact that the big drug companies who were supporting the journal articles ignored H. pylori was far more effective than actually saying that a bacterial cause was not true because if they had said it was false, or not important, they would have created a controversy and maybe media interest.”

“If the drug companies were truly into discovery, they would have gone straight after the Helicobacter,” Dr. Marshall said, but they did not because of the success with H2 blockers. “Had these drugs not existed, the drug companies would have jumped on our findings,” he added.

*Not invented here: the fresh thinking was coming from what many doctors regarded as a medical outpost, Perth.

*Closed minds: All the factors created a type of rigidity that many doctors say still exists for better or worse. There was skepticism from colleagues who mostly did not want to know, or believe, what Dr Warren was describing. “Anyone could see the bacteria through a microscope, but the clinicians did not want to see them.” Skeptics asked Why was he the only one seeing the bacteria? Why had others not described them earlier? and Dr Warren did not know the answer. “Once I started looking for them, they were obvious,” he said, “but convincing other people was another matter.”

*Counterarguments and difficulty of proof: Even doctors who peered down the barrel of a microscope and did agree bacteria were present said they must be opportunists, not the cause of stomach ailments. Dr. Warren pointed out that the bacteria were all the same, not the variety that would be expected of secondary invaders. But, he said, “It was hard for me to prove them wrong.”

*Ignoring the literature: Dr. Marshall painstakingly searched for papers published decades earlier than those listed in the United States National Library of Medicine’s electronic data base that starts about 1965. Although a few doctors had described the curved bacteria in the late 19th century, the findings were passed over in the hundreds of peer-reviewed articles published thereafter.

*General caution about novelty: “In the 1970’s and 1980’s there was a bit of a mind-set that all the important stuff in medicine had been discovered”…. “The medical world wanted convincing proof and there was a lot of urgency to publish data” but many American researchers, Marshall said, “seemed more interested in carefully studying the mechanism of how H. pylori produced stomach damage rather than driving straight in to treat people”….. “The medical profession is brought up to be very careful with new findings, and that is probably a good thing for most patients because you have to be fairly careful with new findings or otherwise you may do something stupid.” Experience has taught that rushing to use a new therapy without the backing of findings from controlled trials can have serious, if not lethal, outcomes. One example was that freezing the stomach cured ulcers, when it sometimes resulted in dead tissue.

*Need to retain authority: It can be hard for doctors, like others, to admit error. Sometimes the caution is excessive and it, too, can cost lives.

*Infatuation with current idea: Dr. Alfred Sommer, the former dean of the Johns Hopkins Bloomberg School of Public Health, recalled how medical leaders in the 1980’s rejected evidence that inexpensive vitamin A pills could prevent death from infections as well as blindness. Now it is standard therapy. Dr. Samuel Hellman, a former dean of the University of Chicago’s Pritzker School of Medicine, said that doctors “often fall in love with a hypothesis, and that holds in my field, cancer.” Medicine’s peer-review system for deciding what articles to publish and which grants taxpayers should support “discriminate against the truly inventive, exciting, far-out ideas,” Dr. Hellman said. Peer review “tends to adhere to things that are consistent with prevailing beliefs and models,” he said, and “really new ideas usually just get thought of as crazy.

So why did the two Australians prevail after ten or fifteen years, when the dissidents in HIV?AIDS, for example, have not in twenty?

*Persuasive demonstration: Dr. Marshall performed a famous self-experiment in which he swallowed a culture of H. pylori, got sick, documented that he developed an inflamed stomach and was cured of the gastritis with an antibiotic.

*Reading earlier literature: Dr. Marshall painstakingly searched for papers published decades earlier than those listed in the United States National Library of Medicine’s electronic data base that starts about 1965. Although a few doctors had described the curved bacteria in the late 19th century, the findings were passed over in the hundreds of peer-reviewed articles published thereafter.

The article mentions two suggested solutions to such difficulties:

*Funding should be assigned to novelty: Medicine’s peer-review system for deciding what articles to publish and which grants taxpayers should support not “discriminate against the truly inventive, exciting, far-out ideas, Dr. Hellman said.

The National Institutes of Health, a federal agency, supports biomedical research at its campus in Bethesda, Md., and in medical schools and centers throughout the country and abroad. But, Dr. Hellman said, “innovation does not get funded at the N.I.H. right now because it can pay for only a very low percentage of approved grants.”

*Open minds: Helicobacter has opened people’s minds to the possibility of an infectious cause of all those other diseases whose cause is unknown.”

Needless to say anyone who studies the HIV?AIDS situation finds many of the same negative factors at work in spades:

*Profits are high for the drug companies involved, and some of the money is distributed to doctors and even to activist orgnaizations.

*The theory and mental framework has become as rigid and entrenched, both medically and politically correct and any review treated with hostility.

*Practical evidence: The practical evidence is freely available but the interpretation is political and escapes peer review, and within the scientific literature the theory has been rejected without refutation but the rejection ignored.

*Funding bias: There have been no funds for reexamining the standard theory of HIV?AIDS since the federal level press conference announcing HIV as the culprit before the science was published, let alone confirmed.

*Political strategy: The politics of HIV?AIDS has been very similar in that the strategy of dispensing with review and dissent by ignoring it has been very successful.

Is it too much to hope that Altman, who notes that “all these factors created a type of rigidity that many doctors say still exists for better or worse” might be prompted to review his own reporting on AIDS in this light?

(show)

The New York Times

October 11, 2005

Nobel Came After Years of Battling the System

By LAWRENCE K. ALTMAN, M.D.

When two Australian scientists set out in the early 1980’s to prove that a bacterium, Helicobacter pylori, caused stomach inflammation and ulcers, they met opposition from a medical-industrial complex entrenched in the belief that psychological stress was the cause.

Opposition to their radical thesis came from doctors with vested interests in treating ulcers and other stomach disorders as well as from drug companies that had come up with Tagamet, which blocked production of gastric acid and was becoming the first drug with $1 billion annual sales.

Ulcer surgery was lucrative for surgeons who removed large portions of the stomach from patients with life-threatening bleeding and chronic symptoms. Psychiatrists and psychologists treated ulcer patients for stress.

The concept of curing ulcers with antibiotics seemed preposterous to doctors who had long been taught that the stomach was sterile and that no microbes could grow in the corrosive gastric juices.

A bacterial cause “was just too wild a theory for most people” to accept, and something so ingrained as stress causing ulcers was too difficult to dismiss, Dr. J. Robin Warren, one of two who won the 2005 Nobel Prize for Physiology or Medicine on Oct. 3, said in a telephone interview.

Blame focused on psychological stress in part because many patients had stressful lives and scientists lacked another explanation.

Also, Tagamet and similar drugs, known as H2 blockers, safely made ulcers and their symptoms disappear. But the H2 blockers were not one-shot cures. Ulcers often recurred, requiring repeated courses of the drugs, providing a steady stream of profits.

“The opposition we got from the drug industry was basically inertia,” said Dr. Barry J. Marshall of the University of Western Australia, the other Nobel winner, and “because the makers of H2 blockers funded much of the ulcer research at the time, all they had to do was ignore the Helicobacter discovery.”

“If the drug companies were truly into discovery, they would have gone straight after the Helicobacter,” Dr. Marshall said, but they did not because of the success with H2 blockers.

“Had these drugs not existed, the drug companies would have jumped on our findings,” he added.

Then, too, the fresh thinking was coming from what many doctors regarded as a medical outpost, Perth.

All the factors created a type of rigidity that many doctors say still exists for better or worse.

Further, Dr. Marshall said, “The fact that the big drug companies who were supporting the journal articles ignored H. pylori was far more effective than actually saying that a bacterial cause was not true because if they had said it was false, or not important, they would have created a controversy and maybe media interest.”

Right from the moment in 1979 when Dr. Warren, a pathologist, first saw bacteria in stomach biopsies at the Royal Perth Hospital, he said: “I met skepticism from my colleagues who mostly did not want to know, or believe, what I was describing. Anyone could see the bacteria through a microscope, but the clinicians did not want to see them.”

Why was he the only one seeing the bacteria? Why had others not described them earlier? He did not know, Dr. Warren said in answer to the skeptics who asked. “Once I started looking for them, they were obvious,” he said, “but convincing other people was another matter.”

Even doctors who peered down the barrel of a microscope and did agree bacteria were present said they must be opportunists, not the cause of stomach ailments.

Dr. Warren pointed out that the bacteria were all the same, not the variety that would be expected of secondary invaders. But, he said, “It was hard for me to prove them wrong.”

Proof took years.

Early support came from Dr. Marshall’s efforts in the library and laboratory. Aided by a librarian in Perth, Dr. Marshall painstakingly searched for papers published decades earlier than those listed in the United States National Library of Medicine’s electronic data base that starts about 1965.

Although a few doctors had described the curved bacteria in the late 19th century, the findings were passed over in the hundreds of peer-reviewed articles published thereafter. Then Dr. Marshall performed a famous self-experiment in which he swallowed a culture of H. pylori, got sick, documented that he developed an inflamed stomach and was cured of the gastritis with an antibiotic.

Many critics took notice of the bacterium’s dangers, Dr. Warren said.

As a practicing gastroenterologist, Dr. Marshall saw many patients go to surgery for ulcers and some die from internal bleeding.

His top priority was to determine which combinations of antibiotics cured ulcers. “There was a lot of urgency to publish data because” the medical world wanted convincing proof, Dr. Marshall said.

But many American researchers, he said, “seemed more interested in carefully studying the mechanism of how H. pylori produced stomach damage rather than driving straight in to treat people.”

There were many reasons for the different tacks.

Dr. Warren said that “the medical profession is brought up to be very careful with new findings, and that is probably a good thing for most patients because you have to be fairly careful with new findings or otherwise you may do something stupid.”

A cardinal rule of medicine is: First, do no harm. Experience has taught that rushing to use a new therapy without the backing of findings from controlled trials can have serious, if not lethal, outcomes. One example was that freezing the stomach cured ulcers, when it sometimes resulted in dead tissue.

It can be hard for doctors, like others, to admit error. Sometimes the caution is excessive and it, too, can cost lives.

Dr. Alfred Sommer, the former dean of the Johns Hopkins Bloomberg School of Public Health, recalled how medical leaders in the 1980’s rejected evidence that inexpensive vitamin A pills could prevent death from infections as well as blindness.

Now it is standard therapy.

Dr. Samuel Hellman, a former dean of the University of Chicago’s Pritzker School of Medicine, said that doctors “often fall in love with a hypothesis, and that holds in my field, cancer.”

Medicine’s peer-review system for deciding what articles to publish and which grants taxpayers should support “discriminate against the truly inventive, exciting, far-out ideas, Dr. Hellman said.

Peer review “tends to adhere to things that are consistent with prevailing beliefs and models,” he said, and “really new ideas usually just get thought of as crazy.”

The National Institutes of Health, a federal agency, supports biomedical research at its campus in Bethesda, Md., and in medical schools and centers throughout the country and abroad. But, Dr. Hellman said, “innovation does not get funded at the N.I.H. right now because it can pay for only a very low percentage of approved grants.”

When this reporter interviewed American medical leaders about the Australian findings in 1984, some dismissed them as unimportant because a bacterial cause of ulcers had not been discussed at recent national scientific meetings.

Reflecting on his road to the Nobel Prize, Dr. Marshall said: “In the 1970’s and 1980’s there was a bit of a mind-set that all the important stuff in medicine had been discovered.

“So maybe we started something that was more important than we thought because Helicobacter has opened people’s minds to the possibility of an infectious cause of all those other diseases whose cause is unknown.”

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