MEDICAL HISTORIES – The final instalment in our short series discusses the evolution of evidence-based medicine.
Like bleeding, doctors' intuition was a central part of medical practice until it was categorically proven not to offer patients the best outcomes. This led to the birth of evidence-based medicine. But it was a painful and protracted birth that tells us much about the nature of medicine and the identity of medical practitioners.
Medical practitioners used the therapy of venesection (bleeding) for centuries. It was a crucial element of the medical armamentarium from the ancient Greeks to the nineteenth century. Surveying images of venesection, like Gilray’s “breathing a vein”, we see how connected it was to the identity of the doctor.
To be a doctor was to bleed patients. As a therapy it was beyond question, so tightly was it bound to medical identity and practice.
Then, from the early 1820s, the French physician Pierre Louis started questioning the dogma of venesection. He used a new method designed to show whether the therapy worked or not – using simple statistics, he compared the clinical outcomes for patients treated with bleeding and those treated without it.
In every single condition he explored, whether it was pneumonia or phthisis (tuberculosis of the lungs), Louis demonstrated that bleeding, that most medical of therapies, was actually harmful to patients. Louis, then, has a claim to the title “father of the clinical trial”. His experiments are the ground zero of what would, in the hands of epidemiologists like Richard Doll (1912-2005), become the randomised controlled trial (RCTs).
It is, perhaps, surprising that Louis’ numerical method took so long to catch on. But the clinical judgement of individual consultants was ingrained in medicine’s culture as strongly as venesection was a few generations back. In certain elite institutions, like the London teaching hospitals, intuition was what one clinician called “the incommunicable knowledge” of the art of medicine. It was valued more highly than the application of science or technology to practice.
Writing towards the end of his life Doll reminisced about this older clinical style:
When I qualified in medicine in 1937, new treatments were almost always introduced on the grounds that in the hands of professor A or in the hands of a consultant at one of the leading teaching hospitals, the results in a small series of patients (seldom more than 50) had been superior to those recorded by professor B (or some other consultant) or by the same investigator previously.
Doll wanted to change this by bringing statistical methods into the clinic. Using rigorous statistical methods, he became one of the first scientists to identify the link between smoking and lung cancer in 1950. He also designed and ran one of first RCTs proper, when, with his long-time collaborator Austin Bradford Hill, he explored the treatment of tuberculosis with the antibiotic streptomycin.
All of the most important features of the RCT featured in this trial. They were the random assignment of patients to the drug group and control groups; the exclusion of unsuitable patients from the trial; bias reduction by masking the identity of the groups to which each patient belonged; and the consideration of ethical issues surrounding the withholding of a potentially effective treatment from patients with a fatal disease.
The trial was an outstanding success, demonstrating this antibiotic could treat the white plague TB. In principal, it provided medicine with a new gold standard of testing therapeutic efficacy, and the foundation upon which a truly scientific biomedicine might be built.
But it took time and several disasters before RCTs became the only recognised means of testing new drugs and bringing them to market. It wasn’t until the 1960s that RCTs became the main means of testing drugs. In the interim lay the spectacular disaster of thalidomide to remind the world of what happens when ad hoc testing is combined with an absence of ethics.
Grunenthal, a German pharmaceutical company, was searching for a synthetic antibiotic. A molecule that had promised much was a dud but appeared to have sedative properties. To test this, the researchers resorted to a jiggle test, comparing the amount a dangling cage swayed when filled with dosed or un-dosed rats. The cage jiggled less with the dosed rats, which, they believed, demonstrated the molecule’s sedative properties.

Thalidomide was brought to market with no adequate testing, and Grunenthal gave German GPs samples to distribute willy-nilly to their patients. The drug was licensed with little or no evidence in many countries including the United Kingdom. Only in the United States did the diligence of Frances Kelsey, then-reviewer for the US Food and Drug Administration (FDA), prevent the licensing of the drug. We are still living with the results.
From the early 1970s, increasing efforts were made to develop a reliable evidence base for medical therapies, bringing science into a clinical setting. Even so, there was considerable resistance from clinicians. As US epidemiologist Alvan Feinstein commented in 1983,
the most vigorous defenders of the clinical art may want not only to resist further attempts at bringing science into clinical medicine, but also to roll back the clock … to an earlier era of clinical practice that relied upon intuition individual judgement rather epidemiological analysis.
It is unsurprising in the face of this resistance that it was not until 1992 that the manifesto for evidence-based medicine announced the emergence of “a new paradigm for medical practice”. This new paradigm combined systematic reviews and meta-analysis to ensure that medical education and therapy were as effective as they could be.
With the widespread adoption of evidence-based medicine, the older clinical style has finally withered away. But rather like venesection, it hung around long past its sell-by date because of its powerful attraction to the identity of clinicians.
This is the final part of Medical Histories – click on the links below to read other articles:
Part One: Hypochondriac disease – in the mind, the guts, or the soul?
Part Two: Spermatorrhoea, the lesser known male version of hysteria
Part Three: Culture and psychiatry: an outline for a neglected history
Part Four: Curing addiction: Twelve Steps or fixing the brain?
Sue Ieraci
Public hospital clinician
There is another related phenomenon here: as medicine has moved away from "trust me" paternalism to using more scientific evidence, our population is concurrently spending more and more on non-science-based therapies.
No longer "trust me, I'm a doctor" - it's now "trust me - science doesn't know everything" and even "trust me, I'm a homeopath - my therapy doesn't have to conform with the laws of science.
Is there some fundamental aspect of humanity that craves simple, directed answers? IF your GP says "I'm not sure what it is - let's watch and see what happens" - do we prefer the certainty and simplicity of "here - take some drops of this. If it doesn't work, we'll try another." ?
Can the author make any comment about why some "therapies" have withstood DESPITE evidence? When everyone else stopped bleeding and injecting bismuth, why did some people continue with their "law of similars" and infinite dilutions, despite the accumulating science around them?
Cat Mack
logged in via Facebook
I think this is a very interesting question however, I also think there is another closely related one, why are patients prepared to go with dubious treatments in the face of contrary evidence? My own view is that this is at least in part due to the nature of medicine. Medicine is really not just about science or even just about curing. It is also about providing meaning and comfort in the face of the unfathomable nature of material existence. I go to my particular GP (despite the fact that she is…
Read moreSue Ieraci
Public hospital clinician
I largely agree with you, Cat. It would be great if all GPs had both the experience and the operational ability to operate in that way.
As you say your GP is often running late (so is mine). The GPs that run late are spending extra time fitting more people in and spending extra time with people who need it. The need to respond to urgent situations and unplanned needs.
If everyone were willing to spend out-of-pocket what they spend on the homeopath, but pay their GP for a long consultation, perhaps they could get the best of both worlds.
If have no problem with the concept of empathy and debriefing as therapeutic encounters. My issue with the non-science-based providers is that they are selling faux "remedies", and they are not standardised in their health training - or even their counselling skills.
Tom Hennessy
Retired
Just because people cannot understand WHY venesection works , doesn't mean it doesn't work.
"Repeated blood withdrawals"
"Resulted in disappearance of hypergycmia, glycosuria, ketonemia, and
ketonuria; disappearance of iron from the liver and pancreas; and restoration of islet beta granules to the control level."
"NTBI (non-transferrin-bound iron ) was commonly present in diabetes: 59% in newly diagnosed diabetes and 92% in advanced diabetes"
Then there is the NIH who tested bloodletting…
Read moreDavid Semmens
logged in via Twitter
Tom,
It is first necessary to establish that something does work before preceding to look at why it works. Louis demonstrated that bleeding was unhelpful in treating a number of diseases for which it was used. That does not mean it is unhelpful in treating all diseases. But, it should be shown to work for those diseases.
Tom Hennessy
Retired
"first necessary to establish that something does work"
Venesection was used for thousands of years and THEN it was stopped therefore being 'grandfathered'. The onus must be upon doctors to prove bloodletting doesn't work , as opposed to proving it does.
David Semmens
logged in via Twitter
You've got the onus of proof the wrong way around. But, the reason that bloodletting has been stopped is that it has not only been shown to be ineffective, but has been shown to be harmful in treating several diseases for which it was used. So, no matter which way you look at the burden of proof, it's all down to the proponents of bloodletting to show its efficacy.
John Zigar
Researcher
Tom, no offence, but I hope you're not a doctor!
Tom Hennessy
Retired
"the reason that bloodletting has been stopped is that it has not only been shown to be ineffective"
Actually , I've already provided the information , three different studies , done by reputable researchers and STILL you deny ?
This is a conversation , remember , and if you WISH to continue in your blind acceptance of what you've learned , you will never UNDERSTAND , just like I pointed out in the first post.
Clear your mind. There is no iron deficiency in the world. You , me , that little…
Read moreTom Hennessy
Retired
"Tom, no offence, but I hope you're not a doctor!"
Actually it wasn't too long ago the cupper was the man to call. Doctors seem to think they 'know' it all but it seems they don't understand a whole lot , it must have to do with the lack of logical thinking .
David Semmens
logged in via Twitter
"it must have to do with the lack of logical thinking"
Pot. Kettle. Black...
"I've already provided the information , three different studies , done by reputable researchers and STILL you deny ?"
You provided a few quotes and the only study you linked to provides no data showing the effectiveness of bloodletting or 'taking iron away'. It is a commentary speculating on the potential utility of reducing iron.
Sue Ieraci
Public hospital clinician
Venesection works for removing excess iron in people who have polycythaemia (usually a congenital inherited condition, such as PRV).
It also has some effect in people with acute congestive cardiac failure, but has long been replaced by much more effective and safer therapies, such as CPAP.
For the rest, Mr Hennessy, "blood letting" is about as effective as homeopathy, but has is more invasive and has more side-effects.
Tom Hennessy
Retired
"bloodletting" is about as effective as homeopathy"
You believe homeopathy doesn't work. So you believe bloodletting doesn't work. It really is a good thing you don't have final say on a whole lot .. isn't it.
"Consecutive blood letting and peginterferon alfa-2a/ribavirin standard treatment compared to peginterferon alfa-2a/ribavirin standard treatment alone for naive patients with hepatitis C virus genotype one and elevated ferritin levels"
Tom Hennessy
Retired
"You provided a few quotes and the only study you linked to provides no data showing the effectiveness of bloodletting or 'taking iron away'"
Quotes , you put in Google and voila. As to data , this is a conversation and if you don't believe I have placed enough information to allow you to find the three studies then I will assume your ability to find any OTHER studies is going to be nonexistent. There isn't a disease which hasn't been linked to increased oxidative stress and iron causes oxidative stress / rust.
Tom Hennessy
Retired
"Polycythaemia and agoraphobia"
Read more"Hemochromatosis and depression "
"Hemochromatosis of tongue"
"Iron reduction therapy by phlebotomy may be useful in other diseases caused by lipid peroxidation and oxidative stress such as
nonalcoholic fatty liver disease,11 diabetes mellitus,8 and obesity"
"Venesection improved the headache substantially in frequency, intensity, and duration of attacks"
"Decreasing prevalence of headache (P =3D 0.02) and migraine (P =3D 0.01) with decreasing haemoglobin…
Tom Hennessy
Retired
"Repeated small bleedings have proved effective in relieving the agonizing tightness of angina pectoris and other symptoms of coronary disease"
Tom Hennessy
Retired
"None of these patients developed hepatocellular carcinoma (HCC)."
http://cancerres.aacrjournals.org/cgi/content/abstract/61/24/8697
Clinical Investigations
Normalization of Elevated Hepatic 8-Hydroxy-2'-Deoxyguanosine Levels in Chronic Hepatitis C Patients by Phlebotomy and Low Iron Diet
Tom Hennessy
Retired
These researchers believe iron reduction may replace statins.
"If it is found that the effect of statins on iron metabolism is a
mechanism of their beneficial action, this consequence of statin use can be clinically replicated by other methods, such as controlled reduction of body iron stores."
http://www.ncbi.nlm.nih.gov/pubmed/23097387
John Zigar
Researcher
Great article, James. Now we need to wait for GPs to get over their paternalism and adopt evidence based medicine in every day practice.
Laurie Willberg
Journalist
Best evidence is a lofty and worthy goal. Unfortunately the downside is clinicians practising "cookbook medicine" based on whatever studies they may happen to read or being subject to practise guidelines set up by a medical association that don't tend to individualize treatment. Human nature being what it is, doctors are going to go with the easiest way out -- cookbook medicine. It's been around for centuries and it's not going to be eradicated by lip service to an "evidence base". What happens when…
Read moreSue Ieraci
Public hospital clinician
Laurie Willberg makes a lot of incorrect assertions. Doctors generally do not resport to "cookbook medicine" - in fact, the proponents of adherence to guidelines are more often commenting about variability than too much consistency.
GPs in particular have to navigate the multitude of individual-system based guidelines and find the best combination or compromise to recommend to their patients.
Drug companies are not "dictating what is taught in medical schools", Laurie Willberg. Thereaputics…
Read morerory robertson
rory robertson is a Friend of The Conversation.
former fattie
Dr Bradley, like others I applaud the long-term shift to evidence-based medicine and science, and encourage the University of Sydney to belatedly introduce it to its "nutrition science" area.
Sue, the "trust me - science doesn't know everything" approach finds favour I guess because of high-profile examples where what should be competent "science" demonstrably is not. And yet instead of correcting the false information, the scientists use it to either inadvertently or deliberately misinform…
Read moreJames Bradley
Lecturer in History of Medicine/Life Science at University of Melbourne
I would be loathed to comment on this particular case, which I don't know enough about. But Ben Goldacre's latest book Bad Pharma, which I've reviewed for the Conversation but hasn't been published yet, goes into forensic detail about the way that the pharmaceutical industry, the regulators, and some academics and doctors, have fatally undermined EBM. Clearly, across the board, there is a need for better systems to ensure that ethical standards of research are maintained. Some would argue that the problem is toothless regulation. Others would argue that it is something that arises out of the nature of our economic system. Goldacre takes the former view, and while I think there is some mileage in this, I am more inclined to the idea that our economic system does not serve us very well and that that might be a good starting place for reform. Obviously, whichever side you take, self-regulation is not an option.
Paul Rogers
Manager
I am an ardent supporter of evidence-base medicine and a harsh critic of shams, scams, corporate self-interest, and plain intransigence in the health sciences. I note your reference to the 1992 introduction of "evidence-based medicine" as a watershed, which is surprising in itself.
I also note you reference to Richard Doll and his work on RCTs (also smoking and lung cancer). Yet Doll, in 1955, also noted the powerful association between asbestos exposure and lung cancer, some of which we now know…
Read moreJames Bradley
Lecturer in History of Medicine/Life Science at University of Melbourne
I think one of the things that really suprised me was how recent the EBM programme was, which is what prompted me to write this piece. That's not to say that EBM wasn't being practised before 1992, just that it wasn't the gold standard. The fact that Archie Cochrane's work appeared revolutionary in the early 1970s and that Alvan Feinstein, who was a major figure in developing clinical method, was equivocal about it, demonstrates the protracted nature of the process. Achieving gold standard status took an enormous amount of time, due in part to the resistance of older cultural ways of practising medicine. I suspect there are still those who mourn the demise of this system.
Laurie Willberg
Journalist
What's the bet that when a patient asks their doctor to supply this "evidence" the response is going to be "trust me I'm a doctor" or looks and antics that mean "how dare you question me"?
rory robertson
rory robertson is a Friend of The Conversation.
former fattie
Sue Leraci, you really got stuck into Laurie Willberg. As a journalist, what a duffer he turned out to be. Lucky you were here to correct him on every point. Sue, everyone seems to have been so busy learning really good stuff in medical science at the University of Sydney when you were there. I assume that the other science streams also were pretty sharp back then. So how come the University of Sydney's highest-profile nutritionist scientists and food-industry service providers were not taught…
Read morePaul Rogers
Manager
Rory, you're getting boring and we aren't listening to you. The sugar data have been elucidated elsewhere and it looks like the Sydney Uni people are on the right track, allowing for some uncertainties in the data.
See Bill Shrapnel's analysis here:
http://scepticalnutritionist.com.au/?p=514
Laurie Willberg
Journalist
Sue Ieraci goes on another of her "because I say so" tirades. Investigative journalism sure beats uninformed/biased opinions from hospital clinicians, like this little gem from the New York Times revealing that even prestigious medical schools like Harvard have been shown to be corrupted by pharma influence. And the people who have been the most scandalized are the medical students! http://www.nytimes.com/2009/03/03/business/03medschool.html?_r=2&emc=eta1&
Read more"The students say they worry that pharmaceutical…
rory robertson
rory robertson is a Friend of The Conversation.
former fattie
Paul Rogers, I'm sorry I have bored you. I had you confused with the other Paul Rogers, the one who earlier claimed to be "an ardent supporter of evidence-base medicine and a harsh critic of shams, scams, corporate self-interest, and plain intransigence in the health sciences". The first Paul wouldn't have stumbled at the first hurdle, Paul 2, being so silly as to promote as reliable the bogus information funded and "framed" by the sugar industry, the same bogus information that your Mr Bill Shrapnel…
Read morePaul Rogers
Manager
Rory, can you repeat that please; I didn't quite get it the first 42 times?
I won't be responding on the sugar issue (although I could) because your false position (and science) on the hazards of sugar have been debunked very well by others in 'The Conversation' forums and elsewhere. That you continue to pose the same arguments ad nauseum is neither relevant nor informative.
It seems to me your attacks on the University of Sydney people are 'straw man' arguments designed to draw attention to your failed position on the science of sugar and obesity.
rory robertson
rory robertson is a Friend of The Conversation.
former fattie
Paul, apparently you did not "get it", either the first time or the 42nd time. You won't respond in detail to expose me as clueless, although you "could" if you wanted. Yeah, right. Like Sue, you know I am wrong but you just can't put your finger why. Even if your life depended on it. If I had to take a wild guess - and I could easily be wrong, Paul - I would guess that like Dr Karl, Sue Leraci, David Driscoll and Bill ShrapneI, you have some sort of link to the University of Sydney that has…
Read morePaul Rogers
Manager
Rory, even if the sugar consumption data are uncertain (not conceding they are), and mistakes have been made, what is the relevance?
Obesity is not only about sugar, or fructose, it's about overeating anything and everything, and moving less. In addition, you have displayed a basic misunderstanding of the metabolism of sugar and fructose in concert with a popular book on the subject, and many experts have shown this, and you, to be incorrect.
None of the people you reference in your diatribe will be supporters of excessive sugar consumption or 'Big Sugar' as you call it. I know because I've seen their work over many years.
And even if it was shown that sugar consumption was increasing, such an ecological reference to causation (of obesity) is the lowest form of evidence and virtually worthless.
rory robertson
rory robertson is a Friend of The Conversation.
former fattie
Paul, thanks but I'll trust my reading of the science over yours. After all, you were absolutely clueless regarding simple facts here just yesterday when you - like Sue and Bill before you - were aggressively promoting the sugar industry's Green Pool report as reliable. As I have shown, it is a disturbing piece of misinformation, by design.
On the science, Gary's Taubes's assessment is that modern doses of sugar are a profound health hazard. I've not seen anyone lay a glove on that claim…
Read morePaul Rogers
Manager
"Have you read "Good Calories, Bad Calories, Paul? It should be compulsory reading for everyone with an interest in the nutrition space."
Yes, I've read most things. It's bullshit.
rory robertson
rory robertson is a Friend of The Conversation.
former fattie
Paul, it was inevitable that you would be chopped up when you started defending University of Sydney's doomed Australian Paradox paper. As you now know, the "shonky sugar study" is indefensible.
But I'm surprised you chose to "out" yourself as clueless on nutrition in general. "It's bullshit", was your neat summary of the book "Good Calories, Bad Calories".
So, the science writer for The New York Times spent five years reviewing the detail of developments in "nutrition science" over the…
Read morePaul Rogers
Manager
Rory, I was reading Gary Taubes before you were fat. I don't care if he writes for 'Science' (which he did); it's still a false premise, and I can prove it, but I'm not inclined to waste my time. However, I will admit he is a cunning and talented writer as far as his writing skills are concerned, with the obvious consequences for a naive public.
Have a good day. (BTW, you think I've not written for the NY Times establishment?)
rory robertson
rory robertson is a Friend of The Conversation.
former fattie
Paul, I don't think the naive public will lose much - except girth - if they follow Taubes's advice not to eat refined sugar and other refined carbohydrates.
That would be life-lengthening rather than life-threatening wouldn't it?
Gary Taubes is a "cunning and talented writer"? Well, things look set to get even more interesting for the pro-sugar University of Sydney nutrition underperformers, because Taubes is currently writing a book about the particular evils of sugar.
In any case, Paul, I'm actually fascinated by your PS: "(BTW, you think I've not written for the NY Times establishment?)" If you post a few links of your work, I would be interested to look at it. I may have underestimated you. You are not rally a "manager" are you? You are a nutritionist of some note?
rory robertson
rory robertson is a Friend of The Conversation.
former fattie
Paul Rogers,
I have found your website and for what it is worth I am very impressed (http://foodfithealth.com/ ). You clearly are a scholar of nutrition and fitness of some note. If we interact again at a later date, you will find me much more respectful. To be clearer, I would like to apologise for my "tone" in our discussion the other day.
I mistakenly "burred up" when you mistakenly defended the deeply flawed Australian Paradox paper, by promoting a disingenuous post that falsely declared…
Read morePaul Rogers
logged in via Twitter
Rory, I've been around online forums for a long time and I don't take offence easily. In any case, now you embarrass me.
I got internet access in the late 80s, and the Usenet newsgroup sci.med.nutrition was the big discussion forum in those early days. I even had my own private online access to the US National Library of Medicine Medline databases (now PubMed) in 1983 - with a 300 bps modem. (Yes, '83)
I know you've got an agenda on sugar and fructose and you enjoy pursuing it, but sometimes…
Read morerory robertson
rory robertson is a Friend of The Conversation.
former fattie
Just one clarification before you go, Paul. Actually, my agenda has morphed over time, from concerns about added sugar/fructose being a serious health hazard (in part via serious damage to "appetite control"), to concerns about academic and scientific integrity at the University of Sydney and in the Australian nutrition space in particular. I figure that giving the Australian Paradox dispute the prominence it deserves - and in the process encouraging the University of Sydney to do the right thing with its "shonky sugar study" (correct it or retract it) - ultimately will help to tidy up the cosy ill-disciplined sloppiness that seems to characterise the Australian nutrition space (see Slide 27 in http://www.australianparadox.com/pdf/22Slideshowaustraliangoestoparadoxcanberrafinal.pdf ).
Again, avagreatweegend. Rory
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