The most influential health research of the last 100 years

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8 pieces of health research that have changed our world


Ever wondered which research papers are behind the huge leaps – and back steps – in medical knowledge over the past century?

Scientific progress is usually a slow march, with individual studies building incrementally on previous findings just like bricks in a wall. Hence Isaac Newton’s famous line, “If I have seen further than others, it is by standing upon the shoulders of giants.” That said, sometimes the pursuit of knowledge is a two-steps forward, one-step backward dance. Yet from time to time a piece of research comes along that makes a much bigger difference, for better or worse, and creates far-reaching ripples. This is our very subjective pick of the top such studies over the past 100 years.

1) Swine Flu conspiracy PhD THESIS

Making a splash, but not for the right reasons, was the PhD thesis that claimed Big Pharma and the WHO conspired to declare the 2009 swine flu outbreak a pandemic in order to sell vaccines.

According to the author, vocal anti-vaccination activist, Judy Wilyman, a WHO committee with ties to the pharma industry overstated the importance of the flu outbreak in a deliberate bid to stir up hysteria and bolster vaccine sales.

The PhD thesis was accepted by the University of Wollongong and approved by an academic who had previously linked AIDS to contaminated polio vaccines.

While Wilyman’s paper was roundly condemned by healthcare professionals and just about anyone who wasn’t an anti-vaxxer, the incident did highlight how easily people can publish in areas in which they have no relevant expertise.

The university cited freedom of thought and expression as the reasons behind publishing the paper.

But immunologists pointed out scientific inaccuracies and dodgy practices referenced in the paper, published in the Faculty of Law, Humanities and the Arts.

This included cherry-picking scientific literature, including a 30-year-old paper showing no links between HPV and cervical cancer, and ignoring a recent trial that found a strong link.

Accepting and publishing this paper was bound to stoke the fires of the anti-vax movement, raising the question: what responsibility do universities have regarding the government money they are entrusted with.

Wilyman, Judy, A critical analysis of the Australian government’s rationale for its vaccination policy, Doctor of Philosophy thesis, School of Humanities and Social Inquiry, University of Wollongong, 2015.

2) Andrew Wakefield’s study linking MMR vaccine to autism

Perhaps one of the most damaging studies to public health was the publication of Dr Andrew Wakefield’s 1998 paper linking the MMR vaccine to autism in children.

The paper boosted the Lancet’s impact factor thanks to the number of times it was cited. Except the link wasn’t a real one, and Wakefield had largely made the findings up.

Despite the paper being retracted and Dr Wakefield being stripped of his medical licence to become Mr Wakefield, the damage was done.

Vaccination rates in the UK and the US dropped. And almost two decades later, vaccine scepticism is at an all-time high.

While the paper was fully retracted in 2010, numerous medical bodies such as the CDC, Cochrane institute and the NHS have had to publish further research or analysis of the data to quell fears about the vaccine.

Wakefield claimed that eight of the 12 children in the trial underwent developmental regression in the two weeks following their MMR vaccine.

But there was woefully inadequate reporting on how the data was collected, and Wakefield was found to have collected the data unethically – subjecting the children to unnecessary lumbar punctures and colonoscopies without proper approval.

All the while, the dodgy financials behind Wakefield’s research were covered up. The initial trials were established with funding from a lawyer, Richard Barr, who had plans to take action against vaccine manufacturers. Wakefield would eventually receive more than £400,000 from the lawsuit.

More than just fame and accolades, there were also business opportunities in linking the MMR vaccine to autism. Launching his own business, Wakefield hoped to profit from parents seeking tests for the detection of Crohn’s disease, an alternative vaccine and even in treating autism.

The deceit was exposed, but we’re still feeling the damage 18 years later.

Lancet. 1998 Feb 28;351(9103):637-41.

3) Blue eyes-brown eyes experiment

This study showed many white Americans for the first time just what it might be like to be on the receiving end of racism, and how humiliating and debilitating it could be.

The study was the subject of much controversy, both for its findings and implications, but also because no ethics approval was sought. It was a major impetus for the introduction of diversity training in America and later England, Australia and other countries.

The researcher, Jane Elliott, was a primary school teacher with a keen interest in activism inspired by Martin Luther King’s assassination. After realising that a class discussion on racism wasn’t sinking in for her students, Elliott decided to split the class into two groups based on eye colour, with blue-eyed children treated as the superior group.

Children with brown eyes were forced to wear brown collars, were separated from the blue-eyed children, and frequently chastised, whereas the blue-eyed children received special privileges.

Very quickly, the schoolwork of the brown-eyed students’ deteriorated, while the blue-eyed students became bossy and mean to their ‘inferior’ counterparts.

Subsequently, Elliott was criticised for unethical and cruel treatment of the primary school children, with one angry letter demanding: “How dare you try this cruel experiment out on white children?”

4) British Doctors smoking study

It’s hard to remember a time when smoking wasn’t synonymous with bad health, but half a century ago the habit was seen as relatively harmless, and perhaps even healthy.

It was really only when epidemiologists Richard Doll and Austen Bradford Hill published their landmark 1954 study that the world saw convincing statistics linking smoking with lung cancer.

In what’s now known as the British Doctors study, Doll and Hill followed up two thirds of all male British doctors (35,000) and found smoking rates were closely linked to lung cancer deaths.

While it was initially supposed to last for only five years, the study instead continued for 60, all the while finding more links. Over time, it emerged that smoking took 10 years off a lifespan.

It was a breakthrough study in terms of epidemiology too, helping to establish its role in public health. This was such a change from the retrospective studies that were relied upon at the time, that the 1954 paper had to include a definition of what a ‘prospective’ study was.

Doll and Hill 1954: BMJ 1954; 328(7455): 1529–1533

5) Oxygen in myocardial infarction

The AVOID (Air versus oxygen in ST-elevation myocardial infarction) study was a game-changer in terms of the management of patients with STEMIs.

Despite the widespread practice of giving supplemental oxygen to patients with myocardial infarction, Australian researchers found it didn’t improve outcomes unless patients had an arterial oxygen saturation of less than 94%.

Infarct size and mortality were not improved in patients given oxygen, and in fact those in the oxygen group were at greater risk of myocardial injury, recurrent myocardial infarction and major cardiac arrhythmia.

The 34-month study followed Victorian paramedics, who randomised patients to receive oxygen via facemask or not at all unless their SaO2 fell below 94%. They also followed up with a cardiac magnetic resonance test at six months to determine infarct size, and found oxygen was associated with a larger infarct size at this point.

Circulation 2015; 131(24):2143-50

6) Prophylactic pill for HIV

The end to the HIV epidemic is in sight, and that’s partly thanks to the discovery of a prophylactic pill.

Truvada (tenofovir/emtricitabine) began to emerge as an option for pre-exposure prophylaxis (PrEP) over the last few years, but it was a 2014 study which found daily use drastically reduced HIV transmission in a real world setting.

Now health experts are hoping  Australia could see the virtual elimination of new HIV cases by 2020 by providing PrEP to high-risk groups such as men who have sex with men.

The researchers found those taking PrEP regularly (but not daily) had a 92% reduction, and estimated that  men taking the pill daily were 99% less likely to contract HIV than those taking a placebo.

Countries across the world are also hoping the medication may be part of the armament which will bring about the end of the HIV epidemic. UNAIDS set the bar for 90-90-90 by the end of the decade, meaning that 90% of the population living with HIV will know their status, 90% of people diagnosed with be on antiretrovirals, and 90% of those will have viral suppression.

As was the case with the introduction of the birth control pill, PrEP faces opposition from groups who argue it could encourage further unsafe sex and reduce condom use.

NEJM 2010; 363:2587-2599

7) Milgram shock study

Stanley Milgram’s famous shock experiment changed many people’s views on what it means to be evil, and how atrocities might occur in the real world.

Instead of people being inherently evil or sadistic, the experiment seemed to show that normal, everyday people could wind up performing torturous or even lethal acts on another human being, simply by obeying authority.

The study itself pushed ethical boundaries, and is one of a number of psychological studies unlikely to be repeated.

Milgram’s question was whether the millions involved in the Holocaust were “just following orders”.

In the 1961 study, participants were asked to take part in a learning and memory test that consisted of three people: the ‘teacher’, the ‘learner’ and the ‘experimenter’.

Two men drew slips of paper from a hat to determine which of them would be the ‘learner’ and which the ‘teacher’. Unbeknown to that subject, he would always end up as the teacher, and the other man was an actor.

The experimenter then asked the ‘teacher’ to deliver the ‘learner’ shocks every time they got the answer to a memory test wrong, increasing by 15 volts for each wrong answer.

Incredibly, 65% of the participants continued to shock the ‘learner’ to the maximum 450 volts, despite him showing visible signs of distress. And despite hearing a pre-recorded tape of someone, allegedly the learner, screaming in pain and complaining about a heart condition.  None of the participants stopped before 300 volts.

Notably, the participants weren’t facing punishment if they stopped delivering the shocks, and had been promised payment regardless of outcome. It seems the pressure came from the experimenter urging them on with predefined responses, such as “Please continue”, “Please go on”, “The experiment requires that you go on” and “It is absolutely essential that you continue”.

The study has been repeated across different cultures with similar results.

J Abnorm Psychol 1963; 67(4) 371-378

8) Nazi hypothermia experiments

The Nazi immersion-hypothermia project was conducted at the Dachau concentration camp between August 1942 and May 1943.

It is widely accepted the experiments were brutal crimes committed under the guise of medical research, however there is controversy about the use of the data obtained from those studies.

For around three decades the results from the Luftwaffe’s 1940s hypothermia experiments were cited in scientific literature, without much acknowledgement given to the sickening costs of obtaining the data.

On the one hand, some argued that expanding our knowledge of the effects of severe cold and reheating on the human body could prove useful for the management of medical emergencies.

And if that were the case, wouldn’t we have an obligation to use it and save lives, some academics claimed, in turn raising other questions. Is it enough to cite the data with a strong condemnation of the way it was obtained? Or will the use of this data make researchers complicit in the murders? Does using the data somehow justify the torturers’ behaviour?

In the late 1980s, Robert Pozos, a physiologist specialising in hypothermia, tried to gain access to the results, arguing they could be key to saving lives and advancing our knowledge of hypothermia.

But the NEJM’s editor-in-chief held quite a different opinion, saying the experiments were “such a gross violation of human standards that they are not to be trusted at all”.

It’s not hard to see why, the testing was performed on around 300 Dachau concentration camp prisoners – around 100 of whom may have died as a result of the procedures.

The experimenters immersed victims in tanks of icy water, recording their body temperatures and how long it took them to die. Some men were placed in boiling water for reheating, one assistant reported.

Looking back, serious doubts have been raised about the methodology of the ‘experiments’. Basic data like the time spent in the bath, initial body temperature and the subject’s initial health are missing, leaving only thoroughly flawed research with inadequate methods and an erratic execution.

JAMA. 1946;130(9):572-573

NEJM 1990; 322:1435-1440

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