Avoiding the trap of belief-dependant realism

The Believing Brain: how we construct beliefs and reinforce them as truths by Michael Shermer. Times books, New York. 386pp. ISBN 978-0-8050-9125-0. Reviewed by Martin Wallace.

Aa a member of NZ Skeptics I have become increasingly aware of the huge and ever-growing list of unsubstantiated beliefs in our society, including religion, alternative medicine, alien abductions, ESP, flying saucers, vaccination refusal, and so on and on. Why are there so many of them and their adherents, and so few of us skeptics?

In his new book Michael Shermer sets out the reasons for this situation. It is our believing brains, evolved hundreds of thousands of years ago, that are responsible. Belief without evidence is a salutary behaviour when facing a trembling bush behind which a predator may be lurking. Don’t wait for evidence – just go! Survival is selected for by belief.

Michael Shermer is the founding publisher of Skeptic magazine in the US, writes a regular column in Scientific American, and is an adjunct professor at Claremont Graduate University. He lives in Calfornia.

In this book he explores beliefs in many fields, and how we select data after forming the beliefs, to reinforce them. He describes how deeply inherent is our desire to detect patterns in our sensory information, and the evidence from neurophysiology and behavioural genetics which shows how and where this occurs. Religion for example exists in all cultures and can be called “a universal”.

Dr Shermer explores the history of empiricism and the extraordinary prescience of Francis Bacon (c 1620) in his recognition of those human behaviours which inhibit the determination of reality, and the need for a new approach.

He makes a strong argument for the teaching of scientific method in our schools as well as teaching the nature of the world revealed by that process. It is the unwillingness to apply that method which has resulted in the perseverance of our plethora of beliefs. We are not endowed by evolution with that aptitude, which after all is only 400 years old. We have to learn it.

Unsubstantiated beliefs have been part of our nature for a million years. This is why there are so many of them, and why they are so widespread. Shermer writes: “Science is the only hope we have of avoiding the trap of belief-dependant realism. It is the best tool ever devised to determine: does belief equate with reality?”

The prologue is available on Shermer’s web page (www.michaelshermer.com) and gives some idea of what lies within. There are liberal notes for each chapter and a comprehensive index.

I would recommend this book to anyone, sceptic or not, who wishes to better understand our human nature.

Martin Wallace is a retired physician who is resuming his education in literature, natural history, and in trying to understand human behaviour.

The natural origins of morality

The Moral Landscape: How Science can Determine Human Values. Sam Harris. 2010. Free Press, New York. ISBN 978-1-4391-7121-9 Reviewed by Martin Wallace.

If faith is belief without evidence, then it is not open to scientific enquiry by a weighing of evidence. This attitude was supported and promulgated by Stephen Jay Gould. He claimed that there are “non-overlapping magisteria” of science and religion (NOMA).

However, what if it could be shown that there are events in the world of human brain physiology which can account for such “religious” activity as a sense of moral values?

This question is discussed brilliantly in this new book by Sam Harris. He says: “Questions about values are questions about the well-being of conscious creatures.” A sense of well-being is dependant in sentient beings like us on cerebral events and is therefore open to scientific investigation.

Well-being is engendered for example, by happiness, kindness, and compassion. Harris is a neuroscientist and has studied brain function by magnetic resonance imaging while subjects consider propositions. He has shown that the same part of the brain is active when considering scientific suggestions as when considering moral or religious precepts. The process of belief is the same, irrespective of content.

The part of the brain involved is that where activity can be seen with the placebo effect.

Harris makes interesting comments about the damaging effects of religion and politics on our sense of well-being. Given his past writing, we can expect some acerbic comments:

” For nearly a century the moral relativism of science has given faith-based religion-that great engine of ignorance and bigotry-a nearly uncontested claim to being the only universal framework for moral wisdom.”

He dismisses “cultural relativism” as a creation of academics. Well-being is shared by all members of all human cultures given the same conducive surroundings, as is our shared physiology.

He also is very firm about “scientific relativism” and the inhibitory effect it has had on human well-being. There can be no such thing as Christian physics or Muslim algebra!

The text of this book is accompanied by an expansion of the arguments in extensive Notes which are listed in the Index. There is also an extensive list of references.

This book answers the question my mother put to me 60 years ago. “It is all very well to talk about your lack of belief in religion, but what will you put in its place?”

Manipulation, chiropractic, and the idols of Francis Bacon

Chiropractic has had a colourful history since its invention in the 19th Century.

Chiropractic has had an extraordinary history, but the vehement response of its practitioners to criticisms of its claims is nothing if not human. These unwelcome aspects of human behaviour – a readiness to believe and a violent reaction to well-founded criticism – were recognised and categorised by Francis Bacon 400 years ago.

Chiropractic has been defined as “a system of treating bodily disorders by manipulation of the spine and other parts”.1 The Oxford English Dictionary gives a number of meanings for manipulation, including “The act of operating upon or managing persons or things with dexterity, especially with disparaging implications, unfair management or treatment”. Manipulate, among other meanings, is “to manage by dexterous contrivance or influence, especially to treat unfairly or insidiously for one’s own advantage”.

[Until 1818 English dictionaries gave only one meaning for manipulation: the method of digging for silver ore.]

The practice of chiropractic began in the US in 1885. It is one of a number of strange behaviours and belief systems which have had their origins in that country, including osteopathy, craniosacral manipulation, applied kinesiology, scientology, creationism science, Christian Science, and Mormon beliefs. It was in that country too that homeopathy received its greatest support after its invention in Europe. Why this should have happened is an interesting question. An American friend says that it springs from an overwhelming desire to avoid the perceived errors of Europe with its suppression of religious freedom.

David Daniel Palmer was born in Ontario in 1845, and brought his family to the US where by 1865 they were living in Davenport, Iowa. He was a grocer, and a bee-keeper, and had a deep interest in spiritualism. He practised ‘magnetic healing’ and called himself ‘Doctor’. 2, 3, 4

He later said that the idea of chiropractic came to him as ‘received wisdom’ at a séance in 1885, from a certain Dr. Jim Atkinson, deceased at that time. Shortly after this, on 18 September, 1885, he treated a man who had been deaf for 17 years. He said: “I examined him and found a vertebra racked from its normal position – I racked it into position by using the spinous process as a lever, and soon the man could hear as before.” He went on: “There was nothing crude about this adjustment; it was specific, so much so that no chiropractor has equalled it”.

Palmer called the spinal irregularity he had found a “subluxation”, a term borrowed from orthodox medicine where it means a partial dislocation of a joint. Only chiropractors can find, feel, or see their patients’ abnormalities, which they proceed to correct.

Palmer decided there must be a single cause for all diseases: “I then began a systematic investigation for the cause of all diseases and have been amply rewarded.” He had a friend coin the word ‘chiropractic’ from the Greek ‘cheir’, hand, and ‘praxis’, action. He said that the free flow of the body’s ‘innate intelligence’ (or ‘psychic energy’) to all parts of the body was interrupted by spinal vertebral subluxations, and this was the cause of 95 percent of all illnesses.

He said: “I occupy in chiropractic a similar position to Mrs [Mary Baker] Eddy in Christian Science. Mrs Eddy claimed to receive her ideas from the other world and so do I. I am the fountainhead.”

Palmer was hugely successful. In 1897 he opened the ‘Palmer School of Care’ in Davenport. Admission was by payment of tuition fees and no other qualification. In 1905 it was renamed ‘The Palmer School of Chiropractic’ and it has gone on to occupy a large campus on what is now called Palmer’s Hill, in Davenport.

His son, Bartlett Joshua (‘BJ’), took over the business in 1906, while his father was in prison for practising osteopathy and medicine without a licence. DD and BJ fell out and DD opened a rival school.

By 6 August 1908, the US congress was considering a bill to regulate the practice of chiropractic and to licence chiropractors.

David Daniel Palmer died in 1916 a short while after being run over by BJ in an automobile. The death certificate said ‘typhoid fever’.

Bartlett Joshua Palmer made a fortune, and promoted chiropractic in Canada, Australia, and the United Kingdom. He stressed salesmanship as he taught, and his classrooms were decorated with such slogans as:

“The world is your cow, but you must do the milking”

and

“Early to bed and early to rise, work like hell and advertise”.

BJ marketed a patented machine called the Neurocalometer which he said could detect subluxations, whether or not the patient had symptoms. It is still sold today as the Nervoscope and costs about $US799.

BJ founded a radio station, WOC (Wonders of Chiropractic) in 1924.

In 1926, HJ Jones in Healing by Manipulation stated there were more than 8000 chiropractors in the US and Canada.

BJ died a multimillionaire in 1961.

This story is one of extremely successful entrepreneurship in the best tradition of American showmanship. It has nothing to do with science, and a lot to do with evangelical know-how.

In 2007 there were 19 colleges of chiropractic in the US, two in the UK, at least one in Australia and one in New Zealand.

Repeated examinations of x-rays, MRI scans and autopsy material have failed to show any evidence for existence of the ‘subluxation complex’. The American Association of Chiropractic Colleges states that “the subluxations are evaluated, diagnosed, and managed through the use of chiropractic procedures”.

Because of Palmer’s initial dogma, many chiropractors reject the role of infectious agents in disease and hence deny the value of vaccination.5 Chiropractic neck manipulation is associated with an increased risk of vertebro- basilar vessel damage.6 Chiropractors insist on spine x- rays even when the risk of unnecessary exposure to radiation is raised, and this despite the absence of x- ray changes consistent with a ‘subluxation’.

A careful examination of all the scientific evidence7 has resulted in the conclusion that chiropractic offers some help for low back pain but otherwise has no more effect than that of a placebo for any other complaint.

In 1999 an American chiropractor, Samuel Homola, published Inside Chiropractic: a Patient’s Guide8. He supported manipulation for back pain, but rejected what he described as chiropractic dogma. He confirmed that the chiropractic profession had little tolerance of dissent.

“Its nonsense remains unchallenged by its leaders, and has not been denounced in its journals. Although progress has been made, the profession still has one foot planted lightly in science, and the other firmly rooted in cultism.”

He was labelled a ‘heretic’ by his colleagues.

Some commentators divide chiropractors into ‘straight’ dogmatists and ‘mixers’ who will use some science.

Chiropractors and defense by legal action: the American Medical Association Saga

In the US, doctors encouraged the arrest of chiropractors for practising medicine without a licence. By 1940 it is said that 15,000 prosecutions had been brought. However 80 percent of these had failed, with the United Chiropractors’ Association, encouraged by BJ Palmer, giving financial support to the defendants.

The AMA Committee on Quackery lobbied in 1963 to have chiropractors relegated to a non- medical status. The committee argued that chiropractic should not be recognised by the US Office of Education, citing the lack of scientific evidence, the denial of germ theory, the claim to be able to treat 95 percent of all diseases, and the use of the ‘E- meter’.

In 1976 the Chiropractors’ Association, having become aware of further action planned by the AMA, brought a suit against the association on the grounds that it planned to limit chiropractors’ practice, and this was in breach of anti- trust legislation as it was anti-competitive.

In 1987 the Court found in favour of the chiropractors, and an appeal by the AMA in 1990 failed.

The chiropractors had shifted the issue from science to rights of commercial practice. This was totally in keeping with their history of astute business acumen – and lack of scientific evidence.

The 1978 NZ Royal Commission of Inquiry into Chiropractic

In a context of legal and political mechanisms, the NZ Chiropractors’ Association with its supporters, and the NZ Medical Association and its supporters, battled for and against official recognition of chiropractic as a national health resource, and the access of its practitioners to the rewards from the Accident Compensation scheme.

The chiropractors bolstered their position with hundreds of letters to the commission from satisfied customers, and the NZMA responded by scathing and dismissive comments as to the worth of such letters, and by decrying the lack of science in the practice of chiropractic.

Kevin Dew9 suggests that the result was a negotiated settlement exchanging a proposal by chiropractors to restrict their practice to musculoskeletal conditions, in return for official Government recognition, and the addition of chiropractic to New Zealand’s health resources.

The controversy was resolved without any resolution as to the scientific validity of the claims of chiropractic. It was thought there were only 100 chiropractors in New Zealand at that time.

Recent publications6show that the majority of chiropractors in the English- speaking world continue to make claims for their treatment which extend well beyond the realm of musculo- skeletal disorders.

There were 391 chiropractors advertising in the Yellow Pages in New Zealand in August, 2010.

Simon Singh and the British Chiropractors’ Association

In 2008, Simon Singh and Edzard Ernst published a book called Trick or Treatment.7

On 19 April 2008, Singh wrote an article in The Guardian, pursuing the topic canvassed in the book, that chiropractic was alternative medicine and there was no evidence for any effect except on lower back pain.

“The British Chiropractors’ Association claims that their members can help treat children with colic, sleeping and feeding problems, frequent ear infections and prolonged crying even though there is not a jot of evidence. This organisation is the respectable face of the chiropractic profession, yet it happily promotes bogus treatments”.

The BCA quickly sued him for libel, and on 7 May 2009 the court handed down a verdict in favour of the chiropractors.

Meanwhile in New Zealand

On 25 July 2008, the NZ Medical Journal published a paper by Andrew Gilbey reporting evidence that some chiropractors in NZ were using the title ‘Doctor’ in a manner which could mislead the public. In the same issue an editorial by David Colquhoun appeared, critical of chiropractic, and the qualifications of its practitioners. He wrote:

“For most forms of alternative medicine, including chiropractic and acupuncture the evidence is now in. There is now better reason than ever before to believe that they are mostly elaborate placebos, and at best are no better than conventional treatment.”

In the next issue of the NZMJ the editor published a letter from a lawyer, Paul Radich, representing the NZ Chiropractors’ Association, threatening legal action under the NZ Defamation Act, against the journal, Gilbey, and Colquhoun. The letter demanded apologies from all parties, and outlined the financial penalties for all.10 The tone was intimidatory.

In his comments about the position of the NZMJ as a scientific publication, the editor, Frank Frizelle, invited the chiropractors to an evidence- based debate with these words: “Let’s hear your evidence, not your legal muscle”.

The NZMJ published an invited response from the NZ College of Chiropractic in its next issue11 and I understand there has been no further correspondence from the lawyer (personal communication from the editor, NZMJ, September 2010).

Back to London

A month after the initial court procedure in London, Simon Singh announced his intention to appeal the finding in favour of the BCA.

On 1 April 2010 the Appeal Court handed down its verdict. The Lord Chief Justice of England and Wales, The Master of the Rolls, and Lord Justice Sedley stated that Singh(s comments were not libellous, and that they were matters of opinion backed by evidence. They went on to quote an American judge, Judge Easterbrook, now Chief Justice of the US 7th Circuit Court of Appeals.

In Underwager v Salter 22 Fed.3d 730 (1994):

“Plaintiffs cannot, by simply filing suit and crying ‘character assassination’ silence those who hold divergent views, no matter how adverse those views may be to the plaintiff’s interests. Scientific controversies must be settled by the methods of science, rather than by the methods of litigation. More papers, more discussion, and more satisfactory models – not larger awards of damages – mark the path toward superior understanding of the world around us.”

Back to New Zealand

As it happens, nine days after Singh’s appeal was upheld, Ernst and Gilbey authored a paper in the NZMJ: “Chiropractors’ Claims in the English-speaking World”.5 They examined 200 individual chiropractors’ websites and nine chiropractic association sites in Australia, Canada, New Zealand, the UK and the US. They concluded:

“The majority of chiropractors and their associations in the English-speaking world seem to make claims which are not supported by sound evidence. We suggest the ubiquity of the unsubstantiated claims constitutes an ethical and public health issue.”

On 11 June 2010, Shaun Holt and Andrew Gilbey wrote a letter to the editor of the NZMJ12 drawing attention to the wider public scrutiny of chiropractic claims and nature following the success of Simon Singh’s appeal.

Francis Bacon and his ‘idols’

Francis Bacon (1561-1626) lived at a time when the new empiricism was disturbing the security and comfort taken in accepting the opinions of established authorities. He was a lawyer, a legal theorist, a judge, and a writer. He became Lord Chancellor, but was charged by Parliament with corruption, and having taken bribes from those appearing before him in court. He pleaded guilty and wrote: “I was the justest judge that was in England these fifty years, but it was the justest censure in Parliament these two hundred years.”13

Bacon wrote a series of ‘Axioms’ towards the end of his life. I would like to use some of these to examine aspects of human behaviour that the history of chiropractic reveals. It has been a considerable surprise to me to realise the prescience of this man.

He used the term ‘idols’ to list aspects of human behaviour.

Axiom 41: “The Idols of the Tribe”

These have their foundation in human nature itself.

“For it is a false assertion that the sense of man is the measure of things. On the contrary, all perceptions, as well of the sense as of the mind, are according to the measure of the individual, and not according to the measure of the universe.”

We are all subject to our nature, and seek security and certainty, and believe the evidence of our eyes. If we get better after manipulation, then clearly the manipulation made us better. Emma Young says: “We are causal determinists – we assume that outcomes are caused by preceding events”.14

Axiom 42: “The Idols of the Cave”

These are the idols of the individual man, due to our own peculiar natures, our education, our own experiences, or to reading from authorities we admire. “The spirit of man is in fact a thing variable and full of perturbation”. If we are told by our parents or teachers that someone else is better after manipulation, then we will believe that it is a ‘true’ relationship.

Axiom 43: “The Idols of the Marketplace”

“Formed by the intercourse and association of men with each other. For it is by discourse that men associate, and words are imposed according to the apprehension of the common understanding. The ill and unfit choice of words wonderfully obstructs the understanding. Words plainly force and overrule the understanding, and throw all into confusion and lead men away into numberless empty controversies and idle fancies.”

The choice of the word ‘subluxation’ for example, to describe an undemonstrable change! Or the claim for the existence of ‘psychic energy’. A radio station extolling the “Wonders of Chiropractic” is a wonderful Idol of the marketplace.

To take legal action and gain the publicity which is sure to follow with extensive argument about the meaning of, for example, ‘happily’ has great appeal in the marketplace.

Axiom 44: “The Idols of the Theatre”

“Which have migrated into men’s minds from various dogmas, and the wrong laws of demonstration. All the received systems are but so many stage plays – many more plays of the same kind may yet be composed.”

How well aware of this human trait are all showmen and charlatans. The Palmers, father and son, exploited this behaviour. To claim that new knowledge has come from beyond the grave is wonderful ‘theatre’, full of drama and mystery. To maintain the dogma of the wonderful in the face of evidence to the contrary is so much easier than to examine the evidence.

All these human behaviours can be seen in the history of chiropractic, and in so many other catastrophes such as the anti- vaccination campaign, the Peter Ellis trial, the Cartwright affair, the anti- fluoridation campaign and so on and on.

The history of chiropractic, and the response of chiropractors to criticism about the absence of science in their beliefs, illustrate the profound insights of Francis Bacon about our nature. It is our nature which results in the persistence of the perverse, and which resists the truth.

The responses of those without objective evidence for their personal beliefs often include ad hominem attacks, threat of legal action and financial injury, professional ridicule, and public invective. All these are seen in the chiropractors’ responses.

References

  1. Collins’ Concise Dictionary of the English Language (1988).
  2. Shapiro, R 2009: Suckers: How Alternative Medicine Makes Fools of Us All. Vintage Press, London.
  3. Carroll, RT 2003: The Skeptics’ Dictionary; A Collection of Strange Beliefs, Amazing Deceptions and Dangerous Delusions. John Wiley & Sons, NJ.
  4. Goldacre, B 2008: Bad Science. Fourth Estate, London.
  5. Ernst, E; Gilbey, A 2010: NZMJ, 123(1312) 36-44.
  6. Ernst, E 2007: J. R. Soc. Med. 100(7) 330-338.
  7. Singh, S; Ernst, E. 2008: Trick or Treatment: Alternative Medicine on Trial. Transworld Publishers, London.
  8. Homola, S 1999: Inside Chiropractic: A Patient’s Guide.
  9. Dew, K 2000: Sociology of Health & Illness, 22(3) 310-330.
  10. Editorial, 2008: NZMJ, 121(1279) 16-18.
  11. Roughan, S 2008: NZMJ, 121 (1280)72-74.
  12. Gilbey, A 2010: NZMJ, 123(1316) 126-127.
  13. Hollander, J; Kermode, F 1973: Oxford Anthology of English Literature. OUP, London & New York.
  14. Young, E 2010: New Scientist 2720.

Truth is the daughter of time, and not of authority: Aspects of the Cartwright Affair

The ‘Unfortunate Experiment’ at National Women’s Hospital has entered the national folklore as a notorious case of medical misconduct. But there is still disagreement about what actually happened.

It is 22 years since the Cartwright Inquiry published its findings. Arguments about the whole affair persist, with repeated public support from those who say it was a valuable and proper exposure of damaging improprieties by the medical profession, and from those who say that the inquiry and the events which led to it are based on an erroneous interpretation of a scientific paper, and selective evidence gathering at the Inquiry.

If indeed an error has been made, then the vilification of the medical people involved, which has occurred and which still goes on, must be redressed.

I want to consider two aspects of this affair, and if the evidence shows a miscarriage of justice, to offer reasons as to why this might have happened.

I shall:

  • consider the contention that an unethical experiment was performed at National Women’s Hospital (NWH) by Professor Green and his associates, and whether or not the Inquiry made a fair and just assessment of the current (1988) internationally accepted management of carcinoma-in-situ of the cervix (CIN3);
  • discuss what factors in our scientific literary world might be contributing to error.
  • describe unwelcome aspects of our human behaviour which allow an issue of this magnitude to survive in our society, unresolved for 22 years, and how writers have described these for many centuries. I have chosen as my title a quotation from Aulus Gellius in his Attic Nights, written in c.150 CE to emphasise the long-standing nature of the problem.

It is important to have a clear outline of the sequence of events over time at NWH and here is a timeline for reference:

1966: Green proposed to the NWH Medical Committee that CIN3 should be managed by cone biopsy if indicated and regular review. This was in response to considerable doubt worldwide about the natural history of the condition, for which many advocated hysterectomy. The committee agreed.

1973: Editorial in the British Medical Journal, “Uncertainties of Cervical Cytology.”1

1974: Article in New Zealand Medical Journal (NZMJ) by Green showing evidence that “The proportion progressing to invasion must be small.”2

1975: The NWH Medical Committee reviewed the management protocol and agreed it should continue.

1982: Professor Green retired.

1984: “The Invasive Potential of Carcinoma-in-situ of the cervix” was published.3 This was the paper on which Sandra Coney and Phillida Bunkle based their Metro article.

1985: A letter to the NZMJ by Skrabanek and Jamieson was critical of a national cervical screening programme for CIN3 as a detection and treatment method for carcinoma of the cervix (14 August).

1986: A letter from David Skegg was published in the NZMJ supporting a cervical screening programme. “The case for the effectiveness of screening does not rest on the unfortunate experiment at NWH in which women with abnormal smears were treated conservatively and a proportion have developed invasive cancer” (22 January).

1987: “An Unfortunate Experiment at National Women’s” appeared in the June issue of an Auckland magazine,Metro. Within 10 days the Minister of Health (Michael Bassett) has announced the inquiry, and that it was to be chaired by Sylvia Cartwright.

1987/1988: The inquiry sat, and published its report in 1988.

1988: A book, An Unfortunate Experiment, by Sandra Coney was published.

1990: Jan Corbett, a journalist, wrote an article in the July issue of Metro reviewing the errors in the Coney and Bunkle paper, and the way in which the data in the 1984 paper had been distorted.

2008: A conference was held to commemorate the Cartwright Inquiry. A number of papers including Charlotte Paul (a medical adviser to the inquiry), and Sandra Coney, were presented endorsing the inquiry findings.

2009: A book, A History of the ‘Unfortunate Experiment’ at National Women’s Hospital, by Linda Bryder, a professional historian, was published.

2009: A book, The Cartwright Papers, published by participants in the 2008 conference, and now including a vehement criticism of Linda Bryder and of her book.

2010: The NZMJ publishes a letter from Dr Helen Overton, “In defence of Linda Bryder’s Book.”4

The 1984 paper

“The Invasive Potential of Carcinoma-in-situ of the Cervix” was written by two gynaecologists from NWH (McIndoe and Jones), a pathologist from NWH (McLean) and a statistician (Mullins).

I have read this carefully, and made a summary of its contents. It described the follow-up data for 948 women with carcinoma-in-situ of the cervix. The women were followed for five-28 years by repeated smears and observation according to the 1966 proposal, unless they showed evidence for spreading cancer. The women were seen at three, six, and 12 months after presentation, and yearly after that. The women’s records showed that at 24 months after presentation, 131 continued to have an abnormal smear. (Of course, the other 817 had normal smears, or had had removal of the cervix by hysterectomy or other treatment.) There was no difference in age or parity between those in either group.

The division into the two groups was made retrospectively by the authors on the evidence for the presence or absence of an abnormal smear at 24 months.

They compared the outcomes in the two groups in terms of the development of invasive cancer (22.1 percent in the group with positive smears at 24 months, 1.5 percent in the larger group). They also compared the number of deaths in each group at the end of the observation period (June 1983). Four women who had had normal smears at 24 months had died (0.5 percent) and eight women had died who had had abnormal smears at 24 months (6 percent).

Treatment

There was no withholding of treatment in that group with the persistently abnormal smears – see Table 1.

Initial treatment Eventual treatment
Total hysterectomy Cone biopsy or amputation Total hysterectomy Cone biopsy or amputation
Group 1 (n=817) 217 (26.6%) 576 (70.9%)
Group 2 (n=131) 33 (25.2%) 88 (67.2%) 62 (47.3%) 166 (126.7%)

Table 1. Initial and eventual treatment of patients with normal smears, or who had cervixes removed by hysterectomy or other treatment (Group 1), and of patients with persistent abnormal smears (Group 2). Percentages exceeding 100 percent reflect the need for two cervical procedures in some women.
The authors said in the paper’s discussion, “the almost universal acceptance of the malign potential of this lesion has made prospective investigation into the natural progression of CIS ethically impossible”. That would require an experiment where women had no treatment. This is quite clearly not the case in this reported series.

It is clear that in this report of the management of CIS there is no evidence of withholding of treatment, nor of an experiment.

Three years after this paper was published, it was used by Sandra Coney and Phillida Bunkle as evidence for gross wrongdoing by the medical staff at NWH. Here is what they wrote:

“The study divided the women into two groups – 817 who had normal smears after treatment by conventional techniques, and a second group of 131 women who continued to produce persistently abnormal smears. This group is called in the study the conservative treatment group. Some had only biopsies to establish the presence of disease and no further treatment.”

Later in the article the authors refer to “group two women who had little or no treatment”.

This paper in a popular magazine was used by the Cartwright Inquiry as some of the evidence which led to its conclusions.

In 1990, Liggins said, “The famous 1984 article which emanated from the National Women’s Hospital and on which the Metro article which stimulated the cervical cancer inquiry was based, was misinterpreted by the authors of the Metro article and by the judge”.5

Was the management of cervical carcinoma-in-situ unethical?

This is the second aspect of the Cartwright affair that I wish to examine. In June 2010 the statement was made that “treatment with curative intent was withheld in an unethical study” at NWH from 1965 to 1974.6

It is important to make clear what we understand by ‘ethical’, ‘unethical’ and ‘conventional’, or we shall be reduced to the state of the Looking-Glass world: “‘When I use a word,’ Humpty Dumpty said in a rather scornful tone, ‘it means just what I choose it to mean – neither more nor less.'”7

Ethical: “In accordance with principles of conduct that are considered correct, especially those of a given profession or group”. (Collins Concise Dictionary, 1988.)

Unethical: Not in accordance with these principles.

Conventional: Relating to convention or general agreement. (OED)

Convention is a general agreement or consent. (OED)

Was the protocol for the management of CIN3 by Prof Green and his colleagues at NWH an unethical experiment? If he had proposed to divide the women as they presented into two groups, one of which was treated and the other not, then that would have been unethical. Although uncertainty existed as to what proportion of women with an abnormal cervical smear developed an invasive cancer, it was agreed that an abnormal smear meant that the woman was more likely to develop cancer than if she had a normal smear.

His protocol did not deny women treatment.

There was widespread international uncertainty as to the best form of management. If Prof Green had withheld an acknowledged proven treatment that was agreed to by the majority of workers in the field, and replaced it with an unproven treatment, then that would indeed have been unethical.

He didn’t do that.

During 1966-1984 there was no international agreed conventional treatment for this condition. As Iain Chalmers of the James Lind Library in Oxford points out, 8 Linda Bryder in her book has made a thorough review of the contemporary medical literature on this subject which makes it clear that there was no worldwide, generally accepted treatment of CIN3. The evidence called by the Cartwright Inquiry did not reflect the lack of an international consensus. It was indicative of only one aspect of the issue. It has all the attributes of ‘cherry-picking’.

The accusation that Green and his colleagues behaved unethically in these matters is not sustainable. Unless his detractors can show that there was a single international conventional treatment which he ignored, then repeated accusations of “unethical behaviour” are wrong. These accusations continue to be made, as recently as 1 June, 2010.6

Why do manifestly false beliefs persist over time?

There are features of our human behaviour which are conducive to the persistence of untruths, and they include a desire for uniformity in the interest of the maintenance of a coherent and more easily managed society.

Once a decision has been made, it is easier for all of us to go along with it, and not to ‘rock the boat’.

There have been trenchant criticisms of the Cartwright affair and its outcomes, often met with strident objections and not much logic. To accuse the whistle blower of “intransigence and arrogance” rather than meet the questions fairly is shameful.

Another feature of the last 22 years is the increasing number of papers published in the medical literature which on close examination are of poor quality. An example of this is the paper published on 1 June, 2010.

This was published as an abstract online. The authors include a medical adviser to the Cartwright Inquiry, a medical witness at the inquiry, and one of the authors of the 1984 paper. There is the old accusation that “treatment with curative intent was withheld in an unethical clinical study of the natural history of CIS at NWH in the years 1965-1974.” But in the results it is stated that 51 percent of these women had treatment with curative intent! The group treated with the diagnosis made in 1975-1976 had curative intent treatment in 85 percent. Prof Green retired in 1982; his proposal for the management of carcinoma in situ was approved in 1966.

Treatment with curative intent was not defined in the abstract.

The results include P values of 0.0005 for the significance of differences between groups, for a difference which defines the grouping.

The number of new patients in the year 1975-1976 was half that in each of the two previous decades. There is no explanation for this in the abstract. This group was not included in the comparison of risk for cancer of the cervix or vaginal vault. There is no explanation for this.

The medical science literature shares with all scientific paper publishing a current deterioration in standards. This contributes to the persistence of error. This issue has been recently addressed in an editorial in The European Journal of Clinical Investigation.9

“Why would scientists publish junk? Apparently the current system does not penalise its publication. Conversely, it rewards productivity.
Nowadays, some authors have been co-authoring more than 100 papers annually. Some of these researchers only published three or four papers per year until their mid-forties and fifties. Then suddenly they developed this agonising writing incontinence.”

Another factor in our society which feeds our appetite for orthodoxy is the popular press. Truth is often submerged in the sensational. An example of this occurred in the NZ Herald on 1 June, when their health reporter wrote a report of the on-line article6 with the headline:

“Otago research backs cancer inquiry findings: Unfortunate experiment at National Women’s not imagined, says report”

There followed 40 column centimetres supporting the headline, including two which stated: “The cancer death rate differences between the periods and sub-groups are not significantly different”. This information is not included in the on-line published paper. The reporter’s statement is not correct in his summary of the report. In addition he cites information which suggests he has access to the complete (as yet unpublished on June 1st) paper.

The television ‘press’ included that morning an interview with Charlotte Paul, one of the authors, and that evening, an interview with Clare Matheson, the woman named as ‘Ruth’ in the original Metro article. There was no reference to the valid criticisms of the Cartwright affair which have been made over the years.

It is not my case that the medical profession to which I belong is without fault, and I accept that since 1988 more attention has been paid by doctors to issues such as informed consent. But the means, by this miscarriage of justice, do not justify the ends.

Our human desire not to alter our beliefs in the face of contrary evidence, the willingness of the popular press not to disturb established ‘truth’, the current deterioration in the standards of the world medical press, and an unquestioning respect for ‘authority’ are factors recognisably active in the persistence of the myths surrounding the Cartwright affair. These behaviours are not new, and their effects on the emergence of truth have been recognised for centuries. Francis Bacon (1561-1626) in his Axioms wrote, in number 46:

“The human understanding when it has once adopted an opinion (either as being the received opinion, or as being agreeable to itself) draws all things else to support and agree with it. And though here be a greater number and weight of instances to be found on the other side, yet these it either neglects and despises, or else by some distinction sets aside and rejects; in order that by this great and pernicious predetermination the authority of its former conclusions may remain inviolate.”

References

  1. Editorial. 1974: BMJ, 5891, 561-2.
  2. Green, GH. 1974: NZMJ 80, 279-287.
  3. McIndoe, WA; McLean, MA; Jones, RW; Mullins, PR. 1984: Obstetrics and Gynecology 64, 451-458.
  4. Overton, H. 2010: NZMJ 123, 95-96.
  5. Liggins, CC. 1991: Australia and New Zealand J. Surgery 61, 169-172.
  6. McCredie, MRE; Paul, C; Sharples KJ; Baranyai, J; Medley, G; Skegg, DCG; Jones, RW. 2010: Australia and New Zealand J Obstetrics and Gynaecology, ‘earlyview’ on-line 1 June.
  7. Carroll, L. 1871: Through the Looking-Glass. Chapter 6.
  8. Chalmers, I. 2010: NZMJ Letters to the Editor. 30 July.
  9. Editorial. 2010: European J Clinical Investigation 40(4), 285-7.

The physiology of the placebo effect

Placebos may contain no active ingredients, but they have real effects on the human brain. This article is based on a presentation to the NZ Skeptics 2008 conference in Hamilton, September 26-28.

Earlier this year, Dr Tipu Aamir of the Auckland Pain Management Service drew my attention to something peculiar. In a double-blind, randomised, placebo-controlled trial of morphine after a standard knee operation, 30 percent of those receiving a placebo get pain relief. When those people are given a specific morphine antagonist (‘antidote’), their pain comes back! In the words of a former contributor at an annual conference of this society, this was an epiphany. I needed to know more.

After all, how could something that was ‘all in the mind’ be changed predictably by a substance with a known pharmacological action?

Any study of homeopathy raises the issue of the placebo effect. As a result of a meta-analysis in 2005 of a number of studies comparing homeopathic remedies with orthodox treatment, Shang et al stated in their conclusion that the effect of homeopathic remedies was no greater than that of a placebo. Not that they had no effect, but it was no greater than that of a placebo.

We skeptics are often happy to accept the explanation that if a response to some arcane practice is a placebo response, that settles the issue.

Over the last 30 years there has been a large amount of research into the undoubted effects of placebos. I thought it might be of interest to review this work in the context of our frequent use of ‘placebo effect’ to explain the unscientific.

Placebo is a Latin word for “I shall be pleasing, or acceptable”. It is the first word of the first antiphon of the Roman Rite of the Vespers for the Dead (!), Placebo Domino, dating from the seventh to ninth centuries. Chaucer called one of his characters Placebo in the Merchant’s Tale, because the word had come to mean a flatterer, a sycophant, or a parasite, by the 14th century.

“Placebo seyde: Ful little need had ye, my lord so deare, Council to ask, of any that are here But that ye be so ful of sapience.”

He also uses it in the Parson’s tale: “Flatterers be the Devil’s chaplains, which sing ever ‘Placebo’.”

In the 1811 edition of Hooper’s Medical Dictionary, placebo was defined as “an epithet for any medicine adopted more to please than benefit the patient”. In a recent edition of Collins’ Concise Dictionary of the English Language it is defined as “an inactive substance administered to a patient to compare its effects with those of a real drug, but sometimes for the psychological benefit of the patient through his believing he is receiving treatment”.

However, placebos do benefit patients, and they are certainly not inactive in the context in which they are given.

The most dramatic example of this that I saw in clinical practice involved a young man on artificial kidney treatment. When erythropoietin became available for the treatment of the severe anaemia seen so often in this situation, he was the first patient in our unit to receive it. Erythropoietin is a hormone made in the healthy kidney, which increases the number of red cells in the blood and the amount of the oxygen-carrying haemoglobin. The synthetic version has achieved notoriety as a performance enhancer in sport, for example in the Tour de France. We were all very enthusiastic about this improvement in management for our patient, and he was given his first dose with much interest from all of us. That night he went home, recovered his bicycle from the shed where it had been undisturbed for many months, and rode all around his town with great energy and pleasure. He hadn’t heard the information that the drug took three weeks to act on the anaemia.

We are left with some questions. What was the physiology of his sudden ability to exercise at a ‘normal’ rate, long before there was any change in his blood count? What does ‘it’s all in the mind’ mean? Was he somehow at fault, or was it me and the staff who were lacking in understanding?

I would like to consider:

  • The psychological processes involved in the placebo effect
  • The physiological mechanisms in the brain
  • The site of this activity in the brain
  • Why there is variation in the placebo effect from individual to individual
  • What are the implications for the classical drug trial format?

Psychological mechanisms

Those who study the psychological processes of the placebo effect cite two major mechanisms.

Conditioning. Pavlov (1849-1936) showed that dogs given meals as a bell rang would subsequently salivate when the bell rang despite not being given food. This process has been explored in humans, who will experience pain relief when a placebo is substituted for a pain reliever when a sequence of active analgesia has been associated with an environmental cue. It is an unconscious process. At the nerve cell level, conditioning leads to a stronger and more sustained response.

Expectancy. This effect is seen when the patient has ‘great expectations’ of the substance being given. These are raised by the conscious or unconscious attitude of the therapist. It is a conscious process on the part of the patient.

It is currently suggested that both conditioning and expectancy are active in the placebo effect, and that in fact, as an inert placebo can have no effect per se, what we see is the effect of the context in which the treatment is given.

Neurophysiology of placebo pain relief

Over the last 30 years, there has been much interest in the neuro-physiological mechanisms of the placebo response.

In 1975, Hughes et al identified in the brain two related pentapeptides (a chain of five amino acids linked together) with potent opium-like action. There are many more now identified. These compounds act on specific receptors on the membranes of neurones, and via intracellular metabolic changes increase synaptic transmission. They are made in the pituitary and hypothalamus, and are called endorphins.

A digression

In pharmacology the term agonist denotes a drug with an effect, and antagonist, a drug which specifically blocks the effect of the first substance.

When I spent a year in the pharmacology lab in Dunedin (1959) it was becoming recognised that drugs exerted their effects by way of a specific receptor molecule at the cell surface. The actions of adrenaline, for example, were explained by the presence of two different molecules to which it could attach, which mediated different effects. Noradrenaline would latch on to only one, explaining its more limited range of action. With their usual desire for learned coherency, pharmacologists called them alpha and beta receptors. Antagonist molecules attach to the receptor molecule and block access by the agonist. Hence the term ‘beta-blockers’. These are substances which block the action of adrenaline on its beta receptor. They are widely known for their action in the control of blood pressure, and recently for their unwanted effects when given to protect patients at risk of heart trouble when undergoing operations.

Agonists and antagonists are related by similarities in molecular size, shape, and charge.

Morphine antagonists have been available for some time. In 1961 as a house surgeon in casualty, I was asked to manage an opium addict, brought in because he was deeply unconscious, and breathing perhaps once a minute. He had been without the drug for some weeks, due to market fluctuations. When access was resumed, he used a dose which was the same as his habituated dose. This was much more than he could now tolerate. I had access to nalorphine, a specific morphine antagonist, and 30 seconds after an IV injection, the patient took several deep breaths, sat up, expressed considerable surprise at his surroundings, and then lapsed back into his former state. I was able to repeat this dramatic procedure several times until he recovered!

In 1978 a group of dental surgeons working in California (Levine et al) carried out the following experiment. Patients who had had an impacted wisdom tooth extracted were treated routinely with nitrous oxide, diazepam and a local anaesthetic. At three hours after the procedure they were given either a placebo or naloxone, a specific morphine antagonist. At four hours they were given a placebo or naloxone. Those who had initial pain relief with the first dose of placebo (39 percent), when given naloxone had an increase in pain.

The authors concluded that “this was consistent with the hypothesis that endorphin release mediates placebo analgesia in dental postoperative pain.”

The elegance of this study lies in the unequivocal evidence that a supposedly psychological state (placebo analgesia) was reversed by a specific opioid antagonist. Note that none of the patients was given morphine. There must be a physiological cause for placebo analgesia.

This sort of study has been repeated many times, and always naloxone reverses placebo analgesia.

The site of action of opioids in the brain

The site of this process has been determined. The sites for opioid receptors in the brain can be found by specific cell staining methods and histology on brain tissue. But more exact, ‘real-time’ evidence comes from positron emission tomography (PET) scans.

Another digression

PET utilises short half-life radioactive elements which undergo spontaneous beta decay. In the process, they emit a positron, which collides with an adjacent electron resulting in mutual annihilation, and the generation of two high-energy photons at a near-180 degree angle. These can be detected, and with many, many such events, used to build up a tomographic picture of the source in relation to surrounding tissue. In the studies of the brain, radioactively-labelled glucose is injected, and congregates where activity (utilisation) is greatest. PET scans are used to monitor metabolic activity in specific organs. For example, the extent of heart muscle damage after a heart attack.

In 2002, Petrovic et al were able to show that both opioid and placebo analgesia are associated with increased brain activity in specific regions: the anterior cingulate cortex and the brain stem. There was no increase of activity in these regions with pain only.

Similar localised brain activity has been shown in placebo responses in Parkinsonism (dopamine) and some depressive states (serotonin).

I find these studies exciting and provocative.

Genetic predilection

A further question can be asked in the light of the evidence for a physiological mechanism for the placebo effect. Why does it occur in only 30-40 percent of us for a given situation? It may occur in a greater proportion of a population sample if the context is made more convincing. But why don’t we all have the benefits? Variation in a physiological function begs the question of a genetic predilection.

De Pascalis et al (2002) have shown that individual differences in suggestibility contribute significantly to the magnitude of placebo analgesia. The higher the suggestibility score (there are several tests available) the greater the placebo analgesic effect.

As early as 1970, Morgan et al showed that there was a correlation of suggestibility between monozygotic twins but not dizygotic (fraternal) twins. (Monozygotic twins are the result of the fertilisation of one ovum by one sperm. The resulting zygote splits into two cells which each develop into an individual. These individuals have exactly the same genes.)

Wallace and Persanyi (1989) looked at hypnotic susceptibility and familial handedness. Subjects with close left-handed relatives scored lower in a test for hypnotic susceptibility.

At the 2008 conference, I carried out an experiment with a group of clearly non-suggestible Skeptics. I asked those in the audience to raise their hands if they, or a close relative, were left-handed. If the hypothesis was correct, more than 10 percent of our attendees should have been left-handed. In the event, 22 of 84 attendees indicated they or a close relative were left-handed.

The control study should be done with a church congregation, Protestant or Catholic. In fact, we could do this on both and answer the question as to which is the less suggestible! I haven’t had the nerve to ask. Thomas Bouchard, beginning in 1979, has carried out a number of studies on twins who for a variety of reasons were reared apart. He compared correlations between identical twins and between fraternal twins. The studies from his group (in Minnesota) have shown a large group of correlations in identical twins reared apart, which do not occur in fraternal twins reared apart. The correlations differ very significantly. Table 1 has some examples in twins reared apart:

Similar studies have given similar results in Australia and Western Europe.

Because the nurture of these twins is different, and identical twins have identical genes, the similarities must be genetic. This approach to behaviour has lead to the science of behaviour genetics. (Physical attributes are of course also correlated more between identical twins reared apart, than fraternal twins reared apart.)

Amir Raz (2005, 2008) and his group in New York State have shown that a genetic polymorphism (more than one version of a specific gene) exists for a gene on chromosome 22, which codes for an enzyme active in the breakdown of dopamine, a neurotransmitter. One amino acid substitution (valine for methionine) in the gene alters the enzyme activity by a factor of four times. Since we have a copy of this gene from each parent, we may have val/val, or val/meth, or meth/meth genotypes.

Val/meth heterozygote confers the greater suggestibility. The enzyme is called COMT or catechol-o-methyl transferase.

Brain pathways in which opioid receptors are active are linked to those in which dopamine is the transmitter (nerve to nerve). If there is genetically conferred variation in dopamine activity it is likely that this will influence the result of changes in activity in the opioid pathways.

We must remember that we are talking of a genetic predisposition to be suggestible, and not a gene for suggestibility. It is not that 69 percent of identical twins vote Republican, but that if one does there is a 69 percent probability that the other one does too.

The implications for drug trials

In 2003, Benedetti and his colleagues in Turin examined pain relief in patients after thoracotomy. Patients were allocated to either open infusions of morphine, with information about the efficacy of the drug, or to receive hidden doses of morphine by infusion without any information and without any doctor or nurse present (the open / hidden model for drug trials).

With the same dose, same infusion rate, same timing and same drug, pain relief was less in the ‘hidden’ group.

In the ‘open’ group, the ‘meaning-induced’ expectations had enhanced the drug effect.

This research group has gone on to postulate that in all drug treatment the effect is the sum of actual physiological effect and the effect of expectations. This means that the placebo effect will always cause part of the usual ‘physiological’ response to active drugs. They say that the classical double blind randomised placebo-controlled trial does not allow for expectation effects, and may suggest that a drug has a specific effect gre’open/hidden paradigm’ will give more meaningful results.

Conclusions

  • The analgesic placebo effect is accompanied by a distinct, observable, and locatable physiological event in the brain.
  • Susceptibility to the placebo effect varies in the population at large.
  • This susceptibility is at least in part genetically determined.
  • It may be possible to harness this facet of human behaviour for the benefit of individuals, and to prevent its on-going exploitation by charlatans.
  • Although placebos are inert and cannot have any effect on the healing processes, their meaning and the context in which they are given can.
  • All drug effects include some placebo effect, except when the drug is given surreptitiously. This should alter the classic clinical trial structure.

We have come a long way from the Vespers for the Dead!

Placebos are inert substances but the context in which they are given can alter neurophysiology in such a way as to cause subjective and objective effects.

This is not due to the ‘molecular memory’ of water, nor to strange force-fields as yet unknown to physicists. It is due to our human nature, how we react to our environment, and the relationship, between our minds and our bodies.

Full references available from the editor.