Just why is ‘pioneering’ cancer treatment so expensive?

A heartstring-tugging appeal in the NZ Herald doesn’t tell the full story.

Jesse Bessant is a little boy from Auckland with a very rare brain tumour. He has a ganglioglioma, a tumour that arises from ganglion cells in the central nervous system. As these tumours are very slow-growing, and with the location of his tumour (close to his brain stem) making surgery very risky, Jesse’s doctors have advised a ‘wait and see’ approach. However, the Bessant family have opted instead to try the Burzynski clinic in Houston, Texas, where Dr Stanislaw Burzynski offers his ‘pioneering’ antineoplastin treatment.

The catch? It’s going to cost the Bessants $375,000 to join one of Dr Burzynski’s clinical trials. The family’s fundraising appeal was covered by the NZ Herald in early March under the headline: “Hope for toddler with rare tumour”.

So what are antineoplastins and why is a clinical trial at the Burzynski clinic so expensive? Let’s start with those ‘pioneering’ antineoplastins. Might they be the next big thing in the treatment of cancer? I’m afraid to say that this is unlikely, as it turns out that Dr Burzynski has been trialling antineoplastins for over 35 years and has never produced strong evidence that his approach actually cures patients or increases their chances of long-term survival.

In fact the results of his trials don’t seem to have been published in the peer-reviewed medical literature and the American Cancer Society has gone so far as to recommend that people don’t spend their money on antineoplastin therapy. Dr Burzynski coined the phrase to describe a group of peptides that he identified first in human blood and then in urine and which he claimed to be “natural, non-toxic compounds that cure cancer”.

It turns out that the peptides can also be made by the body metabolising the drug sodium phenylbutyrate, which is how Dr Burzynski has been administering them for several decades now. Rather alarmingly, each 500 mg tablet of sodium phenylbutyrate contains approximately 62 mg sodium, meaning there is considerable risk of side effects including lethargy, weakness, irritability, seizures, coma and even death.

So if antineoplastins are just the by-product of sodium phenylbutyrate, why are Dr Burzynski’s clinical trials so expensive? After all, patients don’t usually have to pay hundreds of thousands of dollars to join a clinical trial. Sometimes they might even be reimbursed for taking part! It turns out that Dr Burzynski doesn’t just treat patients with his ‘antineoplastins’ anymore. Instead, he seems to be exploiting a very legitimate trend in real cancer therapy, often referred to as personalised medicine. Here patients are tested for particular disease markers which have been shown to respond to specific therapies. Orac, of the Respectful Insolence blog, has described Dr Burzynski’s “Personalized Gene Targeted Cancer Therapy” approach as “throwing everything but the kitchen sink” at the tumours. In fact, Dr Burzynski’s personalised therapy is part of a complaint against him by the Texas Medical Board, which is currently awaiting a hearing date. The complaint describes Dr Burzynski’s treatment of a patient with metastasised breast cancer, which included prescribing sodium phenylbutyrate with another four very expensive immunotherapy agents, none of which are approved for the treatment of breast cancer, and in combination with a chemotherapy agent.

In fact, it also transpires that Dr Burzynski owns the pharmacy that supplies the drugs he prescribes. His pharmacy is also accused of overcharging for drugs. A former patient, Lola Quinlan, has filed a lawsuit, claiming Dr Burzynski swindled her out of nearly $100,000 by using false and misleading tactics, including charging $500 per pill for drugs that could be bought elsewhere for a fraction of that price. And as well as the cost of drugs, there are his consultation fees, listed on one potential patient’s blog as:

  • Review of medical records prior to commencing treatment – $500
  • Initial consultation appointment – $1,000
  • “Genetic Tumor Markers” test – $4,000
  • Monthly treatment fee (with treatment suggested to last 4 to 12 months) – $4,500 – $6,000

All of which might explain why Dr Burzynski lives in a mansion with his initials in gold on the gates! But none of this was covered in the NZ Herald article. Don’t those being asked to donate deserve to know where their money is going? Instead, my emails to the journalist remain unanswered and Letter to the Editor unpublished. And the Bessant family continue to raise funds to send their child to be treated by a man who is accused by the Texas Medical Board of “unprofessional or dishonorable conduct that is likely to deceive or defraud the public or injure the public”. Pioneering? More like profiteering, if you ask me.

Newsfront

Autism paper binned

Twelve years after it induced panic among parents world-wide, a paper linking the measles-mumps-rubella (MMR) vaccine to autism has been withdrawn (NZ Herald, 4 February).

The paper, published in the Lancet in 1998, was withdrawn after a preliminary verdict by a panel from Britain’s General Medical Council found Dr Andrew Wakefield and two of his co-authors had acted “dishonestly” and “irresponsibly”.

“It has become clear that several elements of the 1998 paper by Wakefield et al are incorrect,” the Lancet‘s editors stated. “… In particular, the claims in the original paper that children were ‘consecutively referred’ and that investigations were ‘approved’ by the local ethics committee have been proven to be false. Therefore we fully retract this paper.”

The paper was based on just 12 children, some of whom had bowel disorders and autism which had developed after vaccination with MMR. It led to sharp falls in vaccination rates and, said Auckland University’s Immunisation Advisory Centre director of research Helen Petousis-Harris, many preventable cases of disease.

“There are still many parents who are concerned about the Wakefield claims. We hope that this news [the retraction] will add further reassurance that the MMR vaccine is not associated with autism or any other developmental problems.”

The Lancet announced a partial retraction in 2004 after it emerged that Dr Wakefield had received payments for his research from the Legal Aid Board which he had not declared. This was a fatal conflict of interest, the journal said.

Stargazers at odds

Obviously, it came in the middle of the silly season when papers struggle to find copy, but journalist Rebecca Lewis had a lot of fun with astrologers’ predictions for the year ahead (NZ Herald, 3 January).

Pitting one astrologer against another, she checked out what various authorities in the field had to say about Sagittarians. A certain Anne McNaughton picked 2010 as a year in which a full moon in the “financial sector” would get things off to a good start for them. On the other hand Jenny Blume in Woman’s Day reckoned changes at work and home would leave Sagittarians feeling “skint” in autumn.

Someone on the Universal Psychic Guild website calling herself Astrogirl reckoned they would ditch their club-hopping ways and start “nesting”. Marie Claire promised the coming year would be about being daring and outgoing, and astrology.msn.co.nz claimed 2010 would bring out the “practical” side of Sagittarians, with a primary focus on finances.

“Confused?” asked Lewis. “Yup.”

The truth is in there

UFO researchers UFOCUS NZ are excited at the prospect of hundreds of secret files on mysterious sightings which are to be released by the New Zealand military (The Press, 23 January).

The files cover the period 1979 to 1984, and include the famous Kaikoura sightings of December 1978. They were to have been public in January, but are having personal information removed first to comply with the Privacy Act.

UFOCUS NZ director Suzanne Hansen said the group had been in discussion with the NZ Defence Force for many years. “It is frustrating from a research perspective because we would like to collate these sightings with international research.”

New Zealand Skeptics chairwoman (sic) Vicki Hyde said the files would not be as interesting as they appeared. “The Government is required to log these things and it can give a false impression that there is a vast amount of activity out there.

“There is probably intelligent life elsewhere, but whether it has come here to play silly buggers with us in a game of cosmic hide and seek is another matter.”
“It is a big jump from ‘there was something in the sky and I don’t know what it was’ to ‘that was a craft piloted by aliens’.”

Scientologists to the rescue

Among all the tragic stories coming out of the Haiti earthquake was the strange tale of John Travolta flying his own private jetliner to the beleaguered country with 7000lb of medical supplies – and doctors and ministers from the Church of Scientology (NZ Herald, 27 January).

Scientologists at a hospital in the capital Port au Prince said they were healing patients through “the power of touch to reconnect nervous systems”.

Sylvie, a spokeswoman, said: “We are trained as volunteer ministers. We use a process called ‘assist’ to follow the nervous system to reconnect the main points”.

“I didn’t know touch could heal gangrene,” said one sceptical doctor.

St Bathans a ghost town?

An Invercargill man on a ghost-hunting trip to Otago has come away with a spooky photo – but not of the building that’s supposed to be haunted (Southland Times, 5 February).

Andrew Watters had gone to St Bathans to have a look at the Vulcan Hotel and its supposed ghost. The pub apparently had only the regular type of spirits and it wasn’t until later that a friend noticed in one of his photos a shape in the upstairs window of the old post office nearby that looks remarkably like an elderly woman.

Vulcan Hotel leasee Jude Cavanagh said it was the first she had heard of a ghost sighting at the post office. “It’s a very spirited town, so who knows?”

The post office, managed by the Department of Conservation since the 1950s, had been vacant for about a year, at least in the bodily sense, she said.

Ghost, or reflection of a cloud? I suppose we’ll never know…

Sweat lodge ends in tragedy

A sweat lodge at an Arizona “spiritual retreat” ended up steaming three people to death last October, according to a leaked police report (NZ Herald, 4 January).

The retreat charged thousands of dollars for five days of motivational talks and spiritual tasks. Following the deaths, self-styled guru James Arthur Ray faces a murder investigation.

The report showed participants vomited, passed out and screamed for help. Ray was outside the only entrance, controlling the flap that let people in and out. One witness said Ray told scared participants three times: “You are not going to die. You might think you are, but you are not going to die.”

The two-hour ceremony followed two days of fasting and not drinking water. When the ceremony was over and people were trying to get the victims out, Ray called attempts to remove blankets from the walls “sacrilegious”. One victim had been subjected to such intense heat his lungs were scorched.
Critics say that such tasks are a sort of confidence trick that exists at the extreme end of America’s US$11.5 billion ($15.8 billion) self-help industry.

‘Ghosts’ find buyer

Two “captured ghosts” sold on Trademe have gone to a company which sells electronic cigarettes (The Press, 9 March).

The “ghosts” were sold by Avie Woodbury of Christchurch, who says they are the spirits of an old man who lived in the house in the 1920s and a powerful little girl who turned up after a ouija board session. They have been kept in holy water which “dulls the spirits’ energy”.

The auction recorded more than 200,000 page views and made international headlines. Safer Smoke NZ had bid $5000, but the final price dropped to $2830 after a last-minute bidder was revealed to be a fake seeking to push the price up.

Ms Woodbury will donate the proceeds to the SPCA – once exorcist’ s fees have been paid.

Forum

A non-remedy for a non-disease

I had to wait for my prescription at the pharmacy and while browsing the shelves noticed a new homeopathic remedy for white-tail spider bites. At $18.40 a small bottle it’s money for jam! No, that metaphor will just not work; perhaps money for water would be better? White-tail spider bites have been blamed for a huge range of injuries but the scientific evidence has discounted this attribution. (Those pesky skeptics again…!) Still, I thought it rather amusing to see a ‘non remedy’ for a ‘non disease’.

John Welch, Picton

The printed word – the best communication there is

Readers may be as amused as I was by the following quote from Tim LaHaye:

“The best way to reach the minds of people is the printed page. God chose the printed page to communicate with mankind. So how can you improve on that?”

No respectable skeptic would believe that even an American fundamentalist could be that stupid, so the reference is: Have a Nice Doomsday, by Nicholas Guyatt: an interview with LaHaye p 275.

Jim Ring, Nelson

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.

Natural products chemistry – the road from nature to pharmaceutical

Many pharmaceuticals originate from nature, but their development is very different from that of so-called natural health products. This article was originally presented at the 2005 Skeptics Conference.

The field of natural products chemistry deals with the scientific study of chemicals isolated from living organisms. This can be anything from isolating indigo dye from woad, distilling lavender oil from the lavender plant, working with plant oils and animal fats to make soap, to trying to find the active ingredient in a plant extract that reduces fever.

Interest in compounds from living organisms dates back to the beginnings of civilisation. More recently it also gave birth to what we now call ‘organic chemistry’. Initially, organic chemistry was natural products chemistry, when people thought that carbon containing molecules were imbued with a ‘vital force’ and could only be made by living organisms — hence the name ‘organic’. Friedrich Wöhler shattered that idea in 1828 when he became the first to make urea (an organic molecule) from inorganic precursors. Now we define organic chemistry simply as the chemistry of carbon containing compounds.

Unfortunately this mystical feeling that “natural” things are somehow better, or special, has survived till today, and many people are still convinced that “it’s natural, so it’s got to be good!” When dealing with natural substances that have biological activity, one must ask why they have any physiological effect. The answer is chemical defense: plants that do not have thorns, for example, have evolved chemical substances to poison animals that would otherwise eat them. The ‘natural’ effect of any herbal product then, is to make the user sick! We should not be talking about ‘natural is good’, but about chemical warfare.

Chemical warfare

The mould Penicillium notatum produces and secretes an antibiotic, a compound that inhibits bacteria that could compete with it for food or resources. This is chemical warfare on the microscale, a life and death battle for survival between the mould and its enemy. The mould certainly does not make the antibiotic for the benefit of mankind — any beneficial effect to us is an accidental advantage. But we can certainly make good use of that! The antibiotic in question is of course penicillin, the first discovered antibiotic. It has revolutionised medical treatment of bacterial infections and earned its discoverers Sir Alexander Fleming, Ernst Chain and Sir Howard Florey the 1945 Nobel Prize in Medicine.

We certainly exploit this type of biological activity to our great advantage. Natural products, or compounds derived from natural products, comprise the majority of pharmaceuticals in use today. So what is the difference between them and ‘herbal remedies’ that are sold in health shops and supermarkets?

The big difference is that herbal remedies are not tested. Not tested for efficacy (we don’t know whether or how they work), they are not tested for safety (we don’t know whether they are toxic or have side effects). They are not regulated in any way, so you don’t know what you are buying at all!

Drug development process

Before a natural product can be approved for use as a human pharmaceutical, it must go through a rigorous process of testing during clinical trials. And before it even enters those, it must be fully identified and characterised. This precise analysis is what makes the known and well understood pharmaceuticals stand apart from herbal remedies. For the most part, we know very little, if anything, about their chemical composition and effects.

Once the initial discovery process is complete, the natural product is subjected to a barrage of tests in vitro (in the test tube) and in vivo (in lab animals). Once biological activity and initial safety is demonstrated, the potential pharmaceutical can be admitted to the Phase I clinical trial. This involves a small group of healthy volunteers who are given the compound to determine its safety (that is, evaluate any toxicity and side effects) and tolerated dosage. Phase II trial follows, where the effectiveness of the compound at curing a disease is finally tested on a small number of human patients.

Finally, Phase III is a large scale trial on 1000 to 3000 patients, verifying effectiveness and monitoring any adverse effects from long term use. At the end, all the data are submitted to the monitoring agency (in the US this is the Food and Drug Administration) for evaluation. Once approval is given, the drug can be launched onto the market, where it still undergoes long-term safety monitoring and additional tests during the so-called Phase IV trial.

On average, out of 5000 compounds that undergo pre-clinical testing, only five are deemed promising enough to enter clinical trials. Out of those five, only one is approved — others fail because they do not show effectiveness once trialled in humans, or exhibit unacceptable levels of toxicity or side effects. From discovery to prescription, the whole process takes on average 12 years, with costs estimated to be in the hundreds of millions of US dollars.

While the process may not be perfect, it does attempt to ensure that the medication we are prescribed is first of all safe, and that it works. Herbal remedies cannot claim the same.

The Story of Taxol

In the 1960s the National Cancer Institute (NCI) launched a screening programme to test various plants for potential anti-cancer activity. Over the next two decades they screened more than 114,000 plant extracts. This included, in 1962, a collection of bark from the Pacific Yew, Taxus brevifolia. Immediately, this shrub generated great excitement as it showed interesting activity in biological assays. A research project was launched to investigate these properties, and in 1967 the active ingredient was isolated and named paclitaxel. The structure was not solved until four years later in 1971, a reflection of its high degree of complexity. Paclitaxel exhibited a broad spectrum of activity against cancer cells in vitro, and in 1979 scientists discovered its mode of action in the cell — a completely novel way of stopping and killing cancerous cells. In vivo testing showed phenomenal successes — paclitaxel stopped the growth and even shriveled breast cancer tumours in mice. All of these results made paclitaxel the hottest natural product around. Everyone wanted to get their hands on some, but paclitaxel had many hurdles yet to overcome.

Researchers rushed the compound into clinical trials, but immediately faced a problem. Paclitaxel was not soluble in anything. As one researcher put it, “it had the solubility of a brick.” How were they going to administer it to patients? Finally a concoction consisting mainly of castor oil was found to be effective, but was almost the drug’s undoing. Paclitaxel proceeded to clinical trials, and was almost rejected right then and there, as it showed unacceptable levels of side-effects. Fortunately, someone figured out that most of these were due to the castor oil, and after the formulation was changed somewhat, the drug continued to Phase II clinical trials.

The results were astonishing: against the most virulent forms of ovarian cancer, paclitaxel showed unheard of levels of response. Doctors and researchers were suddenly clamouring for more and more of the drug. But Taxol faced its greatest challenge yet: that of supply.

The compound paclitaxel is present in only minute amounts in the bark of Taxus brevifolia. Fifteen kilograms of the bark yield barely half a gram of the active compound, which means it would take six 100-year-old trees to treat one patient. Quite aside from the ecological impact of the large scale logging operation required, there simply are not enough Pacific Yew trees in the world to treat all the cancer patients.

Making the compound in the lab was not an option. Though a successful synthesis of paclitaxel was reported in the literature, the molecule was too complex for this to be a viable route to obtaining large quantities. Fortunately however, researchers discovered that the much more common English Yew (Taxus baccata) contained relatively large quantities of a compound that is related to paclitaxel. Eventually in 1989 they succeeded in transforming this 10-deacetylbaccatin into paclitaxel. This semi-synthetic pathway is how Taxol is made even today.

The billion dollar wonder molecule

Having successfully completed clinical trials, paclitaxel was launched onto the market in 1993 under the trade name Taxol as a drug to treat ovarian cancer. Sales of Taxol grew exponentially, rapidly reaching and passing the US$1 billion mark. Today, Taxol remains the leading treatment against ovarian, breast and lung cancers, and Karposi’s sarcoma. Yet it had not been an easy journey: from bark to drug it took 31 years, and with an estimated cost in excess of US $300 million.

Victoria University Marine Chemistry Lab

Most of the natural products that have “made it” as pharmaceuticals come from the terrestrial environment, not surprisingly, as terrestrial plants, animals and fungi are most easily accessible to researchers. In the last few decades however, with the advent of scuba diving, a whole new world has opened up: the marine environment. The Marine Chemistry Lab at Victoria University studies chemical compounds found in marine plants and animals. We examine a wide variety of organisms, including sponges, seaweeds, sea-slugs and others. Our ultimate goal is to discover new, biologically active chemicals from marine organisms and develop them into pharmaceuticals.
G

Discovery of peloruside

In 1998, Lyndon West (who was at that time doing his PhD in our lab), discovered a new compound from the sponge Mycale hetsheli. He named it peloruside, after Pelorus Sound where the sponge came from. The compound looked very interesting right from the start, so patents were filed right away, and biological testing initiated. Indeed, exhaustive in vitro tests revealed that peloruside had the same mode of action as Taxol! This news generated a lot of interest, and in 2004 a deal was signed with Reata, a US Pharmaceutical company. Their tests in mice showed very promising results: injections of peloruside into grafted tumours radically reduced their growth. With exciting results like that, everyone is now keen to start clinical trials.

Unfortunately, we face a supply problem even worse than the Taxol people did: the compound is once again present in only small amounts in the sponge. In addition, sponge populations are scarce in the wild, and difficult to reach. They also show a large variability in the amounts of peloruside they produce, depending on depth, season, geographical location and even individual animal.

Aquaculture

But, we have a solution: aquaculture! Fortunately for the project, the sponge can be propagated from small cuttings. We have taken bits of wild sponges and tied them to ropes that have been suspended off the anchor lines of a mussel farm in the Marlborough Sounds. The sponge has grown well — our sponge farm yielded almost 100 kilograms of the sponge in 2005. Some of this mass was returned to the ropes to grow again for this year, the rest has been harvested and is now being processed in our lab. We hope to get gram amounts of peloruside and hopefully start clinical trials with Reata Pharmaceuticals in the US this year.

Could peloruside be the next wonder drug against cancer? Well, it has a long way to go yet. But it certainly shows promise, so watch this space.

The Royal healing touch

The medical community in Britain is suffering a severe attack of lèse majesté, and it is feared some distinguished heads will roll on Tower Green.

Prince Charles, in his untiring care for the health of his future subjects, has set up The Prince of Wales’ Foundation for Integrated Health, and, with the help of several hundred thousand pounds of taxpayers’ money, this Foundation has published Complementary Health Care: a guide for patients. It helps readers to locate homeopaths, reflexologists, cranio-sacral therapists, and other types of healer. This 45-page treasury is being sent free to all GPs in Britain.

This well-meaning attempt by the philanthropic heir to the throne and his disciples to help the sick has been spurned by the medical fraternity, in the harshest and most hurtful terms. The British Medical Association has criticised it for recommending treatments which have no evidential support. More biting remarks have come from Professor Edzard Ernst, occupant of Britain’s only Chair of Complementary Medicine. When he saw a draft version, he said it was “hair-raisingly flimsy, misleading and dangerous”. He offered to correct it free of charge, an offer which was declined (Of course! How dare he presume to rewrite a text which had the Imprimatur of HRH?).

Having seen the published version, the Professor is even more scathing (see www.guardian.co.uk/g2/story/0,,1442930,00.html) “… scandalous waste of public funds … the most spurious I have seen for years … reads like a promotional booklet”.

No expense seems to have been spared in the production of the “Guide”; it is in full colour, with lots of photos of folk receiving various therapies. Though it concedes, even emphasises, the need to see your doctor and to keep him/her fully informed, the contents will otherwise be familiar to students of Complementary Medicine; no mention of evidence (though a scholarly-looking list of 141 references), much talk of “… believe that … ” and “… used by many people for …” and of those mysterious entities beloved of these practitioners: “energy” and “meridians”. There is, of course, no discussion of the mutually exclusive nature of some of these therapies, nor of the complete absence in many cases of evidence of efficacy. You know, of course, the meaning of the verb “to heal”. It is therefore puzzling to see one of the 16 therapeutic modalities included in the “Guide” is known as “Healing”. Surely it is not implied that none of the other 15 can cure your trouble? “Healing”, in this context, looks to be our old fraudulent friend Therapeutic Touch. If you are visiting Britain, and feel the need for a little cranio-sacral therapy, help is at hand. The Guide, with relevant addresses, can be downloaded free from www.fihealth.org.uk. Be cheered, also, by the claim that over half the GPs in Britain will direct you to CAM practitioners; indeed, many have such people working in their medical centres.

Deadly Ignorance

Pseudoscientific beliefs can be dangerous when they form the basis of government policy

In my last column, I mentioned that conspiracy thinker Phillip Day travels the world (he again toured New Zealand late last year) with his message that there is no Human Immunodeficiency Virus (HIV), that Acquired Immune Deficiency Syndrome (Aids) is not sexually transmitted and that the “highly poisonous Aids medications” are part of a “calculated and inhumane population control agenda which has been sanctioned at the highest political levels.”

So absurd are these claims that readers may doubt whether people such as Day attract much of a following. Why should Skeptics bother to speak up? Sadly, misinformation can be deadly to entire populations when policy makers adopt it. A shocking example is the case of Aids in the Republic of South Africa.

In 1982 the first cases of HIV were diagnosed in South Africa. The government was very slow to respond to the growing crisis. By 1998, when 50% of adult medical admissions to hospital in Gauteng province were Aids related, there was still no national treatment plan, public education about Aids was almost nonexistent, and superstitions were widespread. When health worker Gugu Dlamini made her HIV status public on World Aids day, she was stoned to death by a mob that included her neighbours.

The reason for the government’s slow response became clear: ignorance among the leadership of the ruling African National Congress. The South African president, Thabo Mbeki, who succeeded Nelson Mandela as president in 1999, shocked the world health community when he said Aids is caused by poverty, not by HIV. By 2000, 10% of South Africans were HIV positive, but in May of that year he appointed a panel and charged them with solving the country’s Aids problems. One of the panel members chosen by Mbeki was American scientific outcast Peter Duesberg, who says Aids is caused by anti-Aids drugs, such as AZT, but not by HIV! Mbeki ruled out providing AZT to HIV positive pregnant women, claiming the drug did more harm than good. In fact, the drug has been proven effective in drastically cutting the transmission of the deadly virus to the baby in childbirth. Thousands of HIV positive babies continued to be born every month. Duesberg said he doubted South Africa was experiencing an Aids epidemic, and the panel debated whether Aids is spread by sex or not. Mbeki thus wasted precious time and resources. In July 2000, about 5000 doctors and scientists took the extraordinary step of releasing The Durban Declaration as a rebuke to Mbeki. The document said the link between HIV and Aids is “clear-cut, exhaustive and unambiguous.” South Africa’s doctors appealed for an end to the debate which they said was confusing people who should be fighting Aids, which was spreading faster in South Africa than anywhere else on Earth.

Mbeki continued to downplay the threat of Aids. His government continued to ban doctors from providing antiretroviral drugs to HIV infected women, thus ensuring that the disease was passed on to thousands more babies. The cheap or free drugs that pharmaceutical companies had been offering for five years were not accepted.

Indeed, the Ministry of Health at great expense distributed a pamphlet justifying this deadly nonsense. In 2001, Mbeki again refused to link HIV with Aids, even though he agreed “that’s what the scientists say.”

Progress slowly came. President Mbeki found himself increasingly isolated as members of his cabinet and government supporters stated that they accepted the link between HIV and Aids. He also came under fierce international criticism from scientists and medical experts for his ignorance and lack of action.

In November 2003, the government reversed its position on the antiretroviral drugs and planned to quadruple its spending on HIV/Aids. President Mbeki, however, continues to lash out at efforts to provide scientific treatment. Phillip Day praises Mbeki’s bizarre beliefs.

The World Health Organisation says Aids is the biggest cause of death in South Africa, where it affects nearly six million people, more than in any other country. About one million people died in South Africa last year from Aids.

No society in history has had to deal with an epidemic like this. There is no containing an epidemic that has already infected 30% of adults in Durban. By 2010, life spans will probably be reduced in South Africa from about 70 years (in the absence of Aids) to about 36. Millions of deaths from Aids that have occurred in South Africa and millions that will happen were avoidable. When leaders fall for crank ideas, the results can be massively tragic.
Dr Raymond Richards is a Senior Lecturer in History and American Studies at Waikato University. He can be reached at [email protected]

A Skeptical Response

Occasionally, the NZ Skeptics receive correspondence from members of the general public. Recently, Chairentity Vicki Hyde took the time to reply to one of these. Portions of the original letter are indented.

Dear Margaret

Thank you for your comments, though it’s sad to see that you believe the general stereotype of skeptic:

The mere term ‘skeptic’ is enough to conjure (oops, not a word skeptics like, I’m sure) up an image of a cynical, dogmatic person, afraid to step outside the realms of their small, unen-lightened world.

“Conjure” would actually be a very suitable term used in skeptical circles, as we have many magicians as members, as well as teachers, homemakers, researchers, a broad sweep of humanity. There are very few who fit the stereotype you have assumed, as about the only thing we have in common is the desire to actually step outside the realm and find out what makes us what we are, what encourages us to think how we do and to respond the way we do to the world around us.

About the only type of person we don’t have in the skeptical ranks are fundamentalist dogmatics, as they are taught to never question authority, and skeptics, by their very nature always ask questions and, in many cases, accept that there are some things we will never have the answers for.

I imagine that Rande, who was featured on a programme about homoeopathy on TV1 last night is typical of the average “skeptic” who desperately goes around trying to “debunk” anything that is not “clinically proven in a scientifically controlled experiment”.

No, not debunking, but investigating — most of us don’t like the term “debunk”, as it implies a biased viewpoint to start with, but the media does persist in using it.

We always try to investigate with an open mind and with the knowledge that everyone is fallible, we are all able to be fooled or biased. And that when extraordinary claims are made, it should involve an extraordinary level of proof.

Randi was asked in because magicians have a very clear professional understanding of how people can be mistaken or hood-winked, whether intentionally or accidentally.

Scientists, however, work in an environment of collegial honesty, which makes them more vulnerable, in some respects, to deception or assumptions. That’s one of the reasons why science encourages investigation, repeated observation, independent corroboration and all the other aspects that help us to differentiate between what we think we know and what we know, to try to eliminate our own biases, prejudices and assumptions in learning about the world.

I wonder if you skeptics ever experience a ‘hunch’ or a ‘gut feeling’ or, dare I say it, intuition … I imagine not — I mean, how can you prove it?

Yes we do. I had a long interview with a reporter this year about the nature of intuition. Sadly the editor wanted to hear only about “just so” intuition anecdotes, rather than the interesting story of why humans feel so strongly about intuition, how it has proven useful to us and why we have such difficulty remembering when it doesn’t work.

I think that intuition is the capacity for apparently making reasonably accurate predictions about the near future based on a combination of both definable and, for the most part, indefinable factors. We’ve all experienced those times when we “just know” something and, when we’re proved right, that’s an immensely powerful reinforcing factor for a belief in intuition or psychic abilities or whatever you think such an experience is based upon.

Humans are, after all, a pattern-seeking animal — we look for patterns in the stars and try and find meaning in them; we analyse our dreams; we try and find cause-and-effect in all manner of connections.

What we humans don’t do, is readily recall the experiences which provide counter-examples to the belief in causal relationships or intuition. We don’t bother thinking “gee, I felt something bad was going to happen today and nothing did!” Instead we look for confirmation of our beliefs — “gee I felt something bad was going to happen today, and look, a week later, I had a car crash!”

However, in our enthusiasm to over-simplify and gain control over our destiny, we have often taken such things too far — that star up there makes the Nile flood (bzzt, wrong!); bleeding a patient will rebalance their humours (bzzt, wrong!); that person is inferior to me because they are a different gender/race/religion/skin colour (bzzt, very wrong!).

There are hundreds and hundreds of people whose flashes of intuition or desperate hopes or even sheer bloody hard work, did not succeed, but you don’t hear about them, they don’t have the compelling story, they don’t get the column-centimetres in the glossy magazines.

Which demonstrates another key psychological point — one strong personal example will always far outweigh collective experience and general statistics.

As in, “my child got a bad reaction to immunisation which means yours will too” generates a much more powerful response in parents than millions and millions of non-affected children in some faceless study. And you see that in operation on Holmes every time the immunisation debate heats up…

I have had, on at least four occasions over the past 20 years, very strong feelings that my father had died or something had happened to him. Once I even rang him in the middle of the night from Japan, where I was living, just to check that he was OK, the feeling was so strong. I was wrong all four times. And the week he did die, I had no inkling at all, much to my sorrow.

I once had an incredibly vivid dream that my second son Perry fell off a bridge into a fast-flowing river. Very, very vivid dream — wind blowing, sharp streetlight shining on the water, his face disappearing beneath the muddy swirls, a terrible gut-churning wrench. Still makes me shudder even six years later. But he was just a toddler in my dream and he’s well past that now, at nine years old. And no, he’s never fallen off a bridge.

Now I am very conscious of the importance of counter-examples, so I have made a point of remembering those times when I have had strong feelings or dreams that haven’t panned out so I can say honestly that we do have such feelings and sometimes they are wrong.

But if my father had had problems within a week or so of any of those times I had worried about him, I could easily claim it as “proof” that intuition works…

Part of it comes down to an understanding of the statistics of coincidence. If I had continued to have dire warnings of my Dad’s imminent demise, then odds-on I would have had one some time close to the point he did die.

Thank goodness the majority of the world is comprised of thinking, feeling, spiritual beings who are intelligent and open minded enough to realise that life is comprised of such complex, multi faceted components which make up our universe and which no scientist or skeptic could possibly begin to understand or prove in a laboratory.

I’d agree with you with the first part — skeptics are incurable optimists and we’d love to believe that the majority of the world is comprised as you describe. It may be that you are confusing skepticism with scientism; the latter is the dogmatic view that science explains everything. Ironically enough, very few real scientists subscribe to it, although the stereotypes assume that they do…

As regards the second assertion, I don’t think any scientist or skeptic worth their salt would suggest that all things are explicable or provable in a lab. We recognise the need for humility in the face of the universe’s complexity, but we also appreciate that some of the complexity can be known better and appreciated in all its glory, if we but ask questions.

As a medievalist, I know that the stars were once regarded (at least in the Judaeo-Christian West) as bright points of light fixed in an immoveable globe of crystal. As a keen amateur astronomer, I know that the universe is much more complicated than that. I would say that the later knowledge is no less beautiful, fascinating and uplifting than the former view, and all the more powerful for being based in reality and shared with millions of others regardless of their culture or world view.

I see you skeptics are making submissions regarding complementary health in New Zealand. Don’t waste your time… Natural medicine is the fastest-growing industry in the world and will continue to be …

Yes, we know it is very popular, which is why it is important to be sure that it is both safe and effective — we can ask no less of anything which we use as medicines, regardless of whether it is herbal or industrial in origin. Anything less is not only potentially dangerous but also ethically unacceptable.

We don’t allow used-car salesmen to make unsubstatiated claims about their vehicles or sell unroadworthy ones (or if they do, we prosecute them). Our health, and the health of our children deserves no less scrutiny.

We recognise that medically useful things have come from chance discoveries, which is why it is important to keep an open mind. What we need to do is ensure that any practice or product we use is safer and more effective than whatever we currently have. That’s the gist of our Complementary and Alternative Medicine (CAM) submission — have you read it? (You can see it online at the Skeptics website, as we believe in open, transparent communication.)

Oh by the way, did you know that 80% of pharmaceutical drugs have no proven efficacy.

I’m not sure where your figure comes from, but certainly there is far too much useage and far too little scientific underpinning for many widely used products. That awareness has led the push for reexamining what drugs we use, how effective they are and whether there are better alternatives.

That’s why you’ll find skeptical groups as equally vocal about the over-prescribing of antibiotics as they are cautious about the claims for mega-vitamin dosages.

It’s why we often point out that a good two-thirds (if not more) of what ails us will get better within three days, regardless of whether you visit a GP or a homeopath.

It’s why we support evidence-based medicine which looks at safety and efficacy issues, critically examing our own assumptions about long-held medical beliefs. We know, for example, by looking at the evidence, that earache in children is best left alone and monitored, rather than treated with antibiotics. We know, by looking at the evidence, that episiotomies for childbirth aren’t warranted in the vast majority of cases, and have been pleased to see their use drop significantly.

We wouldn’t know these things if we didn’t stop to ask questions, to assess the evidence. And, if we are going to hand over our money or our lives to any kind of medical practitioner, surely it makes sense to ensure that they know what they are doing?

…and that 13,000 New Zealanders a year die from the side effects of medically prescribed drugs. Now that is a worry and something you skeptics would be far better off being skeptical about…

That’s an astonishing figure if you stop to think about it (which, after all, is all that skeptics ask people to do…). Where does it come from?

Lessee, that’s half of all deaths in New Zealand annually (I’m using the figures from the 1995 NZ Yearbook, which is the most recent one I have to hand, but I don’t think the figures have changed that much; it cites 26,437 deaths in total).

I guess if you assume that everyone who has cancer or heart disease or cerebrovascular disease died purely as a result of their medication (which assumes they were on medication in the first place), then you’d get somewhere near the figure you quote. But I don’t really think that that is a valid assumption, do you?

Given the type of disease and the likely demographics, then it wouldn’t be unsurprising to have a large number on medication, but the mere fact of that would not be enough to warrant the assertion that it was the drugs wot did it! While we can be critical about regulatory systems, medical practice, the public health system etc, a death rate of that size solely attributable to side effects from medicine would be Big News.

I don’t think that the aspirin my Dad was taking for his heart disease killed him, for example — he died because his heart finally stopped working. And, in fact, I believe that it may well have given him an additional 15 years he would not have had otherwise (the time between his first heart attack and his final), given the evidence for aspirin’s use in heart problems.

We can only find out whether there is a causal relationship between things by examining case after case after case, hence the importance of evidence and record keeping.

We’d encourage CAM practitioners to be involved in this (and some of the best are), not only to help their clients but also to help a better understanding of health issues and responses themselves.

My apologies for the length of this response, Margaret, but the issues you raise are not simple ones, and there are no simple answers. I hope you’ve taken the time to read this far — it’s a sad irony that we often find it’s those who are involved in alternative viewpoints who are not willing to hear other views or reconsider their beliefs. I guess that’s the nature of humanity, but one always lives in the hope of encouraging others to think more deeply — that’s what the NZ Skeptics are all about.

Sincerely
Vicki Hyde
Chair-entity

Complementary and Alternative Medicine Submission Now Out

The Word-based submission to the CAM discussion document which was sent out in our (NZCSICOP) name is now available for you to read at http://skeptics.org.nz/cam

My apologies for not being able to circulate this prior to sub-mission, but we only just finished the proof-read five minutes before submissions closed, with the much appreciated help of researchers world-wide (Stephen Barrett of Quackwatch has even sent his own submission in with a line-by-line critique of the proposals!).

I’ve tried to be as hardline as possible in those areas which are not negotiable. And I’ve tried to provide some grounds for cooperative, rational development in those areas where CAM may prove its utility, rather than rejecting it out of hand.

I hope that for the most part I have the mix about right, and that you consider it a reasonably representative view of our organisation.

Exhaustedly,
Vicki Hyde

The list below, taken from the submission’s introduction, covers the general recommendations it makes; each point is covered in detail in the remainder of the document.

Problems of Basic Focus

  • The basic question is whether CAM can help, not how;
  • Ministerial Advisory Committee on Complementary and Alternative Health (MACCAH) definition of CAM is too broad;
  • Better definitional analysis of CAM is required;
  • Categorisation and prioritisation necessary for evaluation, research and application;
  • Broader representation on MACCAH needs to be addressed for credibility of policy recommendations.

Regulation

  • Need to recognise public demand for regulation;
  • Does training imply competency? Disclosure and liability responsibilities must be enforced;
  • Regulations required against disproven and unsafe practices and products;
  • Need to ensure that apparent safeguards arising from regulation are not misleading to consumers;
  • Costs should be borne predominantly by CAM industry with independent monitoring;
  • Regulations need to recognise range of risks;
  • Lower standards for CAM harm its own credibility and should not be accepted;
  • Self-regulation is inadequate and inappropriate;
  • Issues of public accountability and enforcement have to be addressed;
  • Failure to regulate products leads to public harm;
  • Clear, consistent product regulation is vital and achievable;
  • Recommended response to ensure safety and efficacy.

Consumer Information Needs

  • Informed choice should be a primary requirement and must include totality of available evidence;
  • MOH database needs to be balanced, neutral to achieve credibility;
  • Vested sources can be inaccurate, misleading and potentially dangerous;
  • Publication bias has to be recognised and assessment provided.

Research, Evidence and Efficacy

  • Identify practices, products outside the scope of research;
  • CAM is big business and should contribute to research;
  • Credible research programmes can provide useful information;
  • Public research programmes need to prioritise promising approaches over questionable ones;
  • Public funding should be based on results and capped at appropriate levels;
  • All research programmes need to be robust and defensible;
  • Binding negotiated research protocols required;
  • Negative results need to be acknowledged, accepted and publicised;
  • Anecdotal evidence should be treated as an indicator for research, not a research result.

Integration

  • First, do no harm; second, do some good;
  • Education and training required: acknowledged where limited or conflicting;
  • Evidence of safety and efficacy vital prior to integration;
  • Integration efforts require monitoring and evaluation as current examples are inadequate;
  • Ethical standards necessary regarding declaration of commercial interests;
  • Cost-benefit analysis required prior to integration.

Newsfront

Australians turn up the Heat on Pan

Breaking news as this issue goes to press (Waikato Times, April 30 and elsewhere) is the recall by Australia’s Therapeutic Goods Administration (TGA) of 219 products manufactured by Pan Pharmaceuticals. This is the biggest recall of medical products in Australia’s history; the TGA has also withdrawn Pan’s licence for six months.

Pan is Australia’s largest contract manufacturer of herbal, vitamin and nutritional supplements, representing 70 per cent of the Australian complementary medicine market and exporting to dozens of countries. It also makes some over-the-counter medicines including paracetamol, codeine, antihistamines and pseudo-ephedrine.

TGA principal medical adviser John McEwen said other products manufactured by Pan but sold under different brand names would be added to the list as they were discovered. Dr McEwen said Pan lost its licence following evidence of substitution of ingredients, manipulation of test results and substandard manufacturing pro-cesses.

Consumers have been warned not to take any vitamins or herbal supplements and even to check the label of headache pills.

The TGA said it was considering laying criminal charges as it continued the investigation.

Equipment at Pan’s headquarters in Sydney was not cleaned between batches, potentially contaminating products.

The investigation was sparked by a travel sickness pill, Travacalm, which the TGA said had sent 19 people to hospital and caused 87 adverse reactions.

“Some people were very, very ill. They tried to jump out of planes, off ships and things like that because of the hallucinatory effect,” federal parliamentary health secretary Trish Worth said. “I’ve been reliably informed it was fortunate nobody died.”

She said Pan’s vitamin A and natural remedy teething gels could be very harmful to pregnant women and children.

The Complementary Health-care Council said the entire health industry would be hurt by a loss of public confidence. The council’s technical director, Ian Crosthwaite, said manufacturers were holding crisis meetings and seeking an urgent meeting with the TGA to stop any further recalls. But the TGA’s Dr McEwen, said: “There is a clear risk with these products of serious injury … the longer we leave these products in the market the risk grows.

Pan recorded a $A13.6 million ($NZ15.30 million) profit last financial year, however founder James Selim saw his personal wealth of $A210 million collapse by $A26 million as shares plunged after the recall.

The Australian Stock Exchange is demanding answers as to why Pan failed to call for a trading halt in its shares as soon as it learned its licence had been suspended.

Sections of the market had the news of the licence suspension for 30 minutes before trading was halted.

A report by ECM Research on Pan Pharmaceuticals in September last year said about 40 per cent of its sales were exported and New Zealand was the most important destination, followed by Asia and Europe. The New Zealand market accounted for about a third of its market revenue.

The report also said Pan was supplying SAM-e, a natural antidepressant, into Australia and New Zealand. SAM-e is listed in advertisements for product recall. Other Pan products sold in New Zealand include libido enhancer Horny Goat Weed.

Great Balls of Fire

Thai scientists are to launch a probe into a famous fireball phenomenon occurring in the Mekong River once a year in the country’s north, (Sydney Morning Herald, April 14). Every year on the first full moon of the 11th lunar month, which coincides with the end of Buddhist Lent, hundreds of red, pink and orange fireballs soar up into the sky from the Mekong, drawing crowds of spectators.

The event known as Naga’s Fireballs, which has been reported by locals for generations, has long mystified scientists. Now nine experts are to start collecting soil and water samples from the areas where the fireballs appear to originate, deputy permanent secretary of the Ministry of Science and Technology, Saksit Tridech, told the Bangkok Post.

“We are quite sure the fireballs are a natural phenomena,” he reportedly said, adding that the team’s initial assumption was that the fireballs were caused by methane and nitrogen. Decomposition of accumulated plant and animal remains on the bottom of the Mekong could lead to the release of the gases, which rise to the surface of the water when the sun heats the water to a certain temperature, Saksit said.

Legend, however, says the flames come from a mythical Naga, or serpent, living in the Mekong river. “Society needs an explanation for this phenomenon,” said Saksit.

Claims by a television program last year that the fireballs were actually caused by tracer bullets fired by Laotian soldiers across the border caused uproar among locals, who called the suggestion insulting.

Abductees Stressed Out

People who claim to have been abducted by aliens suffer many of the same trauma symptoms as Vietnam veterans and World Trade Centre survivors, even though their memories are not real (Dominion Post, February 19).

A Harvard University team found that when recalling experiences they show many of the physical and psychological effects normally seen in post-traumatic stress disorder, including nightmares, anxiety, racing heartbeats and sweating palms.

The team suggests most abductees are not mentally ill and genuinely believe they have been kidnapped, but are experiencing false memories induced by sleep paralysis. This affects 30 per cent of the population at some stage in their lives, and occurs when a patient wakes during rapid eye movement sleep, when dreaming takes place and the entire body is paralysed with the exception of the eyes. It can often lead to frightening visions referred to as hypnopompic (upon awakening) hallucinations as elements of a dream impinge on wakefulness.

Sufferers usually report being unable to move while seeing shadowy figures around their beds, feeling electric currents coursing through their bodies, or levitating. The phenomenon probably explains the witch crazes of the 16th and 17th centuries, ghost sightings and other paranormal events, says Harvard psychology professor Richard McNally.

“Today, in Cambridge, Massachusetts, it’s interpreted as abduction by space aliens.”

All 10 abductees in the study recounted reasonably consistent details of their experiences, but these were almost certainly culturally determined. “Their memories were of being subjected to sexual and medical probing on spaceships. I certainly think we can say the X-Files probably helped with all that.”

Extraterrestrial Culture Day

The good folk in Roswell, New Mexico, who would no doubt dismiss the above item, can now celebrate every second Tuesday in February as “Extraterrestrial Culture Day”, after a local lawmaker’s proposal won House approval (Dominion Post, 25 March). Some scoffed at the idea, but memorial sponsor Republican Dan Foley said life on other planets — if you believe in it — surely has its own set of cultural beliefs. He claims aliens have contributed to recognition of New Mexico, and he wants a copy sent into space as a token of peace.

Calling All Spoon-benders

Mind readers, telepaths and anyone who attracts ghosts have been invited to participate in a new course at Griffith University in Australia (Dominion Post, February 21). Senior lecturer Martin Bridgstock says the subject, Scepticism, Science and the Paranormal, will give students the opportunity to study areas of science made famous by television shows such as The X-Files and The Twilight Zone.

Dr Bridgstock said he decided on the subject because he was impressed by the large number of people he encountered who believed in the paranormal. Opinion polls showed a majority of the population believed in psychic healing, while substantial minorities believed in astrology, mind-reading, UFOs and ghosts.

He said he would welcome anyone who approached the university claiming paranormal powers. “I would get the class together and I would invite this person to say exactly what he or she thinks they can do. Then we would try to devise an experiment which would enable that person to show if in fact they could do it under tightly controlled conditions.”