Bruce Ames: Environmental Prophet or Apostate?

What is the link between chemicals and cancer?

Forty years ago, Bruce Ames was a young microbiologist working at NIH in the day and enjoying Scottish country dancing in the evening, when he had an inspiration: to use the rapid growth of bacteria as a method for determining whether a particular chemical was able to cause mutations. If the chemical was positive — i.e., was mutagenic — it might be considered as a possible cause of cancer. This method, soon called “the Ames test”, became widely used. It was cheap, fast, and sensitive. One of the first discoveries was that a dye commonly used in children’s pyjamas had mutagenic properties. Bruce Ames became a hero to the environmental movement when he led a successful campaign to ban such dyes.

Ames was more interested in reducing the death toll from cancer than he was in attacking new chemical technology. As more results from the Ames test accumulated, he realised that many naturally occurring chemicals were also giving positive results. Even more disturbing, the number of chemicals that seemed to be positive in high-dose tests on mice and rats was, he felt, excessive. In an extensive series of important reviews, published in prestigious journals such as Science and Proceedings of the National Academy of Sciences, he has attempted a quantitative estimate of the difference in human cancer. Because his figures show manmade chemicals in food and the environment to be quite insignificant compared to natural or self-inflicted factors, the name of Bruce Ames is now anathema to the same environmental movement that once applauded him. Nevertheless many professional scientists believe that Ames’ position is basically correct. If the inventor of the Ames test now says that most methods for detecting carcinogenicity are invalid, it is certainly not a case of sour grapes. This article is an attempt to summarise his beliefs. Those who are sufficiently interested should read some of the papers listed in the bibliography.

(1) What do we know about the incidence of cancer?

First, cancer risk increases according to the 5th power of age. That is, a 40-year-old is 100,000 times more likely to be cancerous than a 20-year-old. There are more cancer cases per 100,000 population simply because we are living longer and no longer dying of infectious diseases.

Second, the age-corrected mortality (death rate) from cancer has been declining since 1950 except in those over 84. Overall decline has been 13%. Naturally much of this decline is caused by improved detection and treatment. The only exceptions are lung and skin cancer, clearly caused by tobacco smoking and by increased exposure to sunlight. There are occasional claims that certain types of cancer are increasing slightly, but improved methods for detection are probably responsible.

Thirdly, some mostly unknown environmental factors have a major influence on the types of cancers that are likely. Japanese, for instance, have a high incidence of stomach cancer, yet Americans and Japanese-Americans have a low incidence. On the other hand, American men have much more likelihood of prostate cancer than do Japanese.

(2) What are the major known causal factors in cancer?

The single most important factor is smoking. This accounts for one-third of all US cancer deaths, not to mention one-fourth of heart disease. Each year, smoking causes 400,000 premature deaths in the US and 3 million deaths around the world.

Chronic infections contribute to about one-third of cancer on a world- wide basis. As mentioned below, any factor that causes body cells to divide increases the likelihood of cancer. Hepatitis B and C infect 500 million people, mainly in Asia and Africa. This liver infection is a major cause of “hepatocellular carcinoma”. Two different Schistosomiasis worms infect Chinese colons and Egyptian bladders, being associated with increased cancer risk in those two organs. Liver flukes cause chronic inflammation of the biliary tract, hence risk of cholangiocarcinoma. A bacterium, Helicobacter pylori, is adapted to living in the human stomach and is now believed to be a major cause of stomach cancer, ulcers and gastritis. (So much for the classical psychogenic explanation for ulcers!)

Overall about 70% of cancers might be caused by environmental factors, but pinpointing the exact causes is very difficult. There remains some 30% that cannot be ascribed to any factor other than age and bad luck.

(3) How does cancer develop?

The first requirement is that a dividing cell suffer some sort of damage to its DNA. (DNA is the basic material of our genes.) DNA damage occurs all the time, but our bodies have excellent repair mechanisms to detect and destroy damaged DNA. Based on the amount of DNA breakdown products in the urine, Ames and co-workers estimate about 10,000 “hits” on DNA every single day in an adult. These repair mechanisms are not 100% perfect, and some damaged DNA does escape.

DNA damage is mostly caused by oxidants. The oxidants in turn arise from both internal and external sources. Internal oxidants come from mitochondria, peroxisomes, cytochrome P450 enzymes, and phagocytic destruction of infected cells. The production of oxidants when infected cells are destroyed may be a factor in the connection between chronic infection and cancer. External sources of oxidants include the nitrogen oxides of tobacco smoke, iron and copper salts, and natural plant phenolics like chlorogenic and caffeic acid.

If oxidants are bad, then antioxidants should be good. They are: antioxidants protect against disease. Natural antioxidants include ascorbic acid (vitamin C) and tocopherol (vitamin E). Synthetic antioxidants are also good. One worker estimated about 5% reduction in cancer because of approved antioxidants added to our food.

The health benefits of antioxidants, provided mostly by fruits and vegetables, are statistically highly significant. The quarter of the US population with the lowest intake of fruits and vegetables has double the cancer rate of the quarter with the highest intake. This applied to “epithelial” cancers (lung, mouth, larynx, oesophagus, stomach, pancreas, cervix, bladder, and colorectal) plus ovarian cancer. Breast and prostate cancer, on the other hand, is less affected by fruit and vegetable diets. (Although there is at least a statistical link between fat/calorie intake and breast cancer.)

Persons taking daily tocopherol or ascorbate had one-third the risk of developing cataracts. In contrast, smoking and radiation (both well known oxidative stresses) are strong risk factors for cataracts. Smoking seems to destroy ascorbate: smokers need to take double or triple amounts of ascorbic acid to achieve the same blood levels as non-smokers. Incidentally, smoking by the father seems to affect sperm production and health; smoking fathers increase the risk of birth defects and childhood cancer in their offspring.

Excess food, at least in rats, is “the most striking rodent carcinogen ever discovered”. Even a 20% increase in calories over the optimal results in shorter life, with more endocrine and mammary tumours.

Excessive cell proliferation (cell division) is a very important factor in cancer production. This has been mentioned above in relation to chronic infection. Major dietary factors, such as salty pickles in the Japanese diet, have been hypothesised to be involved in the high rates of stomach cancer in this population. Even table salt, at high enough concentrations, can cause stomach cancer.

That cell proliferation predisposes to cancer is a major source of false positives in chemical screening as normally carried out. Test chemicals are repeatedly applied to animals at the “MTD” (maximum tolerated dosage). This is like chronic wounding, “which is known to be both a promoter of carcinogenesis in animals and a risk factor for cancer in humans”. Many chemicals that purportedly have caused cancer at high dose (MTD) levels, may therefore not be true carcinogens. The infamous saccharine tests are a case in point: only female mice dosed with nearly toxic levels of saccharine showed an increase in bladder tumours.

For these chemicals that “cause cancer” at high doses only by tissue irritation, a tenfold reduction of dose in a rat or mouse experiment would show much more than a tenfold reduction in risk. This seems to have been confirmed. One analysis of 52 tests showed that two-thirds of the purportedly positive results for carcinogenicity would not have been found if the dosage had been cut even by one-half! (I suspect that commercial cancer-screening laboratories get new contracts in direct relationship to how many “successes” they have had previously.)

(4) How do synthetic and natural chemicals line up as causes of cancer?

The conventional cancer-screening techniques are, as stated above, too sensitive. There are not merely a few chemicals that show up as carcinogenic. Instead, nearly one-half of all chemicals tested seem to be positive in these tests. The ratio is the same for both natural and manmade chemicals, even though very few natural chemicals have been tested. Thus we cannot generalise that natural chemicals are inherently safer or riskier than synthetic chemicals. We must look instead at the quantities of chemicals ingested.

Plants contain surprisingly large quantities of natural pesticides. One of Ames’ greatest achievements, in my opinion, has been to compile convincing evidence about how many natural chemicals have pesticidal functions. (In my youth, the question of the function of different “secondary” plant products was much debated. Some thought that products like alkaloids and lectins were mere accidents of metabolism, a plant process gone wild. I personally thought that the main role of these chemicals was to provide research material for young biochemists.) Ames pointed out that up to 5% of the fresh weight of vegetables can be natural pesticides.

The list is very long, and a sample limited just to non-toxic plants would include: the sharp flavours of mustard and other cabbage-family crops; piperine (10% of weight of black pepper); light-sensitising psoralens in parsnip and celery; chlorogenic and caffeic acid in coffee beans; nerve-poisoning alkaloids in potatoes, tomatoes and eggplants. The cat-attracting chemicals in catnip are actually very good insect repellents. The vast majority of plants are inedible by us. Even so we are at risk of poisoning if cattle or sheep graze on them. Abraham Lincoln’s mother died when she drank milk of cows that had grazed on snakeroot. A California infant was born deformed when fed milk from a goat that had been eating lupin. The concept that “natural is harmless” is simply false.

Ames has published numerous estimates of the amounts of natural pesticides that we eat every day. He calculates that we eat about 10,000 times more natural pesticides than synthetic pesticides. More usefully, he and his coworkers have attempted to estimate the relationship between the amounts of different chemicals we are exposed to, and their potency as carcinogens. After all, it is the dosage that makes the poison, to coin a phrase. Some of his calculations are shown in Table 1, rewritten from Ames et al., 1987. The last column (HERP%) is a relative risk. A 5% HERP doesn’t mean a 5% risk of cancer!

Material Carcinogen, dose to 70kg person Rodent Potency Risk (HERP%)
Tap Water Chloroform, 85 ug 90 0.001*
Contaminated Well water Trichloroethylene, 2800 ug 940 0.004
Home air Formaldehyde, 598 ug 1.5-44 0.6
PCB’s, daily PCB’s 0.2 ug (US average) 1.7-9.6 0.0002*
DDT/DDE, daily DDE, 2.2 ug (US average) 13 0.0003*
Bacon, cooked Nitrosamines, 0.4 ug 0.2 0.003-.006
Peanut butter Aflatoxin, 64 ng/sandwich 0.003 0.03
Brown mustard Allyl isothiocyanate, 5 mg 96 0.07
Mushroom, 1 raw Hydrazines 20-300 0.1
Beer, 350 ml Ethyl alcohol, 18 ml 9110 2.8*
Wine, 250 ml Ethyl alcohol, 30 ml 9110 4.7*
Comfrey-pepsin tablets, 9/day Comfrey root 626 6.2
Diet Cola, 350 ml Saccharin, 95 mg 2143 0.06*
Phenacetin pill Phenacetin, 300 mg 1246-2137 0.3**
Phenobarbital, 1 sleeping pill Phenobaribital, 60 mg 5.5 16***
Formaldehyde, industrial Formaldehyde, 6.1 mg 1.5-44 5.8
EDB, industrial exposure Ethylene dibromide, 150 mg 1.5-5.1 140

Table 1: Calculated risk factors for common chemicals.
* Material not believed to be gene-damaging; that is, acting as a carcinogen only by irritation or damage at high concentrations.
** Some evidence for increased kidney (renal) cancer after long-term use.
*** Apparently no cancer risk to people taking it for decades.

How then do these theoretical risks relate to the “real world”? A few links can be found. There have been perhaps dozens of cases of liver damage from comfrey-pepsin tablets, although this has been as “hepato-occlusive disease” rather than cancer. These comfrey-pepsin tablets have a risk factor (HERP%) of about six.

Although alcohol is a low-potency carcinogen, large quantities are consumed by some people. Alcoholics have significantly increased risk of cancer in the mouth and throat. Thus HERP’s around five seem to be genuine risks. On the other hand, the HERP value of 16 for one phenobarbital sleeping pill is apparently not connected with any risk of cancer. (Note that phenobarbital is one of the numerous so-called carcinogens that shows up as positive only at tissue-irritating concentrations.)

One interesting point is that TCDD (the dreaded “dioxin” of milk cartons and teabags) is known to cause most of its effects by reacting with an animal component called “Ah receptor”. There are chemicals in broccoli, mainly indole-carbinol, that also react with the Ah receptor. Both chemicals can protect against cancer if administered before challenge with a carcinogen. Both chemicals can promote cancer if administered after the carcinogen has already acted.

Taking potency into account, a 100 g portion of broccoli has 20,000 times more effect on the Ah receptor than a legally allowable TCDD intake of six femtograms/kg/day. (Perhaps it is not surprising, then, that experiments in which rats given a carcinogen were protected by including broccoli or cabbage in their diet. There is evidence that humans too are protected by these vegetables: People who are high-crucifer eaters are significantly less likely to wind up in cancer wards.)

(5) How pesticide regulations and chemical scares diminish public health.

Diet is one of the key routes to better health. Only 9% of the US population eats sufficient fruit and vegetables, higher consumption of these would decrease cancer as well as other diseases. There is plenty of margin to increase fruit and vegetable eating.

To discourage consumption of vegetables and fruits is to diminish public health. Excessively strict limits on harmless levels of synthetic pesticides act to increase vegetable and fruit prices, by reducing production and by increasing cost of production. Thus these regulatory restrictions may well be harming health rather than helping it.

Similar comments could be made about the attacks on Alar a few years ago, when apples disappeared from the lunchboxes of many children.

This then is one reason why Bruce Ames is hated by many “environmentalist” groups. He has shown that they are, in all likelihood, damaging public health under the guise of protecting it against non-existent or unimportant risks.

Acknowledgement:

This review was inspired by an article by Dr Arthur B Robinson in Access to Energy, April 1994.

References

B.N. Ames. 1983. Dietary carcinogens and anticarcinogens. Science 221: 1256-1262.

B.N. Ames, R. Magaw, and L.S. Gold. 1987. Ranking possible carcinogenic hazards. Science 236: 271-280.

B.N. Ames and L.S. Gold. 1990. Environmental pollution and cancer: some misconceptions. In: Science and the Law (Ed. Peter Huber).

B.N. Ames and L.S. Gold. 1990. Too many rodent carcinogens: mitogenesis increases mutagenesis. PNAS 87: 7772-7776.

B.N. Ames, M. Profet and L.S. Gold. 1990. Dietary pesticides (99.99% all natural), mitogenesis, mutagenesis, and carcinogenesis. PNAS 87: 7777-7781.

B.N. Ames, M. Profet and L.S. Gold. 1990. Nature’s chemicals and synthetic chemicals: comparative toxicology. PNAS 87: 7782-7786.

B.N. Ames, M.K. Shigenaga and T.M. Hagen. 1993. Oxidants, antioxidants, and the degenerative diseases of aging. PNAS 90: 7915-7922.

B.N. Ames. n.d. Does current cancer risk assessment harm health? Published by The George C Marshall Institute, 1730 M Street, N. W., Suite 502, Washington, D. C. 20036-4505. ($US 5.00) [Not seen by me yet — JDM]

Forum

Where Were the Hunters?

The account of the meeting between the Moa hunters and the Christchurch Skeptics was interesting, but contained some very odd statements. How many skeptics had done any hunting, I wonder? The account reads as though there were no experienced hunters present who could challenge some of the statements made. That is rather like examining key-benders without a magician present. However, the account, like many UFO sightings, contains several inconsistencies which are not obvious to the inexperienced.

I have shot many hundred deer, plus pigs, goats, chamois, wild cattle and sheep so I count as an experienced hunter.

While hunting, one sees difficult-to-identify objects all the time. It is very hard to spot animals unless they move, even when cover is light. Any bush, rock or shadow that is approximately the right colour needs to be scanned. Many a deer or pig turns out to be something inanimate when examined through binoculars or telescope. It will perhaps astound the inexperienced to be told that this applies even to objects which are very close.

Sometimes one could swear the thing moved.

One of the odd things about the story is that there is no mention of binoculars or telescope; were they not used?

“His rifle didn’t even go near his shoulder”. This implies no telescope and suggests he is not a very serious hunter. My rifle, on a hunting trip, would be constantly at my shoulder — not to shoot but to carefully examine objects through the ‘scope. It is essential not to shoot until one is certain of the identification.

“The beast was unmistakably not a deer.” That is simply the voice of inexperience. If the party had no binoculars and no telescope then their story cannot be taken seriously however close the object was. Anyone with moderate experience in looking at wildlife should know that the human eye without the aid of magnification is incapable of such assessment.

To my horror, I once found I had shot a goat, not a deer. I had wrongly identified a very close goat with a distant deer in excellent light! The bullet had struck high of course. But I was certain of my target; I was just wrong. The diagnosis was simply that I needed to start wearing my glasses and have done so ever since.

In a long career of shooting there will inevitably be a number of targets which were allowed to escape because positive identification was impossible. I can think of several — I am still not sure what they were. But I never thought they were extinct birds. I suggest it takes a particular mindset to make such an identification.

If this is the first Unidentified Running Object the party had seen then they simply lack experience, however many years they claim.

Jim Ring, Nelson

Missing Address

In the December Skeptic you have a note by B. Premanand asking New Zealand skeptics to help their Indian counterparts by subscribing to Indian Skeptic. However, he does not give an address. Do you have one?

Gordon Hewitt

Apologies for omitting the address. It is:

B. Premanand
Convenor, Indian CSICOP
10 Chettipalayam Road
Podanur 641-023
Tamilnada
India

Skeptics Meet Moa Spotters

It was a surprise to many outside observers, especially those who don’t well understand the Skeptics. Paddy Freaney, Rochelle Rafferty, and Sam Waby, the trio who gained world attention early this year by their claim to have glimpsed a living moa in the Southern Alps, were invited to put their case before a meeting of Canterbury Skeptics.

The discussion was serious, friendly and good-natured, without sarcasm or hostility. Sam Waby began with a passionate defense of the claim. He’s been stalking deer up there for 30 years, he explained, but when he sighted the big bird, his rifle didn’t even go near his shoulder. He spoke with intense conviction, and was backed up by Rochelle who also said the beast was unmistakably not a deer. Beside describing his encounter and short chase after the animal, Paddy Freaney complained with some bitterness about the failure of Department of Conservation investigators to take the claim seriously.

In their coherence, consistency and sense of sincerity, these three were remarkable. No one forced them to front up. The very fact that they accepted the Skeptics’ invitation in the first place has to be seen favourably. Were the episode a hoax, it would have been far easier to have been “too busy” to accept the Skeptics’ invitation.

On the other hand, the difficulties with the story seem intractable. The apparent bird was large. Paddy claims recently to have seen damage to bushes possibly consistent with moa browsing, but where are the droppings? The site was a remote, unvisited area, but it is still implausible that a bird that large could survive undetected for so long. He readily acknowledges these problems, but sticks to the story.

After an evening in which careful intelligent questions were asked by an audience of about fifty, it was very hard to imagine the trio was lying. I had an experience immediately after the meeting that is worth relating. A handful of us remained in the bar of the University Staff Club. At one point I overheard Freaney and Rafferty talking privately in a corner of the room. She complained that he hadn’t given her enough chance to speak, to which he responded with friendly but exasperated surprise that she didn’t even want to come along at first.

The tone and content of this exchange (I don’t repeat it all) was not what you’d conceive of as coming from two lying conspirators — unless they were accomplished and well-rehearsed actors who even in private even put it on for themselves.

That’s logically possible, but few Skeptics left the meeting thinking the moa sighting was an intentional hoax. Pace Waby’s passion, still a deer perhaps, or something else. As Vicki Hyde points out, there are only three possibilities: it was a hoax, a moa, or something else. If the first is to be eliminated, and the second seems still remote, we’re driven to the third. Still, as I pointed out in an editorial earlier this year, hope for a living moa glimmers in the heart of even the driest Skeptic.

This is the one point on which all in the room agreed — New Zealand needs a moa. The big bird remains a splendid and tantalising possibility. Paddy is continuing the search. The Skeptics wish him luck.

The Crackpot Index

On open access computer bulletin boards, any entity with a theory can expound on it at length. Many do — usually to a very unappreciative audience. A seemingly-large proportion of such expositions are surprisingly similar in style. The following scale (tentatively attributed to John Baez of Usenet sci.physics) will help readers establish just how crackpotted something is…

A simple method for rating potentially revolutionary contributions to physics.

  1. A -5 point starting credit.
  2. 1 point for every statement that is widely agreed on to be false.
  3. 2 points for every statement that is logically inconsistent.
  4. 5 points for each such statement that is adhered to despite careful correction [by other readers].
  5. 5 points for using a thought experiment that contradicts the results of a widely accepted real experiment.
  6. 5 points for each word in all capital letters (except for those with defective keyboards).
  7. 10 points for each claim that quantum mechanics is fundamentally misguided (without good evidence).
  8. 10 points for each favorable comparison of oneself to Einstein, or claim that special or general relativity are fundamentally misguided (without good evidence).
  9. 10 points for pointing out that one has gone to school, as if this were evidence of sanity.
  10. 20 points for suggesting that you deserve a Nobel prize.
  11. 20 points for each favorable comparison of oneself to Newton or claim that classical mechanics is fundamentally misguided (without evidence).
  12. 20 points for every use of science fiction works or myths as if they were fact.
  13. 20 points for defending yourself by bringing up (real or imagined) ridicule accorded to one’s past theories.
  14. 30 points for each favorable comparison of oneself to Galileo, claims that the Inquisition is hard at work on one’s case, etc..
  15. 30 points for claiming that the “scientific establishment” is engaged in a “conspiracy” to prevent one’s work from gaining its well-deserved fame, or suchlike.
  16. 40 points for claiming one has a revolutionary theory but giving no concrete testable predictions.

Monkeying with Your Private Parts.

Rejuvenation! The wish of many a tired old man, and not so old: to regain the physical and sexual vigour of youth.

During the early decades of this century it was widely though not universally believed that such a rejuvenation, a turning back of the clock, could be achieved. It was thought that the secret of youth lay in the primary sex organs, so transplantation of the testis from young to old was the method adopted. In the 1920s a dozen or more surgeons around the world were ministering to this fervent desire by grafting the testes of young animals into those patients who could afford the fee.

We now know that this operation was quite useless, yet the surgeons and their hundreds of patients were on the whole convinced that the latter were indeed made to feel younger and fitter. Since that time we have discovered what formidable barriers the body raises against the introduction into it of “non-self” tissues. Material even from close relatives is rejected, and only in very recent times have methods been found for breaching the body’s defences to allow the intrusion of carefully matched foreign organs. This type of operation still makes newspaper headlines. Grafting between different species, using the techniques of sixty or more years ago, is impossible; rejection, the complete killing of the graft, would have been very rapid.

We have here, then, a most powerful example of the placebo effect, so a closer look at these events would follow naturally on Bill Morris’s article on the subject in the previous issue (Skeptic 27).

To set the scene, the medical background to the activities of the gland grafters, we note that as the century began the science of endocrinology was just beginning. The powerfully acting secretions of the endocrine glands were slowly being discovered and studied. First, the effect of extracts of thyroid glands on cretinism and myxoedema, then in the early twenties the anti-diabetic action of the pancreas extract insulin.

Gland Extracts to Restore Virility

It seemed a natural extension that an extract of the testis gland should restore flagging virility, and some unsuccessful trials along these lines took place. (when a hormone was, many years later, isolated from testes, and named testosterone. it was found not to have the effect sought.)

Seeking a more successful way of using the sex gland, surgeons looked to grafting. It was known at that time that cornea and bone could be transplanted from one person to another; it was not then realised that these successful grafts were rare exceptions — rather they were taken to indicate that grafts between people of any organ were possible. This view was strengthened when the discovery of blood groups enabled doctors to avoid the disasters which attended many of the early attempts at blood transfusion. The fact that some skin grafts did not “take” was ascribed to less-than-perfect technique, and many apparent “takes” were only the growth of the recipient’s own skin, and not the graft at all.

So the grafters got to work, initially on animals, and then on human patients. The usual technique was to excise the testis from the donor animal, open the scrotum of the recipient, and to place either the whole donor testis, or a slice, close up against one of the recipient’s testes, and then to sew him up again. In most cases the implanted tissue appeared to persist over time, giving the impression that the graft had “taken”. From our present standpoint we view this effect as the result of the rapid invasion of the graft by host cells, so the apparent “extra” gland was merely inactive host tissue.

Some of the earliest transplants into humans (1919 on) were carried out on those well-known experimental subjects, the residents of US gaols. These were man-to-man transplants, the “death row” of the prison serving as a regular source of fresh donor material. Dr Leo Stanley, chief Medico at San Quentin Prison in California, was the leader in this work, and carried out many transplants into “volunteer” prisoners during the 1920s. He and his patients were generally pleased with the results, and he impressed his fellow physicians sufficiently that several of them underwent the operation themselves.

In spite of this, there is no doubt that the most famous of the testis grafters was Serge Voronoff, a Russian émigré doctor of great wealth and charisma, active in Paris from the 1880s until the Second World War. Already in his 50s, and with a successful and fashionable medical career behind him, he turned in 1919 to the work that made him famous, his rejuvenation treatment. Lacking access to human material, he chose as donor animal the chimpanzee.

Believing that human grafts were possible, he picked on man’s closest relative as being the most likely to provide a transplant acceptable to the recipient’s tissues. Despite the expense (the chimpanzees alone cost a small fortune, as they each had to be caught in Africa and brought safely to France), he had many patients.

Voronoff’s fame during the 1920s arose not only from the “success” of his grafts, but also from his copious output of books on the subject, which he continued to publish long after the operation had passed out of favour. He had had from the outset critics who doubted the efficacy of the testis grafts, but it is uncertain whether, judged by the knowledge of the time, they had more reason for their skepticism than Voronoff had for his optimism.

The two British doctors’ journals took differing views: the Lancet was consistently critical of Voronoff’s medical claims and reviewed his books unfavourably, while the British Medical Journal was generally more approving.

Perhaps surprisingly, Voronoff’s undoing came not from a medical but a veterinary quarter. Emboldened by his success with human patients, he returned to his earlier interest in animals, and put his talents at the service of French agriculture. In 1924 he secured the use of a flock of sheep at an agricultural station deep in the French colony of Algeria. Some of the young rams of this flock received a testis graft, others were left unoperated. On reaching maturity, the operated rams were found to be heavier, and yielded more wool, than the unoperated controls. Not only this, but the progeny of the grafted rams also gave more wool.

Success?

Conclusive proof! Surely this evidence would silence those who had doubted. The animal results could be assessed objectively, unlike the confidential and subjective observations on the human patients. So groups of veterinarians and agriculturalists were invited to inspect the “super sheep.” All but one of the international visiting parties were quite convinced; only the British put their fingers on the fatal flaw in Voronoff’s case.

Translated into present-day statisticians’ jargon, he had failed to randomise his young rams at the start of the trial. It is as if we judged the winner of a race by noting who first crosses the finish line, without ensuring that all competitors started from the same place at the same time.

Knowing now that these grafts must have been rejected, we can only conclude that Voronoff had, perhaps unconsciously, selected the better quality rams for the transplant group, and that this superiority had carried on into the animals’ maturity, and to their offspring.

Voronoff’s claims for the superiority of the offspring of his grafted rams implied “inheritance of acquired characteristics;” thus, all unwittingly, he had strayed onto the battlefield between the Lamarckians and the Darwinians. So, by his sheep experiments, he widened the area of interest in his work beyond the medical, attracting the attention of veterinarians, agriculturalists and finally general biologists.

By 1930 medical opinion was already turning against him; the scrutiny of the non-medical scientists hastened this process. By their nature, his human operations were very private, confidential affairs, the results of which were quite inaccessible for objective assessment by others.

When the fad for this operation died down, and its uselessness was realised, the practitioners were widely ridiculed, and reviled as quacks and charlatans. This was incorrect and sadly ungenerous; with few exceptions these surgeons were sincere men who wholeheartedly believed in what they were doing. Voronoff himself defended his work until his death in 1951.

A Change of Glands

That is not quite the end of the story of the gland-grafters. At the same time as testis transplants were going out of fashion, as described above, endocrinology was discovering more and more hormones produced by the body’s many glands, and these were available for “treating” a wide range of disorders.

The pituitary gland, in particular, was found to have a special role in controlling the activity of other glands (it was at one time called “the conductor of the hormonic orchestra”). Injection of cells of the pituitary, then, could be used by unscrupulous doctors to treat whatever glandular deficiency the patient could be persuaded he had.

The leading practitioner, Dr Niehans, a Swiss, was active until the 1950s, and counted Top People (from Hollywood to the Vatican) among his patients. None of his injections could have been of any use.

What lessons ought we to learn from this story, this false turning in medical science? Firstly, we see that misguided enthusiasts can be as dangerous as unscrupulous quacks. Furthermore, we should all subject our enthusiasms to rigorous self-scrutiny.

If Voronoff had kept better records of his operations, and taken a more objective view of the results, he might eventually have seen his error. Had he invited a histologist to examine his early sheep grafts he might have been convinced that they had indeed been rejected by the host. From the patient’s viewpoint, a person unhappy with his present state of health, having undergone a very expensive and uncomfortable operation, carried out by a charming, confident and persuasive surgeon, can almost be guaranteed to confirm whatever outcome of the operation the surgeon suggests to him.

A last thought: in a period which delivered to women the suffrage, protective labour laws and power-driven domestic appliances, the “rejuvenation” movement was almost entirely male-oriented. No-one seems to have considered whether anything could be done to help the post-menopausal woman who longed to be twenty again.

I am indebted for the information in this article to The Monkey Gland Affair by David Hamilton, London: Chatto & Windus, 1986.

Bands of Hope

Lewis Jones

Can a cotton wristband and a plastic button alleviate seasickness? The British Consumer’s Association thinks so, but scientific evidence indicates otherwise.

The sea has always brought out the best in me. Such as a good lunch. So all those ads for Sea Bands have been striking a responsive chord. You know the things. They keep coming up in those glossy colour brochures that fall out of your magazines and into your waste paper basket.

How the Royal Navy Fights Seasickness — you can’t speak plainer than that. If the navy doesn’t know about being seasick, who does? “The Royal Fleet Auxiliary tested the system in 1986, and declare it a useful, drowsiness and side-effect free alternative to drugs.”

At this point you look at the accompanying photograph and see what looks like a cotton wristband with an inset plastic button the size of an asprin. You look closer and examine the picture in careful detail to see what a Sea Band really is. It turns out to be a cotton wristband with an inset plastic button the size of an asprin.

Curiosity eventually got the better of me, and I decided to follow the Sea Band trail and see where it lead. When I contacted the Royal Fleet Auxiliary’s Principal Medical Officer, Dr Driver, I struck lucky right away. It was Dr Driver who tested the Sea Bands aboard Sir Lancelot in the South Atlantic. Of the 17 people tested, two-thirds said they thought the Sea Bands effective and one-third didn’t. This is a very small sample, so how about a control group? Well, another test had been planned on the good ship Tristram, without the plastic buttons, but there wasn’t enough bad weather. Dr Driver emphasised that such evidence as there was, was anecdotal.

Consumers’ Association Test

Then the British Consumers’ Association (CA) decided to hand out Sea Bands to 27 passengers on a cross-channel ferry. About two-thirds thought they felt less ill than usual, and one third didn’t. Still no control group. And again the sample was small. The CA admitted this was not a controlled clinical trial, but couldn’t resist going on to enthuse about results that were “quite dramatic.” They reported giving Sea Bands to children who felt sea-sick, and within minutes, “They were up and frisking around again.” And there was one young girl who stopped being seasick when she put the bands on, but was sick again when she took them off to fill in the questionnaire.

The CA don’t agree that they were misleading their readers, in spite of a forthright picture-caption saying, “Sea Bands might work for you” (and so might touching wood). They saw it as an advantage that Sea Bands do not produce side effects (neither does touching wood).

Naval Assessment

Enter the Institute of Naval Medicine (INM), who tested Sea Bands against the drug hycosine, sometimes known as scopalomine. (At sea, this gives good control of symptoms for some hours). But the INM also tested against two placebos. One was a dummy drug (Vitamin C), and the other was a dummy band (the Sea band with the plastic button reversed so that it didn’t press against the wrist. Eighteen male volunteers were exposed to a “cross coupled nauseogenic motion challenge.” In other words, they were blindfolded and rotated in a chair while they performed head movements to commands from a loudspeaker above them.

This may sound pretty innocuous, but in fact it’s a fairly severe test. It will bring on the first symptoms of vomiting within 15 to 20 minutes on average. Each subject was tested on the motion challenge on four separate occasions, with at least a week between each. The results? The hycosine had an effect. But Sea Bands? No better than the dummy remedies. In fact, it emerges that the US Naval Aerospace people had tested Sea Bands back in 1982. The results then? No benefit.

You can browse through Gray’s Anatomy until your thumb is sore, without ever finding any connection between your wrist and being seasick. So why on earth did anyone think there was anything in the idea in the first place?

The Acupuncture Connection

It turns out that a Mr D.S.J. Choy had come up with a “seasickness strap” in New York in 1982. The idea was to find a way of pressing against the Nei Guan or P6 acupressure point, which is situated two Chinese inches away from the wrist crease. Why? At the end of the trail we open The Treatment of Disease by Acupuncture by Felix Mann, President of the Medical Acupuncture Society. He lists the ailments you can cure by pressure on the wonderful P6 point:

“Headache, insomnia, dizziness, palpitation of heart, epilepsy, madness, easily frigthened, swelling under armpits, cramp of elbow, cardiac pain, vomiting, middle regions blocked full and swollen, spleen and stomach not harmonised, stomach very painful, gastritis, enteritis, swelling of abdomen, diarrhoea, hiccoughs, coughing, depleted and weary, summer-heat diseases, rheumatism of foot, jaundice, irregular periods, post-partum bleeding and dizziness, spermatorrhoea, nearly pulseless.”

It’s difficult enough to come up with a remedy that can make a firm claim to cure one specific ailment. Remedies that claim to cure everything from hiccups to madness can only expect to be taken seriously by mediaeval visitors from a time warp.

Sea Bands does list a medical advisor: Dr Stainton-Ellis, a retired medical man. But Dr Stainton-Ellis said he had little contact with the company, and it is not clear that he is actually called upon to do anything. He told me that Sea Bands “are now being used in pregnancy, radiotherapy and chemotherapy.”

In fact, in these areas Sea Bands have not so much been “used” as put under test, usually by the same small group of enthusiasts. These studies have been heavily criticised for their statistics, their poor methodology, their lack of double-blind controls, and the fact that other researchers have been unable to reproduce the results. But acupressure is a mere ghostly cousin of acupuncture. So is it worth considering acupuncture itself before a sea voyage?

Dr Peter Skrabanek has surveyed the needle scene, and reported to the medical journal The Lancet on 26 May 1984: “numerous controlled trials have shown that the claims for acupuncture have no scientific validity<193> Let us leave quackupuncture to quacks and let us tell the misinformed patient the truth, so that he or she can choose.”

This article appeared recently in the The Skeptic (UK) and is reprinted by permission of the author.

Update

Bernard Howard

1) After seeing Sea Bands advertised in the magazine of the Institute of Advanced Motorists, Mr Jones made a formal complaint to the British Advertising Standards Authority, on the basis of the facts in the article above. The Authority’s response:

CONCLUSION: Complaint upheld. The advertisers failed to provide evidence for any of the claims. The Authority was concerned that the advertisers were unable to support the claims for the product as required by the Code, and requested that they cease making any claims for the wrist band until adequate substantiation could be made available.

2) Of a similar nature are “Isocones,” which are said to induce sleep in insomniacs by pressing on the acupressure point in the wrist. Unlike the Sea Bands, you must use a fresh Isocone each night on each wrist. Whether the acupressure points concerned with seasickness and sleeplessness are identical is not revealed by the advertisements for these products. If the points are different, it must require skill to press the right spot to produce the desired effect; if identical, the effect produced must depend entirely on the expectations of the subject, that is, our old friend the placebo effect.

3) For those interested, a member reports seeing Isocones for sale in a New Zealand pharmacy. Whether Sea Bands are available here is something we have not bothered to discover