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发表于 2006-9-25 22:22:32
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Science is not always a neutral, disinterested search for knowledge, although it
may often seem that way to the outsider. Sometimes the story can be very
different.
Smoking and health have been the subject of argument since tobacco was
introduced to Europe in the sixteenth century. King James I was a pioneer
antismoker. In 1604 he declared that smoking was "a custome lothsome to the eye,
hatefull to the Nose, harmefull to the braine, dangerous to the Lungs, and in
the blacke stinking fume thereof, neerest resembling the horrible Stigian smoke
of the pit that is bottomelesse." But like many a politician since, he decided
that taxing tobacco was a more sensible option than banning it.
By the end of the century general opinion had changed. The Royal College of
Physicians of London promoted smoking for its benefits to health and advised
which brands were best. Smoking was compulsory in schools. An Eton schoolboy
later recalled that "he was never whipped so much in his life as he was one
morning for not smoking". As recently as 1942 Price’s textbook of medicine
recommended smoking to relieve asthma.
These strong opinions for and against smoking were not supported by much
evidence either way until 1950 when Richard Doll and Bradford Hill showed that
smokers seemed more likely to develop lung cancer. A campaign was begun to limit
smoking. But Sir Ronald Fisher, arguably the greatest statistician of the 20th
century, had noticed a bizarre anomaly in their results. Doll and Hill had asked
their subjects if they inhaled. Fisher showed that men who inhaled were
significantly less likely to develop lung cancer than non-inhalers. As Fisher
said, "even equality would be a fair knock-out for the theory that smoke in the
lung causes cancer."
Doll and Hill decided to follow their preliminary work with a much larger and
protracted study. British doctors were asked to take part as subjects. 40.000
volunteered and 20,000 refused. The relative health of smokers, nonsmokers and
particularly ex-smokers would be compared over the course of future years. In
this trial smokers would no longer be asked whether they inhaled, in spite of
the earlier result. Fisher commented: "I suppose the subject of inhaling had
become distasteful to the research workers, and they just wanted to hear as
little about inhaling as possible". And: "Should not these workers have let the
world know not only that they had discovered the cause of lung cancer
(cigarettes) but also that they had discovered the means of its prevention
(inhaling cigarette smoke)? How had the MRC [Medical Research Council] the heart
to withhold this information from the thousands who would otherwise die of lung
cancer?"
Five year’s later, in 1964, Doll and Hill responded to this damning criticism.
They did not explain why they had withdrawn the question about inhaling. Instead
they complained that Fisher had not examined their more recent results but they
agreed their results were mystifying. Fisher had died 2 years earlier and could
not reply.
This refusal to consider conflicting evidence is the negation of the scientific
method. It has been the hallmark of fifty years of antismoking propaganda and
what with good reason may well be described as one of the greatest scandals in
500 years of modern science.
A typical example of such deception appeared in the same year from the American
Surgeon General. This was "Smoking and Health",
the first of many reports on smoking and health to be produced by his office
over the next 40 years. It declared that in the Doll and Hill study "…no
difference in the proportion of smokers inhaling was found among male and female
cases and controls." Fisher had shown this was not so. Fisher’s assessment and
criticism of the Doll and Hill results is not mentioned, not even to be
rejected. Unwelcome results are not merely considered and rejected. They cease
to exist.
The work of Doll and Hill was continued and followed up over the next 50 years.
They reintroduced the question about inhaling. Their results continued to show
the inhaling/noninhaling paradox. In spite of this defect their work was to
become the keystone of the modern anti-smoking movement: Defects count for
nothing if they are never considered by those who are appointed to assess the
evidence.
But their work had a far more serious and crippling disability.
From its inception the British doctors study was known to have a critical
weakness. Its subjects were not selected randomly by the investigators but had
decided for themselves to be smokers, nonsmokers or ex-smokers. The kind of
error that can result from such non-random selection was well demonstrated
during the 1948 US presidential election. Opinion polls showed that Dewey would
win by a landslide from Truman. Yet Truman won. He was famously photographed
holding a newspaper with a headline declaring Dewey the winner. The pollsters
had got it wrong by doing a telephone poll which at that time would have
targeted the wealthier voters. The majority of telephone owners may have
supported Dewey but those without telephones had not. A true sample of the
population had not been obtained.
The new Doll and Hill study was subject to a similar error. Smokers who became
ex-smokers might have done so because they were ill and hoped quitting would
improve them. Alternatively, they might quit because they were exceptionally
healthy and hoped to remain so. Quitting could appear either harmful or
beneficial. To avoid this source of error another project, the Whitehall study,
was begun.
In 1968 fourteen hundred British civil servants, all smokers, were divided into
two similar groups. Half were encouraged and counselled to quit smoking. These
formed the test group. The others, the control group, were left to their own
devices. For ten years both groups were monitored with respect to their health
and smoking status.
Such a study is known as a randomised controlled intervention trial. It has
become increasingly the benchmark, or as it is often referred to, the "gold
standard" of medical investigation. Any week you can open The Lancet or British
Medical Journal and you will likely find an example of such a trial to determine
the benefits or harm of some new therapy. Such trials are fundamentally
different to that of Doll and Hill. This is ironic because Hill had published
the influential and much-reprinted textbook " rinciples of Medical Statistics"
where he considers the relative merits of controlled and uncontrolled trials.
His praise is reserved for the former. Of the latter he is particularly
critical: Such work uses "second-best" or "inferior" methods. "The same
objections must be made to the contrasting in a trial of volunteers for a
treatment with those who do not volunteer, or in everyday life between those who
accept and those who refuse. There can be no knowledge that such groups are
comparable; and the onus lies wholly, it may justly be maintained, upon the
experimenter to prove that they are comparable, before his results can be
accepted." This criticism by Hill can accurately be applied to the Doll and Hill
study. According to Hill’s own criteria, his work with Doll can only be
described as second-rate, inferior work. It would be for others to conduct
properly controlled trials.
So what were the results of the Whitehall study? They were contrary to all
expectation. The quit group showed no improvement in life expectancy. Nor was
there any change in the death rates due to heart disease, lung cancer, or any
other cause with one exception: certain other cancers were more than twice as
common in the quit group. Later, after twenty years there was still no benefit
in life expectancy for the quit group.
Over the next decade the results of other similar trials appeared. It had been
argued that if an improvement in one life-style factor, smoking, were of
benefit, then an improvement in several - eg smoking, diet and exercise - should
produce even clearer benefits. And so appeared the results of the whimsically
acronymed Multiple Risk Factor Intervention Trial or MRFIT, with its 12,886
American subjects. Similarly, in Europe 60,881 subjects in four countries took
part in the WHO Collaborative Trial. In Sweden the Goteborg study had 30,022
subjects. These were enormously expensive, wide-spread and time-consuming
experiments. In all, there were 6 such trials with a total of over a hundred
thousand subjects each engaged for an average of 7.4 years, a grand total of
nearly 800,000 subject-years. The results of all were uniform, forthright and
unequivocal: giving up smoking, even when fortified by improved diet and
exercise, produced no increase in life expectancy. Nor was there any change in
the death rate for heart disease or for cancer. A decade of expensive and
protracted research had produced a quite unexpected result.
During this same period, in America, the Surgeon General had been issuing a
number of publications about smoking and health. In 1982, before the final
results of the Whitehall study had been published, the then Surgeon General C.
Everett Koop had praised the study for "pointing up the positive consequences of
smoking in a positive manner". But now for nearly ten years he fell silent on
the subject and there was no further mention of the Whitehall study nor of the
other six studies, though thousands of pages on the dangers of smoking issued
from his office. For example in 1989 there appeared "Reducing the Health
Consequences of Smoking: 25 Years of Progress". This weighty work is long on
advice about the benefits of giving up smoking but short on discussion of the
very studies which should allow the evaluation of that advice: you will look in
vain through the thousand references to scientific papers for any mention of the
Whitehall study or most of the other six quit studies. Only the MRFIT study is
mentioned, and then falsely:
"The MRFIT study shows that smoking status and number of cigarettes smoked per
day have remained powerful predictors for total mortality and the development of
CHD [coronary heart disease], stroke, cancer, and COPD [chronic obstructive
pulmonary disease]. In the study population, there were an estimated 2,249 (29
percent) excess deaths due to smoking, of which 35 percent were from CHD and 21
percent from lung cancer. The nonsmoker-former smoker group had 30 percent fewer
total cancers than the smoking group over the 6-year follow up."
This was untrue, as the Surgeon General was later to admit.
What the MRFIT authors themselves had to say about their work was quite
different:
"In conclusion we have shown that it is possible to apply an intensive long-term
intervention program against three coronary risk factors with considerable
success in terms of risk factor changes. The overall results do not show a
beneficial effect on CHD or total mortality from this multifactor intervention."
(Multiple Risk Factor Intervention Trial Research Group, 1982)
But in 1990 the Surgeon General published "The Health Benefits of Smoking
Cessation" and at last the subject was addressed. The Whitehall study was
rejected because of its "small size". A once praiseworthy study had become
blameworthy. The MRFIT results were described, this time truthfully: "there was
no difference in total mortality between the special intervention [quit] and
usual care groups." This and the other studies were rejected because the
combined change in other factors - eg diet and exercise - made it impossible to
apportion benefit due to smoking alone. This is absurd and illogical reasoning.
If, say, a 10% improvement in life expectancy had been found then it might
indeed be difficult if not impossible to say how much was due to smoking alone.
But there was no improvement. There was nothing to apportion. Nevertheless, with
such deceptive words the Surgeon General turned to an unpublished, unreviewed,
un-controlled, non-intervention, non-randomised survey conducted for the
American Cancer Society ("American Cancer Society: Unpublished tabulations").
The gold standard of modern science was rejected and replaced by the debased
currency of what is by comparison little better than opinion and gossip.
This rejection of consistent results from controlled trials and the acceptance
of far inferior data would not be countenanced in any other area of medical
science. Anyone who suggested doing so would be met with howls of derision and
questions as to their intelligence if not their sanity. But where smoking and
health are being considered this debasement of science is commonplace and passes
without comment.
In Australia in the same year there appeared a similar publication "The
Quantification of Drug Caused (sic) Mortality and Morbidity in Australia" from
the Federal Department of Community Services and Health. Its authors waste no
time in discussing intervention trials. These receive not a mention, not even to
be rejected. Instead the authors turned to several surveys of the kind
ultimately used by the Surgeon General. In particular they used yet another
study conducted for the American Cancer Society by E.C.Hammond, a gigantic study
of a million subjects, another uncontrolled, non-intervention, non-randomised
survey. This was a particularly bad choice. The dangers of very large surveys
are well known to statisticians: because of their size it is difficult to do
them accurately. The flaws in Hammond’s work were revealed when the initial
results were published in 1954. Hammond himself was later to admit that his
study had not been conducted as he had intended and as a consequence his results
are to an unknown extent erroneous. But it was worse than that. His work became
literally a textbook example of how not to do research. It can be found as
example 287 in "Statistics A New Approach" by W.A.Wallis and H.V.Roberts. This
was the ignominious and undignified fate of work which should only be quoted as
a salutary example of the pitfalls which can await the researcher.
Two problems bedevil both Hammond’s work and other similar studies.
First, some of the volunteers who enrolled their subjects told Hammond that
contrary to his instructions they had selectively targeted ill smokers. These
results he was able to scrap but necessarily an unknown proportion of his final
results must be suspect. Second, as was demonstrated at the time, his subjects
were quite unrepresentative of the general public in a number of respects. In
particular, there were relatively few smokers. It seems quite plausible that
many healthy if indignant smokers would refuse to take part in his trial and
this would produce such an aberration. These two vitiating defects are of the
kind which have led to the widespread preference for gold standard trials.
But the continuation of Hammond’s work, with its demonstrated
faulty methodology, was used by the Australian authors to deduce that smoking
causes premature death to the extent of 17,800 per year in Australia. Their
conclusions should be compared with the results of a survey by the Australian
Statistician in 1991 of 22,200 households, chosen at random. This showed "long
term conditions", including cancer and heart disease, to be more common in
non-smokers than smokers.
Even if they had used sound data to calculate deaths caused by smoking, this
still would not have shown that smoking is overall harmful or causes an excess
of deaths. Antibiotics kill some susceptible, allergic individuals but this fact
does not show that antibiotics reduce life expectancy. If the data used by these
authors is examined more closely it can in fact be shown that the mean age at
death from smoking-related causes (eg lung cancer) is about 1 year greater than
from nonsmoking-related causes (eg tetanus). See:
http://members.iinet.net.au/~ray/finch2.pdf
for details. This result does not necessarily show that smokers live longer than
nonsmokers: smokers as well as nonsmokers die from both nonsmoking-related
causes and smoking-related causes. But it is certainly not evidence for the
belief that smoking reduces life expectancy.
During all this time health authorities have repeatedly and persistently lied to
the public. Consider just one of innumerable examples. In June 1988, in Western
Australia the Health Department in full page advertisements in local papers
declared: "The statistics are frightening. Smoking will kill almost 700 women in
Western Australia this year. If present trends continue, lung cancer will soon
overtake breast cancer as the most common malignant cancer in women". What was
frightening was not the statistics but the fact that a Health Department should
lie about them. In 1987 the same Health Department in its own publications had
said: "Suggestions by some commentators that lung cancer deaths in women will
overtake breast cancer deaths in the next few years look increasingly
unlikely…female lung cancer death rates have fallen for the last 2 years." It
was predicted that breast cancer would far outweigh lung cancer for the next 14
years. What the public were told was not just an untruth but the reverse of the
truth. This is classic Orwellian Newspeak. The public are given what George
Orwell in "1984" named "prolefeed" – lies. Orwell must have smiled wryly in his
grave.
Above all has been the repeated and world-wide directive that smokers should
quit and live longer when every controlled trial without exception has
demonstrated this claim to be false.
Is there anything that can be said with certainty about the health and life
expectancy of smokers and non-smokers? The evidence indicates little difference.
One important fact often causes confusion: an agent can be a certain cause of
death and yet have the effect of extending life. Smoking could be a major cause
of lung cancer or even the only cause yet also be associated with long life. The
Japanese are amongst the heaviest smokers in the world. They also live the
longest. The Frenchwoman Jeanne Calment smoked for a hundred years before dying
at 122 as the world’s oldest ever person.
The resolution of this paradox lies in the simple fact that most agents have
both good and bad effects on health and life expectancy and it is the net result
which is of primary importance. This simple but crucial fact is often ignored or
forgotten by medical researchers. Coffee causes pancreatic cancer says the
newspaper article. Perhaps it does, but if it has a bigger and beneficial effect
on heart disease then those who drink coffee may well live longer than those who
don’t. Hormone replacement therapy may increase the incidence of certain cancers
yet still have overall a beneficial effect. (See "The Contrapuntists").
It may now be apparent why there is such a general belief that smoking is
dangerously harmful. There are 3 reasons. First, studies which in any other area
of science would be rejected as second-rate and inferior but which support
antismoking are accepted as first-rate. Second, studies which are conducted
according to orthodox and rigorous design but which do not support the idea that
smoking is harmful are not merely ignored but suppressed. Third, authorities who
are duty-bound to represent the truth have failed to do so and have presented
not just untruths but the reverse of the truth.
It may be argued that this is news about an old and settled subject. And who
cares about smoking anyway. But smoking is really a secondary issue. The primary
issue is the integrity of science. This has no use-by date. When the processes
of science are misused, even if for what seems a good reason, science and its
practitioners are alike degraded. |
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发表于 2006-9-25 18:02:44
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