Clinical significance of immune-system laboratory tests

The Italian Journal of Anatomy and Embryology has now published (volume 116 #1, supplement, 2011, p. 157) the abstract of the poster shown in AIDS Rethinking presented in Mainstream Conferences (posted on 2011/09/29). The mainstream literature now contains this summary of crucial deficiencies of HIV/AIDS theory, in a journal abstracted by PubMed.

Clinical significance of immune-system laboratory tests
Marco  Ruggiero 1 ,  Stefania  Pacini 2 ,  Tiziana  Punzi 2 ,  Gabriele  Morucci 2 ,  Massimo  Gulisano 2   Claus
Koehnlein 3 , Henry H. Bauer 4
1  Dipartimento di Patologia e Oncologia Sperimentali, Università degli Studi di Firenze, Italia
2  Dipartimento di Anatomia, Istologia e Medicina Legale, Università degli Studi di Firenze, Italia
3  Internistische Praxis, Koenigsweg 14, 24103 Kiel, Germany
4  Chemistry and Science Studies, Virginia Tech, Blacksburg, VA 24060-5623, USA

Anatomists  and  many  other  medical  specialists  rely  on  clinical  laboratories  for
critical information to assist in diagnosis, prognosis, and the evaluation of treatments.
However, the clinical laboratories do not always accompany their numbers with
sufficient  information  about  the  significance of certain results: how great the quantitative
variation  of  a  given  parameter  might  be  in  healthy  subjects,  and  how  likely  it
might  be  that  a  given  qualitative  (“yes”  or  “no”)  result  is  a  false  positive  or  false
negative. This situation has been particularly troublesome in the case of HIV, because
there is no “gold standard” HIV test and the typically quantitated measure, CD4, varies
widely  for  a  variety  of  reasons  that  have  nothing  to  do  with  HIV  infection.  For
example, a person pronounced HIV-positive after having some vaccinations became
HIV-negative  again  after  a  time,  something  that  is  not  regarded  as  possible  if  HIV-
positive  denotes  definitely  active  infection,  as  is  commonly  assumed.  An  important
consequence  of  deficient  information  about  HIV  epidemiology  is  that  students  of
anatomy may fear risking possible infection in dissection laboratories when the actual
risk  is  negligible  even  in  respect  to  anonymous  cadavers  in  South Africa  where  the
supposed  incidence  of  HIV  is  particularly  high.  We  have  previously  pointed  to  the
need to improve HIV epidemiology and related public policy by recognizing and taking
into  account  the  weaknesses  in  HIV  testing,  which  are  the  probable  reason  for
at  least  some  of  the  troubling  conundrums  and  mutually  contradictory  data  that
seem inexplicable: conflicting estimates of HIV infections and of  HIV-disease deaths
from  equally  authoritative  sources;  apparently  drastically  different  primary  modes
of  transmission  in  different  geographic  regions;  extreme  racial  disparities  in  HIV
infection,  with Asians  and Asian Americans  consistently  less  affected,  by  about  one
third,  than  white Americans,  while  black Americans  are  affected  by  as  much  as  an
order of magnitude more than white Americans. Testing uncertainties doubtless also
contribute  to  the  confusion  as  to  whether  certain  conditions  (e.g.  lipodystrophy  or
nephropathy) should be described as HIV-associated or as AIDS-associated. In recent
work  we  have  found  that  the  immune  system,  including  CD4  counts,  can  be  markedly
enhanced by easily modified dietary supplementation that has none of the toxic
side-effects  of  the  antiretroviral  drugs  currently  used  in  the  attempt  to  elevate  CD4
counts in HIV-positive people.

HIV/AIDS exemplifies scientific illiteracy

HIV was never shown to have caused AIDS.
Nevertheless, during three decades huge arrays of people and organizations have become engaged in a variety of activities based on the mistaken belief that HIV is an infectious immune-system-killing virus that caused and continues to cause AIDS.
That such a mistake could metastasize so massively seems incredible to the conventional wisdom, which regards it as impossible that “science” could go so wrong — after all, this is a scientific age in which all manner of technological marvels are accomplished all the time; and science itself can’t go wrong because it uses the scientific method and is self-correcting.

The conventional wisdom can hardly accept that it’s wrong about HIV/AIDS so long as it doesn’t realize that it’s wrong about science. It needs to be understood that
1. Science is not self-correcting.
2. Science is not done by “the scientific method”.
3. Scientists are not the appropriate experts to explain science to policymakers, the public, or the media. On the whole*, scientists know only the technical intricacies of what they do; they don’t understand the epistemology and sociology of science and they are ignorant of or mistaken about the history of science.

Science is not unique in this respect. Quite generally, those who do things don’t necessarily understand what they’re doing.
That’s to say, they don’t necessarily understand how what they’re doing fits into the larger picture. Why are they’re doing it? Why does it exist to be done? Why has the wider society made it possible to do it? Does it connect with other aspects of human society? How? Are the connections beneficial — and if so, to whom? Is it worth doing, in other words, and if so, in whose opinion?
Practitioners are obsessed with the parts of a tree, and their view doesn’t extend to the surrounding forest, as the hoary old metaphor would put it.
Politicians, for example, may be extraordinarily adept at getting elected and working within their particular system; but if you want to understand what’s going on in political matters, politicians are not the people you want to consult; you can get better guidance from historians, political scientists, journalists, novelists.
Within the social sciences and the humanities, this is universally understood, at least implicitly. Critics explain the wider significance and value and meaning of novels, plays, poems; the novelists, playwrights, poets do their own things, but they don’t see those things in perspective.

What’s understood in and about the humanities and social sciences is not understood with respect to science and medicine. The experts consulted and cited about matters of science and medicine are scientists and doctors; they are supposed to explain to the rest of us what science and medicine are about, what they mean to our culture and our society, how we should use what they produce. Scientists and doctors represent Science and Medicine in the same way as priests represent Religion: as unquestionable authorities.
But scientists don’t understand science in the same sense that politicians don’t understand politics and novelists don’t understand literature, and doctors don’t understand medicine in the same sense that politicians don’t understand politics and novelists don’t understand literature. There’s the need for science critics and for medicine critics just as there’s the need for art critics, literature critics, music critics.
Above all, public policy should be informed by science critics and by medicine critics, not by scientists or doctors.

So far, science criticism has barely emerged, and insofar as it exists it has not emerged from the academy into public discourse, where it belongs.
Only within the last few decades has the intellectual basis for science criticism begun to form as philosophers, historians, sociologists, political scientists and others cooperated in ventures like programs in “Science and Society”, “Science Studies”, “Technology Studies”. This nascent interdisciplinary field does not yet even have an agreed nomenclature or canonical literature. Nevertheless, there is massive consensus on a few points like those above:
1. Science is not self-correcting.
2. Science is not done by “the scientific method”.
3. Scientists are not the appropriate experts to explain science to policymakers, the public, or the media.
And also:
4. Any distinction between “pure” and “applied” science has essentially dissipated.
5. The inputs and outputs of scientific research now depend as much on factors external to science as on internal matters: funding, political attitudes and controls, social acceptability, bureaucratic aspects and the like influence heavily what research is done, how results are disseminated or suppressed, how society benefits or suffers as a result of scientific research.

Once these points are established, everything about the HIV/AIDS mess becomes explicable, because the view that HIV causes AIDS became accepted as a consequence of social and political factors, not scientific ones:
The initiating event was not any scientific publication, it was the press conference on 23 April 1984 at which Margaret Heckler, then Secretary of Health and Human Services, announced the discovery of the “probable” cause of AIDS by Robert Gallo of the National Cancer Institute.
The National Institutes of Health, which is an agency within the Department of Health and Human Services, is the chief provider of public research funds to biologists and clinical researchers. The press conference served to alert them to the best approach for getting research funding: study the AIDS-causing virus.
And so it went. The history of HIV and of AIDS has been written about by many people from a variety of viewpoints. No matter the differences among these accounts, close reading of just about any of them will illustrate how social and political rather than scientific factors were influential; where technical matters are mentioned, keep in mind that force was given to those technical issues by the mainstream hegemony, which is viewed as authoritative in interpreting data. For example, Rethinkers, and fence-sitters or -jumpers like Root-Bernstein, have interpreted the evidence relating to HIV, AIDS, and hemophiliacs quite differently than the mainstream, but the latter carried the day so far as journalists and policy makers are concerned. Again, Rodney Richards has shown how the detection of “HIV antibodies” came to be taken as proof of infection without benefit of evidence, purely as a result of decisions within and statements from the bureaucracy of the Centers for Disease Control and Prevention.
The science relating to HIV and to AIDS has never supported the mainstream assertions. Vested interests determined the course of events: careerism, political exigencies, empire-building in government agencies, financial benefits for companies and individuals. Once an activity commands billions of dollars of annual expenditure, mere scientific findings can exert little if any practical influence.

HIV/AIDS was not built out of science, and it will not be destroyed purely by science. The necessary science has been available for a long time. What’s needed is for the conventional wisdom to recognize that mainstream science and medicine are not necessarily right; and for that to happen, the conventional wisdom must abandon its misconceptions about science and medicine.

The conventional wisdom will not be changed directly by the growth of academic ventures in science and technology studies (STS). Possibly those who are educated in those fields may eventually exert an influence if they gain relevant positions in government or the media or foundations or think tanks. For the nonce, though, there remains a sad lack of sorely need science criticism: informed critiquing of very specific matters — not abstract wide-ranging criticism of “science” as a whole. or of “technology” as a whole, but criticism as practiced in the arts and humanities: criticism grounded in a passion for the general activity and seeking to explicate particular instances of it and their significance.
For lengthier discussions of this need, see
Maurice Goldsmith, The Science Critic : A Critical Analysis of the Popular Presentation of Science, Routledge & Kegan Paul, 1986.
Eugene Garfield, “Science needs critics”, THE SCIENTIST, 12 January 1987.
Don Ihde, Why not science critics?  in Expanding Hermeneutics: Visualism in Science, Northwestern University Press, 1999.
Declan Fahy, “Skeptical of science”, 28 September 2011, The Observatory — Columbia Journalism Review.

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* “On the whole”: Of course there are individual exceptions, as always. Those exceptions have no more influence on and significance for public policy than, for instance, AIDS Rethinkers have with respect to mainstream HIV/AIDS dogma.

Scientific illiteracy? Innumeracy? Lack of common sense?

We’re deluged with assertions about everything, typically via TV and newspapers and magazines bringing statements from experts and authoritative organizations. Those assertions are to be trusted only at your peril.
Assertions in advertisements are obviously deceitful to a greater or lesser extent, and thereby perhaps less dangerous than those coming from apparently independent, disinterested sources. However, those purportedly independent, disinterested sources can be ignorant in a frighteningly high proportion of cases.
That assertion of mine was prompted by an episode of the Daily Show with Jon Stewart. I mean it quite literally when I insist that the Daily Show and the Colbert Report offer nowadays the soundest commentary to be found anywhere in the media on matters of culture and politics, because they are not ideologically prejudiced  nor snowed by experts; they make experts’ assertions run the gauntlet of common sense.
Sometimes, of course, I can’t be sure whether they’re making something up or reporting it. So it was when the Daily Show presented a news item to the effect that one could increase by 20% one’s chances of contracting colon cancer if one ate a hot dog every day. A clip showing a doctor representing the Physicians Committee for Responsible Medicine suggested that the Daily Show  was indeed reporting and not creating this absurdity. My Google search revealed that the Physicians Committee for Responsible Medicine (PCRM) exists; and it does warn that one hot dog — and more generally “just one 50-gram serving of processed meat” — “consumed daily increases the risk of colorectal cancer, on average, by 21 percent”. To bring this warning to the general public, PCRM set up a billboard comparing the risk of hot dogs to that of smoking:

 The same message was disseminated by the American Institute for Cancer Research
(AICR).

To what should one ascribe this idiocy about hot dogs and colon cancer? Are AICR and PCRM suffering from innumeracy, scientific illiteracy, or just a lack of plain common sense?
I think there are two ways of discerning that the assertion is idiotic, a less technical one — common sense — and a slightly more technical one  — elementary statistics and snippets of general knowledge about oncology, toxicology, biology generally.
Common sense, by the way, is not something one has; it is something one ought to use: “having” common sense means thinking. With matters like hot dogs and cancer, common sense can usually recognize the absurdity by asking the question,

HOW COULD THAT POSSIBLY BE KNOWN? *

The sweeping claim about cancer-causing processed meat cannot be based on actual experience. It could only be validated by an enormous clinical trial in which the diets of two groups of people were controlled so that processed meat was the only difference between them; and the two groups — one eating the purportedly dangerous meat and the other avoiding it — would have to be matched for every conceivably relevant characteristic: age, sex, environment, lifestyle, genetic predispositions. Quite literally impossible.
On what are these claims based, if not on actual data?
On studies on animals and statistical associations.
Extrapolating effects on animals to human beings involves a number of obvious uncertainties. No non-human animals have exactly the same physiology, nor the same proneness to cancers. Except in extreme cases (something like cyanide, say), results on animals can only be suggestive. Translating critical dosage in animals to human beings is typically done with a ratio of respective body-weights, which presumes no significant differences in physiology or proneness to cancers.
On these common-sense grounds alone, claims like cancer-causing hot dogs are better described as sheer speculation than as scientific findings.

Some bits of general knowledge about technical matters can also help against being snowed by such assertions about technical matters.
ALWAYS bear in mind that associations, correlations, links, do not identify CAUSES. Almost all of what the media disseminate on matters of health and diet are mere statistical associations. Economic and social status are often found to be “linked” to diet and health; so anything else that’s “linked” to diet or health is likely to be linked also to economic or social status. Hot dogs and processed meat in general form a larger part of the diet at lower economic levels than at higher ones. So maybe colon cancer is “caused” by poverty?
Highly recommended reading: Darrell Huff, How to lie with statistics; Joel  Best, Damned lies and statistics: untangling numbers from the media, politicians, and activists and More  damned  lies  and  statistics:  how  numbers  confuse  public issues.
Furthermore, “statistically significant” never means “real”, “correct”, “true”. It merely states an arbitrary probability of being so.
That arbitrary probability, in social science and medicine, is typically “p<0.05” — less than 5% probability that the apparent link, correlation, association is owing to pure chance. On the face of it, this means 1 out of every 20 “statistically significant” correlations is not a correlation at all.
Furthermore, that a correlation is not owing to chance doesn’t entail that the correlation is owing to what the researchers or observers take it to be: there may be some unknown factor involved.
Because this approach only tests how likely a result is to be owing to chance, it greatly overestimates the statistical significance of the hypothesis actually being tested, the more so, the less inherently likely the correlation is on general grounds, grounds of experience, grounds of common sense — see R. A. J. Matthews (1998), “Facts versus factions: The use and abuse of subjectivity in scientific research”, reprinted as  pp. 247-282 in J. Morris (ed.), Rethinking Risk and the Precautionary Principle, Butterworth, 2000; and (1999), “Significance levels for the assessment of anomalous phenomena”, Journal of Scientific Exploration, 13: 1-7.
Keep in mind too that if one looks for a large number of possible associations, some will crop up purely by chance: 1 out of every 20 if one uses the simpleminded interpretation of p<0.05. Therefore if one looks for a possible connection between processed meat and 20 different kinds of cancer, one is likely to find an apparent but spurious correlation with one of them.
If one looks for a correlation between colon cancer and 20 different possible constituents of diet, one is likely to find an apparent but spurious correlation with one of them.
For all these reasons based in statistics, any claim of  a 20% change in risk is more than questionable. Given all the uncertainties, perhaps claims of a several-fold change might suggest that there’s something to the claim. A claimed 20% is easily shrugged off. When it is stated more precisely as 21%, it becomes absolutely ridiculous.

An often-overlooked aspect of the miracles of life is the degree to which living systems are able to protect themselves against harm and to repair damage. One of the typical extrapolations made in assertions like cancer and hot dogs is that effects are linear, that eating 100 hot dogs has 100 times the effect that eating 1 hot dog has. This is wrong. Our bodies can repair certain damages at  certain rates, and harm comes only if the damage comes at a greater rate. In small amounts delivered not too rapidly, a toxic substance may actually improve health, a phenomenon known as hormesis; see for example J. M. Kauffman, “Radiation hormesis: Demonstrated, deconstructed, denied, dismissed, and some implications for public policy”, Journal of Scientific Exploration 17 (2003) 389-407; A plausible explanation is that the toxin (or radiation) stimulates the immune system to work “overtime” and wipe out not only the toxin but other threats as well.

When it comes to cancer, the mechanism that sets it going is not known. Much mainstream belief holds that several steps are needed as well as some predisposition in the form of oncogenes. That makes it unlikely in the extreme that any single factor like processed meat could decrease by some universally average amount the risk of contracting any given cancer.

There is absolutely no reason to give even a moment’s credence to the asserted connection between colon cancer and processed meat.

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It’s easy and rather natural to accept at face value organizations that call themselves something like American Institute for Cancer Research or Physicians Committee for Responsible Medicine. However, there are reasons for not doing so automatically: “let the buyer beware” (caveat emptor) remains excellent advice. For instance there is the phenomenon of “astroturfing”, organizations that pretend to be genuine “grass roots” but which are actually fronts for self-interested commercial or political entities. Even when charities and non-profits are independent, honestly sui generis, we are warned periodically to check their bona fides and financial arrangements before contributing to them, to assess for example how much is spent on the organization’s professed purpose as against how much benefits the management and staff. So I looked briefly into PCRM and AICR.

PCRM is a not-for-profit cancer charity, with revenues of $8.8 million in 2009 of which $2.6 million was spent on salaries and wages. The website advertises a book (21-Day Weight Loss Kickstart) and book-tour by PCRM’s president. There is fairly extreme dietary advice, about the cheese-obesity link, for example, or the risks from milk: “In a study of 142 children with diabetes, 100 percent had high levels of an antibody to a cow’s milk protein. It is believed that these antibodies may destroy the insulin-producing cells of the pancreas. . . . The lactose sugar, when it is digested, releases galactose, a simple sugar that is linked to ovarian cancer and cataracts.” PCRM also campaigns against the use of animal subjects in research.

AICR is a not-for-profit cancer charity that spent $5-6 million on research in 2010 and about the same on salaries and wages.  Three times that much (>$17 million) was spent on “public health education”, nearly $4 million on management and more than $7 million on fund-raising. Eight officers received >$100,000 each. The company contracted to raised funds by phone solicitation brought in nearly $11 million, but at a cost of $7.5 million, whereas direct mail solicitation raised  $11 million at a cost of only $650,000. The cancer-prevention advice offered by AICR seems banal and anything but original (see Schedule O of “FY 2010 Form 990” on the AICR website).

None of this means that what these groups assert is necessarily wrong; but it should not be taken as disinterested and purely evidence-based. With cancer and hot dogs, as I have just shown, they are not to be trusted.

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* For a full discussion of this approach, and of how to reach a personal decision as between mainstream dogma and unorthodox claims, see chapter 7 in Science or Pseudoscience: Magnetic Healing, Psychic Phenomena, and Other Heterodoxies)