Tag Archives: hypothesis

Claim to fame of the hygiene hypothesis

The recent encyclopedia article about the hygiene hypothesis seems to be well written. At least on the first instance … in reality it is more a novel than a scientific review.

For many years already, the hygiene hypothesis has been called an outdated concept; various times it was revised and transformed, and finally it gave birth to novel hypotheses.

In other words, the hypothesis has been rejected for being wrong . Even many revisions did not change that. There seem to be only one proven fact – the obsession of some authors with hygiene and nouvel Rousseauism.

Anyway, the hygiene hypothesis has promoted radical rethinking of infections, microbiota, and coevolution of mankind and microbes.

There is nothing radical in backward thinking. We still carry tons of microbes, freezer and antibiotics only did some qualitative but not so much quantitative changes,

With the advent of novel high-throughput sequencing technologies the human microbiome, which is sometimes called the ‘forgotten organ,’ has attracted much attention and is currently being implemented in a wider concept of self-foreign relationship, which may even include recognition of the nonmicrobial nonself as a vital stimulus to a well-developing immune system.

  1. So the interest is technology and not science driven.
  2. The microbiome is not an organ.
  3. The hype is already over.
  4. The Self is not defined by any bacterium.
  5. Most bacteria are excreted and not vital stimulus.

Given the many molecule classes regulating immune functions across individuals such as short RNAs, the hygiene hypothesis may eventually come back as a surprising explanation of the phenomena evoked by crowding, day care, sibship size, orofecally transmitted diseases, and respiratory infections.

Why that?
A comeback of the hygiene hypothesis by short RNA?
The listed phenomena are not intrinsically related, but are occuring only at the same time scale.

Even the old birth order effect might be rediscovered as epigenetic programming someday. Admittedly, these notions are entirely hypothetical, but without hypotheses, proven or not, science hardly advances.

So if David Strachan’s birth order effect would be really caused by  epigenetic programming – why would that be related to hygiene at all?

Science is is not so much about proven or unproven but about reasonable and non reasonable hypotheses.

 

On verification

Most recently, I came across of another euphoric hygiene hypothesis review and wonder how this could ever happen. The evidence here is mixed and largely ambiguous.
Probably it would be best to follow some basic journalistic rules as summarized in the online “Verification Handbook for investigative reporting”

As with the verification of user-generated content in breaking news situations, some fundamentals of verification apply in an investigative context. Some of those fundamentals, which were detailed in the original Handbook, are:

– Develop human sources.
– Contact people, and talk to them.
! Be skeptical when something looks, sounds or seems too good to be true.
! Consult multiple, credible sources.
– Familiarize yourself with search and research methods, and new tools.
– Communicate and work together with other professionals — verification is a team sport.

Journalist Steve Buttry, who wrote the Verification Fundamentals chapter in the original Handbook, said that verification is a mix of three elements:

– A person’s resourcefulness, persistence, skepticism and skill
– Sources’ knowledge, reliability and honesty, and the number, variety and reliability of sources you can find and persuade to talk
– Documentation

An epidemic of nonsense

13 € for a paperback, this is “An Epidemic of Absence. A new way of understanding allergies and autoimmune disease”. It is written by Moises Velasquez-Manoff , a journalist otherwise working for the “The Christian Science Monitor”. As his online bio reports “he dreamed of writing novels”. I would wish he would done so.

The outset is rather clear – Velasquez-Manoff wants to find a cure for his own autoimmmune disease. While this may be a legitimate justification for collecting information about a given topic, the method by Velasquez-Manoff is not. At a first glance, it looks like a serious book, well written, interesting facts presented in a coherent manner followed by numerous references. Maybe that made such an impression on the (numerous) positive reviewers. Maybe all the positive reviewers are experienced science journalists that judged by the overall impression plus some common sense plus some specific knowledge. But, Velasquez-Manoff did never hear the other side (on p.310, he even admits who has read and commented on sections of the manuscript: exclusively scientists in favor of the hygiene hypothesis). To recognize that you need to be a scientist – journalists would not notice that.

I compiled a long list the errors but feel now, that it would be too time consuming to write that down here. As far as it concerns me (p. 99) there was no grant to win in Munich as the study Velasquez-Manoff is talking about was a commissioned study. And sorry (p.100) I wrote the full grant application comparing East and West Germany children and did large part of the field study. Furthermore, I am not convinced (p.101) that the East West German differences ever supported the hygiene hypothesis, it is something different. And it was not in 2000 (p.102) that someone published on day care (p. 102), we wrote that already in 1999. Audiatur et altera pars, yea, yea.

(1S,3Z)-3-[(2E)-2-[(1R,3aR,7aR)-7a-methyl-1-[(2R)-6-methylheptan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidene-cyclohexan-1-ol

or briefly vitamin D3. There seems to be another vitamin D /allergy abstract at the forthcoming EAACI congress from the KOALA study. The authors find

Risk for AD was highest for children in the fourth quintile of maternal 25(OH)D level [adjusted odds ratio (aOR) 2.08; 95%CI 1.07-4.03] compared to those in the third quintile; P for trend over the quintiles 0.03]. Continue reading (1S,3Z)-3-[(2E)-2-[(1R,3aR,7aR)-7a-methyl-1-[(2R)-6-methylheptan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidene-cyclohexan-1-ol

Probability that a genetic association is false positive

An (anonymous) reviewer of our forthcoming EJHG paper on IgE and STAT3 pointed me towards a JNCI paper that has a nice supplement – an excel sheet to calculate the probability that a positive report is false. It basically relies on (i) the magnitude of the p-value (ii) statistical power and (iii) fraction of tested hypothesis. While we certainly know (i) and (ii), (iii) is always hard to know with many datasets including hundreds of traits that allow indefinite numbers of subgroups. Are you really interested in a new paper about “An African-specific functional polymorphism in KCNMB1 shows sex-specific association with asthma severity” that encompasses 1 of virtually 100 ethnic groups; 1 or virtually 25000 genes; 1 of 2 sexes; 1 or virtually 50 asthma related traits, yea, yea.

Time to give Blackley the credit he deserves

I am currently doing some historical studies if the vitamin hypothesis fits also the temporal relationship of allergy prevalence. While ordering RKI files for my next trip to the Berlin document center, I found that farming and lower allergy sensitization is known much longer than I anticipated. Continue reading Time to give Blackley the credit he deserves

Delusion or poor scientific hypothesis

Delusion is a common symptom of paranoid schizophrenia ICD10 F20.0, usually combined with hallucinations (either auditory – noises or voices, visual or other perceptions of smell or taste). The most common paranoid symptoms are delusions of persecution, reference, exalted birth, special mission, bodily change, or jealousy. It has been most impressing (and harrowing) to see these patients as a medical student in Vienna at Baumgartner Höhe. Of course I visited Berggasse 19 but there have been more pioneers in Vienna like Krafft-Ebing).

We are arriving now at my main question: What is the difference between delusion and a scientific hypothesis? This question stems from a recent appraisal of the “TH17 revision” of the TH1/TH2 hypothesis by Lawrence Steinman

A historical perspective on the TH1/TH2 hypothesis is illuminating, both for its insights into important immunological phenomena and for its revelations about how groups of highly trained intellectuals, in this case immunologists, can adhere to an idea for so many years, even in the face of its obvious flaws.

He refers mainly to predictions of EAE outcomes – as an allergologist I could add more examples where the simple TH1/TH2 paradigma did not work. What is the difference between delusion and a scientific hypothesis? In my opinion the answer is context dependent as there is not so much difference – delusion will not be so persistent over time (although it is nearly impossible to convince somebody that he is captured by a delusion) while a poor hypothesis is usually more persistent (but there is a good chance to convince somebody that a hypothesis is wrong). Steinman also has some advice

We should not become fixated on the hypothesis, as if it were a ‘Law’, which in any case may fall in the face of new data that such a Law cannot explain. Most importantly, we should not ignore aberrant data that cannot be explained by a concept, whether it is deemed a Law or, more modestly, a Hypothesis. We should always be careful to explain those quirky aberrant points in the data and those annoying blemishes and flaws in the scientific theory. They may be hiding a tremendous new insight.