Nosodes Redux: “I hate those meeces to pieces!”

Life and medicine generate facts and experiences that require conceptual frameworks that aid in understanding.  It is no good have a pile of facts if they cannot be understood within a broader understanding.

The practice of Infectious Diseases, while certainly aided by understanding anatomy, physiology, microbiology, chemistry and the other sciences that form the core of medicine (referred to in Medical School as the basic sciences), gains a broader  appreciation from the concepts of evolution.  Infectious Diseases, at its most fundamental level, is applied evolution, and understanding evolution often adds greater insight into infectious diseases.  Me find bug, me kill bug, me go home may be my motto, but it is meant in jest.

There have been papers or books that have added conceptual frameworks to my understanding of the natural world and medicine.  Besides evolution, there was Observations on Spiraling Empiricism a classic that all health care providers should read, as it outlines the cognitive errors we all make in prescribing medications; I have discussed this article before.

There is  The Drunkard’s Walk: How Randomness Rules Our Lives by Leonard Mlodinow.  So often the explanation of why something  happens is a shrug of the shoulders; feces occurs. The book formalized my understanding that much of what happens is random and without cause.  The challenge in medicine is trying  find a pattern in the randomness of life upon which to base a diagnosis. It is equally important to recognize when patterns are not there. All too often what is seen as a pattern is our imposing structure on what are random events.  Or maybe that really is a bunny in the clouds.  Clinical study results often occur by chance and having a significant ‘P’ value may still be due to randomness if the study is measuring nonsense.

Recently, Why Most Published Research Findings Are False,  by John P. A. Ioannidis has added to my understanding of the old saw that half of everything you learn in medical school will be proven false after you graduate, the problem is that they do not tell you which half.

Ioannidis has 6 rules for evaluating studies that stem from his evaluation of the literature:

Corollary 1: The smaller the studies conducted in a scientific field, the less likely the research findings are to be true.
Corollary 2: The smaller the effect sizes in a scientific field, the less likely the research findings are to be true.
Corollary 3: The greater the number and the lesser the selection of tested relationships in a scientific field, the less likely the research findings are to be true.
Corollary 4: The greater the flexibility in designs, definitions, outcomes, and analytical modes in a scientific field, the less likely the research findings are to be true.
Corollary 5: The greater the financial and other interests and prejudices in a scientific field, the less likely the research findings are to be true.
Corollary 6: The hotter a scientific field (with more scientific teams involved), the less likely the research findings are to be true.

It is why much of medicine and science is tentative and emphasizes the importance, as best as can be determined at a given time, of considering all the information.  I tell the residents that a big part of becoming a Doctor is learning to be comfortable with incomplete and changing information.  Being a specialist is being ignorant with style.

What matters is the totality of the evidence… instead of chasing statistical significance, we should improve our understanding of the range of R values—the pre-study odds—where research efforts operate. Before running an experiment, investigators should consider what they believe the chances are that they are testing a true rather than a non-true relationship.

It is where the Cochrane reviews fail, and fail so spectacularly, on topics as diverse as the efficacy of influenza vaccine to the efficacy of homeopathy.  Failure to consider all the information casts doubt on the former and suggests legitimacy of the former.  In the world of clinical medicine, when considering an intervention, I have to take into consideration as much of the literature as I can, from basic plausibility to the always messy clinical trials.

What separates a proponent of science based medicine from practitioners of SCAM’s is that those in SBM are aware of the all too numerous foibles and errors to which humans are prone,  distorting a true understanding of the natural world.  What makes a good skeptic, and a good doctor, is an understanding of the multitudinous ways we fool ourselves and others.

Which brings us back to nosodes and the reference  Do homeopathic nosodes protect against infection? An experimental test by WB Jonas.

Just on the basis of the first five corollaries of Ioannidis, the odds are the study is wrong, not to mention that the pretest probability, the R,  that this study, if positive, will be will be testing a true relationship is, lets see.  Exactly zero.  There is zero pretest probability that any positive result of a homeopathic invention represents an effect from the homeopathic nostrum.

Dr. Jonas, the sole author, is a former director of National Center for Complementary and Alternative Medicine, so, while the study was done at Walter Reed Army Institute of Research, Corollary 5 jumps to mind as perhaps more important than where the study is done.

Lets look at the quality of the study.

Groups of 4 to 6 mice (Corollary 1) received either ethanol (70%) or a varying dilutions of pureed leptospira infected mouse lung/liver/spleen  in 70% alcohol. Some of the nosodes  had measurable proteins in it. The author measured the amount of proteins in the nostrums using the Lowry procedure,  a semiquantitative measurement of proteins, which I remember using as a fellow.  It is less accurate when there is a host of other organic materials in the mix, as one might expect from a melange of liver, lung and spleen.

For me, ingestion of 70% alcohol leads to amnesia,  so how 70% alcohol can ‘remember’ the initial material better than water is not mentioned in the study.  Is a study with 70% alcohol meaningful for ‘classic’ water based homeopathy?  Are serial dilutions of 70% alcohol applicable to homeopathy as practiced?  Stupid questions, since homeopathy has nothing to do with reality.  Must. Remember. This. Is. Tooth. Fairy. Science.

Mice received about 16 doses of a nosode or placebo before infection challenge and about 40 doses after the infectious challenge with leptospirosis.

Compared to alcohol (which is not a placebo, since alcohol does have a variety of immunomodulatory effects, one example from where you find others,) over all the nosode group died after 18.6 hours and the control after 13.7  hours with a  P of .002.  Overall mortality was 75% in the control, 53 % in the nosode.  Standard vaccination was, of course, vastly superior to alcohol or nosode,  with 100% protection. There was no dose dependent result, which would be a surprise if a real medication were being used, but not, perhaps, an antigen.

If you expose an animal to a pathogen, say Candida, and then shortly thereafter infect the animal with, say, Listeria, the animals that had the prior exposure to Candida will have decreased mortality compared to those that were not exposed.  The immune response is primed for subsequent infectious challenge.

One telling aside in the study is that one mixture had no effect, and that was a 1000C nosode prepared by a commercial pharmacy.  The author postulates “perhaps handling while in transit or differences in preparation of the commercial nosode affected the 1000C level.”  He also worries that the mechanical succussion does not have the same effect as hand succussion, which in the real world is akin to worrying that Tooth Fairies exchanged the real nosode for mere alcohol while he slept.  Of course, Tooth Fairies only concern themselves with teeth, so a bad example.

I suspect, having been involved in bench research back in the day isolating and measuring proteins, that the author did a bad job at making his dilutions (but not the commercial pharmacy) and the nosodes were more contaminated with puree of infected mouse innards than he suspected. The result is the typical mild protective effect you get from prior exposure to antigens.  Alternatively, it is just the usual random results you see in small studies combined, perhaps, with yet another example of seeing N-Rays.

Overall not impressive and a low quality study and of little applicability to ‘classic’ homeopathy.    And, like many studies in the SCAM literature, not repeated with a better methodology. The author states at the end, “Attempts to replicate these experiments under more controlled conditions (eg with complete blinding (!!) and using aerosol methods for more uniform dosing) are underway.”  That was 11 years ago. I wonder what happened to the results.  Follow up with improved methodologies is not the strong suite of researchers in the SCAM field. Squirrel!

There must be a less expensive and less cruel way to kill off  142 mice.  D-Con is cheaper and spring loaded traps are quicker.  Given that homeopathy is divorced from reality, this is more needless cruelty to animals than a reasonable scientific study.

My colleagues use the terms  like ‘highly unlikely’, or ‘highly implausible’ to describe the precepts of homeopathy.  I guess I am not a true skeptic.  Some things are, as the world is currently understood, impossible.  Perpetual motion machines are impossible, accelerating past the speed of light is impossible.  There are few SCAM’s I would classify as impossible out of hand.  Stick needles in people, or pop their neck, and you will get some sort of effect, perhaps not the effect intended (infection and stroke).  There is always the possibility that the SCAM is doing something, perhaps not in ways envisioned by the practitioner.  Even something as goofy as iridology or live blood analysis has the opportunity, albeit very rare,  to make a real diagnosis.  Only homeopathy has the honor of being the only SCAM based totally on fantasy.

I would classify the basic precepts of succussion and dilution to increase potency as impossible, not implausible.   I’m sorry, not dilution, potentiation, or as it is more appropriately called in fantasy fiction, casting a spell.  Homeopathy is 100% nonsense, and, like its nostrums, uncontaminated by reality. Sometimes it is argued that in the lower concentrations of spells,  there may be a molecule or two of an agent that could have an effect, to which I call shenanigans.   I subscribe to the concept of dose-effect of agents and there is a concentration below which molecules will have no effect.  The alleged toxins in vaccines are not toxic because the concentrations are inconsequential; the effects of homeopathic nostrums at initial spell castings are as equally unable to have an effect as the later spell castings.

If homeopaths were to say the act of serial dilution and succussion slowly transformed the water into Unicorn tears,  a universal curative, it would not make the underlying concepts less rational or divorced from the natural law.  I may not be doing a very good job of suppressing my total lack of respect for the  underlying fictions of homeopathy.

At one time, as an example, we did not know how aspirin worked, only that it was effective.  But the science of chemistry, pharmacology, etc. eventually lead to the understanding that aspirin results in  irreversible inactivation of the cyclooxygenase enzyme, which prevents the production of prostaglandin and thromboxane.  As you increase the dose of aspirin, the receptors are filled until all the receptors are used up and then there is no more effect by giving more aspirin.   Elucidating the action of aspirin did not require a completely new understanding of the basic sciences.  If homeopathy did indeed work, then all we know of the natural world is wrong.  Which is more likely: all of the basic sciences are correct or homeopathy is correct. And maybe homeopathy does give us a deeper insight in to the natural world, since science as we know it as about to be overturned.

In the end, I wonder at times if  SBM and medical journals are the correct forum for discussions of the validity of the underlying precepts of homeopathy.  What is the proper forum for the discussion of magic?  The fantasy fiction section, not the science section, of the library.  Or perhaps homeopathy is the purview of the anthropologist and psychologist as a cultural delusion.

Delusions are irrational beliefs, held with a high level of conviction, that are highly resistant to change even when the delusional person is exposed to forms of proof that contradict the belief. Non-bizarre delusions are considered to be plausible; that is, there is a possibility that what the person believes to be true could actually occur a small proportion of the time. Conversely, bizarre delusions focus on matters that would be impossible in reality. For example, a non-bizarre delusion might be the belief that one’s activities are constantly under observation by federal law enforcement or intelligence agencies, which actually does occur for a small number of people. By contrast, a man who believes”  that the fundamental precepts of homeopathy  are true “holds a belief that could never come to pass in reality.

In medicine we determine that a behavior is pathologic when it starts to have negative consequences for the patient or others.  Alcohol is the classic example where use blends from fun to pathologic as harm accrues in the patient and his environment.  Homeopathy would appear to be another.  I look forward to the inevitable ‘when you point a finger you have three pointing back at yourself’ reply.

When I was first in practice, I saw a patient in clinic for ‘parasites.’  The room reeked of garlic as he was continually chewing on raw garlic cloves as he said it suppressed the parasite.
In discussing his symptoms he told me that the air was full of these parasites, and they would land on his skin and burrow in.

Probably Delusions of Parasitism, I thought, as no parasite has this life cycle. But it is not unusual for patients to mis-attribute symptoms to an erroneous cause, so I had to make sure he did not have some illness he was mistakenly attributing to parasites.

“How do you know they are parasites?”
“I collect them.” he said, holding up a large brown jar that rattled dryly as he shook it.
“Can I see them?  And where do you get them?”
“From my nose,” he replied as he dumped three cups of dried boogers on the exam table.

To my credit I neither screamed nor vomited, although I could not eat garlic for over a year.

I see no conceptual difference between that jar of ‘parasites’ and a jar of homeopathic nostrums, save the former, to my knowledge, never killed a child.

Posted in: Homeopathy, Humor

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