Talmudic Question #40

by Richard Moxon

Can you think of any human disease that does NOT have a possible microbial component?

Comments

[Earl Pursell]

I also thought of mesothelioma. Add Black Lung, too. If you are counting genetic disorders as diseases, you can add hemophilia, sickle cell anemia, and cystic fibrosis. Although genetic diseases may not have microbial causes, many have very interesting microbial interactions, as with sickle cell anemia and malaria.

[Ramy Aziz]

Sterility? :))

Elio says: Funny alright.

[elio]

Elio replies:

Granted, prion diseases are not microbial (except by stretching the term microbe to the breaking point). But surely, people and animals with such diseases have bacterial and viral superinfections, no?

[Kristin]

Prion diseases are believed to be an normal cellular protein that folds abnormally seeding other normal prion proteins to the abnormal form. This and this alone (or at least most of the field) believes that no microbe is involved. As I am not very familiar with other protein misfolding diseases, I would put the idea out there that many of them are general misfolding of proteins with no microbes involved (Alzheimer, Parkinsons etc).

[Jeremy Cherfas]

Regarding the question about nutritional deficiency diseases, I know that iron deficiency is linked to improved resistance to certain pathogens, so there's a component there, I think.

[Suzanne Portnoy]

I'm not sure if I agree with the comments that genetic diseases such as depression have no microbial component. If that is true why is schizophrenia -- a disease with genetic etiology -- also linked to maternal prenatal viral infection. Perhaps we are just not widening our focus enough.

Can prenatal infection tilt the system towards a dysfunctional phenotype?

Ok, it's easy to poke holes. But how much do we know about the interplay of pathogens, immunity and the developing embryo?

[Chuck Haas]

Wouldn't any of the classical nutritional deficiency diseases (scurvy, rickets, etc.) be such examples?

Nov. 10, 2008:
Dr. Moxon has asked the so-called Talmudic question #40, whether we can think of a disease that has no microbial connection (presumably he is referring to all kinds of tiny biological aggregates or substances that have some of the remarkable properties of a living organism). The question is intrinsically inefficient as it simply wants to know if you have a positive feeling for the possibility. If we truly know such an example, it would be the result of actual negative experimental findings or strong intimations of a non-involvement, in which case there is no need to tell Dr. Moxon about the negative observations (well, maybe a PubMed citation). But anyone can propose that the previous researchers simply haven’t looked hard enough, no matter how many experiments they did. Proving that a guess is wrong can be a difficult, never-ending project and grant evaluators are unlikely to support such a project.

If Dr. Moxon is really asking the question “Why don’t you look for such a connection?” it would not interest the many researchers now doing just that. The recent discoveries of microbial disease instigations and adventitious infections have already started an important field of research.

Sincerely, your fellow questioner, Norman S. Radin

[Mark O. Martin]

I tried to post something earlier, but it "didn't take." I am less and less tech-savvy as the technology marches on.

First, much kudos to Professor Moxon---I have learned a lot from his research group's journal articles! Thanks for posting the Talmudic Question. It's a great "student discussion" question...and I in fact plan to use it in the next week or so in my own course.

Second, I think that we are moving toward a very ecological, interrelated/interactive view of the microbiota that are associated with every human being. Thus, I cannot think of a human disease that would not, potentially, alter myriad microenvironmental niches within the human body. The microbiota would surely alter its population structure in response.

Heck, I remember reading that clostridia can be infused into cancer patients, and the tumors become infiltrated by the obligate anaerobes. Here is an older review:

http://www.nature.com/nrmicro/journal/v1/n3/abs/nrmicro777.html

This argument isn't necessarily causative, I know. But the issue of polymicrobial diseases are taking us farther and farther way from a "Kochian" view of causation, microbes, and disease...toward what I can only call a "ecological" approach to medical microbiology.

Finally, I haven't seen anything recently from Paul Ewald (now at the University of Louisville, I think), who has long argued for a microbial component in the majority of human diseases, including some mental illnesses.

[John Ireland]

Assuming disease is meant to be limited to those disorders caused directly or indirectly by an external agent (thereby eliminating the obvious genetic disorders), I would put forth mesothelioma. Mesothelioma is specifically triggered by the prescence of asbestos fibers (an inorganic material) in the lungs. This analogy could be expanded to include any of the diseases caused by direct toxic exposure (i.e. radiation sickness).

[Wm Tanksley]

Sure... If "disease" means "dis-ease", and "possible" means "according to the evidence" and not "logically possible". Depression and genetic disorders are examples of obvious individual diseases that have no microbial component; economic turbulence is less obviously a disease (and perhaps don't meet your criterion for "human"), but at least meets the broad definition of dis-ease, and undeniably has no necessary microbial component.

Of course, I could also stretch the meaning of the word "microbial" and question whether viruses and prions are "bios" (alive).

I was about to ask whether questioning the word definitions was fair game... And then I noticed the word "talmudic" in the title. In other words, YES!

-Wm

[Mark O. Martin]

That is a tough question, because a human being is comprised of a huge number of subtle ecological niches. Almost any disease alters one or many of those niches (and those niches can interact, as well). Microbiota will take advantage of those changes.

Unless, Professor Moxon (and I admire your work, incidentally) means prokaryotes that are causative to the disease state...