Friday, October 18, 2019

I was really something

I was really something (2016), by Judith Carlin. A fungus may live in your brain for years while meddling only as much as necessary with your neurons. Beyond a certain age it gets less benefit and has less incentive to keep you mentally healthy. One result may be Alzheimer's.

Behavior manipulation has been perfected by many organisms: viruses, bacteria, worms, and insects. Fungi, however, seem to be the champions:

Fungi probably represent a special case study in this general field because of several unique factors peculiar to this Kingdom. The first and most prominent is the range and complexity of behavioral manipulation by fungi of arthropods. [...] It is difficult and perhaps futile to rank manipulation across different kingdoms of life and argue that fungal manipulation is more complex than that observed when the manipulator is in the Kingdom Animalia (eg, trematodes). However, what is clear is that the diversity of strategies is greater than that observed in other groups. In addition, it is evident that behavioral manipulation has arisen multiple times independently. (Hughes et al. 2016)

You've probably heard about "zombie ants." A fungus invades an ant's brain and makes it leave its nest, climb up a plant, and fix itself in place with its mandibles. The fungus then kills the ant, and a fruiting body sprouts from behind the ant's head and showers spores onto the forest floor below.

There are other examples. A fungus invades the body of a flying insect and causes a hole to form on the side of the abdomen. It then releases spores through that hole while its host is flying. The infected body gradually falls apart, except for its nervous system and its wings. Is the insect still alive? Not really. The bits and pieces that remain have become extensions of the fungus (Hughes et al. 2016).

Other fungi imitate the smell or visual appearance of a sexually receptive female to lure male insects, who then become infected (Hughes et al. 2016).

In the above cases, the fungus mutilates and kills its host in ways that are not only ghastly but also easy to observe and study. But what about the more subtle cases where the host's behavior is simply altered? Those are the ones we know much less about. Our knowledge is biased toward the most obvious cases of infection. As Greg Cochran observed:

The most conspicuous transmission chains occur when disease manifestations are externally apparent in a high proportion of infected individuals, when they occur soon after the onset of infection, and when contact between infected and susceptible individuals is easy to observe. Under these circumstances chains of transmission are apparent through everyday experience. (Cochran et al. 2000)

Even when we can detect the presence of a pathogen, the causal link with certain effects is far from obvious because the effects are either subtle or long-term:

Pathogens are often classified as relatively harmless or even commensal without sufficient long-term study to warrant such a classification. The historical record illustrates the consequences of this error. Epstein-Barr viruses and human papillomaviruses were once thought of as relatively harmless on the basis of their linkage to relatively benign diseases that occur soon after infection (infectious mononucleosis and warts respectively). But each virus can cause lethal cancers. Bacteroides was once thought to be a harmless commensal, but recent evidence indicates that it may be linked to ulcerative colitis. (Cochran et al. 2000)

Many slowly developing diseases are probably of pathogenic origin. This seems especially the case with various forms of senile dementia. The pathogen targets your brain and gains some benefit while you’re still socially and sexually active. At that stage, it’s living in a commensal relationship with you and confines its neuronal meddling to the minimum necessary. Beyond a certain age, however, it gets less benefit from you and has less incentive to keep you mentally healthy. One result may be Alzheimer's:

The possibility that Alzheimer's disease (AD) has a microbial aetiology has been proposed by several researchers. Here, we provide evidence that tissue from the central nervous system (CNS) of AD patients contain fungal cells and hyphae. Fungal material can be detected both intra- and extracellularly using specific antibodies against several fungi. Different brain regions including external frontal cortex, cerebellar hemisphere, entorhinal cortex/hippocampus and choroid plexus contain fungal material, which is absent in brain tissue from control individuals. Analysis of brain sections from ten additional AD patients reveals that all are infected with fungi. Fungal infection is also observed in blood vessels, which may explain the vascular pathology frequently detected in AD patients. Sequencing of fungal DNA extracted from frozen CNS samples identifies several fungal species. Collectively, our findings provide compelling evidence for the existence of fungal infection in the CNS from AD patients, but not in control individuals. (Pisa et al. 2015)

Alzheimer's is a late onset disease. What is the fungus doing to your brain during the long time when you’re not mentally impaired? 

Another example may be multiple sclerosis:

Many biomarkers of MS are consistent with fungal infections, such as IL-17, chitotriosidase, and antibodies against fungi. Dimethyl fumarate (DMF), first used as an industrial fungicide, was recently repurposed to reduce MS symptoms. Its mechanisms of action in MS have not been firmly established. The low risk of MS during childhood and its moderate association with herpes simplex virus type 2 suggest genital exposure to microbes (including fungi) should be investigated as a possible trigger. (Benito-Leon and Laurence 2017)


Benito-Leon, J. and M. Laurence. (2017). The Role of Fungi in the Etiology of Multiple Sclerosis. Frontiers in Neurology 16 October

Cochran, G.M., Ewald, P.W., and Cochran, K.D. (2000). Infectious causation of disease: an evolutionary perspective. Perspectives in Biology and Medicine 43: 406-448.  

Hughes, D.P., J.P.M. Araujo, R.G. Loreto, L. Quevillon, C. de Bekker, and H.C. Evans. (2016). Chapter Eleven - From So Simple a Beginning: The Evolution of Behavioral Manipulation by Fungi. Advances in Genetics 94: 437-469.

Pisa, D., R. Alonso, A. Rabano, and I. Rodal. (2015). Different Brain Regions are Infected with Fungi in Alzheimer's Disease. Scientific Reports 5(15015) 


Sean said...

The brain plaque characteristic of dementia is increasingly thought to be part of immune system attacks on bugs in the brain (P. gingivalis, Herpes ect). In a high parasite load population young adults carrying the Aβ (multiple times the risk of Alzheimer's) allele had better cognition.

It is my impression that immune response knocks seven bells out of brain infection (especially in those bearing amped up immune gene variants) and keeps bugs doing little or nothing at all until latter years, when aging results in dysregulation and an immune firestorm. Sorry to be so negative, but by my way of thinking the brain's immune cells are necessarily most active and efficient during prime reproductive years and gives a good account of itself even though it can't eliminate an infection from the brain it inactivates it. An analogy for the damage of Alzheimer's would be the devastated landscape once the US army 'destroyed the village to save it'. To put it another way, Alzheimer's is a Pyrrhic victory for a bug, because the immune system increasingly uses scorched earth tactics as the brain ages.

Peter Frost said...


First, I don't mind negative comments in an academic debate. The only exception would be a debate where the other person keeps repeating a criticism that I have answered and creates the impression that I have never addressed the criticism. I also dislike debates where the playing field is not even, i.e., the other person has a disproportionate ability to retaliate. In that situation, I would appreciate it if you stood clear.

Multiple sclerosis seems to be due to pathogenic fungi that infect glial cells in the brain and release toxins that trigger an auto-immune response:

My main interest is not in infections that trigger an immune response. Those are the ones we are are most aware of, but they are really just the tip of the iceberg. My interest is in those brain infections that exist for years without triggering any immune response. Such infections become obvious later in life because (a) the body's immune system is becoming hypersensitive and (b) the pathogen no longer has an incentive to keep its host healthy. Its host is no longer useful and will die soon.

Morris said...

Interesting article. I believe (with some personal evidence) that all human microbes are parasites and are increasingly harmful with time because they accumulate until there is there is little room left. This may help explain the exponential (low exponent, sharp rise at the end)symptom manifestation. The harm is stealing energy directly and promoting the need to expend to expel the microbe. There must be mechanism dedicated to expelling microbes but it does not seem to attract research. That mechanism suggests that individual cells posses energy stores. Again this seems to be not of interest.
As an anecdote I have discussed these points with very woke but also very educated (PhDs in the soft sciences)and they were aghast at the notion that microbes in humans are parasites, that cells are individuals that possibly posses their private energy stores. Maybe this is an example of microbes influencing human behavior. Tellingly they would not engage in examining reasons for/against this line of thinking, simply asserting that our relationship is self evidently mutualistic.

Sean said...

You are being specific about the mechanism in a way Cochran has avoided. That gives more things to pick on. I think his vague 'inexorable natural selection would eliminate homosexuality so it cannot be in the genes' argument is flawed in the light of Andreas Wagner on how evolution navigates the valleys between fitness peaks by means other than natural selection.

Something you said about pre 20th cent homosexuality having often been a hetero adult assault of boys made me think that you see the rapid spread of bug behind the rapid transition to modern gay behaviour. Yet consider: up until the opening of the first gay bathhouses in the 1920s, self indentified homosexuals looked down on having sex with one another. Their main thing was servicing apparently straight men, After WW2 those who had got a discharge from the armed forces as unsuitable due to homosexuality were the basis of the first gay communities in San Francisco ect. It seems to me the group gay sex that took place in dedicated facilities in major cities' from the 60s on was likely to have caused infection with a lot of things. Some may have caused/intensified sexual compulsions. Since Hiv ended that era, the trend increasingly seems to be male homosexuals presenting as women (“transgirls”) while never having sex change operations, even though they may take female hormones.

"[G]ay men who tell me they feel sidelined in a space originally designed for them. It’s especially prevalent in Washington, D.C., where a college friend tells me it’s “surreal” to go to a gay friendly space and see people explicitly ruling out gay sex. “To read ‘no homos’ or ‘no men’ on a gay male app is troubling,” he says. — is openly homophobic. This is one consequence of the trans revolution." To present as a woman is to be as passive as possible.

Bradley said...

Great blog, thanks for posting

Anonymous said...

Not cean spreading spurious allegations and historical forgeries again