Science Trends very kindly reached out to me to write about my recently-published hypothesis proposing that some cases of amyotrophic lateral sclerosis (ALS), also known as motor neurone disease, are caused by a type of bacteria, Mycobacterium avium subspecies paratuberculosis (MAP).
MAP causes a chronic gastrointestinal illness in domestic livestock such as dairy and beef cattle, goats, and sheep called Johne’s (“Yo-knee’s”) disease. MAP has long been investigated as a possible cause or trigger of Crohn’s disease because of the similarities between Crohn’s disease in humans and Johne’s disease in animals.
Most MAP researchers believe that the only human disease that MAP causes is Crohn’s disease. Several brilliant “MAP theoreticians,” however, have proposed that MAP, like other zoonoses, may cause a range of diseases in its human host that MAP doesn’t cause in its animal hosts. These MAP theoreticians have proposed that MAP causes a wide range of human autoimmune and neurologic diseases in addition to the Crohn’s type of inflammatory bowel disease. One of these brilliant MAP theoreticians, J. Todd Kuenstner, first mentioned in passing in a 2015 article that MAP may cause ALS.
I have been unable to ascertain how Dr. Kuenstner came up with the idea that MAP may cause ALS. Unfortunately, the idea occurred to me by accident. I was preparing a talk for the 2017 Philadelphia MAP conference. The conference presentations can be seen at https://humanpara.org/2017-map-conference-videos/.
Most MAP researchers believe that the only way humans are infected with MAP is by drinking MAP-contaminated milk or eating MAP-contaminated dairy products. But if MAP is a zoonosis, an animal microorganism that causes disease in humans, it will come from an infected animal’s feces or manure as well as from an infected animal’s milk. MAP is excreted in an infected animal’s feces or manure (I am using these terms as synonyms), as well as being secreted in an infected animal’s milk. See this figure from Iowa State University’s Center for Food Security and Public Health.
MAP is particularly heavily excreted in an infected dairy animal’s feces. Only a few drops of manure contain enough MAP organisms to cause infection in a dairy calf. A MAP-infected dairy cow excretes12-14 gallons of such heavily contaminated feces per day, containing over 25,000 infectious doses of MAP.
An organism excreted in an animal’s feces contaminates the ground the animal defecates on. MAP is an unusually durable organism; it lasts indefinitely in the environment once excreted in feces.
MAP organisms are found throughout the soil in countries where MAP infection of domestic livestock is extensive and longstanding. It’s everywhere in the soil, like other environmental nontuberculous mycobacteria. People who play outdoor sports in these countries, therefore, are playing in MAP-contaminated dirt or soil.
My talk at the 2017 Philadelphia MAP conference was about how manure is the major source of human infection with MAP, not milk, and about what diseases people might get, in addition to Crohn’s disease, from living near bodies of water contaminated by domestic livestock manure and breathing in MAP-contaminated water, or from living near the domestic livestock farms themselves and breathing in MAP-contaminated soil, dirt, and dust. Note from the chart above, about transmission routes of zoonotic diseases, that MAP may be able, like other zoonoses, to “get in” to humans through the skin, through cuts and abrasions in the skin, or perhaps even through intact skin. This route is described under “direct contact” with the animal, but this direct contact may also be with the zoonosis-contaminated manure or feces. Below is one of the slides from my conference presentation, summarizing how MAP “gets into” humans:
I had always wondered why Steve Gleason got ALS. Mr. Gleason grew up in Spokane, Washington, and in the 1980s, Spokane had the highest rate of Crohn’s disease in the whole world. This high rate was due to the dairy farming in the Spokane Valley, a city just east of Spokane. So on a whim, I googled “ALS clusters,” and what showed up first were not the clusters of ALS in football, soccer, and rugby players, but the ALS cluster in the early 2000s at the Kelly Air Force Base in Bexar (“Bear”) County, Texas.
There are clusters of ALS in football, rugby, and soccer players because they are throwing themselves, being thrown into, kicking up, and playing in MAP-contaminated dirt.
My husband played football in junior high and showed me pictures of him with dirt-covered knees and lower legs during practices. Football players throw themselves and each other into MAP-contaminated dirt a lot. Football players who are in “speed positions,” who throw themselves into MAP-contaminated dirt forcefully, are more likely than their non-speed counterparts to develop ALS.
There are no clusters of ALS in baseball players because it probably takes a lot of contact with MAP-contaminated dirt/soil in order to get infected with MAP. Lou Gehrig was an especially prolific baseball player, playing in a record number of games, and stealing a record number of bases. He initiated the headfirst slide into bases. There are many pictures of Gehrig sliding into bases, kicking up clouds of MAP-contaminated dirt.
I am proposing that MAP gets into people from dirt, MAP-contaminated dirt that gets into their skin and into their mouths. ALS symptoms start where MAP-contaminated dirt gets in; if the MAP-contaminated dirt gets into the mouth, the tongue is the first organ affected. If MAP-contaminated dirt gets in through the skin on the arm, the arm (often the dominant arm, as that is the hand holding the ball) is the first organ affected. If MAP-contaminated dirt gets in through the skin on the leg, the legs have the first symptoms. MAP organisms may directly infect lower motor neurons and travel within lower motor neurons to upper motor neurons. This would explain the focality of initial ALS symptoms and their contiguous spread.
After a lot more googling, I discovered exactly how MAP causes ALS. Normal zinc- and copper-containing superoxide dismutase (SOD) prevents neuronal apoptosis. A zinc-deficient copper containing SOD causes neuronal apoptosis. Patients with familial forms of ALS have this particular zinc-deficient, copper-containing, neuronal-apoptosis-causing SOD. Tucked away in a single article is a description of MAP organisms producing the same kind of zinc-deficient, (in MAP’s case, containing no zinc at all) copper-containing, neuronal-apoptosis-causing SOD that patients with familial ALS produce.
The possibility that some cases of sporadic ALS may have an infectious etiology is not new. There is one known cause of ALS – the AIDS virus. Since ALS caused by HIV responds to antiviral medicine, it is known as ALS-like. There are other proposed infectious causes of ALS, including species of Brucella, Cyanobacteria, and Schistosoma. The most well-known post-infectious motor neuron syndrome is the post-polio syndrome.
I published this idea in the hope of encouraging the medical community to think about ALS differently and to give hope to patients with ALS that they may have a treatable rather than fatal disease.
This hypothesis is described in the article written by Ellen S. Pierce entitled How did Lou Gehrig get Lou Gehrig’s disease? Mycobacterium avium subspecies paratuberculosis in manure, soil, dirt, dust and grass and amyotrophic lateral sclerosis (motor neurone disease) clusters in football, rugby and soccer players, recently published in the journal Medical Hypotheses.