Mad as a Hatter
Want to know what poison causes pathological shyness and is historically associated with being mad as a hatter? What causes dancing cat fever and might have contributed to the death of John Wilkes Booth? Listen to find out!
This is the Pick Your Poison podcast. I’m your host Dr. JP and I’m here to share my passion for poisons in this interactive show. Will our patient survive this podcast? It’s up to you and the choices you make. Our episode today is called The Mad Hatter.
Want to know what poison causes pathological shyness and is historically associated with being mad as a hatter? What causes dancing cat fever and might have contributed to the death of John Wilkes Booth? Then stay tuned!
Today’s episode is about a really interesting poison. It’s caused so many problems in the past, both permeant damage and deaths, I originally imagined it as a historical episode. Unfortunately, the toxin continues to cause significant morbidity and mortality in the present.
Our, regrettably, modern episode starts deep in the Amazon rainforest. A friend asks you to help in his medical clinic in Suriname. The clinic is chronically short on funds and chronically understaffed. You take a few days off and travel to the remote location. Suriname is located on the northeast coast of South America just above Brazil and its one of the most sparsely populated countries on earth.
A five-year-old girl sits on the exam table. Her mother is also in the room, holding a tightly swaddled baby. The mother is tearful and upset. She rushed her daughter into the clinic today because the patient lost consciousness, had rhythmic jerking movements in her extremities, and urinated on herself.
It’s not hard to guess what happened. This is a classic description of a seizure. The little girl is very solemn, but very cute, watching your every move with wide eyes. When you ask, she says she feels fine and she wants to go home.
Seizures are common across all age groups. I’m sure you’ve seen someone have a seizure, know someone with epilepsy or febrile seizures in childhood. Mom says the child wasn’t febrile and hasn’t had recent cold or flu symptoms, so it’s probably not a febrile seizure. At this point, we’re not too concerned. Seizures are upsetting to see, especially as a parent, but unless you’re swimming, driving, in a bathtub, or doing some other high-risk activity, they’re not typically life-threatening.
Seizures are so common, neurologists often say everyone is allowed one seizure in their lifetime. Typically, they don’t recommend treatment because many people never have another. If a person has a second or multiple seizures, they’ll recommend antiepileptics at that point. You try to reassure mom and proceed with your physical exam.
The patient’s vital signs are normal as is her mental status. Her heart, lungs and muscle tone are normal. Everything looks fine until you ask her to get up and walk. A normal 5-year-old will jump off the table and run around the room with even minimal encouragement.
Our patient stands up slowly, she’s very unsteady on her feet. Her trunk is swaying back and forth, this is called ataxia. You ask her to reach out with her finger and touch it to your finger. She keeps missing, called past pointing.
Uh oh. Taken together these are concerning neurological disturbances. This probably isn’t an isolated seizure.
The baby in mom’s arms starts to cry. Not the howling of a hungry or tired child, but a weak, disturbing sound. Mom unswaddles the baby to soothe it. You don’t need a physical exam to see this child has serious neurological deficits. You can’t tell from looking if it’s cerebral palsy, a chromosomal disorder, or something else.
Is this a family with an undiagnosed congenital disorder? You ask about the family history. Mom is fine, with no health issues, as is Dad. Mom doesn’t work outside the home. Dad works as a gold miner, not surprising given this is the main local industry. There’s no history of seizures or congenital disease in other family members. Mom is aware the baby’s development isn’t normal and says the other mothers in the village whose children have developmental challenges are very supportive of each other.
Wait a minute.
The closest village is tiny, with only 50 inhabitants. Just how many children have neurological issues? Mom says several, and in addition several others have difficulty walking, and some have had seizures. Obviously, this is an extremely high percentage in such a tiny village. Assuming they’re not intermarrying each other, something else is going on.
Our 5-year-old’s symptoms point to her cerebellum, the area of the brain which controls balance and fine motor tuning. A classic cerebellar poison we’re all familiar with – alcohol. Intoxicated people have difficulty walking, difficulty with balance and fine motor skills.
If our patient presented for medical care in a place with resources, she’d certainly get a head CT, an MRI, lab work and maybe a spinal tap, to check for encephalitis, among other things. We’re in the Amazon, so infectious diseases are top twenty on my differential diagnosis list. Our little girl’s case is fiction, so let’s assume we’re able to get enough testing to exclude common neurological and infectious diseases. The patient’s lab work looks normal. She’s able to travel to a larger city to get a CT scan which is negative.
This is a toxicology podcast so let’s get right to it. We could start down our usual route and list potential toxins causing her symptoms. This week, let’s take a different approach and instead consider potential exposures.
Mom says the only medicine in house is acetaminophen or Tylenol, a reflection of the lack of medical care and challenges facing the residents of this remote area. Toxic plants would be at the top of my list, since this is the Amazon, there are probably hundreds of poisonous plants around her house. Locals typically know which plants are safe and which aren’t. Certainly, the five-year-old might’ve eaten a berry or something she shouldn’t have, but the six-month-old baby and the other sick children in the village wouldn’t all have eaten the same plant.
What stands out to me here is her father’s job. Gold-mining is one of the biggest occupations in Suriname. The mines aren’t big operations run by huge corporations, but rather small-scale operations. The miners are in business for themselves or working in small cooperatives. While gold-mining suggests wealth and riches, in reality, these are often poor, underserved areas with disadvantaged people. The gold-mining might provide income to feed a family, but not much else.
Let’s talk about toxins associated with small-scale gold mines. Given that this entire village appears to be affected, an environmental toxin is certainly a consideration. The list is longer and far more toxic than I would’ve guessed. Compounds used include arsenic, lead, mercury, copper, and cyanide, just to list a few poisons.
Question number one. Which toxin associated with gold-mining is the most likely cause of our patient symptoms?
A. Cyanide
B. Arsenic
C. Copper
D. Mercury
Answer D. Mercury.
You don’t need me to tell you cyanide and arsenic are toxic. Cyanide is rapidly lethal causing seizure, coma and death. Yes, our patient had a seizure, but she’s not on the brink of death. Acute arsenic toxicity causes neurologic problems as well as gastrointestinal problems. If this were acute arsenic toxicity, again she’d be much sicker. Chronic arsenic toxicity is possible, but typically it causes bone marrow suppression which we don’t see on her lab work. Arsenic contamination of water also leads to chronic skin changes and gangrene, which is not what’s going on in this village.
Lead we’ve touched on before. The classic symptoms are joint pain and gastrointestinal distress. Lead toxicity is a consideration, it does cause developmental delay and can cause toxic encephalitis. Our patient’s presentation isn’t classic but a lead level would be useful. Copper can cause seizures and encephalitis. However, it’s associated with significant gastrointestinal effects like vomiting up blood and diarrhea, again it seems unlikely here.
The best answer in this list is mercury. Let’s take a few minutes to talk about mercury poisoning because it causes different syndromes based on which type of mercury the patient is exposed to.
First is elemental mercury exposure, like breaking an old thermometer. The liquid mercury is quicksilver. I don’t recommend it, but you can hold quicksilver in your hand without getting poisoned. It’s the vapors that cause a problem. In your lungs, inhaled mercury causes pneumonitis, or inflammation which can progress to respiratory failure. Quick side note if you break a mercury thermometer, do not, I repeat do not, vacuum it up as this aerosolizes the mercury increasing the risk of toxicity. Call your local poison center or health department for help.
The second type of mercury exposure is inorganic mercury, common in occupational exposures. If you’ve been waiting since the last episode, this is where we get the term mad as a hatter. Lewis Carroll did not invent the term for Alice in Wonderland but his character the Mad Hatter is a wonderful depiction of many of the symptoms associated with inorganic mercury poisoning.
Why the mad hatter? Hatmakers in the 1800s frequently developed this disease. Mercury nitrate was used to turn animal pelts into felt to make hats. So the disease came to be called hatters disease. It was also called the Danbury shakes after Danbury Connecticut, the center of the US hat industry.
The symptoms include salivation, twitching and tremor, gingivitis and tooth loss, a very labile affect meaning mood swings, and extreme, pathological, shyness. The medical term, typically used for the neurological effects is erethism or erethism mercurialis. These symptoms can progress to muscle weakness, renal failure, and delirium. In the 1900s workplace protections were instituted in England and France with minimal toxicity reported thereafter. Unfortunately, these precautions were not adopted in the US and mercury toxicity continued amongst hatters well into the 1900s.
Does inorganic mercury poisoning explain our patient’s symptoms? No, they don’t fit. Additionally, she’d have to be working with mercury directly. While the problem of child labor in mines is significant, it’s not the case here. I’d worry about her father and the other miners, but not their children.
It’s worth discussing why and how miners use mercury to understand the risks. Mining practices of course differ in different places. Often in Suriname, miners use high pressure hoses to wash away the top layer of soil, hoping to reveal gold in the layers underneath. They then throw liquid mercury, quicksilver, directly into the water. Mercury forms an amalgam with gold, extracting even small amounts of gold dust. Not surprisingly, tailings from the mines contain very high levels of mercury. The water from the tailings can travel hundreds of kilometers, affecting a huge area. Once the gold is collected, the mercury is burned off and the gold is once again left behind. It’s estimated 1 million kg of mercury per year is getting into the environment and 10-20 million people worldwide are exposed to mercury from these practices.
This practice is illegal, including in Suriname where its use is widespread. Why? Because of the third type of mercury poisoning, organic mercury poisoning. Once inorganic mercury is released into the environment, it undergoes biotransformation by bacteria in the water. Inorganic poisoning is famous from a tragic environmental disaster in Minamata Japan.
Let’s take a trip into the past because history illuminates the scope of inorganic mercury poisoning much more vividly than any recitation of facts.
In April 1956, an outbreak of neurological symptoms was noted in Japan by medical practitioners. The patients, many of them children, first developed numbness in their hands and feet, then progressive neurological disease and eventually seizures, coma, and death. The initial case fatality rate was 35%. An investigation found the victims were clustered in fishing villages around Minamata Bay.
Another unusual feature was noted. Sick animals. Cats went crazy and started jumping into the bay. The locals called it dancing cat fever. Crows fell from the sky, fish died. Seaweed stopped growing. By November, the symptoms were linked to heavy metal poisoning from fish in the bay.
Then things got complicated. It didn’t take long for suspicion to fall on the local chemical manufacturer, the Chisso Corporation, employer of 25% of the local population. It wasn’t till February 1959, three years later, that testing confirmed massively high mercury levels in the water, and defiantly proving Minamata Disease was due to inorganic mercury poisoning, specifically, methylmercury. There was more than 2 kg of mercury in each ton of sediment in the bay. This level is high enough to start a mercury mine.
Hair analysis is tricky to interpret in the setting of mercury but testing in this case left no questions. Those with Minamata disease had as much as 700 ppm of mercury in their hair. Those who lived in the bay, but didn’t have symptoms had 190 ppm. People who lived outside of this region had 4 ppm.
That data is hard to argue with. Why did it take three years? It’s multifactorial of course. But, the biggest reason, the Chisso Corporation’s attempts to deflect the blame. Before this podcast, I know about the horror of Minamata disease, but I had no idea just how nefariously the Chisso company behaved to cover up their involvement.
The company’s own testing revealed high levels of mercury in the bay, a fact they didn’t share with investigators. They actually funded investigations into causes other than their wastewater to confuse and distract the team. At one point, they changed their wastewater output from the harbor in the bay where the research was focused, to the Minamata River. This greatly increased the number of people affected by the disease as previously healthy villagers along the river also became sick.
In their own lab, they conducted an experiment, feeding cats food mixed with wastewater. Four hundred cats developed symptoms of poisoning and autopsy confirmed changes in the brain due to mercury. They concealed this information. It was only revealed during a trial years later when the primary investigator was on his deathbed.
As if all this wasn’t bad enough, they opened a water purification plant to a huge amount of fanfare, claiming to eliminate mercury from their wastewater. The water purifier was a complete fake. It didn’t extract so much as a drop of mercury. The company ultimately paid eighty-six million dollars to the victims and lawsuits are still ongoing to this day.
There are so many tragic aspects of Minamata Disease and what happened in Japan. One of the most heartrending is the congenital birth defects caused by methylmercury. In many cases mothers without any symptoms had children with drastic neurological deficits, leaving the children unable to care for themselves, even when adults. Researchers knew the placenta protected mothers by sequestering methylmercury. However, they didn’t realize until later that in fact methylmercury becomes concentrated in the fetus, the reason asymptomatic mothers can have severely poisoned children. Methylmercury causes decreased birth weight and muscle tone, severe developmental delay, deafness, blindness, seizures and severe spasticity.
This devastating outcome was the subject of a Life Magazine article with photos by W. Eugene Smith. The most famous photo entitled Tomoko and Mother in the Bath became representative of the tragedy. Reminiscent of the Pieta by Michelangelo, it shows the mother in a traditional Japanese bath cradling her severely disabled teenage child. The family consented to and suggested the bath setting in the original photograph. After Tomoko’s death, they requested it no longer be used, saying they wanted her be laid to rest. The photographer’s wife returned the rights to the family.
In 2013, most countries around the world ratified the Minamata Convention Treaty pledging to eradicate the use of mercury. You may be surprised to hear Suriname was one of those countries. Mercury is indeed banned. Unfortunately, it’s smuggled in.
Why are the miners in Suriname, and around the world, still using mercury? It’s not necessary for gold mining, large scale gold mines don’t use it. They use cyanide instead which is less toxic to the environment. The miners know it’s illegal. In many cases, they know it’s poisoning themselves, their children, and their neighbors.
Sounds easy to say, from here at my desk, just stop using mercury. The reality is far more complicated. Mercury is cheaper than other methods of gold extraction, including cyanide, even after price inflation due to smuggling. China is thought to be a big source. Small shops, even deep in the Amazon, sell essentials like Coke, condoms and mercury.
The miners are not panning for gold to strike it rich, rather fighting to feed themselves and their families. They’re worried about surviving today, not 10 years from now. Of course, people are advised not to eat fish in areas of pollution, but again it’s just not that simple, when in many places, fish is the main dietary staple.
Back to our little girl. She and most likely the other children in her village, are suffering the effects of organic mercury poisoning. Minamata Disease, not in 1950, but right now, today. There are a number of different ways to test for mercury poisoning none of which are completely reliable. Suffice it to say it’s best to rely on a toxicologist or other expert rather than “normal and abnormal” values.
What can we do to treat our little patient? Certainly, if she has multiple seizures, we can start her on antiepileptic drug. What else? That’s question #2.
A. Pump her stomach (ie gastric lavage)
B. Dialysis
C. Chelation
D. Supportive care
Answer: C. I’d recommend chelation. Despite this, I’m sorry to report I wouldn’t expect it to have a dramatic effect on her health. Chelation is giving a medicine that binds to the heavy metal. The idea is the metal is then sequestered, and can be excreted from the body. Sounds great in theory, in practice it rarely works as well as we’d like it to.
Chelation is recommended for mercury toxicity to reduce the body’s burden of mercury. It does not reverse serious neurological changes. In fact, it’s really never been proven to help, but the hope is that by reducing the total body burden, we might prevent worsening disease. Studies in mice show that chelation does reduce brain mercury levels and that’s pretty much the best we can say about it.
Small scale miners are at risk for all three types of mercury poisoning. Elemental from the quicksilver itself, though this appears to be a lower risk since it's often used outside where the vapors are carried away by the air. Inorganic mercury exposure occurs when the miners, or those who refine the gold, burn the mercury off. The mercury becomes oxidized, turning from elemental mercury to inorganic mercury. This is a much higher risk as it’s often done in an enclosed space, like a shop or building. Organic mercury poisoning is a threat to everyone in the surrounding regions thanks to the mine tailing runoffs.
This is a fictional case, as are all our cases, to protect the innocent. But it is based on real poisonings. In Suriname alone, 1 in 5 births is complicated by low birth weight, disability and death. This is double the rate in the US, a country not exactly renowned for its low rate of birth complications.
While we are on the topic of mercury, let me clear up some misconceptions. People are not being poisoned by mercury in dental amalgams. Thimersol, a mercury containing element previously used in vaccines does not cause mercury poisoning or autism.
Also, while eating seafood causes mercury levels to rise (pretty much all seafood is contaminated) it rarely causes significant toxicity. In fact, numerous studies show the benefits of eating fish and prove its cardiovascular benefits effects far outweigh any mild elevation in mercury.
Mercury, despite its well-known toxicity at the time, was used to treat which of the following conditions in the past?
A. Teething
B. Syphilis
C. Constipation
D. Infection
E. All of the above.
Answer: E. All of the above. Calomel lotion contained mercury and disturbingly was used for teething. Pink’s disease or acrodynia was seen, mercury toxicity causing pink, painful, discoloration of the hands and feet. Mercury was touted as a treatment for many, many medical problems. To treat syphilis, it was put into open wounds and directly into the vagina and urethra. Yikes. If the patient didn’t die of syphilis, they might die of mercury toxicity instead.
While these are historical problems, I actually saw vestiges of this during my residency. It wasn’t uncommon to see a patch of white in the buttock of an elderly patient getting on an abdominal Xray. My attendings explained it had nothing to do with the patient’s current abdominal pain, but was a mercury injection to treat syphilis. Penicillin wasn’t used until 1943, so the injections were from the 1930s or early 1940s. Astonishing to see the history of medicine in a modern setting.
One more fascinating fact, because there are just so many. We discussed madness, psychosis, as a complication of mercury poisoning. Every American knows John Wilkes Booth assassinated Abraham Lincoln. Booth was himself assassinated. A man named Boston Corbett was part of the army regiment dispatched to apprehend Booth with orders to take him alive. Corbett shot Booth instead. Initially he was arrested for disobeying orders, but later released as a patriot.
Corbett worked as a hatter and was by all accounts a very disturbed person, so much so that he castrated himself with scissors in order to reduce his urges. Later in life he was put into an asylum from which he escaped and was apparently never seen again. Was mercury responsible for the assassination of Abraham Lincoln’s assassin? We’ll never know, but maybe.
I don’t want this episode to last all day. So, last question. Question 4. Which famous composer had mercury poisoning?
A. Paganini
B. Mozart
C. Brahms
D. Tchaikovsky
Post your answers on our Twitter and Instagram feeds both @pickpoison1. Follow so you see the answer when I post it. Remember, never try anything on this podcast at home or anywhere else.
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