Toxicology: diagnosis and cure of poisoning, version 1.6
Regarding toxic proteins, and other stuff - this post will be revised regularly
(1.3 If someone could post this to Twitter, I’d be much obliged)
PROLOGUE: ROOT CAUSE ANALYSIS IN MEDICINE
During the 20th century, the term “root cause analysis” emerged. Its many applications are a big topic, but it has made little progress until now at entering the world of medicine. Hence, we get the label “idiopathic” for illnesses - idiopathic hypertension would be the best known - which translates into common speech as “high blood pressure of unknown cause.”
(Surgeons may jump in at this point and say “we’re all about fixing root causes!” Also a topic for another day…)
There is one branch of medicine which has been dedicated to root cause analysis from day one, and that is toxicology - the study of poisons, poisonings, and antidotes.
THE HISTORY OF POISON 1.0
This topic is huge, and in version 1.0 I am going by memory. Socrates was killed using Hemlock juice, several hundred years BC, as a judicial execution. This tells us that the properties and dosing of hemlock juice were well-known.
The Hippocratic Oath, also from pre-Christian times, makes explicit reference to poisoning, and the statement: “I will not administer poison.” Evidently, some physicians did administer poisons, and Hippocratic physicians distinguished themselves by not doing so.
Paracelsus, a famous and still-controversial medieval European physician is said to be the source of the proverb “the difference between a medicine and a poison is in the dose.”
The Medici family of Italy, during the European Renaissance, is said to have excelled in the use of poisoning, both acute and chronic, in maintaining power and killing their enemies.
POISON AND ANTIDOTES
Interestingly, the city of Sao Paulo in Brazil is one of the largest antidote manufacturers of antidotes in the world. The reason: snake, scorpion, and spider antivenin.
Doubly interesting, the Butantan Institute repurposed some of its manufacturing capacity during covid to produce…the Astra Zeneca vaccine.
Many antidotes in the field of venom toxicology are based upon creating monoclonal antibodies against the proteins that are created by some snakes, spiders, and scorpions.
1.2. One medication that has an antidote derived from antibodies is digoxin, which can be dangerously toxic (see James Bond in Casino Royale - a little inaccurate but gives a flavour). The antidote, called Digibind, consists of antibodies that gather up digoxin in the blood.
1.5 HOW DO ANIMALS DEAL WITH TOXINS? THE AMAZING LIVER
It is probably fair to say that the liver is the most chemically complex organ in the human body. Among its many many roles are protecting us from poison. There are a few substances that are known to cause liver failure: acetaminophen, toxic mushrooms, alcohol. One could say that the liver is our “toxin immune system.”
1.6 DETOXIFICATION IS A BUNCH OF SHIT
There is an unusual condition arising when the liver is low-functioning, as is the case in cirrhosis - hepatic encephalopathy. This is when a person with liver failure gets delirious and many even proceed to a coma.
What is astonishing about it is its cure: making the person get diarrhea.
This shows us a couple of things about how the body handles poison. First, only people with very weak livers get hepatic encephalopathy. This shows us that the majority of us are constantly protected from having our brains poisoned by the functioning liver. Second, it shows us that when the liver can’t do its job of detoxification well enough, the intestines will try to do it by flushing themselves out.
This also suggests the possibility that our intestines help out with the detoxification process all the time, via expelling substances that are unhealthy for us, through our stool.
HOW DO YOU BYPASS THE LIVER’S AMAZING DETOXIFICATION ABILITY?
For a wide variety of reasons, physicians have been bypassing the liver in order to deliver medications to other organs in the body.
How is this bypass done?
Most simply, by introducing the medicine to the body via some other route than the mouth. It could be through the skin, or inhaled through the lungs - however, medicine is especially known for injections - which are, at their heart, a way of bypassing the liver.
VERSION 1.1: Diving into the literature, first pass attempt
Nano-antidotes for drug overdose and poisoning | Science Translational Medicine
1.4 Monoclonal antibodies are artificially-produced antibodies, which are used in medicine for antidote-type treatment, as mentioned above with digoxin and venom. They are increasingly used for other treatments also, such as Crohn’s Disease and multiple sclerosis. And they were successfully used during Covid, as they could bind with spike proteins from the virus.
Here is the article count in PubMed for monoclonal antibodies. Basically, it took off in the early 70s, slowed a bit, and then has steadily grown ever since, including accelerated growth in 2020, likely related to covid.
I trust that readers see where I am going with this.
https://twitter.com/mikezimmer_gmz/status/1557494660045479936?s=20&t=og5IdmNZpX6WcxOs7Bozaw
Dr. Benoit I miss you on Twitter! I'm so glad to have found your substack✌️❤️🙌