The deadly disease in cows that led to a rat killer swallowed by a President
Plus a monkeypox update, the best podcast episode ever, and the origin of chickens 3500 years ago
Where do chickens come from?
Answer- the grocery store or the butchershop.
Jokes aside, though every meat supposedly “tastes like chicken” and packaged meat doesn’t make us think of the animal it comes from, chickens are sentient animals that were once domesticated.
Today, chickens are everywhere. There are about 80 billion of them. That's around 10 for every man, woman, and child! Until a landmark study published earlier this month, it was widely thought that the chicken was first domesticated in India during the Harappan age.
A team looked at chicken bones from hundreds of sites around the world and concluded that the first chickens came from an area in Thailand around 3500 years ago. Details of the study and the history of the chicken are in my column.
Many scientists still think that bones from Mohenjo-Daro and Harappa show chicken domestication in India. But the current study says these bones are too big to be chicken bones. There's also no mention of chickens in Vedic texts until 1200 BCE.
For hundreds of years, chickens were respected and admired. Some used in fights. But rarely eaten. We find intact bones of old animals buried at sites instead of cut and tossed without care. The Romans popularized chicken eating in Europe, followed by the Catholic Church which allowed them during times of fasting since they’re two-legged animals.
But suffice it to say that chickens were never considered "prestige" meat. In the U.S., they were cultivated by minorities. In India, many caste Hindus would not eat them. The perception of the chicken changed in the 1950s with the "Chicken of Tomorrow" contest which developed monstrous broiler chickens.
Even in my own family, my grandfather never ate chicken or chicken eggs (duck eggs were fine). Now, chicken is the least offensive meat to most. It is everywhere. Commercial breeding and the use of antibiotics have made chickens 3x in size compared to their early relatives.
A poison fit for a President
The story of how a mysterious and deadly bleeding disease in cattle in North America led to the creation of a rat poison which ended up being one of the most prescribed drugs in history is absolutely incredible.
A President swallowed a rat poison. It has saved many lives.
I have a fascination with how drugs are discovered and how they work. Earlier, I recounted how a mouldy muskmelon found by Mary Hunt at an American market in Peoria, Illinois became the source of much of the world’s penicillin, years after its discoverer, Alexander Fleming, gave up hope of using the mould as a practical drug.
But the story of the discovery of a blockbuster drug that has helped patients around the world by preventing pulmonary embolism, deep-vein thrombosis, and stroke is so fantastic that it is hard to believe. A series of events had to occur in a precise order with the main characters playing key roles.
In the 1920s, in the prairies of North America, farmers noticed that their healthy cattle were suddenly dying of internal bleeding. No one could fathom the cause, but to the farmers, it was a catastrophic problem. These farmers had already been squeezed by the economic hardships of the Great Depression and the loss of cattle amounted to a loss of livelihood.
Two veterinary pathologists, Frank Schofield and Lee Roderick, cracked the mystery. What was happening was that cattle were consuming sweet clover hay that was damp and had become a breeding ground for certain kinds of moulds.
In normal times, farmers would've discarded damp sweet clover hay, but times were hard during the Depression. Schofield and Roderick called the disease "sweet clover disease" and recommended farmers discard contaminated hay. Or else give infected cows blood transfusions.
Fast forward ten years. In the middle of a major snowstorm in Wisconsin, a farmer named Ed Carlson drove 200 miles with a dead cow, a hundred pounds of hay, and a milk can of unclotted cow blood in his truck. He headed to an agricultural experimental station.
Nearly everyone had gone home that night. Carlson searched around and found one office open. That was the office of scientist Karl Link. As I write in my column, "It was a serendipitous turn of events that would change the course of medical history."
Carlson deposited the milk can with unclotted cow blood, a hundred pounds of sweet clover, and his dead cow in front of Link who must've been shocked. Link sent Carlson back saying there was nothing he could do.
But Link starts to set up experiments to look into what exactly was causing the cows to die. They design new experiments on blood clotting with rabbit plasma and start to chemically take apart mouldy sweet clover hay. It takes them six years to find the chemical.
What Link and his colleagues find is that there's an enzyme in moulds in contaminated hay that links a naturally occurring compound called coumarin into an anticoagulant, dicoumarol.
Dicoumarol was the culprit. It was causing cows to bleed to death.
Most of the world soon forgets about dicoumarol. Except Link. Years later, while Link is recovering from a terrible bout of pleurisy from an earlier infection of TB, his mind wanders. Why not use dicoumarol as a rat killer? Rats that swallow dicoumarol might die from bleeding.
It is a brilliant idea. Except dicoumarol doesn't work well enough. So with funding from the Wisconsin Alumni Research Foundation (WARF), they began tweaking dicoumarol.
They design 150 compounds. No 42 which they name WARFarin is the most suitable rat killer.
Karl Link and a rat killer called warfarin
After World War II, warfarin is marketed as a potent rat killer. But this is where the story takes yet another bizarre turn.
An army soldier tries to kill himself by ingesting warfarin. Doctors save him by giving him vitamin K which counteracts the effects. It is then that researchers began to realise the full potential of using warfarin, not as a rat killer, but as an anticoagulant drug.
Warfarin had significant advantages over other anticoagulants in use at the time since it was highly soluble in water and could be used as an oral drug. Its effects could also be reversed with vitamin K.
And in 1955, after U.S. President Dwight Eisenhower suffered a heart attack, he was prescribed a rat poison called warfarin.
One of the best podcast episodes ever
I’ve got plenty of other stories of how drugs are created, but I can’t mention drugs without mentioning one in particular that every chemical biologist is familiar with.
It is the subject of one of the best podcast episodes by Radiolab and I encourage you to listen to it in entirety. Avir Mitra has done a fantastic job unfolding this bizarre story featuring a desi immigrant hero.
Here’s the Radiolab blurb—
Doctor-reporter Avir Mitra follows the epic and fantastical journey of a molecule dug out of a distant patch of dirt that would go on to make billions of dollars, prolong millions of lives, and teach us something fundamental we didn’t know about ourselves. Along the way, he meets a geriatric mouse named Ike, an immigrant dad who’s a little bit cool sometimes, a prophetic dream that prompts a thousand-mile journey, an ice cream container that may or may not be an accessory to international drug smuggling, and - most important of all - an obscure protein that’s calling the shots in every one of your cells RIGHT NOW.
‘Nuff said.
A monkeypox update
As a DNA virus, the monkeypox virus is not supposed to mutate rapidly, but a new study has found that there are around 50 changes in the virus causing the current global outbreak. The virus is adapting to spread in humans. This is the subject of a really great paper in Nature Medicine.
Still, as I’ve said before this is not the COVID-19 pandemic. Spread is mainly by close personal contact including touching and nearly all cases to date outside of Africa have occurred in men in physical relationships with other men.
Overall, these is low human-to-human spread making it unlikely there will be a large-scale outbreak affecting a lot of people everywhere all at once. Monkeypox should be easier to contain than COVID with far less draconian measures.
What else I’ve read
People who smell similar are more likely to be friends
Certain viruses make victims smell better to mosquitoes
Six months in space leads to a decade’s worth of long-term bone loss