If someone in your family has a thrombotic condition, you've definitely seen warfarin.
If you still have no impression of this drug, it is better to change the perspective, in the current popular mobile game "Ark of Tomorrow", there is also such a character named "Warfarin", this game character is this antithrombotic miracle drug in neta reality.
The character image is very close to the characteristics of warfarin's main action on the blood.
In the game, Warfarin is set as a suckling mother character of a vampire race, who can help other companions regain health during battle and give them a certain buff buff.
In reality, warfarin is currently one of the most popular oral anticoagulants in the world, and is widely used in thromboembolic diseases, myocardial infarction, post-valve replacement and other fields, according to statistics, once in every 100 Britons, 1 person will have used warfarin.
If you think about it, isn't this just a different kind of femininity!
However, what many people don't know is that this drug that can treat thrombotic diseases is actually a rat poison that is still active in the front line of rat eradication!
Why is this miracle drug that has saved thousands of thrombotic patients be used as rat poison? How was it discovered and developed? Don't worry, let's introduce the research and development experience of the legend of Warfarin.
The origin of warfarin
To introduce the history of warfarin, we have to introduce a person, who is the developer of warfarin, Karl Paul link.
Carl Link (1901-1978), born in Laporte, Indiana, was a young man who fell into a middle class, but poverty did not prevent Carl Link from pursuing his studies, and he was admitted to the Agricultural College of the University of Wisconsin in 1918 and received a doctorate in agricultural chemistry in 1925.
Not only that, but the scholar did not stop his footsteps, with the financial support of the National Scholarship in the United States and the Board of Education, he went to Europe for postdoctoral studies and studied under famous teachers, and finally returned to the University of Wisconsin to teach in 1927.
Fritz Pregel, winner of the 1923 Nobel Prize in Chemistry, was one of Link's teachers
Paul Kahler, winner of the 1937 Nobel Prize in Chemistry, was one of Link's teachers
And the story of warfarin that we are going to tell is also starting from this moment.
One winter day in 1933, a herder named Ed Carlson carried a dead cow, a bucket of uncoagulated blood from a dead cow, and hay for feeding the cattle to the office of Carl Link, an associate professor at the University of Wisconsin.
He had come to ask for help, because his herd was dying one by one for unknown reasons, and the causes of death were also very peculiar, often because of small injuries and bleeding, or spontaneous bleeding. He couldn't sit still, so he had no choice but to rush to ask for help.
Link happens to know a little about such symptoms. In fact, as early as the 1920s, there were a large number of similar cattle and sheep bleeding continuously, as if they had hemophilia and died, a strange disease that people at that time called "grass and tree disease".
Because under the investigation of the herders at that time, it was found that these cattle and sheep had eaten moldy grass and trees (melilotus officinalis). One of the most common local feeds, it is a high-quality pasture imported from Europe, but it is very susceptible to mildew after being stored for too long.
sweet clover
And the United States was in the Great Depression at that time, herders may have to eat moldy things themselves, even if they can take care of livestock forage, so these moldy grasses caused very tragic consequences at that time.
Americans who received free food during the Great Depression
As Link expected, the herdsman brought moldy grass and trees. However, at that time, many people also did research on moldy grass and trees, but they could not find the cause of the violent death of cattle and sheep. Although the old herdsman found Link, Link had no solution.
The unknown areas aroused Link's curiosity, and after sending the herders away, Link plunged into the experiment. After observing the non-coagulating blood brought by the herders, Link speculated that there must be something in the moldy grass and trees that interfered with the coagulation system.
Link who does experiments
To find out which ingredient it is, you can only purify the ingredients in the grass and wood trees one by one, and then test them one by one, which is not a simple project, Link spent a full 6 years, until June 28, 1939, finally found the culprit that interfered with the coagulation system - double coumarin.
The final birth of warfarin
It turns out that fresh grass and trees originally contain an ingredient called coumarin, which is non-toxic. However, because coumarin will react with mold, the two molecules of monomer coumarin will oxidize into dicoumarin.
coumarin
Dicoumarin
The molecular structure of dicoumarin and vitamin K is similar, and the two will produce competitive antagonism. And because vitamin K plays a key role in the coagulation process, the antagonism caused by dicoumarin will prevent vitamin K from synthesizing coagulation factors, so that the fibrin and platelets produced by it cannot be combined, and eventually lead to the failure of coagulation function.
On the left is a rabbit that eats fresh grass and trees, and on the right is a rabbit that eats rotten grass and trees
Now that the substance had been discovered, Professor Link began to consider whether he could put it into practical use. He quickly mastered the way to synthesize dicoumarin and applied for a patent. After that, with dicoumarin as the core, as many as nearly 100 compounds were developed and synthesized.
Unfortunately, these nearly 100 compounds have their own defects and cannot be put into the application of the human body. Professor Link himself was sent to a nursing home for a recurrence of tuberculosis.
In the nursing home, I don't know what inspired Professor Link, he suddenly thought, since dicoumarin can not be applied to medicine for the time being, why not continue to play its function of making animals bleed?
In the previous experiments conducted by Professor Link on animals, he found that mice were most sensitive to the response of dicoumarin, so the unlucky mice became the object of experiments, Link tested all the dicoumarin compounds on them, and finally found that the compound 42 benzyl acetone coumarin was particularly effective.
Because the study was funded by the Wisconsin Alumni Research Foundation, the drug was named warfarin, which is the first letter of the foundation's full name, warf plus the last four letters of coumarin.
Yes, warfarin was indeed commercially used as rat poison in the first place. At that time, the rat repellent was not perfect, but the effect of warfarin was surprisingly good, and the rat extermination rate could reach more than 90% within three weeks after the bait, and the harm of accidental ingestion of warfarin was also small, and it would hardly cause casualties.
The rodenticide bromideron is an upgraded version of warfarin
Therefore, warfarin rat poison was soon sought after by everyone and became the best-selling rat poison. To this day, we can still see the figure of warfarin rat poison, if you see the roadside rat killer box on the word "please take a lot of vitamin k after accidental consumption", most of them are warfarin with warfarin ingredients.
From rodenticides to life-saving drugs
Speaking of this, in fact, the experience of warfarin can already be called very legendary, but no one expected that the truly brilliant deeds of warfarin would start from here!
Although Professor Link made a lot of money for developing warfarin rat poison, he was not satisfied with it, and he always remembered his original idea of putting warfarin into the medical field.
Because although warfarin can lead to the failure of the coagulation system, on the other hand, it also means that warfarin can effectively prevent blood clotting, thus achieving medical effects such as eliminating blood clots!
Moreover, the mainstream anticoagulant drug heparin used on the market at that time had many disadvantages, such as the need for intravenous injection and difficulty in preservation. However, warfarin can be swallowed orally in the form of pills, which is very convenient and undoubtedly a better anticoagulant.
Soon, some medical staff and scientists other than Professor Link recognized the huge potential of warfarin and participated in the development of warfarin as a clinical drug. Finally, after years of research and development and clinical trials, in 1954, warfarin was approved for use in humans and marketed as an anticoagulant drug.
But after all, warfarin is well known as rat poison for the public, so the promotion of warfarin anticoagulant drugs at the beginning suffered a lot of resistance, patients are not willing to eat the same thing as mice, not to mention that this thing was originally used to poison rats, who knows what will happen after eating themselves!
Changing the false impression of warfarin in people's minds should have taken years to work. However, an unexpected event reversed the trajectory of Warfarin's life and added a touch of legend to Warfarin's experience.
In 1955, Eisenhower, a world war hero, a five-star general, and then the president of the United States, suffered a heart attack after playing golf, and for a time, the eyes of the whole United States were focused on the safety of the president.
In the end, the president managed to escape from the clutches of death, and it just so happened that the doctor used the warfarin to treat the president! This is equivalent to Eisenhower using his own life to give Warphalin an earth-shattering advertisement in the United States and even the world!
Suddenly, Warfarin was put on the throne of the altar and touted by the media as a "magical blood thinner".
Warfarin has gradually reached the peak of life, and is widely used in the treatment of myocardial infarction, atrial fibrillation, stroke and other diseases, until today, has become the most popular clinical anticoagulation drug. Although new anticoagulants are gradually emerging, the historical status of warfarin is still difficult to shake.
End
Looking back at the history of the origin of warfarin, it is not difficult for us to find that warfarin eventually became today's "miracle drug", which was stacked by countless accidental events:
If there had been no Great Depression in the United States, herders would not have fed cattle with moldy hay; if Carlson had not come to college, he would not have met Professor Link; if Link had not developed rat poison on a whim, Warfarin might not have gained fame; if the president had not fallen ill, Warfarin would not have become so popular so quickly...
And all the accidental events just bumped together, making today's "anti-condensation drugs". Such a coincidence, such a wonderful thing, it is really emotional.
About author:Supermodel Jun, self-media blogger of mathematics education and life, new science and engineering dad. Published "Mustard Sumiya · The Little Story of the Great Scientist; The Journey of Mathematics: 54 Mathematicians Who Shine on Mankind; The Comic Math: The Mathematician Who Shines on Mankind; The Schrödinger's Cat: The Little Cute Pet of the Great Scientist. Follow-up mathematical culture is creative, welcome to pay attention to understanding!