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Viagra began as sildenafil, a Pfizer drug first tested on volunteers in Wales in the early 1990s as a treatment for angina, chest pain caused by narrowed arteries. It did little for angina, but it had an unexpected side effect, and Pfizer developed it for erectile dysfunction instead.

Wales, early 1990s

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The story behind the card

Sildenafil was made by a team led by Simon Campbell at Pfizer's research centre in Sandwich, Kent. It relaxes the muscle in blood vessel walls, which widens the vessels, and the hope was that this would improve blood flow to the heart. The early trials, the first of them at Morriston Hospital in Swansea, showed little effect on angina, but men reported erections as a side effect. A much-repeated story says some volunteers did not want to hand back their leftover tablets. Pfizer changed course, and the drug was approved as Viagra in 1998. Under the name Revatio, sildenafil also treats pulmonary arterial hypertension, dangerously high blood pressure in the arteries of the lungs.

Türkçe oku
Viagra aslında Pfizer'ın anjina, yani kalp damarlarının daralmasından kaynaklanan göğüs ağrısı için geliştirdiği sildenafil adlı bir ilaçtı. 1990'ların başında Galler'de gönüllüler üzerinde denendiğinde göğüs ağrısına pek yaramadı; ama beklenmedik bir yan etkisi vardı ve Pfizer ilacı sertleşme bozukluğunun tedavisine yöneltti.
Galler, 1990'ların başı

Sildenafili, Pfizer'ın İngiltere'nin Kent bölgesindeki Sandwich araştırma merkezinde Simon Campbell'ın yönettiği bir ekip geliştirdi. İlaç damar duvarlarındaki kasları gevşetip damarları genişletiyor; amaç kalbe giden kanı artırmaktı. İlki Swansea'daki Morriston Hastanesi'nde yapılan denemelerde ilacın anjinaya pek etkisi görülmedi; buna karşılık erkek gönüllüler yan etki olarak sertleşme bildirdi. Sık anlatılan bir hikâyeye göre bazı gönüllüler ellerinde kalan hapları geri vermek istememişti. Pfizer yön değiştirdi ve ilaç 1998'de Viagra adıyla onaylandı. Sildenafil bugün Revatio adıyla, akciğer atardamarlarındaki basıncın tehlikeli ölçüde yükseldiği pulmoner arteriyel hipertansiyonun tedavisinde de kullanılıyor.

Sources and further reading

Background reading: Sildenafil
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The idea that the face can feed back into feelings, called the facial feedback hypothesis, goes back to Charles Darwin and William James. In a famous 1988 experiment, Fritz Strack and colleagues had people hold a pen in their teeth, which forces a smile, or between their lips, which prevents one, and those in the first group rated cartoons as funnier. In 2016, seventeen laboratories repeated that experiment exactly and found no effect. A 2019 review of 138 studies concluded that the effect is real but small and varies from study to study. The 2022 Many Smiles Collaboration, led by Nicholas Coles and designed jointly by supporters and sceptics of the idea, found that deliberate smiling could both strengthen and start feelings of happiness, while the pen method remained inconclusive.

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The estimate comes from Ron Sender, Shai Fuchs and Ron Milo of the Weizmann Institute of Science in Israel. Their reference man is 20 to 30 years old, 170 cm tall and weighs 70 kg. The ten-to-one figure, they found, went back to a single rough calculation from 1972 that had been repeated for decades. Almost all the bacteria live in the colon, the last part of the gut, and together they weigh only about 0.2 kg. Among human cells, red blood cells dominate the count, making up about 84 per cent, while fat and muscle cells, far fewer but much larger, make up most of the body's cell mass. The balance also shifts through the day: a single trip to the toilet empties a quarter to a third of the colon's contents.

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Ron Sender and Ron Milo combined the number, mass and lifespan of every major cell type in the body. Short-lived cells dominate the count. Red blood cells live about four months, and neutrophils, the most common white blood cells, only days, so the bone marrow must make vast numbers of them every day. By mass, the largest shares come from blood cells and from the cells lining the gut, which are shed and replaced within days. At this pace, a number of cells equal to all the roughly 30 trillion human cells in the body is replaced in about three months. That does not mean the whole body is renewed: most nerve cells in the brain last a lifetime, and heart muscle cells are replaced only very slowly.

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Scientists call this link the gut–brain axis. The gut has its own network of about 500 million nerve cells, the enteric nervous system, sometimes called the “second brain”, which can run digestion largely by itself. It is connected to the brain mainly through the vagus nerve, a long nerve running from the brainstem down to the abdomen, and most of its fibres carry messages upwards, from the gut to the brain. More than 90 per cent of the body's serotonin, a chemical messenger, is found in the gut. Gut bacteria play a part too: in a 2004 Japanese study, mice raised entirely free of germs overreacted to stress. Stress can speed up or slow down the gut, one reason it often worsens irritable bowel syndrome, a common gut disorder. Most research on the microbes' role has been in animals, and human evidence is still limited.

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The word placebo is Latin for “I shall please”. One of the first clues that the effect is physical came in 1978, when Jon Levine and colleagues studied patients recovering from wisdom tooth removal. They gave them a placebo and naloxone, a drug that blocks the effect of endorphins, the body's own painkilling chemicals. In patients who had responded to the placebo, naloxone increased the pain, which suggested that the placebo relief came from endorphins. In 2004 Tor Wager and colleagues used brain scans to show that a placebo painkiller reduced activity in pain-processing regions during a painful stimulus. Expectation works the other way too: in the nocebo effect, from the Latin for “I shall harm”, expecting harm makes symptoms worse. None of this means the pain was imaginary, or that placebos can replace effective treatment.

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