A new medicine Usually starts with tragedy.
Peter Ray knew. Born in Zimbabwe, now a child of mechanics and radiology technicians, Ray fled to South Africa with his family during the Zimbabwe Liberation War. He remembered his journey there in 1980 in a convoy of armored vehicles. As the sun shines, a soldier teaches 8-year-old Ray how to fire a machine gun. But his mother had to stop. She was uncomfortable.
A doctor in Cape Town diagnosed her with cancer. Ray remembers to go for radiation therapy with her, the ward, and the colostomy pocket. She likes the beach and likes to walk along the lines of land that meets the water. But she has a hard time leaving. Sometimes she came home from the hospital for a while and it seemed like things would get better. Thunder was full of hope. Then things will collapse again. Surgery, radiation, chemotherapy (treatment on the table in the 1980s) will soon be exhausted. When she was dying, he assured her that he would make a difference. He is 13 years old.
Ray studied to become a medical chemist, first in South Africa, borrowed a loan to fund his studies and then provided funding at the University of Liverpool. He has worked in pharmaceutical companies across the UK and has worked in numerous projects. Now, at the age of 53, he is one of the leading drug designers at a pharmaceutical company called Recursion. He thought a lot about his mother’s promise. “It lives with me all my life,” he said. “I need to absorb drugs that affect cancer in the market.”
The desire to stop one’s own tragedy from happening to others can be a powerful driving force. However, the drug discovery process has been grinding and is very slow. First, ray-like chemists are in their targets, usually a protein, a long string of amino acids coiled and folded around themselves. They call its model on the computer screen and watch it spin with black voids. They noticed curves and tendencies on the surface, where a molecule could dock in the dark like a spacecraft. Then, Atom by Atom, they try to build the spacecraft.
Animation: Balarama Heller
When the new molecule is ready, chemists pass it on to biologists, who test it in living cells in a warm room. More tragedies: Many cells die, the cause is not always clear. Biology is complicated and new drugs don’t work properly. Chemists will have to create another, and the other is often adjusted, tweaked for years. A biologist, Keith Mikule of Insilico Medicine, told me about his experience at another pharmaceutical company. After five years of work, their best molecules have unpredictable dangerous side effects, meaning they no longer take action. “There are a large group of chemists, a large group of biologists, thousands of molecules that have made it without real progress,” he said.
If a team is very lucky, they will get a molecule that in the mouse can do what it should do. They had the opportunity to hand it over to a small group of healthy human volunteers, which was a Phase I trial. If volunteers stay healthy, they donate it to more people, including those related to the disease, in the second phase. If the sick people are not much sick, they will have the opportunity (phase 3) to give more patients, as many groups as possible, and as diverse as possible.
At each stage, for reasons few can understand, and few can predict that a large amount of drugs will fall off. More than 90% of hopes fail along the way. When you meet a drug hunter, you may ask them cautiously and tenderly if they have ever had drugs. “It’s very rare,” said Mikul, whose name has a drug (Nilaparib, used for ovarian cancer). “We are unicorns.”
