WorldNobel Prize in Medicine: "Cancer treatments were like trying to fix a...

Nobel Prize in Medicine: “Cancer treatments were like trying to fix a television with a hammer”

Physician William Kaelin did not want to win the Nobel Prize in Medicine. His wife, renowned oncologist Carolyn Scerbo, predicted that he would eventually win. Together they had fun thinking about how the Swedish prize, which turns winners into demigods in the collective imagination, would change their lives. In 2015, she died of lethal brain cancer at the age of 54. Kaelin, without her “best friend, soul mate and life partner,” wished year after year not to receive the call from Stockholm. I no longer wanted to win it, but I was on every bet. The doctor, a 63-year-old New Yorker, helped discover the mechanism by which cells detect available oxygen and adapt to it, a discovery that opened the door to new treatments against its great enemy, cancer, as well as against anemia. On October 7, 2019, his phone rang in the middle of the night. I had just won the Nobel Prize in Medicine.

Kaelin of Harvard Medical School answers questions from EL PAÍS from her home in Boston, before participating by videoconference in a meeting with young scientists at the Global Health Institute in Barcelona as part of the Foundation-supported Nobel Prize Inspiration Initiative AstraZeneca. “I hope we discover something in the next 10 years that will completely change the fight against cancer,” says Kaelin. He’s on the front line to get it.

Question. One of your professors at the university said you had no future in science.

Response. Yes, he has already passed away. I was in the wrong lab, with the wrong teacher, and the wrong project. But I was a kid in my late twenties and I believed the criticism. Only after talking to other scientists later did I realize that maybe the problem wasn’t me.

FOR. When you were young, you thought biology was “terribly boring”.

A. Yes, I’m not the only one. I read the bios of many biologists of my generation and many of them, like me, thought biology was very boring because it was very descriptive, like collecting stamps. In the 1960s and 1970s it was necessary to memorize countless names of plants and animals, but we lacked the tools to carry out explanatory experiments. When you’re in high school, the most important thing you can learn is to think clearly, logically, and rigorously. If you learn by studying biology, wonderful, but you can also do it in other subjects. You can reinvent yourself several times along the way, but you need to learn to think.

FOR. You were born in 1957, the year of the launch of the Soviet Sputnik satellite, and you even attended the parades to welcome American astronauts who landed on the moon in 1969. Do you think today’s children have enough scientific heroes?

A. When Barack Obama was president, he said we needed another Sputnik moment. And I knew perfectly well what he meant: that moment when people’s imaginations expand and new opportunities appear. I benefited from the interest in science and engineering in the 1960s, fueled by the space race and the Cold War. I think that, at least in the US, and I’m afraid that in other parts of the world, politicians sometimes disrupt the workings of science and question scientists’ motivations if they don’t like the conclusions. There it is, for example, climate change. There are people who, for political and economic interests, question the motivations of scientists. This worries me because it confuses young people.

FOR. When your wife died of brain cancer, you asked those attending the funeral not to bring flowers but to make donations for cancer research. Do I need more money?

A. Having more money and resources just helps. The more science is invested, the more knowledge is generated and disease treatment progresses. But it is not just a question of money, the whole ecosystem is important: it is necessary to support science and have a powerful educational system. If these conditions are met, the more resources, the better. Sometimes we don’t fund science enough.

FOR. Now that we have a better understanding of oxygen sensors in cells, what will happen? What drugs can we have in the short term?

A. We already have new drugs that, by taking them, trick the body into thinking it is not getting enough oxygen and responding, for example, by forming more red blood cells. One of these drugs, roxadustat, which I was involved in, was recently authorized in Europe as a treatment for anemia. We now know that cancer often hijacks the system, controlling oxygen sensors, to trick the body into supplying the tumor with blood. There are new drugs, such as so-called HIF-2 inhibitors, that are very promising in certain types of cancer. The first of these drugs was approved in August for the treatment of von Hippel-Lindau disease, a rare disease that causes cancer, but I will be very surprised if they are not approved for other tumors as well, including kidney tumors.

FOR. In your Nobel speech you stated that, in fact, your discoveries begin with an 1894 study by British physician Edward Treacher Collins. [sobre o estranho crescimento de vasos sanguíneos nos olhos de dois irmãos]. Science is sometimes very slow. How can you go faster?

A. There was a tipping point in the year 2000, with the publication of the first draft of the human genome. Someday we’ll look back and say that was the Big Bang, because it’s radically accelerating progress in the biomedical sciences. We are in a golden age. It’s no accident that it took me so long to decipher what Treacher Collins had described. It’s just that we didn’t have the tools. Now everything goes much faster.

FOR. What was cancer treatment like in the eighties?

A. It was based primarily on drugs discovered for their ability to kill and inhibit cancer cells in lab dishes. But there was no real knowledge of the molecular secrets of these tumors. We didn’t know which genes were altered. It was like trying to fix a television with a hammer. Now we can develop drugs that actually target these molecular mechanisms, rather than relying on drugs that indiscriminately kill cancer cells and normal cells.

FOR. Perhaps in the near future, in 10 or 20 years, we will look at the current stage and think that we were also fixing the television with a hammer.

A. I think things changed in the year 2000. At the risk of using another analogy, I think we are trying to fix a car and in the year 2000 at least we were able for the first time to open the hood and see the engine. That was the tipping point.

FOR. How do you imagine the fight against cancer in 10 or 20 years?

A. There is a big difference between science and engineering. When [o presidente norte-americano John Fitzgerald] Kennedy said we were going to put a man on the moon in a decade, because sending a man to the moon was mostly an engineering problem. The necessary scientific principles were already known in 1960, so it could be reasonably calculated that in 10 years it would be possible. In science there is much greater unpredictability. Suddenly, we learn something that completely changes the way of thinking and opportunities appear that we could not even imagine. I’m always a little cautious in predicting what cancer treatment will be like in a decade, because I would be disappointed if all my predictions were correct. I hope we discover something in the next 10 years that will completely change the fight against cancer. That said, we need to move towards this precision medicine instead of the old chemotherapies that were very rudimentary. Many precision remedies are currently used as the only treatment, but we need to combine them because we know this is the way to cure cancer and prevent resistance from arising. One drug can kill cancer cells, while another activates the immune system to be more effective against cancer. I can also imagine new ways to fix defective genes involved in cancer. In 10 or 20 years we can see new approaches that we can’t even imagine now.

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