Doctor Hall, the wise man of biomedicine: “We will never cure cancer, it will be a chronic disease”

A few hours after landing in Bilbao to pick up the BBVA Foundation Frontiers of Knowledge Award in Biology and Biomedicine, Michael Hall, Professor of Biochemistry at the Biozentrum of the University of Basel (Switzerland), went viral on social networks for calling anti-vaccines “idiots”. It caused a stir, but it was an accurate presentation of his speech: precise, direct and sometimes sly, delivered in perfect Spanish with an accent from Puerto Rico, where he was born in 1953.

Hall shares the award with David Sabatini, MIT professor, for discover the mTOR pathway (mammalian Target of Rapamicyn), the mechanism that regulates cell growth. A finding that started from the rapamycin, an immunosuppressant synthesized from a fungus collected by a scientific expedition in the 1960s Rapa Nui, Easter Island. “It’s a very, very interesting story of scientific biochemistry. And I’m not saying it just because I’m the protagonist!” Recalls Hall, joyful. “It started in a distant, unknown land, and has grown, spilling over into other fields to this day.”

Those areas include possible therapies against neurogenerative diseases such as Parkinson’s or Alzheimer’s, obesity, diabetes and especially, because of its potential to inhibit cell reproduction, against cancer. But Hall is the first to cool expectations. “Cancer changes very quickly, tumors become resistant. If a drug extends life by three months, we already consider it a success. That’s why I think We will never cure it. We are going to make it a chronic disease, changing drugs, treatments and therapeutic targets“.

The mTOR pathway has been defined in a way that excites those of us who work on the Internet: the ‘project manager’ –project manager– of the cell.

I see it more like your brain: it captures the nutrients that are around it and decides from there how the cell is going to behave.

Before describing this mechanism, was the cell considered to be using nutrients and growing somewhat arbitrarily?

Broadly speaking, yes, and it was a very strange idea: that cell growth was not controlled, that it was a passive system. We now know that nothing in biology is arbitrary. Everything works according to an exact, precision mechanism.

How would you define your discovery?

First, the most important thing we have discovered is that growth is controlled by a mechanism in all living things: yeast, plants, animals, and humans. This is essential. Everyone knows us for having discovered TOR, the protein that functions as the ‘switch’ of the system, but that is secondary to me. We didn’t know why immunosuppressive drugs like rapamycin worked. No one had ever wondered how cell growth was controlled, because it was not thought that there was something controlling it.

One of the most interesting dimensions of the work you describe is the leap from basic science to practice. Do you consider it a success story?

Yes. We started what we call a curiosity driven research (“inquiry guided by curiosity”). We didn’t know where we were going to go, we just had some very interesting material, although it may not be important. But we were interested in the relationship with the immunosuppressive drugs that had allowed us to transplant organs, a medical revolution in the 80-90s. No one knew how they worked, until we discovered that they bind to the TOR protein.

The mechanism also explains another factor that haunts the planet: how caloric restriction is related to longevity.

It’s another example of how TOR research has opened up new areas for us. We found that what flips this switch are nutrients. And when we treated the cells with rapamycin, we saw that they behaved as if they were fasting. So we can simulate caloric restriction using this drug, without the need to fast. We have observed it in worms, in yeast, in flies; later, as a big step, in mice. Now many people are taking rapamycin to live longer, but we have not done the trials in humans yet. They are doing it now with monkeys and dogs!

Do you think that is the way, taking drugs to increase our longevity?

I think that is precisely what we should not do. I think of the Greek myth of Titono, the mortal lover of the goddess Eos: she asked Zeus to grant her immortality, and he did, but it turned out that he was aging eternally, to the point of wanting to die without being able to do so. We want the opposite: the optimal thing will be to live very healthy, without having to go to the doctor, until the day, let’s say 85, in which we drop dead. Why would we need more people in this world? Not enough problems already? And why do we need a longer life? Quality of life is more important.

Does the basis for a long but healthy life necessarily lie in taking fewer calories?

In mice, that works. In humans, we still can’t be sure. But since 1935, caloric restriction has been associated with a healthier life.

Observational studies seem to indicate that this is the case: people who fast tend to live longer, and suffer fewer degenerative diseases.

But they are anecdotal evidence. It needs to be studied in depth, and controlling diet in randomized trials is very difficult.

Investigator Michael Hall during the interview.

Investigator Michael Hall during the interview.

How do you see that, precisely now that science has faced a challenge such as the pandemic, hostile and denialist movements proliferate?

I don’t understand these people. I don’t know what motivation they have to deceive others. Do they do it to make money? In the US they are selling products and drugs that they say work better than vaccines. And they do take them!

It is the paradox: many do not question other medications, not even other vaccines, only those of the Covid that have a much greater effectiveness.

And billions have already taken them! We can say it: they work. I am vaccinated, I am a scientist, I understand how they work. I consider messenger RNA vaccines even less dangerous than traditional vaccines, which inject you with a virus. These people are idiots.

In that regard, we hear popularizers and doctors advocate not to confront deniers, but to try to convince them with evidence.

The ones I have seen are people who cannot be convinced. The advantages of the vaccine are so obvious that if they don’t see it themselves, no one will be able to convince them.

Are you then in favor of restrictions on access to the unvaccinated, in public and work places? A form of punishment, shall we say?

It’s the only way. But in Spain it works very well. Is incredible! Spaniards have accepted vaccination in a generalized way.

A report by the BBVA Foundation explained that Spaniards are the Europeans who trust science and health the most because they come from years of delay, and because they associate them with the progress that came later.

That’s why countries go like this [ondea con la mano]. Spain goes up, the United States down. In Switzerland we are less than 60% vaccinated. It’s a shame, they are almost the worst in Europe. We have an image of a very organized and responsible country, but it is the Spanish who are really behaving like this.

How do you appeal to the vocation for basic science among young people?

You have to introduce them to science very early, from school. The life of the scientist is not easy. Young people want to be rich, and generally you don’t get rich from science. You have to love it, be curious, and for those who have that passion, it is a magnificent life.

The problem of precariousness among young scientists in Spain is not that they do not get rich, it is that they are poor.

Yes, that is true. Its a big problem. But that’s where the government has to intervene. Switzerland is a very small country, without natural resources. It is pure mountain! It should be poor, but it has invested in education, research and innovation. In people’s brains. And that’s why I’m here, because I dedicate a lot of money to it. It is the model for other countries. Investing money in science is risk-free, it always pays.

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