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January 17, 2023

INTERVIEW: Adriano Aguzzi

Adriano Aguzzi is a professor and director of the Institute of Neuropathology at the University of Zurich. He has devoted the past 25 years to studying the immunological and molecular basis of prion pathogenesis, combining transgenetics with molecular and immunological techniques to clarify the pathogenesis of the disease, and to identify cells and molecules involved in prion neuroinvasion. He serves on the editorial board of Science and has won many prizes (including the Ernst-Jung Prize, the Robert Koch Prize, and the medal of the European Molecular Biology Organization).

What do you think about how science is funded in the United States versus Switzerland?

When it comes to research funding, I think that Switzerland is better. It’s amazing how good we have it here. Tenured professors have quite generous core funding which is (more or less) guaranteed until retirement, plus competitive grants.

On the positive side, the US system has spawned amazing inventions and discoveries. But it’s also competitive in ways that can be brutal. If you’re expected to bring in half of your salary from grants, and then your grant gets rejected—what do you do? In the US, the lack of security that exists at all levels of society, not only in academia, is frightening.

This is a reason that Europe is becoming competitive in recruiting American professors. Not everyone can cope with that level of pressure. Maybe you can do it when you’re young and have no dependents. But when you get older, it can become frightening.

What if it’s the case that soft money actually hurts innovation, because people are afraid to propose risky ideas that might not work out?

It’s a delicate balance. A common strategy is to write a grant where 90% of the work has already been done, so they’re sure that they will deliver on the proposal. This is actually encouraged by many funders. I think it’s not a good development, as it removes the incentive to start something fundamentally new.

On the other hand, it’s understandable that funders want some assurances that applicants will indeed deliver on their plans, and “preliminary” results can go a long way towards assuring that. The problem, of course, is that research is not the same as building a house. You can’t expect to predict exactly where research will turn out over the next few years.

Should we fund the person not the project?

Yes, but with some caveats. You can take young scientists who show promise, and tell them “I trust whatever you do will be interesting, and I give you $20 million for the next 20 years”. In a way, such schemes exist. If you’re a director at the Max Planck Institute in Germany, that’s pretty much the deal you get.

But the problem is that people can become inefficient, and their trajectories aren’t consistent. Some people are intrinsically motivated and driven until very old age (my mentor Charles Weissmann is one of them), but others quit doing good work at some point, or spend all their time running companies instead of doing academic work.

I myself have a very cozy position, admittedly. My university has generously funded my lab for 25 years, and in addition I have gotten >$50M in competitive, philanthropic and industrial funding during this period. I continue to be super-excited by science, and spend my entire waking time on it (my family is not always happy about that).

What works best is a mix of two models: a competing source of funds where you have to renew your grant every couple of years (e.g. the European Research Council, which has immensely improved the research landscape in Europe), versus the trust model where you give a big chunk of money to someone hoping that great things will happen.

In practice, you need assurances that people stay productive and therefore you shouldn’t remove all need to acquire competitive funds. But if you force people to reapply for funding just to keep their salary, that will inhibit risk-taking and will kill innovation.

So we need a mix of the two schemes. In that aspect, Switzerland is doing that very well. Every professor has core funding that will never be taken away, and you can get extra grants on top of that.

But you can’t always have the cake and eat it: the downside of the Swiss system is that we have mandatory retirement at age 65. For me this is a reasonable compromise. It’s a regrettable but true fact that very few people get better in old age.

What do you think about Alzheimer’s and the amyloid hypothesis—people complain about not getting funded if they don’t study amyloid?

If I look at what is being funded, most of it nowadays is inflammation and has nothing to do with amyloid hypothesis. In academic research, I am 100% convinced that good ideas supported by credible preliminary results has always had a chance. If I look at people who complain that they can’t get grants because of the “amyloid mafia”, often they aren’t doing very good science.

What people bemoan is that the pharmaceutical industry has put billions into the amyloid hypothesis. But was it really that stupid for companies to put so much money onto one single target? If there had been better alternatives, companies would have invested in that as well. But for a long time, A-beta was the only target they knew of.

Nonetheless, the whole field is contaminated by the amazing amount of money that is flowing in. I have zero skin in the game about amyloid or non-amyloid, but I feel that much of the emotion in this debate is due to the fact that there is a lot of money involved. When people get dollar signs in their eyes, scientific depth is the first casualty.