Open Basic Science Needed for Significant and Fundamental Discoveries

文/邁克爾·萊維特 （Michael Levitt）

Michael Levitt, tenured professor of Structural Biology at Stanford University. He was awarded the Nobel Prize for Chemistry in 2013, for “the development of multiscale models for complex chemical systems”.

Basic science is about new things. A fundamental principle for basic science is luck. I have been very, very lucky throughout my life. Early on, I got to work with some of the most outstanding scientists globally, including British scientists in Cambridge, people like Francis Crick, John Kendrew, and Max Perutz. These are the scientists who redefined life as physics and chemistry in the 50s and 60s of the 20th century. They were also excellent mentors and role models to me. But one thing that they recognized was how important it was to give young people independence.

I will show you one of the best examples of this, which is not well known. Francis Crick is well known for discovering the structure of DNA with Jim Watson and published probably the most famous paper ever published in Nature in 1953. Interestingly, when Crick was doing his work on DNA, he was Max Perutz's Ph.D. student. But the paper is not Perutz's because he realized that there's nothing more important than giving young people independence. If he put his name, which everybody would do today, on that paper, it would diminish the dependence of Crick. So this is a vital lesson for us all. I was very independent early on. I was doing independent research at the age of 20, and essentially no one ever told me what I should do. This kind of independence is critical for basic science.

Basic Science is unexpected, and it must enable future work. Here are some examples of biomedicine. Fred Sanger discovered the sequencing of proteins and DNA in Cambridge; he has two Nobel Prizes, one for sequencing proteins and 20 years later for sequencing DNA. All of these things are fundamental properties of biology. Yet, they were all unexpected. So now we have a problem because we'd like to have five-year plans. We'd like to know what's going to happen. So how do you plan something that is only unexpected? And this is the challenge of basic science.

Countries actually all need basic science. You could say that if everything is open, one country could do all the fundamental work, and a different country could do the transformation work. Foreign countries could do the engineering work. Why should they do fundamental science in all countries? The reason is that fundamental science is almost a discipline. It teaches people to explore the unknown. The unknown is not only in science but also in governance and handling economies. Every situation is full of unknowns. And the technique that basic sciences have perfected is how to deal with the unknown.

Let's look at basic science in the United States. There were two kinds of institutions: Some places have research universities that also need to teach, and then there are pure research institutes, like the American National Institute of Health, the Bell Labs, and medical schools. Most researchers don't do clinical work, and they don't teach. So, they are working 100% of the time on basic science. So, in some ways, all countries focus, sometimes on pure basic science.

Let's now look at basic science in the world versus basic science in the USA. Here, I show basic medical science. Before 1940, there were very few American Nobel Prizes. America was great in motor cars, the telegraph, railroads, many inventions. Most of those inventions were made in Europe, but they were protected in the United States. And that is very good. But then, around 1940, things changed. And suddenly, USA's Nobel Prizes became more and more. And then, for about 40 years, from 1970 to 2010, the USA had more Nobel Prizes than the rest of the world. It's not clear why. And I might say a few words about that. Generally, about half of the Nobel Laureates worked with other Nobel Prize winners. So you could say that they were selected because they were good, but you could also say that they met Nobel Laureates and realized that they were just ordinary people.

Other Nobel Laureates supervised many Nobel Laureates. The most extended tree has eight links (8 winners) and extends a hundred years. There are also significant key centers like Rockefeller University and Stanford University. So it seems that there are places where there is the mentality of fundamental basic science. It's interesting to ask, how much does the Nobel Prize cost? I'm not going to talk about how much a paper costs. But how much do different countries spend on research?

Many Countries spend a considerable amount of money on research. For example, statistics from 2015 show that the USA spended more than 453 billion dollars annually and China over 243 billion dollars. But let's do a game and say, we have the spending, we have the number of Nobel Prizes. What is the average cost of a Nobel Prize in different countries? I'm not taking this very seriously. The USA spends the most, and it gets the most important prizes. The lowest country is 1000 times less than the highest country, both in terms of Nobel Prizes and spending. The cheapest Nobel Prize is 13 billion dollars of research money over 20 years. It's very, very high. For China, winning Nobel Prizes is expensive.

Now you should realize I started science independently at the age of 20. By the time I was 25, I had finished all the work that would bring me the Nobel Prize. But it took another 43 years for that to be recognized. So, it's essential to realize that the spending, the state of Nobel Prizes today, really measures where your science was 30 or 40 years ago. It takes so long because the world committee wants to ensure that the right people are getting the prize.

It's clear that for good basic science, we need money. We need a full-time research commitment. So it's better to have people working as their primary job, but not always. There are some very interesting examples of people who got Nobel Prizes for working in a company. But then, when you hear the story, you discover that the head of the company saw this person as a genius and said, do whatever you like. So, independence is essential.

So what else is needed? And how can we find out? I tried the exciting exercise of looking at two places in the world with lots of Nobel Prizes in the same institute. I titled this how to win many Nobel Prizes.

The Rockefeller Institute in New York is very fascinating. Rockefeller, before he formed the new university, his name was associated with money, with railroads. And then, he had an excellent idea. He would establish a university, and he did this very early. And for more than 100 years, the Rockefeller University, which encouraged almost no teaching, except for graduate students, a lot of independence, good funding, and trying to bring in the best people from all over the world, managed to get 24 Nobel Prizes over 100 years.

I wanted to talk about a different place, the Medical Research Council Laboratory of Molecular Biology (LMB) in Cambridge. This is the laboratory where Crick, Kendrew Watson, and Perutz were, and it was a laboratory formed by Perutz.

The LMB, when I was there, was a small building. Recently, it has become a cathedral to science rather than a scientific laboratory. It's a massive building with open spaces and hanging officers. The LMB has 28 Nobel Prizes, more than Rockefeller University. But what's interesting is that they've got these Nobel Prizes over only 60 years. So they've got a much more significant character relation. And these people are genuinely giants people like Fred Sanger. So being there was a huge luxury.

Cesar Milstein invented monoclonal antibodies. And what was interesting about this was that he thought this idea would be suitable for a patent. So, he approached the Medical Research Council leadership to ask, should this be patented? They formed a committee, and the committee met very distinguished people. Three months later, they came back and said this idea would never make any money. Therefore, it shouldn't be patented. However, this idea is probably worth several hundred billion dollars a year.

So, it just shows that sometimes you really can't tell what's going to be necessary. The Nobel committee could advise, but they had to wait.

So, what is the recipe for Nobel prizes? Firstly, research support. The average group gets around 1 million sterling a year for support in Cambridge.

Secondly, the groups are small. A typical group is with five people. Even these great scientists never had groups of 20. Why does this make sense? Let's imagine I decided to convert the audiences of the lecture into research groups. We'll have half the space working for me and half the room working for an academician. It sounds logical because we are good leaders and have experience. But the right thing to do is maybe take pairs or three people in different combinations and tell them to do whatever they like. Do the craziest things, often try to be wrong. Because if you're not trying to do hard things, you will never be right.

Thirdly, no hierarchy. I felt just as good as a Nobel Laureate when I was in Cambridge. There were fewer students in that laboratory than Nobel Laureates.

Fourthly, intense peer pressure. The pressure is not what was the last paper you published in Nature? No one cares about your final paper. No one cares about your record. What is your following paper? What are you working on now? That is very important.

Finally, we need no visible bureaucracy. Every organization has bureaucracy. But in many ways, the leaders in Cambridge were a firewall that kept the bureaucracy from infecting the students, the scientists, and the postdocs. They said that young scientists should not waste their time on anything but thinking about ideas. When I was there, you didn't have to fill a form in if you wanted anything. You didn't have to say a leader approved it. You just signed your name. If I went there now and wanted an iPad, I'm sure they would say which color you would like? You would sign your name.

It is a deliberate effort to realize that the most valuable resource in the world is young people. I don't mean 50-year-olds or 35-year-olds are not young. How old was Steve Jobs when he founded Apple? How old was Bill Gates when he founded Microsoft? More recently, the two founders of Google had to give up their Stanford Ph.D. degrees to establish a company. Things are done by people who don't know enough. All the older people know too much and, therefore, will not change the future. This is a real worry because we have many more older adults today than 50 years ago. I would guess that the number of people over 65 in Britain has increased 3 or 4 times from what it was in the 50s as a fraction of the population. So we need always to be aware of young people's independence.

Max Perutz said, “In science, truth always wins”, which I keep on thinking about, particularly in the time of corona. (This article is based on the speech records of the Global Science and Technology Innovation High-Level Think Tank Forum of 2021 ZGC Forum, and has not been reviewed by the author)