Interview transcript

Professor Sir James Black, welcome to this Nobel interview. The Nobel Prize that you were awarded in 1988 was kind of unusual I would say, you got the prize for the discoveries in drug research, and this was the first prize in this area in 31 years. Were you very surprised when you got the news?

Sir James Black: You bet that.  Astonished.  Yes, I didn’t think it was prize worthy frankly.

 No? Do you think it was?

Sir James Black: I have no way of judging that.  I mean I just played the cards that someone dealt me.

 But the drug that you have worked on is broadly spread today, it is beta-blockers from the beginning, everybody knows what it is.

Sir James Black: Yes, but you see my notoriety is by an accident, the accident is that the drugs I developed made a lot of money.  Now the science could have just been the same and the drugs might not have made much money and then I wouldn’t be here.  I’m not here for the science; I’m here because of the notoriety of the widespread use.

 Why do you think so? Don’t you think that the development of drugs, there is commercial interests in it …

Sir James Black: The citation was for a new method and that’s true in this sense that it so happened that when I got the idea for my first drug a discovery had been made and the discovery was that we have hundreds of messenger molecules that make our cells work together, we call them hormones. The discovery was that these messenger molecules have two properties, a property of, a cognition property, they recognise a cell which has a sight on it that they can, so there’s recognition and then they do some things to switch it on.  The discovery was that these two properties, cognition and efficacy were separable. I wanted to stop the effects of adrenalin on the heart and so I reckoned maybe I can take adrenalin and get rid of its efficacy and leave behind the affinity which in essence was what happened.

But don’t you think that most of the discoveries are kind of a surprise even for the discoverer?

Sir James Black: It’s hard to go back, you know, we take memories and we smooth them like pebbles so we’re comfortable with them and I think memory isn’t about recollection, it’s about reconstruction and so I’m not at all sure now, at this stage, what I was actually thinking or planning or doing, all I know is outcomes and … But motives are very hard to be sure about.

You have worked both for the university and for companies, industries …

Sir James Black: About half my life in each.

Half your life …

Sir James Black: In each.

How do you they compare?

Sir James Black: I have worked as an employee for three drug companies and I have collaborated with a fourth and these companies are like people, they have quite different cultures, characters, but like people they have common diseases.  I once thought I’d write a textbook of institutional pathology and the diseases are largely problems of magnitude, problems of communication. A technical company is very people intensive, it’s not something that you can scale up with the equipment and machinery, you have to have a lot of people and when you have a lot of people, you have the problems of communicating between them so that’s the industrial side.  It’s very hard to make a general statement about companies because they’re all different.  Universities on the other hand, the problem with universities is they have been changing continuously during my association with them …

In what way?

Sir James Black: … and I’m not too comfortable about the way we’re going, because more and more, the big universities, are becoming like companies, more and more they’re concerned mainly with the cash flow, more and more are they concerned with whether or not the intellectual output of the people can be turned into property and start-up companies, spin out companies, there’s huge obsession with making money and I don’t think this is compatible with the job of a university.  The job of the university is to make discoveries, not to make inventions.  Discoveries are about finding out something which, if you like, is already there but no one knew, whereas an invention … When I made a drug, that was an invention, there hadn’t been anything there before, but the invention was built on other people’s discoveries.  If Ray Ahlquist and so on had not done their work, I couldn’t have done mine. So the job of academia is to make discoveries, it’s the job of business to make inventions I think and so I’m unhappy about this. One of the worrying things today is that scientists, because of pressure on them to raise money, either from grants or from private venture capital, are making promises, you know, once we get the protein, once we know it’s structure, once we get the gene, then we’ll get the drug. This is unwise because we’re leading the public, who ultimately are our paymasters, we’re leading them to have expectations.  Now if …

So you’re afraid of a blacklash …

Sir James Black: I am afraid of this. If I was running a business and was making my shareholders promise like that they’d have me in prison, but scientists can get away with it. We’ll not get away with it forever, time will catch up with us because here’s the problem. The rate of accumulation of knowledge, the information, is so vast, none of us can take it in, but knowledge just adds, and you might think that all this knowledge will make progress but progress isn’t based on knowledge, it’s based on ideas, and whereas knowledge adds, ideas have to substitute. You have to replace the idea you already have with a new one and that’s painful and that’s slow and that is the rate limiting stamp.  For example we’ve had now the human genome project, that has taken 125 years from the time when chemists were extracting material from spermatozoa, from the nucleus and getting out this gooey stuff and then showing there was four bases in there, that was in the 1870s, staying right through now to get a nearly complete map of the sequence of bases in the human genome but that’s, it’s just not even the beginning of the story because now the problems are conceptual.  Suddenly we find there’s only about a third of the genes we expected, and we don’t know how they work. The big problem …

Why and what and …

Sir James Black: … and this is going to be the slow thing, our exploitation of the knowledge about the genome is going to require changes in our conceptions from what they are at the moment.  At the moment we are still thinking that our gene does our job and so if you can find out the job the gene does, why you can control it, but it isn’t going to be like that.

No, it sounds too simple.

Sir James Black: It’s too simple.

So even if you get more money for thinking the process will take time anyhow …

Sir James Black: Yes.

… even if more people will do it?

Sir James Black: There are some problems you cannot solve just by throwing money at them.  AIDS for example, we’ve been trying for what 25 years to get a vaccine for AIDS, so far we’ve failed.  Now we’ve been making vaccines, you know, for a century.  We want a vaccine, so we throw money at it and we’ve failed and we have to learn from these things that the wish is not enough, there has to be the understanding which is the platform for achieving what you want to do.

Yes, the creative process takes time.

Sir James Black: And the time, the slowness, is the thinking, the concept, that’s the hard bit.

Yes. I have another question to you. As a Nobel Prize winner, you are asked lots of questions and on Thursday you are going to discuss even terrorism.

Sir James Black: No, I’m not.

You’re not. Others are.

Sir James Black: Some maybe, but no, my views on terrorism are the same as yours, we’re against it.

Has your life changed after winning the Nobel Prize?

Sir James Black: There is a period when it’s hectic, yes.

And you become an official person …

Sir James Black: And the problems are we’re not trained, we don’t know how to handle it, we’re not film stars.

No. How did you manage?

Sir James Black: Badly.

And that means?

Sir James Black: It means I had to make a lot of rather messy compromises I suppose, compromises between doing what other people wanted me to do and doing what I wanted to do which was to get on with my work. One of the things people want you to do in this sort of ‘star business’ is give lectures, attend seminars and so on and I just happen not to like it. I have one thing I enjoy and that’s sitting in a room with maybe 10-15 young graduate scientists and just talking. Then I’m happy, but these stand-up lectures I don’t like.

I understand. So what was the problem that you were working on that was known since 1905?

Sir James Black: What I’ve been doing is I gave you the principle earlier and I just keep applying that principle, that’s why I’ve applied that to adrenalin, to histamine, to another small molecule called 5-hydroxytryptamine and then to a bigger molecule cholecystokinin and gastrin, but the principle is always the same.  These molecules are messenger molecules, they do things, so I recognise each of them as being a messenger molecule because I have a piece of tissue or something which responds to them characteristically, that is I have an assay. I have the assay, I have the hormone, I expose one to the other and the system does something, it may secrete, contract or … I take this molecule and I walk around it, look at it and think, Well now, maybe if I take that piece off, maybe that will get rid, see. I make this new molecule and now I compete the hormone molecule with my new molecule and … First of all I try it on its own, does it do anything?  Then I compete them. It’s an iterative process, it’s like Darwinian evolution only I synthesise, I test, I re-synthesise and on we go.

The one thing which is certain is it’s slow and this is why, in the drug industry today, this method which I have described and which everybody who’s tried it, it always works, you just don’t know how long it’s going to take. The beta-blockers was six years, histamine antagonist was nine years, 5-HTP was eight years, these are long periods. The drug industry has become inpatient, and it has now, if you like, got rid of this method which works and they’ve replaced it with a method which they don’t know yet if it’s going to work and this is now technological advances. We can now screen a hundred thousand molecules a day against proteins in one can or another, we have the technology to make hundreds of thousands of molecules, we have the technology to screen for them and what they’re looking for are leads, a molecule which does something.  I never start a project without a lead and yet it still takes me these long periods of time. At the moment the drug industry has doubled its expenditure on research and development in the last ten years and the productivity as judged by newer drugs coming out has fallen by a fifth.  This is not sustainable, and this is the thing, our earlier conversation about can you force drug discovery just by throwing money at it?  The evidence is you can’t. There was a very well-known American philanthropist, but he was a psychiatrist, a scientist, he had trained as an artist, he became a great collector of paintings, gave them all to the Met eventually, but near the end of his life he summed his life up by saying that art is a passion pursued with discipline. Science is a discipline pursued with passion; passion is the engine of science and if you haven’t got that then give it up.

Thank you for taking your time and sharing your thoughts with us. Thank you very much.

Sir James Black: Thank you.

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