â€œOn a summer day in the late fifties a delegation from the Soviet Union appeared in Cambridge demanding to see the “Institute of Molecular Biology”. When I took them to our shabby prefabricated hut in front of the University Physics Department, called Cavendish Laboratory after its nineteenth century benefactor, they went into a huddle until finally one of them asked me: “And where do you work in winter?” They wanted to know how I had planned our successful Research Unit, imagining that I had recruited an interdisciplinary team as Noah had chosen the animals for his ark: two mathematicians, two physicists, two chemists, two biochemists and two biologists, and told them to solve the atomic structure of living matter. They were disappointed that the Unit had grown haphazardly and that I left people to do what happened to interest themâ€Â Max Perutz Nobel lecture https://www.nobelprize.org/nobel_prizes/themes/medicine/perutz/
The other day getting into work through my favourite route, the New Museum site next to the old Cavendish laboratory in the Center of Cambridge â€“nothing scenic, by the way-, I noticed a dramatic change, a hole in a familiar landscape. A small one floor building in the form of a large bungalow or hut occupied by Rolls Royce for the last few years, was gone. Instead, one of those modern multi story bicycle parking lots had been erected. But the loss was, is, historic as this was the old â€˜hutâ€™, home to the toilings of Max Perutz, Sydney Brenner and Francis Crick amidst others in the 1960s when they were laying down the basis of Molecular Biology (picture from https://www2.mrc-lmb.cam.ac.uk/?attachment_id=2631). It was in that hut that myoglobin was crystallized, that phage mutations leading to the genetic code were isolated and interpreted. That was the place of interesting discussions to which we owe much of what we do in Biology today. Surely one could take a moment to reflect. Change is necessary and, after all, the hut was a relic without much use or future, hardly noticed by passers by and in any case hardly known by many of the people who work around the site on a daily basis. Its demise led me to reflect on a number of issues that are associated with the hut and made me think that a way of doing Science so attached to the spirit of the hut, has also gone. The reflection that followed, and that follows here, is not intended as a nostalgic yarn but as a statement of fact, as a wake up call to a reality that we need to accept and work around. Science, Biology, as we have known them, is gone and is not coming back.
If you have read some of the classics of the history of molecular biology: â€œThe eighth day of creationâ€, â€œPhage and the origins of molecular biologyâ€ to cite but two of the greatest, you will not find there stories of discussions with editors, rejected papers or grants or glossy statements in High Impact Factor magazines/journals. Instead you will find a riveting story of pursuit of some of the deepest secrets of Nature. The heroes that we so often praise did not spend their time arguing with editors, or doing experiments to satisfy reviewers and editors comments. They spent their time doing experiments,Â writing and publishing progress reports â€“which did not go through two rounds of review and excess comments by editors- and, within a competitive environment, moving on and along. There was a collective sense of what was important, people competed but also respected each other and the experiments and Science, rather than the publication, was what mattered; as it ought to be. They did not ask â€˜where did you publishâ€™ but rather â€˜what did you publish?â€ â€œwhat did you find?â€. Those were different times. I cannot imagine M. Nierenberg in the famous Moscow meeting at which F. Crick saw the tip of the genetic code, trying to catch the interest of an editor of Cell, Nature or Science. It is difficult to imagine Brenner having anything but contempt for journals telling him how to shape his legendary paper on phage mutations and the genetic code and I really canâ€™t imagine J. Watson â€“whatever I or you think of him- in front of a career development award panel. The focus of Science then was research and important questions not careers or publications. When I came to Cambridge in the early 1980s there was still some of that spirit. The question at the time was not the molecular basis of heredity or the genetic code but, equally enthralling, the molecular underpinning of embryonic development. And we pursued this with a spirit not dissimilar to that of the 60s: toiling with questions and techniques, trying to get answers to questions we felt would be important. Journals were, still â€“but just-, vehicles to report progress, subservient to our needs. Change, however, had started and in some ways the emergence of Cell â€“run by an ex-lecturer from the University of Sussex and aiming to shape the content and form of contemporary Biology- was starting to take hold of the field. Then imperceptibly and in parallel with an explosion in terms of the number of researchers, fields of studies and journals, all changed.
Today it is unclear what is the relationship of what we do to Science as understood in the past. Nothing wrong with this but I do feel uncomfortable when at some meetings, panels of over 50s scientists gather with students and postdocs to advice them on their future. Often they tell them how they â€“the old guard- became great and that all the young generation has to do is follow the same steps. This is, at the very least misleading if not disingenuous. To survive today in Science, particularly in Biology, requires more than a good question or an original idea, much more than focused hard work, good judgement and luck. I say survival with intent and donâ€™t mention â€œsuccessâ€ because this, more than ever, is relative. Today you need a combination of ingredients of which good Science (in the old fashioned way) is just one. If you try the old recipe, unless you are very lucky, you will fail. Times change and the advice need to go with the times. My advice is that if you are starting a lab today you should not model it on the attic at the Institut Pasteur where Lwoff, Jacob and Monod peered into the secrets of gene regulation, but on a small business. What you will face is the need to get funds to maintain an enterprise which, if you are lucky (which these days often mean to end up in a well endowed institute for a few years), will be close to your interests but which, in general, will have to adapt to fashions and funding needs. Your currency will not be your ideas or your results but your publications and while we wean ourselves off the pernicious influence of the HIF journals, you will have to keep an eye on them and live under their shadow because them (and the scientists that form their core) determine the agenda -my heart sinks every time I hear the pernicious and mistaken mantra that you need a HIF publication (warholian fifteen minutes of fame) to get a job, that the perception of the value of those papers, when published, will determine your value in some virtual and ethereal stock market of labs which, in turn, will determine how much funding you have and thereby the performance of your business. Things are changing and we have to push for change but, for now and while change comes, we need to be aware of the reality. In this climate you have to be careful and strategic.
And as part of this advice let me tell you that the best time to do Real Science today is your PhD because, if your supervisor allows you, it is the only time in your career when you are going to have some time to explore freely what you want to do. Afterwards, your work will be marked in a more or less open manner by a business model in which the name of the game is to survive, you will have to think carefully about what you do because your future will depend on it and this will become more apparent if you are not in one of those large Institutes which have the potential of doing a lot of good (and many do) but which for the most part suck resources from the environment and contribute to an increasing gap between different tiers of research. There is a lot of technical quality around and most people can do a competent job which increases competitiveness. Furthermore, Biology will never fail to produce a â€˜newâ€™ situation, either a new job for a well known gene or a new gene for a well known function and there are endless way of looking at DNA and RNA. This means that competition for resources is fierce and how you â€˜sellâ€™ what you do is more important (or at last as important) as what you sell (do). And the problem is that (maybe just my opinion) a question, let alone a good question, is not easy to find (see Coda on Einstein and Valery) and gets buried in a sea of data and techniques. While we are good at finding flaws in papers, we are not good at defining their context and, for the most part, we get lost in a forest of three letter acronyms and data. Unfortunately, in an age of shrinking budgets, translational pressures, data collection and technology driven projects, good old fashioned real questions and problems is not what shines (though I should say that come committees and institutions can sometimes throw a surprise or two of judgement).
It is difficult to gauge what is fundable and target it. It is not easy to tread the thin line between real science and a business model. If you want to survive and have the small amount of shallow success that will allow you to get funding, you need to go to meetings, be some part of the small circus that journals have created, talk to editors, to PIs who like to feel important and are influential. More importantly, be aware that the short term future of Biology lies in collaborations, formal collaborations. Brenner, Perutz, Crick, Sanger, the inhabitants of â€˜the hutâ€™ were collaborative, intellectually, they fed on their discussions and each otherâ€™s ideas but now it is different. One has to show coherence, added value, joint up projects. This is the reality and there is no point in looking away.
As I said above and repeat here, I do not yearn for bygone times, the spirit of the hut or the way science was done. I like to read and think about all this and feel proud to be part of that tradition. I am not nostalgic for history but, it is important that we know and accept that today those times and places are not a model for us more than Newton is a model for modern physicists at CERN. It is not right to tell people today that because they do good science they will succeed (whatever this means). The definition of good science has changed. Today people will not recognize a good idea if they see one; what matters is how you sell what you do. Ah, and as an average PI you will find yourself chasing money, going to meetings, dealing with editors and reviewers and, if you are in a high profile institute you will have to deal with periodic reviews. Nothing like the â€˜spirit of the hutâ€™. It is important to acknowledge where we are and look for ways to evolve it and to make the most of it.
For me the disappearance of â€˜the hutâ€™ has been a statement of the times and a reminder that a way of doing Biology is gone and that, like the hut, is not coming back. Perhaps there is something metaphorical in that the space of the hut has been occupied by a bicycle parking because this, in some ways, what has happened to Biology. What you will get with your PhD is a bicycle which you should use to move around and sell your skills which are not the same that they would have been if you had been working in Biology 40 years ago. I insist, nothing wrong with this, just be aware of it and donâ€™t try to follow the paths of those days; they donâ€™t work. In this regard I shall finish by saying that I do not expect The Crick, one of the examples of corporate science in the UK, to produce anything like what the hut did. The reasons for this is the changes I have been discussing. Science today is differentâ€¦â€¦
CODA on ideas: It is said that Paul Valery, french poet and philosopher with an interest in the nature of creativity and the process of creation once met Albert Einstein. In the course of the conversation Valery asked Einstein how he worked to which Einstein explained that often he took walks and that during the walks he ran thoughts through his mind. Valery quickly retorted that surely he would have a pencil and a paper with him. Einstein was puzzled: a pencil and a paper? What for? Valery sighed; but â€˜bien sureâ€™ when you have an idea you write it down. Ah, now I understand; you see, Einstein said, I do not need those items, an idea is so rare that if I had one, I would remember it.