Morphogenalia

In recent architecture news, The Francis Crick Institute has been nominated for the Carbuncle Prize [Link]. This is the satirical prize run by Building Design magazine, awarded to “the ugliest building in the United Kingdom completed in the last 12 months”. Although it’s probably not something I should celebrate, I think it was almost certainly inevitable we would be in contention for the prize. Over the years, just about any major new building that doesn’t conform to some nostalgic Victorian or Georgian aesthetic appears to have been proposed for a Carbuncle award. So the Crick’s nomination – given its size and prominence – didn’t come as a surprise.

Carbuncle

World class research institute

Of course, critical reception to modern buildings is nothing new. Buildings such as the Eiffel Tower in Paris, Tower Bridge in London, and the Guggenheim Museum in New York were all widely condemned when first built. The writer Guy de Maupassant was said to eat lunch in the Eiffel Tower, not for the food, but because it was the only place he could go where he was sure he wouldn’t have to look at Eiffel’s construction. And one critic described the newly completed Guggenheim Museum as “a war between architecture and painting, in which both come out badly maimed”. Despite these initial reactions, within a few years the critics and the public had changed their minds and come to appreciate and even enjoy these buildings.

Likewise ground breaking scientific work is often greeted with skepticism and sometimes outright hostility. Famously, several Nobel prize winners have talked about how the work that went on to win them the prize was initially rejected by prominent journals. Hans Krebs’s paper describing what became known as the Krebs Cycle was editorially rejected in less than a week by Nature only later to be published in Enzymologia (1937, Enzymologia, 4, 148-156). Similarly, Nature rejected, without review, Leland Hartwell’s paper on the genetics of cell cycle control in yeast (later published in Science 183:46–51) and Lynn Margulis’s proposal of the endosymbiotic theory as the origin of eukaryotic cells was rejected by 15 scientific journals before finally being published (J Theor Biol. 14: 255–274). So having new ideas rejected seems to be one thing that unites scientists and architects.

The nomination for the Carbuncle Prize also seems an appropriate award for a medical research institute. A carbuncle is a medical condition describing a large pus filled boil, caused by an inflammatory immune response to a bacterial infection. One of the missions of the Crick is to better understand infectious diseases and how our immune system fights them. You never know, some of this research may offer new insight into carbuncles and help treat them. This is far from trivial because, in an era where common infectious bacteria are becoming resistant to multiple antibiotics, there is a real danger that a carbuncle could turn monstrous, and even lethal.

There’s also another way in which I think that being nominated for the Carbuncle Prize is relevant to the Crick. A carbuncle is formed by inflammation, which results from the attraction and concentration of potent immune cells to a site of infection. The purpose of this is to help the body fight the infection by promoting collaboration between the immune cells and interactions with the bacteria. In a similar fashion, the goal of the Crick is to attract the finest scientists from around the world to form a critical mass of researchers that interact in new ways. The idea is that this “scientific inflammation” will generate a collaborative environment and promote cutting edge research. I’m not sure I’d want to extend this analogy much further and in the end, whether or not the building wins the Carbuncle Prize, and whether or not it’s ugly, is less important than whether we can recruit the best scientists and support their research. So, on reflection, maybe I should be celebrating the Crick’s nomination for the Carbuncle Prize – it’s a useful reminder of the literal and metaphorical purpose of the Institute.

Moving out of our building in Mill Hill means the end of some long standing traditions and an opportunity for a little bit of nostalgia. A few weeks ago we had our last ‘Friday Talk’. These have been a long running fixture for all the cell and developmental biologists at Mill Hill and I’m sure all those that took part will remember them with great fondness.

Friday Talks were started more than 25 years ago by Peter Rigby who was then one of a group of young developmental biologists at NIMR. The late 1980s and early 1990s were an exciting time in developmental biology. Molecular biology and developmental genetic techniques were converging and being applied to the big questions in embryology. Rapid progress was being made. Gene functions were being identified and molecular mechanisms unraveled. Peter wanted a forum to discuss the latest results and encourage the exchange of ideas. He initiated an internal seminar series in which two researchers gave 30-minute talks each week to discuss their most recent work. He decided that these should be at 4.30pm on a Friday afternoon so that discussions could continue in the institute bar – handily located just outside the seminar room – after the seminar hour had passed. This arrangement ensured a lively and interactive atmosphere. And the Friday Talks were born.

The format, timing and culture of Friday Talks has continued uninterrupted since Peter’s time. It has been a great opportunity to hear about work in progress, often long before it’s published. Over the years, results and ideas that subsequently became key concepts had their first airing in a Friday Talk. Some of these are now chapters in developmental biology textbooks: work from Rosa Beddington on the organiser function of Anterior Visceral Endoderm; studies deciphering the molecular mechanism of sex determination by Robin Lovell-Badge and colleagues; and Robb Krumlauf’s labs work on the regulation of Hox genes, all got talked about in Friday talks before being published in journals. I can also think of more recent talks, some of them about work yet to be published, that I expect will also make its way into the textbooks and developmental biology courses of the future.

New ideas are questioned, discussed and refined in these seminars. The culture of discussion and openness that Peter and colleagues established is key to the success of these seminars. The audience is always eager to ask challenging questions. Presenters know sloppy thinking or half-baked ideas will be found out, but the atmosphere is supportive and encouraging. The breadth of knowledge in the audience allows connections between new results and existing or ongoing work to be made. This all makes for excellent training and many of the students and post-docs that have presented in the Friday Talks have gone on to establish their own successful labs. But it’s not only the presenters that benefit – it has also offered a great way to gain confidence in asking questions and discussing science. I always enjoy seeing a student ask their first question or raise a point that everyone else has missed.

Sharing results with colleagues, learning about the latest techniques and finding inspiration, directly or indirectly, from new results is at the heart of research. Having a critical mass of individuals with common interests, and an interactive environment, is the real strength of an institute. As we move into the Crick we are re-establishing but rejigging the seminar series. Just as the early 1990s saw major changes in developmental biology, I think the field is undergoing another revolution today that incorporates developments in stem cell biology, tissue engineering and systems biology.  Reflecting this there will be new participants from the CRUK groups and there will of course be a new venue for the talks. But we’ve managed to keep the same time slot – last thing on a Friday afternoon. And the importance of the post-seminar discussion remains. So the discussions will continue, but now in the bars and pubs of Kings Cross.

There’s an old joke about a tourist lost in the West of Ireland asking a local farmer for directions to Dublin. He replies: ‘Well, if I were you, I wouldn’t start from here’. I think this is a good metaphor for the recent past of NIMR and how the Crick came into existence.

There are authoritative and comprehensive accounts of the history of NIMR at Mill Hill, here for example [http://www.historyofnimr.org.uk/], but I wanted to write down my own personal recollection before the mists of time descend. Doing this also reminded me about the unintended consequences of decisions – an idea that seemed relevant given the current uncertainty about the UK and the EU.

For me, the story of the Crick started in March 2003. I remember it very clearly as I was sitting in a colleague’s office at NIMR interviewing potential graduate students. During a break in the schedule he checked his email and began swearing. This was the reaction of most NIMR staff when they read the MRC’s Forward Investment Strategy (FIS) report. The report, by a subcommittee of the Council of the MRC – which was then our funding body – was proposing to close the Mill Hill site and open a new institute, half the size of NIMR, at Addenbrooke’s Hospital, Cambridge. Various reasons were given for the relocation, including that the NIMR building was too expensive to maintain, that its location on the outskirts of London was too remote, that we need to be adjacent to a hospital to do translational research. However, most of us at NIMR suspected that the real motivation was the pressure the MRC was under to reduce costs but maintain its support to researchers based at universities.

The weeks and months that followed the release of the FIS report was a turbulent and angst ridden time. There were objections, protests and demonstrations. We organised an international campaign to ‘Save NIMR’, which gained support from scientists around the world. There were hearings in Parliament, letters to newspapers and editorials in scientific journals. I forget the exact order of events, but it was a lively time for us all. To deal with the crisis a “Task Force” was set up to examine other options and, eventually, from this an idea to move NIMR to central London in partnership with UCL emerged. A site in central London was proposed and purchased by the MRC, but it turned out to be too small and the uncertainty at Mill Hill continued.

Then, sometime in 2005-2006 there was a major turning point. The London Research Institute (LRI) of CRUK, based in Lincoln’s Inn Fields, also needed a new building and a merger between NIMR and LRI was proposed to allow the construction of large enough building to accommodate us both. This would nicely kill two birds with one stone. Paul Nurse, then director of the Rockefeller in New York, became the chair of the planning committee for the new institute and the prospects for the future of NIMR’s research began to look more positive.

From this point onwards it seemed to me that things moved quickly. In addition to UCL, Imperial College, Kings College London and the Wellcome Trust backed the project, support was pledged at the highest levels of government and Paul Nurse agreed to become the director of what, at that time, was known as the UK Centre for Medical Research and Innovation (UKCMRI). In 2011 it was announced that the institute would be called The Francis Crick Institute, ground was broken for the new building on the St Pancras site and we began preparing in earnest for the move and the merger. The rest, as they say, is history.

In 2003, I was a junior tenure-track investigator, consequently the various twists and turns of this story has been the background for most of the time I’ve been running a lab. It’s certainly been an interesting period to live through and I’ve learned a lot by watching from the inside as these events unfolded. Despite the destabilising effect and uncertainty that the FIS caused to NIMR in 2003, I was surprised and reassured that instead of morale and cohesion crumbling, it acted as a focus to bring the labs together. It challenged us, as an institute, to explain clearly and publicly our strengths and shared purpose. It encouraged discussions and interactions between people from all corners of the institute and I expect this resulted in friendships and collaborations that might not otherwise have occurred. I think this places us in a much better position as we face the inevitable hitches that the move to the new building and establishing a new institute will bring.

It also became obvious to me that major strategic decisions can take on a life of their own. Although they have a long term consequences, decisions are often taken to solve short term problems. The people making the big decisions don’t always stick around for long and this allows others to get involved, resulting in radical changes of direction. This seems familiar given the current situation we find ourselves in the UK following the EU referendum vote. I can only hope that, just as the exciting prospect offered by the Crick came out of the turbulence and angst associated with the FIS report, that the uncertainty and bleakness I currently feel about the future of UK is turned into a brighter future. I remain to be convinced. I certainly think that if our intended destination is a brighter future, I wouldn’t start from here.

Similar to most scientists (and almost everybody I know) I’m deeply concerned by the result of the UK’s referendum on EU membership. It’s difficult to see the outcome as anything but a huge step backward, damaging to the country’s future and to science. I expect the next few months will be the equivalent of watching a slow-motion car crash, the extent of the damage gradually being revealed.

Academics and life scientists in particular were almost unanimous in their support for Remain. I saw several polls of scientists and university staff that put support for remaining in the EU at ~90% (what the other 10% were thinking I have no idea). There are obvious, self-serving reasons why most UK scientists are in favour of the EU. The Royal Society published figures showing that while the UK contributed €5.4bn to the EU science budget between 2007-2013, researchers in the UK had been awarded grants and funding of €8.8bn in the same period. Many of us know the UK is disproportionately successful at winning EU funding. We are skeptical whether the ~£3bn or more of EU funding that will be lost from the UK over the next 5 years will be replaced by our national government. Moreover, UK scientists often take leadership roles in multinational European collaborations. Leaving the EU will jeopardise the authority and influence that these roles offer and result in UK science being increasingly sidelined. I’ve already heard stories of UK scientists being asked to step down from applications for European funding because of the uncertain status of the UK over the next few years.

However I think there is a much deeper and more fundamental reason why most scientists are pro-Remain. In addition to the funding, the importance of freedom of movement and the free exchange of ideas is at the heart of science. Seeing the bureaucracy and hassle that some non-EU members of my lab have to go through to travel to another European country would have been enough of an incentive alone for me to vote for the EU. But for most researchers the freedom of movement is not simple expediency or minimising delays in airports. Science is fundamentally an international endeavour that transcends national boundaries. The sharing of ideas, people and material is an essential part of research. It enhances both senders and recipients. Anything that prevents or even just discourages exchanges is detrimental to science and the country. The perception that the UK is now less welcoming, less open, less enlightened makes me feel bleak.

This idea is not new but has been the case for centuries. In the run up to the referendum vote I was reading Andrea Wulf’s biography of Alexander von Humboldt http://www.andreawulf.com/about-the-invention-of-nature.html. The book is an engaging description of the life and influence of the Nineteenth century polymath. Wulf discusses how he made fundamental contributions to our understanding of our natural and physical environment, inspiring later generations including Charles Darwin and John Muir, founder of the Sierra Club. Many aspects of Humboldt’s career would be familiar to scientists working in Europe today. Wulf describes that, despite living through the turmoil of the Napoleonic wars, he was closely connected with other scientists across Europe. Born near Berlin, he spent a considerable time living and working in Paris and had extended stays in several other cities, including London; a CV is similar to many of today’s researchers. He also corresponded extensively with other scientists, answering up to 5000 letters a year – a century and a half before email. It was these interactions and collaborations that gave Humboldt’s major work ‘Kosmos’ its breadth and reach and his global outlook was also responsible for Humboldt’s influence on future generations.

Although no one is likely to have the impact or importance of Humboldt again, one of the great pleasures of being a European researcher today is how the diversity of people in our labs and in our fields enrich both our intellectual and cultural life. It is essential that UK remains an open and attractive destination for scientists from Europe and the rest of the world. I strongly believe that the EU was important for this and I worry about the consequences now. It’s crucial that international researchers are allowed to visit and work in the UK and that we still have access to EU funding and European collaborations. I’m sure the Crick, like all international research institutes, will do its best to remain open and welcoming to scientists wherever they come from. But a chilling consequence of the referendum is the message of disdain and contempt it sends to the rest of the world. Countering this is as important as whatever new criteria for visas and funding eligibility are put in place. One of the benefits of our move to the Crick is that it’s located right across the road from the Eurostar terminus at St Pancras. Now Paris, Brussels and stations beyond, are just a couple of hours away from the Crick. So rather than the 5 day journey, by coach, horses and boat that Humboldt took to get from Paris to London we now just hop on a train. I hope this proximity helps to reduce any perceived increased distance. It will certainly be up to us to make the extra effort that will now be necessary to keep the UK open for science. We might be facing a future of borders and visas but, unlike Humboldt, at least we won’t have Napoleon’s armies to contend with on our travels.