Thoughts from 30,000 feet

It’s 10pm on a Saturday night as I write this and I’m on a flight from London to Boston. I’m heading to the Marine Biological Laboratories in Woods Hole, Massachusetts where I will be spending the week teaching on an advanced study course, aimed at graduate students and post-docs in my field. I’ve participated in this course for the last five or so years and it’s something I’ve grown to look forward to every year [Link]. In part this is because I always find it stimulating and inspiring experience. Like all courses at Woods Hole it’s intense, the participants are always engaged and committed, they will pull all-nighters to work on their projects and then still want to ask questions and discuss details when you lecture the following morning.

On top of this, the other faculty who teach on the course are leaders in the field and spending a week with them catching up, discussing science, exchanging ideas is both motivating and enormously enjoyable. There’s something about the face to face social time that produces open discussion and leads to new ideas. The environment of Woods Hole is particularly good at encouraging this: we all stay in the same halls, eat together and spend most of our waking hours in each-others company. And because the course has a particular theme, it gives everyone a common focus. While electronic communication, whether email or Skype, is great for maintaining friendships and collaborations, it doesn’t come close to replacing this kind of interaction.

The other reason I look forward to returning to Woods Hole every year is because October is the perfect time to be visiting this part of the world. The summer season is over, the trees are on the turn and there’s a morning chill in the air. Many of the houses are holiday homes and these are shuttered for the winter, it all adds up to a dignified but austere look to the place.


The trip reminds me what a great job I have that allows me to travel and see the world like this. It’s not the first or last trip I’ll make in a year that has taken me from India to LA and places in between. International travel wasn’t something I had realised would be a feature of a career in research. I hadn’t travelled much before leaving university and the opportunity to travel wasn’t mentioned when science careers were discussed in school – in fact I imagined a scientist’s career to be a lifetime spent in a lab working away in some corner of academe. Perhaps this has changed over my lifetime – today there seems to be a wider appreciation that research is an international endeavour. But I’m still not sure we highlight this aspect of research enough when we talk about career choices. This is a shame because it is something many people look for in a job and I can’t think of another career where it would have been so easy for me to visit so much of the world, live and work abroad and have friends and colleagues in so many places.

Of course there are downsides to this. The days of airline travel being glamorous, if they ever existed, are long gone. There are many evenings when I would happily swap a hotel room for the chance to spend the evening at home and in my own bed. And I know I would love for my best friends to live at the end of the road, rather than on another continent. But until we find a way of interacting with our fellow human beings that is as good as meeting them face to face, I am going to sit back, relax and look forward to spending a week in a beautiful part of the world.

The Three Billion Dollar Question

In the last few weeks, two technology companies have announced major investment in – and huge ambitions for- medical research. Microsoft hit the headlines with their proposal to “solve the problem of cancer” within ten years. Simultaneously the Chan-Zuckerberg foundation, led by the Facebook founder Mark Zuckerberg and his physician wife, Priscilla Chan, promised to invest $3 billion over ten years in basic research with the goal of helping cure, prevent and manage all diseases within their children’s lifetime. These are big, bold and ambitious goals – and seemingly large sums of money.

I’ve been reflecting on these announcements and what struck me was the amount of money being committed to these projects is similar to the research spend of my own institute, the Crick. The $3 billion pledged from the Chan- Zuckerberg foundation is certainly a headline grabbing number, but that amounts to $300m a year over the proposed ten years of the project. Compare that to our yearly budget of around £120 million, which equates to a little under $200 million per year, at current exchange rates. We too have an ambitious strategy [Read it here].


Our aims include supporting research that will advance biomedical knowledge and clinical practice but we haven’t committed to curing, preventing disease or eradicating cancer within a specific timeframe. Instead our strategy focuses on advancing knowledge, ensuring that new understanding is used to improve health and wealth, and training future generations of scientists to continue the process. So is our strategy too modest? By not promising to make the lame walk or revive the dead, are we setting our sights too low?

I don’t think so, because biology poses fundamentally different challenges from the ones engineers and technology companies are generally used to dealing with. Firstly, many health and medical problems are not simply about the lack of a technical, therapeutic solutions. Many are inextricably linked to economic and societal problems. At their root is often poverty and disadvantage. In the developing world this is perhaps most obvious. Modern drugs are expensive, often involve extended courses of treatment, preventative measures require concerted government action, vaccines need refrigeration and so on. These are difficult to provide in poor countries where government and public institutions are weak. In rich countries, inequalities in wealth result in health problems concentrating in disadvantaged sectors of society. Smoking and obesity rates, major contributors to poor health, are highest in lower income groups resulting in a striking gradient of life expectancy, with the richer living substantially longer and in better health than the poorer. Investing in medical research won’t change this.

Secondly, biology has the habit of fighting against anything we try to do. Twenty years ago, when I was a graduate student, there was much excitement about designer drugs, principally kinase inhibitors, directly targeting the cause of specific cancers. There has certainly been significant progress in this area and notable successes. But in many cases these only provide limited periods of remission before evading mutations arise, allowing the tumour to resume its relentless course. Indeed studying the effect of these natural selection-like events in tumours has become a fruitful research field and new understanding has the potential to offer insight into how to design better therapeutic regimes. Likewise, the rise of antimicrobial resistance offers a salutary lesson on how evolution can make powerless previously potent therapies. These examples, and many more, mean that the biomedical researchers have learnt to respect the ability of biology to confound even our smartest and most dedicated efforts. Natural selection is a powerful and inescapable force, it is insidious and inexorable. This may be difficult to appreciate if you come from an engineering field where technology has progressed amazingly rapidly, and where any problem encountered can be overcome with imagination and enough computing power. However, technology problems tend not to fight back. In biological systems, evolution generates feedback that leads to complexity, resulting in the whole being greater, and much more difficult to understand, than the sum of the parts. Problems are never permanently solved. At best you win the battle and learn to fight the next one a little better.

Office surprise

I’ve started preparing for my move from Mill Hill to Midland Road (this is the street address and the name used in-house to refer to the new Crick building). One of the tasks I’ve been doing is clearing out my office: identifying the things that need to move with me, boxing up items I want to archive and disposing of accumulated detritus. Unsurprisingly, the last category is the largest. It’s taken me longer than I expected. I don’t have a big office – it can accommodate three people for a meeting, as long as everyone knows each other pretty well and we agree the order that people want to enter and exit the office before we start. Nevertheless it has a lot of shelves and I seem to have collected a lot of stuff over the last 15 years, much of which I’d forgotten about until it was rediscovered  in a box file, or under a pile of other bits and pieces. I found several Secret Santa presents that I’d be given over the years, these includehedgehogd a small cuddly toy in the shape of a hedgehog, a coffee mug with a hedgehog on it and a box that had contained a cupcake shaped like a hedgehog – apparently I’m either very easy or very difficult to buy for. In addition, I found boxes of CDs, DVDs, 3.5” hard disks, Jaz drives and various other now obsolete data storage formats. I’m sure there are several papers’ worth of results on these, if only we still had the means to read them. There was also a whole shelf of reprints of papers I’ve authored, spanning from 1993 until sometime in the mid 2000s, which was the point I decided that, since no one requested reprints anymore, I would stop ordering them. Like 3.5” hard disks, reprints feel like historic objects, I’m fairly certain the graduate students in my lab, more used to reading a paper on their phone than in an actual journal, wouldn’t know what they were or why they were used.

Another reason for the large quantity of stuff cluttering up my office is that when I joined NIMR I brought notes, data and assorted files with me from both my PhD and post-doc. And part of the reason it has taken longer than I expected to clear my office is that I’ve been distracted by looking through these and reminiscing. One of the things I found was a yellowing fax containing the referees’ comments for the first paper on which I was an author. Back in the day, before online manuscript handling systems and emailed notifications, editorial decisions and referees comments used to arrive on the office fax, which in my case was shared between half-a-dozen labs on the same floor. Whoever happened to be in the office when the fax arrived would bring it through to the relevant lab, after having had a quick read. Consequently the good or bad news would spread quickly around the floor. I remember very clearly getting this particular fax. I also very clearly remember the day, about six months before, when we got the initial experimental results that led to the paper. At the time, I was a fairly new graduate student and was working closely with an experienced post-doc. We were trying to identify a gene with a particular function, by testing a set of what we thought were likely candidates. This involved exposing the experimental assay to photographic film, then developing the film to see if we could detect a positive signal. (I still have some of these photographic films in one of the boxfiles I found on a top shelf.) To get a good signal on the film we usually had to wait overnight, but we were always impatient, so our routine was to set up the experiment in the evening, go to the pub for an hour to two then come back and develop the film. If the film was held up to the light at just the right angle you could get a hint of whether the result was going to be positive or negative. We would then re-expose the experiment and confirm the result the next day. After a few weeks of doing this and getting only negative results I was becoming somewhat disillusioned.  Neverless although I was tempted to stay in the pub that evening, I was conscientious enough to go back to the lab and develop the film. I remember angling the film to the fluorescent strip light, squinting at it, expecting another negative result and seeing the unmistakable smudge of a positive signal. I was elated. I don’t remember if we went back to the pub or not that night, but I do remember developing the experiment again the next day and seeing the clear and distinct positive signal.

It was the first time I had experienced that ‘Aha’ feeling of seeing a result and knowing it explained something that hadn’t been known before. I’ve heard this called a ‘dopamine moment’ to describe the pleasure and excitement generated in the brain. It was certainly memorable and it motivated an intense few months of further experiments that culminated in the faxed referees’ comments from the journal editor. There have been a few similarly exciting results in the subsequent 20 years. Unfortunately, they are rarer than I’d like, but then again, if they were more frequent I guess they wouldn’t be so enjoyable. These days they don’t come from peering at underdeveloped films but more likely from a graph of data plotted on my screen, or someone sticking their head around the office door and saying “I think I’ve got an interesting result….”. And now, with the date of our move getting closer and our attention increasingly focused on the practicalities of packing up and relocating, I’m looking forward to the first dopamine moment in Midland Road. I hope its not too long in the future.


Labs don’t live here anymore

I’ve returned to Mill Hill after two weeks away and in my absence a lot has changed. It’s now a couple of months since the move into the new building started, however up until recently this has mainly been relocating and recommissioning large pieces of equipment – the NMR machines, electron microscopes, DNA sequencers and so on – relatively few people had moved. But while I was away, the first research labs left Mill Hill and took up residency in the new building. Many of Mill Hill’s Drosophila and structure biology labs have moved and every week from now until Christmas more labs will be moving. From what I hear, people are excited and impressed by the building. The move of lab equipment and lab reagents seems to have gone better than expected. But there are inevitable teething problems – some sockets are in the wrong place, the purified water isn’t working yet and the canteen hasn’t opened. And of course there’s a lack of familiarity for everyone. Like moving house and learning where the light switches are, I imagine it will take some time to settle in to the new building. It will be interesting to hear how opinions and feelings change over the next few weeks and months as each of the labs make themselves at home.

Back at Mill Hill there are noticeably fewer people around, particularly on some of the floors. I think there are few sights more depressing than a bare and abandoned lab, but they are now starting to appear around our once packed building.

EmptyLab Seeing them makes me think of all the hard work and long hours given by the people who had occupied the labs and also the interactions and discussions I’ve had with the people that have left. It is those conversations that I have come to value the most about being at Mill Hill. Indeed, one of the reasons for funding research institutes is that putting a large number of researchers together creates the critical mass necessary for collaborations that wouldn’t happen otherwise. To support this argument, statistics about joint publications, grants and research projects are often cited. However, my own personal experience is that these statistics only capture part of the benefits. At least as important as these formal interactions are the informal exchanges and corridor discussions. These can be mundane and difficult to quantify. It might be the sharing of a critical reagent, a handy little tip about how to get a piece of equipment to work, or who to ask for advice. On the other hand, they can also be scientific discussions about each other’s projects or about a paper that’s just been published. I’ve frequently found these stimulating and useful. They might be on subjects far from my own research interests, but on more than one occasion these have made me aware of a connection that I hadn’t noticed before or suggested a useful comparison that I hadn’t previously thought about. These can lead to further ideas and more discussion and offer a new perspective to the problem I’m thinking about.

I was particularly reminded of this because I spent the two weeks I’ve been away from Mill Hill at Kavli Institute for Theoretical Physics in UC Santa Barbara participating in a summer school that brings together biologists and physicists interested in embryo development and morphogenesis. I always enjoy attending summer schools, in part because I usually learn at least as much as the students. But also summer schools tend to have a more relaxed atmosphere than a typical conference and this offers a great opportunity to discuss ideas and learn new things, especially from researchers outside my own field. KITP is particularly good in this respect, because, as the name implies, for most of the year it hosts theoretical physicists. This means the culture of discussion and interaction is encouraged, almost to the point of compulsion. Signaling this, on arrival everyone is issued with a coffee mug with your name on it. KITP_mugEveryday at 3pm, a message is sent that coffee and cookies are served in the Common Room and as you drink your coffee the mug serves the same purpose as a conference name badge. This ritual means even the more introverted visitors are encouraged to talk to new people. I spent several enjoyable and thought-provoking afternoons wandering the KITP corridors, with my coffee mug, meeting new people and dropping into offices to chat and exchange ideas. Whether anything will come of these discussions, I don’t know, but it’s certainly a great way for new ideas to bubble up or to get a new view on an old idea.

It also made me realise that as research scientists we develop two groups of colleagues. A set of people in our home institutes who we interact with on a daily basis and whose views and ideas we become very familiar with; then a second group, scattered around the world, who share our interests and approaches, but who we only meet occasionally. It’s a privilege to be in this situation and the contrasting views and ideas that come from these two groups mean that I’m rarely lost for inspiration. It’s also fascinating to see how the ideas and discussions develop over time, presumably influenced by all the other conversations happening at other institutes, conferences and summer schools. Over the next few months, I’ll miss the spontaneous discussions with colleagues that have left Mill Hill but I look forward to rejoining them when it’s my turn to move. When I do move, the bonus will be that there will be new colleagues there too and for a while I expect it to feel a bit like a summer school with all the new people and new ideas.


Carbuncle and collaboration

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.

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.

That Friday Feeling

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.


I wouldn’t start from here

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 [], 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.