By early next month, the vast bulk of the building work at Europe¡¯s largest biomedical institute will be complete. Standing taller than its neighbouring London landmarks, St Pancras station and the British Library, the Francis Crick Institute has cost about ?700 million to build and, by the end of next year, will house 1,250 scientists and boast an annual operating budget of more than ?100 million.

But the Crick is more than just an enormous building and a series of huge numbers. The brainchild of its Nobel prizewinning director and founding chief executive Sir Paul Nurse, the institute is intended to pioneer a new approach to doing science. Minimal organisational structure and strategy, reduced pressure to publish and architectural innovations such as transparent walls are all intended to give the world¡¯s brightest young scientists an unrivalled opportunity to apply their collective minds to tackling biomedicine¡¯s knottiest problems.

The new institute has its origins in the Medical Research Council¡¯s decision, a decade ago, to relocate the ageing National Institute for Medical Research from North London to University College London. But the project really took off when the idea was hatched ¨C in the wake of a call in 2006 by the government-commissioned for greater collaboration and innovation in biomedical research ¨C of merging the NIMR with Cancer Research UK¡¯s London Research Institute.

The MRC¡¯s ?300 million contribution and UCL¡¯s ?40 million were bolstered by ?120 million from the Wellcome Trust and ?160 million from CRUK, whose forerunner organisation, the Imperial Cancer Research Fund, was headed by Nurse from 1984 to 1988. And at the end of 2007 the Labour government announced that the UK Centre for Medical Research and Innovation, as it was then known, had been selected as the favoured project for the government-owned St Pancras site ¨C with its scientific planning to be led by Nurse.

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But that was back in the pre-crash days of expanding science budgets. And although King¡¯s College London and Imperial College London both opted to join the party in 2011, each putting ?40 million towards the capital costs, the freezing of the science budget since 2010 means that money is much tighter than it was. Times ºÚÁϳԹÏÍø went to press before yesterday¡¯s 2015 spending review, but no one was expecting anything better than another flat-cash settlement. So might it, in hindsight, have been a mistake to put so much money into a scientific behemoth that some fear will suck up cash at the expense of other research centres elsewhere in the country on account of its being ¨C as Kieron Flanagan, senior lecturer in science and technology policy at the University of Manchester, puts it ¨C ¡°essentially too big to fail¡±?

¡°We are a big single building under a single way of working. That we accept,¡± Nurse tells THE in an interview conducted at the Crick¡¯s temporary offices in the Wellcome Trust¡¯s headquarters nearby. But he insists that the proportion of the total amount spent on UK bioscience that will go to the institute is ¡°really very small¡±. While its operating budget of about ?130 million a year is large, it is considerably lower than that of any number of biomedical divisions at large research universities, Nurse points out. The University of Oxford¡¯s medical division, for instance, had ?300 million in research income in 2012-13, he says. Moreover, although the Crick¡¯s building is new, its operational budget largely is not, since most of it will come out of the funds previously allocated to the NIMR and LRI (?50 million each from the MRC and CRUK), plus an additional ?16 million from the Wellcome Trust. Competitively won grants are expected to contribute only about ?14 million a year to the total.

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¡°So the idea that we¡¯re absorbing lots of new money is completely incorrect,¡± Nurse says, adding a broadside against those who ¡°shoot their mouths off without knowing what the facts are¡±.

The MRC and CRUK researchers currently remain in their old premises, but are already technically part of the Crick ¨C complete with newly branded mugs and lanyards. This has allowed the Crick to claim its first Nobel prize: Tomas Lindahl, formerly director of CRUK¡¯s Clare Hall laboratories in Hertfordshire, now also subsumed into the Crick, was awarded the Nobel Prize for Chemistry in October.

Transferred staff currently account for about two-thirds of the Crick¡¯s headcount. Most of the group leaders among them are senior researchers on permanent contracts (subject to acceptable scientific performance). Others ¨C about 240 ¨C will be academics from King¡¯s, Imperial and UCL, who will be selected by peers from both their own institution and the Crick to for, typically, between one and six years (see ¡®Serendipity knocks: how coffee and conversation lead to breakthroughs¡¯ box, below), before returning to their parent institutions.

Nurse¡¯s aspiration, though, is that eventually two-thirds of the Crick¡¯s group leaders will be outstanding younger researchers, hired on fixed-term 12-year contracts (subject to review after six years). But can he really expect to attract the world¡¯s best without offering them permanent positions?

Yes, Nurse insists. He explains that, during the second half of these researchers¡¯ stay, the Crick will look to line them up with another university in the UK, perhaps creating a joint position for them for their final three years. In addition, they will be able to take their lab equipment and grant funding with them, so that ¡°anybody leaving us has got a flying start¡±. That is only true, of course, if they choose to remain in the UK ¨C but Nurse believes that many will indeed put down roots in the UK during their 12 Crick years. So rather than sucking the life out of bioscience in the rest of the country, as some fear, the Crick is designed to function more like a geyser, drawing in talent from the rest of the world, and then spraying it over the regions.

What about the expense of living in London? Earlier this year, a billboard campaign called ¡°¡± highlighted this problem by quoting those forced out of the city by high housing costs; several billboards featured academics or graduate students. But Nurse is sanguine: ¡°Most of the people we¡¯ll be attracting in ¨C graduate students, postdocs, junior leaders ¨C are of an age where they will probably feel that the attractions of one of the greatest cities in the world¡­will compensate for not living in the largest flat that they could do if they lived somewhere else.¡± The Crick may even offer a year¡¯s accommodation to those new to the city, Nurse adds, particularly in the case of scientists from abroad.

London is crowded below ground as well as above, and one big challenge that will need to be addressed is that of protecting the institute¡¯s highly sensitive subterranean equipment, such as electron microscopes, from vibrations and electromagnetic interference from the new tunnels planned for the second Crossrail project. This is a severe enough worry that ¡°there is a risk that the [MRC] will not be able to maximise the value of its investment in the Crick¡±, the council wrote in its .

According to Nurse, the issues ¡°can be solved if they put [Crossrail] somewhere else¡± or carry out ¡°expensive changes¡± to the line, although he acknowledges that ¡°it¡¯s a big problem for us¡±. Nevertheless, he would ¡°absolutely¡± still build the Crick in Central London if he could revisit that decision ¨C not least because 1,000 of the scientists who will be moving in are already based in the city.

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Asked the same question, Sir John Savill, chief executive of the MRC, is slightly less sanguine, but thinks that the original arguments for siting the Crick in St Pancras ¡°probably still hold¡±, and he has not heard of London universities struggling to recruit young scientists.

Quizzed on whether the Crick is indeed too big to fail, Savill is adamant that if it ¡°is not a success, then its funders will withdraw from it¡±. Yet he also says that the prospect of failure is ¡°unconscionable¡±, ¡°just as the idea that my own university, Edinburgh, should fail, is unconscionable¡±.

The pressure on Nurse to get his approach right is clearly immense, and ¡°Sir Paul¡¯s cathedral¡±, as it has been dubbed by some of its employees, has been carefully designed to fizz with interactions between scientists from different disciplines (see ¡®Sir Paul¡¯s cathedral: glass, steel and soaring potential¡¯ box, below). Not all of its features are entirely unprecedented. The MRC¡¯s Laboratory of Molecular Biology (LMB) in Cambridge, often described as the UK¡¯s Nobel prize factory, also recently moved into an expensive new building that is designed to encourage serendipitous encounters between otherwise unrelated researchers. According to Hugh Pelham, the LMB¡¯s director, its equipment, like the Crick¡¯s, is shared so that scientists ¡°bump into each other going up and down the corridor¡±. The LMB¡¯s canteen is also explicitly designed to foster mingling, with new researchers given coupons for 10 free cups of coffee so that they can start to get to know their colleagues. But in terms of organisation, the LMB is not as radical as the Crick. It is split into four divisions, each with its own head; in contrast the Crick¡¯s structure will be almost completely flat, with scientists expected to form their own interest groups themselves, in an approach Nurse has previously described as ¡°gentle anarchy¡±.

While the Crick may be big, it is not about big science, Nurse insists. Rather, it will be ¡°an umbrella for little science to survive¡±. The top-down scientific strategies common in other research institutes will be ditched in favour of a ¡°guerrilla warfare¡± approach. This has , but Nurse dismisses the criticism as ¡°nonsense¡±.

Such curt dismissals are a recurring theme when he is asked to respond to quibbles about the Crick¡¯s modus operandi. But why do so many people ¡°talk nonsense¡± about his plans?

¡°I think they are frightened of a high-quality institute of this sort, to be honest,¡± he says, thumping the table. ¡°Academics are renowned for whingeing all the time. When [critics] say we have no strategy, they mean we don¡¯t finely prescribe what will be done.¡±

The Crick, instead, asks a ¡°series of overarching questions¡± that ¡°people are free to choose how to address¡±. Places with top-down strategies are usually ¡°tired, out of date and don¡¯t attract the best people¡±, Nurse argues. Smaller institutes do often need a focused strategy, but one that is too focused on a current issue ¨C stem cells, for example ¨C will find it difficult to move on.

Such arguments do not convince everyone, however. Asked to comment on the Crick¡¯s minimal science strategy, Julia Lane, a professor of practice at New York University¡¯s Center for Urban Science and Progress, remarks that ¡°hope is not a plan¡±.

¡°Imagine that you¡¯re a venture capitalist and a bright-eyed and bushy-tailed person comes in and says, ¡®I don¡¯t have a plan but I¡¯m sure good things will happen¡¯. What would the venture capitalist say?¡± she asks.

¡°Science is work, it¡¯s not magic,¡± she argues. The Crick¡¯s approach ¡°may work¡± but then again, she says, ¡°I may throw money out the window and make people rich.¡± Again and again, Lane emphasises the need for such an institute¡¯s model to be based on scientific evidence about what works.

¡°One of the things that gives one pause is that scientists don¡¯t apply the scientific method to their own activities,¡± she argues, adding that there are many ways the Crick could test the effectiveness of its model if it chose to.

Flanagan agrees. While there is evidence that a large number of small groups is more productive than a smaller number of larger groups, ¡°there is no evidence whatsoever for (or indeed against) the larger claimed mechanism by which the Crick is meant to work: that massive co-location of groups with some overlapping interests but a diversity of expertise and perspectives will automatically lead to interactions that will increase the chances of serendipitous links being made that will in turn raise the productivity of all the groups. Essentially, as with most things in science policy, the Crick model is somewhere between fashion and folk wisdom,¡± he says.

Asked what evidence the Crick¡¯s scientific model is based on, a spokeswoman responds that the design of the laboratories is based on Nurse¡¯s past experiences, including his time as president, from 2003 to 2011, of Rockefeller University in New York City, ¡°where open spaces resulted in more interaction and collaborations between research disciplines¡±. She concedes that the Crick is not planning specific research about the effectiveness of its approach, but ¡°the standard scientific productivity metrics would apply, and our founders will want to assess the general effectiveness of the approach as part of our five-yearly institute review¡±.

There will be other ways in which the Crick is distinctive. Nurse says that its scientists will not be judged ¡°at all¡± on the impact factors of the journals in which they publish. Their performance will be reviewed, ¡°but essentially, we¡¯re not asking for high-profile papers. We¡¯re not ticking [off] the Natures, the Cells, the Sciences and so on,¡± he says. ¡°If [researchers are] taking on the big problems we¡¯re not going to ask for something back in two or three years, because [that] doesn¡¯t happen.¡±

There is a similar philosophy when it comes to commercial translation. David Roblin, the Crick¡¯s chief operating officer and director of translation, explains that rather than setting targets for spin-out revenue, performance will be judged according to a more qualitative assessment of broader commercial impact. But that impact will certainly be valued, and over the course of five years, Roblin ¨C the former head of research for Pfizer in Europe ¨C hopes that the majority of Crick group leaders will be asking how they can incorporate an applied scientist into their team in order to foster translation of their research.

So will all research one day be conducted along Crick lines? ¡°I like plurality; there are different ways of doing things,¡± Nurse says. ¡°But universities need to be fleeter of foot. You can see what happens ¨C you get a baron in place¡­running a department¡­and they look for people who are similar to them. It was good, but then it gets a bit ossified.¡±

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By contrast, the Crick¡¯s constant refreshment of its staff means that it will be much more flexible and responsive to change. When Nurse implemented this model at Rockefeller, it meant that the institution was able to ¡°find [scientific] areas that are moving before the rest of the world has noticed them¡±, he says. ¡°The Crick can move where science goes.¡±

Sir Paul¡¯s cathedral: glass, steel and soaring potential

Sitting behind St Pancras station and the British Library, the Francis Crick Institute feels slightly tucked away. But up close, it is vast: 170m long, eight storeys high (with a further four underground), and capped with a curved glass shell that mirrors the station roof opposite.

Running lengthways through the building is a vast atrium, so big that a 450-seat auditorium sits comfortably within it on the ground floor. This cavernous space is criss-crossed by walkways, and on both sides of the building most labs have glass walls so that researchers can see their colleagues working away even if they are on opposite sides of the building.

In the corner of each floor sits an important piece of equipment ¨C a mass spectrometer, for example ¨C designed to draw users from different disciplines together. Breakout pods and tea and coffee points on each level, as well as a sizeable canteen, will also encourage interdisciplinary mingling.

The building is so spectacular that despite being unfinished it was chosen as the location for BBC journalist Evan Davis to in the run-up to the May general election. Given the building¡¯s cost and the hype around its potential to transform science, expect to see politicians¡¯ noses pressed up against all that glass in years to come, asking where all the Nobel prizes are.

Serendipity knocks: how coffee and conversation lead to breakthroughs

Ewa Paluch is an experimental biophysicist whose discipline-spanning career exemplifies the kinds of links the Francis Crick Institute hopes to build among scientists.

The professor of cell biophysics at University College London started her career as a particle physicist before moving into biosciences. Now working as a research group leader at the Medical Research Council¡¯s Laboratory for Molecular Cell Biology at UCL, Paluch will have a satellite lab at the Crick for two members of her group.

¡°I¡¯m completely sure it can work,¡± Paluch says of the Crick¡¯s multidisciplinary model that fits physicists, computer scientists and mathematicians into an institute otherwise dominated by life scientists. She says that a similar multidisciplinary system worked well at the Institut Curie in Paris, where she completed her PhD.

It also worked at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden. She recalls working as an experimental biophysicist alongside a student biologist on why it is that cells sometimes divide in a lopsided way ¨C with all kinds of health implications. Over coffee, a collaborating theoretical physicist mentioned a 19th-century scientific paper that examined the behaviour of attached, lopsided spheres in soap bubbles. Reading the paper was the foundation for a very significant article and several follow-up projects.

The article, which was published in Nature in 2011, even used diagrams of soap bubbles to help to explain the behaviour of splitting cells (the theoretical physicist who alerted Paluch to the soap bubble research, Guillaume Salbreux, is now a group leader at the Crick). ¡°I think coffee helps [the scientific process],¡± Paluch says. ¡°Putting people [from different disciplines] in one place is really the way to go.¡±

Paluch is one of the first cohort of researchers from the Crick¡¯s partner universities ¨C University College London, Imperial College London and King¡¯s College London ¨C to be placed in the institute on secondments, satellite placements or sabbaticals. Paluch¡¯s ¡°satellite¡± status means that she herself will largely remain at UCL, working a couple of days a month at the Crick.

The idea is that these researchers will bring new areas of expertise into the Crick for a set period of time ¨C typically three to six years for secondments, up to three years for placements and a year for those on sabbaticals.

Birth of a nation¡¯s superlab: Francis Crick Institute timeline

February 2005
The Medical Research Council announces that its National Institute for Medical Research at Mill Hill, London, will move to University College London.

October 2006
Amid spiralling costs and opposition from within NIMR, Colin Blakemore, the MRC¡¯s chief executive, admits that the project may not go ahead unless the government steps in with additional funding.

December 2006
The government-commissioned Cooksey Review ¨C officially called ¨C calls for enhanced collaboration and innovation in UK bioscience.

December 2007
Gordon Brown, the prime minister, that a new UK Centre for Medical Research and Innovation (UKCMRI) will be built on government land next to St Pancras station, merging the NIMR with CRUK¡¯s London Research Institute. The scientific planning will be led by Sir Paul Nurse, president of Rockefeller University in New York.

December 2009
Architectural plans are unveiled.

July 2010
Nurse is as director and chief executive of the UKCMRI.

October 2010
George Osborne, the chancellor, confirms in his spending review that the government will contribute ?220 million towards the MRC¡¯s share of the building costs.

December 2010
Planning permission is , despite for the site to be used for housing.

April 2011
Imperial College London and King¡¯s College London are announced as new UKCMRI partners, committing ?40 million each.

May 2011
The Commons Science and Technology Committee describes the case for locating the institute at St Pancras as ¡°not overwhelming¡±.

July 2011
Ground is broken on construction and the UKCMRI is renamed the Francis Crick Institute, after the British co-discoverer of the structure of DNA.

April 2015
The NIMR, LRI and CRUK¡¯s in Hertfordshire officially become part of the Crick Institute.

December 2015
Construction of the building is due to be completed.

March 2016
Preparing and checking building services due to be complete.

Summer 2016
Main phase of scientists¡¯ relocation to take place.

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Late autumn 2016
Likely official opening.