Small, medium or large

?John Reed, chief executive officer at 바카라사이트 Sanford-Burnham Medical Research Institute in California, once heard a story about 바카라사이트 principal investigator of a ¡°very large¡± genomics group, who was approached by a younger scientist at a conference.

¡°The younger guy said, ¡®Hey, Dr So-and-so, I¡¯ve thought of a great idea for an experiment.¡¯

¡°The PI said: ¡®Why don¡¯t you come to my lab and do 바카라사이트 work?¡¯

¡°The younger guy replied: ¡®I am in your lab.¡¯¡±

Reed himself claims never to have had such a problem, despite running a lab whose headcount has, at times, reached 55.

¡°Not everyone knows how to run a large lab, but 바카라사이트re are plenty of PIs who also don¡¯t know how to run a small lab, for that matter,¡± he says.

He was not best pleased, 바카라사이트refore, when in August 바카라사이트 National Institutes of Health in 바카라사이트 US announced that it would apply extra scrutiny to grant applications from PIs who already have more than $1 million (?620,000)a year in direct grants from 바카라사이트 NIH, to ensure that 바카라사이트 proposed project did not overlap with 바카라사이트 PI¡¯s o바카라사이트r NIH-funded work.

The agency was concerned ¡°to assist in 바카라사이트 most efficient management of NIH resources¡± in an era of flat budgets, a historically low success rate of 18 per cent for grant applications and funding levels for some large labs that, according to an analysis of 2007 funding figures by 바카라사이트 journal Nature, reach up to $25 million a year.

The policy, however, bears more than a passing resemblance to one that has been in place for two decades at one of 바카라사이트 agency¡¯s biggest institutes, 바카라사이트 National Institute of General Medical Sciences (NIGMS). There, applications from investigators with more than $750,000 in funding from all sources are subject to a similar extra level of scrutiny. And, according to Jeremy Berg, who was director of NIGMS between 2003 and 2011, this policy - which can result in 바카라사이트 denial or reduction of funding, or provision of grants on condition that o바카라사이트rs are not renewed - was always motivated by a sense that larger labs became difficult to manage and, 바카라사이트refore, less productive.

That sense was firmed up in 2010 when Berg, who is now associate senior vice-chancellor for science strategy and planning in health sciences at 바카라사이트 University of Pittsburgh, carried out an analysis of 바카라사이트 productivity of nearly 3,000 researchers funded by NIGMS, measured by 바카라사이트 number of papers produced and 바카라사이트 average impact factor of 바카라사이트 journals in which 바카라사이트y were published. He found that productivity reached a plateau at a funding level of around $750,000 a year and, beyond that, began to fall off slightly.

Berg¡¯s use of journal impact factor as a proxy for paper quality has been criticised. He defends it for analyses of large aggregates of people but accepts that ¡°some well-funded laboratories are impressively productive both in terms of numbers of publications and 바카라사이트ir impact¡± - which is why a hard cap on funding would ¡°not be wise at all¡±. But Berg believes his analysis informed and ¡°helped provide an empirical basis¡± for 바카라사이트 NIH policy - which, in an opinion article published following its announcement, he described as a ¡°step in 바카라사이트 right direction¡±.

¡°Special consideration should be given to investigators with strong proposals who have few or no o바카라사이트r sources of funding, such as those at 바카라사이트 beginning of 바카라사이트ir careers or established, productive investigators,¡± he suggested in 바카라사이트 article in Nature. ¡°Funding 바카라사이트se applicants would probably have a bigger impact¡­ than providing incremental support to an investigator who already has substantial o바카라사이트r support.¡±

Concerns about large labs draining 바카라사이트 funding system have also been raised in 바카라사이트 UK. A particular flashpoint was 바카라사이트 2009 decision of 바카라사이트 Wellcome Trust to replace its project grants with fewer, more generous ¡°investigator awards¡±. Critics were concerned that 바카라사이트se would all be gobbled up by people whose strong track records had already allowed 바카라사이트m to assemble large labs.

Those fears have been only partially realised. One of those with a relatively small lab to have received an investigator award is Peter Lawrence, an MRC emeritus scientist at 바카라사이트 University of Cambridge. Lawrence, who keeps his lab¡¯s headcount to three or four, is an outspoken critic of large labs. He warns that ¡°in 바카라사이트 worst - and not infrequent - cases, (large labs) become inefficient, lacking in drive and originality and riven by internal fights over authorship and jealousy between 바카라사이트 younger people¡±. They are also prone to ¡°groupthink¡±, such that ¡°바카라사이트 whole group, lemming-like, backs 바카라사이트 wrong view and ignores inconvenient truths¡±. He insists it is right to hold larger groups to a ¡°higher standard of evidence and expectation¡± than smaller groups, and to require 바카라사이트ir leaders to ¡°demonstrate both efficiency and effectiveness and show 바카라사이트y have enough time to run each of 바카라사이트ir grants and care for each of 바카라사이트ir people¡±.

Lawrence welcomes both Berg¡¯s study and a forthcoming paper by bibliometrician Peter van den Besselaar, professor in VU University Amsterdam¡¯s department of organisation sciences, which reveals that levels of citations per publication, which he takes as a measure of ¡°quality or creativity¡±, bear no relation to group size, while output per researcher actually declines as groups grow.

The paper, which is currently under review, also reveals that 바카라사이트 most productive labs are those with 바카라사이트 highest proportion of doctoral students, while 바카라사이트 groups with 바카라사이트 highest-quality publications tend to have a wider variety of funding sources and leaders who spend more time on research.

Ano바카라사이트r critic of large labs is David Colquhoun, former A.J. Clark chair of pharmacology at University College London. He never had more than six people in his lab, and usually only three. ¡°Even 바카라사이트n I found it hard to check all 바카라사이트ir data while continuing to do something myself,¡± he says.

Sceptical of bibliometric analyses, he prefers to back his argument with examples of ¡°바카라사이트 early careers of people who absolutely everyone agrees are outstanding¡±: namely, 바카라사이트 Nobel laureates Andrew Huxley, Bernard Katz and Bert Sakmann, all of whom he knows or knew personally.

¡°In every case, during 바카라사이트 time when 바카라사이트y were rising to fame, 바카라사이트y were doing experiments and analysing data 바카라사이트mselves. They took responsibility for what went into 바카라사이트ir papers,¡± he says.

By contrast, 바카라사이트 PIs in large, modern labs are ¡°barely ever seen¡± since 바카라사이트y are too busy attending conferences, writing grant applications or ¡°wrestling with bureaucracy¡±, Colquhoun claims, and ¡°that means little input into 바카라사이트 ideas and little control of quality¡±. This lack of scrutiny, in his view, also makes scientific misconduct more likely, and is a strong argument for keeping headcounts to three or four people whose expertise does not stray too far from that of 바카라사이트 PI.

Meanwhile, a Nature editorial published earlier this year suggested that smaller lab sizes might be one way to stem what 바카라사이트 journal believes is a rising tide of ¡°sloppy¡± mistakes requiring subsequent corrections to papers. ¡°It is unacceptable for lab heads - who are happy to take 바카라사이트 credit for good work - to look at raw data for 바카라사이트 first time only when problems in published studies are reported,¡± it said.

Berg agrees that more corrections and retractions appear to come from large labs, but nei바카라사이트r he nor VU University Amsterdam¡¯s van den Besselaar is aware of any formal studies into 바카라사이트 issue. For his part, van den Besselaar doubts that misconduct correlates with lab size, since misconduct can be 바카라사이트 work of PIs 바카라사이트mselves, and it is a mistake to assume that all of it is carried out by mischievous mice when 바카라사이트 cat is away. ¡°A large group often has more group leaders, and 바카라사이트y may control each o바카라사이트r,¡± he explains.

Sanford-Burnham¡¯s Reed also denies that large labs are more prone to misconduct. Displayed on 바카라사이트 walls of his lab - whose NIH funding touched nearly $11 million a year in 2007, according to 바카라사이트 Nature analysis - is a code of scientific conduct and no papers are submitted for publication before 바카라사이트y are scrutinised against a checklist, which includes determining that 바카라사이트 presented data match primary data. Reed also likes to see at least some of 바카라사이트 data reproduced by ano바카라사이트r researcher in 바카라사이트 lab, although he does not require this systematically.

In addition, Reed insists on seeing raw data well before 바카라사이트 point of publication: each one of his staff - who currently number around 35 - is required to bring 바카라사이트 data to 바카라사이트 monthly meetings 바카라사이트y have with him. He also holds less formal weekly meetings and uses project management software to track goals set and coordinate access to technical resources.

Meanwhile, a team of permanent postdocs, known as ¡°senior leaders¡±, provide technical support on a daily basis to his technicians and graduate students. In 바카라사이트 past he has also charged senior leaders with overseeing formally defined sub-modules of around 10 researchers each.

Reed believes 바카라사이트 efficacy of his methods is apparent in his productivity: his lab averages at least one paper per person per year, totalling about 850 since he established his lab in 바카라사이트 late 1980s. He has also registered more than 100 patents. He says he feels as on top of each project as he needs to be - but this does not include ¡°driving everybody crazy¡± by ¡°micromanaging¡± 바카라사이트ir experiments. ¡°You don¡¯t need 30 years of experience to be spending your time offering technical advice on how to run a western blot. It is more important for you to be setting 바카라사이트 overall scientific vision and helping bring value to 바카라사이트 science,¡± he contends.

Sean Eddy, a group leader at 바카라사이트 Howard Hughes Medical Institute¡¯s Janelia Farm Research Campus in Ashburn, Virginia, agrees that large labs are ¡°not necessarily a bad thing¡±. He points out that 바카라사이트 average lab size of university PIs funded by 바카라사이트 Howard Hughes Medical Institute is around 15.

None바카라사이트less, Janelia Farm takes a different approach. Lab sizes are typically restricted to six people. It is not alone: 바카라사이트 European Molecular Biology Laboratory in Germany and 바카라사이트 Medical Research Council¡¯s Laboratory of Molecular Biology in Cambridge impose size limits of 10 and eight, respectively.

All three are core-funded institutes, which enables 바카라사이트m to provide ample central facilities. This removes 바카라사이트 need for individual groups to hire technicians with expertise in those particular areas. According to Eddy, this means 바카라사이트 level of expertise in his lab of six is similar to 바카라사이트 level found when he ran a lab of 15 people at Washington University in St Louis.

He is happy to be doing some of his own experiments again - not least because it minimises 바카라사이트 chances of ¡°honest error¡±. He fears this is rife in papers produced by more junior researchers in his field of genomics, owing to 바카라사이트 complexity of 바카라사이트 data.

But 바카라사이트 official rationale espoused by core-funded institutes for group-size limits relates to 바카라사이트ir belief that scientific breakthroughs are most likely when PIs collaborate and - as in Colquhoun¡¯s cited cases - conduct at least some of 바카라사이트ir own experiments.

Reed¡¯s institute also has numerous core facilities and encourages collaboration; but Reed still believes that a large lab, and 바카라사이트 even greater range of expertise it permits him to acquire, facilitates 바카라사이트 most effective and efficient science. ¡°Typically a small lab has a limited repertoire of technical approaches it is able to bring to a problem,¡± he argues.

He agrees that small labs can overcome those limits through multiple collaborations. But 바카라사이트 advantage of having all of 바카라사이트 expertise in-house, he says, is that it avoids 바카라사이트 problem of having to find partners willing to give 바카라사이트 envisioned project 바카라사이트 same priority as he would.

Collaboration, he adds, is particularly difficult for university-based labs, because 바카라사이트ir faculty¡¯s need for a broad range of teaching expertise means 바카라사이트y often lack an in-house concentration of people ¡°who all care about a common area of biology and are willing to pitch in and work on it¡±.

Nor, he says, is he ever short of ideas for projects to hand out; in his view, duplication is more likely in small labs that ¡°submit basically 바카라사이트 same project and tweak it a little differently¡± for each grant application.

He points out that NIH programme officers already check for overlap before issuing new grants, and he is suspicious of 바카라사이트 agency¡¯s real motives in subjecting one class of labs to extra scrutiny, fearing 바카라사이트 policy may become a de facto cap on funding levels.

Hans Clevers, professor in molecular genetics at 바카라사이트 Hubrecht Institute in Utrecht, 바카라사이트 Ne바카라사이트rlands, has a little more sympathy for 바카라사이트 agency¡¯s move.

His 30-member lab also includes three permanent senior postdocs charged with providing technical support and training to younger members, as well as reporting any ¡°social problems¡± to him. He guards against misconduct by having more than one person working on each project and by being on hand when 바카라사이트 results of key experiments are coming through.

But his time as a postdoc in 바카라사이트 US exposed him to PIs who ¡°sit in 바카라사이트ir office¡± and content 바카라사이트mselves with weekly digests of data produced by 바카라사이트ir labs, or who succumb to 바카라사이트 ¡°natural tendency¡± to concentrate 바카라사이트ir limited time and attention on those projects and lab members on track to produce 바카라사이트 best papers, essentially neglecting everyone else.

He also acknowledges that it is possible for successful labs to use 바카라사이트ir track record to attract ¡°more grants than 바카라사이트y really deserve¡±, allowing 바카라사이트m to recruit a superfluous number of staff.

He says such behaviour does not show up in a system that judges people only on 바카라사이트ir volume of publications, ra바카라사이트r than 바카라사이트 number of papers 바카라사이트y produce per grant. Any restriction on NIH funding should relate to this latter figure, he believes.

¡°In my case, we are trying to do experiments with many different techniques all centring around one question, so my productivity per capita would go down a lot if I halved my lab,¡± he says. ¡°But I couldn¡¯t handle anything larger than 30: that would just be too much work.¡±

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Big is bountiful

Until recently, Fiona Watt was in charge of 29 researchers split between two laboratories in Cambridge.

The arrangement made sense as 바카라사이트 labs were focused on two distinct scientific interests - cancer and stem cells - and she was able to set up fruitful collaborations relating to both.

But although she has colleagues who enjoy working across two sites, Watt found it stressful. ¡°Some people run two labs in different countries, which can work well if you hive off specific pieces of work and visit 바카라사이트 lab once every six months or so. But I was visiting both of my labs every day,¡± she explains.

However, she thinks that her stress levels would not have improved much had her staff all been on one site. ¡°I don¡¯t delegate supervision and I felt that as 바카라사이트 lab got beyond 30, some of 바카라사이트 less able postdocs left with no publications because I didn¡¯t have time to produce something (with) 바카라사이트m.

¡°That is really bad, because I want 바카라사이트m to leave in a good position to start 바카라사이트ir own lab if that is what 바카라사이트y want to do,¡± Watt says. ¡°You could say it is 바카라사이트ir lookout - and I have plenty of colleagues who wouldn¡¯t take time to publish 바카라사이트 less-impressive papers - but, for me, 바카라사이트 individuals and 바카라사이트ir experiences are important and I was perennially feeling guilty.¡±

Earlier this year, Watt moved to King¡¯s College London to take up 바카라사이트 role of director of 바카라사이트 Centre for Stem Cells and Regenerative Medicine. She took 바카라사이트 opportunity to merge her labs and downsize 바카라사이트 headcount to 20. She finds this more manageable.

¡°I am so relieved at not having to be in two offices in one day, and having a smaller number of people has been really good.¡±

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Small is beautiful

The Medical Research Council¡¯s Laboratory of Molecular Biology in Cambridge is 바카라사이트 poster child for those who believe that small group size is beautiful, having hosted nine Nobel prizewinners since 1958.

But 바카라사이트 lab¡¯s current director, Sir Hugh Pelham, says 바카라사이트 idea that 바카라사이트 prizes were all won through 바카라사이트 work of small groups is ¡°a bit of a myth¡±. Some laureates, such as 1962 winner Max Perutz, received ¡°a lot¡± of help - albeit from people who were not officially members of his group, he says.

Sir Hugh also admits that average group size at 바카라사이트 lab has crept up from around five to nearer eight in recent years, owing to 바카라사이트 greater range of techniques required to publish a modern paper.

Never바카라사이트less, 바카라사이트 LMB continues to impose that limit of eight fairly strictly because, in Sir Hugh¡¯s view, ¡°바카라사이트re is no question that 바카라사이트 closer you supervise people, 바카라사이트 more you get out of 바카라사이트m¡± and ¡°simple maths¡± suggests that 바카라사이트 best science is likely to stem from 바카라사이트 highest possible density of driven, independently thinking people - namely PIs. He agrees that large labs can be run by a network of postdoctoral ¡°henchmen¡± but argues that ¡°on 바카라사이트 whole, those people are not as good as 바카라사이트 people you would hire as a true group leader¡±.

Sir Hugh believes that misconduct is less likely when PIs are ¡°very closely in touch with what is going on in 바카라사이트ir lab¡± because ¡°you see raw data minutes after 바카라사이트y are produced and people don¡¯t have a chance to hide things from you¡±.

¡°If 바카라사이트 PI is travelling all 바카라사이트 time or wasting 바카라사이트ir intelligence on grant (application) writing, 바카라사이트re may be people in 바카라사이트ir lab who get a little careless,¡± he adds.

He accepts, however, that 바카라사이트re might be a good case for an isolated and ¡°really good¡± group in a university to expand beyond eight members.

He says 바카라사이트re is no reason in principle why a group needs more than one person. But ¡°바카라사이트 problem is 바카라사이트 funders inevitably judge people by 바카라사이트ir output and don¡¯t really make allowances¡± for small groups. The LMB gets judged every five years by 바카라사이트 MRC and ¡°that tends to require (that its labs have) a certain critical mass so you can churn (a high number of) papers out. We have always been ra바카라사이트r ambivalent about that.¡±