https://www.nature.com/articles/d41586-024-02085-2 Skip to main content Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Advertisement Advertisement Nature * View all journals * Search * Log in * Explore content * About the journal * Publish with us * Subscribe * Sign up for alerts * RSS feed 1. nature 2. comment 3. article The strategy behind one of the most successful labs in the world Download PDF * COMMENT * 26 June 2024 The strategy behind one of the most successful labs in the world One UK institute has produced a dozen Nobel laureates and biomedical breakthroughs across the board. How does Cambridge's Laboratory of Molecular Biology do it? Our study found out. By * Luka Gebel^0, * Chander Velu^1 & * Antonio Vidal-Puig^2 1. Luka Gebel 1. Luka Gebel is a PhD candidate at King's College London and incoming assistant professor of strategy and entrepreneurship at the Global Business School for Health, University College London. View author publications You can also search for this author in PubMed Google Scholar 2. Chander Velu 1. Chander Velu is professor of innovation and economics at the Institute for Manufacturing, Department of Engineering, University of Cambridge, Cambridge, UK. View author publications You can also search for this author in PubMed Google Scholar 3. Antonio Vidal-Puig 1. Antonio Vidal-Puig is professor of molecular nutrition and metabolism at the Institute of Metabolic Science, University of Cambridge, Cambridge, UK. View author publications You can also search for this author in PubMed Google Scholar * Twitter * Facebook * Email John Kendrew with forest of model colour rods from the 1960s. Biochemist John Kendrew working on a structural model of a protein at the Laboratory of Molecular Biology in Cambridge, UK, in the 1960s. Credit: MRC Laboratory of Molecular Biology You have full access to this article via your institution. Download PDF Download PDF The Medical Research Council's Laboratory of Molecular Biology (LMB) in Cambridge, UK, is a world leader in basic biology research. The lab's list of breakthroughs is enviable, from the structure of DNA and proteins to genetic sequencing. Since its origins in the late 1940s, the institute -- currently with around 700 staff members -- has produced a dozen Nobel prizewinners, including DNA decipherers James Watson, Francis Crick and Fred Sanger. Four LMB scientists received their awards in the past 15 years: Venkatraman Ramakrishnan for determining the structure of ribosomes, Michael Levitt for computer models of chemical reactions, Richard Henderson for cryo-electron microscopy (cryo-EM) and Gregory Winter for work on the evolution of antibodies (see Figure S1 in Supplementary information; SI). Between 2015 and 2019, more than one-third (36%) of the LMB's output was in the top 10% of the world's most-cited papers^1. What is the secret of the LMB's success? Many researchers and historians have pointed to its origins in the Cavendish Laboratory, the physics department of the University of Cambridge, UK, where researchers brought techniques such as X-ray crystallography to bear in the messy world of biology. Its pool of exceptional talent, coupled with generous and stable funding from the Medical Research Council (MRC), undoubtedly played a part. However, there is much more to it. None of these discoveries was serendipitous: the lab is organized in a way that increases the likelihood of discoveries (see 'New questions, new technologies'). To find out how, we conducted 12 interviews with senior LMB and external scientists to provide insights into the organization. We also analysed 60 years' worth of archival documents from the lab, including research publications, meeting minutes, external assessments and internal management reports (see SI for methods). New questions, new technologies The LMB's approach is to identify new and important scientific questions in uncrowded fields that require pioneering technologies to answer them. The lab develops that technology to open up the field; continual improvements bring more breakthroughs, which can be scaled up to enter markets. Here are three examples. DNA sequencing. In the 1940s and 1950s, biochemists Max Perutz and John Kendrew sought a way to discriminate between normal and pathological haemoglobins and myoglobin. The LMB developed molecular fingerprinting and chromatography technologies^11 that allowed various biological questions to be addressed, such as how genes are regulated or how molecular programming is involved in cell death. Protein and DNA sequencing also enabled the study of molecular mechanisms of viruses and organ development. Transferring these discoveries into clinical and industrial settings changed drug discovery from a process of screening compounds to one of active design. Antibodies. At the LMB in 1975, biologist George Kohler and biochemist Cesar Milstein discovered a method to isolate and reproduce individual (monoclonal) antibodies from the many proteins that the immune system makes. This breakthrough enabled the characterization of antibodies, and sparked inquiries into gene regulation and programmed cell death. Monoclonal antibodies now account for one-third of new treatments that reach the clinic. Cryogenic electron microscopy. The LMB has a long-standing history in the development of electron microscopy, with Aaron Klug's group using it in the 1960s to elucidate the structure of viruses. Cryo-EM visualizes atoms in biological molecules in 3D. It was developed on the back of three decades of the LMB's accumulated expertise in areas from optimizing cooling and vacuum technology to microscopy, computing-based imaging and electron detectors. The method has revolutionized protein research and many other areas. We identify the LMB's management model as the key -- it sets a culture with incentives and provides oversight to optimize the interplay between science and technology. By integrating high-risk basic science with innovative technology, the LMB facilitates a knowledge feedback loop that helps the institute to identify promising questions and continuously push scientific boundaries (see SI, quote 1). In the context of economics and management theory, the LMB behaves as a 'complex adaptive system'. Here, we outline our findings and encourage research organizations, funding bodies and policymakers to consider adopting a similarly holistic and coherent approach to managing basic scientific research. In short, they should prioritize long-term scientific goals and effectively manage scarce resources; foster economies of scale and scope by promoting complementarities between different areas of scientific research; and create value by establishing synergies and feedback between scientific questions and engineering-based technology solutions. Integrated management The LMB's management strategy prioritizes three elements -- culture, incentives and management oversight -- that sustain a feedback loop between science and technology development (see SI, Figure S2). Culture. The LMB sets a coherent culture by promoting scientific diversity among its staff, encouraging the exchange of knowledge and ideas and valuing scientific synergies between different areas of research. Senior managers view this culture as central to an evolutionary process in which a broad and diverse talent pool helps the organization to be flexible and to adapt and survive. Scientific discovery emerges from it in a sustainable but unpredictable way. Cesar Milstein viewing anautorad output at a machine. Cesar Milstein analysing DNA.Credit: MRC Laboratory of Molecular Biology The LMB recognizes the importance of having a defined, yet broad and open, institutional research direction. It encourages the recruitment of groups with diverse but aligned interests that are complementary (see SI quote 2). This approach has ensured that the LMB can achieve a critical mass of expertise in specific research areas. It enables economies of scale while retaining the flexibility to innovate by pioneering new avenues and emerging fields. It also recognizes that not every promising direction can be followed. Scientific diversity has been a trait from the start. Although the lab was founded by physicists and chemists, its researchers today include mathematicians, engineers and zoologists (see SI quote 3). Yet too much variety is to be avoided in case it dilutes the culture. Minutes of an executive committee meeting from 1997 reveal the reticence of lab heads to appoint purely clinical researchers on the grounds that this might alter the lab's culture and its focus (see SI quote 4). [d41586-024] We can make the UK a science superpower -- with a radical political manifesto A diverse portfolio of related and aligned themes makes it easier to share techniques and methods between projects and inspires programmes to aim at bolder goals (see SI quote 5). For example, the development of cryo-EM to examine macromolecules benefited both the structural-studies division and the neurobiology division, and led to a better understanding of molecular pathways in neurodegeneration. Incentives. The LMB uses an incentive structure to align the organization's culture with the goals of its people. Actively promoting shared values and common aims helps researchers to feel part of the LMB community and proud to belong to it, fostering long-term loyalty. "The LMB has always had a non-hierarchical structure -- one in which emphasis lies in the quality of the argument, rather than in the status of the proponent," a 2001 external review of the LMB noted (see SI quote 6). Unlike many labs, the LMB focuses on investing in and promoting junior members rather than bringing in external talent. This is reflected in the high standards of its junior scientific recruitment. Many of its Nobel prizewinners, including Richard Henderson and Gregory Winter, began their careers at the lab and were promoted internally. Prioritizing small teams also optimizes the sharing of technologies and budgets and incentivizes scientists from different fields to converge on the same projects. Although the LMB is structured in divisions, almost all career scientists have independent but aligned scientific programmes. This connectivity often leads to rapid and creative combinations of ideas between teams. It also allows for the sharing of failure and resilience to it, which is inevitable in high-risk, high-stakes innovative research (see SI quote 7). Daniela Rhodes discussing a project in her office at LMB in 2008. Structural biologist Daniela Rhodes studies chromatin structure and regulation at the LMB.Credit: MRC Laboratory of Molecular Biology LMB resources are allocated in ways that encourage innovative collaboration between internal teams and divisions. For example, limits are set for research groups to bid for external grants, because these tend to have short-term, results-oriented requirements that might not align with the LMB's longer-term ambitions. Furthermore, the LMB's director can flexibly allocate funds to promote innovative collaborations and initiatives. Recent examples include forays into synthetic biology (using engineering to develop or redesign biological systems) and connectomics (the study of the connections in the brain and nervous system). Management oversight. The LMB uses a management oversight system that resolves tensions between technology and science priorities, which would otherwise affect productivity. Technologists aim to develop and improve tools to match the best specifications for as many potential users as possible. Scientists help to define technology specifications that are based on their aims and data, which are usually on the cutting edge of existing capabilities. [d41586-024] Want to speed up scientific progress? First understand how science policy works Tensions are present in the differences between how technology developers and scientists speak, define problems, operate and organize their project milestones and risk assessments. Technologists often focus on developing solutions for relatively well-defined practical problems that are amenable to rigorous project-management techniques, whereas scientists tend to work on uncertain, ambiguous questions and problems that require flexibility in experimental processes and resource allocation^2. To address these issues, the LMB uses a mixture of interventions and a robust process for selecting which scientific questions it focuses on. For example, technology developers with distinct specialisms operate in a dedicated workshop unit to develop prototypes. Experienced principal investigators act as go-betweens, translating scientific terms into technical engineering requirements and vice versa. Decisions around scientific resources are delegated to the divisions; money for major technology development is allocated centrally through the lab's executive committee. Thus, the feedback loop between science and technology that facilitates innovation is enhanced (see SI quote 8). Long-term potential Because the LMB's strategy focuses on long-term, transformational goals rather than short-term incremental gains, its internal evaluation system for researchers is more concerned with the potential of the overall scientific programme^3 than with standard individual performance metrics, such as the number of journal publications and citations, personal impact factors, grant funding, awards and collaborations. Scientists must openly assess which questions hold the highest value according to the LMB's focus areas, and balance that with the cost of technology development and risks of failure while sustaining diversity in their research portfolio. To manage these competing demands, the LMB integrates internal expertise and external reviews. The quinquennial external review process by the MRC is a strategic approach to innovation that anticipates future trends and brings fairness to decision-making. In our interviews, managers articulated the importance of quinquennial reviews to inform and stress-test the scientific direction of the organization. These reviews include visits from a committee of reviewers who are aware of the lab's culture and who score a group leader's scientific productivity and originality on the basis of reports, internal reviews and interviews. Max Perutz operating an X-ray crystal machine. Biochemist Max Perutz preparing a sample for examination using X-ray crystallography.Credit: MRC Laboratory of Molecular Biology Individual labs are evaluated on the usual metrics, such as results from past research, but more emphasis is placed on the future outlook. As a result, a young investigator's potential and the impact of their research might result in tenure, even if they have a limited number of publications. Marks below a certain point mean the research group will be closed within a year. But this remains an exception so that the long-term nature of programmes is not lost. The review process also plays a crucial part in identifying emerging scientific trends and opportunities. For example, in 2005, the visiting review committee identified the need for a new animal facility that would highlight the potential of mammalian biology -- a concept that had not been prioritized previously (see SI quote 5). [d41586-024] US agency launches experiments to find innovative ways to fund research Indeed, the LMB generally declines projects that require scaling up technology and large physical spaces, in case they come to dominate the lab's work and space requirements beyond the financial income that the project can generate. In 1996, for example, the lab decided to forgo projects that involved scaling up its profitable protein and antibody engineering successes (see SI quote 9). The LMB could be seen as a high-quality incubator for early-stage innovative projects, with a high turnover of research projects. This turnover does not compromise the viability of the research, because the small group structure allows for flexibility of research projects and mobility of staff. The LMB focuses on projects until they become successful, fundable and scalable by having access to funding opportunities closer to later stages of scientific development and translational research. A complex adaptive system Although these rules govern the LMB, the outcomes are more than the sum of their parts. The organization's management strategy gives rise to emergent behaviours and deliverables that align with its long-term research goals. The management model has emerged from a set of actions taken by management over time that collectively result in a coherent approach to achieving the overall aim of the LMB^4. In management theory terms, the LMB is a complex adaptive system, similar to an ecosystem. A complex adaptive system is a self-organizing system with distinctive behaviour that emerges from interactions between its components in a manner that is usually not easy to predict^5. Components might include individuals and their activities; material parts, such as technologies; and the ideas generated from these interactions^6. Effective management of this complex adaptive system is fundamental to the LMB's success. Through continual adaptation and evolution, the LMB can generate new knowledge more effectively than most other institutions can. For example, the LMB helped to develop cryo-EM for application in the biological sciences through collaborative efforts involving scientists and engineers and the integration of software and advanced cooling techniques. Rather than one individual orchestrating and coordinating all the steps, this multidisciplinary team exhibited self-organization and iterative adjustments, bound by its shared culture. This allowed the emergence of new solutions, mirroring the adaptability seen in ecosystems. Lessons and challenges ahead In our view, the LMB system should be considered a framework for how funding is allocated to basic science more widely. Looking to the future, however, we see three challenges that the LMB and the life-sciences community will need to overcome. First, scientific questions in the basic biosciences are becoming more complex, requiring ever more sophisticated and expensive equipment^7. Developing such tools might be beyond the capability of one lab, and wider institutional collaborations will be required. The LMB building exterior in 2021, Cambridge, England. The Medical Research Council's Laboratory of Molecular Biology in 2021.Credit: MRC Laboratory of Molecular Biology Second, institutions dedicated to basic life sciences are increasingly urged by funders and society to transition quickly into clinical applications, which risks undermining the quality and competitive edge of their fundamental research^8. The gap between fundamental bioscience and clinical translation is notoriously hard to bridge^9 (see also Nature 453, 830-831; 2008). It is also high risk. In recent years, some funders have pulled out of basic bioscience. For example, more of the US National Institutes of Health's extramural funding over the past decade has gone to translational and applied research than to basic science (see Science 382, 863; 2023). Some highly reputable basic-science research institutions have suffered as a result and have even been dissolved, such as the Skirball Institute in New York City^10. However, it is crucial to resist the temptation of dismantling basic science research, considering the complexity and difficulty of re-establishing it. In response, a lab such as the LMB might enhance the translation of its discoveries by strengthening connections with the clinical academic sciences and private-sector industries. Leveraging strengths in the pharmaceutical industry -- in areas such as artificial intelligence and in silico modelling -- can bolster basic science without compromising a research lab's focus. The LMB's Blue Sky collaboration with the biopharmaceutical firm AstraZeneca is a step in this direction (see go.nature.com/3rnsvyu). Third, it is becoming increasingly challenging for basic science labs to recruit and retain the best scientific minds. Translational research institutes are proliferating globally. Biotechnology and pharma firms can pay higher salaries to leading researchers. And researchers might be put off by the large failure rates for high-risk projects in fundamental research, as well as by the difficulties of getting tenure in a competitive lab such as the LMB. As a first step, governments must recognize these issues and continue to fund high-quality, high-impact fundamental science discoveries. The use of effective research-management strategies such as the LMB's will make such investments a better bet, de-risking discovery for the long-term benefit of society. Nature 630, 813-816 (2024) doi: https://doi.org/10.1038/d41586-024-02085-2 References 1. MRC Laboratory of Molecular Biology. Quinquennial Review 2021 (MRC LMB, 2021). Google Scholar 2. Nightingale, P. Res. Policy 27, 689-709 (1998). Article Google Scholar 3. Tansey, E. M. & Catterall, P. P. Contemporary Record 9, 409-444 (1995). Article Google Scholar 4. Mintzberg, H. & Waters, J. A. Strat. Mgmt J. 6, 257-272 (1985). Article Google Scholar 5. Markose, S. M. Econ. J. 115, F159-F192 (2005). Article Google Scholar 6. Velu, C. Business Model Innovation: A Blueprint for Strategic Change (Cambridge Univ. Press, 2024). Google Scholar 7. Park, M., Leahey, E. & Funk, R. J. Nature 613, 138-144 (2023). Article PubMed Google Scholar 8. Kupferschmidt, K. Science 370, 392 (2020). Article PubMed Google Scholar 9. Spector, J. M., Harrison, R. S. & Fishman, M. C. Sci. Transl. Med. 10, eaaq1787 (2018). Article PubMed Google Scholar 10. Sfeir, A. et al. Cell 185, 755-758 (2022). Article PubMed Google Scholar 11. Perutz, M. F., Kendrew, J. C. & Watson, H. C. J. Mol. Biol. 13, 669-678 (1965). Article Google Scholar Download references Reprints and permissions Supplementary Information 1. Supplementary figures, methodology, quotes and acknowledgements Competing Interests The authors declare no competing interests. Related Articles * [d41586-024] We can make the UK a science superpower -- with a radical political manifesto * [d41586-024] Want to speed up scientific progress? First understand how science policy works * [d41586-024] US agency launches experiments to find innovative ways to fund research * [d41586-024] How to track the economic impact of public investments in AI * [d41586-024] How I run a virtual lab group that's collaborative, inclusive and productive * [d41586-024] How to set up your new lab space * [d41586-024] I was denied tenure -- how do I cope? Subjects * Research management * Lab life * Molecular biology * Scientific community Latest on: Research management What it means to be a successful male academic What it means to be a successful male academic Career Column 26 JUN 24 How I'm using AI tools to help universities maximize research impacts How I'm using AI tools to help universities maximize research impacts World View 26 JUN 24 Is science's dominant funding model broken? Is science's dominant funding model broken? Editorial 26 JUN 24 Lab life What it means to be a successful male academic What it means to be a successful male academic Career Column 26 JUN 24 Is science's dominant funding model broken? Is science's dominant funding model broken? Editorial 26 JUN 24 How researchers navigate a PhD later in life How researchers navigate a PhD later in life Career Feature 25 JUN 24 Molecular biology Mechanism for the initiation of spliceosome disassembly Article 26 JUN 24 Programmable RNA-guided enzymes for next-generation genome editing Programmable RNA-guided enzymes for next-generation genome editing News & Views 26 JUN 24 Bridge RNAs direct programmable recombination of target and donor DNA Bridge RNAs direct programmable recombination of target and donor DNA Article 26 JUN 24 Nature Careers Jobs * Research Postdoctoral Fellow - MD Houston, Texas (US) Baylor College of Medicine (BCM) [] * Assistant Professor (Tenure Track) of Biomolecular Engineering for Health The Department of Biosystems Science and Engineering (D-BSSE) (www.bsse.ethz.ch) at ETH Zurich invites applications for the above-mentioned position Zurich, Switzerland ETH Zurich [] * Suzhou Institute of Systems Medicine Seeking High-level Talents Full Professor, Associate Professor, Assistant Professor Suzhou, Jiangsu, China Suzhou Institute of Systems Medicine (ISM) [] * Faculty Positions in Westlake University Founded in 2018, Westlake University is a new type of non-profit research-oriented university in Hangzhou, China, supported by public a... Hangzhou, Zhejiang, China Westlake University [] * 2024-2025 Westlake Fellowship Applications Open A Quick Career Path from Fresh PhD to Faculty Hangzhou, Zhejiang (CN) Westlake University [] You have full access to this article via your institution. Download PDF Download PDF Related Articles * [d41586-024] We can make the UK a science superpower -- with a radical political manifesto * [d41586-024] Want to speed up scientific progress? First understand how science policy works * [d41586-024] US agency launches experiments to find innovative ways to fund research * [d41586-024] How to track the economic impact of public investments in AI * [d41586-024] How I run a virtual lab group that's collaborative, inclusive and productive * [d41586-024] How to set up your new lab space * [d41586-024] I was denied tenure -- how do I cope? Subjects * Research management * Lab life * Molecular biology * Scientific community Advertisement Sign up to Nature Briefing An essential round-up of science news, opinion and analysis, delivered to your inbox every weekday. Email address [ ] [ ] Yes! Sign me up to receive the daily Nature Briefing email. I agree my information will be processed in accordance with the Nature and Springer Nature Limited Privacy Policy. Sign up * Close Nature Briefing Sign up for the Nature Briefing newsletter -- what matters in science, free to your inbox daily. Email address [ ] Sign up [ ] I agree my information will be processed in accordance with the Nature and Springer Nature Limited Privacy Policy. Close Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing Explore content * Research articles * News * Opinion * Research Analysis * Careers * Books & Culture * Podcasts * Videos * Current issue * Browse issues * Collections * Subjects * Follow us on Facebook * Follow us on Twitter * Subscribe * Sign up for alerts * RSS feed About the journal * Journal Staff * About the Editors * Journal Information * Our publishing models * Editorial Values Statement * Journal Metrics * Awards * Contact * Editorial policies * History of Nature * Send a news tip Publish with us * For Authors * For Referees * Language editing services * Submit manuscript Search Search articles by subject, keyword or author [ ] Show results from [All journals] Search Advanced search Quick links * Explore articles by subject * Find a job * Guide to authors * Editorial policies Nature (Nature) ISSN 1476-4687 (online) ISSN 0028-0836 (print) nature.com sitemap About Nature Portfolio * About us * Press releases * Press office * Contact us Discover content * Journals A-Z * Articles by subject * protocols.io * Nature Index Publishing policies * Nature portfolio policies * Open access Author & Researcher services * Reprints & permissions * Research data * Language editing * Scientific editing * Nature Masterclasses * Research Solutions Libraries & institutions * Librarian service & tools * Librarian portal * Open research * Recommend to library Advertising & partnerships * Advertising * Partnerships & Services * Media kits * Branded content Professional development * Nature Careers * Nature Conferences Regional websites * Nature Africa * Nature China * Nature India * Nature Italy * Nature Japan * Nature Middle East * Privacy Policy * Use of cookies * Your privacy choices/Manage cookies * Legal notice * Accessibility statement * Terms & Conditions * Your US state privacy rights Springer Nature (c) 2024 Springer Nature Limited