Gregory Winter

Gregory Winter
Born	Gregory Paul Winter 14 4, 1951
Birthplace	Leicester, Leicestershire, England
Nationality	British
Occupation	Molecular biologist, biochemist
Title	Master of Trinity College, Cambridge (2012–2019)
Employer	MRC Laboratory of Molecular Biology University of Cambridge
Known for	Humanisation of antibodies, phage display of antibodies, antibody engineering, Cambridge Antibody Technology, Domantis, Bicycle Therapeutics
Education	Royal Grammar School, Newcastle upon Tyne
Awards	Nobel Prize in Chemistry (2018) Royal Medal (2011) Knight Bachelor (2004)

Sir Gregory Paul Winter Template:Post-nominals (born 14 April 1951) is a British molecular biologist whose pioneering work on the therapeutic use of monoclonal antibodies has had a transformative effect on modern medicine. Based for nearly the entirety of his research career at the MRC Laboratory of Molecular Biology (LMB) in Cambridge, England, Winter developed techniques to humanise antibodies derived from mice, making them suitable for use in human therapeutics, and later devised methods using phage display to create fully human antibodies. These innovations addressed a fundamental obstacle in antibody-based medicine: the human immune system's rejection of mouse-derived antibodies. The first pharmaceutical developed using his methods, adalimumab, was approved in 2002 and is used to treat rheumatoid arthritis, psoriasis, and inflammatory bowel disease, among other conditions. For these contributions, Winter was awarded the 2018 Nobel Prize in Chemistry, shared with George P. Smith and Frances Arnold. Beyond his scientific achievements, Winter served as Master of Trinity College, Cambridge from 2012 to 2019 and has been instrumental in founding several biotechnology companies that translate antibody engineering research into clinical applications.

Early Life

Gregory Paul Winter was born on 14 April 1951 in Leicester, Leicestershire, England. He attended the Royal Grammar School, Newcastle upon Tyne, a selective grammar school in the northeast of England with a long tradition of academic excellence. Details of his family background and early childhood remain largely private, though his trajectory from Leicester to one of England's leading grammar schools and subsequently to Cambridge suggests an early aptitude for the sciences.

Winter's formative years coincided with a period of significant expansion in molecular biology, as researchers across Britain and the world were building upon the foundational discoveries of DNA structure and protein biochemistry that had emerged from Cambridge in the preceding decades. The MRC Laboratory of Molecular Biology, where Winter would spend the bulk of his career, had been established in 1962, and by the time of his education it had already produced multiple Nobel laureates. This intellectual environment would prove instrumental in shaping his subsequent career path.

Education

Winter pursued his undergraduate and postgraduate studies at Trinity College, Cambridge, one of the largest and most prestigious colleges of the University of Cambridge. He earned a Master of Arts degree from the university before undertaking doctoral research under the supervision of Brian S. Hartley. His doctoral thesis, completed in 1977, was entitled "The amino acid sequence of tryptophanyl tRNA synthetase from Bacillus stearothermophilus" and focused on the detailed characterisation of a key enzyme involved in protein synthesis in a thermophilic bacterium. This early work in protein chemistry and enzyme characterisation provided Winter with the rigorous technical foundation in protein structure and function that would underpin his later, more applied work on antibody engineering. His time at Trinity College also established a lifelong connection with the institution, to which he would return decades later as its Master.

Career

Early Research at the MRC Laboratory of Molecular Biology

Following the completion of his PhD in 1977, Winter joined the MRC Laboratory of Molecular Biology in Cambridge, where he would remain for the bulk of his scientific career. The LMB, funded by the Medical Research Council, had by that time established itself as one of the world's foremost centres for structural and molecular biology, having been the workplace of such figures as Francis Crick, James Watson, Max Perutz, John Kendrew, Frederick Sanger, and César Milstein. Winter's arrival at the LMB placed him at the nexus of groundbreaking research in protein and nucleic acid chemistry.

Winter initially worked on problems related to protein structure and engineering. Over time, his research interests gravitated toward immunoglobulin molecules — the antibodies produced by the immune system — and the possibility of engineering them for therapeutic purposes. This direction was influenced in part by the LMB's own legacy: it was at the LMB that César Milstein and Georges Köhler had developed the technique for producing monoclonal antibodies in 1975, work for which they received the 1984 Nobel Prize in Physiology or Medicine. However, these monoclonal antibodies were produced using mouse cells, and when administered to human patients, the human immune system frequently mounted an immune response against the foreign mouse proteins, severely limiting their clinical utility.

Humanisation of Antibodies

In 1986, Winter and his colleagues developed a technique to "humanise" mouse antibodies — that is, to replace most of the mouse antibody protein sequence with human sequences while retaining the specific antigen-binding regions (known as complementarity-determining regions, or CDRs) from the original mouse antibody. This approach dramatically reduced the immunogenicity of therapeutic antibodies in human patients, as the human immune system recognised the bulk of the antibody molecule as self rather than foreign. Only the small CDR loops, which are responsible for binding to the target molecule, remained of mouse origin.

This technique, known as CDR grafting or antibody humanisation, represented a major conceptual and practical breakthrough. It opened the door to the development of antibody-based drugs that could be administered to patients with far fewer adverse immune reactions. The humanisation approach became a cornerstone of the rapidly growing field of antibody therapeutics and formed the basis for the development of numerous drugs that would subsequently enter clinical use.

Phage Display of Antibodies

Building on the humanisation work, Winter made his most celebrated contribution by applying phage display technology to the creation of fully human antibodies, eliminating the need for mouse-derived components entirely.

Phage display, a technique originally developed by George P. Smith in 1985 for displaying peptides on the surface of bacteriophages (viruses that infect bacteria), was adapted by Winter to display antibody fragments on the surface of phage particles. By creating vast libraries of phage, each displaying a different antibody fragment on its surface, Winter and his team could screen billions of antibody variants simultaneously to identify those that bound most effectively to a given target molecule. This process of selection mimicked natural evolution in a test tube, allowing researchers to "evolve" antibodies with desired binding properties without the involvement of any animal immune system.

The use of phage display to generate fully human antibodies was a transformative advance. It not only avoided the immunogenicity problems associated with mouse or partially mouse antibodies, but also allowed for the rapid identification and optimisation of antibody therapeutics against virtually any molecular target. The first major pharmaceutical to emerge from this technology was adalimumab (marketed as Humira), which targets tumour necrosis factor alpha (TNF-α) and was approved by the U.S. Food and Drug Administration in 2002 for the treatment of rheumatoid arthritis. Adalimumab subsequently received approval for use in psoriasis, inflammatory bowel disease, and several other autoimmune conditions, and became one of the best-selling drugs in pharmaceutical history.

Leadership Roles at the LMB

In parallel with his research, Winter assumed a series of leadership positions at the MRC Laboratory of Molecular Biology. He served as Head of the Division of Protein and Nucleic Acids Chemistry from 1994 to 2006. From 2006 to 2011, he held the post of Deputy Director of the LMB, and he served as acting Director from 2007 to 2008. He was also Deputy Director of the MRC Centre for Protein Engineering from 1990 until its closure in 2010.

These administrative roles placed Winter at the centre of strategic decision-making at one of the world's leading molecular biology research institutes, and he played a role in shaping the direction of the LMB's research programme during a period of significant growth in the application of structural biology and protein engineering to medicine.

Biotechnology Ventures

Winter has been notable among academic scientists for his active involvement in translating research findings into commercial biotechnology enterprises. He co-founded Cambridge Antibody Technology (CAT), which played a central role in the development of adalimumab using the phage display technology Winter had pioneered. Cambridge Antibody Technology was subsequently acquired by AstraZeneca in 2006.

Winter also co-founded Domantis, a company focused on the development of domain antibodies — small, single-domain antibody fragments that retain the binding specificity of full antibodies but offer advantages in terms of size, stability, and manufacturing. Domantis was acquired by GlaxoSmithKline in 2006.

A further venture, Bicycle Therapeutics, was co-founded by Winter and is based on a novel class of therapeutic molecules called bicyclic peptides. These constrained peptide molecules combine some of the advantages of small-molecule drugs (such as tissue penetration) with the specificity of antibodies.

Winter has served in advisory capacities for several other biotechnology and pharmaceutical companies. He has been listed as a scientific advisor to F-star, a biopharmaceutical company focused on bispecific antibodies, and has been associated with other companies including Heptares Therapeutics and Covagen.

Master of Trinity College, Cambridge

On 2 October 2012, Winter was appointed Master of Trinity College, Cambridge, succeeding Martin Rees, Baron Rees of Ludlow. The Mastership of Trinity is one of the most distinguished positions in British academic life; the appointment is formally made by the Crown on the advice of the Prime Minister. Winter served in this role until 2019, when he was succeeded by Dame Sally Davies.

During his tenure as Master, Winter continued to be active in the scientific community and in promoting the translation of basic research into practical applications. His appointment to this prestigious role reflected both his scientific eminence and his broader contributions to the University of Cambridge and to public life.

Personal Life

Winter has maintained a relatively private personal life throughout his career. He is a Fellow of Trinity College, Cambridge, with which he has been associated since his undergraduate years. He is known to reside in Cambridge, where the LMB and the University of Cambridge are located.

In a 2025 interview with Nanyang Technological University in Singapore, Winter discussed his scientific career, including the role of failure and persistence in research, and the importance of ideas that endure beyond individual experiments. In a separate interview at the same institution, he reflected on the broader implications of antibody engineering for medicine, framing his work in the context of unlocking therapeutic possibilities from the natural mechanisms of the immune system.

Recognition

Nobel Prize in Chemistry

On 3 October 2018, the Royal Swedish Academy of Sciences announced that Winter had been awarded one half of the 2018 Nobel Prize in Chemistry, shared with George P. Smith, "for the phage display of peptides and antibodies." The other half of the prize was awarded to Frances Arnold "for the directed evolution of enzymes." The Nobel Committee recognised that Winter had used phage display to direct the evolution of antibodies with the aim of producing new pharmaceuticals, noting that the first drug based on this method — adalimumab — had been approved in 2002.

The award was reported extensively in the scientific and general press. Chemical & Engineering News described the trio as being recognised "for harnessing evolution to identify new enzymes and binding proteins." The law firm Goodwin, which had professional connections to Winter's commercial enterprises, noted that the Nobel Prize recognised Winter "for revolutionizing both chemistry and the development of new pharmaceuticals."

Other Honours

Winter was elected a Fellow of the Royal Society (FRS), one of the highest honours in British science. In 2011, the Royal Society awarded him the Royal Medal, one of its most prestigious awards, for his work on therapeutic antibodies.

Winter was appointed a Commander of the Order of the British Empire (CBE) and was subsequently knighted as a Knight Bachelor in 2004, entitling him to the style "Sir." He is also a Fellow of the Academy of Medical Sciences (FMedSci).

He has served as a member of the advisory council of the Campaign for Science and Engineering in the United Kingdom, reflecting his commitment to science policy and advocacy.

Legacy

Gregory Winter's contributions to molecular biology and medicine have had a lasting impact that extends well beyond his individual scientific publications. The techniques he developed for humanising and fully humanising antibodies using phage display have become foundational methods in the pharmaceutical industry and have enabled the creation of an entire class of therapeutic drugs. Adalimumab, the first fully human antibody drug derived from phage display technology, became one of the highest-grossing pharmaceuticals in history and has been administered to millions of patients worldwide for conditions including rheumatoid arthritis, psoriasis, and Crohn's disease.

The broader impact of Winter's work is reflected in the dozens of antibody-based drugs that have subsequently been developed and approved using the principles and techniques he pioneered. Monoclonal antibody therapeutics now represent one of the fastest-growing segments of the pharmaceutical market and are used in the treatment of cancer, autoimmune diseases, infectious diseases, and other conditions. The ability to engineer antibodies with high specificity and low immunogenicity — capabilities that flow directly from Winter's innovations — has fundamentally altered the landscape of drug development.

Winter's career also exemplifies the translation of basic academic research into commercial and clinical applications. Through the founding of companies such as Cambridge Antibody Technology, Domantis, and Bicycle Therapeutics, he demonstrated a model for bridging the gap between laboratory discoveries and patient treatments. This model has been influential in shaping the culture of translational research at the MRC Laboratory of Molecular Biology and at the University of Cambridge more broadly.

His appointment as Master of Trinity College, Cambridge, placed him in a lineage of distinguished scientists and public figures who have led one of the world's most storied academic institutions. In his public engagements following the Nobel Prize, including appearances at institutions such as Nanyang Technological University in Singapore in 2025, Winter has continued to advocate for the importance of curiosity-driven research and the acceptance of failure as an integral part of the scientific process.