John Kendrew’s legacy
“Without John Kendrew there would have been no EMBL”, wrote Ken Holmes in his memoir of the institute’s first Director-General. On the occasion of what would have been his 100th birthday, we take a look at the man who shaped the philosophy and spirit of the organisation
As World War II broke out, John Cowdery Kendrew had just graduated from the University of Cambridge with a degree in chemistry. Inspired by discussions with scientists J.D.Bernal and Linus Pauling, he decided to return to Cambridge to study the structure of proteins after the war. So began a life-long interest in the fields of protein crystallography and molecular biology.
Kendrew joined Max Perutz at the Cavendish laboratory to work on the problem of solving the molecular structure of two related proteins that transport and store oxygen – myoglobin and haemoglobin. A decade or so earlier, one of Bernal’s students, Dorothy Crowfoot (later Hodgkin), realised the potential of X-ray crystallography to determine the structure of molecules such as proteins. Crystallography describes the process by which, when shone at a protein in crystalline form, X-rays will be diffracted by the atoms in the crystal, producing distinct diffraction patterns. These can be interpreted to determine the atomic structure of the protein. Crowfoot was interested in insulin, but while she had shown that the crystals of insulin will diffract X-rays if kept wet, insulin is so large it proved too difficult to interpret the patterns at the time. Kendrew and Perutz were embarking on a journey to determine the structure of molecules much larger.
Crowfoot earned the Nobel Prize in Chemistry in 1964 for her work on structures of smaller molecules such as penicillin and vitamin B12, but it took until 1969 to solve the structure of insulin. Crowfoot and Bernal had also used a technique called isomorphous replacement to help solve the position of atoms in a protein. By soaking a protein crystal in heavy metal ions, some atoms of the protein in known positions will be replaced by the metal. By comparing these with unaltered crystals, the 3D atomic structure of the protein can be pieced together. Kendrew and Perutz refined this method successfully and it was a considerable breakthrough in their endeavour.
The beginnings of computing played an important role in working out what the enormous molecules of myoglobin and haemoglobin looked like.Converting diffraction patterns from these molecules into three dimensional shapes was extremely time-consuming to do by hand so Kendrew and collaborators wrote computer code to calculate maps of their proteins. Kendrew’s vision for the potential of modern computers had given them the breakthrough they needed, and kick started the field of computational biology. Their pioneering work earned Kendrew and Perutz the Nobel Prize in 1962.
Kendrew’s interest in emerging technologies later shaped the research profile of EMBL, and today embracing and developing technologies remains a characteristic of the institute. Protein crystallography and computer science at EMBL have grown into world-leading research fields.
Kendrew’s friend and collaborator Ken Holmes remembers Kendrew as “a convinced European who could communicate in four languages”. By the 1960s he was concerned about the growing number of European scientists moving to the States to pursue their careers. About the same time the physicists Leo Szilard and Victor Weisskopf had been having similar discussions and invited Kendrew and others to join them in September 1963 for talks. Although he was not alone in developing the idea of a European laboratory for molecular biology it was by all accounts Kendrew’s conviction, his diplomacy skills, and determination that drove the project from idea through to realisation many years later.
Kendrew’s main priority was to establish a European laboratory that would be able to achieve more than individual countries alone, but it soon became clear that a European organisation which would award fellowships and run training courses was a first step. The European Molecular Biology Organisation (EMBO) was established and invited scientists to join as members, successfully securing funding and gathering support from participating member countries. In 1969 Kendrew was elected Secretary-General of EMBO, and he continued to push the idea of a European laboratory.
Kendrew was well travelled and had a love for both the arts and sciences, moving freely between disciplines. His scientific career instilled in him a firm belief that interdisciplinary and international work was key for molecular biology research. In an article published in the journal Nature in 1968 entitled “EMBO and the Idea of a European Laboratory” Kendrew states, “the special feature of molecular biology is that it is highly inter-disciplinary. Effective research in this field demands the co-operation of many different disciplines and techniques, some biological, some chemical and some physical; and, more important, it demands the closest mutual interaction between people interested in the same problems but viewing them against diverse scientific backgrounds. It follows that a small, geographically isolated group is at a serious disadvantage compared with the large multi-disciplinary centre.” This is as true today as it ever was and it remains a key part of EMBL’s philosophy and culture, with scientists from many different disciplines working together. EMBL also promotes this spirit in schemes such as the EMBL Interdisciplinary Postdocs (EIPOD) initiative.
While EMBO got off to a good start, the “Laboratory project” as it became to be known, “had a lukewarm or even hostile reception.” In the 1968 Nature article, Kendrew’s conviction for his subject and frustration at not being able to progress faster with his plans come through in his writing. “To someone in the field like myself it seems so clear that the European laboratory could be one of the best in the world that it is really very hard to understand why some of one’s colleagues from other disciplines are so unenthusiastic….”
Slowly but surely, Kendrew’s persistence paid off. It was decided that the laboratory would focus on providing equipment and technologies too large for individual laboratories or countries. At the beginning of the 1970’s, Gerd Rosenbaum and Ken Holmes demonstrated the potential of intense X-rays produced by large synchrotrons for structural determination of biological molecules. Holmes suggested to Kendrew that this should be included in the laboratory proposal and the idea of an additional EMBL site in Hamburg on the site of the Deutsches Elektronensynchrotron (DESY) campus was agreed upon. “Later a second outstation at Grenoble was added for neutron diffraction” remembers Holmes. “The amended plan was submitted to the EMBO’s council in the autumn of 1970. John’s persistance (sic) and diplomacy was rewarded. Now there was enthusiasm for the laboratory.”
EMBL was established on 4 July 1974 and Kendrew became Director-General in January 1975. Now his work turned to building up the laboratory – from interior decorating to structuring the research of the lab. In many ways, he was ahead of the times. “Very importantly, a central cafeteria should function as a place for swapping ideas,” remembers Holmes. “Moreover, the organisational structure he foresaw for the EMBL was not unlike the very successful model of the Laboratory of Molecular Biology (in Cambridge which he’d also helped develop): three strong divisions representing instrumentation, structural studies and cell biology.”
These three divisions exist today and have flourished over the years, with key instrumental developments including detectors for synchrotron beamlines, as well as method developments such as cryo-electron microscopy by Jacques Dubochet’s team. Several major breakthroughs have been made in the field of cell biology too. “One very important article was by Ari Helenius and Kai Simons on how viruses get into cells” remembers Kendrew later. Kendrew was also far-sighted enough to look for new fields and methods to focus on. Against much advice, he decided to invest in synchrotron radiation, for example, which has gone on to have a large impact on the field of structural biology and protein crystallography.
The EMBL spirit
Although Kendrew initially intended to bring the great scientific minds of the time to EMBL, it soon became apparent the institute could not attract people away from long-term tenure track professorships. “We looked for excellence and promise” said Kendrew later. At EMBL, young group leaders found academic freedom and room to explore new ideas. The early days of EMBL began to look slightly different to the original plan. “Much of the strength turned out to be in establishing networks rather than monolithic ‘big science’,” writes Holmes.
Today EMBL’s network includes more than 7000 alumni, many of whom stay connected with the institute and play important roles in training, as ambassadors, and as mentors and advisors. Kendrew also recognised early on that there was a need for training that could not be supported by smaller labs or universities and knew it should be an important part of EMBL’s culture. 2017 marks 40 years of training at EMBL. From the first course on Electron Microscopy in 1977, the training programme has grown and expanded substantially, now encompassing near to 100 courses and conferences per year across all five sites.
Kendrew remained Director-General of EMBL until his retirement in 1982. He left a flourishing and growing laboratory which still bears his mark. In his memoir, Holmes included a quote from Piet Borst of the Netherlands Cancer Institute:
“The EMBL is a place where the major discoveries are being made, a breeding ground where talent can mature, a meeting place that vibrates with excitement….”
Sir John Cowdrey Kendrew died on the 23rd August 1997 at the age of 80.
The John Kendrew Young Scientist Award was established in 2007 in honour of Kendrew. It recognises excellence in science and science communication.