Professor Frank McCapra obituary
4 July 1934 – 21 April 2023
Frank McCapra was born and brought up in Glasgow and met his future wife Jean McLaughlin when both were chemistry students at the University of Glasgow. On graduation in 1956, he was awarded a Carnegie Scholarship and began research in Glasgow, moving to London with DHR (later Sir Derek) Barton. He completed his PhD at Imperial College London in 1959, working on the long-range effects of steroids, an aspect of conformational analysis, which was the subject for which Barton later shared the Nobel Prize in Chemistry in 1969.
The biochemist W. D. McElroy had obtained support to determine the chemical structure of luciferin, the light generating chemical of the firefly and a chemist was needed to complete this difficult and important task. Frank moved to the Biology Department at Johns Hopkins University to take up this challenge.
Only very small amounts of luciferin were available and the sole spectroscopic tool was a uv spectrometer, making the problem a challenging one. In the event, degradative work led Frank to suggest a sensible structure which he was able to prove unambiguously by total synthesis.
Although Frank's research interests also ranged over the fields of enzyme mechanism, biosynthesis and metabolism, photochemistry and medicinal chemistry, this early success, the first of many, led to his lifelong interest in chemiluminescence and bioluminescence. From Johns Hopkins, he moved to Glasgow on an ICI Fellowship followed by a move to the University of British Columbia in 1962 as Assistant Professor. He was promoted to Associate Professor there in 1965 and came to Sussex in 1966 as Reader in Chemistry. He was promoted to Professor in 1980.
Frank's arrival at Sussex coincided with the preliminary publication of a revolutionary theory showing how conservation of orbital symmetry controls the feasibility and stereochemical consequences of all concerted reactions. By applying this to a general mechanism of bioluminescence that he had proposed earlier he was able to show how an electronically excited state would arise from the reactions involved. This work was cited as a key example when the theory of conservation of orbital symmetry was published in full. He also suggested that the small group of atoms at the heart of his mechanism would provide a basis for a whole range of chemiluminescent reactions.
Experimental work by Frank's early Sussex group concentrated on light emission in luminescent organisms other than the firefly. Luminous bacteria, co-opted by many marine organisms for their own uses of light emission, were isolated and used in these studies. Light production in nature requires the natural cofactor ATP but, by preparing a synthetic analogue of a luciferin of the marine organism Cypridina and coupling it with a phenyl ester, the group were able to produce light chemically. Other work suggested how such light-emitting molecules could have evolved in nature and how they were assembled in the organism.
Frank received early recognition for his work in 1968 when he was awarded the Corday Morgan Medal and Prize by the Royal Society of Chemistry.
Frank's interest now moved to the use of chemiluminescence in medical diagnostics. His first patent, a chemiluminescent glucose assay, resulted from collaboration with Malcolm Topping and David Tutt at Sussex. This would have led to the first hand-held glucose monitor for the control of diabetes and the patent rights were obtained by the MRC in conjunction with the University. Neither, however, showed sufficient interest in commercialising it.
Use of radioactive iodine in immunoassays was widespread but by the 1970s it was recognised that a replacement was needed for this expensive and environmentally dangerous method. Chemiluminescence seemed well placed to provide an alternative and Frank commenced collaboration with a research group at The Welsh National School of Medicine who would provide the biochemical expertise. This collaboration led a new method of labelling proteins and antibodies with acridinium esters. The series of compounds produced were safe and produced light using the simplest of reagents. The sensitivity of the resultant test was well above what was available from any alternative using radioactive iodine.
Frank received many invitations to deliver lectures complete with demonstrations to universities and industrial companies in the UK and worldwide. He also appeared on popular science programmes in national media. Over the years he was Visiting Professor at Wisconsin, Harvard, Demokritas (Athens), West Indies, Geneva, Kings College London, and Brunel.
He was elected to the Society of Scholars of Johns Hopkins University in 1977, and in 1980 was invited to give a Royal Society Review Lecture, a Royal Institution Friday Discourse and a plenary lecture to the British Association for the Advancement of Science. Plenary lectures were also delivered at Gordon Conferences, Burgenstock conferences and IUPAC conferences. He was elected President of the Society of Bioluminescence and Chemiluminescence in 1997.
When two of Frank's former research students decided to start their own immunodiagnostic company, London Diagnostics, they invited Frank to be vice president and chief scientific officer. This led to a scientifically interesting but personally stressful period involving commuting between Sussex and Minneapolis. The company's first target was to correct a principal drawback to the use of acridinium esters in immunoassays. Twelve patents eventually appeared describing compounds which were superior in fact and conception to those produced by their competitors.
A further patent was obtained, based on Frank's idea to use a cascade of reactions involving photochemically generated singlet oxygen to achieve chemical amplification in addition to electronic amplification of the light emitted. One application of this was gene detection and, with the help of the School of Biological Sciences at Sussex, the c-Myc cancer gene from material derived from Burkitt lymphoma was detected at a level required for a generalised diagnostic test.
An interesting use of the company's assay for thyroid stimulating hormone came when President G.W. Bush suffered an apparent heart attack at Camp David. Bush suffered from hyperthyroidism and it was an attack of this which had mimicked a heart attack. The Walter Reed Hospital found that the immunoassay kit from London Diagnostics was the preferred diagnostic option.
London's portfolio of immunoassays was by this time impressive and included ferritin (for anaemia), prolactin, follicle stimulating hormone and luteinising hormone (for fertility monitoring), human chorionic gonadotropin (for pregnancy testing), immunoglobulin E (for allergy testing), and parathyroid hormone (for calcium levels and bone disease monitoring). This led to considerable takeover interest from a number of companies and eventually the Nichols Institute in California took over the company on condition that Frank agreed to act as consultant. This led to his appointment as Academic Associate for the Nichols Institute in 1992.
Frank's retirement from The University of Sussex in 1996 coincided with retirement from Nichols and so he was free to pursue his many other interests and hobbies. He played the clarinet in orchestras for many operas, operettas and musicals and was Chairman of The Seaford Music Society until a few years before his death.
He is survived by Jean and their children Alastair and Fiona and five grandchildren. Their son Neil predeceased him.
Douglas Young
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