A passport to Pimlico for streptococci

Acclaimed for his work in London in the first half of the 19th century, he has memorials that include a plaque on his home, a statue in Pimlico and a pub bearing his name in Belgravia. Pimlico’s Eccleston Square is representative of his work: a collection of handsome, five-storey, stuccoed houses laid out around a large private garden. It was built in the 1830s on what had previously been osier beds (where willows were grown for basket-making) on land in-filled with spoil excavated during the construction of St Katharine Docks a few miles downstream. At various times the Square has welcomed residents as notable and diverse as the Labour Party and the TUC at the time of the General Strike, Sir Winston Churchill, and the first man to fly over Mount Everest. 

Taking an appreciative stroll around the Square, an acute observer may notice that in its northeast corner, numbers 73 and 74 are followed (across the road) by 79, which abuts on to a post-war office block, currently shrouded in scaffolding and screens. Known perhaps only to the postman, this numerical discontinuity marks the tragic deaths of two of Britain’s leading microbiologists, one of whom played a key role in the foundation of molecular genetics. 
 
Shortly after midnight on 17 April 1941, 8 months into the Blitz, a parachute mine landed on number 75 Eccleston Square, destroying the house and severely damaging an adjoining former church that was being used as a refugee and homeless persons’ post, killing five people in all. Number 75 belonged to the family of Fred Griffith, who was killed along with his colleague William McDonald Scott and the resident housekeeper. Griffith’s niece, who was also staying at the time, survived. Griffith and Scott had worked together for some years in the Ministry of Health’s Pathological Laboratory, at Dudley House in Endell Street near Covent Garden. Prior to the war this was the only national reference laboratory in the country, principally concerned with typing haemolytic streptococci and salmonellae. By all accounts the laboratory was a rather basic affair on the third floor of a building otherwise occupied by the Post Office, comprising an office, a lab shared by Griffith and Scott, where they did all their own benchwork, and a media kitchen where two technicians worked. Both men were famously modest and reticent, Griffith allegedly once having to be forced into a taxi to go and present a paper at an international congress being held in London, but they excelled in these spartan conditions and were unfailingly generous to those who sought their help and advice. At the start of World War 2, Dudley House became part of the Emergency Public Health Laboratory Service (EPHLS) established to deal with the public health consequences of anticipated mass bombing and the possibility of germ warfare, and Scott and Griffith had both acquired additional responsibilities at EPHLS laboratories in Oxford and Cambridge, respectively. 
 
Fred Griffith graduated in medicine from Liverpool in 1901 and had worked with his elder brother, (Arthur) Stanley Griffith, on the connection between bovine and human TB for the Royal Commission on Tuberculosis before joining the Local Government Board of the Ministry of Health in 1911. Later, at Dudley House, he focused particularly on the biology and epidemiology of the pathogenic streptococci. From this, in 1928, he published a 46-page paper in the Journal of Hygiene entitled ‘The Significance of Pneumococcal Types’ describing his work on the serotypes of streptococci causing lobar pneumonia. It was known that virulence of the pneumococci was associated with encapsulated strains, designated S (smooth) to describe their colonial appearance. Strains that produced granular colonies, termed R (rough), lacked the capsule that conferred protection against phagocytosis and were avirulent. Griffith showed that R strains could be produced from different types of S strain by growing them in the presence of the corresponding anti-serum. Crucially he also found that when mice were inoculated with dead cells of a virulent S type along with a viable culture of a non-virulent R strain, culturable S cells could later be isolated and, most significantly, these were of the same type as the injected dead S cells, not that from which the original R strain had been derived. The prevailing view was that serotypes were invariable, but this experiment had resulted in the acquisition of an inheritable change of character, termed ‘transformation’ by Griffith. His results were swiftly confirmed by others but it wasn’t until 1944 that Avery, MacLeod and McCarty at the Rockefeller Institute in New York identified the ‘transforming principle’ as DNA – a discovery that initiated investigations into the structure of DNA, the nature of gene replication, the genetic code and all that followed. Though Griffith left it to others to pursue his findings, there is no denying that his work was a milestone along the way to modern molecular biology. 
 
Remarkably Fred Griffith was not the only family member to play a role in the story of DNA. In the early 1950s, his nephew John, brother of the niece who survived the Eccleston Square bomb in 1941, was a theoretical chemist at Cambridge with an interest in gene replication. Following a discussion with Francis Crick, he calculated the forces between the flat surfaces of the bases in DNA to see whether attractive forces supported a scheme of base pairing and complementary replication rather than gene duplication. In the event, this was not the case and, as is now well known, hydrogen bonding is the force responsible. However, in a distinguished career, John Griffith did later anticipate the prion hypothesis of Prusiner by proposing that the causative agent of scrapie might be a protein capable of directing its own replication. In his 1967 Nature paper, noting the apparent challenge his theory posed to biology’s central dogma, he remarked, ‘… a protein agent would not necessarily be embarrassing, although it would be most interesting’. 
 
Further reading 

Williams G. Unravelling the Double Helix. London, UK: Weidenfeld & Nicholson, 2019.