The pioneering, brilliant, passionate and often controversial public health research scientist Professor Ephraim Anderson - known to his colleagues as "Andy" - who has died aged 94, was a former director of the Enteric Reference Laboratory at Colindale, north London. His warnings during the 1960s and 1970s of an emerging worldwide danger from multiple drug-resistance in bacteria eventually changed the views of doctors and governments.
A master of laboratory techniques, he had, by 1960, taken optical microscopy into new realms in microbiology. This he did by using ultra-violet fluorescence to visualise the tiny dots of genetic material in bacteriophages (bacterial viruses), whose diameter is barely 1/20th of a micron and which, according to routine resolution theory, are far too small to be seen. This achievement, creating a low-cost laboratory technique employing ordinary optics for the investigation of viruses, was revealed in an elegant paper, Observation of Virus Growth with Aminoacrinides, at London University during the ninth symposium of the Society of General Microbiology in 1959.
This important work by Anderson and his group was promptly denounced as "impossible" by their peers - predominantly by the Nobel laureate Salvador Luria, an influential expert on phages, who had delivered the keynote paper and dominated debate at the meeting. Electron microscopy had, by this time, revealed the true and miniscule dimensions of the phages, which hitherto had been regarded as unfilterable and invisible. Luria confused the wavelength-based limits of resolution of light micro- scopy with the limits of visibility; his declaration that Anderson's micrographs were spurious was technically wrong and unjustified. It was, however, widely accepted and damaging.
To Anderson's embitterment, although the basis for fluorescence microscopy was already established - and had been reviewed in his paper - his pioneering micrographs were greeted with scepticism. Nevertheless, he continued to develop fluorescence techniques and produced the first micrographs of phages multiplying within and bursting from bacteria. Paradoxically, because of its ability to "visualise the optically invisible", fluorescence microscopy rapidly became a standard technique in many other research fields.
Sadly, his achievements were not formally acknowledged until 1997, two decades after his retirement, when one of his 1961 micrographs showing phages bursting from the typhoid organism they had killed was reproduced on the cover of the Royal Microscopical Society's monthly journal, Microscopy. The journal's editorial belatedly reminded its readers that they all stood on the shoulders of such giants. An international expert on typhoid bacteria (the salmonella group), on which he had worked during the second world war, Anderson inevitably focused on phage-types because these identify bacterial strains and serve as an aid in the investigation of outbreaks.
Phages infect their host bacteria in several ways and may kill their hosts or transfer genetic material. By the late 1950s, Anderson, perhaps more than others in this field, was probing the public health significance of the genetic information being transferred. Drug-resistant bacteria had been identified first in Japan and then in Britain, where, significantly, Dr Naomi Datta showed in 1962-63 that structures with some similarity to phages can also transfer drug-resistance genes. These structures, now termed plasmids, can transfer from cell to cell. The plasmid transfer of antibiotic resistance quickly became the focus of Anderson's career.
Working with samples from outbreaks of enteric (intestinal) infection (then principally involving salmonella typhimurium) sent to the Central Public Health Laboratory, also in Colindale, Anderson identified patterns of multiple drug resistance so specific that they were outbreak markers which could be used as a means of tracking sources. To the fury of the drug companies and many farmers, he also showed that selective pressures imposed by low-dose antibiotics in animal feeding stuffs, used to increase livestock weight-gain and profitability, were forcing multiple drug resistance development in livestock enteric bacteria.
Threateningly, the genes endowing these patterns could be readily transferred by plasmids to organisms of importance in human disease. The central problem was that the antibiotics then used in animal husbandry were also crucial components of the armoury against human disease. Anderson demonstrated in the laboratory that genetic factors endowing resistance to major drugs used against human disease could be transferred by plasmids from minor pathogens, such as salmonella typhi-murium - a common cause of scouring (diarrhoea) in livestock and of food poisoning diarrhoea in humans - to lethal human pathogens, such as the typhoid organism itself. Anderson's definitive book on the drug resistance problem in the typhoid group, The World Problem of Salmonellosis (1964), marked a watershed in modern medicine. He argued that unless antibiotics were protected, medicine might lose its new "miracle drugs" and find itself back with the problems of the 1930s. Although a pathogen nicknamed "hospital staph" (now called MRSA) and extremely resistant to a wide range of antibiotics was already emerging in medical wards, Anderson's work and arguments came under fierce attack, primarily from drug companies and most frequently outside Britain.
At home the problem was taken on board by the government. The 1969 Swann Report on the use of antibiotics in animal feeding stuffs - to which Anderson was a senior adviser - banned, or put tight controls on, this use of all antibiotics of value in human medicine. Other countries were slower to react because bacterial drug-resistance was still regarded as a transient phenomenon controllable by drug change or withdrawal. By the 1990s, however, Anderson's predictions were emerging as worldwide realities and once again becoming a focus of scientific interest.
Anderson worked his associates hard, never suffered fools gladly and had a great gift for rubbing folk up the wrong way. That he was brusque and, on occasions, downright rude was perhaps because he had to fight for everything, even when right.
Born of Estonian-Jewish immigrants in a working-class area of Newcastle upon Tyne, and brought up during the hard years of the first world war, Anderson revealed his extraordinary gifts while at school at Rutherford College, won a scholarship to King's College medical school, Newcastle (then part of Durham University) and graduated when only 22, having swept up all the major prizes on the way. He emerged into the depressed early 1930s, keen to enter medical research and obviously cut out for it. But there were few posts to be had - and he was Jewish, which meant at the time being relegated to the bottom of the list.
After five years in general practice and working as a hospital physician, in 1939 he joined the Royal Medical Corps and spent five years tracing typhoid carriers and other sources of outbreaks in Cairo. Blessed with a gift for languages, he spoke fluent Arabic and ultimately headed his own field investigation team, which went into Iran and elsewhere to trace individuals who had been employed by the British army and identified as carriers, but had made a run for home instead of accepting treatment.
It was at this time, after a military academic course in pathology and bacteriology, that Anderson decided that his future lay in bacterial research and public health. Immediately after the war he spent a year as registrar in bacteriology at the Royal Postgraduate Medical School, joined Arthur Felix at the Lister Institute of Preventive Medicine, London, to study typhoid phage types and, in 1947, went to the Enteric Reference Laboratory, becoming director in 1954. From then until 1978, he was also director of the International Reference Laboratory for Enteric Phage Typing and, from 1960 to 1978, director of the WHO Collaborating Centre on Drug Resistance in Enterobacteria, both at Colindale. From 1968 to 1978, he chaired the international committee on enteric phage typing.
Elected a fellow of the Royal Society in 1968, Anderson gave invited lectures at the Harvard school of public health in 1972. During the 1980s, he worked as a locum in various microbiology laboratories. His 1959 marriage to Carol Thompson ended in divorce, and he is survived by three sons.
John Threlfall, director, Health Protection Agency laboratory of enteric pathogens, writes: Working with Andy Anderson was akin to driving a car without springs across a lava field - frightening, stimulating, sometimes frustrating, but something that shaped for the better the careers of individuals who survived. I joined his team in 1969 as a young postdoctoral scientist, when speculation about the use of antibiotics in animal husbandry had resulted in the Swann report, and his work on transferable drug resistance was receiving international acclaim.
I soon learnt a scientific maxim that has guided me, and many others, throughout their careers - never believe a result without repeating the experiment at least five times, but then let the world know about it.
Andy's work on resistance led to conflict, some of which was of his own making but some of which came from deliberate attempts by scientific peers and by industrial interests to undermine his conclusions. Of particular note in his later years at Colindale were his long-term work with Betty Hobbs on the basis of phage type change in strains of salmonella typhi responsible for the 1964 Aberdeen typhoid outbreak, and his studies on the genetic basis of drug resistance in the typhoid bacillus, which are continuing to this day.
Andy was a hard taskmaster, and some who could not cope with his abrasive and perfectionist approach fell by the wayside. But his inherent kindness came out whenever people had a personal problem, and in the years following his retirement he was always ready to give advice if called upon.
His talents outside science ranged from music, history, politics, travel and languages to the manufacturer of perfume - which he attempted, somewhat unsuccessfully, on several occasions in rather antiquated bottles in one of the laboratories. He was a scientist, who, in his own words, was "a seeker after truth which will never be attained without strife and sacrifice".
· Ephraim Saul 'Andy' Anderson, bacteriologist, born October 28 1911; died March 14 2006
· This obituary has been revised since Anthony Tucker's death in 1998
