Profiles in Toxicology

Abstract

John M. Barnes, the first director of the Toxicology Research Unit of the British Medical Council, was educated as a physician and spent his early years at the Sir William Dunn School of Pathology, University of Oxford. One day in 1938—as he himself related the story to me and my wife, Christine, in 1966 during a relaxed evening in a Swiss mountain resort—he was approached by a colleague who had developed what looked to be a most promising drug. Before treating people, however, the investigator thought that some toxicity evaluation was in order, and so he asked Barnes to do a few rudimentary tests. Barnes took the compound, injected it intraperitoneally into three mice, found them alive and well the next morning, and reported his findings as “your drug seems not to be toxic.” He then was offered to participate in further evaluations of the drug, but declined because, as he told me, he did not really believe in miracle drugs. The investigator who had approached him was Howard Florey, the drug was penicillin, and as Barnes admitted somewhat ruefully, with his disbelief in miracle drugs, he simply had talked himself out of a Nobel Prize. In 1942, Barnes joined the British Defense Research Establishment in Porton. A paper describing some of his research at the time deserves to be mentioned. (Barnes eventually would publish around 120 papers, half of which were original research and reviews, the other half matters concerning the safe use of chemicals and the hazards they present to man). This particular paper coming out of Porton, “The development of anthrax following the administration of spores by inhalation” (Barnes, 1947) would not have raised much interest a few months ago, but now certainly has some new actuality. Some of the conclusions seem not to fit with current perceptions of the disease and its threat to mankind: “Evidence obtained during the carrying out of the spore count on the lungs of exposed animals (rabbits, guinea pigs and mice) suggest that the anthrax spores find the lung a very uncomfortable medium in which to germinate” and “Much higher minimum lethal doses of anthrax spores are necessary to produce infection by inhalation than by subcutaneous injection.” In 1947, the Medical Research Council established the Toxicology Research Unit, charged with experimental investigations of toxicological problems, with special reference to industrial hazards. Barnes was appointed its first director, a post he held until his untimely death in 1975. Other members were F. A. Denz, V. H. Parker, and W. N. Aldridge, eventually a winner of the Society of Toxicology Merit Award (Johnson, 2001). The first scientific problem studied in the unit was the toxicity of beryllium (Aldridge et al., 1949). During his entire career at the Medical Research Council, Barnes continued to maintain a high interest in beryllium, particularly its immunogenic properties, and was actually to some extent chagrined that research on beryllium toxicity mostly dealt with biochemical mechanisms of liver cell death rather than to address what seemed to be the real problem, pulmonary disease. Other early research efforts focused on dinitro-ortho-cresol (Parker et al., 1951), research that later led to some fundamental studies on the uncoupling of oxidative phosphorylation, and on the toxicity of new organic phosphorus compounds that were being developed as promising pesticides (Aldridge and Barnes, 1952). After the unit moved to Carshalton, Barnes became instrumental in developing and maintaining an excellent research climate. He was very encouraging toward young people and fully supported their growth as truly independent investigators. He cared deeply for the quality of science that was conducted in the unit, but he also saw to it that the results of fundamental research were used for practical purposes wherever possible. Although he gave much encouragement to what might be called “mechanistic” research these days, he was truly a biologist and genuinely committed to pathology. He made several unexpected findings in his research and recognized their broader implications: delayed skin sensitivity caused by beryllium in guinea pigs, single-dose carcinogenesis by nitrosamines, behavioral changes caused by trimethyltin, and two types of poisoning caused by pyrethroid pesticides. Beginning in the 1950s, Barnes had become a very much sought-after consultant for the World Health Organization, particularly in regard to the worldwide use of pesticides. He was firmly convinced that pesticides, responsibly used, would benefit mankind by improving food production and would not constitute an undue health hazard, particularly not at the low levels found as food residues. He believed that research eventually would enable toxicologists to deal with the problem of 1 For correspondence via fax: (530) 752-5300. E-mail: hrwitschi@ ucdavis.edu. TOXICOLOGICAL SCIENCES 68, 267–269 (2002) Copyright © 2002 by the Society of Toxicology