30 Salisbury Rd., Banstead, Surrey, England SM7 2DR, U.K.
Norman Aldridge was fascinated by the interaction of chemicals with living systems. He firmly believed that understanding how and why chemicals exert their toxic effects was fundamental to safety evaluation for chemicals used in the workplace or environment. He loved research with "an insatiable urge to make sense of things," but also loved to apply the results to real-life issues. He encouraged his students, postdoctoral fellows, and visiting scientists from around the world to do the same.
From the age of 16, Norman worked as technician in a dye works. His interest in toxicology started during World War II at the U.K. Chemical Defence Establishment at Porton, where he worked as an assistant to the renowned physiologist Professor Sir Charles Lovatt-Evans on practical problems of protection against chemical warfare agents. He proved himself a careful investigator, and in part-time study, he obtained a B.Sc. in chemistry and physiology. Norman cited Lovatt-Evan's dictum, "I don't think it will work, but you try it," as a formative influence on his attitude, and subsequently it rubbed off onto many of his own students and colleagues. In 1947 John Barnes, who was also at Porton at that time, was appointed director of the Medical Research Council's new Toxicology Unit located at Carshalton, Surrey. Barnes' remit was broad: "Do something" to help face health problems that might arise as the postwar chemical industry burgeoned. He recruited Norman as the unit's first scientific staff member. Over the next 40 years, Norman worked on the mechanism of toxicity of chemicals, including beryllium, organophosphorous compounds, acrylamide, organotin and organolead compounds, and pyrethroid insecticides. He drew visitors from all over the world but never built an "empire" preferring to train, encourage, and liberate his students.
In his early work, Aldridge established much of the basic enzymology on the interaction of organophosphorus esters with esterases. He classified these into A, B, or C esterases according to whether organophosphorus esters were hydrolyzed by them, were inhibited, or did not interact either way. With Elsa Reiner, Aldridge worked on the interaction of carbamate esters with acetylcholinesterase. Together they wrote a textbook entitled Interaction of Esterases with Esters of Organophosphorous and Carbamic Acids (Elsevier, North Holland, 1972), which is still a standard text. Aldridge initiated the search for the esterase that was thought to be associated with peripheral neuropathy caused by certain organophosphorus esters. He supported and encouraged Martin Johnson in his studies, which led to the discovery of what is now called "neuropathy target esterase."
In the 1950s he turned his attention to the toxicity of organotin and organolead compounds, the stimulus being an unfortunate poisoning that occurred in France when more than 100 people were treated for boils with a poultice containing triethyltin. From this event research developed over many years, which led to a wider understanding of the interaction of di- and trisubstituted tin and lead compounds with mitochondria and the process of oxidative phosphorylation. These chemicals are selectively toxic to the central nervous system and in collaboration with Alwyn Brown, Aldridge was the first to show that trimethyltin produces selective neuronal cell death in the hippocampus, in contrast to triethyltin, which produces edema in the myelin sheath.
Selective biological responses such as the above provided the stimulus for many of Aldridge`s investigations, and his scientific attitude is captured in his book entitled Mechanisms and Concepts in Toxicology (Taylor and Francis, 1996).
Throughout his career Norman persisted in laboratory work and revelled in the data generated by his students, visiting scientists, and colleagues, especially the anomalous findings that did not fit the current theory. He did not tolerate loose thinking and always had probing questions and suggestions on how to further test the data to lead to a clearer understanding of the findings. His terse questions "Why?" and "How?" jolted many a woolly thinker into more self-critical mode!
In 1966 he was appointed head of the Biochemical Mechanisms Section in the Medical Research Council Toxicology Unit, a post he held until he retired in 1985; he was also deputy director for his last 10 years. Following his retirement he took up a position as Professor of Biochemical Toxicology at the University of Surrey, where he actively contributed to the teaching of toxicology to postgraduate students. He received many awards. He was the founder Chairman of British Toxicology Society, first recipient of the John Barnes award of the Society, and was the first honorary member of the Society. Both the European Societies of Toxicology (EUROTOX) and the American Society of Toxicology bestowed upon him their Merit Award in recognition of his contribution to the science of toxicology. In 1977 Queen Elizabeth II awarded him the Order of the British Empire for his services to toxicology. He was active internationally in toxicology as a member and then as secretary-general of the International Union of Toxicology. Norman was keen to promote European collaboration and the exchange of students in toxicology. As a member and then chairman of the European Science Foundation programme of Grants in Toxicology, he was able to stimulate such interactions.
During his career Aldridge's advice was sought both nationally and internationally on issues related to toxicology. His interest in tackling real issues meant he was an advisor in many of the major chemical disasters over the last four decades, such as the contamination of cooking oils in Morocco with tri-ortho-cresyl phosphate, the toxic oil epidemic in Spain, and the pesticide plant explosion in Bhopal, India. He played an active role as the Director of the World Health Organization collaborating laboratory, based at Carshalton, in the poisoning incident with malathion, when several thousand malaria control sprayers in Pakistan became ill and five died. He conducted a series of studies which showed that malathion upon storage under hot and humid conditions degraded to form isomalathion. He further showed that this impurity was a good inhibitor of carboxylesterase enzymes in the liver, which in healthy persons readily degrades any malathion that may enter the body during normal working conditions. This basic work led to changes in the manufacturing and storage procedures for malathion and other pesticides to prevent this type of event occurring again. Until shortly before his death in June 1996 after a brief illness, he was advising on the problem of postevent identification of signs in a patient of a transient neurotoxinthe notorious "Case of the Poisoned Professor" in New Zealand; he successfully advocated use of a mass spectrometric biomonitoring method of detection of exposure to acrylamide developed by colleagues in the Toxicology Unit. He fertilized the field of toxicology worldwide with a passion for understanding molecular mechanisms that will never be erased from the discipline. It is fitting that the British Toxicology Society has recently established Norman Aldredge Travelling Fellowships to support international visits enabling young scientists to widen their experience of research in toxicology.
NOTES
1 To whom correspondence should be addressed.