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P. Meera Khan (1935-1998)

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P. Meera Khan (1935-1998) © Indian Academy of Sciences P. Meera Khan (1935-1998) i Following a short hospitalization for liver cancer, Prof. Prof. Meera Khan, known to his friends and colleagues as Meera Khan, member of the editorial board of this journal, Meera, was born in Ambajipeta, Andhra Pradesh state, India, passed away on 1 April last year. He left behind his wife in 1935 and graduated from Andhra Medical College, Prabha, two sons and four grandchildren. Visakhapatnam, in 1959. During this period he had the By H.F.A. VASEN, The Netherlands Foundation for the Detection of Hereditary Tumours, Leiden University Medical Centre, Poortgebouw Zuid, Rijnsburgerweg 10, 2333 AA Leiden, The Netherlands; Department of Gastroenterology, Leiden University Medical Centre, Leiden, The Netherlands; Department of Endocrinology, University Hospital Utrecht, Utrecht, The Netherlands. Journal of Genetics, Vol. 78, No. 1, April 1999 63 H. E A. Vasen unique fortune to come into contact with J.B.S. Haldane, of ideas, unrestricted access to a personal library of books who was interested in establishing genetic studies on disease and periodicals, and his numerous thought-provoking resistance in human populations. In Meera Khan Haldane scientific and popular articles. The outcome of the study on saw someone with the interest and ability to set up such the frequency of consanguinity in Andhra Pradesh was investigations, and in 1959 convinced him to commence published in the Journal of Heredity (Dronamraju and research on the relationship between consanguinity and Meera Khan 1960). The publication was the first of more inherited diseases. For Meera this was the start of a 40-year than 250 scientific contributions made by Meera Khan over career in human genetics. the years. This career can be roughly divided into three periods, After completing the study, Haldane introduced Meera to with different lines of research. From 1959 until 1965 he Marcello Siniscalco, an Italian geneticist who was working conducted several studies in India and Italy under the on genetically determined abnormalities alleged to give pro- patronage of Haldane. In 1966 he joined the Department tection from malaria. Siniscalco had found that the of Human Genetics, State University of Leiden, The frequencies of thalassaemia and enzyme deficiencies were Netherlands. Over the following years, he developed new both high in the formerly malarial areas of Sardinia. He was methods for analysing the isoenzymes present in somatic interested in performing comparable studies in an area of cell hybrids. These analyses were to play a major role in gene India from where malaria had not yet been eradicated. In mapping. Then, around 1980, his interest shifted to cancer 1962, to learn the techniques, Meera worked with Siniscalco genetics. in Naples and in Sardinia. In the same period, he visited This article tries to summarize his scientific contributions London and had discussions with two of Haldane's former over the years. Information on the first period was derived colleagues, Harry Harris at King's College and L.S. Penrose mainly from an article written by Meera himself, entitled at the Galton Laboratory. Both visits made a lasting impres- 'Some of my reminiscences of Prof. J.B.S. Haldane' (Meera sion on Meera, and greatly influenced his further scientific Khan 1993). Information on the second period was collected career. In 1963 the study suggested by Siniscalco was from his thesis (Meera Khan 1971) and his extensive carried out on the western bank of the fiver Godavari at scientific publications. I had the opportunity to collaborate Polavaram, India, where epidemics of Plasmodium falci- with Meera Khan during the most recent period. Part of the parum malaria had occurred. Meera, an officer of the Andhra information on this period is thus drawn from personal Pradesh Government Medical Services, was in charge of the experience; the remaining is derived from his colleagues and expedition at the Indian end, while Siniscalco was respon- Ph.D. students. sible for planning and directing the project. Unfortunately, in the same period, Haldane was diagnosed with rectal cancer and was therefore unable to join the expedition. He 1959-1965: The first steps in genetic research died of metastatic disease on 1 December 1964. Haldane's under J.B.S. Haldane death marked the end of the first period in Meera Khan's career, which had been so strongly characterized by the In 1959 Meera Khan was in the final year of his medical special relationship between them. In 'Some of my remini- training at Andhra Medical College in Visakhapatnam in scences of Haldane' Meera wrote that it was difficult for Andhra Pradesh when he attended a lecture by J.B.S. him to ascertain whether he was Haldane's student, disciple, Haldane, who had migrated to India in the 1950s. Haldane associate, colleague, collaborator, prot~g& or beneficiary. was well known in India both for his scientific articles and However, it is clear that Haldane's lessons had laid the basis for his popular writings in the newspaper The Hindu. Shortly for his further career. Haldane had taught the members of after the lecture, one of Haldane's coworkers discussed his Human Genetics Team 'to search for, and discover new various research programmes with Meera Khan. One of the scientific truths and to spread old ones'. In addition, he topics they discussed was the widespread practice of consan- reminded them regularly of the principles of moral courage, guineous marriages in Andhra Pradesh and the relevance of scientific honesty, and intellectual integrity. In the following this to inherited diseases. Haldane wanted to conduct a study section it will become clear how Haldane's principles had on this subject and proposed to involve Meera, who at that also become those of Meera. time was a full-time house surgeon at the King George Hospital (Visakhapatnam). Motivated by the clinical relev- ance of the project and inspired by Haldane's enthusiasm, 1965-1980: The early period in Leiden: somatic cell Meera agreed to perform the study in his spare time. From hybridization and gene mapping then on he became part of Haldane's so-called Human Genetics Team in India. He regularly visited Haldane at In 1965 Meera joined the Department of Human Genetics at home (Calcutta) to discuss the progress of the study. Each the State University of Leiden, The Netherlands, which had of these visits was--as Meera himself put it--like a new just then been established by Marcello Siniscalco. Under the chapter in his growing book of learning. The facilities for leadership of Siniscalco, he started studies using the study provided by Haldane included a continuous flow technique of somatic cell hybridization. The successful 64 Journal of Genetics, Vol. 78, No. 1, April 1999 Meera Khan demonstration of the occurrence of mammalian somatic cell number of enzyme markers in human and animal cells hybridization in in vitro cultures in the early sixties had given grown in vitro and in the somatic hybrids between them. In biologists new food for thought. Usually, an attempt to graft particular, an electrophoretic-autoradiographic procedure a piece of tissue from an individual of one of the higher was devised for characterization of the enzyme HGPRT organisms to another of the same species results in rejection. in the human-mouse cell hybrid. The distinction between As a consequence, the finding (reported by Barski et al. in murine and human HGPRT has been of critical importance 1960) of fusion between two types of mouse tumour cells in deciding whether the exceptional hybrid clones identified astonished biologists. Barski's work was soon confirmed, were the result of backmutation at the murine HGPRT and then extended to other established cell lines derived locus or breakage of the human X chromosome. Meera from diverse strains of laboratory mice. The phenomenon of studied a large series of hybrid clones derived from the chromosomal loss and segregation first observed in mouse- fusion of HGPRT-deficient mouse cells with human diploid mouse somatic cell hybrids had encouraged optimism. In cells for their G6PD patterns. He found that about half of the meantime, Littlefield (1964) had developed a model for them were exceptional in the sense that they possessed only isolating pure hybrid cells by selecting against biochemi- murine G6PD, even though their HGPRT was of the human cally marked parental cells by means of a selective medium. type. These findings suggested mitotic separation of the Ephrussi and Weiss (1965) obtained a cross between cells two human X-linked genes, and set the basis for studies on derived from mouse and rat, announcing for the first time X-chromosome mapping at the level of somatic hybrid that the interspecific barrier evidently does not apply to the cells. In addition, a large series of human-mouse and fusion of somatic cells in vitro, and that cells from the most human - Chinese hamster hybrid clones were studied for diverse species can be induced to fuse and to form viable their HGPRT, G6PD and PGK patterns in order to prove somatic hybrids. Harris and Watkins (1965) were able to the hypothesis of X linkage of the human PGK locus increase the efficiency of fusion considerably by using UV- suggested by one human pedigree segregating for a deficient inactivated Sendai virus as a fusing agent. The combined mutant at this locus. The results of Meera's studies gave use of this fusion technique and the Littlefield selective conviffcing support to the X linkage of human PGK, and procedure had been of great significance for the advance- demonstrated the versatility of somatic cell hybrids for the ment of studies of somatic cell hybrids. Weiss and Green mapping of the human X chromosome. The results of these opened a new approach to the mapping of human chromo- and related studies were the subjects of a series of papers somes by producing human-mouse somatic cell hybrids in published in Nature and other journals, and were presented 1967.
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