A 'Nobel Class' scientist

Print edition : April 28, 2001
G.N. Ramachandran, 1922-2001. P. BALARAM S. RAMASESHAN

Based on an editorial that appears in the April 25 issue of

published by arrangement.

OUR present-day understanding of the shapes of molecules and the connections between three-dimensionality and chemical function, or stereochemistry, rests to a large extent on the insights that Linus Pauling had between the 1930s and 1950s. The subject itself was born in Paris in the mid-19th century when Louis Pasteur serendipitously observed that the optically inactive form of tartaric acid was actually an equimolecular mixture of two optically active forms of the substance whose molecular structures were mirror images of each other. In a spectacular leap of intuition Pasteur recognised, a quarter of a century before Vant Hoff and Le Bel, that molecular structure and optical activity were related.

The first triumph of stereochemical thinking in biology was Pauling's realisation in 1948 that the 'non-integral alpha-helix' provided a spectacular solution to the search for folded polypeptide structures. The Watson-Crick double helical structure of DNA appeared in 1953 - clearly the pre-eminent example of a three-dimensional model that instantly reveals the basis for biological function.

UNIVERSITY OF MADRAS

In 1954, the structure of collagen, the most abundant protein of connective tissue, was described by G.N. Ramachandran and G. Kartha, working at the University of Madras. The structure, an intertwined three chain triple helix, elegantly accounted for the limited experimental data and provided a compelling rationale for the unique amino acid composition of collagen. It also marked the emergence of a new star in the fledgling field of structural molecular biology - G. N. Ramachandran.

G. N. Ramachandran's death in Chennai on April 7, marked the end of one of the most remarkable chapters of modern science in India. He was born in 1922 in Ernakulam, Kerala, and brought up there. He did his intermediate from the Maharaja's College, Ernakulam, where his father, G. Narayana Iyer, was the Principal. He did his B.Sc.(Hons) in Physics from St. Joseph's College, Tiruchi, in 1942 after which he moved to the Indian Institute of Science (IISc), Bangalore.

Ramachandran began his journey in science at the IISc as a student in the Electrical Engineering department. He realised very quickly that his interests lay in physics, a subject then overwhelmingly dominated in Bangalore by the presence of C.V. Raman. Inevitably, Ramachan-dran deserted electrical engineering and embraced physics; an event that appears to have been accompanied by Raman's soothing words to the Professor of Electrical Engineering: "I am admitting Ramachandran into my department as he is a bit too bright to be in yours." Ramachandran eventually became the most distinguished of Raman's students.

In Bangalore he first submitted a thesis entitled "Optics of Heterogeneous Media" for an M.Sc. degree of the University of Madras and later in 1947 a doctoral thesis, which contained some of the earliest applications of X-ray diffraction to the study of crystal perfection. He spent two years in Cambridge University, obtained a Ph.D. degree working with W.A. Wooster and returned to Bangalore in 1949. There he began an independent career as an Assistant Professor of physics, working in the X-ray diffraction laboratory that he was instrumental in building as a student.

But he did not stay there long. Madras University beckoned with a professorship and the position of Head of the Department of Physics. Ramachandran moved to Madras when he was just 30, to begin an extraordinary burst of scientific activity. In Madras he flourished under the benign and supportive influence of an enlightened Vice-Chancellor, A. Laksh-manaswamy Mudaliar. It was a relationship reminiscent of that between Asutosh Mukherjee and C. V. Raman in Calcutta.

J.D. Bernal visited Madras in 1952, and in a casual conversation suggested that the structural proposals for collagen were unsatisfactory. The Central Leather Research Institute was virtually next door to Ramachandran's laboratory. He soon had a sample and X-ray diffraction photographs.

The triple helix emerged in two papers in Nature in 1954 and 1955, introducing the coiled coil concept - a fundamental advance in the understanding of polypeptide structures. But in a sharp critique, Francis Crick, fresh from his DNA success, together with Alexander Rich argued that the Madras structure was "stereochemically unsatisfactory".

Out of the brewing collagen controversy was to emerge what is undoubtedly Ramachandran's finest contribution to structural biology. Spurred by the criticism of unacceptably short interatomic contacts in his collagen structure, he set out to investigate the criteria for describing stereochemically acceptable structures for polypeptide chains. Using the simple hard sphere model for atoms and driven by the insight that each residue in a polypeptide chain is allowed only two degrees of torsional freedom, Rama-chandran, together with his colleagues C. Ramakrishnan and V. Sasisekharan, laid the foundations for the conformational analysis of polypeptide chains. Their seminal paper, published in the Journal of Molecular Biology in 1963, titled "Stereochemistry of polypeptide chain configurations", introduced the two-dimensional map which was to bear Ramachandran's name eventually. Today, for beginners in biochemistry protein structures are introduced with a discussion of the Ramachandran map, which also forms the cornerstone for many discussions of protein folding.

While polypeptide stereochemistry was a dominant theme in Ramachandran's career between the 1950s and 1970s, his sharp and incisive mind turned often to his first love, X-ray crystallography. Fourier Methods fascinated him and he authored along with colleague R. Srinivasan an influential book on Fourier Methods in Crystallography. Ramachandran's paper on a "A new method for the structure analysis of non-centrosymmetric crystals" was instrumental in promoting the use of anomalous scattering to solve the crystallographic phase problem.

In 1971, Ramachandran together with A.V. Lakshminarayanan published a key paper on three-dimensional image reconstruction, which was to have important applications in Computer Assisted Tomography.

Ramachandran had a remarkable ability to cut through unnecessary details and go straight to the heart of a problem. This quality, coupled with his formidable physical insights and mathematical skills, allowed him to make many important contributions in biophysics and crystallography. He was an excellent teacher and lecturer. His clear grasp of the fundamentals of a problem allowed him to convey to listeners the key elements of a scientific issue, shorn of complicating details.

RAMACHANDRAN was widely honoured in India and abroad for his work. In recognising his work most agencies in India honoured themselves and conferred a new lustre on the awards they instituted. Yet, a dispassionate analysis of his work will reveal that he did not, in large measure, get his due. The Government of India, undoubtedly advised by the scientific establishment, never found it fit to include him in the annual Republic Day honours list. This act of omission in no way diminished his stature; instead it forever dimmed the lustre of these awards in recognising scientific accomplishment. The Royal Society belatedly recognised Ramachandran in 1977, almost towards the end of his active scientific career and over two decades after his remarkable work on collagen.

Ramachandran was clearly a "Nobel Class" scientist, to borrow a phrase from Eugene Garfield. But his active career was all too brief by modern-day standards. For the last 20 years Ramachandran was not really visible internationally. This reminds us of one of the ironies of modern science: achievement alone is not enough, packaging and marketing play an important role. In India, where administrative positions are often considered a mark of scientific success, Ramachandran was essentially an "outsider" to the establishment. We have yet to learn that idiosyncratic personalities often make the most original contributions to science.

Ramachandran did all his work in India, following in the footsteps of his mentor C.V. Raman. In the 1960s and 1970s he did travel regularly to the United States, to the University of Chicago where he held a visiting professorship. In Madras, Ramachandran's work brought an unprecedented level of recognition to the university. Two international conferences he organised in 1963 and 1968 brought to Madras some of the most famous names in molecular biology and biophysics: Linus Pauling, Severo Ochoa, Maurice Wilkins, Stanford Moore, David Phillips, Ephraim Katchalski, Harold Scheraga, Paul Flory, Elkan Blout and John Schellman.

Ramachandran returned to Bangalore to set up the Molecular Biophysics Unit at the IISc in 1971. His move from Madras was catalysed by the deteriorating academic atmosphere of the university. Indeed, Ramachandran's two decades at Madras University clearly showed that the highest levels of research could be practised within our university system. His departure signalled an impending change. We have all watched with varying degrees of helplessness the steady decay of university science in India over the last three decades.

In Bangalore during the period between 1971 and 1979, Ramachandran fashioned a new department, which has grown into a major centre of structural biology.

AS in the case of many extraordinarily gifted individuals, Ramachandran often had an uneasy relationship with his surroundings. It was not easy for him to come to terms with mediocrity. Elevated to the position of the head of a university department at age 30, he grew to be isolated from his colleagues, rarely establishing the easy academic relationships that make science a pleasure. But even at the height of his career Ramachandran most enjoyed scientific discussion; unfortunately his surroundings could rarely rise to the levels he demanded.

His last years were troubled. A stroke and the steady onset of Parkinsonism curtailed his movements and activities. The loss of his wife Rajalakshmi, after 53 years of marriage, in 1998 was a blow. In many ways, when the end came it was indeed time to go. But Ramachandran has left behind a rich scientific legacy. His achievements will serve as a source of inspiration for generations to come. He was undoubtedly one of the most outstanding scientists of post-Independence India and a jewel in the crown of Indian science. For the authors, it was a very special privilege to have known him.

Ramachandran is survived by three children, two sons and a daughter, all of whom pursue science in different fields.

P. Balaram is Professor, Molecular Biophysics Unit, Indian Institute of Science, Bangalore; S. Ramaseshan is Distinguished Professor-Emeritus, Raman Research Institute, Bangalore.

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