Three Indian Nobel Prize winners and their remarkable contribution to medical science

1. Ronald Ross
2. Har Gobind Khorana
3. Venkatraman Ramakrishnan
4. References

Let’s imagine we lived in a world where we lacked the scientific knowledge that we have today. Imagine breaking your leg, but not knowing that one could use X-rays to examine what was happening inside. What if you started developing a terrible fever with chills and a headache, but had no clue that it was actually a little mosquito that had transmitted malaria causing bugs into your body. Picture a diabetes patient with uncontrollable blood sugar levels, but having no access to insulin.

It would have been a scary world indeed, and for the longest time, we humans lived in such a world. In fact, it is only in the recent centuries that scientific observations have helped solve some of humanity’s most fundamental problems. The Nobel Prize, which has been awarded since 1901 recognises such critical scientific observations.

Established by the Swedish chemist - Alfred Nobel, the Nobel Prize is awarded each year to distinguished people for their work in the fields of physics, chemistry, medicine, literature, peace and economics. Alfred Nobel believed that people are capable of improving the society by means of knowledge, science and humanism. He hence decided to reward the discoveries that greatly benefited mankind.

With a long list of Nobel laureates, here in this article we focus on three Nobel Prize winners of Indian origin who have made significant contributions specifically to the field of medicine and chemistry.

Ronald Ross

Ronald Ross was born in India in the year 1857 to Sir C.C.G. Ross, a general in the English army. As a young boy he wished to be a poet, novelist or a mathematician, but like many parents of the time, his father wished for him to be a doctor. He hence started his journey to become a doctor by studying medicine in London, soon after which he joined the Indian Medical Service. It was here that his interest in malaria peaked, as he wished to understand how the disease spread from person to person. He experimentally proved that mosquitoes played a key role in the spread of malaria, and this eventually won him the Nobel Prize in Physiology or Medicine in the year 1902.

After his work in India, Ross eventually moved to England and worked for decades to come in the field of tropical medicine. His main interest throughout his journey was the prevention of malaria in countries across the world, including India, West Africa and Greece (Rajakumar and Weisse, 2007).

Ronald Ross’ research in brief

Malaria was a mysterious disease in the past. Nobody seemed to understand how it spread from one person to another. In fact, in ancient times, it was even believed that malaria was carried by vapours. As a fresh medical graduate, Ronald Ross decided to test the hypothesis that mosquitoes may act as agents in the transmission of malaria from person to person.

To this end, he bred 1000s of mosquitoes and fed them on patients infected with malaria. He then dissected the mosquitoes one by one to see if he could find the same malaria causing parasite found in the patients, in any of the mosquitoes. On one lucky day in Secunderabad, while dissecting a specific brown coloured mosquito (Anopheles sps.), he finally spotted the malaria parasite. This observation successfully proved that malaria spread from person to person, through mosquito bites (Ross, 2003).

His research laid the foundation to our understanding of malaria today and has helped us device important therapies and vaccines against the disease. Scientists are now also in the process of creating genetically modified mosquitoes, which have a lowered ability to spread the malaria parasite (Hoermann et al., 2022).

Har Gobind Khorana

Har Gobind Khorana was born in Raipur, in the Punjab province of what is now Pakistan and then India, in 1922. Being one of the most literate children in his village, he pursued his bachelors and master’s degree in chemistry from the University of Punjab. He then moved to the University of Liverpool in the UK to pursue a PhD. It was, however, during his post-doctoral research that he began to get interested in these unique molecules called nucleotides - the repeating units that make up our DNA.

Har Gobind Khorana’s research in brief

His interest in nucleotides took him to the University of British Columbia, where he started his own lab. Here, with the help of his colleagues, he artificially synthesised several nucleotides and related molecules. However, he soon moved to the University of Wisconsin, where he set his goal even higher. He aimed to artificially synthesise the gene (Sakmar, 2012).

Our genes are made up of long sequences of repeating nucleotides. Considering that we have just four nucleotides (A - Adenine, T - Thymine, G - Guanine and C - Cytosine), a gene can be synthesised by stringing together these nucleotides in different combinations. Khorana used this basic principle to chemically synthesise long nucleotide sequences. The ability to synthesise genes led him to take a deep dive into understanding the genetic code.

So what is the genetic code? The proteins in our body are made of a sequence of molecules called amino acids. We have a total of 20 amino acids, each of which is coded by a specific sequence of nucleotides in our gene. Khorana, with his ability to synthesise genes, was able to figure out that a unique sequence of three nucleotides coded for each of these amino acids. In other words, our genes are made up of triplet genetic codes, each triplet code coded for a specific amino acid. This discovery eventually won him the Nobel Prize in Physiology or Medicine in the year 1968, along with Robert W. Holley and Marshall W. Nirenberg (Khorana et al., 2012).

Understanding the genetic code laid the foundation for modern molecular biology. Among many things, it has made it possible for us to edit our genes using the CRISPR technology in order to treat genetic diseases. It has also enabled us to create modern mRNA vaccines, which have been successfully used against COVID-19.

Venkatraman Ramakrishnan

Venkatraman Ramakrishnan was born in Chidambaram, in Tamil Nadu, to parents who were both researchers. Having been brought up in a very scientific environment, Ramakrishnan went on to pursue a graduate program in physics and a PhD in biology. Soon after his PhD, he began his post-doctoral research in Yale University. Here, he started to explore certain specific proteinaceous structures present in our cells - the ribosomes.

Venkatraman Ramakrishnan’s research in brief

Ribosomes are very important organelles present in our cells, responsible for synthesising proteins. It is made of two subunits - a small and a large subunit. His main goal was to understand the 3D structure of the smaller subunit. His fascination with ribosomes led him to eventually take up a position in the Lab of Molecular Biology in Cambridge, where he aimed to use X-Ray crystallography to decipher the structure of ribosomes (Nair, 2011).

X-Ray crystallography uses X-Rays which are bombarded against crystallised ribosomes. This helps in obtaining the 3D picture of the ribosome. He and his team worked relentlessly for years, until they finally obtained a high resolution image of the smaller ribosomal subunit. His work led him to win the Nobel Prize in Chemistry in the year 2009, along with Thomas A. Steitz and Ada E. Yonath (Wimberly et al., 2002).

His work finally helped us understand how antibiotics (like tetracycline and streptomycin), which work by binding to ribosomes, actually function. It has also given us immense insight into antibiotic resistance and helped us come up with ways of overcoming it.

The three scientists mentioned in this article have indeed helped us understand some important fundamentals in human pathology and biology. However, it might also be worthwhile to note that no research endeavour can be fully attributed to just one individual. In truth, it takes thousands of scientists and their constant efforts in putting together little pieces of the puzzle, which eventually leads to a significant discovery. The announcement of the Nobel Prize each year sheds much-needed light on such discoveries.

References

1. K. Rajakumar and M. Weisse, The Centennial Year of Ronald Ross' Epic Discovery of Malaria Transmission: An Essay and Tribute ♦ 895. Pediatric Research. 43, 155-155 (2007). 10.1203/00006450-199804001-00916. context
2. R. Ross, THE RÔLE OF THE MOSQUITO IN THE EVOLUTION OF THE MALARIAL PARASITE.. The Lancet. 152, 488-490 (2003). 10.1016/s0140-6736(01)81400-8. context
3. A. Hoermann et al., Gene drive mosquitoes can aid malaria elimination by retardingPlasmodiumsporogonic development. Science Advances. 8, (2022). 10.1126/sciadv.abo1733. context
4. T. Sakmar, Har Gobind Khorana (1922–2011): Pioneering Spirit. PLoS Biology. 10, e1001273 (2012). 10.1371/journal.pbio.1001273. context
5. H. Khorana et al., Polynucleotide Synthesis and the Genetic Code. Cold Spring Harbor Symposia on Quantitative Biology. 31, 39-49 (2012). 10.1101/sqb.1966.031.01.010. context
6. P. Nair, Profile of Venkatraman Ramakrishnan. Proceedings of the National Academy of Sciences. 108, 15676-15678 (2011). 10.1073/pnas.1113044108. context
7. B. Wimberly et al., Structure of the 30S ribosomal subunit. Nature. 407, 327-339 (2002). 10.1038/35030006. context