I have recently finished reading the book The Gene: An Intimate History authored by Siddhartha Mukherjee. This was his second book after The Emperor of All Maladies: a biography of cancer. Mukherjee is very good at explaining complex biological terms in simple metaphors. In The Gene he showcased it again with the compelling story about the history of solving DNA puzzle. I wonder how much amount of scientific journals he have studied to compose an astonishing popular science book like this. This book helped me to understand deeply about genes and the way we unfolded DNA through these years. Genetics is always an interesting topic to discuss as it is going to decide the future of Sapiens.


 

The concept of heredity was itself a very old one, we knew it since ancient times, but it was recorded into mainstream research only when a 34 year old physics teacher in 1856, conducted experiments on plant hybridisation. Widely referred as the Father of Modern Genetics, Gregor Mendel, an enthusiast in gardening, began experimenting on different varieties of plants by cross pollinating them to record the traits in the next generation. He found that the hereditary information carried to the successive offspring was independent and indivisible even though the alleles were sometimes dominant or recessive. But this profound work of Mendel was widely neglected till three decades.

It was in the beginning of 20th century, Mendel’s work was rediscovered again by Hugo de Vries who reproduced the same results. In 1905, Mendel’s units of heredity were given a name called “gene(s)” by William Johannsen. Later in 1910, Thomas Morgan discovered that genes were physically linked to each other on chromosomes. He brought up the idea of cross over where the gene can swap places from paternal chromosome to maternal chromosome or vice versa to produce mixed traits. But the question about the physical and chemical nature of gene remains unresolved for a decade until some surprising discoveries by Griffith and Muller.

Frederick Griffith was the first scientist to discover the process of horizontal exchange of genes, a type of gene transformation which involves swapping of genes (best example is bacteria which can exchange genes with a neighbour bacteria, but mammals cannot exhibit this transformation as they transmit genetic information through reproduction only). By this mechanism, Griffith demonstrated that the gene has to be made of matter, mostly, a chemical molecule. Hermann Muller in 1920, confirmed this idea by his experiments on flies, producing a mutation in their genes through the exposure of radiation. This idea of chemical nature of gene sparked a huge awakening for biochemists who had later broken cells apart to reveal their chemical constituents which led them to broaden their knowledge on proteins and nucleic acids.

By the early 1920s, Nucleic acid was known to be existed in two forms- De-oxyribose nucleic acid (DNA) and ribose nucleic acid (RNA). Both were long chains made of four bases (A, G, C, T in DNA and A, C, G, U in RNA), strung together along a string like chain or backbone, with ‘four bases protruded out form the backbone’ (which later proved to be the other way). Beyond these details, nothing was known about the structure or function of them. But in 1940s, through his rigorous experiments, Oswald Avery found that the DNA was itself the carrier of genetic information. This remarkable discovery led biochemists to shift their focus on the structure of DNA, particularly Maurice Wilkins, whose studies along with his colleague Rosalind Franklin in 1950, produced first clear X-ray images of DNA. He collaborated with two young researches, James Watson and Francis Crick to construct three dimensional models of DNA. In 1953, with further research inputs, Watson and Crick finally demonstrated the correct model of DNA with a double helix structure of nucleotide strands having bases turned inside. Watson and Crick along with Wilkins were awarded Noble prize for these extraordinary contributions.

The revelation of the structure of DNA raised even more fundamental questions: What was the genetic code? How did the four bases of DNA determine the physical traits? In the later years, researchers found that DNA (say, a set of code: ACT-GAC-CAC-GTG- ) provide instructions to build RNA and RNA provide instructions to build proteins, which perform vide variety of cellular functions. Genes (codes) even make proteins to regulate and replicate genes itself. Alteration in the sequence of DNA (mutation) may change the structure of protein and hence its function. Even the recombination of DNA (swapping between paternal and maternal chromosomes) is also a kind of mutation. By the time of mid-1980s, hundreds of disease linked genes like diabetes, hypertension, infertility, obesity were mapped in DNA, but the technology was lacking to find the exact location of these disease linked sequences in the vast human genome.

During 1970s, research on DNA sequencing was extensively carried on, most importantly, Fredrick Sanger, a two time Noble prize winner, developed a chain termination method to sequence DNA and successfully sequenced entire genome of a virus which contains 5000 base pairs. But Sanger method was incapable of sequencing vast human genome which contains 3 billion base pairs. Instead, shotgun method was later developed based on Sanger method to sequence long DNA strands. This in fact marked the beginnings of sequencing entire human DNA through prestigious Human Genome Project, which ran from 1990 to 2001. [As the samples were collected from various donors, the genome from HGP would be a combined mosaic of anonymous individuals.] By the completion of HGP, researches were able to sequence 92% of Human DNA with a 99.99% accuracy. It was indeed, the complete blueprint of human species available to us till dateIt contains almost 3.2 billion base pairs, with 20,687 genes, encrusting the information of our anatomy, instructions to build proteins and functions, our evolutionary history and even our future.

Post genome, solving the puzzle of genes gave rise to new ideas in research. How about modifying the genetic mutations ? How about introducing the “right genes” ? which could cure gene based diseases like sickle cell anaemia, schizophrenia and cancer. These questions resulted in the research of gene therapy i.e introducing normal genes in cells in place of defective genes to correct genetic disorders. It is even possible to diagnose (genetic diagnosis) heredity illnesses at embryonic stage and alter them (genetic alteration). But this embarked huge ethical issues since the prenatal diagnosis from genetic perspective can increase the rate of termination of pregnancies. Although genetic therapy methods are quite operational in medicine to modify specific non reproductive cells (like blood, brain or muscle cell), new technologies like genomic editing and genetic surgery can modify genes of an embryo itself through embryonic stem cells. This can permanently bring the alteration in human genome i.e the traces of genetic diseases can be completely eliminated in the next offspring.

What these research outputs in genetics suggests? Are we moving towards a human society with “no suffering” by editing our own genes ? Are we going to produce our future generations with “super intelligence”? Are we becoming our own “gods” ? We don’t have answers for these now. It may even take the other turn also. From the beginning itself, technology seems like a double edged sword. Our deep understanding of nuclear physics enacted us to produce nuclear power to supply energy needs and even nuclear bombs to end humanity. Internet revolution has connected the whole world together and even introduced insecurity, frauds, crimes and psychological worries. What’s the fate of genetic engineering then ?


 

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