Chemistry Nobel Prize 2020

Prof Homendra Naorem *

Chemistry Nobel Prize 2020
For
Development of New Precision Genetic Scissors for Custom Design of Genes and Rewriting the Code of Life

While the entire world is under lockdown to somehow eschew from the clutches of the obnoxious Corona virus, the Royal Swedish Academy of Sciences, undeterred by the Covid-19 pandemic, announced in clock like regularity that the Chemistry Nobel Prize for 2020 will jointly be awarded to Prof. Emmanuelle Charpentier (51) and Prof. Jennifer A. Doudna (56) for the development of genetic scissors and methods for genome editing.

Nobel prizes are always unique but this year’s Chemistry Nobel Prize is even more unique - it is for the first time in the history of Nobel Prize that the Prize has gone to a ‘women only team’ that too at relatively much younger age, in the their fifties to be precise! In fact, very few women have received Nobel Prize in Chemistry and Charpentier and Doudna would be the 6th and 7th women to do so – but the number still is in single digit.

Within the first five years of institution of the Nobel Prize, Marie Curie became the first woman to win the Nobel Prize – she won not only once but twice: 1905 - Physics and 1911 - Chemistry. Curie's daughter, Irène Joliot-Curie, also won the Chemistry Nobel Prize in 1935 – a Nobel heredity? A total of 57 women have so far received the Nobel Prize in different disciplines – 4 women have won in Physics, 12 in Physiology/medicine, 15 in Literature, 17 in Peace, 2 in Economics and, of course, 7 in Chemistry.

While everyone was busy with the statistics of women who have excelled to the Nobel, it is ironical that Prof. Charpentier boldly identified herself ‘a scientist’ first and the gender later. She is of the opinion that their (the women team) winning the prize would send a positive message to young girls to follow the path of science showing that women in science can also have an impact in the scientific research.

Reacting on the cliché that no matter what women do, their work will not be recognized the way it would be if they were a man, Prof. Doudna said, ‘I think this prize refutes that. It makes a strong statement that women can do science, women can do chemistry, and that great science is recognized and honored’. When this year’s Nobel in Physiology/ Medicine or Economics have gone to men only team, no one comes out with any gender based statistics – so much for the gender equality and stout patriarchs’ crusade for gender neutrality!

Rapid advancements and understanding of matter at molecular and atomic levels have long bestowed chemists the edge over other fellow scientists with the expertise of maneuvering matter at atomic and molecular level enabling them to tailor-make or synthesize any material with desired properties infused into them, ranging from macro to nano scales.

Chemistry in fact is the only branch of science where hundreds and thousands of new molecules with unique properties are created and added annually in the universe. Chemists are arguably the best bet to custom-design and tailor-make any material of choice including biomolecules or bio-materials.

One of the glaring examples of uncanny tailoring or synthetic skills of chemists is that of Prof G Mehta who once synthesized fancy classes of organic compounds which could not be readily named even after the rules like IUPAC - these class of compounds were, as proposed by Prof Mehta, named as garudane (1,4-Bishomo [6] prismane) which may have its garudene or garudyne analogs like alkane, alkene or alkyne! He could synthesize such garudanes with precise cage-opening size to use them as molecular waste basket for immobilizing unwanted molecules of a given size (e.g. JCS, Farad Trans-2, 1989) taking synthesis to newer heights.

But it was when Chemistry began to penetrate the domain of life sciences and the discovery of the helical structure of DNA by Crick and Watson long ago that scientists began to realize that life processes at the very bottom is all but Chemistry, laying the foundation for molecular biology save the perplexing issue of mind and soul phenomena. In fact, Chemists have found the field of life sciences a fecund arena for exploratory research paved with large number of Nobel Prizes – many have been unearthed and many more still remain yet to be! A good portion of the Nobel Prizes in chemistry has indeed come from studies related to life processes.

If your parent or any grandparent had diabetic, anemia or some diseases like that, you always run a fair chance of inheriting the same or, in other words, it is in your heredity or genes! Genes are made of DNA (deoxyribonucleic acid) which is the hereditary material in all living cells including human cells. Study of the genes or heredity is known as Genetics and it is about how and why physical characteristics such as the color of the skin or the eye are passed on from one generation to another, how diseases and conditions run in families.

From Chemistry view points, DNA is a molecule composed of two polynucleotide chains that coil around each other to form a double helix and it carries genetic instructions an organism need to develop, live and reproduce. An organism's complete set of DNA is known as the genome of the organism and it is unique for every organism - there are roughly 3 billion DNA base pairs, or letters in the human genome.

Gene theory provides the basis for understanding how genes enable parents to transmit traits to their offspring and they are so unique that the parental linkages may be identified through the patterns in DNA profiling – perhaps the time is not far when the present ‘Aadhaar’ will be replaced by one based on DNA profile! Every individual organism is supposed to have the same set of gene or DNA and any changes (mutation) in the genes cause aberrations in the organism.

Recent reports indicate that random mistakes in DNA, not heredity or environmental factors, account for two-thirds of cancer mutations in cells. Nature has its own intricate ways of mutating the genes which when happened is manifested as abnormalities. We do not understand why and how nature mutates the genes. Can we intervene or stop such mutations?

More importantly, can the genes or the DNA in an organism be manipulated in a desirable manner to cause a particular effect? That has remained a million dollar question! Chemistry Nobel Prize 2020 has thrown open the possible ways in which humans can not only imitate but perhaps better the process of mutation in genes in living organism!

While working with the common harmful bacteria - Streptococcus pyogenes associated with pharyngitis, tonsillitis and scarlet fever, etc. - Prof. Charpentier discovered a previously unknown molecule, tracrRNA, which is part of bacteria’s immune system, identified as CRISPR/Cas (Clustered Regularly Interspaced Short Palindromic Repeats are pieces of DNA that the bacteria snip off from the viruses that once attacked them) that can help in recognizing threatening viruses and in disarming them by snipping off parts of their (virus) DNA like genetic scissors.

After publishing her results in Nature in 2011, Charpentier began a collaborative research with Prof. Doudna, an experienced biochemist with vast knowledge of RNA, towards recreating the bacteria's genetic scissors. They eventually succeeded within a short span of time in recreating the bacteria’s genetic scissors in a test tube and even simplified the scissors’ molecular components to make them easier to reprogram and use.

With the new technique the natural scissors which could recognize only the DNA from viruses may be so tuned as to control-cut or edit any DNA molecule at a predetermined site and replaced by a newly edited one – rewriting the code of life! The new CRISPR/Cas9, the so called genetic scissor, they developed allows for deleting, altering, adding or, in short, editing the genomic code in living beings like a text file in a computer is edited using an editor like Microsoft (MS) word or Page maker!

With this new genetic scissor tool, researchers can change the DNA of animals, plants and microorganisms with extremely high precision. Imagine the enormous power of this tool and the huge impact - both wanted and unwanted – it will have on the life processes. If code of life can be edited, it will empower the mankind to direct and even change the course of life.

The discovery of the CRISPR/Cas9 genetic scissors in 2012 has already brought significant gains in crop resilience by altering their genetic code to better withstand drought and pests in plants. On the medicine front, already large number of clinical trials of new cancer therapies is underway and the possibility of liberating ourselves from heredity inherited diseases through gene manipulation has never been so real. Prof Doudna is already employing CRISPR in the battle against the Covid-19 as a co-founder of biotech startup Mammoth, which has tied up with GlaxoSmithKline to develop a test to detect infections.

Is the CRISPR/Cas9 genetic scissor the first one to be successfully developed? Obviously not! There have been other genome editing techniques like TALENs and Zinc-Finger Nucleases that can do similar jobs but not with the same ease. Scientists all over the globe consider the Charpentier-Doudna tool more adaptable and easier to use.

In fact, the commercial potential of the genetic scissor is so huge that there already is a dispute over the ownership of the intellectual property rights (IPR) of the genetic scissor between University of California and the MIT’s Broad Institute based on the claim that Feng Zhang of the MIT Broad Institute. Zhang had discovered a way to deploy the system in eukaryotic cells and patented it before Prof. Doudna’s patent was granted though her patent covered the process more generally. The patent dispute is still going on with both sides claiming victory on their own terms.

On the other hand, the menace of the misuse of the new tool with evil design of causing unwanted consequences is simply frightening. For example, in 2018 a Chinese scientist by the name He Jiankui used CRISPR to create the first gene-edited humans by altering the DNA of human embryos triggering a scandal which eventually led his excommunication from the scientific community. In absence of firm and strict regulations and code of ethics, the scissor may end up as the tool for ‘designer babies’ opening up a battery of unimaginable consequences.

Emmanuelle Charpentier, born in 1968 in France, obtained her Ph.D in 1995 from Institut Pasteur, Paris, France. She is serving as the Director of the Max Planck Unit for the Science of Pathogens, Germany. Jennifer A. Doudna, born 1964 in USA, obtained her Ph.D. in 1989 from Harvard Medical School, Boston, and is serving as Professor of Biochemistry at the University of California, Berkeley, and also as Investigator, Howard Hughes Medical Institute. Charpentier and Doudna will equally share the prize amount of about $1.1 million or more than Rs.8 crores.

It will again be a unique case that the in-person ceremony of awarding the Nobel prize held on every Dec 10, the death anniversary of the Great Chemist, Alfred Nobel, has been cancelled for this year due to the Covid-19 pandemic issues. It will be replaced with a televised ceremony showing the laureates receiving their awards in their home countries.