“The opportunity of defeating the enemy is provided by the enemy himself” – Sun Tzu
Last few months made us aware of Viruses. We all, those who do not belong to the biology-related fields, suddenly, sometime in February 2020 got ourselves informed that viruses can create havoc..!! It brought entire human race to its knees and we are still crawling and struggling to get up and walk!
To most of us, viruses are known, but not understood. As I tried to dig a bit more on these microscopic creatures, I realised that we are not the only ones who have to “deal with” these. There are other prokaryotes, like bacteria, fungi and so on, who have their own struggle to combat Viruses.
This article is an attempt to link these viruses to the recent Nobel Prize winners for Chemistry for 2020.
So, humans learn from the nature and nature is full of organisms, who we think, in-some-sense, inferior. However, that’s not true. They are already doing funny (and intelligent) things which we can only understand if we observe them carefully. Well, like human-beings, the microorganisms also have their safety ensured through their own defence mechanisms. Microorganisms could be bacteria, viruses, fungi, algae and so on. Just like humans, bacteria are also susceptible to viruses. Viruses can attack the bacteria and eventually destroy them and take total control over their systems.
So, how do bacteria handle these attacks? They use their own genetic manipulation to do this. Let us see few essential biological terms here. Biologically, each individual is different because everybody has a unique DNA. In the fields of molecular biology and genetics, a genome is the genetic material of an organism. It consists of DNA (or RNA). DNA is the molecule that is the hereditary material in all living cells. Genes are made of DNA, and so is the genome itself.
The viruses, who are the invaders (on say, bacteria), are known as “phages”. They attach to the surface of bacterial cells, inject their genetic material, and use the cells’ enzymes to multiply while destroying their hosts. To defend against a phage attack, bacteria have evolved a variety of immune systems. One of these immune systems, known as CRISPR-Cas, when encounters a enemy (phage), the system creates a ‘memory’ of the invader by capturing a small snippet of the enemy’s genetic material. The pieces of phage DNA are copied into small molecules known as CRISPR RNAs, which then combine with one or more Cas proteins to form a group called a Cas complex. This complex patrols the inside of the cell, carrying the CRISPR RNA for comparison; exactly in the way a detective uses a fingerprint to identify a criminal. Once a match is found, the Cas proteins chop up the invading genetic material and destroy the phage.
This technology of bacteria is being studied by humans for a long time. The technology which is then so developed is called as CRISPR Gene Editing technology. CRISPR stands for “Clustered Regularly Interspaced Short Palindromic Repeats”, a term that describes a family of nucleic acid sequences that were discovered in archaea and bacteria in the 1990s containing copies of virus genes. While studying this, it appeared that somehow these organisms had stolen genes out of viruses. So, in short, bacteria, as evolved, has virus RNA as a part of its identity..!
Technologically, this ability to identify specific DNA sequences with precision and break them apart was quickly recognised as a perfect tool for editing genes. A protein called Cas9 can be used in conjunction with engineered CRISPR sequences to hunt down codes and slice them (like a molecular scalpel), allowing geneticists to cut out a target gene, either to remove it or replace it with a new sequence. So it is literally Cut-Copy-Paste and Replace!
CRISPR-based technology has been applied to a variety of tasks in the past decade, from removing genes responsible for diseases, to destroying drug resistant superbugs, to creating molecular recording devices. Cancer screening, Metabolic engineering and manufacturing of high-value compounds are few other important applications.
This was the fundamental base on which two women scientists won the Nobel Prize for Chemistry, this year. The 2020 Nobel Prize in Chemistry was jointly awarded to French microbiologist, geneticist, and biochemist Emmanuelle Charpentier and American biochemist Jennifer A. Doudna for their work on the development of CRISPR-Cas9, a cutting edge, novel method for genome editing.
Charpentier worked on the bacteria Streptococcus pyogenes, which causes around 700 million skin infections in humans each year. While working on this pathogen in the late 2000s, she noticed that the bacteria contained a previously undiscovered molecule called tracrRNA, which was found to be a part of the bacteria’s ancient immune system, the CRISPR-Cas system. Her findings were published in 2011.
Doudna, an expert on ribonucleic acid (RNA) and x-ray crystallography of ribozymes, an RNA enzyme that catalyses a chemical reaction, started work on CRISPR, independently, in 2009. In 2011, she met Charpentier at a conference in Puerto Rico, following which they began to work on CRISPR-Cas together. They recreated the bacteria’s genetic scissors in a test tube and were eventually able to reprogram the entire CRISPR-Cas9 system so that it could be controlled and be used to cut any DNA molecule at a specific site on the genetic sequence, thus fundamentally altering the genetic code of the organism.
Their work has initiated radical leaps in the field of biomedical research. It has been used to modify the genomes of three cancer patients to reprogram the immune system to fight off cancer cells in February this year, with no side effects so far. It has also explored to eliminate HIV from infected cells and is being used to reverse congenital blindness, combat diseases such as Huntington’s as well as chronic pain.
I leave this blog with two thoughts to ponder on:
1. Bacteria have found a solution for its survival by “incorporating” virus signature in itself. Can we then say bacteria as a “Bacteria” or a “Virus”? Is there an identity crisis here? Well, can we talk of humans on similar lines? Time will tell as to how far genetic engineering will take us.
2. We thought that we invented cut-copy-paste technology. But look at bacteria, which we always considered as the simplest form of microscopic organism. It has been using this technology to modify itself, for so long! We are just learning and re-creating it!