Her surroundings and approaches have shifted, but the majority of her research has one common denominator: pathogenic bacteria. Why are they so aggressive? How do they develop their resistance to antibiotics? And is it possible to find new treatments that can stop their progress? During her early days (2002) she thought about the bacteria that cause great harm to humanity: Streptococcus pyogenes.
This decision was the first step down the path of Emmanuelle Charpentier for the discovery of genetic scissors.
Before we walk further along that road, we will find out more about Jennifer Doudna. Because while Charpentier is making detailed studies of S. pyogenes, Doudna hears – for the first time – an abbreviation that she thinks sounds like crisper.
One fine day, Jennifer Doudna gets a phone call from a colleague in a different department. Her colleague, who is a microbiologist, tells Doudna about a new discovery: when researchers compare the genetic material of vastly different bacteria, as well as archaea (a type of microorganism), they find repetitive DNA sequences that are surprisingly well preserved. The same code appears over and over again, but between the repetitions, there are unique sequences that differ. It is like the same word is being repeated between each unique sentence in a book. These arrays of repeated sequences are called clustered regularly interspaced short palindromic repeats, abbreviated as CRISPR. This news was both remarkable and thrilling to her. Jennifer Doudna’s sense of molecular intrigue comes to life and she starts to learn everything she can about the CRISPR system.
A life-changing meeting in a Puerto Rican café
By coincidence, they meet at a café on the second day of the conference. A colleague of Doudna introduces them to each other and, the following day, Charpentier proposes that they should explore the old parts of the capital city together. As they stroll along the cobbled streets, they start talking about their research. Charpentier wonders whether Doudna is interested in a collaboration – would she like to participate in studying the function of Cas9 in S. pyogenes’ simple class 2 system?
Photo: ELOY ALONSO/REUTERS
Jennifer Doudna is intrigued, they and their colleagues make plans for the project via digital meetings. Their suspicion is that CRISPR-RNA is needed to identify a virus’ DNA, and that Cas9 is the scissor that cuts off the DNA molecule. However, nothing happens when they test this in vitro. The DNA molecule remains intact. Why? Is something wrong with the experimental conditions? Or does Cas9 have an entirely different function?
Genetic scissors change the life sciences
Soon after Emmanuelle Charpentier and Jennifer Doudna publish their discovery of the CRISPR/Cas9 genetic scissors in 2012, several research groups demonstrate that this tool can be used to modify the genome in cells from both mice and humans, leading to explosive development. Previously, changing the genes in a cell, plant or organism was time-consuming and sometimes impossible. Using the genetic scissors, researchers can – in principle – make cuts in whichever genome they wish. After this, it is easy to utilise the cell’s natural systems for DNA repair so that they rewrite the code of life.
It is a family of DNA sequences found in the genomes of prokaryotic organisms such as bacteria and archaea. These sequences are derived from DNA fragments of bacteriophages that had previously infected the prokaryote. They are used to detect and destroy DNA from similar bacteriophages during subsequent infections. Hence these sequences play a key role in the antiviral (i.e. anti-phage) defence system of prokaryotes. CRISPR-Cas system is a prokaryotic immune system that confers resistance to foreign genetic elements such as those present within plasmids and phages and provides a form of acquired immunity. RNA harbouring the spacer sequence helps Cas (CRISPR-associated) proteins recognize and cut foreign pathogenic DNA. Other RNA-guided Cas proteins cut foreign RNA. CRISPR are found in approximately 50% of sequenced bacterial genomes and nearly 90% of sequenced archaea.
Hope of curing inherited diseases
In medicine, the genetic scissors are contributing to new immunotherapies for cancer and trials are underway to make a dream come true – curing inherited diseases. Researchers are already performing clinical trials to investigate whether they can use CRISPR/Cas9 to treat blood diseases such as sickle cell anaemia and beta-thalassemia, as well as inherited eye diseases.
They are also developing methods for repairing genes in large organs, such as the brain and muscles. Animal experiments have shown that specially designed viruses can deliver the genetic scissors to the desired cells, treating models of devastating inherited diseases such as muscular dystrophy, spinal muscular atrophy and Huntington’s disease. However, the technology needs further refinement before it can be tested on humans.
The power of genetic scissors requires regulation
Alongside all their benefits, genetic scissors can also be misused. For example, this tool can be used to create genetically modified embryos. However, for many years there have been laws and regulations that control the application of genetic engineering, which include prohibitions on modifying the human genome in a way that allows the changes to be inherited. Also, experiments that involve humans and animals must always be reviewed and approved by ethical committees before they are carried out.
One thing is certain: these genetic scissors affect us all. We will face new ethical issues, but this new tool may well contribute to solving many of the challenges now facing humanity. Through their discovery, Emmanuelle Charpentier and Jennifer Doudna developed a chemical tool that has taken life sciences into a new epoch. They have made us gaze out onto a vast horizon of unimagined potential and, along the way – as we explore this new land – we are guaranteed to make new and unexpected discoveries.
AFTERMATH
Their contributions in the pioneer of CRISPR technology gave themselves the Nobel prize in chemistry of the year 2020.
Credits:© Nobel Media. Ill. Niklas Elmehed.
Read another article about the same discovery: “Have a glance at Nobel Prize 2020 Winners in Chemistry”
Author
