Nobel Prize in Chemistry 2020: CRISPR/Cas9 Genetic Scissors and Genome Editing

This note covers the Nobel Prize in Chemistry 2020: who won it, how the CRISPR/Cas9 genetic scissors let scientists cut and rewrite DNA with great precision, how the discovery unfolded from bacterial immunity studies to a programmable tool, why it matters for medicine and farming, and quick facts for exams.

What was the Nobel Prize in Chemistry 2020 awarded for?

The Royal Swedish Academy of Sciences awarded the prize with the citation: "for the development of a method for genome editing".

In plain words, the two laureates found and perfected a molecular tool that can cut a strand of DNA at an exact, chosen spot, so that scientists can then edit the genetic code at that point.

The official name of this award is the Nobel Prize in Chemistry. It was announced on 7 October 2020 and the laureates shared a prize amount of 10,000,000 Swedish kronor.

Genome editing means changing the sequence of DNA inside a living cell in a controlled way.

Before this discovery, doing this was described by the Nobel Committee as time-consuming, difficult and sometimes impossible; the tool the laureates built made it possible to change the "code of life" within a few weeks, according to the press release.

Who are the laureates?

Emmanuelle Charpentier

Emmanuelle Charpentier was born on 11 December 1968 in Juvisy-sur-Orge, France. At the time of the award she was Director of the Max Planck Unit for the Science of Pathogens, Berlin, Germany. She received one half of the prize.

Charpentier's own research on the harmful bacterium Streptococcus pyogenes led her to discover a previously unknown RNA molecule, tracrRNA, and to show that it is part of the bacterium's ancient immune defence called CRISPR/Cas.

She published this discovery in 2011 and then proposed the collaboration with Doudna that led to the full discovery.

Jennifer A. Doudna

Jennifer A. Doudna was born on 19 February 1964 in Washington, D.C., USA. At the time of the award she was a professor at the University of California, Berkeley, CA, USA, and an investigator at the Howard Hughes Medical Institute. She received one half of the prize.

Doudna was an experienced biochemist with deep knowledge of RNA. Working with Charpentier, she helped recreate the bacterial genetic scissors in a test tube, simplify their components, and then reprogram them so they could cut any chosen DNA sequence rather than only viral DNA.

What problem were they trying to solve?

Scientists had wanted to manipulate DNA ever since James D. Watson and Francis H.C. Crick described the structure of DNA in 1953. Changing genes inside cells, plants or animals used to be, in the committee's words, time-consuming, difficult and sometimes impossible.

The clue to a solution came from an unexpected place: bacteria themselves. Researchers studying bacterial and archaeal genomes from the late 1980s onward kept finding odd, repeated DNA sequences separated by unique "spacer" sequences. These repeats were named CRISPR, short for clustered regularly interspaced short palindromic repeats.

By 2007, experiments on Streptococcus thermophilus showed that bacteria which survived a virus infection added a piece of the virus's own DNA code into their CRISPR region as a kind of memory.

If the same virus attacked again, the bacterium could recognise and destroy its DNA. This was, in effect, an ancient immune system that worked by cutting the invader's DNA using special CRISPR-associated (Cas) proteins.

Charpentier's work on Streptococcus pyogenes, a bacterium causing conditions such as tonsillitis and sometimes life-threatening infections, placed her directly inside this puzzle.

Doudna, meanwhile, had spent years on RNA and was drawn in when a colleague described the mysterious CRISPR repeats in 2006. The two fields, bacterial immunity and RNA biochemistry, were about to meet.

How does the CRISPR/Cas9 genetic scissors work?

In its natural bacterial form, the CRISPR/Cas system studied by Charpentier belongs to a simpler group called Class 2, which needs only one large protein, Cas9, to cut DNA, unlike the more complex Class 1 systems that need several proteins working together.

Charpentier discovered that an extra RNA molecule, tracrRNA, pairs up with the CRISPR-derived RNA (called crRNA) and is needed for the crRNA to mature into its working form.

When she and Doudna tested this system in a test tube, nothing happened until they added tracrRNA together with Cas9 and crRNA; only then was the target DNA molecule cut into two pieces.

The pair then carried out what the press release calls an "epoch-making experiment": they fused the tracrRNA and crRNA into a single engineered molecule called guide RNA, and showed that by changing the code of this guide RNA, they could direct Cas9 to cut a chosen gene at five different predetermined sites, with the cuts falling exactly where intended.

The general steps of how CRISPR/Cas9 edits a genome are:

1. A short guide RNA is designed with a sequence matching the DNA site to be edited.
2. The guide RNA combines with the Cas9 protein to form an active complex.
3. Cas9 searches the DNA for a short marker sequence next to the target, called the protospacer adjacent motif (PAM).
4. Once the PAM and the matching DNA sequence are found, Cas9's two cutting regions slice both strands of the DNA at that exact spot.
5. The cell's own natural DNA-repair machinery then mends the cut, which can be used to delete, disrupt or insert new genetic code at that location.

Draw a long double DNA strand with a short guide RNA molecule paired to one strand near a labelled PAM sequence; show the Cas9 protein clamped around the RNA-DNA pairing with two small triangular "blades" cutting both DNA strands at the same point, leaving a clean double break.

Draw a bacterium's chromosome with a row of repeated identical blocks (the CRISPR repeats) separated by different short pieces (spacers), each spacer matching a piece of a virus's own DNA that previously attacked the bacterium, to show how the bacterium "remembers" past infections.

How did bacteria's defence become a programmable tool?

The breakthrough that made the system usable in any cell was the discovery that the scissors' natural target, viral DNA, could be swapped for any DNA sequence simply by changing the guide RNA's code.

The only requirement that remained was that a PAM sequence had to sit next to the target site.

Charpentier and Doudna published their findings in 2012. Soon afterwards, other research groups showed the tool worked not only in bacteria but also in mouse and human cells, which is what made it a general-purpose method for genome editing across living things, rather than just a bacterial curiosity.

How did the discovery unfold?

Why does this discovery matter?

Because the CRISPR/Cas9 tool is relatively easy to use, it spread quickly into basic research, where scientists use it to switch genes off or change them so they can study what each gene does, including in the course of disease.

In agriculture, researchers have used the scissors to edit plant genomes directly, without needing to insert antibiotic-resistance genes as older methods did.

Edited rice varieties with lower cadmium and arsenic absorption have been developed, along with crops bred to better withstand drought, insects and pests.

In medicine, the Nobel Committee points to ongoing clinical trials of new cancer therapies, and to trials testing whether CRISPR/Cas9 can treat inherited blood disorders including sickle cell anaemia and beta thalassemia, along with some inherited eye conditions.

Animal studies have also tested delivering the scissors to treat conditions like muscular dystrophy, though the technology still needs refinement before such delivery methods can be tested on humans.

The committee also flagged an open concern: because the tool is so powerful, including the possibility of editing human embryos, it stressed that genetic scissors need careful regulation, and that experiments on humans and animals must be reviewed and approved by ethics committees.

How does this connect to what you study?

CRISPR/Cas9 links directly to school topics in genetics and biotechnology: the structure of DNA, how genes are expressed, what a mutation is, and how a cell repairs broken DNA strands using its own natural repair machinery.

It also connects to microbiology, because the whole tool began as a bacterium's own defence system against viruses. Studying how a simple organism like Streptococcus pyogenes protects itself turned into one of the most powerful tools in modern biology.

The story also illustrates the scientific method itself: researchers in different fields, bacterial immunity and RNA biochemistry, combined their separate findings to solve a shared puzzle. Students studying the double-helix structure of DNA, first described by Watson and Crick in 1953, can see this as a direct continuation of that story, since the 2020 chemistry prize rewarded a practical way to finally manipulate the DNA that Watson and Crick had only described decades earlier.

Lessons on enzymes are also relevant, since Cas9 works as a type of nuclease, an enzyme that cuts nucleic acid strands, a concept found in basic biochemistry.

What ethical questions does this technology raise?

Because CRISPR/Cas9 makes it easy to change DNA in almost any living thing, the Nobel Committee stressed that such a powerful tool cannot be used without careful thought.

Genetic scissors can, in principle, be used to create genetically modified embryos, which raises serious questions about whether and how human genetic material should ever be permanently altered in a way that could be passed on to future generations.

For many years, laws and regulations have controlled the use of genetic engineering, including rules that prohibit changing the human genome in ways that children could inherit. Experiments involving humans and animals must always be reviewed and approved by ethics committees before researchers can carry them out.

The World Health Organization set up a global expert panel to study the scientific, ethical, social and legal challenges raised by human genome editing, with the aim of building a shared, worldwide framework for governing the technology.

The Nobel Committee's own view, as reported in the press release, was direct: Claes Gustafsson, chair of the Nobel Committee for Chemistry, said "there is enormous power in this genetic tool, which affects us all", adding that it has revolutionised basic science, led to new crops and will bring about new medical treatments.

This combination of enormous promise and serious risk is why genetic scissors need to be regulated even as they open up vast new possibilities for medicine and agriculture.

Quick facts for exams

The Nobel Prize in Chemistry 2020 was awarded jointly to Emmanuelle Charpentier and Jennifer A. Doudna for developing the CRISPR/Cas9 method of genome editing. The prize was announced by the Royal Swedish Academy of Sciences on 7 October 2020.

Charpentier, born in France, worked at the Max Planck Unit for the Science of Pathogens in Berlin, Germany, while Doudna, born in the USA, worked at the University of California, Berkeley.

Each received half of the 10 million Swedish kronor prize. Their discovery, building on bacteria's natural defence against viruses, lets scientists cut DNA at a precisely chosen site, enabling edits in plants, animals and human cells for research, agriculture and emerging medical therapies.

Note: Source. The prize facts in this note are from the Nobel Prize's official site, nobelprize.org.

Glossary

• CRISPR — clustered regularly interspaced short palindromic repeats, a repeated DNA pattern found in many bacteria and archaea.
• Cas9 — a bacterial protein that cuts DNA at a site chosen by a matching guide RNA.
• tracrRNA — trans-activating CRISPR RNA, discovered by Charpentier; it is needed to activate crRNA and guide Cas9 to cut DNA.
• crRNA — CRISPR RNA, a short RNA made from the CRISPR region that matches a piece of invading viral or plasmid DNA.
• Guide RNA — the engineered, fused form of tracrRNA and crRNA used to direct Cas9 to a chosen DNA sequence.
• PAM (protospacer adjacent motif) — a short DNA sequence next to the target site that Cas9 must recognise before it can cut.
• Genome editing — making deliberate, precise changes to the DNA sequence of a living cell or organism.
• Nuclease — an enzyme, such as Cas9, that cuts strands of DNA or RNA.
• Spacer — the unique DNA sequence stored between CRISPR repeats, derived from a past viral or plasmid invader.
• Zinc finger nucleases and TALENs — earlier, more difficult to design gene-editing tools that CRISPR/Cas9 largely replaced.
• RNA interference — a cell process using small RNA molecules to regulate gene activity, a field Doudna worked in before CRISPR.

Common errors and misconceptions

• Misconception: CRISPR/Cas9 was invented entirely from scratch by Charpentier and Doudna. Correct: It is based on a natural bacterial immune system; the laureates discovered how it works and reprogrammed it into a general tool.
• Misconception: Cas9 can cut any DNA with no restriction. Correct: Cutting requires a PAM sequence next to the target site, and the guide RNA's sequence must match the target.
• Misconception: The discovery was an isolated event in 2012. Correct: It followed decades of work on CRISPR repeats and Cas genes by many researchers, with Charpentier's 2011 tracrRNA finding as a key step.
• Misconception: CRISPR/Cas9 is only used in medicine. Correct: It is widely used in basic research and in developing improved crops, as well as in emerging medical therapies.
• Misconception: Any CRISPR edit on a human is already routinely approved. Correct: The sources state that experiments involving humans must be reviewed and approved by ethics committees, and regulation is an ongoing concern.
• Misconception: Charpentier and Doudna worked in the same laboratory. Correct: Charpentier was based in Umeå, Sweden, and Doudna in Berkeley, USA; they collaborated after meeting at a conference in Puerto Rico.

Exam-style questions with model answers

Q1. Who were the two laureates of the Nobel Prize in Chemistry 2020, and for what citation? [2 marks]

1. Emmanuelle Charpentier and Jennifer A. Doudna shared the prize for the development of a method for genome editing.

Q2. Name the two key RNA molecules involved in the natural bacterial CRISPR system described in the sources. [2 marks]

1. The two RNA molecules are crRNA, made from the CRISPR repeat region, and tracrRNA, discovered by Charpentier, which helps crRNA mature and activates Cas9.

Q3. Explain how Charpentier and Doudna simplified the natural bacterial genetic scissors into a programmable tool. [4 marks]

1. In its natural form, the CRISPR/Cas9 system used two separate RNA molecules, tracrRNA and crRNA, together with the Cas9 protein, to recognise and cut viral DNA at sites matching the bacterium's stored CRISPR memory.
2. Charpentier and Doudna fused tracrRNA and crRNA into a single engineered molecule called guide RNA.
3. They then showed that by changing the sequence of this guide RNA, Cas9 could be directed to cut DNA at any chosen site rather than only at viral sequences, as long as a PAM sequence was present nearby.
4. This turned a specific bacterial defence mechanism into a general, programmable genome-editing tool usable in other organisms.

Q4. Describe how bacteria use CRISPR sequences as a natural immune system against viruses. [4 marks]

1. When a bacterium survives a virus infection, it can insert a short piece of the virus's own DNA into its CRISPR region on its chromosome, between repeated sequences, as a stored memory of the attack.
2. This CRISPR region is transcribed into RNA and processed into short crRNA molecules that each carry one stored viral sequence.
3. If the same virus attacks again, the crRNA pairs with matching viral DNA, and Cas proteins use this pairing to recognise and cut the invading DNA.
4. This destroys the virus's genetic material before it can take over the bacterium, protecting it from a repeat infection.

Q5. Discuss the scientific background and wider significance of the Nobel Prize in Chemistry 2020, including both benefits and concerns raised by the committee. [6 marks]

1. The prize rewarded Emmanuelle Charpentier and Jennifer A. Doudna for developing the CRISPR/Cas9 genetic scissors, a method allowing extremely precise editing of DNA in animals, plants and microorganisms.
2. The discovery grew out of decades of research into repeated CRISPR sequences in bacteria and archaea, and into Cas proteins that bacteria use as part of an adaptive immune system against viruses and plasmids.
3. Charpentier's discovery of tracrRNA in Streptococcus pyogenes, followed by her collaboration with Doudna, led to the 2012 demonstration that a simplified, single guide RNA could direct Cas9 to cut any chosen DNA sequence next to a PAM site.
4. This tool spread rapidly into basic research for studying gene function, into plant breeding for traits such as drought tolerance and lower cadmium and arsenic uptake in rice, and into medicine, where clinical trials are testing treatments for cancers and inherited blood diseases such as sickle cell anaemia and beta thalassemia.
5. The Nobel Committee also stressed that such a powerful tool, capable in principle of editing human embryos, raises serious ethical and societal issues and needs careful regulation and ethical committee review.
6. Overall, the prize recognises how an unexpected discovery in bacterial biology was turned into one of the most widely used tools in modern life sciences.

Q6. What is a PAM sequence, and why is it important for Cas9 activity? [2 marks]

1. A PAM is a short DNA sequence located next to the target site; Cas9 must find and recognise it before it can bind and cut the adjacent DNA.

Q7. State the prize amount and how it was shared between the two laureates in 2020. [2 marks]

1. The Nobel Prize in Chemistry 2020 carried a total of 10,000,000 Swedish kronor, shared equally, one half each, between Charpentier and Doudna.

Q8. Explain two applications of CRISPR/Cas9 outside basic laboratory research. [3 marks]

1. In agriculture, CRISPR/Cas9 has been used to edit plant genomes directly, for example producing rice varieties that absorb less cadmium and arsenic, and crops with improved resistance to drought, insects and pests.
2. In medicine, the tool is being used in clinical trials of new cancer therapies, and researchers are testing whether it can treat inherited diseases such as sickle cell anaemia and beta thalassemia.

Key takeaways

• The Nobel Prize in Chemistry 2020 went to Emmanuelle Charpentier and Jennifer A. Doudna for developing CRISPR/Cas9 genome editing.
• CRISPR is a natural bacterial defence system that stores memories of past virus infections as DNA sequences.
• Charpentier discovered tracrRNA, a key RNA molecule needed to activate the Cas9 protein.
• Together, Charpentier and Doudna fused two RNA molecules into one guide RNA, making the scissors programmable.
• The system cuts DNA at a chosen site as long as a matching guide RNA and a nearby PAM sequence are present.
• CRISPR/Cas9 is now used in basic research, crop improvement and experimental cancer and genetic disease therapies.
• The discovery followed decades of earlier work identifying CRISPR repeats and Cas genes in many scientists' laboratories.
• The Nobel Committee highlighted the need for careful ethical regulation of this powerful technology.

Test yourself

What does CRISPR stand for?

CRISPR stands for clustered regularly interspaced short palindromic repeats, a repeated DNA pattern found in bacteria and archaea.

Which protein does the guide RNA direct to cut DNA in the CRISPR/Cas9 system?

The guide RNA directs the Cas9 protein, which cuts both strands of the target DNA at the chosen site.

Where was Jennifer A. Doudna affiliated at the time of the award?

Jennifer A. Doudna worked at the University of California, Berkeley, in the USA at the time of the award.

What molecule did Emmanuelle Charpentier discover in Streptococcus pyogenes in 2011?

She discovered tracrRNA, a previously unknown RNA molecule needed for the bacterial CRISPR system to work.

Where did Charpentier and Doudna first meet to discuss collaborating?

They met by chance at a café during a conference in Puerto Rico; the next day, while exploring the old town together, Charpentier proposed a collaboration.

Name one medical use of CRISPR/Cas9 mentioned by the Nobel Committee.

Clinical trials are testing CRISPR/Cas9 based therapies for cancers and inherited blood diseases such as sickle cell anaemia.

What is a PAM sequence needed for?

A PAM sequence sits next to the target DNA and must be recognised by Cas9 before it can cut that site.

How much was the total Nobel Prize in Chemistry 2020 amount?

The total prize amount was 10,000,000 Swedish kronor, shared equally between the two laureates.