In March 2011, a chance meeting between two women changed history without anyone being aware of it. It happened in a cafe in San Juan, Puerto Rico, when the American molecular biologist Jennifer Doudna was introduced to Emmanuelle Charpentier, a French professor of Armenian origin in the same field. They hit it off and, within hours, agreed to a research collaboration. The result, a year later, was the discovery of the CRISPR system: a technology that can be used to edit genes.
Eleven years later, CRISPR is a ubiquitous tool in any molecular biology laboratory in the world, allowing research to be carried out at a speed and cost that were previously unimaginable. Gene editing has also made its way into the experimental treatment of many diseases. CRISPR makes mind-blowing applications possible, such as taking white blood cells from a person, rewriting their genomes to transform them into cancer-killing machines and reinjecting them to fight tumors that haven’t responded to conventional treatments.
Charpentier and Doudna won the 2020 Nobel Prize in Chemistry for discovering CRISPR. Charpentier, 53, made her fundamental contribution while searching for a way to kill an implacable enemy: the streptococcus pyogenes bacteria, one of the top 10 causes of deadly infections on the planet. It is known as the “flesh-eating” bacteria because of the horrible wounds it causes if it gets under the skin and reaches the muscle – a type of injury that has been documented since the 5th century, appearing in terrible situations. For instance, it inflicted combatants in the US Civil War and heroin addicts in 1990s San Francisco. This bacteria has even become immune to conventional antibiotics.
The investigation into the molecular mechanisms that this bacterium uses to survive external threats was key to discovering CRISPR. The microbes acted as a kind of bacterial immune system, capable of remembering precise fragments of the virus’ genome, to then cut the virus’ DNA. But the genome of a virus has millions of letters arranged one after the other – how did these microbes manage to identify the genome of the virus and cut it in the exact place?
A few months before the historic meeting in Puerto Rico, Charpentier’s team had discovered an RNA molecule that was essential to guiding a pair of molecular scissors to the exact sequence of the genome of each virus. This was key to putting together all the elements needed to build the new CRISPR gene-editing tool.
Three months ago, CRISPR Therapeutics – the company Charpentier founded in 2019 – published preliminary results from a clinical trial showing that 15 patients with beta thalassemia – a severe type of anemia that requires lifelong reliance on blood transfusions – had gone months without needing them after receiving a drug that edited the gene that caused the disease.
In early September, Charpentier traveled to Yerevan, Armenia to be one of the main speakers at the Starmus VI Festival. In her interview with EL PAÍS, the scientist explains that she is still focused on the same goal as she was years ago: looking for new forms of gene editing to combat antibiotic-resistant infections. These superbugs already kill more people than AIDS, malaria and some cancers. For her, one of the greatest dangers we face is that the basic sciences – which require years of hard work – are no longer attractive to young people, who will need to invent new treatments and medicines in the future. This interview has been edited for the purposes of clarity and brevity.
Question. Where did your interest in science come from?
Answer. At the age of 15, I was obsessed with monasteries… I wanted to be a nun for a while. That’s maybe reflected in my work as a scientist: many hours are spent alone, cut off from the world. This is what I did at the University of Umeå, in Sweden. I made the key discovery for CRISPR there, while living in my scientific monastery in northern Sweden. At the same time, I was very interested in detective stories, searching for enigmas.
Q. Do you believe in God?
A. My parents were Catholics, but they belonged to a very modern and up-to-date branch of Catholicism, with working-class priests. I grew up in this environment and practiced, but I haven’t done it for a long time. For me, believing in God is believing in the good of the human being, the best version of humanity.
Q. Are microbes superior to humans?
A. Probably, yes. Long after we have disappeared from the planet, they will still be here. And let’s not forget that they already existed long before we appeared! They have solved key problems in their own way. They know how to communicate, adapt, fight… they’re extremely versatile. And we’re talking about a huge community, with millions of different species and an exciting social life.
Q. Social life?
A. They are very social. We can learn a lot from them. The human body contains more bacterial cells than human cells. And this community partly determines how we react to stimuli, why we get sick, how our metabolism works, even some brain functions. I believe that the challenge for human beings is to adapt to the enormous change that is taking place in the microbial universe. We have seen it with a single microbe: SARS-CoV-2. And we are going to see it with new viruses that are yet to come. Many of them will, in part, be driven by human activities on the planet.
Q. Just four years ago, when you spoke to EL PAÍS, there were hardly any applications of CRISPR in health. Now, especially after the pandemic, there are more and more. What’s the next big step?
A. In origin, CRISPR is an immune system that allows bacteria to defend themselves against viruses. In the coming years, we must perfect the system and be able to use it in a more personalized way. It’s the future… the study of microbes can solve some of the biggest problems facing humanity. We can create crops that are more resistant to changes in climate and the environment. But the next big step – as is usually the case in science – will be totally unexpected.
Q. And what role will CRISPR play in treating disease?
A. This tool could help interfere with human metabolism in a beneficial way, to eliminate the negative effects of common diets in the Western world. These same problems are becoming more and more prevalent in Asia [the developing world], because the population’s metabolism is not prepared for this type of diet, with lots of meat and enriched carbohydrates. One of the key ailments in this field would be diabetes, for example. Also obesity and infectious diseases.
Q. You head the Max Planck Institute for the Science of Pathogens (Berlin). One of its goals is to combat antibiotic-resistant infections, which are expected to cause the next pandemic.
A. My lab doesn’t have many people. We continue to work in a humble way on the specific mechanisms existing in bacteria, so we can identify therapeutic targets and have new antibiotics ready to combat future infections. The development of antibiotics has stagnated in the last 20 years because the pharmaceutical industry is not interested in developing them. We are now starting to see small biotech companies tackling this challenge. I think it is very important to focus on this.
Q. Don’t we already know how resistant bacteria are able to make us sick?
A. There are many different mechanisms. The problem is that, as soon as you create a new antibiotic, the bacteria develop immunity to it. It’s important to continue researching in this field, looking for new ways to intervene and have different therapeutic compounds. A vaccine is one thing, but you also need antivirals. You have to have different strategies.
Q. What other future issues are you worried about?
A. Being well-armed against resistant bacteria requires a lot of work, a lot of research time. The efforts of many people in different fields, from biologists to doctors, entrepreneurs and businessmen. But the most indispensable are the basic scientists. With the noise of the world we live in today, we see many scientists who finish their doctorates and abandon research. Young generations can’t find their place in the academic world, which has not evolved in 30 years. Meanwhile, everything is moving faster and faster, including business. In the US, you can create a biotech company almost instantly and be successful very quickly.
The basic sciences – which rely on public funding – are ceasing to be attractive, both in terms of funding and mentality. Young people do not want to wait so many years to see the fruits of their labor. Science is being flooded with politics. The system of scientific publications has been filled with marketing. If it continues like this, it will be a very serious problem. Scientists also teach at universities: they are the teachers of the next generations. Without them, not one, but several generations of brains can be lost.
Q. But more and better science is still being done, right?
A. I believe that fundamental biology – and the basic sciences overall – are in danger. Science involves isolating yourself and working very hard. You have to be able to read more than two pages at a time and work more than eight or nine hours at a stretch. We now see that young students have more and more trouble concentrating or working long hours.
Q. Do you see a solution to this problem?
A. No. I think we all – and especially young people – need to ask ourselves what kind of world we want to live in. I think kids in rich countries are going to realize that, if they don’t change their attitude, they’ll be digging their own graves.