Interview with Francis Mojica: “When I Realized What I Had Discovered, I Knew That One Day It Would Appear in Textbooks”

The microbiologist from Elche discovered CRISPR sequences, which enabled the development of revolutionary genetic editing tools.

His down-to-earth attitude and simplicity are striking. Francis Mojica keeps his feet on the ground despite having advanced biology by leaps and bounds and being considered a potential Nobel Prize candidate for years. In the early 1990s, he discovered genetic sequences that repeated at regular intervals — CRISPR, short for Clustered Regularly Interspaced Short Palindromic Repeats — and a decade later he understood that they were part of a bacterial adaptive immune system against viruses: bacteria incorporated fragments of their invaders’ DNA into their genome to keep a record of infections, allowing them to recognize, bind, cut, and destroy those sequences in the future using the Cas protein.

These findings, resulting from the study of microorganisms in the salt flats of Santa Pola, not far from his hometown of Elche, Spain, had a global impact: they opened the door to a revolutionary technology that allows cutting and pasting DNA sequences from any living organism precisely, easily, and affordably. Today, it is used in laboratories worldwide, with applications in medicine, agriculture, and biotechnology that promise to transform humanity. Emmanuelle Charpentier and Jennifer Doudna received the 2020 Nobel Prize in Chemistry for developing CRISPR/Cas9 techniques.

But Francis Mojica is less interested in awards — which he also has, and very prestigious ones — than in understanding. He feels comfortable researching in Alicante, Spain, far from any ambition other than pure knowledge, while enjoying the pleasures of the Mediterranean.

He gave us this interview before the keynote lecture he delivered at CosmoCaixa in Barcelona, as part of the Great Minds of Science series and on the occasion of the 2nd Citizen Science Congress, co-organized by ISGlobal, Science For Change, and Ideas for Change.

-Do you remember that August day in 2003 when it was very hot in Santa Pola and you decided not to accompany your wife to the beach?

-I sure do. I like Santa Pola a lot in winter and less in summer, but you take vacation when you can. I took the opportunity to go to the university to analyze the genomic sequence data of Escherichia coli we had obtained months earlier. When I realized what I had discovered, I ran to the beach and told my wife, “Geli, I’ve found something that will appear in textbooks one day.”

-You saw it clearly.

-I realized it was something big, an impressive contribution to scientific knowledge because nothing like it had ever been described. I explained the discovery a little to my wife: I thought microorganisms had memory, they were capable of learning. She, not being a scientist, said, “I don’t understand anything, but it must be very important by the way you’re telling me.”

-Indeed, you’ve gone down in history.

-Yes. Without seeking it. But that’s almost better.

The Eureka Moment

-How did you get there?

-Ten years earlier, I had come across repeated sequences in the genome of archaea living in the Santa Pola salt flats. They were perfectly ordered repeats, at fixed distances from one another. Initially, we thought the repeats themselves were the important part, but later we realized that the “spacers,” the sequences between repeats, were the key. Each isolate had different spacers, even isolates of the same species. Where on earth did these curious spacers come from? We were determined to find out, and we did. We discovered they were information storage units.

When we discovered it was the only acquired immune system with memory in prokaryotes, it blew my mind! And I won’t even start on what came after. We immediately saw applications in microbiology, health, clinical work, and biotechnology...

-How did you see it?

-One of those E. coli spacers we were analyzing matched the sequence of a virus infecting the bacterium. We knew that particular strain was resistant to infection by that virus, while other E. coli isolates without the spacer were susceptible. We analyzed CRISPR sequences from bacteria and archaea in available databases and found that what we saw in E. coli appeared in about 2% of the 4,500 sequences we examined. Enough to know we were onto something. We concluded that the bacterial strain had “photographed” a virus that infected it and stored it as a spacer. From that moment, it and all its descendants became resistant to that virus.

Democratizing Genetic Engineering

-Your discovery has had global implications.

-It was completely unexpected. When we realized it was the only acquired immune system with memory in prokaryotes, it blew my mind! And everything that came after… immediately, we saw applications in microbiology, health, clinical work, biotechnology. Remember, bacterial populations, and prokaryotes in general, are controlled by viruses. Most pathogenic bacteria, like those causing tetanus, botulism, or diphtheria, produce toxins because they have viruses integrated in their genome. If we can prevent these bacteria from becoming toxic, imagine the possibilities. For example, we can protect yogurt-producing bacteria from viral infections, which are very common.

-Thousands of laboratories now use CRISPR as a key tool.

-Not only to modify microorganisms and make them virus-resistant but also to generate sequence-specific antimicrobials that kill only the target bacteria. CRISPR is widely used in genetic modification, improving crop productivity and quality, in animals, and to identify therapeutic targets. For instance, if a genome region is responsible for a disease, blocking that gene or its expression can eliminate the disease.

From Shoemaker to Scientist

-Aren’t you proud?

-Yes.

-But you remain very humble.

-Ah, my wife keeps me grounded. Whenever I start to get a bit carried away, she reminds me: “Francis, remember who you are!”

-And who are you?

-I’m the son of a very humble family of shoemakers who, unfortunately, couldn’t study. I was lucky to listen to them: when I thought I would stay in my parents’ factory gluing and covering heels, they convinced me to continue studying. Honestly, I never believed I could finish a degree. I thought scientists were very special people, with abilities I certainly didn’t have. But then you realize that if you work hard, you eventually get there.

I’m the son of a very humble family of shoemakers. I thought I would stay gluing and covering heels, but they convinced me to continue studying. I never thought I could finish a degree

-You stayed at the University of Alicante even though you are internationally recognized and presumably receive tempting offers.

-I’m happy there. The University of Alicante is good. And it’s not all work: the climate is nice, I’m close to family, the food is excellent, I earn enough to live comfortably and afford a couple of beers occasionally… I don’t need more. In life, you don’t have to be ambitious. Otherwise, you’re miserable.

An Elusive Nobel

-How did you feel when, in 2020, two scientists received the Nobel Prize in Chemistry for developing a technology based on your discovery?

-Thrilled! I was convinced someone from the CRISPR field should receive the Nobel. It was awarded for developing a very specific technology, not for discovering the prokaryotic acquired immune system. I would have been very surprised if it had been otherwise! For one, there’s no Nobel Prize in Biology. Right now, I’d say even more prizes could be awarded for CRISPR, because there’s the genetic editing tool, and then many more, for molecular diagnostics, for example, or as antimicrobials. That could also become a revolution.

There’s the genetic editing tool, and then many more, for molecular diagnostics, for example, or as antimicrobials

-Where could this lead us? Could we cure genetic diseases?

-Leukemia, deafness, blindness, heart disease, diabetes, hypercholesterolemia… you name it, are already being treated.

CRISPR vs. CRISPR

-After contributing to this discovery and seeing how it flourishes, what do you work on now? What else can be done?

-We are now working on the most exciting part. For ten years, we searched without knowing what we would find. Now we know where we are and can choose where to go. We are working with CRISPR systems very different from all others. They lack “components” of typical CRISPR systems. We believe they are mischievous CRISPRs, viral CRISPRs that inhibit the host bacterium’s CRISPR defense system. We are super excited: CRISPR vs. CRISPR. We also collaborate with companies and other universities to improve crops with CRISPR tools.

-How many are in your team?

-Five.

-Only five?

-Yes. I’ve never had more. It’s ideal.

-Why?

-With more people, the chances of having a “rotten apple” increase.

-So a good team atmosphere is very important.

-Essential. It’s better to have a small team that collaborates and has a good vibe. Unfortunately, that’s hard with large groups.

-How would you like to see yourself in the future?

-Oh, I’d like to continue like this as long as my body allows and my mind keeps working. Sometimes it’s not as fast as before, and I can’t keep up with everything because technology advances incredibly fast. When I see I no longer contribute to the group, I’ll step back discreetly. But as long as I can, I’ll continue. Research is a joy.