“We Don’t Just Need a Few New Antibiotics, We Need an Arsenal”

Nobel Prize winner reflects on her work to visualize the bacterial ribosome—and what needs to happen to avoid turning back the clock on modern medicine

“We Don’t Just Need a Few New Antibiotics, We Need an Arsenal”
Professor Ada Yonath of Weizmann Institute of Science looking through a microscope
Weizmann Institute of Science

In 2009, Dr. Ada Yonath became the first Israeli woman to win a Nobel Prize, when she was awarded the Nobel Prize in Chemistry for her decades-long effort to successfully map the structure of bacterial ribosomes—the complex structures that play a pivotal role in the function of all living cells. By revolutionizing a technique known as x-ray crystallography and mimicking the natural habitat of bacteria, she provided three-dimensional views of the ribosome for the first time. This breakthrough had significant implications for the discovery and development of antibiotics, some of which work by targeting bacterial ribosomes.

Today, Dr. Yonath is director of the Helen and Milton A. Kimmelman Center for Biomolecular Structure and Assembly at the Weizmann Institute of Science in Israel, where she works to leverage her ribosome research to better understand antibiotic resistance mechanisms and facilitate the development of new antibiotics.

This interview has been edited for clarity and length.

Q: Can you tell us about your Nobel Prize-winning work with bacterial ribosomes?

A: Well, when I started my research back in the 1970s, I didn’t have the Nobel Prize in mind. Nor was I thinking about antibiotics. But I was fascinated by the process of genetic code translation to proteins and convinced that determining the structure of bacterial ribosomes would be key to understanding that process and a gateway to game-changing scientific breakthroughs.

Q: So take us back to the beginning of your research.

A: Early on, many highly recognized scientists told me that mapping the structure of ribosomes couldn’t be done. Ribosomes were “too large,” they said, “too complicated,” “not stable enough to map”—and the list went on. But I was a beginner and undeterred.

That’s not to say it was easy, though. Far from it. Ultimately it took me and my team more than 20 years to crack the structure, and there were plenty of failures along the way.

Q: How did you react to the failures?

A: When established procedures didn’t work, I began sourcing ribosomes in new ways and from new places, including so-called inhospitable environments such as the Dead Sea. As it turned out, bacteria that had adapted to living in very unfavorable conditions were hardier than other bacteria and provided more stable samples of ribosomes.

Q: So, problem solved?

A: Well, when I finally succeeded in producing ribosomal crystals that were ready to analyze—after six years I had about 100 of them—every single one was ruined within a couple of seconds of exposing them to x-rays.

Q: Wow. Then what?

A: At that point I seriously considered quitting. But instead, I persisted in looking for new ways to prevent the crystals’ destruction. It went on like this for decades: two steps forward, one step back. We made incremental progress along the way, until eventually, we succeeded! We figured out the structure. I was in heaven.

Q: You weren’t the only one. The Nobel Committee for Chemistry at the Royal Swedish Academy of Sciences also seems to have been impressed.

A: The Nobel Prize was nice, of course. But for me, the real excitement was finally being able to understand the structure and function of the ribosome. Once we determined the structure, we were off to the races: Figuring out the functionality came within just a few months.

Q: What got you interested in bacterial research in the first place?  

A: I’ve been interested in the process of genetic code translation for just about as long as I can remember. Bacteria were a very suitable system for investigating this process, as well as the subject of antibiotics: I have clear memories from when I was a young girl of people talking about these “miracle drugs” that were saving lives. And while I probably would have been fascinated no matter what by these new drugs that were changing the course of medicine, I think I was particularly intrigued by the advent of antibiotics because I lost my dad when I was just 11 years old.

Q: What do you see as some of the biggest challenges in the fight against antibiotic resistance?

A: It seems to me that the biggest challenge is finding truly new ways to fight infection. Over the past few decades there’s been a lot of adapting and improving of existing antibiotics, but hardly anything really novel. We need more research and investment to help translate innovative ideas into drugs—and that process is not simple.

Q: What’s standing in the way?

A: The reality is that drug companies have to make a profit, and they make more money when they manufacture a pill that someone takes every day for 20 years. Antibiotics aren’t like that. So the level and type of research we need from pharmaceutical companies just isn’t happening. Governments are stepping up and contributing important work, but governments alone won’t solve the problem. We have to find a way to get the pharma companies involved again. And we need to be investigating solutions on multiple fronts.

Q: What kind of multiple fronts?

A: Investigating nontraditional approaches to fight bacterial infections. Phage therapy, for example, which uses viruses to attack bacteria, seems quite promising.

Q: You, and other experts, have warned that modern medicine could return to a pre-antibiotic era if new types of antibiotics aren’t discovered soon. That sounds pretty scary.

A: Indeed it is scary. What a lot of people don’t realize is that antibiotics underpin modern medicine. However, increasing resistance minimizes their ability to protect patients with compromised immune systems—like those battling cancer, for example—from pneumonia or other infectious diseases while they’re going through treatment and vulnerable.

Expanding resistance means returning to a pre-antibiotic era, which means returning to what life was like when I was a little girl, when surgeries and so many other medical procedures were significantly more dangerous or not even possible because of the risk of infection.

Q: How can we prevent that?

A: We don’t just need a few new antibiotics; we need an arsenal. And we need them urgently. Bacteria are clever. They want to live. They inevitably find a way to beat everything we do to combat them. So we need multiple lines of defense. We need new antibiotics at the ready when bacteria develop resistance to the ones we’re using now—and to protect us into the future.

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