SPEAKER 1: There’s an expression, someone is feeling no pain. But there are a select few humans who really can’t feel pain. One of those people is Jo Cameron. Here she is in a New York Times interview from 2019.

JOE CAMERON: I was going through childbirth. And I kept thinking, as soon as I feel pain, I’ll ask for it. I’ll ask for it. And before I realized it, I had the children.

SPEAKER 1: She’s also never been anxious or afraid. Researchers have been studying Jo Cameron and her brain in an effort to better understand her sensory experience. And this week, researchers published a new study that looks at the genes and mutations responsible for Jo’s pain-free existence. They hope to use what they learn to come up with better pain management treatments.

Joining me now to talk more about this research is my guest, Andrei Okorokov, Associate Professor at the Wolfson Institute for Biomedical Research at University College London. Welcome to Science Friday.

ANDREI OKOROKOV: Hello. And thank you for having me on the show.

SPEAKER 1: It’s great to have you. You’ve been working with Jo Cameron for about 10 years now. What is it about her condition that makes her so fascinating to study?

ANDREI OKOROKOV: I think it’s a very rare condition when not only we have a lack of pain sensation, but we have other benefits of a mutation she has that allows you to be never having anxiety or depression. And also, she is healing much faster than other people, about 20%, 30% faster. All this together are– is essentially a gold mine for researchers trying to find a connection between mutation and what genes are involved. And so we can try to develop new therapies.

SPEAKER 1: So all of these seeming advantages, the pain management, the mood, the anxiety, nervousness, all of this gets traced back to one gene mutation?

ANDREI OKOROKOV: That is correct. Amazingly enough, the mutation that she has affects a system that is the endocannabinoid system. And the small fatty molecules in the cannabinoids take part in signaling between different cells in our bodies and in our brains. And they signal about pain, about immune response, about appetite, and other mood conditions.

The first signs of that we might be dealing with something like that, Jo was treated with morphine at one of her surgeries. And she was really sick after that. And that tells us that people usually have problems with the morphine treatments when they have mutations or changes with their endocannabinoid system.

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So in 2019, you found this original mutation that seems responsible for all of this cascade of effects. Where have you gone from there? What do you better understand now about her condition?

ANDREI OKOROKOV: I had this analogy with the Wordle game that our back four years, we had only one letter in a word which we knew and the position of it. So now we have all five. And we know their position. So we know the word.

But we still have to put this word and all these pathways between genes in the big context of our human body and make sure that whenever we go and try targeting this in terms of working on potential treatments, we do not affect something very vital and important.

SPEAKER 1: So you mentioned that it’s not just that these genes are completely off, they’re dialed down. Why is that important for you to be able to understand?

ANDREI OKOROKOV: Some of the genes are dialed down, especially the first one, the main original gene where it all starts. Why it’s important for us, well, there were some unsuccessful trials before with chemical drugs developed to inhibit this particular enzyme. And these molecules were aimed to inhibit it completely. And side effects were drastic and very unpleasant.

Therefore, some trials were stopped. So now, knowing that we can regulate this enzyme without targeting it with small molecules or even going back and looking again in all these libraries of molecular compounds being tried and picking up those which are not inhibiting it completely, not having any side effects, but also can target this area of mutation, which is producing a small molecule called RNA, ribonucleic acid.

And it’s a long noncoding RNA. It doesn’t make protein. But it does regulate activity of the main gene. Therefore, we can target somewhere else. And we don’t have to drive a body or organ or tissue or brain into the undesirable side effects.

SPEAKER 1: So we all experience pain differently. Do we know what’s going on with, quote, unquote, “normal people” that feel less pain as opposed to no pain?

ANDREI OKOROKOV: Oh, it’s a very good question. There are over 200 genes which are connected to pain circuits. And it really depends which gene is affected by mutation. For example, we had a family from Italy with the Marcelli family. That’s called Marcelli syndrome, with one of the proteins being mutated. And that rendered them to a condition where they would feel the initial impact of injury. But then it will be very quickly going away.

So they wouldn’t have any chronic pain after that. So it really depends on what mutation people carry.

SPEAKER 1: So on one level, it sounds great not to be able to feel pain and not to have anxiety, not to be afraid. Are there any downsides to this?

ANDREI OKOROKOV: The downsides come when you’re child, when you develop because pain is of our cognitive protector. It protects us from behavior which may lead to injury. So essentially, it’s very useful for kids to have some level of pain sensation, of course.

SPEAKER 1: So what’s next for the 10 years ahead in studying this?

ANDREI OKOROKOV: Recruit more funding, of course.

[LAUGHTER]

The more funds we have, the more we can work on it, start looking into other things like anxiety, depression, and fear because we were primarily focusing on pain. Also look more into this long noncoding RNA. And what used to be treated as a junk DNA 20 or so years ago now is something that makes very important regulatory molecules.

So there is a massive part of an iceberg we didn’t look at yet. So that’s probably more than 10 years from now on. But definitely enough things to do for a quite considerable future.

SPEAKER 1: Well, I wish you and Jo Cameron best of luck in your future research.

ANDREI OKOROKOV: Thank you so much.

SPEAKER 1: Andrei Okorokov is an Associate Professor at the Wolfson Institute for Biomedical Research at University College London based in London, England.

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