The Crispr Gene Edition Could One Day Alleviate Human Pain

For Jo Cameron, she needs the sight of the blood or the smell of her burning flesh so that she knows that something is wrong. As the Scottish writer of 71 years told The New York Times earlier this week, she lived a life virtually free of pain, fear and anxiety, thanks to a piece of missing DNA. The doctors discovered that there was something different about Cameron when she came for surgery and that she refused the painkillers after blocking the nervous system of her operation. After years of investigation, they identified the mutation never before seen, which would be responsible for its almost supernatural pain tolerance. Oddly, all the wounds that she heals are also healing faster than others and she does not remember being already feeling anxious, depressed or frightened. They published their findings Tuesday in the British Journal of Anesthesia.

In human biology, it is rare, but not unusual, that a sensation as complex as pain is controlled by a single gene. For decades, scientists have been searching for rare families whose limbs have insensitivity similar to pain and found in their DNA at least one other genetic code chain that functions as a volume knob for human suffering. Pharmaceutical companies are currently well involved in clinical trials of a drug that can simulate these effects. And the advent of Crispr offers an even more attractive possibility. What if you could genetically suppress not only the pain but also the existential fear and anguish of the human condition?

This is a particularly pressing issue as the United States struggles to tackle the deepest epidemic of opioids, killing five people every hour. Medications designed to help people escape the parts of their bodies and minds that hurt them today kill as many Americans every year as guns or car accidents. At present, some medical researchers predict that Crispr and other gene editing tools could give rise to a whole new way of treating pain without a pill. But the revelations of the past year of illicit experiences of Crispr in humans in China raise the ugly prospect of what might follow; this genetic insensitivity to pain may one day become a basic menu for baby designers, or worse, be turned into a weapon as a tool of the 21st century war.

This might seem exaggerated if it was not something Vladimir Putin himself had suggested at a Russian science event in 2017 aimed at students and describing the future of gene editing. A man able to fight without fear, without compbadion, without regret and without pain, he said, "could be worse than a nuclear bomb". You have to give it to this guy, he knows how to crush a Crispr party (for kids no less!). The super-soldiers may be only a nod to the authoritarians at the moment, but that's one of the reasons why the former leader of the American spies James Clapper called gene modification a weapon of mbad destruction in his 2016 report on the threat to national security. The intelligence badessment has in particular indicated the possibility of using technology to modify the DNA of human embryos.

The desire to permanently alter the genes of the next generation has so far been limited both by an intense ethical debate about whether man possesses enough knowledge to direct his own evolution of the species. and by practical challenges. Namely, this DNA rarely acts in a simple way. "We do not really understand how complicated biology is," said Feng Zhang, co-inventor of Crispr 60 minutes in a segment last spring. Hit a gene here or add code there and you could create other problems. Removing a gene called PCSK9, for example, significantly reduces the risk of heart attack. Great, no? But it also increases the risk of diabetes. Compromises for other, less well-studied genes could be even more unpredictable. (For Cameron, the Scottish patient, up to now, the disadvantages of her unique DNA only seem to include forgetfulness and the feeling of never feeling that "adrenaline rush" she has so much heard, nor does it have an internal alarm system to alert bones, degenerated joints, and wounds.)

James Cox, a molecular geneticist at University College London who has identified Cameron's genetic anomaly, says his group is now using Crispr in human cell lines to try to replicate its microdeletion and better understand its effects. This will help them determine the best potential treatment strategy. As the mutation occurs in a pseudogenogen called FAAH-OUT, that is, a gene that makes a long RNA chain that does not encode a protein but acts as a regulator elsewhere in the genome, they will have several options. Some of them include the design and injection of a complementary RNA sequence that represses the production of FAAH-OUT. This could potentially provide temporary and local relief. But the management of chronic pain would require frequent injections or injections. They are therefore looking for a more permanent solution: directly modify the DNA in the cells in order to reproduce Cameron's microdeletion blocking pain. "It's the beginning of your career, so you have to take that into account," says Cox. "But we think that a large group of patients could potentially be helped."

The ability to feel pain, while part of life, has evolved for a reason. It is a way for your body to warn you when something bad happens. Losing this protective sensation completely may seem great, but it can also be dangerous. This is one of the reasons why some of the early projects in the emerging field of gene-based pain therapy are not yet using Crispr (the other is the confused state of exact possession of its intellectual property). editing of genes). "The question with Crispr is that you have to do it to target only the cells of your choice, in this case the nerve cells that cluster along the spinal cord and send axons throughout your body to detect pain," explains Joseph C Glorioso III, a microbiologist at the University of Pittsburgh, is studying both gene therapy and pain management. "If you could only change these cells, you could make them more resistant to pain signaling, but it's permanent and you do not want to be in a situation where you can never feel that way."

In 2014, Glorioso co-founded Coda Biotherapeutics to develop a gene therapy approach for the treatment of chronic pain. Based in South San Francisco, Coda has already mobilized $ 19 million for the engineering of receptors for sensory neurons that can be controlled by a small molecule. The idea is to use a virus that has evolved in nature to infiltrate the hyperexcitable nerves responsible for many types of neuropathic pain, ranging from arthritic joints to back discharges and to nerve damage caused by many treatments against the cancer. A single injection into the skin sends the virus into the nerve cells, providing instructions to make this switch adjustable. When a patient feels pain, he takes the medication, which cuts off the electrical energy of the neurons and blocks the perception of pain, with minimal side effects and risks of dependence on the body. Glorioso predicts that an experimental treatment will be ready for testing in humans in 18 to 24 months. Coda first begins with pain types so severe that they are fundamentally impossible to treat, but the same approach could also be applied to other neurological conditions, including anxiety, says Glorioso.

That is, if you were one of those who saw Cameron's story and thought, "Pinch me in part!", The ability to genetically control pain is not as far away as you think.

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