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Genetic engineering to eradicate deafness

two drops. That's all it took to cure Aisam Dam from homeland destruction, forever. Two drops that were instilled in his ear and gave the 11-year-old boy the ability to hear - for the first time in his life - human voices

Genetic correction of deafness problems. Illustration: depositphotos.com
Genetic correction of deafness problems. Illustration: depositphotos.com

two drops. That's all it took to cure Aisam Dam from homeland destruction, forever. Two drops that were instilled in his ear and gave the 11-year-old boy the ability to hear - for the first time in his life - human voices. Along the way, those two drops mark the continuation of progress in diseases that were considered incurable until now, and also managed to jump start some people in the deaf community - and not for the better.

But let's start at the beginning.


The boy who couldn't hear

Aisam emerged from his mother's womb into a world of absolute silence. The toddler grew up in Morocco expressing his wishes to the environment in a sign language he invented himself. At the age of ten, his family moved to Spain, and the boy got to see a hearing specialist who suggested that they sign up for an extraordinary treatment: a clinical trial in genetic engineering that might cure his deafness.

The reason for the tempting offer is that Issam suffers from a very specific type of genetic deafness, shared by only about 200,000 other people worldwide. The deafness is caused by a mutation in a single gene, called autoperlin (not like auto chocolates, because the P is not stressed). The mutation results in one of the critical proteins in the hair cells in the inner ear being destroyed, so that the cells are unable to receive sound waves from the environment. Unlike other genetic deafness diseases, the mutation in autoperlin does not cause the death of hair cells. They continue to exist, but without being able to perform their function. To cure the disease, one only needs to complete the deficiency by integrating the corrected gene into the DNA of the cells.

We also need patients who will agree to receive the treatment, and this is where Issam enters the picture, along with Eight children in China, because the research was conducted jointly with researchers from the state. All with the support of the pharmaceutical giant Eli-Lilli, and the biotechnology company Akous.

Why do all the children in the study come from developing countries? The answer adds another layer of complexity to the treatment. 


When science fiction becomes history

About a decade ago, people - children and adults alike - started appearing on city streets with a futuristic-looking electronic button attached to their skulls. There's a pretty good chance you've seen these people yourself at school, university, work or on public transport. All those people would suffer from total hearing loss if it weren't for that 'button' that allows them to hear their surroundings and lead a completely normal life.

The button on the skull is only the transmitter - and sometimes also the microphone - that translates the sounds and noises from the environment into electronic signals, and transmits them to the "cochlear implant". What is the cochlear implant? These are electrodes implanted inside the cochlea: an area in the inner ear that transmits information to the brain about sounds coming from the environment. In many deaf people the cells in the cochlea are not able to do their job, so the electrodes replace them and transfer the the information directly to the nerves

The cochlear implants have saved the hearing of many, but in order for them to work well in children, they need to be implanted at a young age. As evidence, you can find toddlers in kindergartens today with the cochlear implant, which allows them to function like their peers. Unfortunately, the implants themselves change the structure and function of the cochlea, and thus they may actually complicate the genetic engineering experiments that are supposed to cure deafness. 

This was the reason that all the patients in the current trial came from poor countries, where it is more difficult to find funding for a cochlear implant for each child. Issam Dam, whose family is not rich in money to say the least, did not receive such a cochlear implant as a child, and therefore qualified to receive the new experimental treatment for free - and even received coverage for the expenses of his stay in Philadelphia, where the same drops with which we opened the article were instilled into his ear.

The drops did their work with extraordinary speed. They contained a large number of harmless viruses, which contained the modified version of autoperlin and injected it into the hair cells of the cochlea. The cells received the correction to their genetic code and began to act on it. 

In less than a week, Issam was able to hear sounds for the first time in his life. 

Two months later, his hearing ability was already close to that of a normal person.

Before we all get excited to the roof - and there is something to be excited about - we must recognize that this is not a fairy tale from the Disney worlds. Issam does not go out into the streets with songs and dances. The brain has a very narrow window of opportunity to develop the ability to speak, and it closes around the age of five. Issam will never speak clearly again, but at least he will be able to tell when others are trying to communicate with him, listen to music and enjoy politicians' speeches. But Eissam, with all respect and joy for the successful treatment he underwent, participated in the experiment only as a way to demonstrate the capabilities of the new treatment. He was never meant to be one of those to get the most out of him.

Who is the new treatment really intended for? For the thousands of babies who are born every year with this genetic deafness, and now they will be able to get rid of it after a single treatment. And every sane person understands that the revolution will not stop here. Other genetic problems that lead to deafness may be more complicated, but sooner or later we will be able to deal with and cure them as well.

And this progress, as exciting as it is, is very scary for some people. especially the deaf.


Deaf culture

Imagine a planet named Eyeth. This is a distortion and pun on the name of the Earth in English - Earth - which includes the word "ear" in it. Well, Ayth in English includes the word "eye" in his name. Eith is the planet of the "people of the eyes". Almost all Aethians use sight as a way to pick up verbal messages: in other words, they communicate using sign language. A very small minority of the residents of Aith are also able to hear.

The people of Ayth maintain a civilization with a rich and fascinating culture. They have several different sign languages ​​of their own, each with its own subtleties. They are sharp-minded and sharp-eyed, and pay attention to the movement of every muscle in Ben Sheyham's face. Although they are unable to hear, they find pleasure in an abundance of social activities and even works of art that do not require receiving sound waves from the air and decoding them in high resolution. When Eighth residents have a child who can hear, parents are often left confused: what to do with the baby who reacts in strange and unexpected ways to the environment? How should they deal with a child who suddenly covers his ears for no apparent reason?

If Eithe sounds like a fascinating place to visit, you don't have to try too hard. Go explore the deaf community on Earth itself, and discover Eighth on Earth. You will also discover that although some deaf people are interested in restoring their hearing, others treat the hearing impairment as an entrance ticket to that community, and as a feature that characterizes and distinguishes them. Some deaf parents hold a party when they discover that their child is also deaf, and therefore can be part of the community. You can understand them. No one wants to abandon the planet, the civilization and culture they grew up in.

It is no wonder that among some members of the deaf community, the possibility of treating deafness with genetic engineering is seen as "An existential threat to the prosperity of the deaf communities.” It scares them, and at the same time it certainly excites and excites other parents from the deaf community, who do not want their children to face the same difficulties they experienced.

The current treatment will not pose too much of a threat to the deaf community, as it is only for one disease. But what will happen when it expands to include other genetic defects that impair hearing? Is it right to deny children their "birthright" to take part in the deaf community? Isn't there a real threat to another culture? There are still no good answers to these questions, and probably each parent will have to decide for themselves how to act.


The price of two drops

The other type of person who isn't quite sure how to react to this happy development is the marketing people working for the pharmaceutical companies. These see the trends and understand where the world is going: for genetic engineering treatments, which are capable almost overnight of changing the condition of a child from a seriously ill person to a functioning individual with a completely normal life expectancy. And that's great, but what will the price tag be for these new drugs?

The currently accepted model in the pharmaceutical industry is the one in which customers purchase drugs - whether they are pills, pills or ampoules for injection - every week or two. Each of the pills is priced in a way that will reward the pharmaceutical company for the extensive research and development it has invested in that drug - a cost that often reaches tens of millions of dollars. Such a cost justifies itself in the long run, as patients often continue to take the pills throughout their lives. 

What happens when they only have to take the medicine once - and that's it?

We are starting to see the answer coming from the field. In 2019, the most expensive drug was Zolgansema, whose one-time administration was priced at 2.1 million dollars. Since then, several other single-use genetically engineered treatments have appeared, and Zolgansema is far behind in terms of prices. The most expensive drugs from the last two years - Skysona for the treatment of a brain problem in children, Alvidis for the treatment of muscular dystrophy and Megenix for the treatment of hemophilia - are already going up More than three million dollars for one treatment

Does that sound like a lot? Well, it's really a lot of money, but you have to remember that it goes to the pharmaceutical companies by right, as a return for all their development efforts over many years. Beyond that, the insurance companies are the ones who cover almost the entire cost of the drug, and if they decide that it does not justify the cost - then the price will drop accordingly. The fact that the drug companies can charge such sums for the drugs indicates that they work well and dramatically reduce the frequency of hospitalizations and the other complicated medical treatments that often last throughout the patient's life. In the end, the medical insurance companies prefer to pay this amount - and even see it as a profitable deal.

Still, this is a very different marketing model from the one most pharmaceutical companies have become accustomed to so far. The sales people will have to get used to the new marketing methods and the new prices. Don't worry about them. they will survive. 


The big meaning

The real significance of the new deafness treatment is that genetic engineering continues to advance and succeed as time goes on. That should make us all happy. Children who grew up in a life of hardship and non-stop medical treatments, are about to receive genetic treatments against beta-thalassemia, hemophilia, deafness - and recover as if they never had the disease in the first place.

This, of course, would be just the beginning.

In a review conducted in 2022, the researchers predicted that by 2025 dozens of new treatments based on genetic engineering would be approved. Clinical trials of such treatments take longer than usual - about 3.5 years for genetic diseases - but if the results are as we have seen so far, then it will be worth the wait. 

The most advanced experimental treatments currently focus on genetic diseases, with more than forty treatments in clinical trials. These treatments cover a variety of genetic diseases with tooth-breaking foreign names: familial chyloemiconemia syndrome, neuropathic amyloid, lipoprotein lipase deficiency, primary hyperoxaluria, and much more. I could write an entire article about the past and present of each of these diseases, but the hope is that thanks to genetic engineering - there will be no need for that. We remove them from the world. The doctors of the future will not learn how to treat these diseases. They will be included in the syllabus in the faculties of medicine only as remnants of the past, just as they do not currently learn to treat the disease of smallpox, which mankind exterminated with great effort almost fifty years ago. 

Genetic diseases are not the only cause of suffering in the world. After the Corona years, there is no need to elaborate on the dangers inherent in infectious diseases of all kinds. The tuberculosis bacterium claims the lives of more than a million people every year. The malaria parasite kills 620,000 people a year, rivaling only the HIV virus that causes AIDS, with 630,000 annual victims. And of course, the man-flu will kill half of humanity sooner or later (although I couldn't find an authoritative scientific source for that particular claim).

What if we could vaccinate humans against these infectious diseases? It might be possible, although it probably won't happen in the next decade. We see that in the earlier stages of clinical trials, it is possible to find more than ninety genetic engineering treatments for infectious diseases, with most of them immunizing the body against those diseases. The focus right now is on providing immunity to AIDS, Covid-19, malaria, Ebola, hepatitis C and B and human papilloma virus infection. 

Success in all of these will not come tomorrow morning, of course. Still, if I survive the man-flu and write about genetic engineering in a decade, there's a good chance I'll already be telling about the first children and adults who received a genetically engineered vaccine against bacteria, viruses and parasites that have been killing humans since the dawn of history. A decade later - when we approach the middle of the 21st century - we may already see large-scale vaccination campaigns that will be given only once, and will eliminate infectious diseases and even some types of cancer from the world.

If and when we do succeed, we can celebrate the success of human science, innovation and research that led us to these great achievements. Parties will be held all over the world, fireworks will be launched into the air and happy music will fill the streets.

Issam Dam, the boy who was born deaf by the decree of fate and was cured by human rights, will be able to hear all these.

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