The debate over gene editing in unborn children has just taken a major turn.
Denis Rebrikov, a biologist for Russia’s largest fertility clinic, the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology in Moscow, recently told New Scientist that he plans to use CRISPR for hearing loss. In other words, he intends to use the CRISPR gene-editing technique to help five Russian couples give birth to a biological child who can hear. He’ll petition the Russian government for permission in the next couple of weeks.
Recessive Deafness Gene
Approximately 80% of hearing loss is hereditary and inherited via an autosomal recessive pattern. “What this means,” Eamon McLaughlin, MD, ENT, tells Parentology, “is that two copies of the abnormal gene — one from the mother and one from the father — must be present to cause the disease. Numerous mutations have been found to be responsible for hereditary hearing loss inherited in this pattern. The most common is the GJB2 gene, which codes for protein connexin 26 … [and] accounts for 50% of autosomal recessive hereditary hearing loss.”
This gene — GJB2 — is precisely the gene that Rebrikov plans to correct using CRISPR.
According to the New Scientist report, it is not uncommon for individuals in Western Siberia to miss one DNA letter in position 35 of the GBJ2 gene. Though having one missing copy of the gene has no effect, inheriting the same mutation from both parents results in deafness from birth.
“The Russian families in question,” McLaughlin says, “are consistent of parents who have both mutations in this gene. Since it is autosomal recessive, neither parent has a functioning copy of the gene to give to their child. Therefore, the child will be born deaf.”
The five couples Rebrikov found do not want their children to be born deaf. If the Russian government approves this, he plans to use CRISPR technology to correct the mutation in IVF embryos.
Using CRISPR to Stop Deafness
Rebrikov plans to use homology-directed repair — a mechanism in cells to repair double-strand DNA lesions — to prevent deafness.
“CRISPR uses enzymes to find a specific segment of DNA, here connexin 26, cut it out and then replace it with a functioning copy,” McLaughlin explains. “Since the disease is autosomal recessive, you only need one good copy of the gene to have normal hearing. This would have to be done on an embryo in the lab. To date, only one scientist in China has claimed to do this.”
“Technically, it is achievable,” CRISPR expert Gaetan Burgio at the Australian National University tells New Scientist. However, the big question is, should it be done?
Safety and Ethical Concerns
Though there is significant potential for human genome editing, a statement by the Organizing Committee of the Second International Summit on Human Genome Editing explains that the technique poses risks that “remain difficult to evaluate.” The committee expresses the concern that editing only select cells in early-stage embryos may lead to the perpetuation of disease by unedited cells and that germline editing could result in unintended harm to the individual and possibly the individual’s descendants.
“Changes to a particular trait may have unanticipated effects on other traits that could vary from person to person and in response to environmental influences,” the statement explains. McLaughlin echoes these sentiments.
“While the procedure is scientifically possible, the real question is should it be done [because] the degree of hearing loss caused by these mutations varies,” he says. “Some patients could be born with mild hearing loss that could be treated with hearing aids, or even patients with more severe hearing loss could be identified early and offered cochlear implants before the age of 1.
“For novel medical technology, especially gene therapy, many people would agree that ethically we should start with cases that would otherwise be fatal or have no other options.”
Safety issues aside, many are also concerned with the preservation of deaf culture. “Many in the deaf community view deafness as a culture and not a disability,” Laughlin says. “When doctors first started implanting cochlear implants, there were protesters at our national meetings.” In fact, according to New Scientist, many deaf parents want their children to inherit the GJB2 mutation for the sole purpose of preserving the unique deaf culture.
Using CRISPR for Deafness — Sources
New Scientist — Exclusive: Five couples lines up for CRISPR babies to avoid deafness
Eamon McLaughlin, MD, ENT
Statement by the Organizing Committee of the Second International Summit on Human Genome Editing: On Human Genome Editing II