1 baby, 3 genetic ‘parents’ — is this the future?

Creating a baby with DNA from three people. It sounds futuristic, maybe even dystopic — but it could offer a way out of a class of devastating genetic diseases that affects 1 in 5,000 across the world.Last week, doctors in the UK announced that eight children born to seven women who were at high risk of passing on these incurable diseases have been doing well — because they were born after a pioneering procedure in which IVF embryos were tweaked to replace “disease-causing” mitochondrial DNA.Mitochondrial diseases are notoriously difficult to diagnose and impossible to cure, as of now.So, if the results of this trial hold, it would mean preventing a host of conditions like Leigh syndrome (a progressive brain disorder), Alpers disease (a progressive neurodevelopmental disease), Leber Hereditary Optic Neuropathy (marked by vision loss) or Progressive External Ophthalmoplegia (which impairs eye movement). The mitochondria has its own genetic systemWhich is separate from the genetic system of a cell. A quick refresher on some school biology — mitochondria is this tiny energy factory inside a cell. It converts nutrients into the energy that powers nearly every function in your cell. In fact, it is believed to have evolved from bacteria that learnt to live within larger cells.Our DNA — the genetic code of how we grow and function — is stored in the nucleus of the cell as a tightly packed sequence of 23 pairs of chromosomes which carry about 20,000 genes. A tiny amount of DNA — just 37 genes — sits separately inside the mitochondria, passed down only from the mother.When mitochondrial DNA mutates — and they are more vulnerable to mutation than nuclear DNA — a person carrying them may or may not experience symptoms. But since mitochondrial DNA is inherited entirely from the mother, a child would inherit the same mutations and, if the proportion of mutated mitochondria is high, the child could develop serious diseases. And most of it is because the mutations reduce energy to tissues that need a lot of energy to function — like in the heart, the brain, the muscles.So, the UK doctors replaced the ‘faulty’ mitochondrial DNAThe treatment is called pronuclear transfer, one of two primary methods for mitochondrial donations.The father’s sperm is used to fertilise two eggs — one from the mother, and one from the donor.Which means there’s a fertilised egg with “faulty” mitochondria, from the mother. And there’s a healthy fertilised egg with healthy mitochondria, from the donor. Then comes the switch.The nuclear DNA is removed from the mother’s fertilised egg and saved. Then, the nuclear DNA is removed from the donor’s fertilised egg and discarded. After that, the mother’s nuclear DNA is placed inside the healthy fertilised egg from the donor. The fertilised donor egg now has the nuclear DNA of the parents, and mitochondria DNA primarily from the healthy donor.UK was the first country to allow itIn 2015, the UK passed a law to allow mitochondrial donation treatments for women at high risk of transmitting mitochondrial diseases to their children. The Newcastle University was licensed to conduct its trial in 2017, and it planned on treating 125 women over five years. But things moved a little slower than they would have liked because getting donors was difficult and some bits of the IVF procedure were harder to sort out, Financial Times reported. “Some of the mothers already had symptoms of mitochondrial disease including vision loss and heart problems. Others had family members with the disease and remain at risk of developing symptoms and passing it on,” the university’s statement said.In any case, pregnancies were confirmed in eight out of 22 patients who underwent pronuclear transfer. And seven of them have given birth — one is still pregnant.The ages of the four girls and four boys born after this procedure (including a set of twins) range from a few weeks to more than two years. And they “show no signs of having mitochondrial DNA disease,” the Newcastle University, where the research team is based, said in a statement. “The mother’s disease-causing mitochondrial DNA mutations were either undetectable or present at levels that are very unlikely to cause disease.”One child developed muscle jerks, which resolved itself without treatment. One developed high blood fats, which had affected the mother during pregnancy and was fixed with a low-fat diet, and an abnormal heart rhythm, which is being treated. And a third child got a urinary infection that went away with antibiotics. None of this, the researchers said, was thought to be related to the mitochondrial DNA mutations because of the low levels of the mutations. “Symptoms for these mutations are only seen with levels above 80%,” the statement added.So, what’s the hold-up? The ‘modified humans’ debateEarlier, even in the UK, sperm, eggs and embryos could only be used in fertility treatment if they were “naturally derived” from the human body and not genetically altered in any way. The laws referred specifically to mitochondrial DNA alterations in its banned list. A slight opening for mitochondrial donations was created in 2009, when the government was allowed to make regulations for this process. And it was only in 2015 that the law allowing it for replacing “unhealthy mitochondrial DNA” was finally passed.A decade on, only one other country — Australia — has explicitly allowed it, and a handful of others — like Ukraine and Greece — have been ambiguous enough with their regulations for actual mitochondrial donations to go through.But if it could prevent an incurable set of diseases, why have lawmakers across the world been so cautious? In 2013, when Sweden was examining mitochondrial donations, its National Council of Medical Ethics had said that the existence of the choice itself might be unethical. “If this technique is permitted, we would thus risk a development towards a society that discriminates, a society that places demands on citizens to reject and make the right choices,” it said.But the broader, more consistent concern of those opposed to it is that it amounts to “genetic modification” of human beings. Because it reduces the chances of certain diseases, it “improves” the gene pool — and that, its opponents say, is a step away from eugenics. When the National Academies of Sciences, Engineering and Medicine was asked to examine the procedure by the US Food and Drugs Administration (FDA) in 2015, its report said that the distinction between eugenics and genetic interventions that help “depends on whether the latter are carried out in contexts where proper safeguards are in place.” Besides, if the procedure turned out to be unsuccessful or, worse, caused adverse changes, “any missteps in the genetic modification and the associated health outcomes would be transmitted irreversibly to future generations.” Another concern among some scientists has been about something called “reversion”. As the MIT Technology Review explained it two years ago, “When you scoop out nuclear DNA, it is difficult to completely avoid taking some of the cytoplasm—including (mitochondrial) DNA—along with it.” So, if a high percentage of the mother’s unhealthy mitochondria is carried over to the donor egg when the nucleus is being moved, over time, it might amplify to a point that causes disease in the child.These caveats notwithstanding, the National Academies report had found it “ethically permissible” to conduct clinical trials for the procedure. “The desire of prospective parents to have children who are at significantly reduced risk of manifesting serious (mitochondrial DNA) disease … is justifiable,” it said. But the ban in the US remained in place anyway because of a bill that stopped the FDA from using its funds for “heritable genetic modification”. Images breaking down the process are from a Newcastle University explainer video here.The lead image has been generated with AI.