Home » News » Heredity Is Nobody’s Fault. Until Now.

<p>Building them better.</p>
 Photographer: Jonathan Nackstrand/AFP/Getty ImagesWe are all unwitting players in a genetic lottery. Take a gene called APOE. It comes in three flavors – APOE2, APOE3 and APOE4. All three are considered normal human genes, but people who were dealt an APOE4 face three to five times the average risk of getting Alzheimer’s disease. Since we inherit a copy of the gene from each parent, a few unlucky people will be stuck with two copies of the APOE4 version and face an even higher risk.

To put it in perspective, by age 75 about 3 percent of people get Alzheimer’s. For those with double APOE4, that rises to about 30 percent.

Now a technology called gene editing could allow us to rig the game. Geneticists say that with a particularly effective new editing tool called CRISPR, it would a relatively simple matter to change one form of the APOE gene into another. That means prospective parents could take their sperm or eggs in for editing, thereby banishing the high-risk version of the gene from their offspring.

The possibility of changing people’s DNA before they are born has led to an eruption of alarming headlines about the hubris, or the promise, of creating the “perfect baby,” or of “engineering the human race.” This kind of hype is a distraction.

But there are ethical and philosophical challenges raised by this technology that should be taken seriously. Today, you can’t blame your parents for passing you an APOE4 gene. Future generations might.

Scientists are understandably excited about CRISPR because it can allow them to make precise changes in the genetic material – the DNA – adding or deleting small sections of code or changing a single code letter. CRISPR is already widely used in lab animals and livestock, including pigs engineered to make their organs more compatible for human transplants.

What has the scientific world unsettled is the capacity to make genetic changes that could be propagated to future generations – altering what’s known as the human germline. That’s been the subject of a series of summits. The most recent, held in early December, led to a statement that it’s “irresponsible” to use editing on the human germline before society reaches some consensus about appropriate use.

But if there’s a market for it, people will move forward whether it’s responsible or not, argues medical ethicist Art Caplan. “There should no longer be any doubt about whether humans will one day be genetically modified,” he wrote in an essay shortly after the summit.

The one thing we don’t have to worry about is the perfecting of the human race. Perfection is in the eye of the beholder. Blond hair and blue eyes are often invoked in the discussion of perfection because that’s what the Nazis preferred, but in sunnier climates, those naturally fair-haired types face a high risk of sunburn, premature wrinkling and skin cancer.

The idea of creating a master race or a generation of superbabies looks even more unlikely in light of the way people have employed currently available genetic screening. Today, doctors can perform genetic testing on embryos conceived through in vitro fertilization – pulling off a single cell to screen for mutations. That way, couples can already create multiple embryos and choose to implant one that doesn’t carry some genetic disease carried by one or both parents.

In a few cases, people have used genetic screening to increase the odds of having children with traits that mainstream society would consider disabilities. Some deaf couples say their perfect baby would be deaf, and people with dwarfism sometimes prefer a dwarf child to one of average height.

Gene editing fundamentally shifts the already charged ethical and philosophical discussion surrounding such cases. Parents could impose their tastes on offspring by altering genes, rather than just selecting from combinations that occurred naturally.

Imagine that you are the child of deaf parents. In a world before CRISPR, you might find out that they used IVF and selected the embryo that carried a gene for deafness, or, conversely, a gene for hearing. It hardly matters which choice they made or whether you agree with it. If they had chosen another embryo, you wouldn’t exist.

Or maybe you have cystic fibrosis because your parents didn’t undergo genetic screening. If they had, they might have had a healthy child. But it wouldn’t be you.

But if germline gene editing is deemed safe and starts to catch on, children of the future might realize that their parents could have chosen a different version of them – one with a different hearing capacity, or a different dose of growth hormone, or a lower risk of Alzheimer’s disease.

Perhaps someday, but in the shorter term, some biologists say a more realistic way someone might use CRISPR to improve on normal kids would be to induce rare mutations already known to exist in humans – ones that appear to to endow their carriers with advantages. There’s a family of Finnish speed skaters known to carry a mutation in their red blood cells that boosts their aerobic capacity, for example. There are mutations that give people unusually low cholesterol and a low risk of heart attacks, and there are mutations that allow people to get away with sleeping less than the rest of us.

Few scientists or doctors would consider it ethical to make such changes in normal human sperm, eggs or embryos, given that the risks aren’t yet understood and the treatments aren’t lifesaving. While the same may be true of certain forms of cosmetic surgery, patients can give consent. Here, the people facing the risk aren’t yet born.

That doesn’t mean it won’t be done, somewhere. And eventually, if animal testing shows it’s safe enough, gene editing could become big business and even a requirement of good parenting.

And yet, there remain long-term unknowns. In the case of the APOE genes, the most desirable type would appear to be APOE2. People with this form have a lower-than-average risk of getting Alzheimer’s disease. And yet the most common form floating around the human gene pool is APOE3, which is associated with average risk. We don’t know whether there are other advantages to APOE3 or even APOE4. Perhaps they give people an edge in something scientists haven’t yet thought to look for. What would happen if we eliminated these forms of the gene and left only APOE2?

Finally, with Alzheimer’s, there might turn out to be a less fraught solution. Gene editing would help a child 75 years in the future. By then there might be a cure.

This column does not necessarily reflect the opinion of the editorial board or Bloomberg LP and its owners.



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