newborn infant in incubator
A Brave New World

CRISPR Will Make Healthy Kids, Not Designer Babies

Thanks to the gene-editing tool CRISPR, scientists can now manipulate DNA to make designer babies and fight inherited disease. Since it has so many practical benefits, genetic engineering will likely become part of the parenting experience — at least for those wealthy enough to pursue cutting-edge medical solutions. But what will the trade-offs be? Researchers suggest they may be minimal if the technology is made available to those with “family diseases” and then rolled out slowly. And the whole thing may prove less controversial than it sounds.

Tinkering with DNA has been a touchy subject for much longer than it’s been a realistic proposition. Back in 1932 — 2 decades before Watson and Crick identified the structure of DNA — Aldous Huxley famously conceived of a Brave New World in which a genetic caste system controlled the fate of bottle-grown human embryos. A Huxleyan future was still way outside the realm of possibility when, in the first true triumphs of genetic engineering, scientists created genetically modified bacteria and mice in the early 1970s. Progress was relatively swift by scientific standards, but even 15 years ago, genetically modifying embryos was not only impossible, it seemed like it was going to be impossible for a long time. As the GMO culture wars raged, homo sapiens went on mutating the old fashioned way.

“Is the goal [of parenting] to create these sort of better and better and better children, or would something be lost if we were to have these opportunities to tinker and improve?”

Then, in 2012, CRISPR, a naturally occurring sequence of genetic code found in the immune system of bacteria, made its big splash in scientific literature. The new tool enabled scientists to modify DNA with ease and precision. Suddenly, the conversation about nature versus nurture versus laboratory manipulation had come to the fore. People were not prepared. But they’re getting there.

dna-string

A Pew poll from last summer found that about one-third of Americans were both worried by and enthusiastic about the prospect of gene editing. And those who were more familiar with the technology were more likely to say they’d like to be able to use it for their children. But, at this point, no one planning to have a child soon should expect to make use of CRISPR.

What Is CRISPR?

Short for Clustered Regularly Interspersed Short Palindromic Repeats, CRISPR is half of a 2-part gene-editing system made up of RNA and a protein called Cas9. CRISPR-Cas9, as the system is called, can identify, delete, and replace specific combinations of amino acids in a genetic sequence.

“Virtually every biology lab in the world is using CRISPR; it’s the way to do things,” says Richard O. Hynes, a biologist at Massachusetts Institute of Technology who helped lead the MGH Scientific Advisory Committee on genetic engineering. “In terms of laboratory research. It’s not the only technique for making genetic manipulations, but it’s the best — and it’s getting better.”

The most promise for a CRISPR-based cure, says Hynes, lies in conditions that are well understood and caused by a single genetic mutation, such as “bubble boy” immunodeficiency diseases.

Currently, the process is used very selectively in humans to treat existing diseases, but not to prevent genetic disorders from being passed down. Last year, Chinese researchers began using the process to alter immune cells in human lung cancer patients. A similar trial is starting at the University of Pennsylvania.

But most of what’s happening with CRISPR involves cell cultures (i.e., stem cells grown in a petri dish) or animal models, not humans. In late 2016, for instance, researchers at the Salk institute used CRISPR to improve vision in blind rats. The same treatment might appear in a human clinical trial, researchers estimated, within the next 5 years, at the earliest.

Other researchers are studying diseases with genetic components, including muscular dystrophy, sickle cell anemia, and cystic fibrosis. According to Josephine Johnston, director at The Hastings Center, the use of CRISPR in such cases will lead to better treatments and understanding of diseases.

dna research

Wikimedia Commons

But the most promise for a CRISPR-based cure, says Hynes, lies in conditions that are well understood and caused by a single genetic mutation, such as “bubble boy” immunodeficiency diseases. It’s hard to predict how long it will take for treatments to go from petri dish to people. But this is where parents can expect to see the next, most direct applications of the technology.

“CRISPR is going to have a significant impact on the treatment of disease post-birth in the next few years, particularly on cancer,” says Hynes. “Immunotherapy seems to work very well and [CRISPR] is a good way of doing it.” If people have children with muscular dystrophy or sickle cell anemia, he adds, “then CRISPR is something to think about for that specific child.” Sickle-cell, in particular, is a high-priority target.

The Hurdles Ahead

As CRISPR is so easy to use, it’s also theoretically easy to abuse. (Think: eugenics.) The most controversial, Brave-New-World-ian applications of it concern germline editing — the modification of human reproductive cells to alter the genes passed down to embryos. But clinical germline trials won’t take place in the immediate future. In fact, Hynes sees them, at the earliest, 5 or 10 years down the line.

Still, experts have already jump-started discussions about the ethics of germline editing for when that day comes. In 2015, an international group of scientists issued a consensus statement recommending a moratorium on germline applications of CRISPR. Then, this past February, a national advisory group of scientists and doctors reversed that position and expressed support for germline editing — but only under certain conditions.

As CRISPR is so easy to use, it’s also theoretically easy to abuse.

Among other requirements, the report stipulated that germline editing should only be done to prevent serious diseases from being passed down; when there are no reasonable alternatives; when research is coupled with a “long-term, multigenerational follow-up” plan to protect personal autonomy; and after the benefits/risks have been assessed and public opinion has been accounted for.

While small, these new stipulations mark a small opening in a door that could widen as CRISPR progress moves forward.

The Promising Future Of Genetic Engineering

The biggest hope is that germline engineering will make it possible for people who have Huntington’s, Tay-Sachs, and other such rare genetic disorders in their families to eliminate the chance of passing on their mutations. And that’s because CRISPR works differently than solutions that are available currently.

newborn in incubator

Wikipedia

Today, prospective parents can use IVF to make multiple embryos and then discard those that test positive for the relevant disease. CRISPR would eliminate this trial-and-error process. Still, even in theory, Hynes says, it wouldn’t shield children from such genetic problems as Down’s Syndrome that are caused by spontaneous mutations in the embryo.

Researchers have already performed germline editing in mice, but the consequences make it too risky for human experimentation.

“Basically what happens is when you try and do it on an embryo very often some of the cells get edited and others don’t,” says Hynes. “So now you have an embryo that’s a mixture of fixed cells and not fixed cells. And that’s okay for mice, but it’s not something you want to make a baby from.”

The biggest hope is that germline engineering will make it possible for people who have Huntington’s, Tay-Sachs, and other such rare genetic disorders in their families to eliminate the chance of passing on their mutations

Regardless, both Johnston and Hynes urge the general public to keep up with developments in CRISPR research. Public opinion, they explained, is going to be factored into policy decisions going forward. And Johnston thinks that CRISPR, and gene-editing in general, raises questions that are relevant to everyday parenting issues.

“Some of the conversations that gene-editing sparks are helpful for us to think about in terms of determining what the goals of parenting are,” says Johnston. “Is the goal to create these sort of better and better and better children, or would something be lost if we were to have these opportunities to tinker and improve? It’s a question of how much information, and how much control, do you really want to have?”

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