We got a glimpse of an amazing future last week when doctors at the Children's Hospital of Philadelphia (CHOP) used a gene splicing technique to repair the genetic sequence of an infant suffering from a life-threatening genetic disorder.
Dr. Rebecca Ahrens-Nicklas, an assistant professor of pediatrics and genetics at the hospital, says, "This shows the potential — that we can really open the door for these transformative treatments for patients who really have no other options. It really is sort of limitless in terms of what the possibilities are."
According to an Associated Press report, more than 350 million people around the world suffer from genetic diseases. Most of those illnesses aren't treatable with drugs or surgery. Repairing the DNA sequence causing the disease using the gene-splicing tool CRISPR (clustered regularly interspaced short palindromic repeats) has shown promise in past applications. But this is something totally different.
The infant, KJ Muldoon, received a personalized treatment that was designed to fix the tiny imperfection in his DNA sequence. KJ was born with a severe CPS1 deficiency, meaning he lacked an enzyme needed to remove ammonia from the bloodstream. Ammonia is a waste product produced by the liver. The liver converts ammonia into a less toxic waste product called urea, which the kidneys convert into urine.
KJ's parents, Kyle and Nichole Muldoon, had a lot to consider when deciding what to do to save their baby.
“We were, like, you know, weighing all the options, asking all the questions for either the liver transplant, which is invasive, or something that’s never been done before,” Nicole said.
“We prayed, we talked to people, we gathered information, and we eventually decided that this was the way we were going to go,” her husband added.
The doctors used the CRISPR technique to fix the faulty gene in KJ's body. CRISPR won its inventors, Emmanuelle Charpentier of France and Jennifer A. Doudna of the United States, a Nobel Prize in 2020. The technique involves splicing the faulty gene strand. This personalized approach involves a "technique that flips the mutated DNA “letter” — also known as a base — to the correct type," says AP.
It’s “very exciting” that the team created the therapy so quickly, said gene therapy researcher Senthil Bhoopalan at St. Jude Children’s Research Hospital in Memphis, who wasn’t involved in the study. “This really sets the pace and the benchmark for such approaches.”
In February, KJ got his first IV infusion with the gene editing therapy, delivered through tiny fatty droplets called lipid nanoparticles that are taken up by liver cells.
While the room was abuzz with excitement that day, “he slept through the entire thing,” recalled study author Dr. Rebecca Ahrens-Nicklas, a gene therapy expert at CHOP.
After follow-up doses in March and April, KJ has been able to eat more normally and has recovered well from illnesses like colds, which can strain the body and exacerbate symptoms of CPS1. The 9 ½-month old also takes less medication.
While the benefits of gene editing are self-evident, the downside can be equally troubling.
First, the cost of the technique is prohibitive. Pharmaceutical companies are reluctant to do the research and develop treatments because, while genetic diseases are not uncommon, a treatment would have to be developed for each of the dozens of genetic defects. The economics of gene therapy don't make sense.
Beyond that, there are the moral implications of this technology being used for questionable purposes.
Much of the world became aware of CRISPR in 2018, when Chinese scientist He Jiankui revealed he had helped make the world’s first gene-edited babies, to try to engineer resistance to infection with the AIDS virus. His work was denounced as unsafe human experimentation, and he has been sentenced to prison in China.
In September, an international panel of experts issued a report saying it is too soon to try such experiments because the science isn’t advanced enough to ensure safety.
“Being able to selectively edit genes means that you are playing God in a way,” said American Chemistry Society President Luis Echegoyen, a chemistry professor at the University of Texas El Paso.
“New technology often presents this dichotomy — there is immense potential for human benefit, especially for disease treatment, but also the risk of misapplication," said Dr. George Daley, dean of Harvard Medical School.
One potential "misapplication" is the use of the technology to create "designer babies." The film "Gattaca" gave us a glimpse of such a dystopian future where perfect humans were given the best jobs, the best opportunities while those whose parents couldn't afford the gene therapy saw their children become second-class citizens.
Should we create babies that are immune to certain diseases? Or should the technology only be used to treat genetic diseases such as KJ's illness? It's a moot point because once the technology matures and "designer babies" become a reality, no moral or ethical boundaries are going to be observed everywhere by everyone.
