In December 2017, the FDA approved a gene therapy for the treatment of a rare, inherited form of retinal blindness. For the first time in the nation’s history, a gene therapy was approved for the treatment of a genetic disease. The therapy, known as LUXTURNA™ (voretigene neparvovec-ryzl) and developed by researchers at Penn and Children’s Hospital of Philadelphia over the course of many decades, significantly improves eyesight in patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy. For patients living with this mutation, many of whom become totally blind by mid-life, this was a life-changing moment. For the medical community, it marked a figurative crossing into a much larger world; the world of gene editing.
Whether academic or athletic, there is a limit to what modern humans are capable of. The reasons for this have much to do with our genetic makeup. Parents who are both four feet tall are more likely to give birth to a child who will grow to a similar height. Likewise, an all-star basketball player has a greater chance of passing on the genetic characteristics that make them so successful at that particular sport. For many, this could be seen as a disappointing reminder of our own shortcomings as a species. As much as we might want to will the next Nobel prize-winning novelist or theoretical physicist to life, that’s not how genetics work. Certainly technology has advanced to the point where hopeful parents can select embryos with pre-existing genetic characteristics, but, for the most part, it’s still impossible to “insert” traits where they don’t exist. Historically, the passing of heritable traits has relied purely on luck, and not much else.
But what if that changed? What if parents could select traits for their unborn children that would be advantageous for academic achievement? What if farmers could be supplied with cows that produce three times as much milk as the preceding generation? What if the types of genetic changes we observe in populations that typically take hundreds or thousands of years, could be enacted over the course of an afternoon in a lab right down the street?
Clustered Regularly Interspaced Short Palindromic Repeats, better known as “CRISPR,” represents a simultaneously exciting and, at times, scary medical future. CRISPR is a tool for editing genomes, an organism’s complete DNA. In the future, CRISPR could provide the technology to stop children from inheriting serious diseases, create livestock immune to ticks, and improve the health of people all over the world. Beyond this, CRISPR could also be used to build “designer babies,” children with a preselected hair color, height, and other features.
Amy Gutmann, PhD, president of the University of Pennsylvania, and Jonathan D. Moreno PhD, of the Perelman School of Medicine’s department of Medical Ethics and Health Policy, write about CRISPR as both a tool and as an ethical question researchers and geneticists will be grappling with for the foreseeable future. There are multiple reasons for this. The first is that the ability to make “ideal” human beings could open the door to eugenics, or the removal of “undesirable” genes from a given population. The practice of eugenics was widespread in the early to mid-20th century, and is universally viewed as a dark spot on the history of medicine. Writing in the May/June 2018 edition of Foreign Affairs, Gutmann and Moreno note that, “the prospect of such genetic engineering raises the specter of disastrous twentieth-century experiments in eugenics, although today most of the demand would likely come from individuals rather than states.” Furthermore, they say these projects, “would be ill-advised and socially disruptive.”
A second problem raised by the potential of CRISPR is the potential for run-away mutations which may seem helpful at the time, but could have unintended consequences for the environment and various populations. This seems to be specifically problematic in gene editing geared towards non-human species. While gene editing could be used to suppress populations of invasive species, such as certain types of rodents, Gutmann and Moreno believe there should be strict control and protocol over these experiments. “If a genetically modified animal or plant escaped, however, then the gene drive could spread uncontrollably. And if a modified organism mated with a member of another species, it could transmit the changes to new populations. Entire species could be wiped out and ecosystems upended.”
In 2017, the Washington Post reported on the first successful occurrence of human embryo gene editing. By correcting a mutant gene, researchers were able to solve a heritable heart defect, which is responsible for sudden cardiac arrest in young athletes. In this case, there was less of a gene editing or modification and more so a gene correction. Yet, even the label “correction” raises concerns in some. As science progresses and medicine’s ability to harness CRISPR improves, questions regarding the nature of blindness, deafness, and other disabilities will arise. It is likely that there will be many conversations regarding exactly what conditions, if any, “need” fixing.
Moving past the controversy associated with CRISPR, it’s easy to see why this subject is so important and potentially beneficial to patients living with a variety of conditions. Just this month, researchers at Penn where able to inactivate a protein called PCSK9 to reduce cholesterol levels in rhesus macaques, a species of monkey. This research, which lowered the famously “bad cholesterol” type LDL, could have major implications for humans. “Most often these patients are treated with repeated injections of an antibody to PCSK9,” said first author Lili Wang, PhD, a research associate professor in Medicine at Penn. “But, our study shows that with successful genome editing, patients who cannot tolerate inhibitor drugs might no longer need this type of repeat treatment.”
Today, medical science and research sits in a historically unprecedented position. In the past, medicine was applied externally, through pills, surgeries, and therapies. Many of these treatment plans included side effects that could be unpleasant or painful. However, as research, bioethics, and necessity drive the medical community’s understanding and application of CRISPR forward, it is no stretch to say a genetic revolution may be upon us. As Gutmann and Moreno put it, “for all its unprecedented power, CRISPR is of a piece with other research break-throughs in synthetic biology. It has both enormous potential to transform societies for the better and possible malign uses.”