Since the discovery of DNA, scientists have been trying to crack its code. In the past decade, advances in DNA sequencing technology have led to major improvements in the resolution of over 20,000 genes and other pieces that make up the human genome.

With the information the scientific community has gathered about the average human genome doctors can now reach faster, more accurate diagnoses. The hope is that if doctors know more about a person’s genetic background, they can make better predictions about their health outcomes.

Genome sequencing has had a profound effect on how the scientific community is able to understand the human body, but its applications do not stop there. Genome technologies also carry the weight of several social implications.

At present, when an adult learns about their own genetics it is too late for them to do much about it. But ethical questions emerge when discussing the possibility of selecting genes before birth. This is particularly relevant in cases of in vitro fertilization, and when considering future applications for gene editing technologies.

Gene screening for “better” babies

Dr. Clifford Librach is an associate professor in the Department of Obstetrics and Gynecology at the University of Toronto, and the Director of the CReATe Fertility Centre. He explains that when preparing for in vitro fertilization, several eggs are fertilized and then two different types of tests are performed: first, a pre-implantation screen checks whether embryos have a normal number of chromosomes, and second, a pre-implantation diagnosis checks for specific diseases that may be common in the parents’ family or ethnic group.

These two tests are so that physicians more accurately select the embryo that has the greatest chance of leading to a healthy pregnancy for mom and baby — a reasonable, consideration, given how costly and emotionally intense these procedures can be.

However, there is the opportunity to do more tests. Surprisingly, restrictions on screening are not very stringent in Canada — there are only laws against selecting embryos based on sex.

“There isn’t actually regulation at this point for what [else] we can screen for,” Librach explained. While he is not aware of anyone testing for anything other than diseases caused by obvious mutations in single genes, he points out that “now that we’re starting to learn about mutations that can affect eye colour, colour blindness, maybe even related to obesity or cholesterol levels or heart disease … how far do we go? If we’re not just looking for a specific disease that really runs into [problems with] ethics.”

A quick walk past the lined faces of parents at the Hospital for Sick Children might have us all agreeing that if we could prevent parents from having to watch their children suffer, we should. But what about conditions that affect mental health, where the child is still alive and healthy but there is a great burden placed on caregivers?

Down Syndrome (DS), which is associated with intellectual disability and often higher incidences of childhood health complications such as hypothyroidism and heart malformations, has a known genetic cause that would show up in pre-implantation screening. Should we avoid having children with DS simply because we can?

Perhaps the people most qualified to answer this question are the parents. A study recently published by the lab of Dr. Jehannine Austin (PhD, Certified Genetics Counselor, and Associate Professor in the Departments of Psychiatry and Medical Genetics at the University of British Columbia) explored this question by asking how parents of children with DS would feel about a “cure” for their children.

The study found “that similar proportions of parents indicated that they would, and would not, be interested in curing their own child.” The authors of the study wrote that many parents reported a positive affect on their family as a result of having a child with DS. Further, the authors suggested that we should reconsider the assumption that people with DS are suffering, given evidence that indicates these individuals are happy, and have high self-esteem.

Perhaps the most important takeaway is that, “parents in this study asserted that there should be a focus on changing negative societal attitudes and increasing social infrastructure to properly support individuals with DS and their families, rather than trying to change individuals with DS.”

Given this research, we might turn a more skeptical eye to how we define ‘disease.’  When it comes to other mental health conditions, Austin said, “psychiatric disorders are not entirely attributable to genes alone, […] there is certainly no single genetic change that directly causes psychiatric illness. […] So from a very practical perspective, we are a very very long way off from having the knowledge or technical ability to do this [genome screening or editing] for psychiatric illness.”

While it seems that the need to extend thoughts about genetic screening to all psychiatric conditions is still far away, now is the time to proactively collect data on patient and caregiver experiences, as Austin’s group did for DS. Increased uptake among scientists of the neologism “neurodiversity” — a term attributed to sociologist Judy Singer that advocates for the importance of brain differences — might predict that what is normal or expected is not necessarily best.

Tailoring your genes

Recently, the advent of novel strategies that allow for fast and accurate targeted changes in genetic sequence have excited the scientific community. At the forefront of this wave, is the CRISPR/Cas9 system.

These systems will likely have exciting therapeutic applications in the future, and while their efficacy and safety in humans have yet to be assessed, it is important to start considering the ethics of their use.

Dr. Ronald Cohn, MD, FACMG, and Co-Director of the Centre for Genetic Medicine at the Hospital for Sick Children, said, “it is difficult to assess […] but I think we will be able to see the first human application likely within the next 3-5 years.” He predicts the first applications will begin in blood. Corrections in blood cells can be made outside the body, then transplanted back.

“One of the biggest hurdles for other applications is that we need to do a lot of […] animal experiments to see how efficient and safe CRISPR-based therapies can be administered to various organs dependent on the disease,” said Cohn.

If there were ethical concerns related to screening embryos for their genetic makeup, then surely these are intensified when we consider editing the genetic makeup of those embryos. Indeed, this possibility has caused a stir in the biomedical community, and many pioneers in the field have spoken up against the practice.

In the scientific journal Nature, Edward Lanphier, Fyodor Urnov and others wrote, “genome editing in human embryos using current technologies could have unpredictable effects on future generations. This makes it dangerous and ethically unacceptable. Such research could be exploited for non-therapeutic modifications.”

This is largely because the effect of editing an embryo’s DNA would be difficult to assess before the embryo matured and was born. Moreover, since the editing would occur in early stages of embryonic development, they would be incorporated into the DNA of the reproductive cells of the embryo and could be inherited; changes could span many generations. The potential ramifications of these endeavours are therefore riddled with biological and social unknowns.

To this end, the same group wrote, “at this early stage, scientists should agree not to modify the DNA of human reproductive cells,” and that they “are concerned that a public outcry about such an ethical breach could hinder a promising area of therapeutic development.”

How far is too far?

Cohn summed up his own take on the future prospects of gene editing.“There needs to be careful regulation about what should be amenable to gene editing and what [should] not. The focus initially needs to be on disorders that are associated with a high medical burden. In addition, we will need to think about how to work with industries that these therapies won’t be too expensive for the health care system.”

In other words, this technology should be used only in the most severe cases. Society must agree upon what these cases are, and they should be treated consistently when they occur.

While this sounds like a logical solution moving forward, the jury is still out on the details of where the line should be drawn. It is common for people to invest a lot of time and money to improve the lives of their children. It is perfectly reasonable — and often , encouraged — for parents to enrich their childrens’ education and experiences, feed them healthy food, and promote an overall healthy lifestyle.

What is to stop these attitudes from eventually permeating into the emerging field of genetic modification? Librach challenges, “If I told you I could test your embryo for a child that is going to be a genius and go to Harvard – you’d probably like that because everyone wants their child to be perfect, and it’s hard to tell a parent we won’t do that.” It is reasonable to optimize your child’s environment and play with the nurture side of things, but when, if ever, is it appropriate to optimize their nature through genetic editing?

This concept that “natural” things are better is pervasive in modern society: some groups oppose eating plants that are genetically modified but have been eating plants produced by botanists and agriculture experts through strategic breeding for years; some believe supplements that are naturally derived are somehow superior to those made in a lab, even though both are composed of biochemically active ingredients; and some encourage pregnant mothers to eat more fish to increase their omega-3 intake to support the brain growth of their baby, yet we’re hesitant to select for, or edit, genes to make embryos smarter.

The advancements in genome sequencing and editing technologies have too much promise to be stifled due to fear, but both history and Hollywood have taught us that humans are not always champions of the moral high ground, especially under pressure. Caution is therefore key.

Before we can establish regulations in a democratic manner, as Librach suggested, we have to become familiar with the beast we are trying to tame. It is imperative that everyone put in thought to how these new technologies should be regulated both nationally and internationally, and make informed decisions on where to draw the boundaries, especially in cases where the ethical questions outweigh or equal the potential medical progress to be made.

For now, perhaps the best route is to hold off on manipulating the genes of embryos until we can affect them in such away that the resultant humans will be smart enough to deal with the potential consequences of their creation. Until then, the ethics of genetic editing remains shrouded in uncertainties.