Nearly every day, new viral videos spread like wildfire across the Internet about the latest miracle cure or revolutionary device, with headlines proclaiming “Deaf child hears for the first time” or “New device diagnoses malaria in 5 seconds”. It’s clear that biomedical research and technology is evolving and advancing faster than ever before. Concepts that were previously unheard of go from the drawing board, to prototypes, to real life—all seemingly in the blink of an eye.
While it is humbling and awe-inspiring to see this technological revolution unfold before our eyes, the world ain’t all sunshine and rainbows. There are times when our ability to invent and to “do” outpaces the rate of debate (and conclusion) of moral quandaries. One of the biggest of such medical advances and controversies in the past decade involves genotyping and DNA editing.
Humans have dreamed about bioengineering and genomics for many generations, and it was well represented in popular culture before it gained serious foothold and momentum in the science community. In the dystopian society of Aldous Huxley’s Brave New World (1932), test tube babies were artificially bred to fit into predetermined castes. Similarly, in sci-fi film Gattaca (1997), genetic manipulation was used to guarantee that children only received their parents’ best hereditary traits in a futuristic society divided by genetic superiority and inferiority.
It didn’t take long to make these fictional worlds somewhat of a reality. In 1978, the first real-life “test-tube baby” (fertilized in vitro, grown in utero) was born—Louise Brown. From there, IVF and genomics took off, never to look back.
By 1979, the U.S. Ethics Advisory Board approved federal funding for IVF research. By the mid-1990s, embryologist Jacques Cohen developed cytoplasmic transfer, where cytoplasm from donor’s eggs was injected into the patient’s eggs. These bioengineered children each had 3 genetic parents: mother, father, and mtDNA donor.
By 2004, IVF had become “mainstream medical technology” which, despite its hefty price tag, had already successfully given life to around a half million test tube babies worldwide. Infertility clinics offering IVF services for an average cost of $12,400 per cycle (which may be at least partially covered by insurance) are now widely accessible, with a steadily rising per-cycle fertilization rate.
In terms of genotyping, the Human Genome Project (HGP) was launched in 1990 and declared “complete” in 2003. The goal: to generate a representative or reference sequence of the human genome. The major ethical/legal/social debate at that time was the fear that increased knowledge of the human genome could be used to discriminate against people in terms of employment and health insurance. The Ethical, Legal, and Social Implications Project (ELSI) was subsequently created in 1990 to address the issues that arose from HGP. In 1996, HIPAA was passed, in order to protect health information and partially alleviate these concerns of discrimination.
It cost somewhere between $500 million to $1 billion to generate that first human genome sequence. After HGP was completed in 2003, the thirst to sequence individual genomes took over and the technology evolved at a wild pace. By 2006, the cost of generating a high quality draft of an individual’s genome had dropped to ~$14 million. Now? Less than $1,000 for commercial genome sequencing services.
Suddenly, genotyping and genetic counseling became so accessible, so routine, and as with all novelties, so boring.
What, then, was left? It only made sense to turn the attention to DNA editing. We could already sequence the human genome and find the gene mutations that portended poor future development/survival, and we could already conceive a baby artificially/outside the human body. So why not bridge these two abilities by honing the skill of DNA editing, thus putting the information derived from DNA sequencing to use, and using IVF as the tool to bring this modified embryo to life.
Now there are 4 families of engineered nucleases implemented in DNA editing, the most popular of which is the CRISPR-Cas system. CRISPR-Cas9 (“clustered regularly interspaced short palindromic repeats”) works by essentially “cutting and pasting” DNA using an endonuclease and synthetic guide RNA to make double strand breaks. It is a relatively fast, cheap and simple way to make targeted genetic modifications. And, it is the center of many different controversies.
In 2015, a research team in China attempted to edit the HBB (beta thalassemia) gene in 86 human embryos. They used early embryos that were not viable (to lessen the ethical concerns) and successfully edited 28 of these embryos using CRISPR-Cas9. Both the praise and the backlash were immediate. Never before had scientists crossed this line and edited the DNA in human embryos, let alone successfully.
Why support DNA editing? Well, it can help us understand the genes that help an embryo grow, and eventually help to prevent miscarriages. In fact, a research application was granted approval in the U.K. earlier this year to a team looking into this very matter. DNA editing can also be used to modify the mutations involved in (and thus cure) conditions like HIV/AIDS, muscular dystrophy, hemoglobinopathies, blindness, cancer (think: tumor suppressors and oncogenes)—the list goes on.
And how game-changing would it be for parents who, rather than watching their child tormented daily by a merciless disease attributable to DNA mutations (Huntington’s, for example), could elect to have the disease edited out of their child’s genome? DNA editing is a powerful tool that could give those who previously would be limited or crippled by disease a fair shot at life.
DNA editing also gives us the chance to end world hunger (by modifying staple crops to withstand murderous organisms like fungi and mildew), and generate endless clean energy (by modifying yeasts to turn plant matter into ethanol). Isn’t that neat?
What are the pitfalls? Well, a mistake during editing could alter the human genetic blueprint forever and introduce a new mutation or disease that could stick around for generations. Some scientists predict a cascade of global effects, rippling through not just an individual but the entire species, that could deal immense, irreparable damage to the human germline.
We must also consider the slippery slope of “designer babies” and eugenics. Some would wonder, why stop at preventing/curing major diseases if we could also manipulate physical traits, intellect, memory, etc.? Society currently places so much emphasis on being stronger, taller, prettier, and smarter, but if people had unlimited means to select traits for their offspring, we would inevitably create a society similar to Gattaca, fragmented and ruled by genetics. Those who are genetically “flawed” may be brushed aside or even eradicated. It is important to realize that traits that we select for now may not be beneficial in a century. Additionally, genome editing may initially only be affordable by the wealthy, increasing the already growing gap between the rich and the poor. More inequality and discrimination could be created, both in terms of fiscal and genetic wealth. Our population might become at once a lot more homogenous and a lot more stratified. There is so much danger when power and technology like this goes unregulated, but where is the proper place to draw the line, and who has a say?
And lest we forget the principle of autonomy: some critics of DNA manipulation have proposed a Genetic Bill of Rights, proclaiming that humans have the right to be born without genetic manipulation. Embryos obviously cannot voice any opinions on the matter, so is it ethical? Do parents have the power to make such radical decisions for the baby?
Stepping away from all the speculation and back to the real world: an international meeting of scientists in Washington last year decreed that laboratory research in manipulating early embryos would be allowed, but that the DNA editing techniques were far from ready to be implemented in live, pregnant women. That being said, the U.K. became the first country in the world to permit the transfer of genetically modified embryos into women by voting to allow scientists to create babies from the DNA of 3 people. The intent: to prevent the inheritance of potentially fatal diseases from mothers.
All of this to say: technology is advancing faster than ever, especially in the field of genome sequencing and editing. We, as individuals, as a community, and as a population, should periodically reevaluate our stance on topics such as this, before the technology completely overtakes us and spins out of control. This is an argument that spans many fields—technology (are our methods good/safe enough?), medicine (how can this help/hurt our treatment of diseases?), morality/ethics (are we overstepping our bounds?), social (could this permanently transform our society and dynamics?), legal (a whole other can of worms), etc. Arguably the biggest hurdle we have at the moment is coming to a consensus about the morality of gene editing, and whether or not it has a place in our society.
About the Author
Michelle Sheng is a medical student in the Sidney Kimmel Medical College Class of 2018.