Intelligent Design Has Implications for Genome Editing
In five previous posts (here, here, here, here, and here), I have commented on a TEDx talk by recent MIT bioengineering PhD Erika DeBenedictis. In her 11-minute presentation, “It’s Time for Intelligent Design,” Dr. DeBenedictis says, “Yes!” scientists should “play God.” “We can and we should finally intelligently design life.” In my previous responses, I have demonstrated that biology is a lavish display of sophisticated designs exceeding all human engineering to date. This observation calls into question the idea that scientists should “play God” in the sense of improving life’s design.
For instance, I provided some examples of optimality from biology. It is hard to improve on what is optimal, but we can learn from optimality and apply the principles we discover to the field of human engineering. A design perspective also points toward restoring optimality when random chance has corrupted it. In my previous post I also showed from a historical perspective that many cited examples of poor design in biology have been retracted after more insight was gained. This drives home my point that if scientists don’t consider all necessary constraints, they may misinterpret good design as poor design and end up with a redesign worse than the original. In this post, I hope to clarify that while the design framework urges caution in some areas of biotechnology it actually empowers scientists to correct corrupted biological information in the area of genome editing.
Time and Chance
Most actual flaws in biology are the result of time and chance. These are inferred to be flaws by using teleological assumptions, where the original design was good but it has degraded over time. It is a good design perspective that gives us confidence to label these flaws as corruptions of biological information and provides a rational basis to correct them instead of waiting for evolutionary processes to heal them.
The biological situation I am referring to is analogous to when a brand new iPhone has a camera that doesn’t work or when a three-year-old iPhone has scratches and dents. Fixing these flaws requires design intuition — recognizing deviation from an intended state.
Scratches and dents can be spotted in a side-by-side comparison of new and used iPhones. So too, scratches and dents in individual genomes can be spotted today by aligning an individual genome against a reference genome. Note that the reference genome, hg38, is built from an alignment of 13 modern day human genomes and therefore some caution is required. The human genome appears to have been more robust and optimal in the past (Fu et al.), but time and chance have since corrupted information, and today’s genome has more deleterious variations present in protein coding regions.
Leber Congenital Amaurosis
To give an example of how appreciating good design can illuminate our role in correcting corrupted biological information, let’s look at the disease leber congenital amaurosis (LCA). LCA is the most common and severe form of childhood onset blindness. Most often it is caused by a variation c.2991+1655A>G in intron 26 of the CEP290 gene. (Dulla et al.) This variation introduces a cryptic splice site that causes two transcripts to be produced. (Dulla et al.) One transcript is normal but the other includes an extra cryptic exon which introduces a premature stop codon. (Dulla et al.) The result is insufficient production of the CEP290 protein which is required for formation and stability of cilia. (Dulla et al.) Cilia disruptions cause issues with photoreceptors, which is thought to result in retinal dystrophy. (Dulla et al.) Design intuition (selection of the deleterious variant based on rarity and its corruption of the proteins intended function) allows this variation to be classified as pathogenic according to the American College of Medical Genetics. It is a teleological principle that a change from the “intended” reference sequence is harmful and that disruption of the specified function of the protein is harmful. Human genomics, like many scientific fields, relies on but often does not acknowledge teleological principles.
The perspective of good design also provides the only rational justification for treatment of a condition like LCA. If the human mind is the product of blind random processes, how can we even trust our own “intelligent design” instincts? On the other hand, if we are designed and can detect design, then in order to alleviate human suffering, there is a place for us to recognize and restore what time and chance have corrupted.
Restoration Therapy for LCA
As a scientist passionate about advancing applications of biological research, I was overjoyed to learn of a restoration therapy for LCA demonstrated by the ProQR Therapeutics clinical trial in 2017. In this clinical trial, 11 individuals suffering from the c.2991+1655A>G variation underwent a gene editing therapy delivered with a subretinal injection in the hope of restoring their vision. This was a big moment: scientists attempted to restore the intended DNA sequence of someone born blind so that the patient could regain sight! Some might say this type of gene editing is “playing God.” I disagree. It is a recognition of biological design and the repair of corruption brought on by time and chance. It’s an example of repairing a deviation from the normal or standard design. Arguably, doctors do this every time they heal a broken leg.
Unfortunately, if we “play God” in the arena of genome editing, evolutionary assumptions could cause great harm. The use of nucleotide therapy to restore design in clear cut cases, such as the one I cited above, is very different from trying to control (think: designer children), change (think: giving infrared vision to soldiers), or improve (think: altering some aspect of biology from the original design). Controlling, changing, and improving biology are highly controversial subjects in the field of bioethics.
In summary, I strongly caution against premature statements about “poor design” in biological infrastructure that is not well understood. The result may be the establishment of medical practices that cause more harm than good and have other unintended consequences. In my next post, I will conclude this series and offer references.