Genome Editing and Our Posthuman Future

2015–08–29

TAKING CONTROL OF OUR GENETIC DESTINY

The ability to slowly and empirically alter the course of our own evolution as a species has existed since our first pre-human monkey ancestor climbed out of a tree and began awkwardly strutting about on two legs. And trying to mate with the smartest/prettiest girl monkey… This stop and start “improvement” of our species is the result of genetic fitness as well and social and cultural pressures (don’t play well with others, it’s less likely you will pass along your genes). New technologies are now available that will allow precise manipulation of human genomic material. We can control our genetic fate instead of merely taking a random walk through evolutionary eons. These breakthroughs could spell destruction rather than salvation for the human race.

With the identification of DNA as a the blueprint of life came some early attempts to correct naturally occuring misspellings in this genetic code. Even before the human genome was completed, researchers and clinicians were using viruses, natually occuring vectors that co-opt their hosts’ DNA, as a therapeutic means for treating genetic disease. The ’80s and ’90s saw the first attempts to put gene therapy into humans. The hype surrounding gene therapy ended with a high profile death of a boy. Subsequently, mainstream media abandoned the promise surrounding this technique, and gene therapy was relegated to B-list scifi movies and one of the worst James Bond films ever made.

The early 2000s saw a renewed interest in the genetic basis of disease driven, to a large extent, by the completion of the first draft human genome. Now individuals could be more easily compared to this consensus blueprint, and the genetic basis of disease or risk factor more easily elucidated. Non-viral means of modifying genetic material were developed including zinc finger nucleases and TALE nucleases. These technologies allowed more precise targeting of regions within the genome, although both suffered from limited efficiency (how often does it modify the target site) or specificity (does it actually the target position).

The past 5 years have seen the most powerful advance in genome editing technolgy thus far. CRISPR/CAS9, which is derived from a bacterial defense mechanism, allows researchers to guide genome-modifying components directly to the gemomic target using an RNA molecule that perfectly pairs with the target site. This drastically increases both efficiency and specificity of the gene editing reaction.

CURE ALL OF THE DISEASE!

The longterm implications of this advance are still unknown. Therapeutic application will first come in the form of human cell lines specifically engineered to do something useful. Juno Therpeutics has teamed with with CRISPR gene-editing company Editas, and is modifying T-cells to seek and destroy tumors. Other firms continue to develop their own genome editing therapies, just as academic researchers increase the power of these technologies.

In theory, human embryos, often screened before implantation in IVF, could be modified with CRISPR genome editing. A blastocyst containing an aberrant or nonfunctional copy of a gene could be corrected, and a devastating genetic disease avoided. Even variants associated with the really big killers (heart disease and cancer) could be corrected before birth.

HERE’S WHERE IT GETS A LITTLE CREEPY

What is a genetic disease, and what is just part of being a unique human? Being under 6'3 effectively negates any chance at an NBA career. This defect could, most likely, be edited. And having an I.Q. less than 80? Eventually, we may be able to fix that. The really scary thing is that, these are not just single-patient modifications. Altered genomic material will propogate forevermore. It’s like getting cosmetic surgery and passing your nose job to all future generations in your family tree. Your original wonky beak has been lost forever.

Following this line of thinking to it’s eventual conclusion takes us to a very scary place. Altered or enhanced humans will, at least at the outset, be more affluent than their un-enhanced bretheren. After just a handful of generations, they will be virtually unrecognizable compared to regular humans, like a Westminster-winning Great Dane compared to a coyote. As the world continues to shrink and culturally desirable traits converge, it’s possible that the genetically enhanced will become increasingly similar all over the globe, taller, smarter, better looking, less prone to mental and physical morbidities…

Apart from the obvious dystopian societal problems that will result (I forsee uprisings of the unenhanced being brutally put down by the smarter, stronger, wealtheir enhanced), artificial evolutionary convergence will slowly, insidiously, begin to decrease human genetic diversity. This will put humanity at greater risk of a sudden extinction event through global pandemic. Imagine the Spanish Influenza outbreak of 1918, which killed 5% of the global population, where nobody is resistant to the strain. Additionally, traits that are beneficial to the species but not to the individual, such as Picasso’s bipolar disorder, or Hemmingway’s depression, will quickly be removed from the gene pool. More powerful iterations of CRISPR/CAS9 technologies could prove to be more destructive than the Manhattan Project. After all, your average expecting parent isn’t typically tempted by the prospect of using a nuclear weapon…

SLOWING PROGRESS OR AVERTING CATASTROPHE

How do we keep this genie in the bottle, especially in the face of all the good that these technologies can do? Domestic legislation is ineffective when looking at these technologies from an international perspective. Furthermore, legislators seem to have a hard time agreeing on black and white issues like global climate. International moratoriums by the scientific community, like that in place for human cloning, can be effective at slowing things down. But there will always be mad scientists and crazy billionaires out there willing to go it alone. Recently, it was confirmed that Chinese scientists had, in fact, been applying CRISPR technologies to the human germ line. Some scientific moratorium… The Economist recently published an article highlighting some of the dangerous potential of genome editing. Mainstream media has begun to take notice of genome editing.

As a technologist, I steadfastly believe that these technologies can and must be further developed. The short-term potential for good is too great ignore. But average citizens need to pay attention to these advances. Public scrutiny, alignment of the scientific community, and some level of government oversight will be important in limiting the abuse of new genome editing breakthroughs. Technological progress tends to move much faster than ethical discourse.

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Dreamer, thinker, loudmouth. Founder, Octagon Therapeutics, adventurer.

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Isaac Stoner

Isaac Stoner

Dreamer, thinker, loudmouth. Founder, Octagon Therapeutics, adventurer.

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