The Promises and Dilemmas of Gene Therapy


2017 was a big year for the future of gene therapy. Building on over 50 years of research the clinical application of the discovery of DNA is being realized.

Between October 6th and December 9th alone, five gene therapy clinical trials were published. As of December 31st 2017, there are published clinical trials for eight different gene therapies. Cures for certain inherent genetic disorders are now within reach.

Individuals with genetic disorders possess a faulty gene. A gene is a sequence of DNA that encodes for a specific protein. If the DNA sequence of a gene is flawed, the resultant protein may be non-functioning or have reduced function. An analogy for this concept is to consider making a meal from a cookbook. The DNA is the cookbook, the gene is a recipe, and the protein is the meal.

Gene therapy works by introducing a working gene to replace the faulty one. In other words, an incorrect recipe from the cookbook is replaced and the meal is a hit.

One of the successful gene therapy studies mentioned above, published on December 9th 2017, used gene therapy to treat hemophilia A.  This disease is caused by an error in the gene encoding the protein “Factor VIII”, which is a critical blood clotting factor. Replacing the faulty Factor VIII gene with one encoding a functional Factor VIII was the goal in this study.

Nine subjects were included in the study. One subject received a low dose of gene therapy, one an intermediate dose, and seven received a high dose. At the one year mark, six of the seven subjects in the high dose cohort had completely normal circulating levels of Factor VIII. The number of annual bleeding events fell from 16 to 1. The disease was almost completely cured with the high dose regimen.

The other genetic disorders successfully treated with gene therapy last Fall include; Lebel Congenital Amaurosis (causes blindness), Spinal Muscular Atrophy, Junctional Epidermolysis Bullosa, and Hemophilia B.

Altogether, the success rate of gene therapy in these diseases was profound. Very rarely are such consistent positive findings observed.

While gene therapy is exciting for inherent genetic disorders, the applicability to a broad range of health issues is unclear. Take obesity for example; while there may be genetic risk factors, there is no causal genetic mutation for the disease. In reality, most human diseases are not a result of a misstep in a single gene. The manifestation of most human diseases is a result of an interaction between genetic susceptibility, environmental triggers and bad luck. So while this technology will no doubt save lives, it is unlikely our health woes as a population will be cured.

There is another point worth making. It’s a concept you’ve likely heard before, and perhaps debated with your friends. It’s the unforeseen consequences argument. It’s the idea that by going down this road of altering our genes we may encounter repercussions we could never predict.

In his captivating book The Gene, which takes a deep dive into the history of genetics, Dr. Siddhartha Mukherjee touches on this idea of unforeseen consequences. He uses autism as an example. If we take a look back in time, strokes of genius from very special people vaulted our society into new eras of understanding. The most important historical figures of our time including Albert Einstein, Isaac Newton, Michelangelo, Thomas Jefferson, Mozart, and Charles Darwin, have all been reported to display characteristics of at least being on the spectrum of autism.

With the advent of gene therapy, a dilemma presents itself. If a specific gene is found to be linked with autism, do you alter it? From social functioning standpoint, the individual is (likely) better off. But what if we edit out genius? What if Einstein’s genetics were altered as a kid to make him friendlier? Would he still have spent all those hours locked in a Swiss patent office thinking about relativity? Einstein would have had more friends, but we wouldn’t have nuclear energy.

No doubt the next chapter of the human genetics story will be full of success and happy tears. However, questions surrounding unforeseen consequences and where to draw the line will continue to be asked.

By Brennan Smith, PhD

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