Abstract
The annual gathering of the American Society of Gene & Cell Therapy, which took place last month in Boston, is a must-attend conference for CRISPR medicines and genome editing enthusiasts. This year’s conference offered a smorgasbord of clinical progress, technological updates, and business advances, along with a sobering message from Dr. Kiran Musunuru, one of the architects of last year’s gratifying Baby KJ story, that much more work remains to be done.
With the clinical potential of CRISPR-based gene and cell therapies well established, the focus has transitioned to the clinical pipeline and debottlenecking of regulatory and manufacturing constraints to enable the development of accessible next-generation personal medicines.
As CRISPR makes its way into the zeitgeist and gene therapies become relevant to the general public, there remains an ethical conundrum to address: Are we actually making genetically modified (GM) humans?
There remains considerable public concern regarding the dietary consumption of GM foods. Perplexingly, many consumers still deem GM foods objectionable, if not downright dangerous. But there is much less debate on the perception of editing human beings. Intuitively, the somatic correction of a genetic mutation through a gene editing therapy yields a “GM patient,” but is it really the case technically? Is a patient a GM organism (GMO) before or after they are dosed with a gene therapy? Are they GM in their diseased state, or do they become GM once the healthy allele has been genetically restored?
Back to Wild Type
To frame the ethical and perception predicament, let’s start with the premise that a patient with a monogenic disease by definition carries a single mutation (usually) in a single gene. This faulty allele is responsible for the genetic disease and distinguishable from the wild-type sequence commonly found in the majority of the population (although frequencies will differ given the genetic diversity across various population groups).
With CRISPR genomic surgery, genome editing enables caregivers to restore the healthy wild-type allele in patients. But is the patient considered a GMO before or after the intervention? Is the patient GM when they carry the faulty allele or when they are healthy, carrying the newly restored wild-type allele? The conundrum lies in the fact that when the faulty allele has been corrected, they are genetically indistinguishable from the healthy population at that locus, but they may still be considered GMO.
Some may argue that the process is what matters: The fact of altering the original, innate sequence of an individual renders the product (the cured patient) a GMO. The fact that we alter the DNA of an individual renders them GM and, in some ways, perhaps fundamentally objectionable (at least for those objecting to GM foods). Conversely, some may argue that the product is what matters: the fact of correcting the wild-type allele in a patient restores their humanity, as they are now genetically indistinguishable from the rest of the healthy species. If this is the nature of humanity (the healthy allele as the default genotype of the population), how can it be GM or objectionable if it is indistinguishable? If that edited patient cannot be parsed from the rest of humanity, can they be GM? Can they be GMO when they are genetically identical and healthy? Does the process or the product matter?
This quandary has both a philosophical and a technical aspect. What defines humanity, and is it against the nature of humanity to restore the collective wild type in diseased patients? And does the process or the product matter in how we consider patients subjected to gene therapies?
The most critical issue might be figuring out why the public feels so strongly about the safety and acceptability of GM foods, while seemingly so accepting of CRISPR’s ability to perform genetic surgery on human beings.