In his talk at Boston College on Nov. 29, 2019, Dr. George Church, Professor of Genetics at Harvard Medical School, addressed the myriad ways in which CRISPR genome sequencing and editing technology can and should be utilized.
Gene editing therapies can be divided into two major categories: somatic cell therapy and germline cell therapy. Somatic cell gene therapy seeks to restore DNA function to non- reproductive cells. Germline cell gene editing seeks to restore DNA function in a germline cell, a cell with the potential to transmit the genetic edits to offspring (i.e. sperm, egg, or embryo). In Dignitas Personae, the Catholic Church declared somatic cell gene therapy for therapeutic purposes morally licit and germline editing morally illicit.
Additionally, the current state of germ line genetic editing technology necessarily requires in vitro fertilization (IVF), which the Catholic Church has also declared morally illicit. During his talk, Church compared the birth of twins, whose genomes had been edited for HIV resistance with CRISPR by biophysicist He Jiankui, to the birth of the first “test tube baby” in 1978. He said that the stigma around IVF babies was dispelled, that “everyone’s minds changed,” when they saw the cute baby girl that resulted.
Church expressed concern at the lack of equitable access to legal somatic cell gene therapies, and proposed two approaches to assuring wider access. First, he proposed a focus on common genetic diseases in order to drive therapy prices down. Second, he proposed a preventative approach to rare genetic diseases, recommending a type of genetic compatibility matchmaking in the place of today’s post-relationship genetic counseling.
Further, Church described a developing gene therapy he called “aging reversal” which engages in a combinatorial approach to treating the five primary diseases that collectively comprise the aging process. Beyond a general explanation of the approach, Church addressed the ethics of “aging reversal” in the framework of global population control. Referring to current population fluctuations in rural areas and urban centers, he implied that, in the near future, there might be room for extremely prolonged life or near-immortality via aging reversal somatic cell gene therapy.
The National Academy of Sciences (NAS) released a recommendation in 2017 that human germline editing may be ethically permissible if no other treatment were available and if strict criteria were met. During his presentation, Church acknowledged that, when it comes to germline editing as a therapy, “there’s almost nothing you can’t do some other way.”
He listed the advantages of germline therapy (as compared to somatic gene therapy). Whereas somatic cell gene edits can only be delivered via viral vector to specific target cells, a gene edit made in an embryo or gamete can be delivered to every cell that results from the division of the cell during development. Every cell in the body of the person who was embryonically edited contains the same genome with the same heritable edits. Other advantages of germline editing that Church listed were the ability to check for edits, a lower risk of off-target editing, and a zero cost for edits in the genomes of offspring.
The downsides of germline editing that Church listed included the long clinical trial period and the small market for germline editing. His conviction that there is little or no demand for germline editing is based in his assessment that there are essentially no cases for which no alternative treatments are available, as per NAS’s 2017 ethical recommendation. When asked how we are to anticipate negative consequences of germline editing, Church replied that we cannot anticipate those negative consequences, but only ensure that every application of genetic technology has three essential components: off-switch, reversal, and geographical containment.
Church also addressed genetic technology for enhancement in the context of organ enhancement. At present, there have been successful attempts at editing pig genomes to grow human hearts, eyelet cells, and kidneys with 9-month survival. Church said that when they reach 12-month survival, clinical trials transplanting these organs will begin. He described the potential for engineering organs with resistance to pathogens and cancer as well as with enhanced compatibility for cryopreservation with genome editing technology.
Church ended his presentation with a reflection on “The Risk of Doing Nothing,” essentially his idea of an ethical duty to use genetic technology to reverse climate change. His proposition that climate change is best fought by directly attempting to reverse the positive feedback loop set in motion by our human ancestors has led him to focus on the massive carbon sink in the Arctic Tundra. According to Church, the warming of the carbon sink has led to a release of carbon dioxide into the atmosphere, and the best way to fix this is to restore the grasslands in the tundra via deforestation. His unique approach to this deforestation includes the de-extinction (via genetic technology) and reintroduction of mammoths to the Arctic tundra.
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