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Engineering the Human Race: CRISPR

What rhymes with whisper, is simple and inexpensive to use, more significant to the history of medicine than the discovery of antibiotics, and was named [1] a weapon of mass destruction by the U.S. Director of National Intelligence?  It is called CRISPR, an elegant and perilous new scientific method for altering the genomes of living organisms.

The first part of this two-part essay introduces CRISPR and discusses several of its uses.  The second part considers some of the more important ethical questions raised by the new technology.

CRISPR is perhaps the most powerful tool for manipulating biological life [2] in the history of science.  Reaching down to the roots of the DNA that build, structure and maintain our bodily existence, CRISPR places in human hands the power to alter, transform and deform our nature.  According to Jennifer Doudna, one of the founders of CRISPR, “We are at the beginning of a new era of biological mastery, a turning point in which the possibilities are limited only by our collective imaginations.” (Rewriting the Code of Life, NCBQ, Spring 2017, p. 38)

Needed Public Debate

The purpose of this essay is to motivate public discussion about this revolutionary new technology.  The ethical debate over the use of nuclear weapons didn’t begin till after the bombings of Hiroshima and Nagasaki.  Humanity would have been better served if the debate had predated August 1945: a spirited, public debate, stretching beyond scientists and talking-heads to ordinary people, especially the poor, whose lives always suffer the worst consequences of science’s dangerous discoveries.

The debate needs to begin now, between spouses, families, neighborhoods, school districts and political communities.  Everyone needs to be asking: Do we want the future that biologists are ushering in for us all?  Admittedly, tomorrow is already here.  But it’s only still morning.  Now’s the time to ask.

CRISPR Technology

Gene editing techniques have existed for decades.  But till now they have been costly, complicated and inexact.  Drawing on a defense mechanism found in bacteria, scientists have discovered a new and surprisingly-precise way to edit DNA.

As far back as the 1980s [3], researchers observed curious repeating sequences of DNA in some bacteria (thus CRISPR: Clustered Regularly Interspaced Short Palindromic Repeats).  It wasn’t till 2005 [4] that the repeats were found to be part of the bacteria’s immune system.  Protecting itself against viral attackers, the bacteria stores within itself sequences of DNA matching that of the invading viruses.  When the viral DNA enters the bacteria, the defense mechanism recognizes the foreign sequence and so sets in motion a tiny scissors mechanism—an enzyme called Cas (i.e., CRISPR associated proteins)—that, in the words [5] of one science journalist, acts as a “precision-guided weapon,” attaching to the viral DNA, snipping both strands of its double helix and so preventing the virus from replicating (watch video about CRISPR [6]).

Fast forward to 2012.  Observing the remarkable capacity of this mechanism to identify and excise short sequences of DNA, researchers proposed [7] to turn the naturally-occurring gene-splicing system into an intentionally-engineered tool for gene editing.

Since then, milestones have been past at an astonishing pace.  CRISPR has been used to edit the genomes of plants, flies, mice and monkeys.

And at the end of July, a research team in Oregon announced [8] it had successfully used CRISPR to snip out a disease-carrying gene in human embryos.

The journalistic hype over CRISPR has reached [9] heights unseen since embryo destructive stem cell (ESC) research was touted fifteen years ago as a panacea for all human ills.  The difference is that CRISPR is very likely to pay rich dividends whereas ESC research was dead on arrival.  But what human and social costs are we willing to pay for these dividends?

Somatic Cell And Germ Line Editing

Before we can discuss the ethics of CRISPR, we need to understand a distinction.  On humans, CRISPR can be performed in two ways.  The first involves altering the genome of “somatic cells” (i.e., any cell that makes up the human body). The edits performed on somatic cells only affect the patient himself.  The second way is more consequential.  It involves using CRISPR to edit “germ-line cells” (i.e., sperm, eggs) and one-celled embryos.  All edits here are passed on to progeny.

Treating Disease

Labs around the world are racing to generate clinical applications for CRISPR, both treatments for existing diseases and prophylactics for possible diseases.  The disease treatments primarily involve somatic cell gene therapy.  For example, scientists are looking at ways to use [10] CRISPR to program immune cells to target and destroy tumors; and to inject [11] CRISPR directly into the eye to modify the gene that causes age-related macular degeneration; and to use it to correct [12] the clotting protein in patients with hemophilia.

The ethical questions surrounding somatic cell gene editing bear chiefly upon the safety of treatments, risks to patients, and fair access to therapies.  Regulating bodies such as the FDA, and strict protocol for using humans as tests subjects, are obvious safeguards against harms caused by this type of therapy.

Preventing Disease

The more perilous territory is germ-line editing (i.e., editing the cells that influence heredity). CRISPR’s highest hopes are pinned on eradicating hereditable diseases.  According to the Genetic Disease Foundation [13], there are more than 6,000 such diseases, many of which are crippling and even fatal.  The present level of CRISPR technology puts within reach the possibility of correcting genetic disorders caused by single gene mutations, such as cystic fibrosis, muscular dystrophy, Huntington disease, Tay-Sachs disease, sickle cell anemia and phenylketonuria. CRISPR would be preprogrammed to delete from sperm cells, egg cells or young embryos the gene that codes for the disease, and a healthy gene then inserted in its place.  This raises ethical questions bearing upon the integrity of embryonic life, the production of ‘designer children,’ and risks to the human gene pool.

The second part of this essay will be dedicated to examining some of these questions.