Using CRISPR Gene Editing Techniques on Humans, Pigs and Beyond

CRISPR (clustered , regularly interspaced, short palindromic repeats (1)) is a fairly recent genome editing tool that holds great promise. It is not exactly something humans invented, but rather is part of a normally occurring bacterial process—it is a defense mechanism found in a wide range of bacteria. “CRISPR is one part of a bacteria’s immune system, which keeps bits of dangerous viruses around so it can recognize and defend against those viruses next time they attack (1)” The next part of CRIPSR defense is a set of enzymes called CRISPR-associated viruses also known as CAS enzymes which specifically and precisely snip DNA and slice out any invading viruses.  The best-known Cas enzyme is Cas9, and comes from the bacterium that causes strep throat. The CRIPSR/Cas9 system, also known as just CRISPR and is a more precise way of editing the genome using bacterial machinery of editing (3). “Cas9 is an enzyme that snips DNA, and CRISPR is a collection of DNA sequences that tells Cas9 exactly where to snip, therefore all biologists need to do is feed Cas9 the right sequence, called a guide RNA, and then you can cut and paste bits of DNA sequence into your genome wherever you want (2).”

So, why does this matter? Researchers hope to use this quick and efficient gene editing technique in order to adjust human genes to eliminate diseases.  Another specific application is in organ transplants, so adjusting cells of the donor organ organism using CRISPR. Geneticist George Church of Harvard Medical School announced that he and his colleagues had used CRISPR/Cas9 gene editing technology to inactivate 62 porcine endogenous retroviruses in pig embryos (2). These pig viruses are embedded in the pigs’ genomes and cannot be treated, and “it is feared that they could cause disease in human transplant recipients” (3). Church’s lab also identified “genes that encode for proteins that sit on the surface of a pig cells and are known to trigger a human immune response or cause blood clotting” , something that occurs following organ transplantation (3). This seems great, use readily available and relatively inexpensive pig organs, modify them using CRISPR , in a way “humanizing” them in order to increase the success rate of transplant acceptance, and decrease rejection.  But in reality we are far from understanding exactly how this all works. These pig to human transplants have been attempted a few times around the world and have all ended pretty badly, “a Los Angeles woman who got a pig liver died within 34 hours”, and “the last time a doctors transplanted a pig heart into a person in India in 1996, he was arrested for murder” (4). But the most promising pig transplant news came this year as researchers reported they have kept a pig heart alive in a baboon for 945 days (4).

Genetically modifying organisms, whether they be human, pig or baboon, has been up for bioethical debate ever since this technology became available. This year researchers edited non-viable human embryos using CRISPR/Cas 9 to modify a gene that can cause a potentially fatal blood disorder called beta-thalassaemia when it is mutated (5). According to some using CRISPR/Cap9 procedure “if done in a viable embryo, could eradicate devastating genetic diseases before a baby is even born” (5). Others say “that such work crosses an ethical line: in response to the rumors that the work was being carried out, researchers warned in Nature and Science in March that because the genetic changes to embryos—a procedure known as germ line modification—are heritable, they could have an unpredictable effect on future generations” (5). Overall as science and technology advances such as CRISPR/Cas9 emerge, the ethical ramifications of applying those new technologies must be appropriately understood.

1.  Ledford, H. CRISPR the disruptor: A powerful gene-editing technology is the biggest game changer to hit biology since PCR. But with its huge potential come pressing concerns. Nature 03 June 2015. http://www.nature.com/news/crispr-the-disruptor-1.17673

2. http://gizmodo.com/everything-you-need-to-know-about-crispr-the-new-tool-1702114381

3. Reardon, S. Gene Editing record smashed in pigs. 06 Ocotber 2015 Nature

http://www.nature.com/news/gene-editing-record-smashed-in-pigs-1.18525?WT.mc_id=TWT_NatureNews

4. http://www.technologyreview.com/news/540076/surgeons-smash-records-with-pig-to-primate-organ-transplants/

5. Cyranoski, D. Reardon, S. Embryo editing sparks epic debate: In wake of paper describing genetic modification of human embryos, scientists disagree about ethics.  29 April 2015. Nature.
http://www.nature.com/news/embryo-editing-sparks-epic-debate-1.17421