Friday, January 4, 2019

Deformed Animals Highlight Risk Of Gene Editing Technology

Image may contain: outdoorAn artist's rendering of DNA double helix molecules and chromosomes.
Deformed piglet resulted from Chinese efforts to resist viral infection. (From WSJ, Dec. 15-16, p. C3)

Crispr - let's reference - stands for "clustered regularly interspaced short palindromic repeats" - serves as the immune system of bacteria, and has been used to fend off viral attacks.  RNA or ribonucleic acid is a molecule found in all cells.  Like DNA, RNA is a polymer, but much simpler. This is because the latter’s ribose sugar molecules are smaller than DNA’s deoxyribose sugar molecules. So there are fewer monomer units in all to make polymer chains. At the same time, while there is only one type of DNA, there are three types of RNA:

- Messenger RNA or mRNA: really a complementary copy of a DNA segment that conveys information from cell nucleus to cytoplasm. Once there it acts as a template for synthesis of a protein molecule.

- Transfer RNA or tRNA: as the name implies, it couples information in the nucleic acid base sequence to the amino acid base sequence in synthesized proteins.

- Ribosomal RNA or rRNA: forms the ribosomes of cells, from which proteins are made.

The diagram below summarizes the process:

Back in October, 2017,  we learned that scientists had created a new Crispr- based system to edit RNA instead of DNA in human cells,. This offered  a way around some of the ethical and scientific challenges to do with editing the human genome.  This was first reported in the popular press  (WSJ Technology section, Oct. 26, 2017) and referenced a paper published in Science the day before in which the research was described. The new RNA -editing system was dubbed "Repair" by the researchers (based at the Broad Institute of MIT and Harvard)  and was designed to correct a common mutation known to play a role in a number of diseases.

This came on the heels of  attempts by Junjiu Huang  and colleagues to use CRISPR/Cas9 to fix a gene known as HBB, which causes  the blood disorder beta-thalassemia.   The work was done on 86 very early embryos that weren't viable, in order to minimize some of the ethical concerns. Only 71 of the embryos survived, and just 28 were successfully edited. But the process also frequently created unintended mutations in the embryos' DNA. 

Subsequently, Marcy Darnovsky of the Center for Genetics and Society, a watchdog group, wrote in an email :

"This paper demonstrates the enormous safety risks that any such attempt would entail, and underlines the urgency of working to forestall other such efforts. The social dangers of creating genetically modified human beings cannot be overstated. No researcher should have the moral warrant to flout the globally widespread policy agreement against modifying the human germline,"

George Daley, a stem cell researcher at Harvard, agreed, asserting:

"Their data reinforces the wisdom of the calls for a moratorium on any clinical practice of embryo gene editing, because current methods are too inefficient and unsafe," he wrote in an email. "Further, there needs to be careful consideration not only of the safety but also of the social and ethical implications of applying this technology to alter our germ lines."   

These concerns have not been proffered without justification, as we've since learned of other misfires in the gene editing arena  - most of which concern deformed animals unexpectedly generated by the work. (cf. 'Deformities Shadow Gene-Editing Research', WSJ, Dec, 15-16)

What were some of these misfires? As reported in the WSJ piece:

- When Chinese researchers deleted a gene that limits muscle growth in mammals the creations exhibited enlarged tongues.

- Similar experiments on Chinese pigs led a number of them to develop  additional vertebrae.

- Gene-edited calves died prematurely in Brazil and New Zealand. 

- Merino sheep edited to try to generate new coat colors came out spotted like typical Pandas.

In the case of the deformed piglet highlighted in the image the Chinese scientist - Dr. Kui Li-  didn't even use CRISPR (preferred because it's more economical than older techniques) but an older editing method. That involved deleting a gene called MSTN from Chinese pigs in the embryonic stage. The edited cells were then infused into eggs, chemically fertilized in a lab an implanted into the womb of a surrogate.

The experiment did produce leaner pork (up to 12 percent leaner if both copies of the MSTN gene were deleted) but also 1 in 5 pigs that developed an extra thoracic vertebra.  According to Dr. Li, lab tests showed that the meat of the deformed animals was still safe to eat. Maybe, but I'd warrant you'd have a hard time convincing my Bajan biologist friend John Phillips of that! E.g.  

 He will not even touch any genetically modified plant-based foods especially those which include glyphosate.  John still cites a particular paragraph in the Bulletin of the Food & Water Watch, from 2016:

"Very little is known of the long term effects of what GMOs can do to your health because they've not been properly tested. But what facts we do have are alarming. Real lab rats fed GMOs have suffered kidney and liver damage, cancerous tumors and even premature death."

So there's no doubt he wouldn't look twice at genetically modified pork, especially coming from deformed animals.

This then goes to the other effort, conducted at Nanjing Agricultural University - to use CRISPR to edit MSTN out of rabbits to make them meatier.   The unexpected result? 14 of the 34 engineered offspring were born with enlarged tongues. Would John Phillips eat any of these?  "No way, not now or ever!"

The bizarre result led the participating scientists to warn of "abnormalities"  from gene editing in a 2016 research paper on their project as cited in the WSJ piece. As the authors wrote:

"Safety issues need to be addressed in future studies before the technology can be utilized."

To be sure, these Chinese scientists weren't worried about humans getting enlarged tongues if they ate the rabbits. But rather the potential effects from consuming meat from an animal that had been "genetically messed up" to use Mr. Phillip's parlance.  As Phillips put it in a recent email: 

"Would you eat a flying fish I produced from Crispr/Cas9 gene editing that had two heads, two stomachs, and no scales?  How about just one head, but no dorsal fin and crossed eyes? No, I didn't think so! So why eat pork from a genetically-edited  deformed pig, never mind it's just one additional vertebra?"

Still, the beat goes on, and the WSJ article reports that globally "at least a dozen gene -edited livestock projects are aiming to reach consumer markets."

There is also a very good chance we won't know exactly what the condition of the animals was (in terms of deformities)  when their meat is  offered for the markets. After all, in the piglet experiment that went awry the Chinese scientist (Dr. Li) insisted it "was safe to eat".   But what does that mean? Safe in terms of not causing kidney or liver disease, say like glyphosates in GMO foods?  What about the precautionary principle? Is that embraced? (I.e. it is the responsibility of the creators to prove their meat is safe, not for consumers to prove it isn't.)

So I guess we should just  take his word for it,  being a geneticist and all.  As for me, I believe I will stick to the non-gene edited meats,  originating from non-deformed pigs, chickens, beef etc.  - which I am sure will disappoint the Neoliberal market mavens. The same lot who assert Americans need to have many more babies, never mind they can't afford them.

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