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“CRISPR”, Breakthrough or Trouble?

Posted on 16 August 2015 by Jerry

No, the new CRISPR is not a better way to hold fresh produce in refrigerators.  Instead it is a new gene-editing tool that has been described as “Jaw dropping” by Craig Mello of the University of Massachusetts Medical School who shared the 2006 Nobel Prize for medicine.  A June 3, 2015 article in Nature Magazine goes on to say it will “allow researchers to quickly change the DNA of nearly any organism – including humans.  CRISPR is turning everything on its head.”

It allows researchers to alter the DNA of almost all organisms. This is undoubtedly good because it dramatically accelerates experimentation.  It should lead to many medical breakthroughs.  But are there risks?

To some extent CRISPR is a breakthrough that threatens all of us.  It revolutionizes an area that has no direct government regulation.   Researchers can now mix and match the genetic code of any set of disparate animals and do it cheaply.  Unfortunately, it only takes one mistake to create a new organism that we struggle to control.

CRISPR stands for clustered regularly interspaced short palindromic repeats.  CRISPR uses a part of a bacteria’s immune system.  A bacteria keeps copies of the dangerous viruses that prey on it so it can recognize and defend against those viruses should they try to infect it again.  This ability has been borrowed from the bacteria so genetic engineers can take a normal sequence of DNA and define it as the target that is to be cut out – the Cas9 enzyme cuts the DNA.

Its process involves a set of enzymes called Cas or CRISPR-associated proteins, which allow the bacteria to precisely cut out a section of DNA and cut it up as it would an invading virus.  The best-known enzyme, of a number of Cas enzymes, is called Cas9.  It is from the Streptococcus pyogenes or the bacteria that causes strep throat.   It forms the CRISPR/Cas9 system that is most often used.

This tool and new technique dramatically simplifies the ability to edit genomes or genetic chromosomes and has been “likened to editing the individual letters on any chosen page of an encyclopedia without creating any spelling mistakes.”

Professor Mello continued by saying “It’s one of things that you have to see to believe.  I read scientific papers like everyone else but when I saw it working in my own lab, my jaw dropped.  A total novice in my lab got it to work.  The CRISPR technique dramatically ‘lowers the threshold’ for carrying out ‘germ line’ gene therapy on human IVF embryos,” Professor Mello added.

A June 2015 article in Nature magazine quotes James Haber, a molecular biologist at Brandeis University in Waltham, Massachusetts, as saying “That (CRISPR) effectively democratized the technology so that everyone is using it,” says Dr. Haber.  “It’s a huge revolution.”

The article offers another summary of the CRISPR technique,  “It relies on an enzyme called Cas9 that uses a guide RNA molecule to home in on its target DNA, and edits the DNA to disrupt genes or insert desired sequences.  Researchers often need to order only the RNA fragment; the other components can be bought off the shelf.  Total cost: as little as $30.”

An added benefit is the technique takes far fewer cycles than the earlier technology to make a genetic change in a species.  An article on gizmodo.com that ran 5/6/2015 states, “Researchers inject the CRISPR/Cas9 sequences into mouse embryos.  The system edits both copies of a gene at the same time, and you get the mouse in one generation.  With CRISPR/Cas9, you can also alter, say five genes at once, whereas you would have to had to go that same laborious, multi-generational process five times before.”

An article in the June 8, 2015 issue of Nature states about Jennifer Doudna, a CRISPR pioneer at UC Berkeley, that “Her worries began at a meeting in 2014 when she saw a postdoc present work in which a virus was engineered to carry the CRISPR components into mice.  The mice breathed in the virus, allowing the CRISPR system to engineer mutations and create a model for human lung cancer4.”

The article continued “Doudna got a chill; a minor mistake in the design of the guide RNA could result in a CRISPR that worked in human lungs as well.  ‘It seemed incredibly scary that you might have students who were working with such a thing.  It’s important for people to appreciate what this technology can do.’ ”

A June 25, 2015 bloomberg.com article stated, “CRISPR could encourage editing of all kinds of genomes that, if unsupervised, may present unanticipated risks,” says Arthur Caplan, head of medical ethics at New York University School of Medicine.  “The technique could be used to try to amplify genes thought to boost intelligence in adults.”  Use on animals and insects could also lead to ecological havoc, Caplan says.  “You could have a disaster on your hands, and you don’t have to touch a human to do it,” he said.

As documented in a previous article, see “We Need Worldwide Regulation of Synthetic Biology” http://iamaguardian.com/1680/we-need-worldwide-regulation-of-synthetic-biology/, regulation of Synthetic Biology and Genetic Engineering is split amongst five different federal government departments.  Depending on the development, the organizations that have partial responsibilities are the Environmental Protection Agency (EPA), the Department of Agriculture (USDA), the Food and Drug Administration (FDA), the Commerce Department and the Department of Health and Human Services (HHS).

There needs to be absolute regulatory responsibility for genetic engineering and synthetic biology.  When we have small researchers and venture funded startup companies articulating opportunities and experimenting with alterations to life’s genetic codes with only self-regulation or murky departmental responsibility, we must call a halt.  There should not be the freedom to take all of these risks in the name of profit.

We should be writing letters to the editor and letters to our elected representatives to tell them of our expectations.  We need to speak out against self-regulation and murky, conflicting regulations by multiple government departments.  We need to lobby for new legislation and a single department to assume regulatory oversight.

Use the following links to gain additional information or access the original documents used in this article.

http://www.nature.com/news/crispr-the-disruptor-1.17673

http://www.independent.co.uk/news/science/exclusive-jawdropping-breakthrough-hailed-as-landmark-in-fight-against-hereditary-diseases-as-crispr-technique-heralds-genetic-revolution-8925295.html

http://gizmodo.com/everything-you-need-to-know-about-crispr-the-new-tool-1702114381 (scroll down)

http://www.bloomberg.com/news/articles/2015-06-25//the-promise-and-peril-of-crispr

http://www.nature.com/news/crispr-science-can-t-solve-it-1.17806

http://www.nature.com/news/crispr-move-beyond-differences-1.17805

http://www.iamaguardian.com/1680/we-need-worldwide-regulation-of-synthetically-biology/

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