Thursday, March 26, 2015

CRISPR Cas 9 Again

The system used by bacteria to defend against a virus attacking is the CRISPR Cas 9 system. An interesting use of a protein, enzyme, and a DNA segment that can open DNA at desired locations and cut and insert new segments of DNA. We have been discussing this for well over a year now and have discussed its potential and its risks.

Now along come researchers who instead of doing this in somatic cells do it in germline cells, thus changing the potentially maturing entity. Thus each cell has this changed gene or genes.

In a recent Nature article the authors state:

There are grave concerns regarding the ethical and safety implications of this research. There is also fear of the negative impact it could have on important work involving the use of genome-editing techniques in somatic (non-reproductive) cells....In our view, genome editing in human embryos using current technologies could have unpredictable effects on future generations. This makes it dangerous and ethically unacceptable. Such research could be exploited for non-therapeutic modifications. We are concerned that a public outcry about such an ethical breach could hinder a promising area of therapeutic development, namely making genetic changes that cannot be inherited. At this early stage, scientists should agree not to modify the DNA of human reproductive cells. Should a truly compelling case ever arise for the therapeutic benefit of germ­line modification, we encourage an open discussion around the appropriate course of action.

Now this point is well made. Germline cell changes introduce all sorts of issues. Not only is there the issue of what this new gene will do, we hardly have begun to understand gene interactions, but the issues of epigentic factors such as methylation dramatically change the risks.

Frankly I miss Michael Circhton, in this case he would have clearly shown us the mistakes we could be making with an unruly unleashing of this technology. Jurassic Park would be a walk in the park as compared to what these could unleash. Imagine correcting those few genes in Apes and the other close to man mammals and see what we could get!

The again you do have the advocates in Technology Review, that somewhat unidentifiable magazine sent to MIT alumni and others, that states:

When I visited the lab last June, ... proposed that I speak to a young postdoctoral scientist named ..., a Harvard recruit from Beijing who’d been a key player in developing a new, powerful technology for editing DNA, called CRISPR-Cas9. With ..., ...had founded a small company to engineer the genomes of pigs and cattle, sliding in beneficial genes and editing away bad ones. As I listened to ..., I waited for a chance to ask my real questions: Can any of this be done to human beings? Can we improve the human gene pool? The position of much of mainstream science has been that such meddling would be unsafe, irresponsible, and even impossible. But ... didn’t hesitate. Yes, of course, she said. In fact, the Harvard laboratory had a project to determine how it could be achieved. She flipped open her laptop to a PowerPoint slide titled “Germline Editing Meeting.” Here it was: a technical proposal to alter human heredity. “Germ line” is biologists’ jargon for the egg and sperm, which combine to form an embryo. By editing the DNA of these cells or the embryo itself, it could be possible to correct disease genes and to pass those genetic fixes on to future generations. Such a technology could be used to rid families of scourges like cystic fibrosis. It might also be possible to install genes that offer lifelong protection against infection, Alzheimer’s, and, ... told me, maybe the effects of aging. These would be history-making medical advances that could be as important to this century as vaccines were to the last.

 The problem is as the writers in Nature and in Science, led by David Baltimore, have noted, the germ line modifications could be unwieldy.

Just because we have a new technology is no reason to let is loose. The problem with this technology is that it not only can be weaponized but that it can be done in a basement lab. This not building a nuclear weapon. This is potentially setting the world afire.

The again there is the issue of Government regulation. In an interesting piece in Xconomy the author remarks:

But researchers’ and investors’ fear that a patchwork of regulation would cripple biotechnology in the United States did not disappear right away. Biologist Thomas Maniatis of Harvard left his home lab to work on the techniques in tighter-security conditions at Cold Spring Harbor Laboratory in New York. Others went abroad. Biogen, founded in 1978, put its first major lab in Geneva, Switzerland. This was a time of intense concern about environmental dangers from the chemical industry in particular and science in general. It took some years for biologists to gain respect among local state, and federal officials for their sense of responsibility in the recombinant DNA maelstrom of the mid-1970s. But politicians did accept that biotechnology was a significant new industry that other countries, like Japan, might seize if America dropped the ball.

A valid point, but in the 70s we worried about errant scientists. Now we are terrified about terrorist post docs! One wonders what would be worse; the Government Regulators or the Terrorist?