Skeptophilia (skep-to-fil-i-a) (n.) - the love of logical thought, skepticism, and thinking critically. Being an exploration of the applications of skeptical thinking to the world at large, with periodic excursions into linguistics, music, politics, cryptozoology, and why people keep seeing the face of Jesus on grilled cheese sandwiches.
Showing posts with label CRISPR. Show all posts
Showing posts with label CRISPR. Show all posts

Saturday, September 23, 2017

A genetic cut-and-paste

If I had to pick one technology that I think will make the most different to human quality of life thirty years from now, I would pick CRISPR/Cas9.

CRISPR stands for "Clustered Regularly Interspaced Short Palindromic Repeats," a sequence of repetitive DNA in prokaryotes (bacteria) that interacts with a gene called Cas9 to chop up and inactivate foreign DNA.  At first, it seemed like it would interest only someone with a fascination for bacterial genetics.

Then it was discovered that you could guide CRISPR/Cas9 to specific sequences in DNA using a piece of RNA as a guide.  Think of it as a pair of scissors with a laser sight.  Molecular biologists saw the implications immediately; with that tool, you could cut out any piece of DNA you wanted, insert new genes, inactivate old ones -- you veritably have a cut-and-paste function for the genetic code.

The potential applications to treat human disease are nearly endless.  Disorders where the affected individuals have an inoperative gene, and therefore lack the specific protein it produces, might have the error repaired by splicing in a corrected copy.  (Possible candidates for this are cystic fibrosis and hemophilia.)  On the other hand, disorders where the defective gene makes a damaged end product -- such as sickle-cell anemia and Huntington's disease -- might have the faulty gene cut out and discarded.

All of this is still in the future, however.  At the moment, scientists are playing with CRISPR, seeing what it can do.  And just last week, a team at Cornell University used CRISPR/Cas9 on butterflies to inactivate specific genes...

... and completely changed the color patterns on their wings.

One of the species they worked on was the Gulf Fritillary (Agraulis vanillae), a beautiful black, orange, and gold butterfly native to the southeastern United States.

[image courtesy of photographer Jonathan Zander and the Wikimedia Commons]

When a gene called optix was selectively inactivated by CRISPR/Cas9, the result was stunning.  All of the orange and gold regions turned velvety jet black.  White spots became a metallic silver.  Silencing a different gene, WntA, had a different result -- stripes blurred, eyespots disappeared, edges became indistinct.

Anyi Mazo-Vargas, one of the authors of the paper, calls genes like optix and WntA "paintbrush genes."  "Wherever you put them," Mazo-Vargas said, "you'll have a pattern."

They tested optix deletion on other species, and found similar results, even in species that have been evolutionarily separated for 80 million years.  Colorful butterflies come out looking monochrome. "They just turn grayscale,” said Robert Reed, who led the study.  "It makes these butterflies look like moths, which is pathetically embarrassing for them."

The fact that these genes can be inactivated, almost like flipping a switch, and have such body-wide results is nothing short of spectacular.  Of his earlier work in studying color genes in butterflies, Reed said, "It was convincing but we didn’t know exactly what these genes were doing. Without the ability to delete the genes, and see if their absence changed the butterfly wings, we didn’t have the final proof.  There’s been this frustrating wall that I’ve banged my head against...  CRISPR is a miracle.  The first time we tried it, it worked, and when I saw that butterfly come out ... the biggest challenge of my career had just turned into an undergraduate project."

Of their first success -- the jet-black-and-silver Gulf Fritillary -- Reed said, "It was amazing to see that thing crawl out of the pupa... it was the most heavy metal butterfly I've ever seen."

All of this is one more indication of why we should all be in support of pure research.  On one level, this might sound kind of silly to the layperson -- some scientists tinkering around and changing the color of butterfly wings.  But when you see where such research could lead, and the potential application to human health, it's absolutely stunning.

In my opinion, it won't be long before we're using the same genetic cut-and-paste not to fiddle with "paintbrush genes" in butterflies, but to repair genetic defects in humans.  And that would be the biggest leap in medical science since the invention of vaccines.

Monday, September 26, 2016

RNA attack

It's a common strategy.  If simply spouting alarmist rhetoric doesn't cause your target audience to panic sufficiently, throw in some quasi-technical nonsense to make it sound like your position actually has scientific merit.  Unfortunately, it has a way of working, as people like Vani "The Food Babe" Hari discovered when she launched her "if you can't pronounce it, you shouldn't be eating it" campaign, which if it succeeded, would rob your diet of most of its essential nutrients, leaving behind only easy-to-say stuff like "starch."

It's the old "if you can't dazzle 'em with brilliance, baffle 'em with bullshit" approach dressed up in new clothes.  It's a favorite strategy of such anti-science types as the anti-vaxxers and anti-GMOers (who in many cases are one and the same).  Witness the latter's latest sally against the scientific establishment, which revolves around the claim that if you're eating GMO food, it contains RNA (true) and this RNA can alter your own genes (false).

I learned about this bizarre statement from Sterling Ericsson's wonderful blog A Science Enthusiast, wherein we learn that the anti-GMO cadre have gone from the diffuse claim that all GMOs are bad to proposing a specific mechanism by which they do their dirty work -- they contain "engineered RNA" that then can get into your cells and interfere with your normal cellular processes.  And to the non-scientific, even the actual research can certainly sound like the stuff of science fiction; gene-modification techniques like CRISPR, switching genes on and off with RNA interference, inserting DNA from one species into another to generate organisms that express "foreign" genes as they would their own.

[image courtesy of Christopher Bock, the Max Planck Institute, and the Wikimedia Commons]

My objection to the anti-GMO stance has always been that it lies squarely in the midst of the package-deal fallacy; just as our "natural" genes have thousands of different functions, each GMO is different from all the others.  GMOs are no more all bad than genes are, and each one has to be tested for safety individually.  (And they have been, extensively.)  But the addition of the "ingesting engineered RNA" claim adds a whole new layer of pseudoscience to the anti-GMO stance.  Rather than making it stronger, it makes it weaker, and (further) shines a harsh light on exactly how unscientific the claim itself is.

Because all of the food we eat contains nucleic acids, DNA and RNA both.  If you eat lettuce, you're eating (among other things) lettuce DNA and RNA.  If you eat a hamburger, you're ingesting the genetic material from cows (and tomatoes and whatever else you like on your burger).  If you eat "Slim Jims," you're consuming DNA from... well, whatever the hell organism "Slim Jims" are made from.  I dunno.  But presumably it was some kind of living thing at some point that had its own genetic material.

And miraculously, we don't start expression lettuce, cow, tomato, or Slim Jim genes, nor do any of those interfere with our own gene expression.  The reason is that in your small intestine you have enzymes called nucleases that break down the DNA and RNA of the organisms we eat, specifically to prevent us from accidentally incorporating foreign genetic material into our cells, which could cause us to express foreign proteins (depending on what they were and where they were produced, this could certainly be deleterious).  So the DNA and RNA in our food -- which is there even in the most organic-y of organic free-range locavore diets -- never survives the passage through our digestive system intact.

That includes any "artificially engineered" DNA and RNA, because your body can't tell the difference between the genetic material that came from a healthful, natural, non-engineered peach and that which came from BT corn purchased directly from Monsanto.  It all breaks down, natural and artifical alike.  If there's a health effect from eating GMOs, it doesn't come from the DNA and RNA -- it comes from the proteins they produced within the genetically modified organism before you ate it.

And like I said, those have been tested to a fare-thee-well.  But this is not likely to persuade the anti-GMOers, for whom the naturalistic fallacy is very nearly one of the Ten Commandments.

So anyhow, be on the lookout for this.  Call it out for the nonsense it is.  As I've said many times before, you do not make your point stronger by leaning on poorly-understood science.  All you do is make it seem like the rest of your claim has little merit as well -- which in this case, seems to be the truth.