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When Worlds Collide

A newsfeed came across our inboxes that promoted a notion that China was somehow misbehaving regarding the use of CRISPR to create edited humans.  The dialectic was a non-sequitur because earlier press releases on the efficiency of CRISPR read like a high school newspaper writing about the success of its stageplay being a success because it was over, yet was a total train wreck of a production.  CRISPR can indeed edit a genome for the target mutations, however there can be a hundred downstream changes that were neither intended or predicted or controllable.  That used to be called: The Operation Was A Success But The Patient Died.

What is CRISPR?  CRISPR (/ˈkrɪspər/) (clustered regularly interspaced short palindromic repeats) is a family of DNA sequences found within the genomes of prokaryotic organisms such as bacteria and archaea. 

WE HAVE NO IDEA WHAT WE ARE DOING BUT WE ARE DOING IT WITH GUSTO

“In some cases it is absolutely necessary that no off-target mutations are induced in the genome, but the detection of off-target mutations is more challenging than the detection of on-target mutations because the number and position of off-target mutations is unknown.”  

Researchers have traditionally relied heavily on model organisms such as mice and fruit flies, partly because they were the only species that came with a good tool kit for genetic manipulation. Now CRISPR is making it possible to edit genes in many more organisms. In April, for example, researchers at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, reported using CRISPR to study Candida albicans, a fungus that is particularly deadly in people with weakened immune systems, but had been difficult to genetically manipulate in the lab3. Jennifer Doudna, a CRISPR pioneer at the University of California, Berkeley, is keeping a list of CRISPR-altered creatures. So far, she has three dozen entries, including disease-causing parasites called trypanosomes and yeasts used to make biofuels.

Yet the rapid progress has its drawbacks. “People just don’t have the time to characterize some of the very basic parameters of the system,” says Bo Huang, a biophysicist at the University of California, San Francisco. “There is a mentality that as long as it works, we don’t have to understand how or why it works.” That means that researchers occasionally run up against glitches. Huang and his lab struggled for two months to adapt CRISPR for use in imaging studies. He suspects that the delay would have been shorter had more been known about how to optimize the design of guide RNAs, a basic but important nuance.

By and large, researchers see these gaps as a minor price to pay for a powerful technique. But Doudna has begun to have more serious concerns about safety. 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. 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,” she says. “It’s important for people to appreciate what this technology can do.”

Andrea Ventura, a cancer researcher at Memorial Sloan Kettering Cancer Center in New York and a lead author of the work, says that his lab carefully considered the safety implications: the guide sequences were designed to target genome regions that were unique to mice, and the virus was disabled such that it could not replicate. He agrees that it is important to anticipate even remote risks. “The guides are not designed to cut the human genome, but you never know,” he says. “It’s not very likely, but it still needs to be considered.”

BETTER DYING THROUGH CHEMISTRY

But then CRISPR was never what it was sold to be.  Patrick Jordan and Clint Richardson got close to the true meaning in their exploration of Dupont’s role in the food industry, but it wasn’t until after the show that the real reason for CRISPR research was divined.  

Dupont started out as a munitions manufacturer, then diversified over the years to the point where it dominates half of the yoghurt and microbial culture market.  Because of this mafia cover story Dupont was obligated to find a way to control for the growth of bacteriophages that could alter the starter culture for many dairy products thus ruining batches that were made in vats that measured in tons.  Big business.  Big dollars.  But that is where most people get fixated when it has nothing whatsoever to do with commerce or even food.  Dupont started out as a munitions manufacturer.  The still are.  It is just that the face of warfare has changed.  What people either didn’t know or never bothered to figure out because they let group-think tell them what the talking points are is that CRISPR is the ingenious living organic method that bacteria have to avoid viral invasion and takeover.  A bacteriophage can turn bacteria either lytic which means it self-destructs, or toxigenic meaning that it produces poisons like tetanus or botulism.  If bacteria can resist infection by a virus then it can survive.  CRISPR is a survival mechanism.  So, then we just project at this point: if CRISPR is a survival mechanism and Dupont is a merchant of death then what might they be doing with it beyond the stated purpose?  If we were to be conspiratorial then if you learned everything about CRISPR and how it worked then you could disable it to allow viral weapons to be deployed without the ability to stop them.  If you learned everything about CRISPR you could go beyond bacteria, as some have, to use it as an editing tool to cut and paste ANYTHING YOU WANT into ANY LIVING ORGANISM.  They can, and they have.  Not without consequence.  Don’t forget about the 100 downstream mutations.  But then none of that has ever been a worry since we are talking weapons development so additional or collateral damage was never a downside to the equation. Get it?  Never about money or food.  Just Chili con Carnage.

You can tell from the word choice that is their goal is warfare:

CRISPR Gets More Precise, Will Be Used on More Diseases, Daniel Starkey

We’ve written about CRISPR before. Namely how it is a coming genetic superweapon that we’ll use to fight everything from cancer and infection to diabetes. In short, CRISPR allows scientists to cut out a section of DNA and replace it with whatever they choose. It works using hijacked bacterial machinery, so we’ve essentially hacked up a chunk of a bacterium and we’re now using that to swap genes around… cool, right?

uhhhh….not cool.  Words: GENETIC SUPERWEAPON; HIJACKED, HACKED UP.  Not inspiring confidence, plus there is the perennial promise of CURING disease with every ‘new’ ‘science’ technique that, when evaluated coldly, has NEVER produced results, in fact, the world keeps getting SICKER doesn’t it?

Are there risks?

“Off-target” events.

Although we know how to program Cas9 to make specific edits to genes, it’s not always accurate. Sometimes the wrong portion of the sequence is removed and replaced. Other times, Cas9 slices the right sequence but, once inside the cell, starts editing other sequences. Early CRISPR editing accuracy varied wildly, with some studies reporting many “off-target” events and others reporting very few. As you might imagine, editing the wrong genetic sequence defeats the purpose of CRISPR entirely and can even create new health conditions.

The latest updates to the CRISPR tech have made huge strides in accuracy. Using edited Cas9 enzymes from Strep. pyogenes, MIT and Harvard scientists have nearly abolished off-target events, as evidenced by a study from late last year.

Unforeseen “off-target” events.

Right now, they use a composite human genome, a kind of “standard” or “template,” to map and avoid the potential off-target interactions. But in actual real people (or embryos), every genome is unique. No standardized genome map can account for that.  So, the predictive model that works so well in the lab on a homogeneous sample might not play out the same in the real world.

Assuming those get ironed out, what’s the prospect of hyper-intelligent designer babies?

Perhaps the hyper intelligent babies will outlaw the use of CRISPR.

THE CHINA SYNDROME

The sad-but-funny pattern of data gathering by Patrick Jordan is punctuated by folks sending material with the preface: this may be nothing, but…

Creepy “news” about China’s latest bio-chem moves, and plans.  I never trust anything from Princeton, so, as always, have no idea if any of it is useful.  Sending it your way, with reservation(s).

– steve k

“Just a few engineered organisms could irrevocably alter an ecosystem.”

Esvelt’s computer gene drive simulations calculated that a resulting edited gene, “can spread to 99 percent of a population in as few as 10 generations, and persist for more than 200 generations.” Esvelt was discussing gene editing of mosquitoes. Now we are moving on to gene editing of human embryos.

HISTORY REPEATS….HISTORY REPEATS….HISTORY REPEATS…. 

The reason that Jordan wrote a Timeline book is that when certain facts are put together in a coherent way to be seen clustered within a specific date but then also able to be viewed in a linear progression then patterns that would otherwise be occulted come into view.  The Division of Botony began bioprospecting in 1868, the same year that the USDA started studying animal diseases.  By 1898 the USDA was funded to bioprospect in foreign countries.  1898 also saw H. G. Wells’ book War of the Worlds (that is kind of spooky in light of what we are talking about) mention death beam lasers for the first time.  Bacteriophages weren’t quite known back then but their effects like lysing Bacillus subtilis were desribed in Russia.  Epidemic Contagioius Bovine Pleuropneumonia might not mean a thing to you but back in 1898 Emil Roux was cultivating it.  Now, if we said: MYCOPLASMA MYCOIDES, would that then bring the appropriate chill down your spine?  Roux also gained fame for showing that cancer was caused by a virus.  Now, if we said that it was a papilloma virus would it mean anything to you?  But then if we said that Human Papilloma Virus 18 causes cervical cancer and is what was harvested from Henrietta Lacks and was put into the polio shot will you need some hot water bottles for that chilly spine?

1898.

By 1907 the USDA had discovered the bacteria Agrobacterium tumefaciens created well… tumors.  So they did what anyone would do in that situation: they used it to make GENTICALLY MODIFIED ORGANISMS.  If we could get back to your chilly spine for a moment: a tumor is akin to cancer.  So this was a plant cancer agent that was the very basis for GMOs along with Cauliflower Mosaic Virus.  Plant cancer – GMOs Henrietta Lacks – Cancer – People GMOs.

Need a sauna yet?

If your mind is not conditioned to think of facts in a Continuum where every pertinent fact and sometimes non-pertinent fact and even impertinent fact are all connected to each other somehow and that pattern builds a picture that cannot be seen by staring at just a single dot on the wheel, then you will definitely miss the connection here.

IS IT HOT IN HERE? OR IS IT JUST ME?

Another newsfeed came across our inboxes that said that they were playing with the guts of E. coli bacteria.  Now, E. coli to the human intestine is like wheat to bread.  One doesn’t exist without the other.  Therefore all of the impertinent posturing that this particular bacteria was easy to use and easy to study was just a psyop in a biological warfare arena to get you to think that it was a convenience for scientist to use it as they nobly sought answers for the good of mankind.  And, of course, you would be fatally wrong.  E. coli is so ubiquitous and central to the human gut that if a military construct wanted to test and release new weapons then that single bacteria would be the premier vector of choice.  With that in mind then let’s read the article with jaded eyes:

“Our genetic code is made up of four nucleotide bases, but in recent years, scientists have created microbes that incorporate totally new bases. That has opened up new avenues in synthetic biology and protein engineering. Investigators at the Scripps Research Institute have now engineered a microorganism with a genetic code that was artificially expanded. When these bacteria were exposed to temperatures that would normally prevent them from growing, some of the microbes were able to generate newly evolved proteins that could resist the effects of the heat, remaining stable at temperatures that would typically inactivate them.

The researchers used a common microbe called E. coli and altered it so it would generate a protein called homoserine O-succinyltransferase (metA) from a set of 21 amino acids instead of the natural 20.  The protein will become inactive at certain temperatures, killing the microbe. In this study, metA mutants were created that could swap out almost any of its amino acids with an unnatural one – an ncAA. 

The E. coli was then heated to 44 degrees Celsius, at which point normal metA will inactivate. But some mutant bacteria were able to survive the heat, while bacteria that had made normal metA all died. The researchers had exerted pressure on the bacterial population and were eventually able to create bacteria that could live through temperatures that were 21 degrees above normal. “

Steve’s comment:

“This helps explain the “mining” and sale of microbes from Yellowstone National Park (in opposition to Park’s “preservation” mandate) to Diversa.  

We sued the Park to stop the commercialization/privatization of microbes living in geysers and other extreme (heat and minerals) in federal district court and lost — only got a promise to do an EIS before doing it again.”   See: Edmonds Inst. v. Babbitt, 42 F. Supp. 2d 1 (D.D.C. 1999) (No. Civ. A. 98-56 1(RCL))  )

END GAME

Jordan’s comment:

THAT is why they bioprospect in extremeophile ponds.

THAT is why they will NEVER shut down such operations, because they are weapons development projects and NOTHING stands in the way of warfare.  All of the best efforts and altruism in the will would not prevail against the military industrial complex because Steve was up agains a war machine therefore bioprospecting would fall under national security therefore it would never be curtailed.

The Menekian religion was based on PERPETUAL WAR.

There can be no political answer in a biological war.  Only biological solution can prevail.

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