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Wednesday, April 22, 2015

HUMAN EMBRYO GENETICALLY MODIFIED BY CHINA

IT MAY SOUND HARMLESS, BUT IT ISN'T.  

THE HUMAN EMBRYO HAS JUST BEEN "EDITED".

ACTUALLY, 86 HUMAN EMBRYOS.

A TEAM IN CHINA HAS 'REACHED IN' AND "TWEAKED" THE HUMAN GENOME IN A WAY NEVER DONE BEFORE. 

From MIT Technology Review:

"The team did not try to establish a pregnancy and say for ethical reasons they did their tests only in embryos that were abnormal."


"The team injected 86 embryos and then waited 48 hours, enough time for the CRISPR/Cas9 system and the molecules that replace the missing DNA to act — and for the embryos to grow to about eight cells each. Of the 71 embryos that survived, 54 were genetically tested. This revealed that just 28 were successfully spliced, and that only a fraction of those contained the replacement genetic material. “If you want to do it in normal embryos, you need to be close to 100%,” Huang says. “That’s why we stopped. We still think it’s too immature.”

YOU CAN READ THEIR PAPER AT THIS WEBSITE: http://link.springer.com/article/10.1007/s13238-015-0153-5/fulltext.html

BACK IN MARCH OF THIS YEAR, FIVE SCIENTISTS WARNED IN THE JOURNAL 'NATURE' THAT GENOME EDITING , OR GENETIC MODIFICATIONS, COULD PROVE DANGEROUS , "POSED SERIOUS RISKS" AND STATED THAT THE BENEFITS WERE "TENUOUS". 

"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."
" It would be difficult to control exactly how many cells are modified. Increasing the dose of nuclease used would increase the likelihood that the mutated gene will be corrected, but also raise the risk of cuts being made elsewhere in the genome."

"The current ability to perform quality controls on only a subset of cells means that the precise effects of genetic modification to an embryo may be impossible to know until after birth. Even then, potential problems may not surface for years."  
WELL, THE CHINESE TEAM WENT AHEAD ANYWAY. 
ALL AHEAD FULL AND DAMN THE TORPEDOES!  

THE CENTRAL CONCERN IS THE NEW TECHNOLOGY FOR GENE MANIPULATION CALLED  "CRISPR Cas9", AND ALL THOSE ENGAGED IN MOLECULAR BIOLOGY/GENETICS HAVE VIEWED IT AS A SORT OF "HOLY GRAIL" FOR QUITE SOME TIME. 

OTHER METHODS OF CHANGING THE HUMAN GENOME HAVE BEEN TRIED FOR LONGER THAN I CARE TO THINK ABOUT, BUT ALL WERE "COSTLY AND TIME CONSUMING TO ENGINEER".
SCIENCE WANTED A "CHEAP, QUICK FIX". 


AS ONE RATHER 'GIDDY' WEBSITE EXPLAINED: 

"The functions of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and CRISPR-associated (Cas) genes are essential in adaptive immunity in select bacteria and archaea, enabling the organisms to respond to and eliminate invading genetic material. 
These repeats were initially discovered in the 1980s in E. coli , but their function wasn’t confirmed until 2007 by Barrangou and colleagues, who demonstrated that S. thermophilus can acquire resistance against a bacteriophage by integrating a genome fragment of an infectious virus into its CRISPR locus."

"INVADING GENETIC MATERIAL"? 
THAT SOUNDS...OMINOUS? 
WELL, THAT IS HOW DEFECTS ARE SEE...INVASIONS OF THE 'NORM'.  

AND USING VIRUSES TO ACCOMPLISH THIS? 
WELL, BACTERIA, VIRUS, ANYTHING TO 'REPAIR' THINGS, YES?
WHY NOT! 

THE TERMINOLOGY OF ALL THIS AND NICE DIAGRAMS ARE GIVEN ON THE ABOVE-LINKED WEBSITE, IF YOU'RE "INTO" MOLECULAR BIOLOGY AND/OR GENETICS.  

FOR NOW, LET'S FOCUS ON HOW THIS CAN BE A VERY BAD THING. 
WHY ARE THE SCIENTISTS WHO COMPOSED THAT ARTICLE IN 'NATURE' UPSET? 
WHAT'S WRONG WITH MAKING A 'GIANT LEAP' FOR HUMAN GENOME ENGINEERING? 

"OFF-TARGET MUTATIONS". 
"OFF-TARGET CLEAVAGE" OF HUMAN DNA.

HERE'S A HINT AT WHY THAT MAY BE NOT SO GOOD: 
"Of the designer nuclease systems currently available for precision genome engineering, the CRISPR/Cas system is by far the most user friendly. It is now also clear that Cas9’s potential reaches beyond DNA cleavage, and its usefulness for genome locus-specific recruitment of proteins will likely only be limited by our imagination." 

"LIMITED ONLY BY OUR IMAGINATION..." 


"USER FRIENDLY"? 
YES, QUITE SO! 
THIS NEWEST DISCOVERY MAKES IT PERHAPS A BIT TOO EASY TO TARGET SPECIFIC, VERY SPECIFIC, GENOMIC SEQUENCES.  

WHAT IF SOMEONE WANTED TO USE THAT EASE, AND THAT SPECIFIC TARGETING IN A BAD WAY?

AND WHAT IF, SOMEWHERE DOWN THE LINE, SEQUENCES BEGAN AND EXPANDED THAT NO ONE COUNTED ON, NO ONE INTENDED? 

WHAT WOULD BE THE END RESULT?  

A-HA! NOBODY KNOWS!!! 

THEN AGAIN, WHAT IF THEY DID KNOW, BUT NO ONE ELSE WAS PRIVY TO THAT INFO? 

The Problem of Off-target Activity

"Genomes are huge and offer a lot of possible binding sites for a nuclease with an intrinsic potential to bind DNA. 

A certain risk of off-target activity therefore always remains. 
The only solution to deal with this problem is to predict potential off-target sites, optimize the design of the nuclease and screen the generated cell lines for additional unwanted mutations."


UMMM, NO, NOPE... 
NOT A "CERTAIN" RISK...A MOST UNCERTAIN RISK! 

"PREDICT POTENTIAL OFF-TARGET SITES"? 
WITH WHAT, A CRYSTAL BALL? 
THAT WORD "PREDICT" IS JUST NOT COMFORTING, IS IT? 

SO, WE HAVE UNCERTAIN RISK AND ONLY PREDICTIONS BUT WE JUMP RIGHT IN AND SCREW AROUND WITH A HUMAN EMBRYO, HOPE FOR THE BEST, CALL IT "ALL BETTER" OR "FIXED" AND A YEAR, 10 YEARS, 30 YEARS DOWN THE LINE, SOME "OFF-TARGET ACTIVITY" BEGINS, HAS A DOMINO EFFECT, AND WE GET WHAT???

NOBODY KNOWS! 

GODZILLA?
FRANKENSTEIN'S MONSTER? 
A DEAD CHILD OR DEAD ADULT?  
SCREAMING AGONY?  

NOBODY KNOWS!!! 

BEFORE THE CHNESE ANNOUNCED THEIR FEAT, THERE WAS A CAUTIONARY WARNING ABOUT THE VERY SYSTEM THEY USED TO GENETICALLY ENGINEER THE HUMAN EMBRYOS.  

"In the case of Cas9, we find frequent off-target sites with a one-base bulge or up to 13 mismatches between the single guide RNA (sgRNA) and its genomic target, which refines sgRNA design."  

AND WHO WROTE THAT? 
COLLEAGUES OF SOME OF THE SAME GUYS THAT JUST WENT AHEAD AND DID THE DEED! 


BUT OTHERS HAD ALSO ISSUED WARNINGS.

MAY, 2014
"... it has been shown that RNA-guided Cas9 nuclease cleaves genomic DNA sequences containing mismatches to the guide strand. A better understanding of the CRISPR/Cas9 specificity is needed to minimize off-target cleavage in large mammalian genomes.   

Our results strongly indicate the need to perform comprehensive off-target analysis related to DNA and sgRNA bulges in addition to base mismatches, and suggest specific guidelines for reducing potential off-target cleavage."  


FORTY (40) NATIONS CURRENTLY BAN OR STRONGLY DISCOURAGE THIS TYPE OF  RESEARCH AND HAVE DONE SO FOR OVER A DECADE.  

CHINA IS NOT ON THAT LIST. 

BUT NEITHER IS THE USA.

"Although the United States has not officially prohibited germline modification, the US National Institutes of Health’s Recombinant DNA Advisory Committee explicitly states that it “will not at present entertain proposals for germ line alterations” 

OH, WHAT THE HELL!
THE CHINESE TEAM JUST WENT AHEAD ANYWAY! 


AND NOW I'D WAGER EVERYONE WHO HAS WANTED TO DO THIS WILL JUST GO FOR IT!

WHY LET THE "OTHER GUYS" GET AHEAD OF THE PACK, RIGHT?

AND IF SOME BAT GUANO INSANE GUY IN SOME DARK LAB SOMEWHERE HAS A GOOD RUN, WHO KNOWS?

SOMEONE, SOMEWHERE, MAY PRODUCE AN ENTIRE NEW BREED OF HUMANS... MAYBE WITH HORNS AND TAILS OR WINGS AND BEAKS....THE POSSIBILITIES COULD BE ENDLESS!

YEAH, SEE, THAT IS THE PROBLEM.

WE JUST DON'T KNOW.

WE OPEN PANDORA'S BOX AND......


DIALOGUE NEEDED

"Ten years ago, the Genetics and Public Policy Center, now in Washington DC, brought together more than 80 experts from the United States and Canada to consider the scientific and ethical consequences of genetically modifying the human germ line. Now that the capability for human germline engineering has emerged, we urge the international scientific community to engage in this type of dialogue. This is needed both to establish how to proceed in the immediate term, and to assess whether, and under what circumstances — if any — future research involving genetic modification of human germ cells should take place. Such discussions must include the public as well as experts and academics.  


Key to all discussion and future research is making a clear distinction between genome editing in somatic cells and in germ cells. A voluntary moratorium in the scientific community could be an effective way to discourage human germline modification and raise public awareness of the difference between these two techniques. Legitimate concerns regarding the safety and ethical impacts of germline editing must not impede the significant progress being made in the clinical development of approaches to potentially cure serious debilitating diseases."


I HAVE TO THINK ABOUT WHAT I MIGHT DO TO 'REPAIR' SOME GENETIC DEFECT IN ONE OF MY CHILDREN OR GRANDCHILDREN. 

WHAT COMES TO MIND IS, WHAT WOULD I NOT DO TO "FIX IT"?  

THAT IS ANOTHER THING TO CONSIDER.  
WOULD SOMEONE IN THAT POSITION EVER STOP TRYING TO MAKE IT ALL BETTER?  

WHERE WOULD ONE DRAW THE LINE PAST WHICH NO ONE SHOULD GO? 

COULD ANY AGENCY OR NATION POLICE ALL ITS SCIENTISTS TO MAKE SURE NO ONE "GOES OFF THE DEEP END"?

I DON'T SEE HOW THAT'S POSSIBLE.  


THIS IS A HUGE STEP IN THE "LET'S PLAY 'GOD' GAME". 

I HOPE NO ONE TRIPS!  





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