Genetically Modified Monkeys: What's Next?

Researchers in China have used a new method to produce genetically modified monkeys.  Their purpose is to advance medical research by creating monkeys genetically predisposed to develop human diseases.  But the new method is so precise and so successful that one might imagine it leading to genetically modified humans.   

Caption: Researchers achieved precise gene modification in monkeys.  Credit: Cell, Niu et al.

According to a report published in the January 30 issue of the journal Cell, scientists used a new gene editing technique known as the CRISPR/Cas9 system.  The technique allows for very precisely targeted modification of DNA sequences. 

It also allows researchers to trigger more than one modification at a time. And it seems to avoid causing extraneous mutations where they are not wanted.  

With the CRISPR/Cas9 technique, researchers edited the DNA in monkey embryos at the one-cell stage.  As that cell multiplied, all the cells of the body contained the gene edits, probably including the cells the newborn monkeys might someday pass to their descendants. In other words, this is precise germline genetic engineering in primates.  

"Our study shows that the CRISPR/Cas9 system enables simultaneous disruption of two target genes in one step without producing off-target mutations," claimed Jiahao Sha, one of the lead authors at Nanjing Medical University.

The goal for now, Sha said, is to refine the technique and to be able to create "many disease models...in monkeys," according to the press release issued by the journal Cell.  

Just how refined will the technique become?  Consider that the first successful germline modified monkey was only reported in 2001. The current advance offers far more precision.  With enough precision, it might become possible to apply this technique to a single-cell human egg.  

The modification could be verified before the embryo is implanted, using the well-established technique of pre-implantation genetic diagnosis or PGD.  If implanted and brought to term, the human life created this way would have its germline DNA modified, meaning that the modification would pass to future generations.  

No one knows now whether this technique will offer the kind of precision that would be required to move from monkeys to humans.  But just how much precision is, in fact, required?  With PGD as a way to catch any "mistakes," might ethics committees, in a few decades or even sooner, permit couples and researchers to use this technique in order to avoid transmitting genetic problems to future generations?  Will it then be used to add something new or desirable to the genetic inheritance of our offspring?

The article, Niu et al., "Generation of gene-modified cynomolgus monkey via Cas9/RNA-mediated gene targeting in one-cell embryos," is published in the January 30, 2014 issue of Cell.  

Old DNA, New Tricks

Over the past decade, researchers have learned to reconstruct ancient DNA from fossils.  In December 2013, we were stunned to learn that refinements in techniques made it possible to restore human DNA from as far back as 400,000 years ago. 

Quickly on the heels of that advance, another new development has been announced in the 27-31 January online edition of PNAS.  Scientists at the University of Uppsala, in cooperation with the pioneering team in Leipzig, have developed a way to separate the old DNA sequences from contamination.

Photo Credit: Creative Commons, posted by Archaeogenetics, no restrictions.

Why is that important?  Because contamintion is a leading problem when it comes to reconstructing ancient DNA.  Literally thousands of fossils fill draws and shelves in museums around the world.  They contain DNA, too much of it, in fact, to be of any use.  Bits of ancient DNA are surrounded by more modern DNA from humans and from other organisms.  Now, researchers have learned to separate the old from the new. 
 
What makes the new breakthrough exciting is that now, at least some DNA information from many of these old fossils might be retreivable. 

"Many extremely interesting DNA data sets from ancient humans never see the light of day because of contamination. The idea behind this method was to change that," says Pontus Skoglund, a lead author at Uppsala University.
 
To test the new technique, the researchers used it to reconstruct the mitochondrial DNA from a previously unusuable Neandertal bone from the Altai Mountain region of Siberia.  The sample compared well with other known Neandertal DNA sequences in contrast to more modern humans.
 
It is hard to predict just where this new technology will lead.  At the very least, it seems to unlock the file boxes of museums throughout the world.  Previously discovered fossils, some of them very well dated, might be analyzed for the DNA.  Who knows what we will learn.

"There are many really interesting ancient human remains that we can rescue from severe contamination with this method. And the method is not limited to Neanderthals, even remains of anatomically modern humans that are contaminated by modern-day humans can be rescued," says co-investiagor Mattias Jakobsson in a press release from the University of Uppsala.
 
The new technique is described in a paper entitled "Separating endogenous ancient DNA from modern day contamination in a Siberian Neandertal." Skoglund, P.; Jakobsson, M.; Northoff, B.H.; Pääbo, S.; Krause, J.; Shunkov, M.V.; Derevianko, A.P; PNAS Online Early Edition the week of Jan 27-Jan31, 2014.