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CRISPR-Cas9 and germ-line engineering

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How far should we go with this? Is eugenics lurking in the dark corner? The problem is once you have let the genie out you can't pop him back in again.

 

Brief background

 

Bacteria make CRISPR RNAs that recognise the DNA of viruses which prey on them, marking that DNA for destruction by Cas9 and thus protecting the bacteria from infection. Scientists can make RNAs that target any sequence they want. And because of the way that cells repair broken DNA, if they put a new gene into a cell along with the CRISPR-Cas9 system, they can get that new gene to replace an old one. The effect is to give scientists something that works like the find-and-replace function on a word processor.

 

Because it is so simple and easy to use, CRISPR has generated huge excitement in the worlds of molecular biology, medical research, commercial biotechnology—and gene therapy, where it may make it possible to make changes with profound consequences. To date gene therapies have been designed to fix everyday sorts of cells, such as those of the blood, or the retina, or the pancreas. CRISPR makes it possible to think about aiming at the special cells that make sperm and eggs, or the genome of a fertilised embryo awaiting implantation in the womb. In either case the changes made would pass from one generation to the next, and the one after that, in perpetuity.

 

But

Scientists Call for a Summit on Gene-Edited Babies

 

A group of senior American scientists and ethics experts is calling for debate on the gene-engineering of humans, warning that technology able to change the DNA of future generations is now “imminent.â€

 

In policy recommendations published today in the journal Science, eighteen researchers, including two Nobel Prize winners, say scientists should accept a self-imposed moratorium on any attempt to create genetically altered children until the safety and medical reasons for such a step can be better understood.

 

 

http://www.technologyreview.com/news/536021/scientists-call-for-a-summit-on-gene-edited-babies/

Edited by knocker
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I must admit that I've had to do some quick background reading on CRISPR, as I'm old enough to have studies biology (in particular genetics and molecular biology) before it was well-understood and therefore added to textbooks! 

 

It sounds fantastic from the point of view of a researcher, though - you only need an RNA molecule that corresponds to the target DNA sequence (the homologue of the "spacer" in the cas-CRISPR complex in prokaryotes) and the gene you want to insert as opposed to trying to get the cells to synthesise an entire "foreign" protein by designing and producing novel and complex restriction endonucleases.

 

As to the ethics, as far as see it, it doesn't present unforeseen problems, just expands the scope of existing ones (please correct me if I'm wrong on this).

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Well there is the most controversial form of editing—editing the genome of a newly created embryo, or of the cells that produce sperm and eggs. If this could be done safely it would offer the possibility of acting once and for all. By changing a gene in an early-stage embryo, or in the cell that makes an egg, you could ensure that the change is found in every cell in the adult body—including its own eggs or sperm, which would pass it to the next generation and thus on down through the ages. No one is pursuing such avenues  as yet. But the announcement in April that a Chinese group had engineered changes into non-viable human embryos as part of their research into beta-thalassaemia set alarm bells ringing

 

Another example, one particularly impressive—and potentially worrying—application is in the creation of genes that can spread themselves quickly through a population with blithe disregard for the constraints of natural selection. Engineering the CRISPR-Cas9 system itself into a creature’s genome makes it possible for an organism to edit its own genes, and there are ways that this ability can be used to “drive†a gene through a population. Although such a technology might, proponents say, be used to make the mosquitoes that carry malaria, or dengue fever, unable to spread the organisms responsible for causing the disease.

Edited by knocker

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Generally, I'm equivocal on genetics; advancements in medicine will of course come along, sooner or later. It's the other side of the coin that worries me: What's to stop some neo-Nazi (or Communist) loon from creating a deadly pathogen that affects only peeps who carry certain specific genetic traits (gene sequences)?

 

As each and every ethnic group carries its own unique gene sequences, the scope for nefariousness seems almost infinite...

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Well there is the most controversial form of editing—editing the genome of a newly created embryo, or of the cells that produce sperm and eggs. If this could be done safely it would offer the possibility of acting once and for all. By changing a gene in an early-stage embryo, or in the cell that makes an egg, you could ensure that the change is found in every cell in the adult body—including its own eggs or sperm, which would pass it to the next generation and thus on down through the ages. No one is pursuing such avenues  as yet. But the announcement in April that a Chinese group had engineered changes into non-viable human embryos as part of their research into beta-thalassaemia set alarm bells ringing

 

Another example, one particularly impressive—and potentially worrying—application is in the creation of genes that can spread themselves quickly through a population with blithe disregard for the constraints of natural selection. Engineering the CRISPR-Cas9 system itself into a creature’s genome makes it possible for an organism to edit its own genes, and there are ways that this ability can be used to “drive†a gene through a population. Although such a technology might, proponents say, be used to make the mosquitoes that carry malaria, or dengue fever, unable to spread the organisms responsible for causing the disease.

 

Good points - I'm a touch rusty so hadn't fully appreciated the implications of the cas-CRISPR genes being included in the gene transfer, thereby allowing further control after embryogenesis. 

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Editing of Pig DNA May Lead to More Organs for People

 

A gene editing advancement may someday make pig organ transplants into humans possible (The procedure is not called a Reverse-Cameron)

 

 

This month, scientists gathered at the National Academy of Sciences in Washington to talk about Crispr, a new method for editing genes. In the past couple of years, the technique has become so powerful and accessible that many experts are calling for limits on its potential uses — especially altering human embryos with changes that could be inherited by future generations.

 

Among the scientists describing recent advances was one of Crispr’s pioneers, George Church of Harvard Medical School. In the midst of his presentation, packed with the fine details of biochemistry and genetics, Dr. Church dropped a bombshell.

 

In a typical experiment, scientists use Crispr to alter a single gene. But in recent work with pig cells, Dr. Church and his colleagues used Crispr to alter 62 genes at once. The researchers hope that this achievement may someday make it possible to use pig organs for transplantation into humans.

 

But the experiment also raises a deeper question: Could scientists someday alter complicated human traits by manipulating many genes at once?

 

http://www.nytimes.com/2015/10/20/science/editing-of-pig-dna-may-lead-to-more-organs-for-people.html?smid=tw-nytimesscience&smtyp=cur

Edited by knocker

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I was teaching about PGD to my students and showed them the clip of the Chinese research breakthrough announcement, to gauge their opinion and provoke discussion, quite a few seemed to have no qualms about it, many saw it as far too much meddling. On a scale of "bad things" that are done in the world, it is a small thing, but on the whole I think a step too far.

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Very interesting reading Knocker, thank you. Ethically my concern is when certain rather backwards countries start to use this technology. For example India, where they already gleefully participate in gender selective abortion, something any civilised person is disgusted by. Imagine what they'd get up to with this.

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Scientists unveil the 'most clever CRISPR gadget' so far.

For all the hoopla about CRISPR, the revolutionary genome-editing technology has a dirty little secret: it’s a very messy business. Scientists basically whack the famed double helix with a molecular machete, often triggering the cell’s DNA repair machinery to make all sorts of unwanted changes to the genome beyond what they intended.

On Wednesday, researchers unveiled in Nature a significant improvement — a new CRISPR system that can switch single letters of the genome cleanly and efficiently, in a way that they say could reliably repair many disease-causing mutations.

Because of “the cell’s desperate attempts” to mend its genome, said Harvard University biologist George Church, “what often passes as ‘genome editing’ would more appropriately be called ‘genome vandalism,’” as the cell inserts and deletes random bits of DNA where CRISPR cuts it.

https://www.statnews.com/2016/04/20/clever-crispr-advance-unveiled/

Edited by knocker
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On 16/10/2015 at 8:17 AM, Woollymummy said:

but on the whole I think a step too far.

It has the potential to stop many incurable diseases , It's more immoral in my opinion to be against it.

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Depends on the cost benefit ratio and the dice-rolling that goes on before money is allocated in health care budgets. Not sure I could see it bringing more benefits than using the money in other ways.

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12 hours ago, Woollymummy said:

Not sure I could see it bringing more benefits than using the money in other ways.

Such as? I don't know how you can get 'more benefits' than the benefits of many diseases being cured.

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Over on reddit.com/r/science the last week, we've been having genetics themed week with Q&A sessions (called AMAs on reddit) with different researchers and groups working on genetic engineering and other genomic studies.

Ye can read through the previous AMAs here

We've also had a few researchers and groups on to talk specifically about CRISPR, which you can find here

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12 hours ago, Barry95 said:

Such as? I don't know how you can get 'more benefits' than the benefits of many diseases being cured.

I am guessing the germ-line testing and manipulation procedure is expensive, compared to palliative care for existing ill people who have needs. Just my own thoughts, I have no data to back me up, just a gut feeling of what I would prefer: I'd rather havemoney spent on treating my ill adult relative to make his life more bearable, than introducing a procedure to make an as yet non-existent person's life more "normal".

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On 22 April 2016 at 11:39 PM, Barry95 said:

It has the potential to stop many incurable diseases , It's more immoral in my opinion to be against it.

http://www.nature.com/news/crispr-the-disruptor-1.17673

correction of disease causing regions = 0.4%

changes in off-target areas range from 0.1% to 60%

A bit hit-and-miss really. Ok I suppose with fruit flies but not really ok if you are doing this with human embryos, considering the unpleasant side effects of egg harvesting for IVF. Or are you going to use artificial human eggs? 

One of the best students I know: a cystic fibrosis patient, harder working, more resilient and focused than her healthy classmates, growing up and contributing way more than anyone could wish, a lovely person, almost certainly has a shorter lifespan than any of us, but is making the absolute best of what life has thrown at her. That is what I call real progress in humanity, allowing people to live the very best lives while they can.

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11 hours ago, Woollymummy said:

I am guessing the germ-line testing and manipulation procedure is expensive, compared to palliative care for existing ill people who have needs. Just my own thoughts, I have no data to back me up, just a gut feeling of what I would prefer: I'd rather havemoney spent on treating my ill adult relative to make his life more bearable, than introducing a procedure to make an as yet non-existent person's life more "normal".

http://www.nature.com/news/crispr-the-disruptor-1.17673

correction of disease causing regions = 0.4%

changes in off-target areas range from 0.1% to 60%

A bit hit-and-miss really. Ok I suppose with fruit flies but not really ok if you are doing this with human embryos, considering the unpleasant side effects of egg harvesting for IVF. Or are you going to use artificial human eggs? 

One of the best students I know: a cystic fibrosis patient, harder working, more resilient and focused than her healthy classmates, growing up and contributing way more than anyone could wish, a lovely person, almost certainly has a shorter lifespan than any of us, but is making the absolute best of what life has thrown at her. That is what I call real progress in humanity, allowing people to live the very best lives while they can.

So you'd rather the NHS just spend money on relieving pain of people with horrible diseases than trying to cure them?

The average age of death of someone with Cystic Fibrosis is 37, compared to 81 of a healthy person in the UK. How much is 'too much' to extend someones life by 40+ years?

and it's not just a 'non-existent person' that will benefit from this, people living with Cystic Fibrosis now for example, could be cured.

Edited by Barry95

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A pdf of ongoing trials for Lung cancer, Some of the treatments if not all are based on Crispr. I personally think it's well worth the money if it works. 

http://genesdev.cshlp.org/content/29/14/1447.full.pdf

Long read but worth it if you want to understand about the process behind these treatments.

Edited by alexisj9

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3 hours ago, Barry95 said:

So you'd rather the NHS just spend money on relieving pain of people with horrible diseases than trying to cure them?

The average age of death of someone with Cystic Fibrosis is 37, compared to 81 of a healthy person in the UK. How much is 'too much' to extend someones life by 40+ years?

and it's not just a 'non-existent person' that will benefit from this, people living with Cystic Fibrosis now for example, could be cured.

I was saying intervening at the embryo stage seems too far in principle, because no one can guarantee the technique would be limited to curing disease. We all have our own boundaries, some go further than others.

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5 minutes ago, Woollymummy said:

I was saying intervening at the embryo stage seems too far in principle, because no one can guarantee the technique would be limited to curing disease. We all have our own boundaries, some go further than others.

I agree with you on that, no way should they do it to an embryo, that is to far. However when it comes to treating diseases people have that are not curable, if it can delay or completely prevent disabilities or cure, or slow down cancer, I'm all for it.

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Am I right in thinking this technique would be able to quickly get to the rogue gene by rapidly showing which changes knock out the original harmful mutation? As a research and development screening technique? In which case that seems a useful tool. But I thought the original post was about germ line genetic editing?

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