New Chinese Research - modification of human germ-line genes

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Offline Poirot

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New Chinese Research - modification of human germ-line genes
« on: April 28, 2015, 06:15:39 AM »
From the Economist:

ABOLISHING thalassaemia is a noble goal. This inherited blood disease, which can cause severe anaemia and consequent organ damage, sometimes fatal, is a scourge to those who suffer it. And abolished it could be, if the broken gene that causes it (which is called HBB and encodes part of the haemoglobin molecule) were itself to be abolished.

That is not an abstract thought. A newish DNA-editing technique called CRISPR/Cas9 is able, at least in principle, to make precise changes in particular genes. Several groups of researchers are trying to work out a way to use it to clear up beta thalassaemia in individual sufferers, by genetically modifying the stem cells which generate red blood corpuscles. But it is theoretically possible to go further. By modifying HBB in a fertilised egg (known technically as a zygote), and letting that zygote develop into a human being, you would abolish the disease not only in the resulting individual but also in his or her "germ line"—the line of descent. By doing this, though, you would create one of the bugaboos of bioethics: a genetically modified human.

That controversial prospect has just been the subject of a real experiment. Huang Junjiu of Sun Yat-sen University in Guangzhou, China, and his colleagues have just published, in Protein & Cell, a description of an attempt to do this, as a proof of principle, in non-viable zygotes. The attempt failed. But it yielded lessons that might make a subsequent try more successful.

CRISPR/Cas9 is a large bit of molecular machinery (see picture) derived from a bacterial defence system that chops up the DNA of invading viruses. In nature, it recognises DNA sequences that are foreign to the bacterium, but the recognition mechanism can be modified to search for any given sequence and cut the DNA there. If this is done to a gene in an animal or plant cell, the cell will try to repair itself using the other copy of the gene present (for there is one from each parent) as a template. That can be subverted by injecting an artificial template of the desired DNA sequence, thus effecting a repair to a previously broken gene.

Dr Huang and his colleagues tried this on HBB with 86 zygotes they had obtained from local fertility clinics. These zygotes were unviable because each had been fertilised by two sperm. They were, nevertheless, suitable for experiment.

Of the 86, 71 survived the procedure and 54 of these were tested to see if it had worked. In 28 the DNA had indeed been cut by CRISPR/Cas9 and then repaired by the cell. In only four of these cases, though, had the artificial template been used for the repair. On top of this, Dr Huang found that there were many “off-target” mutations in other parts of HBB, or in other, similar genes, which would have caused serious damage if expressed in an actual human being.

On the face of things, then, the experiment did not work. But even failure can provide lessons. Knowing which bits of DNA are susceptible to off-target modification, for example, might allow the approach to be refined. Moreover, Dr Huang’s team are probably not alone in their endeavours. A report in Nature says at least four groups in China may be working on human germ-line gene modification.

The controversial nature of the work also led to the paper’s actual publication being a cloak-and-dagger matter. Though neither journal has commented, rumours in the field suggest Dr Huang offered it to Nature and Science (generally regarded as the world’s premier research journals), but both turned it down. Meanwhile Protein & Cell, the work's eventual home, labels it as having been received on March 30th and accepted on April 1st. That is a speed of acceptance most researchers can only dream of.

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Offline Waleed

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Re: New Chinese Research - modification of human germ-line genes
« Reply #1 on: April 28, 2015, 07:33:35 PM »
Really thankful to you for sharing this.

Coincidence is that I just told my boss last week about my disease, he was like  :quiver, and it is our weekend task to read Economist over the weekend and discuss it on Sunday,1st working day in Saudi . I disclosed it because I need to get thalassaemia included in my insurance. Thalpals please pray for me that I get it as we are facing big problems getting treatment here and that I will discuss later on.
Waleed

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Offline jay

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Re: New Chinese Research - modification of human germ-line genes
« Reply #2 on: April 28, 2015, 09:47:38 PM »
Poirot,

Amazing isn't it? Here is the direct link to the study http://link.springer.com/content/pdf/10.1007%2Fs13238-015-0153-5.pdf

The problem is since this is a non western study people started apposing it without seeing any merit in the study and how much success it offers. (I am subject to my point of view)(magazine Science and Nature better know how they run their business and merits of not to publish the study)
In principle from layman's point of view this is similar technique used in gene therapy. Recently scientists including the scientist behind 'CAS9' has issued warning about gene therapy and its experiment in Science magazine in which Bluebird also published article. (I have not read it because it costs few dollars and i was trying if i can get that issue in national library)

Also read the stuff from UK http://en.wikipedia.org/wiki/Three-parent_baby
soon there will be debate in western world that should we allowe couples with 'same orientation' to have their own baby.

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Offline Poirot

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Re: New Chinese Research - modification of human germ-line genes
« Reply #3 on: May 04, 2015, 02:56:18 PM »
I disclosed it because I need to get thalassaemia included in my insurance. Thalpals please pray for me that I get it as we are facing big problems getting treatment here and that I will discuss later on.

I hope you get it included, Waleed. I was once offered a job in Saudi, back in the 90's - before taking it up, I had a free and frank discussion with the owner ("sheik) of the business about Thal and whether they would cover the costs - he said no, but he was good enough to find out the costs for me - cost of blood tx in Riyadh. I eventually turned down the offer because it did not make sense financially - although they were willing to pay for my entire family moving over.

Poirot

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Offline Poirot

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Re: New Chinese Research - modification of human germ-line genes
« Reply #4 on: May 04, 2015, 03:04:42 PM »
Poirot,

Amazing isn't it? Here is the direct link to the study http://link.springer.com/content/pdf/10.1007%2Fs13238-015-0153-5.pdf


Thanks, Jay, for the original research paper. Well, Science and Nature are hidebound - but, I like them that way. It is better to err on the side of being conservative while publishing scientific papers. I don't know if you have been following the whole scam of paying "scientific" journals to publish your papers? Very soon, it will become extremely difficult for the lay person to distinguish between genuine scientific research papers and "paid papers by hacks".

I have been following the "three-parent" baby issue, too.

China is doing a whole bunch of original research now - despite having a significantly lower base of Ph.Ds compared with India. I really wonder what is wrong with the Ph.Ds and scientists in India - apart from ISRO, no decent original research worth the name. There is some original research in agri related areas - but even there, the likes of Monsanto, etc are way ahead and they bought the only real innovative seed company India had originated. Very little original research in medicine or engineering. No home-grown economists worth the name, either. And, for every Bhagwati, we get 10's of morons like Amartya Sen!

Cheers

Poirot

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Offline jay

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Re: New Chinese Research - modification of human germ-line genes
« Reply #5 on: May 05, 2015, 07:49:58 PM »
Poirot,

Thumps up for your Bhagwati / Sen analogy.
Yes China is going ahead now days and specially in biotechnology I was checking out patent analysis by country in field of genetics and biotechnology and China is at distant second running steadily trying to minimise gap with US.

Any way I do not agree with Nature and Science not to publish it for 'ethical reasons' (they have clarify it according to state broadcaster here in Norway). I deeply doubt that there is cartel of western scientist having wasted interest than pure science the reason I am saying this is that the news has spread like a wind all over the world and every news is portraying it as negative while almost all of readers comments are against the negativity in the news and supporting the study.

Regarding the Ph.D situation in India I am not just disappointed very angry too. I live in Baramati which has a biotechnology college and the college had genome sequencer from 2006 one of the early three sequencer in India inaugurated by Ambani most of the students don’t know how to operate and research fellow don’t get access to it. I started HLA typing myself with one of the lab assistant over there but then stopped it because 23andme.com gave me very very good service.
« Last Edit: May 06, 2015, 05:37:21 PM by jay »

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Offline jay

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Re: New Chinese Research - modification of human germ-line genes
« Reply #6 on: May 06, 2015, 05:57:43 PM »
I am going nuts, how could CAF oppose this technique?
They are talking about the ethics; my goodness i am finding myself difficult to restrain my freedom of speech. Hushsh.. i am speechless. Three parent baby doesn't cross their line of ethics.
Painful, sad, nonsense, betrayed, irony.
I am experiencing chills. Huh
« Last Edit: May 06, 2015, 06:07:53 PM by jay »

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Offline Andy Battaglia

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Re: New Chinese Research - modification of human germ-line genes
« Reply #7 on: May 07, 2015, 02:24:04 PM »
Jay,

Most of the world's scientists oppose this research as it crosses a line that the world has agreed would not be crossed. And this research demonstrated why. Yes, they did have unforeseen mutations occur. I completely agree with those who believe we should not be permanently altering the human genome without first understanding ALL potential consequences. Should we chance wiping out humanity to cure thalassemia or any other condition? I agree with the vast majority of scientists who say "no."

For those supporting this research as is, please be aware that you are in an extremely small minority. Please think about the potential for disaster that this technology presents.
Andy

All we are saying is give thals a chance.

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Offline Andy Battaglia

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Re: New Chinese Research - modification of human germ-line genes
« Reply #8 on: May 07, 2015, 02:24:57 PM »
By the way, being ethical is exactly the opposite of of what you are suggesting, Jay.
Andy

All we are saying is give thals a chance.

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Offline jay

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Re: New Chinese Research - modification of human germ-line genes
« Reply #9 on: May 07, 2015, 08:02:50 PM »
Andy i do not endorse it neither denay it but the manner and the speed in which this is refuted concern me.
The extent at which you are extrapolating it has no base.

There are two things a. CAF and gene therapists know deep shit about it (apology i couldn't find other word) and b. I/we don't know it and haven't been told.

There are far bigger non ethical things in the world which has protection of the man made laws it doesn't mean this is non ethical or ethical either.

On one hand scientific and medical community or CAF does not endorse simple measure available at backyard for complete prevention of the suffering and other hand oppose wild or legitimate or may be ethical wishes.

This is not the way forward man.

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Offline Andy Battaglia

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Re: New Chinese Research - modification of human germ-line genes
« Reply #10 on: May 08, 2015, 04:34:56 PM »
The way forward is not to endanger the future of humanity. The way forward is not to defy the international consensus about DNA splicing in humans. The way forward is to know what the potential consequences will be before it's too late to change it. I agree completely with CAF and the vast majority of the world community on this issue. The ethical reasons alone, should be enough to stop this from proceeding, but the very real danger of introducing unknowns into the human genome should make everyone stop in their tracks. I am amazed that people are attacking CAF over this, as all they did was agree with the world scientific community.

What CAF said.
Quote
CAF Opposes Gene-editing Research Involving Human Embryos; NIH Agrees

NIH_Master_Logo_Vertical_2ColorCAF recently issued a statement that while it supports ethical applications of technology that advance the search for a cure for thalassemia, the Foundation does not condone the use of technology in a clinical setting in a manner which is inappropriate or inconsistent with U.S. regulatory guidelines. In so doing, CAF made it clear that an international consensus on the proper use of such technology is warranted and should be followed.

In a statement issued April 29, NIH Director Francis S. Collins, MD, PhD, concurred, stating that “NIH will not fund any use of gene-editing technologies in human embryos.” Dr. Collins added that altering the human germline in embryos for clinical purposes raises both safety issues and ethical issues.

And my post on thalpal on Facebook.

I agree completely with the statement by CAF. A reckless approach to this technology could have disastrous results, and there are ethical concerns that cannot be glossed over. This is a genie that isn't ready to be released from the bottle. Cooleys Anemia put it quite well.
"In so doing, CAF made it clear that an international consensus on the proper use of such technology is warranted and should be followed."

The international consensus is that this should not proceed at this point in time. I'm in no hurry to see DNA manipulated and passed on to future generations without fully understanding all potential consequences and without an international consensus on the involved ethical issues of altering the human genome.
Andy

All we are saying is give thals a chance.

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Offline sofear

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Re: New Chinese Research - modification of human germ-line genes
« Reply #11 on: May 08, 2015, 09:03:27 PM »
international consensus

What exactly does 'international consensus' imply? Did every single country in the world proclaim that they oppose this technology?

Quote
U.S. regulatory guidelines

Never mind, I guess it's really the whole world then. Atleast from an U.S. point of view. :biggrin

The way forward is not to endanger the future of humanity.

How far we should restrict the current generation in the interest of future generations would be an interesting topic to debate. For me personally, it's tough to decide when I have to weigh something like the 'future of humanity' against the suffering of people who are alive or born during my own life time, because the latter is something that is actually able to affect me in an emotional way while the former is not.

The ethical reasons alone, should be enough to stop this from proceeding

Which would be?



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Offline Sharmin

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Re: New Chinese Research - modification of human germ-line genes
« Reply #12 on: May 09, 2015, 04:58:58 AM »
I'm not sure if people are actually understanding this study or its implications.  

As you can see Andy and this group has constantly championed all viable and reasonable treatments for all existing thalassemia patients.  In fact, we have focused heavily in non North American patients.   Going to great lengths to educate people and even send medications at our own expense to patients in other countries.     Kindly do NOT suggest that we are favouring the USA because that is counter everything that we do.  

Bluebird Bio gene therapy, hydroxyurea, bmt, cbt, the latest chelates - we align ourselves with them all because the benefits are greater than the risks.  

Many potential cures are now available.  Our hopes are that they will be safe.  

As for altering the genome of embryos that can be passed on indefinitely????  If a mistake is made it can change the germline forever - causing cancers or other horrible diseases.  In fact, you may not have to wait long it can happen in the human being you create from this process or the very next generation.    

There is great great danger in altering embryonic DNA.  

I'm certain that Andy means international consensus to mean a majority of nations and the added US regulatory guidelines to mean that US guidelines also oppose this research.  

Taking steps like these could create a problem that we may lose control over.  

Yes, unethical things do happen - all over the world but we do NOT encourage them here and the fact the unethical things happen does not justify playing with human germ cells.  

I absolutely DO NIT see how messing with embryos would help existing thalassemia patients in anyway.  In fact, gene therapy etc   Are the only ways to help and Andy and thus group are breaking our backs to champion these efforts.  

Andy, I apologize in behalf of our group and what you have been tolerating on Facebook and on that pal these last few days.  These comments are more attacks then comments or questions.  

My son has thalassemia major, j want more than anything for him to be cured - but I am disgusted by all of this.   As a mother of a thal I can barely tolerate what my son endures.  Why on earth would I want to risk my grandchildren or their children by creating potentially far worse illness?   

We encourage science and medical advancement Her but not dangerous unethical research that has great potential but very little potential for benefit. 

« Last Edit: May 09, 2015, 05:07:10 AM by Sharmin »
Sharmin

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Offline jay

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Re: New Chinese Research - modification of human germ-line genes
« Reply #13 on: May 09, 2015, 06:02:12 AM »
Sharmin you are not my lawyer don't apologize on my behalf, stop patronizing, I can not write my full arguments in details for now because i have to work more than ever and i am working on weekends as well mean while don't take my advocacy.

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Offline Andy Battaglia

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Re: New Chinese Research - modification of human germ-line genes
« Reply #14 on: May 09, 2015, 03:12:13 PM »
Anyone not understanding what international consensus is should investigate this matter further.

I have some very harsh words for the incredibly selfish and shortsighted who are arguing that this technology should proceed without an international consensus as to its limits, which must be very strict, and also complete and total understanding of the long term impact on the human genome. I will keep most of those words to myself. Personally, I am quite saddened that some of the members of this group blindly support this, apparently without a single concern about its safety or the immense ethical issues involved. That is your failing, not mine. The snarky comments are inappropriate and have greatly affected my view of some members of thalpal. Frankly, Lisa would be horrified at this behavior. I did not create the international consensus. but like CAF I fully support it. This isn't Facebook and I will not entertain endless arguments about this. If you don't understand why there is such a loud outcry from most of the world, you haven't done your homework and I am not doing it for you.

And for those not getting it, should we allow this DNA altering technology to move forward without limits? Please do try to see the big picture. Can we create subservient humans to serve us? Should parents be choosing genetic features? Should an enemy be able to create "supersoldiers"? What happens to the guinea pig (your child)? Or should we just say screw it and look at only short term selfish goals? The ethical concerns are immense and cannot be ignored.

Learn something about why the vast majority of international scientists are opposed to this technology proceeding at this point in time. The willful ignorance of some on this issue is not my doing. I have no doubt that at some point, we will understand the potential consequences to see if this is worth developing, but only after all ethical issues have been decided and strict limits as to what can be done are instituted.

Sharmin, as always, thank you for your support. Your comments about the potential unforeseen consequences like cancer are spot on and reveal an understanding of this complex issue that is missing in some others.
Andy

All we are saying is give thals a chance.

 

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