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Synthesising humans, a modern topic of debate?

Synthesising humans, a modern topic of debate?

27/07/2017
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Merogenomics


One genome-related newstory that has stirred the public lately was last year’s announcement of a project to synthetically build a human genome. What do I mean by that? To build an entire human genome, the DNA code that makes each individual unique, with a machine base by base, chromosome by chromosome. You can imagine such information elicited quite a few gasps among the bewildered public. The New York Times, for example, picked up the story once when the project was discussed at a “secret” meeting, and then again when the project was actually announced.

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This is a really difficult topic to grasp from an ethical point of view. On the one hand, the simple fact that the topic has attracted so much attention and debate reflects the collective fear and potential rejection of the idea. And for good reasons, as human lives are not meant to be tampered with. This is the line that probably very few individuals would be okay with, not to mention the already present discomfort and public opposition towards any genetically modified organisms, whatever their practical and potential economic benefits. One can argue that the public is poorly aware of science, and to a degree that would be correct. But public statements on science topics are like a window to our collective ethics regarding such topics, whether the science is understood correctly or not.

On the other hand, the authors and proponents of the project broadcast the potential medical benefits and potential scientific and technological advancements resulting from synthetic generation of a human genome, which no doubt would be true. The Human Genome Project is a valid example of such developments. The medical advances already achieved thanks to such forward steps have saved numerous lives and countless more will be saved. Technological advances, such as cheap and abundant synthesis of DNA would surely have spill-over effects towards progress in medicine too.

But let’s go back to that lingering public fear of the technology. After all, deep down we all know that integrity, morals, and ethics are frequently compromised in the world (everyone can probably think of an example!), so the ethics behind the synthetic design of human genome should be thoroughly explored and not subject to such compromise. The idea of having such powerful tools in the wrong hands is just as disgruntling as the idea of a nuclear bomb being present in wrong hands.

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And even if we ignore that aspect, assuming that no harm shall ever be attempted using the knowledge gained from creating an entire human genome from scratch, there are other questions to ask.

Who will own such a synthetic genome?

What will be the governing body providing oversight of the final product?

Where will the line be of how such synthetic genome is used in scientific studies?

To what degree is recreating a human genome, to which we already have access naturally, going to help with medical advances, unless it is tested, or manipulated.

Will it be used to produce cell lines to study medical problems?

That might seem acceptable, but could the same arguments be used to ask if non-viable embryos could be generated to study medical breakthroughs?

And finally, and perhaps this seems far-fetched, but let’s ask far-fetched question: could a synthetic genome ever be used to produce a living human being?

Is that not the same ground breaking step that in vitro fertilization was?

But what if that human being was not actually completely healthy due to some unforeseen mistakes?

Just as was discovered with cloning.

Perhaps this is a far stretch discussion considering where the technology currently stands. We are not in such an advanced stage of knowledge to just start designing humans. The complexity behind the majority of human traits is vast and awaits to be unravelled. It is the big push towards understanding it that is one of the promises of personalized medicine. But medical treatment is obviously not in the same category as designing “perfect” humans for traits of interest.

Or is it? Is removing a defective gene known to cause a debilitating disease in an early embryo stage, which would save that individual’s life, not a form of designing a human? Because if you are not aware, let me tell you, that is already happening! The first such example of genome editing of a normal viable human embryos for disease-causing genes was reported by researchers in China.

And just as in the past, limitation of the technology (the fabled CRISPR-Cas9 system which allows to target almost any desired location within a genome for alteration) was mentioned by the authors, stating that “[o]ne embryo was completely corrected and another became mosaic, with half of its cells corrected and another half suffered a 4-bp deletion around the mutation.” So this technology is not ready for prime time just yet, but the interest is immense, and China is definitely carving its niche in leading the way.

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Personally I am for use of genome editing technology as a form of medicine, provided that its efficacy and safety is completely understood. But it is only my personal opinion, and I recognize that once again, one would be faced with the question of where are the limits? This is why I was interested in an article published on the blog of Dr. Paul Knoepfler (penned by Elliot Hosman) about a campaign in France calling for the moratorium on the use of CRISPR-Cas9 system of genome editing in human beings. This ought to be a good source; after all, Dr. Knoepfler published a book on the concept of designer babies.

And once again, I find myself conflicted about this issue. I do not agree with the idea of a moratorium on genome editing in humans precisely because of its medical potential. CRISPR-Cas9 might not be ready for everyday clinical applications anyway, but it holds a great deal of potential for the future treatment of diseases. I am talking about the idea of a baby that has either inherited or produced a spontaneous mutation in his/her genome, and using the best means available towards rescue from such disease.

Such clinical trials are already on their way. But we are long ways off before this technology is fully validated. Apart from technology being far from perfect, as mentioned in above example, we do not understand how all the DNA variations discovered in the human genome are interconnected and could be influencing one another. You might think you are removing a disease and produce two more diseases instead! Genome is so complex, how it functions is still being deciphered, so if you are tinkering with it, you better know what you are doing.

The fact that such public debate is occurring is actually fantastic news to me as I do think the public should be very much involved and opinions should be heard. Such a vehement stance on the use of CRISPR-Cas9 technology in humans is a sign that reflects the potential misunderstanding of technology, but it could also be an important collective statement of how the public at large wants its morals to be reflected. Clearly, in the instance of the above cited post, the statement is that playing with human genome is off limits.

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We do need to remember that the editing of a human genome is a normal and naturally- occurring process though. Not that this as an excuse to promote fooling around with a human genome. No way! But it truly does happen and certainly is one of the driving forces behind the evolution of the genome. For example, some viruses can insert themselves into human genomes, and therefore introduce foreign DNA that can then be subject to evolutionary pressure.

Authors of this linked article stated that 8% of human genome is viruses and 40% are other selfish elements, so we are seriously less human than originally considered. And that is just one example. Very unusual chromosomal rearrangements can occur spontaneously during cell division, and this is also one of the driving forces behind cancer.

Then just as those arguing for where do you draw the line in what could be done to human beings to help them medically, I would also ask, to further escalate the intelligent debate, where do you draw the line in what should be prohibited from medical use if it can cure a disease? After all, all medical treatments alter us, be it drugs, vaccines, or radiation, to enact a change that will improve our condition. Any novel treatment has potential dangers that need to be investigated prior to being available for public use. That is what clinical trials are for. And the majority of them will not succeed, precisely due to strict procedures for public safety.

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Thus I agree that public opinion is very important and should be listened to, but so should the opinion of scientists. They are involved in the lab bench work that eventually translates into medical advances, and there is a strong self-regulating ethical approach in science in what is acceptable and what is not. There are governing institutions, regulators and policy makers to attempt to ensure public safety to highest degree. For example, in the novel area of personal genomics, regulatory suggestions and guidelines are published all the time by various scientists and advocacy organizations. There is a prolific discourse on ethical issues in genetic testing, and a usual stance is on the side of caution with very careful considerations on individual impact.

So before policy makers weigh in on any decision regarding genome altering technologies, they would carefully juxtapose the opinion of professional scientific societies with those organizations representing the public, as the more voices contributing to the discussion, the greater the quality of a consensus that can be reached. As stated already, these are very challenging ethical topics to contemplate and it is welcome to see such vigorous discussions are taking place. And I wanted to throw in my two cents as well, and if it provoked you, then jump on the debate bandwagon! Let Merogenomics Inc. know your opinion, then pass it on. The result is more voices contributing to a public stance.

 

This article has been produced by Merogenomics Inc. and edited by Kerri Bryant. Reproduction and reuse of any portion of this content requires Merogenomics Inc. permission and source acknowledgment. It is your responsibility to obtain additional permissions from the third party owners that might be cited by Merogenomics Inc. Merogenomics Inc. disclaims any responsibility for any use you make of content owned by third parties without their permission.

 

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