Science, medicine and technology race ahead relentlessly, changing our world in both wonderful and drastic fashion, depending on your viewpoint, but it is true that sometimes science seems to surge ahead of society's willingness to accept it or even our own (as scientists) readiness to regulate it responsibly.
Major game-changing advances always get announced in a whirlwind of enthusiasm and excitement, but it is the job of medical ethics experts to dampen that furore by pointing out the downside of the upside. And you know, whether it's the internet and wireless technology, smartphones and social media, or our increasing capacity to mainpulate and actually alter the human genome - there always is a downside to the upside.
Historically and currently, one of the most contentious areas of biology has derived from our exponentially increased understanding of our genetic material, how to manipulate it, and how to potentially select for or change particular traits that are undesirable. Now of course this can only be a very good thing when it comes to disease or clear susceptibility to it, but quite obviously it also opens up the possibility of altering other aspects of individual phenotype that have nothing to do with disease, and more to do with vanity. The creep of cosmetic enhancement and plastic surgery from their previous old people's home all the way back to young thirty-somethings says it all in that regard.
In vitro fertilization, gene therapy, stem cell therapy and now gene editing are all areas that have caused contention and considerable debate among scientists and ethicists, and occasionally outright hysteria in the public forum. Somehow we manage to race ahead in spite of the concerns, and this was exemplified recently by the British Parliament approving a form of genetic manipulation that will create children from the DNA of three individuals.
The central concern for many has less to do with what happens when we edit nature itself, particularly if we edit it in an inheritable fashion by playing with the germline, allowing those changes to be handed on to future generations. As much as we predict that there won't be any shocking surprises if we get it right, it is impossible to know how altering a genome that has exquisitely evolved over even millions of years will ultimately impact the human organism.
Of course, what is at the heart of the matter, is specificity. It's one thing to show that a given technique can chop out a small defective piece of DNA from a target gene, and insert a corrective sequence which restores normal function to that gene, in cells in a laboratory or in an intact laboratory animal. The problem arises out of the million dollar question - how can we be sure that we do not alter any other non-target genes in the process? Currently, we have no way of knowing that with certainty and it remains a black box.
While such concerns have been around for some time with respect to gene therapy and to the more contemporary promise of gene editing via either zinc finger or TALEN technologies, the latest evolution in genetic engineering has motivated some big name scientists to take a stand as the process becomes ever more streamlined, sophisticated yet seemingly simple. Simpler means more people are going to have a go at it, and this is where the blood pressure begins to rise.
Nobel laureate David Baltimore made the news this week with a paper in Science calling for a moratorium on the use of the hottest new gene editing technique, known as the CRISPR-Cas9 system: "A framework for open discourse on the use of CRISPR-Cas9 technology to manipulate the human genome is urgently needed". It can appear weird that a scientific pioneer who was known as a trailblazer in his prime now comes across all conservative regarding a major new advance, but the stakes are high.
Nobel laureate David Baltimore made the news this week with a paper in Science calling for a moratorium on the use of the hottest new gene editing technique, known as the CRISPR-Cas9 system: "A framework for open discourse on the use of CRISPR-Cas9 technology to manipulate the human genome is urgently needed". It can appear weird that a scientific pioneer who was known as a trailblazer in his prime now comes across all conservative regarding a major new advance, but the stakes are high.
As controversial as Baltimore has been on occasion, no one questions his intellect and he is accompanied on the paper by some esteemed company such as Keith Yamamoto and Paul Berg (among others), as well as Jennifer Doudna (one of the discoverers of CRISPR) and George Church (a proponent of the technique) who are co-founders of biotech company Editas. The main point of contention is that while CRISPR will almost undoubtedly be clinically useful in human disease, it is a much scarier prospect if unscrupulous use of its power is applied to the germline for inheritable traits, and allows us to play God not only in terms of disease but also with looks and intelligence.
“We worry about people making changes without the knowledge of what those changes mean in terms of the overall genome. I personally think we are just not smart enough - and won’t be for a very long time - to feel comfortable about the consequences of changing heredity, even in a single individual.”
While no one in the USA or Europe is likely to go rogue and attempt unsanctioned use of this new technology, the authors are concerned that in countries with much less stringent regulations there could be attempts to profit from offering would-be parents the genetic traits they want to see in their child, for example. It's one thing to have corrective plastic surgery for a genetically inherited "defect" that is affecting a young person's confidence, and entirely another to attempt to select height, hair and eye colour and brain power from some shopping list that makes up the "ideal" child.
It is my personal opinion that we would be in for some severe shocks when playing with apparently benign traits involving our appearance, when they are altered in the context of the mixed genome we inherit from our parents. Years ago we would never have associated bacteria with stomach ulcers or gingivitis with cardiovascular disease, yet today we know they are linked. Our phenotype is an extremely elegant one, and the days of thinking of it all in separate compartments and separate chemistries are over - we truly are the sum of all our parts and the output is an integrated one involving enormous complexity.
So how do we know or how can we be sure that unnaturally changing aspects of our appearance will have no consequences? Does anyone know what effect turning a black-haired genome into a blond one has, or how producing a green-eyed child from a brown-eyed genome may impact more than just eye colour? The short answer is - no. God only kmows what would happen when we try to mess with the brain and intelligence!
It may be ironic to read a Nobel laureate saying that even in 2015, we are simply not smart enough - but he is right. The key is understanding the message, and not sensationalising it. Like all pioneering advances, CRISPR has opened a world of possibility. So has Google's driverless car. In both cases, until much research is done and we comprehend how to use the technology properly, we need to keep a lid on it, and stop the technology from falling into the wrong hands and being abused.
A driverless car is one thing, with unmanned vehicles patrolling our highways and towns representing a level of progress the dangers of which are readily apparent, but genetically altering a human at even one (in principle) precise segment of DNA is a much more in-the-dark prospect. Perhaps a bit more like the manned car, though with the driver blindfolded - we know where we want to go, but we can't see a thing - so we are driving in the dark, today. Just as we all don't want an umanned car having a brainstorm and speeding off in any direction causing complete havoc, so do we not want a supposed sequence-specific DNA-altering tool to go off the trail and target even one more gene than desired, never mind a few.
The potential of such technology to impact human diseases that have a genetic defect at their root is breathtaking, and we must push forward. As for all groundbreaking discoveries, scientists simply need to take a deep breath, pull back a little, and crank through the meticulous research and clinical development that is at the core of our drug discovery process. This is what Baltimore et al. are asking for, and that no one gets carried away until the techniques are refined and all safety concerns have been addressed.
Indeed, only once we get a crisper grip on all of the safety and ethical issues involved therein, will we be in a better position to realise the full potential of CRISPR! Until then, beginning an international debate on the pertinent questions surrounding this exciting new technology can only be a good thing, and a move that should be encouraged and welcomed by us all.
“We worry about people making changes without the knowledge of what those changes mean in terms of the overall genome. I personally think we are just not smart enough - and won’t be for a very long time - to feel comfortable about the consequences of changing heredity, even in a single individual.”
While no one in the USA or Europe is likely to go rogue and attempt unsanctioned use of this new technology, the authors are concerned that in countries with much less stringent regulations there could be attempts to profit from offering would-be parents the genetic traits they want to see in their child, for example. It's one thing to have corrective plastic surgery for a genetically inherited "defect" that is affecting a young person's confidence, and entirely another to attempt to select height, hair and eye colour and brain power from some shopping list that makes up the "ideal" child.
It is my personal opinion that we would be in for some severe shocks when playing with apparently benign traits involving our appearance, when they are altered in the context of the mixed genome we inherit from our parents. Years ago we would never have associated bacteria with stomach ulcers or gingivitis with cardiovascular disease, yet today we know they are linked. Our phenotype is an extremely elegant one, and the days of thinking of it all in separate compartments and separate chemistries are over - we truly are the sum of all our parts and the output is an integrated one involving enormous complexity.
So how do we know or how can we be sure that unnaturally changing aspects of our appearance will have no consequences? Does anyone know what effect turning a black-haired genome into a blond one has, or how producing a green-eyed child from a brown-eyed genome may impact more than just eye colour? The short answer is - no. God only kmows what would happen when we try to mess with the brain and intelligence!
It may be ironic to read a Nobel laureate saying that even in 2015, we are simply not smart enough - but he is right. The key is understanding the message, and not sensationalising it. Like all pioneering advances, CRISPR has opened a world of possibility. So has Google's driverless car. In both cases, until much research is done and we comprehend how to use the technology properly, we need to keep a lid on it, and stop the technology from falling into the wrong hands and being abused.
A driverless car is one thing, with unmanned vehicles patrolling our highways and towns representing a level of progress the dangers of which are readily apparent, but genetically altering a human at even one (in principle) precise segment of DNA is a much more in-the-dark prospect. Perhaps a bit more like the manned car, though with the driver blindfolded - we know where we want to go, but we can't see a thing - so we are driving in the dark, today. Just as we all don't want an umanned car having a brainstorm and speeding off in any direction causing complete havoc, so do we not want a supposed sequence-specific DNA-altering tool to go off the trail and target even one more gene than desired, never mind a few.
The potential of such technology to impact human diseases that have a genetic defect at their root is breathtaking, and we must push forward. As for all groundbreaking discoveries, scientists simply need to take a deep breath, pull back a little, and crank through the meticulous research and clinical development that is at the core of our drug discovery process. This is what Baltimore et al. are asking for, and that no one gets carried away until the techniques are refined and all safety concerns have been addressed.
Indeed, only once we get a crisper grip on all of the safety and ethical issues involved therein, will we be in a better position to realise the full potential of CRISPR! Until then, beginning an international debate on the pertinent questions surrounding this exciting new technology can only be a good thing, and a move that should be encouraged and welcomed by us all.
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