Twisted Fantasy: Changing lives with the human genome
In Sam Raimi's Spider-Man, Peter Parker is bitten by a genetically enhanced 'Super Spider' while on a field trip to an egregiously unsafe gene laboratory (lock your spider boxes, kids) and falls unconscious soon after returning home groggy and ill. In the following few moments, we are treated to an exciting sequence that shows tiny spiders crawling around inside his cells, and his DNA being cut and spliced in the process that turns him into the arachnid Avatar. This (and the following scenes of him grappling with his new abilities and, importantly, checking himself out in the mirror) is a lot of fun to watch, but viewers who have indulged themselves in high-school biology (and stopped after a couple of years, as I did) may at this point jump out of their seats, throw their Heelys at the TV screen and shout "Hang on, that's not how genes work! You can't meaningfully change your body after you've been born just by editing your DNA!".
Now, friends, this is mostly correct. Despite what camp, pre-MCU superhero movies might have you believe, the work of our buddy DNA is mostly performed before you're born, while your body is creating itself. One can't edit the genes of a few cells and expect to sprout new arms or - dare I say - web-slingers. However, there are some exceptions to this rule, which are being discovered and used today.
The process of gene therapy, which is any medical treatment that deliberately introduces new genes into patients to cure their ails, was first speculated about in the 1970s, became possible in the 1990s, and was first put to use in humans in the 2000s, with Gendicine, a drug which contains the genes needed to make tumour-fighting proteins, approved by Chinese administration in 2003. Since then, a few other treatments have shown promise - for instance, fixing hereditary blindness and colour-blindness by changing the genetic code in retinal cells. It is difficult for gene therapies to get government approval, however, since it takes a long time to ensure that permanent changes to the genome are not going to be dangerous in later life. As well as this, almost all forms of gene therapy currently known target small parts of the body, such as the retina, rather than making all-over change. Sorry, Peter Parker (and the Fantastic Four, and the Hulk, and all those other Marvel superheroes that seem to have relied on sudden gene alteration transforming their entire body).
Now, though, the barriers to effective gene therapy are beginning to break down. Earlier this year, I read a story in the news that truly amazed me. At the Necker Children's Hospital in Paris, a teenage sufferer of sickle cell disease, which prevents blood from functioning as normal and usually requires transfusions throughout one's entire life, had been apparently completely cured thanks to a change in his genes.
The process was unlike any previous form of gene therapy. Instead of the usual method, where viruses (whose speciality is transplanting genetic code) containing the desired genes are injected into a patient, the doctors had removed some bone marrow cells from the boy, edited them in the lab so that they produced the proper Werther's-Original-shaped blood cells instead of the faulty sickle-shaped ones, and then reinserted them after breeding them up to make a substantial amount. What followed was pretty incredible - according to the researchers, his bone marrow started producing only the good blood cells and within two years, he was off all treatment his blood showed no signs of the disease at all.
This shook my expectations of what human gene editing can do. A human had been given altered genes, 13 years into his life, and the effect had swept across his body and actually eradicated the effect of his previous genetic makeup. Now while bone marrow cells are a relatively easy target for this - if I'm correct, they are pretty fast at replicating and renewing themselves - this is still clearly a breakthrough.
The year preceding this story saw a tidal wave of successful gene editing trials, with CRISPR-Cas9 bursting into the mainstream, and for me this felt like the start of the next space race - the first definitive sign that human gene editing could, and would, become a standard part of the medic's arsenal, whether you or I like it or not.
So, how has this played out in the months since? Well, entirely as expected, the use of human gene editing in medicine has rocketed ahead, with new studies hitting the news on a near-weekly basis. Take the first use of CRISPR on viable human embryos, or the first use of the same tool to fix disease-causing genetic problems in human embryos. Research teams in China have been accountable for a disproportionate amount of these trails (whether it is because of a greater public interest in science in the country or simply because it never had The Twilight Zone on TV) but the rest of the world is also catching up. In the USA, it is legal to perform genetic trials on human embryos as long as they are privately funded, and the FDA approved their first two gene therapy treatments over the past two months (the second of these was a lymphoma treatment from the concerningly named Gilead Sciences, with the approval announced as I was writing this post). Note again that the first gene therapy approved by the Chinese government was back in 2003. If you search "FDA gene therapy" on Google, you'll see that there is a cascade of potential treatments raring to go, for afflictions including leukaemia and hereditary blindness.
As with most medical research, the cautious approach is probably the better way to go. Many are concerned about the potential for 'designer babies' shifting the goalposts of societal acceptance and making it even easier to distinguish people based on wealth; another issue is the ethical problems associated with administering treatment to someone before they are born. However, given how life-changing some of these procedures could be, I think it is imperative to push ahead on the research side at least; as for the actual application, the most important factor to consider is safety - remember that genetic changes can never be wiped from your body.
So, is human genetic manipulation the future? Almost certainly yes. Is it the same future presented to us in sci-fi film and literature? Let's hope not - unless, of course, that literature is Spider-Man.
Now, friends, this is mostly correct. Despite what camp, pre-MCU superhero movies might have you believe, the work of our buddy DNA is mostly performed before you're born, while your body is creating itself. One can't edit the genes of a few cells and expect to sprout new arms or - dare I say - web-slingers. However, there are some exceptions to this rule, which are being discovered and used today.
The process of gene therapy, which is any medical treatment that deliberately introduces new genes into patients to cure their ails, was first speculated about in the 1970s, became possible in the 1990s, and was first put to use in humans in the 2000s, with Gendicine, a drug which contains the genes needed to make tumour-fighting proteins, approved by Chinese administration in 2003. Since then, a few other treatments have shown promise - for instance, fixing hereditary blindness and colour-blindness by changing the genetic code in retinal cells. It is difficult for gene therapies to get government approval, however, since it takes a long time to ensure that permanent changes to the genome are not going to be dangerous in later life. As well as this, almost all forms of gene therapy currently known target small parts of the body, such as the retina, rather than making all-over change. Sorry, Peter Parker (and the Fantastic Four, and the Hulk, and all those other Marvel superheroes that seem to have relied on sudden gene alteration transforming their entire body).
Now, though, the barriers to effective gene therapy are beginning to break down. Earlier this year, I read a story in the news that truly amazed me. At the Necker Children's Hospital in Paris, a teenage sufferer of sickle cell disease, which prevents blood from functioning as normal and usually requires transfusions throughout one's entire life, had been apparently completely cured thanks to a change in his genes.
The process was unlike any previous form of gene therapy. Instead of the usual method, where viruses (whose speciality is transplanting genetic code) containing the desired genes are injected into a patient, the doctors had removed some bone marrow cells from the boy, edited them in the lab so that they produced the proper Werther's-Original-shaped blood cells instead of the faulty sickle-shaped ones, and then reinserted them after breeding them up to make a substantial amount. What followed was pretty incredible - according to the researchers, his bone marrow started producing only the good blood cells and within two years, he was off all treatment his blood showed no signs of the disease at all.
This shook my expectations of what human gene editing can do. A human had been given altered genes, 13 years into his life, and the effect had swept across his body and actually eradicated the effect of his previous genetic makeup. Now while bone marrow cells are a relatively easy target for this - if I'm correct, they are pretty fast at replicating and renewing themselves - this is still clearly a breakthrough.
The year preceding this story saw a tidal wave of successful gene editing trials, with CRISPR-Cas9 bursting into the mainstream, and for me this felt like the start of the next space race - the first definitive sign that human gene editing could, and would, become a standard part of the medic's arsenal, whether you or I like it or not.
So, how has this played out in the months since? Well, entirely as expected, the use of human gene editing in medicine has rocketed ahead, with new studies hitting the news on a near-weekly basis. Take the first use of CRISPR on viable human embryos, or the first use of the same tool to fix disease-causing genetic problems in human embryos. Research teams in China have been accountable for a disproportionate amount of these trails (whether it is because of a greater public interest in science in the country or simply because it never had The Twilight Zone on TV) but the rest of the world is also catching up. In the USA, it is legal to perform genetic trials on human embryos as long as they are privately funded, and the FDA approved their first two gene therapy treatments over the past two months (the second of these was a lymphoma treatment from the concerningly named Gilead Sciences, with the approval announced as I was writing this post). Note again that the first gene therapy approved by the Chinese government was back in 2003. If you search "FDA gene therapy" on Google, you'll see that there is a cascade of potential treatments raring to go, for afflictions including leukaemia and hereditary blindness.
As with most medical research, the cautious approach is probably the better way to go. Many are concerned about the potential for 'designer babies' shifting the goalposts of societal acceptance and making it even easier to distinguish people based on wealth; another issue is the ethical problems associated with administering treatment to someone before they are born. However, given how life-changing some of these procedures could be, I think it is imperative to push ahead on the research side at least; as for the actual application, the most important factor to consider is safety - remember that genetic changes can never be wiped from your body.
So, is human genetic manipulation the future? Almost certainly yes. Is it the same future presented to us in sci-fi film and literature? Let's hope not - unless, of course, that literature is Spider-Man.
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