Earlier this summer, I started reading and reviewing a number of books related to gene technology with a specific focus on CRISPR. This was not just for my own enjoyment; I’m teaching a class on Gene Technology this winter so I thought I better brush up on everything. And since I’ve been asked to attract as many non-majors as possible, I’ve decided not to focus on just the technical aspects, but also the social and legal aspects as well.
This brings us to the next book: following the summer’s theme. I’ve written reviews on books that look at the history of the gene and gene technology, on intellectual property, on ethics and more tangentially, on scientific misconduct. With Eben Kirksey’s The Mutant Project – Inside the Global Race to Genetically Modify Humans, I have to opportunity to examine the topic from yet a different lens—that of an anthropologist.
Right from the get-go, Kirksey tells us the book will be a little eclectic; he’s offering us a ‘mosaic portrait.’ Rather than focusing on just one aspect of the gene editing debate or championing a single viewpoint, he presents a potpourri of diverse perspectives. But I’ll be honest; the main one I was chasing down was his perspective on the Hè Jiànkuí case.
So I’ll start there. While Hank Greely’s book went into considerable detail concerning Hè’s work and the fallout, I wanted to see if I can gain more insight into how he ticked. I also wanted to see if I could learn more about the families who participated in the original trial that resulted in the births of Lulu and Nana. From what I had leant previously, I had some serious concerns that they had not offered true informed consent. But I also wanted to know what might’ve motivated these families to show interest in the trial in the first place.
Kirksey has done some great work here; I am impressed with the interviews he was able to carry out. He visits the village where Hè grew up, and finds that it is one of those rural areas that has experienced flight to the cities. And we are talking rural; this is a region where most babies of Hè’s generation were born at home and may not have experienced any interactions with the modern medical establishment until they reached school age. Where, as Kirksey points out, they all got their first vaccines. Often with the same needle. Keep an eye on that detail.
Hè’s first chance to move beyond his rural upbringing though comes at age 12, when he scores entry into the Xinhua School, which is part of a magnet program for gifted children. He then boards from age 15. Make no mistake, young Hè was genuinely a very bright student, and very driven—this is a young man with ambitions. And one captivated by The American Dream and and the pursuit of entrepreneurship. Keep an eye on this too.
On the side of the study participants though? Kirksey does a through job in explaining how HIV stigma is still quite high in Chinese society, and how this intersects with the extreme pressure people are put under to have children, and queer phobia. We might personally see the idea of making gene edits in CCR5 to confer HIV resistance to be a poor choice when so many less invasive ways of preventing HIV infection exist, but for some of these couples, the stigma is so strong, it made sense. (Note again, the risk a young Hè may have been put under with the re-used needles—if you don’t have confidence in your government to implement basic prevention measures, that may also have you weighing your choices differently.)
There are a number of chapters here dedicated to the people working in Hè’s lab during this time, and while I believe that they may have done a good job explaining to the trial participants the technical aspects of IVF and gene editing, everything else seems like it was a shit show. Hè’s work was really dancing across what was considered legal in China, and it seems like the the Silicon Valley philosophy of ‘move fast and break things’ was fully at play. Once the first embryo transfer happened, the lab rushed ahead and transferred embryos to serval other women, without first seeing if the initial transfer took, for example. Due diligence was not taken with regards to record keeping either. Additionally, after the first pair of children were born, the task of verifying as to whether or not they had the correct edits and no off targets (accidental edits made elsewhere) went to an undergraduate student. Yes, the kid sounds like a bioinformatics whizz, but this too high a responsibility to lump onto such a junior member of the lab—dear god! That fact blew me away.
So, after reading this, I did adjust my view of Hè’s choices somewhat; both his early upbringing and the prevailing HIV stigma that he is used to may have made CCR5 a more enticing target for him than I thought—I had initially judged it as a very poor choice and thought the reasoning he gave was pretty specious. But I am still convinced the money and fame behind being ‘first’ was also a huge motivator.
But I also had another mystery solved for me; during many of the initial reports of Lulu and Nana’s birth, there were often veiled references to a third child that had been born from the same trial. What’s the story behind child number three? The parents of said child, referred to together as P3, had already had their embryos edited throughout the course of the trial. But then they got impatient. Rather than waiting for the final analysis from the young bioinformatics whizz for confirmation that everything was ok, the couple went forward without the approval of the laboratory and scheduled a transfer anyway. They were the legal owners of the embryos, so nothing could be done. All that we do know is that they probably don’t have full HIV resistance.
Bloody hell.
But what about the rest of Kirksey’s ‘mosaic portrait?’ I think one of the more eye opening sections concerns the garage biohackers trying to home-brew their own gene editing experiments. Interestingly, the author seems rather surprised with what a home-brew biohacking collective can manage in what was basically their back shed—I am less shocked. I have done high school outreach work where we genetically modified cells for teaching purposes using a haphazard set-up that we packed into the back of a car. Some of the more simple techniques here can be carried out quite cheaply, and if you have a registered company, you might be able to convince suppliers to sell reagents to you. (Many of them will not ship to residential addresses. They are not intended for personal use.)
I did raise my eyebrows at the one guy who successfully introduced jellyfish DNA into dog sperm—he was doing better than I expected. But as noted, he damaged the sperm in the process. I’d wager he wouldn’t have enough viable sperm (especially given sperm are non-propagating and short-lived) to attempt artificial insemination. And I’d lay even better odds he can’t perform canine IVF and intracytoplasmic sperm injection (ICSI) by himself. Glow-in-the-dark, black market rottweilers are probably still a long way off.
Even if many early steps in these processes are fairly straightforward, others are not. Note that even regular IVF clinics have subdued success rates. And when we say we have success with CRISPR editing in professional labs, that’s relative—you don’t see what gets discarded along the way. What’s considered an acceptable level of trial, error, and discard in one species in a lab setting isn’t necessarily acceptable in others, particularly in vertebrates—and especially in humans. I did not get the impression that these people were aware of that.
Some of these lab-free biohackers also claim that they are driven by a sense of social and economic justice, but that doesn’t really come across to me in the writing. Maybe I am cynical, but I suspect there’s a bit of motivated post hoc reasoning going on with these people. That fact that the rest of the story behind Ascendance Biomedical and the DIY biohackers reads like a damned soap opera doesn’t really help (No, really. It’s wild.)
Most of the other sections of the book don’t receive anywhere near as much attention as Hè’s case though. But again, the net is broad; Kirksey does go on to examine questions concerning technology and the arts, people’s perceptions of the technology, even outside the west, and of course, medical justice and equality; ultimately arguing that biomedical science—especially in the United States—cannot be understood as a pursuit of better health, but rather as a system caught up with putting profits over people.
However, sometimes the scattershot mosaic approach runs a little short or comes across as disjointed. I don’t want to diminish the reporting behind the health activists or the horror of a $2 million price tag for the gene therapy Zolgensma. But I was disappointed by how US-focused it was. Kirksey does mention the US federal government could demand that gene therapies become affordable, but I thought the role of government could have been expanded on considerably. That is, after all, how some countries outside the US manage to ensure that the patient (or, given the system here, the consumer) doesn’t get hit with that $2 million cost, thus lowering many of the barriers mentioned here.*
Another part that didn’t quite land for me was a short sections mentioning Cystic Fibrosis and the Human Genome Project. Maybe this is because I read this fresh off the heels of Doctored, where I had similar complaints, but I really do take issue with statements like this (from others, not the author, mind): “We learnt nothing from the genome. Genetic tests initially proved better at putting people in jail than delivering concrete medical benefits.” And “The disease [Cystic Fibrosis] has contributed much more to science than science has contributed to the disease.”
Can we not shit on basic science, please? I know scientists can be reductionist and blinkered at times, but I guess we are not alone here. As I mentioned when reviewing Doctored: clinical science is still research. You can still be thrown curveballs, and outcomes are not proportional to the time and money you pour in. You can’t start with A and then always expect a direct, uncomplicated line to B. Thing’s got a bit too ‘science-y’ on the path between these points? The outcome you were hoping for (or were hyped for) 20 years ago didn’t come to pass the way you wanted? Sometimes, this is because we all misjudged the initial path, and the task at hand turned out to more complicated than we thought.
The human genome is an absolute workhorse—a scaffold for a lot of basic science, the bearer of the grunt work that needs to be done to progress. While we did manage to clone genes and perform PCR prior to the genome project, do you know how much easier it is to do these things with a well-curated reference?** I’ll admit, I was annoyed these statements were mostly left unchallenged by the author when we spent so much time later in the book examining how genome sequencing plays an integral part in CRISPR research.
If you think biotechnology is not serving you well now, imagine how slow is going if we did not spend time and money on the basics.
These quibbles aside, this book is still very worthwhile. Yes, you can say it gave me a lot of food for thought; you can see that I’ve now written about 2000 words on this. I have been pouring over it for a while. Kirksey’s work regarding the Hè Jiànkuí case alone is phenomenal.
For cbr17bingo, this is White.