Let me tell you about one of the more colourful personalities in our story. Her name is Martine Rothblatt and she wants to live forever.
If you haven’t been living under a rock, you may have stumbled across Rothblatt’s handiwork during the last few years—in 2021 and then again in 2023, she provided the pig hearts behind the first two successful pig-to-human heart transplants. The founder and CEO of the biopharma giant United Therapeutics (MCAP 11.7 Billion), Rothblatt has shepherded the eerily sounding field of ‘xenotransplantation’—grafting animal tissues onto humans—from the fringes of medical research to one of its next great frontiers. With other firms promising to put pig-hearts into critically ill babies later this year and the second (initially) successful pig-to-human kidney transplant having wrapped up just a week back, things are popping off with pig organs. And that’s because for over two decades, someone with big ideas and even deeper pockets has been throwing money at the problem.
Rothblatt made her first fortune by sending satellites up into space to create the first satellite radio station, Sirius FM. She then made her second one pivoting into biotech after learning her daughter Jenesis was terminally ill with a congenital lung condition. After founding United Therapeutics in 1996, she transitioned to become a woman that same year and ended up developing the much-needed drug that saved her daughter’s life. Worrying this might be a short-term solution, she then pivoted into xenotransplantation in the late 1990s, snapping up the pig heart firm Revivicore in 2008, a former affiliate of the Roslin Institute, who cloned Dolly the sheep.
Revivicore has been making headlines with its hearts recently, but Rothblatt also has a series of other projects on the go, working to create 3-D printed lungs as well as electric Heliplanes. She wants to keep things carbon neutral, including the transportation of what she hopes will be an unlimited supply of organs for transplant. With over 5000 people dying on transplant waiting lists each year in the US alone, there’s certainly the demand.
“She’s a visionary,” says Dr Mohammed Mohiuddin, one of the two surgeons behind the two successful pig heart transplants. When I spoke to him over Zoom last March, he was sitting in the office of a dedicated department at the University of Maryland, his surgical mask draped above blue scrubs and a cap with “ Xeno ♡ Team” emblazoned along the front. Rothblatt got him to move there. “She gave me 34 million dollars to progress the field,” he recalled. “She definitely knows what she's doing and she's remarkably intelligent. But she's also a business woman —she wants things done and done quickly.” Clinical trials are what’s next in Rothblatt’s sights and given her track record, there’s no reason to they that won’t be soon.
These organs aren’t just for people like her daughter. Rothblatt also founded her own transhumanist religion called Teraseme with the motto: “Death is optional; God is technological.” She wants to live forever and has said as much in the 2015 TED talk “My daughter, my wife, our robot and the quest for immortality.” Pig organs might prove handy therein, but Rothblatt has acknowledged there are significant risks behind scaling the technology, most notably animal-to-human disease transfer (aka zoonosis), which is probably what caused the Covid-19 pandemic.
It’s crazy stuff, this kind of Promethian ambition. Does it come with a hand rootling around Pandora’s box?
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Underpinning much of the hysteria around animal-to-human disease transfer is a biological fact: pigs are so genetically similar to humans that the risk of zoonosis isn’t just germane to the transplant sector, it’s endemic to swine husbandry across the board. When the Spanish Flu swept through the world back in 1918, it was accompanied by a similarly destructive global swine pandemic and some researchers have suggested the latter begot the former. While the transmission of COVID-19 probably didn’t involve pigs as a mixing vessel (pigs are resistant), there are more recent examples of traffic moving two ways. The swine flu of 2009 was probably humans giving pigs the flu before pigs passed it back on, killing 12,000 people in the US alone and many more animals.
This is familiar territory for Rothblatt. In her 2003 treatise on the subject, suggests xenotransplantation shouldn’t move ahead without an appropriate global regulatory body to manage the risk of a global pandemic—given disease doesn't respect national borders, so the argument goes, our precautionary measures shouldn’t either. It’s unclear whether the kind of oversight she describes has materialised twenty years since then but given all the recent news, Rothblatt is clearly undeterred.
Which becomes all the more striking when you consider the first successful one ended up with the transplant recipient, a certain David Bennet Snr, infected with the pig virus cytomegalovirus. The pig was supposed to have been brought up in a germ-free environment but somehow, it wangled its way in—and while Bennet lived for another two months, when he died, some scientists speculated cytomegalovirus was to blame. The people behind the surgery stress we should keep in mind Bennet’s immune system was already critically compromised—one of the reasons he opted for the surgery in the first place, but the infection has some running scared.
Ironically, it was precisely this kind of thing that motivated Rothblatt to get into xenotransplantation in the first place. Back in the 1990s, the field was stopped dead in its tracks when it looked as if humans could catch PERV (porcine endogenous retrovirus) via transplant, all of which motivated Rothblatt to throw her hat in the ring. In the interim period, doubts have been cast over whether PERV is a danger at all and in any case, scientists have demonstrated their ability to knock-out the retrovirus from the pig genome altogether using CRISPR gene-editing. With more stringent biosecurity protocols and CRISPR by their side, most of the dozen or so geneticists I spoke to seemed to think the cytomegalovirus mishap could be dealt with similarly and that now is no time to abandon ship.
Mohiuddin agrees. “I might get permission for clinical trials in a year or maybe two years, but what happened to the patients who need hearts now? They will die waiting,” he said to me. “I’m going to keep approaching the FDA with patients saying, look we what learned these with the first two. We think we can do a better job with the 3rd and the 4th.” Martine evidently feels the same; according to Mohiuddin, she’s been busy with her electric plane transporting pig-organs from Revivicore’s secure facility in Blacksburg Virginia for use in the run-up trial surgeries on Baboons.
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Over the past months, I’ve interviewed over a dozen scientists working in pig genetics and xenotransplantation and if there is one thing I’ve noticed, it’s their invariably staid manner of speaking. That makes sense when the general public’s first point of reference is either Greek mythology or the cyberpunk dystopias of Y2K cinema. They want things to retain a sense of proportion, which is all the more important when rogue scientists are busy going full ‘Gattaca Mode’ and making gene-editing babies (see the Jankui affair of 2018). But amidst all the sober mumbo-jumbo about alleles, kisspepptins and ribonucleoproteins, every once and awhile, someone lets a little zinger slip out and you get a jolt. This is some really crazy shit.
I haven’t managed to interview Martine just yet, but what’s refreshing about her is that she clearly agrees. Re: Pandora’s box (i.e. will fiddling with the pig genome spark a pandemic), I’d wager that anything is possible but if someone does flip it ajar, it won’t be her. Xenotransplantation is a tiny world with a lot of oversight that she has made a point of advocating for. There’s a caveat here though — a lot of the same genetic technologies being used in xenotransplantation are also now being applied in the meat industry. Right now, firms are looking into using CRISPR gene editing to block puberty in pigs and get rid of enormously costly diseases like PRRS, African Swine Fever and even the common flu. The thing about CRISPR is that while it’s great at locating specific genes, its process of altering them is a bit more of a crab shoot, where unintended results of gene edits can crop up in completely different locations of the genome. In many ways, concerns about using it in commercial pig farming mirror those in the xenotransplantation space; but given the vast number of animals involved and the patchwork quilt of different international regulatory regimes, that’s going to be much more difficult to keep tabs on. Fingers crossed…
I’ll leave you with a thought. One of the central tasks for both Rothblatt’s work and xenotransplantation in general is to sufficiently ‘humanise’ a pig organ so our immune systems don’t reject it and go into meltdown. Sounds scary—and just a little close too home, but maybe that’s no bad thing. Could it be that in doing so, we might start to lose patience with factory pig farming?
We have an incredible capacity as humans to ignore what’s going on right underneath our noses. But if the matter in question is within chests, maybe that’s different…?