Just a heart transplant, or a catalyst?

Prime Future 83: the newsletter for innovators in livestock, meat, and dairy

Today’s word is xenotransplantation, ‘the transplant into a human of an organ from a nonhuman animal’.

This week a pig heart was transplanted into a human, the first (so far) successful xenotransplantation of its kind. Somewhat downplayed in the media coverage was the role of CRISPR in making this transplant possible:

Xenotransplantation has seen significant advances in recent years with the advent of CRISPR–Cas9 genome editing, which made it easier to create pig organs that are less likely to be attacked by human immune systems. The latest transplant, performed at the University of Maryland Medical Center (UMMC), used organs from pigs with ten genetic modifications.

To make the pig heart used in the transplant, the company knocked out three pig genes that trigger attacks from the human immune system, and added six human genes that help the body to accept the organ. A final modification aims to prevent the heart from responding to growth hormones, ensuring that organs from the 400-kilogram animals remain human-sized.

…the future of xenotransplantation probably includes tailoring the modifications to suit particular organs and recipients.

Another report said “Researchers reported in 2015 that they had used Crispr, a new gene-editing technology, to inactivate pig viruses that otherwise might infect humans transplanted with pig organs.”

Can we just geek out for a moment about how wild this all is? Not just for novelty’s sake, but because….

…if gene editing can turn off/down genes to ‘inactivate viruses’, why can’t ASF & PRRS be edited away in commercial swine herds? (Research that is already underway.)

…if gene editing can modulate growth hormones, why can’t Average Daily Gain and Feed:Gain metrics be drastically improved in new and novel ways?

…if gene editing can alter how an animal organ interacts with human biology, why can’t gene editing enable meat & milk to play a bigger role in ‘food as medicine’ for humans?

I previously went down the CRISPR path, considering how gene editing could hit livestock:

In The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race the author focuses on human uses for CRISPR, only using the word agriculture once and almost as an afterthought. So, let’s brainstorm how a tiny little biochemical thingamajig could be used to make a potentially big impact in livestock, meat & dairy.

(Heads up: I’m not constraining this list to any nonsensical details like what’s scientifically possible 🙃)

• Efficiency. The most obvious and least exciting use for CRISPR is to improve efficiency of production metrics like growth rates or feed conversion or carcass yield. Could beef someday have the same feed conversion as chicken, or even fish?

• Quality improvements. Can gene editing increase meat tenderness in certain cuts? Increase flavor in pork? Eliminate that nagging issue of woody breast in chicken? Could CRISPR unlock the Honeycrisp apple of the meat case?

• Health management. Imagine if you could eliminate Mastitis in dairy cows, or BRD in beef cattle, or ASF or PRRS in swine, or Coccidiosis in poultry…all of which have massive economic impact around the globe.

• Methane emissions.  Could CRISPR gene editing somehow (magically?) reduce methane emissions and put that whole issue to pasture?

• Demand response. Imagine you could use gene editing to get more of what the market is asking for, like more loin per carcass for a higher ratio of high value middle meats in beef & pork. Or let’s throw common sense to the wind - what if you could get more wings per bird? That would look pretty good in times when wings trade at $3/lb and breast meat trades at $1.

To be fair, this week’s development has no direct impact on livestock production or the milk & meat biz. Zero. It has far more implications for the field of medicine.

Yet there could be game changing indirect benefits, since the animal-organs-for-human-transplant use case for CRISPR gene editing will force regulators to put some guardrails in place. It will also nudge the general public towards an implicit verdict on CRISPR gene editing in animals.

The beauty of the pig heart transplant is that it accelerates the broader CRISPR+livestock conversation, starting with an initial use case that is almost inarguably good for humanity.

I previously described the risks this way:

The only way CRISPR can make a meaningful impact is if both regulators and consumers embrace the technology.

• Regulators. What will the regulatory framework for CRISPR gene editing in livestock look like and who will oversee it? How will different countries approach it? For use in humans, scientists think of CRISPR having 3 different uses: to prevent disease, to treat disease, or for enhancements like making your offspring taller, smarter, stronger, etc. (Obviously there are varied opinions among the CRISPR scientific community about using it only for disease prevention & treatment to alleviate human suffering, rather than selecting for certain characteristics because we can.) Another screen, and debated distinction, is whether gene editing will impact only that patient/generation (somatic editing) or if it will impact that patient/generation and all future offspring (germline editing). If similar screens are applied in livestock, the list of possible CRISPR use cases would change.

• Consumers. If GMOs in plant breeding signals how CRISPR might be viewed in livestock, then the odds of widespread consumer acceptance of CRISPR editing in livestock are less than my chances of competing in the 2021 Olympics. The staggering advantages of GMO's in crop production - less resource use per unit of production - have not satisfied the anti-GMO camp enough to offset their concerns of genetic modification. Good science has not been enough for a good outcome.

However, there’s one factor in livestock that isn’t part of the equation for crops, and that is animal welfare. How will the risk/reward equation adjust itself if CRISPR provides ways to reduce animal disease and therefore improve animal well being?

I have to believe that the xenotransplantation use case for CRISPR will create momentum for additional CRISPR use cases that directly benefit commercial livestock producers and the broader meat industry.

So, was this heart transplant just a transplant? Or, was it a catalyst for all the ways CRISPR could change not just how we think about livestock genetics but nutrition, health, management, and more?

My hypothesis is that history will call this a catalyst for more….how much more, and on what time horizon, remain TBD.

What a time to be alive!

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