Startup looks to begin pig-to-human organ transplants by 2022

Porcine gene edits may allow such transplants without rejection.

Startup looks to begin pig-to-human organ transplants by 2022
Credit: Phoenix Han on Unsplash
  • A company called Revivicor has received clearance from the FDA to use their genetically modified pigs for medical use or as food.
  • The pigs lack genes for alpha-gal sugar, which human bodies reject.
  • Revivicor anticipates the first human transplant trials as early as this year.

Science can run along separate, even contradictory, paths simultaneously. At the same time as some research is revealing more and more about animal intelligence and self-awareness, other research seems to be pursuing novel ways in which humans can expand the exploitation of animals on the assumption that they lack these attributes. Growing appreciation for the intellectual and emotional lives of pigs, for example, is counterbalanced by news that the FDA has just certified that pigs bred by a company looking to harvest their organs for transplantation in humans are safe for food and medical use. The contrast can be head-snapping.

Revivicor, a subsidiary of Maryland-based biotech company United Therapeutics, received the FDA clearance in December 2020. To the FDA, this "represents a tremendous milestone for scientific innovation." Revivicor's chief scientific officer, David Ayares, tells Future Human that the company's "ultimate goal is to essentially have an unlimited supply of organs," and clearance for their "GalSafe pigs" brings that goal one step closer.

Waiting lists

Credit: Talaj/Adobe Stock/Big Think

The U.S. Health Resources and Services Administration says that 109,000 Americans are currently waiting for organ transplants. Seventeen people die each day while waiting, and every nine minutes a new name goes on the waiting list.

Companies such as Revivicor are hoping to meet this need with xenotransplants, in which organs from non-human species are transplanted into humans. Scientists have been seeking a way to perform successful xenotransplantation for decades—a newborn referred to publicly as "Baby Fae" rejected a transplanted baboon heart as far back as 1984.

Ayares says his company is "right on the cusp" of overcoming such rejection issues, anticipating their first transplants may occur in 2021 or 2022.

Animal tissue may also find use in the formulation of medications.

Rejection

Credit: ustas /Adobe Stock

The rejection problem stems from the human body's immune system expelling cells from other animals as foreign substances. (Rejection can also be an issue with human-to-human transplants.)

In 2003, Revivicor began development of GalSafe pigs by removing a gene that appears on the surface of porcine cells, and that produces a sugar called "alpha-gal." It's believed that alpha-gal sugar is the agent that causes the most acute rejections experienced with heart and kidney transplants.

Alpha-gal is also implicated in a meat food-allergy that occurs after a person is bitten by a Lone Star tick that leaves alpha-gal sugar behind in its victims' skin. Over time, the individual develops an allergy to pork, red meat, and lamb. Revivicor's Gal Pigs may one day be available to such people as non-allergenic pork.

Revivicor's manipulation of pig genes to support xenotransplantation compatibility doesn't end with eliminating alpha-gal sugar. Today's GalPig carries a total of 10 different genomic modifications—four pig genes have been turned off and six human genes have been introduced.

Tests so far

The company, working with the National Institutes of Health, says that they managed to avoid rejection of pig hearts transplanted into baboons for six years, though these didn't replace the animals' own, original hearts. Rather, the pig hearts were transplanted into the abdomens of the baboons simply to assess rejection. Ayares also says GalPig kidneys survived in monkeys for over six months, though it's unclear if they were functioning as kidneys or simply implanted.

For human trials, Revivicor plans to begin with kidney transplants before attempting heart replacements. They expect to perform these early trials with people awaiting human transplants. XenoTherapeutics of Boston is already testing GalPig skin transplants as a temporary measure for burn victims as their own skin regenerates.

Other companies are also exploring porcine genetic modifications for xenotransplants, including eGenesis in Boston and its partner Qihan Biotech in Zhejiang, China, who are using CRISPR to perform gene edits.

A landslide is imminent and so is its tsunami

An open letter predicts that a massive wall of rock is about to plunge into Barry Arm Fjord in Alaska.

Image source: Christian Zimmerman/USGS/Big Think
Surprising Science
  • A remote area visited by tourists and cruises, and home to fishing villages, is about to be visited by a devastating tsunami.
  • A wall of rock exposed by a receding glacier is about crash into the waters below.
  • Glaciers hold such areas together — and when they're gone, bad stuff can be left behind.

The Barry Glacier gives its name to Alaska's Barry Arm Fjord, and a new open letter forecasts trouble ahead.

Thanks to global warming, the glacier has been retreating, so far removing two-thirds of its support for a steep mile-long slope, or scarp, containing perhaps 500 million cubic meters of material. (Think the Hoover Dam times several hundred.) The slope has been moving slowly since 1957, but scientists say it's become an avalanche waiting to happen, maybe within the next year, and likely within 20. When it does come crashing down into the fjord, it could set in motion a frightening tsunami overwhelming the fjord's normally peaceful waters .

"It could happen anytime, but the risk just goes way up as this glacier recedes," says hydrologist Anna Liljedahl of Woods Hole, one of the signatories to the letter.

The Barry Arm Fjord

Camping on the fjord's Black Sand Beach

Image source: Matt Zimmerman

The Barry Arm Fjord is a stretch of water between the Harriman Fjord and the Port Wills Fjord, located at the northwest corner of the well-known Prince William Sound. It's a beautiful area, home to a few hundred people supporting the local fishing industry, and it's also a popular destination for tourists — its Black Sand Beach is one of Alaska's most scenic — and cruise ships.

Not Alaska’s first watery rodeo, but likely the biggest

Image source: whrc.org

There have been at least two similar events in the state's recent history, though not on such a massive scale. On July 9, 1958, an earthquake nearby caused 40 million cubic yards of rock to suddenly slide 2,000 feet down into Lituya Bay, producing a tsunami whose peak waves reportedly reached 1,720 feet in height. By the time the wall of water reached the mouth of the bay, it was still 75 feet high. At Taan Fjord in 2015, a landslide caused a tsunami that crested at 600 feet. Both of these events thankfully occurred in sparsely populated areas, so few fatalities occurred.

The Barry Arm event will be larger than either of these by far.

"This is an enormous slope — the mass that could fail weighs over a billion tonnes," said geologist Dave Petley, speaking to Earther. "The internal structure of that rock mass, which will determine whether it collapses, is very complex. At the moment we don't know enough about it to be able to forecast its future behavior."

Outside of Alaska, on the west coast of Greenland, a landslide-produced tsunami towered 300 feet high, obliterating a fishing village in its path.

What the letter predicts for Barry Arm Fjord

Moving slowly at first...

Image source: whrc.org

"The effects would be especially severe near where the landslide enters the water at the head of Barry Arm. Additionally, areas of shallow water, or low-lying land near the shore, would be in danger even further from the source. A minor failure may not produce significant impacts beyond the inner parts of the fiord, while a complete failure could be destructive throughout Barry Arm, Harriman Fiord, and parts of Port Wells. Our initial results show complex impacts further from the landslide than Barry Arm, with over 30 foot waves in some distant bays, including Whittier."

The discovery of the impeding landslide began with an observation by the sister of geologist Hig Higman of Ground Truth, an organization in Seldovia, Alaska. Artist Valisa Higman was vacationing in the area and sent her brother some photos of worrying fractures she noticed in the slope, taken while she was on a boat cruising the fjord.

Higman confirmed his sister's hunch via available satellite imagery and, digging deeper, found that between 2009 and 2015 the slope had moved 600 feet downhill, leaving a prominent scar.

Ohio State's Chunli Dai unearthed a connection between the movement and the receding of the Barry Glacier. Comparison of the Barry Arm slope with other similar areas, combined with computer modeling of the possible resulting tsunamis, led to the publication of the group's letter.

While the full group of signatories from 14 organizations and institutions has only been working on the situation for a month, the implications were immediately clear. The signers include experts from Ohio State University, the University of Southern California, and the Anchorage and Fairbanks campuses of the University of Alaska.

Once informed of the open letter's contents, the Alaska's Department of Natural Resources immediately released a warning that "an increasingly likely landslide could generate a wave with devastating effects on fishermen and recreationalists."

How do you prepare for something like this?

Image source: whrc.org

The obvious question is what can be done to prepare for the landslide and tsunami? For one thing, there's more to understand about the upcoming event, and the researchers lay out their plan in the letter:

"To inform and refine hazard mitigation efforts, we would like to pursue several lines of investigation: Detect changes in the slope that might forewarn of a landslide, better understand what could trigger a landslide, and refine tsunami model projections. By mapping the landslide and nearby terrain, both above and below sea level, we can more accurately determine the basic physical dimensions of the landslide. This can be paired with GPS and seismic measurements made over time to see how the slope responds to changes in the glacier and to events like rainstorms and earthquakes. Field and satellite data can support near-real time hazard monitoring, while computer models of landslide and tsunami scenarios can help identify specific places that are most at risk."

In the letter, the authors reached out to those living in and visiting the area, asking, "What specific questions are most important to you?" and "What could be done to reduce the danger to people who want to visit or work in Barry Arm?" They also invited locals to let them know about any changes, including even small rock-falls and landslides.

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Credit: Hans Hillewaert via Wikicommons
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