Modified pigs to grow humanized lungs

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In a move filled with the promise of scientific innovation but also the prospect of controversy, a company in La Jolla, Calif., is set to announce Tuesday that it will join forces with a biotech firm to create pigs with lungs and other organs that are compatible for transplantation into humans.

The local company is Synthetic Genomics, led by J. Craig Venter, whose world-famous feats include sequencing the human genome. Its partner in the new venture will be Lung Biotechnology – a subsidiary of United Therapeutics, which has a market value of $5.1 billion.

Synthetic Genomics will get a $50 million investment under the research and development agreement, along with milestone payments and royalties from any sales, according to the companies.

Synthetic Genomics plans to use its genomic modification tools to produce pig cells compatible with human immune systems, said Venter, its chairman and CEO.

United Therapeutics – of Silver Spring, Md. – intends to use those cells to make embryos that would be grown into pigs with transplantable organs.

While lungs are the first focus, other organs for “xenotransplantation” will be developed, Venter said. The lung is the most difficult organ to transplant, so if that problem is solved, transplanting other pig organs should also be achievable.

“Hearts, kidneys … livers might also be possible as well,” Venter said. “If we solve lungs, the rest will be much easier.”

Synthetic Genomics will be hiring more employees for the work, particularly people with expertise in fields such as immune responses, Venter said.

Martine Rothblatt, chairman and CEO of United Therapeutics, said in a statement that the multi-year collaboration could develop “an unlimited supply of transplantable organs, potentially helping millions of patients who die from end-stage organ disease.”

Venter said Lung Biotechnology has already made progress in testing lung transplants from genetically modified pigs placed into baboons.

For the new partnership, Synthetic Genomics plans to contribute its precision tools for changing and writing the genetic code. The company will start by determining the exact differences between the human and pig genomes.

“We’re going to generate a very highly accurate version of the pig genome, something that doesn’t exist yet,” Venter said. “We will be working on a number of human and pig proteins. Some are identical. Some vary by just a few amino acids,” which are the building blocks of proteins.

Using that knowledge, Synthetic Genomics scientists would change the pig DNA where the code differs from the human proteins. The goal is to have the genetically modified pigs grown by Lung Biotechnology produce wholly human proteins.

While the partners hailed the medical benefits to be had from “xenotransplantation,” their project was certain to raise ethical and health concerns in some circles.

San Diego animal-rights activist and lawyer Bryan Pease believes animal organ transplantation is a bad idea because it can introduce animal-born diseases into humans, including influenza.

“If it can cross the species boundary, it can cause H1N1 or swine flu,” said Pease, executive director of the Animal Protection and Rescue League.

“A useful area of science for developing organs for human transplant would be human stem cells, which would differentiate into human organs, instead of taking organs from other species and trying to make it fit,” Pease said.

He also believes it is wrong to kill animals to benefit people, although he added that using animals for organ transplants is less ethically objectionable than raising them for food.

“We’re already mass producing millions of pigs in horrible conditions and subjecting them to brutal slaughter methods just because we like the taste of bacon,” Pease said.

Lungs for transplant are in critically short supply. About 400,000 Americans die annually from lung diseases, but only 1,800 lung transplants were performed in 2010, according to the National Heart, Lung and Blood Institute.

Donor lungs must also be screened for immune compatibility with the recipient. The immune barriers between primates like humans and other species are far greater, because non-primates produce proteins that primates don’t make.

In April, researchers reported that genetically engineered pig hearts transplanted into baboons giving immunosuppressive drugs survived more than 500 days. The study, led by Dr. Muhammad Mohiuddin of the National Heart, Lung and Blood Institute, was presented at the American Academy for Thoracic Surgery in Toronto.




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