“I looked it up myself and found out he was telling the truth. There is no specific cure for this disease. No patients survived.” Martina Rothbright recalls.
Rothbright was told by a doctor at Children’s National Medical Center in Washington, D.C., that her youngest daughter, 9-year-old Janice, had a rare condition that could give her only three years to live. The arteries between Her heart and lungs narrowed, blocking oxygen and putting a strain on her heart, which pumps blood to her veins, like water in a knotted pipe. At the time, there were no formal medicines for the progressive disease, known as pulmonary hypertension, except for lung transplants — but few children received them.
So Rothbright started developing drugs on his own. By then, in the mid-1990s, she was a senior lawyer and communications entrepreneur in her 40s who had built a successful career in businesses that included the precursor to satellite radio company SiriusXM and GeoStar, a satellite navigation company.
After his daughter was diagnosed, Rothbright spent every night in the hospital’s basement library poring over medical literature, researching her condition. She trawled through textbooks for every difficult term and every essay mentioned in footnotes, convinced that technology could help her daughter’s plight. “I had no choice,” she said. “My goal in life was no longer to launch satellites into space, but to save Janice.”
Lawyers for a drug company in North Carolina that happened to own a compound Rothbright thought would be a promising drug refused to license the compound to individuals. So Rothbright founded a biotech company, assembled a team of scientists, persuaded the drug company to take her money, and developed a viable drug using the compound that went through a series of clinical trials and eventually won FDA approval. The drug has saved tens of thousands of lives, including Janice’s.
Today, rothbright’s biotech company, United Therapeutics Corp., is valued at about $8 billion. More than 100,000 patients worldwide take the company’s life-saving drug, traprostacycline, making Ms. Rothbright the highest-paid female executive in the United States. Janice, now 36, also works at United Healthcare.
Rothbright knows, however, that we are only halfway there. Traprostacycline is therapeutic, but there is no cure, and its relief varies from patient to patient. Janice could still have lung failure at any time. For pulmonary hypertension, lung transplantation is the long-term solution, but less than 1% of patients who need a lung transplant each year are operated on. In 2019, about 250,000 people died of terminal lung failure, either because they couldn’t wait for a transplant or because they couldn’t get a lung source for other reasons.
Rothbright was once again determined to address the threat to her daughter, this time the global organ shortage. “I thought about it and decided to change the situation.” She said.
| | editing organs
Backed by a nine-figure annual research and development budget and a $2 billion war chest, Rothbright led a team that set out to develop techniques for producing organs without the need for human donors. A few years later, through acquisitions and partnerships, the team expanded from United’s headquarters in Silver Spring, Md., to laboratories and research institutes across the country.
In Jacksonville, Fla., several United Engineers are conducting a lung infusion trial, a technique that evaluates damaged donor lungs for transplant, at a Mayo Clinic branch. At Research Triangle in Manchester, N.H., and North Carolina, UnitedHealthcare has hired scientists to study how to grow human stem cells on decellularanimal organs. Now, Rothbright’s company is about to launch a new initiative: growing human-compatible genetically modified organs in pigs.
At a research facility at the University of Alabama designed by Rothbright, some of the scientists involved in the project to clone Dolly the sheep are creating pigs with custom genes. There were at least ten genetic changes in each pig. Scientists say the transgenic pig organs are similar in size to human organs and will not be rejected when transplanted into a human body. The first organ to be studied is the kidney, but there will be more to come. Pig valves have been used in human heart transplants for decades. Why not just transplant a whole pig heart or a whole pig lung? Maybe one day it could save Janice’s life.
Rosebright (center) and her daughter Janice (left)
Now Rothbright’s team is challenging a problem that has baffled the world’s top scientists for decades: the body’s immune system can’t accept an organ from another person, let alone a pig. “Organs need to interact with the body through hundreds of biochemical connections, whereas drugs only need a few connections. The biochemical challenges of the former are orders of magnitude higher than the latter.” “Rothbright said.
Some analysts say a technological breakthrough is too distant to boost UnitedHealthcare’s revenue valuation. Rothbright’s team, however, has already made a significant advance in gene-editing by transplanting genetically modified pig kidneys into baboons that have survived for more than six months and share 94 percent of the genetic code with humans. In late 2020, United Healthcare received approval from the FOOD and Drug Administration to use its first gene-editing technology in drugs and food.
One obstacle to transplanting pig organs into humans is that differences in the genetic code between pigs and humans could cause blood cells in the human body to react to the transplanted organ as an invasive disease that needs to be destroyed. To find out, scientists put the transplanted organ in a machine running with human blood for several hours.
Once the genes are found in pigs that are activated by human blood, scientists can study their role and then use genetic engineering to modify or remove genes that might trigger an immune response in humans.
After fixing the gene that might have caused the problem, scientists could try to put the genetically modified pig organ back into the machine. If all potential problems are considered eliminated, the organ can be transplanted into a baboon for further testing.
Rothbright’s team is preparing to submit more complex gm pigs to the agency for review. Rothbright declined to disclose UnitedHealthcare’s current technological progress, but she has said the company could begin late-stage clinical trials of pig kidney transplants in humans as early as 2022. In the future, she said, pig heart and lung transplants will no longer be the stuff of science fiction.
| | xenotransplantation
In 1954, a Boston doctor named Joseph Murray performed the first successful human organ transplant, transplanting a kidney from 23-year-old Ronald Herrick into his twin brother Richard. Ronald’s kidneys were protected from immune attack in Richard’s body because the twins were genetically similar. In the early 1960s, French doctors used radiation to temporarily weaken patients’ immunity and transplanted organs from unrelated donors. In the late 1960s, heart and pancreas transplants were performed successfully. In the 1980s, the medical community began to transplant lungs and intestines.
In 2019, doctors around the world performed 100,000 organ transplants, including those donated by the dead and those from living people, according to the nonprofit United Network for Organ Sharing. Forty percent of the 100,000 surgeries were performed in the United States, costing patients and insurers $13 billion.
But supply is still far below demand. In the United States, a patient is added to the 107,000-strong organ waiting list every nine minutes, and an average of 17 people die every day waiting for a donor organ. These numbers do not reflect the true picture, because not all patients who need transplants are on the list, which is calculated based on a complex formula and is reserved for those with the highest chance of survival and those who would benefit most from transplants. The kidney alone is in great demand: hundreds of millions of people around the world with advanced kidney disease rely on dialysis to keep them alive.
Pig hearts and lung transplants will no longer be the stuff of science fiction.
Scientists have been hoping for decades to make a solution like Rothbright’s a reality. To do this, they grew heart valves in cows and pigs, then chemically treated them to avoid rejection after the transplant. Most of the service life of the pig heart valves only 15 years, but it’s still better than more durable carbon mechanical valve, because the use of artificial organs of patients must be lifelong taking anticoagulants, prevent blood clots condensation around the organs in such a way as to cause a stroke, while the use of genetically modified (gm) patients with valvular basically can normal life, and can when friends poking fun at himself as a “half man and half pig”.
However, fully transplanting animal organs into humans is more complicated and can trigger a deadly immune response. The medical vision was long put on hold after concerns were raised that transplanting organs from other species could wake up retroviruses that had lain dormant in animals for years. But in recent years, advances in gene editing have allowed molecular biologists to rewrite the human genome with unprecedented speed and precision. In 2015, George Church, a pioneer in the field of gene editing in mammalian cells, announced that he and his colleagues had successfully eliminated 62 retroviruses from pig embryos using gene editing.
Mr Church co-founded eGenesis, a rival to UnitedHealthcare that has raised $263m. “The question is not if, but when,” said Paul Secoli, the company’s president and CEO. EGenesis said it would use most of the investment to advance kidney transplants from animals to humans, with clinical trials planned to begin in 2023.
Some analysts expect Rothbright to be the first to achieve that goal. “Martina is different,” said Wedbush Securities analyst Liana Musatos. It seems to me that when she sets her mind to something, she does it.”
Jennies is healthy and recently celebrated her 36th birthday, but Rothbright and his team still feel a sense of urgency about the race against time. Janice is currently head of remote and robotics programs at United Healthcare. She reports at the company’s sales meetings, summarizes the year’s results at the annual meeting and shares her own health challenges.
“It’s very real,” says David Ayares, director of the Revivicor xenotransplantation program at United Medical Group. “I go to company meetings, and Instead of talking about budgets or clinical trials, Martina tells me: ‘I want you to make a breakthrough because my daughter needs your pig’s lungs. ‘”