Scientists temporarily attached a pig’s kidney to a human body and watched it begin to work, a small step in the decades-long quest to one day use animal organs for life-saving transplants.

Pigs have been the most recent research focus to address the organ shortage, but among the hurdles: A sugar in pig cells, foreign to the human body, causes immediate organ rejection. The kidney for this experiment came from a gene-edited animal, engineered to eliminate that sugar and avoid an immune system attack.

Surgeons attached the pig kidney to a pair of large blood vessels outside the body of a deceased recipient so they could observe it for two days. The kidney did what it was supposed to do — filter waste and produce urine — and didn’t trigger rejection.

“It had absolutely normal function,” said Dr. Robert Montgomery, who led the surgical team last month at NYU Langone Health. “It didn’t have this immediate rejection that we have worried about.”

This research is “a significant step,” said Dr. Andrew Adams of the University of Minnesota Medical School, who was not part of the work. It will reassure patients, researchers and regulators “that we’re moving in the right direction.”

The dream of animal-to-human transplants — or xenotransplantation — goes back to the 17th century with stumbling attempts to use animal blood for transfusions. By the 20th century, surgeons were attempting transplants of organs from baboons into humans, notably Baby Fae, a dying infant, who lived 21 days with a baboon heart.

With no lasting success and much public uproar, scientists turned from primates to pigs, tinkering with their genes to bridge the species gap.

Pigs have advantages over monkeys and apes. They are produced for food, so using them for organs raises fewer ethical concerns. Pigs have large litters, short gestation periods and organs comparable to humans.

Pig heart valves also have been used successfully for decades in humans. The blood thinner heparin is derived from pig intestines. Pig skin grafts are used on burns and Chinese surgeons have used pig corneas to restore sight.

In the NYU case, researchers kept a deceased woman’s body going on a ventilator after her family agreed to the experiment. The woman had wished to donate her organs, but they weren’t suitable for traditional donation.

The family felt “there was a possibility that some good could come from this gift,” Montgomery said.

Montgomery himself received a transplant three years ago, a human heart from a donor with hepatitis C because he was willing to take any organ. “I was one of those people lying in an ICU waiting and not knowing whether an organ was going to come in time,” he said.

Several biotech companies are in the running to develop suitable pig organs for transplant to help ease the human organ shortage. More than 90,000 people in the U.S. are in line for a kidney transplant. Every day, 12 die while waiting.

The advance is a win for Revivicor, a subsidiary of United Therapeutics, the company that engineered the pig and its cousins, a herd of 100 raised in tightly controlled conditions at a facility in Iowa.

The pigs lack a gene that produces alpha-gal, the sugar that provokes an immediate attack from the human immune system.

In December, the Food and Drug Administration approved the gene alteration in the Revivicor pigs as safe for human food consumption and medicine.

But the FDA said developers would need to submit more paperwork before pig organs could be transplanted into living humans.

“This is an important step forward in realizing the promise of xenotransplantation, which will save thousands of lives each year in the not-too-distant future,” said United Therapeutics CEO Martine Rothblatt in a statement.

Experts say tests on nonhuman primates and last month’s experiment with a human body pave the way for the first experimental pig kidney or heart transplants in living people in the next several years.

Raising pigs to be organ donors feels wrong to some people, but it may grow more acceptable if concerns about animal welfare can be addressed, said Karen Maschke, a research scholar at the Hastings Center, who will help develop ethics and policy recommendations for the first clinical trials under a grant from the National Institutes of Health.

“The other issue is going to be: Should we be doing this just because we can?” Maschke said.

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By Giles Bruce

Researchers are developing a new tool to measure whether children are experiencing the physiological effects of toxic stress, a development that could have far-reaching implications for pediatricians and families.

The JPB Research Network on Toxic Stress, led by Harvard University professor Dr. Jack Shonkoff, is composed of academics from across the country who hope to deliver a biological test for childhood adversity in the next few years.

“The goal in reality is to identify biomarkers that are scalable, that would raise red flags that would tell the pediatrician: ‘There’s something going on here. I don’t know exactly what it is, but maybe I should dig a little deeper,’” said Pat Levitt, a University of Southern California professor of pediatrics and neurogenetics researcher involved in the project.

Chronic stress early in life has been found to put a person at increased risk for a variety of physical, mental and educational problems, and even change the architecture of the brain. Those findings have gained broader awareness in recent years, as journalists have increasingly reported on the effects of toxic stress on children across the nation.

But so far there hasn’t been an easy way to quickly detect dangerous levels of stress in pediatric settings — so that’s the missing tool the team of researchers is trying to develop. This could also change the way health journalists report on early childhood adversity and interventions, by giving a quantifiable way to gauge stress and resilience in kids.

“We are getting progressively closer to having objective, biologically based ‘readouts’ of toxic stress, but there remain two challenges,” said Charles Nelson, a professor of pediatrics and neuroscience at Harvard Medical School who is also associated with the project. “A: Will they work at the level of the individual child? And B: Do they have high specificity? That is — are they picking up a ‘signature’ of toxic stress per se or something broader? My sense is it will still be three to five years before we solve these problems.”

If and when that happens, Levitt said such a measurement tool would be a “game-changer.” That’s because, he noted, there are “things that can buffer toxic stress: strengthening the caregiver skill sets, particularly on executive function; reducing stress levels in the (family) environment; (addressing) mental health issues of the primary caregiver.”

The interventions often focus on the parents, and their past traumas, as much as the children, and involve increasing “serve and return,” a term that refers to the social connectedness and interaction between young kids and their caregivers.

Levitt compared it to the treatment for autism: “While we don’t have a ‘cure’ for autism spectrum disorder, we do have a situation in which more and more kids are getting earlier and earlier interventions, and they’re doing much better than those who are getting interventions later.”

The tool for measuring toxic stress will likely consist of a battery of tests — potentially using samples of saliva, DNA and hair, as well as electroencephalograms or EEG — that can collectively detect elevated stress responses in the body. Such analyses would look for factors like an increase or decrease in certain immune proteins, epigenetic changes, and damage to telomeres, which are protective caps at the end of chromosomes and a measure of cellular aging, Levitt said.

As Levitt explained, “A toxic stress response is really an attack on what we call ‘regulatory processes,’ which is a fancy term for another, single-word term: homeostasis. That is, all our physiological systems become imbalanced. … If it doesn’t return back to baseline, or back to normal, but it maintains some chronic state, that’s when the the problems occur — what we call a ‘physiological load.’”

The current approach from pediatricians is to examine developmental milestones — speech, language and motor-skills — as well as the quality of social interactions between the child and caregiver and even the parents’ mental health, Levitt said. But this approach is limited, in part because primary care providers are generally stretched for time. Research has found that only about a third of kids receive any type of developmental screening.

Some pediatricians also screen for adverse childhood experiences, but often aren’t reimbursed for their times. California recently became the first state to pay health care providers to do these evaluations, under the state’s Medicaid program. However, some experts have been skeptical about the effectiveness of these screenings, and the biomarker battery could eventually supplement — or even replace — them with a more objective approach.

Levitt predicts this will be a “front line” test, like ones required in certain places for lead exposure.

But some parents might have misgivings about getting the biomarker analysis, either because they’re worried about the potential for child welfare involvement or their kids being stigmatized as victims of abuse, trauma or neglect. This could be particularly true for communities of color, whose wariness stems from a long history of unscrupulous medical research.

That’s why, Levitt noted, the research consortium includes community leaders who are addressing these and other ethical issues, as well as how to get community buy-in.

The tool could also be used to measure the efficacy of various early-childhood interventions, by telling us which ones are more effective in returning kids’ stress levels to normal. In addition, researchers have said such biomarker tests could help detect the physiological underpinnings of why some kids can better withstand or overcome the negative effects of adversity.

“If we can identify the genesis of the toxic stress response,” Levitt said, “it should mean we can identify the genesis of building resilience.”

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