National Post (National Edition)
CAN HUMAN CELLS GROW IN AN ANIMAL?
AMERICAN RESEARCHERS SAY THEY ARE CLOSER TO THAT OBJECTIVE AFTER SUCCESSFULLY CREATING HUMAN-PIG CHIMERA EMBRYOS
In what’s being hailed a scientific “tour de force,” American researchers have succeeded in creating human-pig chimera embryos with the ultimate goal of one day growing human organs in animals for transplant.
So far, none of the interspecies embryos have been allowed to grow beyond four weeks. However, the experiments are raising profoundly sticky moral and ethical issues — including the remote but not impossible risk human cells intended to morph into a new liver, pancreas or heart could wend their way up to the animal’s brain. Could that part-human chimera somehow develop human consciousness?
The more human-like we make living organisms the more valuable for research purposes they become, says Timothy Caulfield, Canada Research Chair in health law and policy. “But of course the more we humanize an animal, the more we raise questions about animal ethics,” he said.
The work also provokes a kind of psychological and visceral creepiness. “The first concern is public perception: does it violate some notion of boundaries, or the natural order of things?” asks renowned bioethicist Arthur Caplan.
“You’re going to have to watch carefully what is happening during the course of development, and be ready to shut down something that looks like it’s an unintentional outcome,” he said, meaning a pig embryo with any kind of human feature.
The successful creation of pig-human chimeras is described in this week’s issue of the scientific journal Cell. According to the article, researchers at the Salk Institute for Biological Studies in La Jolla, Calif., injected different forms of human stem cells into pig embryos. Stem cells have the ability to transform into virtually any other type of cell in the body, allowing them, in theory, to regenerate damaged or diseased tissue.
Next, 41 surrogate sows received between 30 to 50 of the hybrid human-pig embryos each, resulting in 18 pregnancies. After 21 to 28 days, 186 embryos were harvested.
Half of them were abnormally small. However, a few dozen were normal size, said co-author and Salk scientist Jun Wu in an interview. “And in some of them, we observed human cells were there.”
Not only did the human cells survive, “they turned into the progenitors for many different tissues and organs,” Wu said.
All in, the effort required 1,500 pig embryos and the contributions of more than 40 people, including pig farmers from Spain, working for more than four years. “This required a tour de force,” lead investigator Juan Carlos Izpisua Belmonte said.
"But in the end we were able to answer a key question — can human cells grow in an animal,” Izpisua Belmonte told the Post.
If the technical hurdles can be overcome, the researchers say it may one day be possible to block or delete genes critical for the development of a given organ (a pancreas, say) in a fertilized pig egg, and then inject human stem cells into the embryo, to fill the gap and grow the missing pancreas.
The human-pig fetus would be born and the chimeric animal raised until the pancreas reached the required size and was needed for transplant.
Wu said “clinical-grade" pig farms would be needed to incubate the human organs. Pigs are ideal, he said, because their organs are similar in size and physiology to humans and their gestation period is a third what it is for humans.
Pig-human chimeras may also hold the potential for life extension, Wu says. Any organ generated in a pig is going to be a young organ. “And these organs will probably function better than the organs we’ve already had for 30 or 40 years,” Wu said. “We might have the ability to rejuvenate our physiology.”
Still, turning a few cells into fully functioning organs will be hugely challenging, the researchers acknowledge. This is the first published proof of principle; vast more research needs to be done.
But, because the organ would be grown from the person’s own cells, theoretically, there will be little risk of rejection.
The proportion of human cells that made up the chimerized embryos was “low, the Salk scientists said — less than one per cent. The researchers said they are developing strategies to prevent human cells from differentiating into the central nervous system, or the germ line — meaning sperm and eggs.
The worst-case scenario, ethicists warned last year in a paper published in Stem Cell Research & Therapy, “would be that a pig producing human sperm could accidentally mate with a sow or vice versa.”
The possibility of producing some kind of man-pig child “is almost non-existent,” they stress, given the “interspecies reproductive barrier is strong.” And pigs bearing human organs could simply be sterilized to prevent them reproducing.
Equally horrifying would be a “humanized pig brain,” should the human stem cells somehow get off target.
“Can you control where these cells go,” asks Caplan, of New York University’s Langone Medical Center.
“There’s less worry about growing an islet cell to help somebody with diabetes than there is finding out human cells migrated into the animal’s brain and grew some structure there,” he said.
“It doesn’t mean that the animal is all of a sudden going to wake up and sign up to take a bioethics course,” he said.
“It just means there are some human cells in there. But still, that bothers us more because that’s where we think the mental states that identify our identity are.”
“Most people don’t say, well, the way I know who I am is by thinking about the cells that are in my pancreas or spleen or something. But we do when it comes to the brain.”
There is also the potential for abuse. “Forget about (the Salk researchers’) work. What if somebody said, ‘I think it would be interesting or fun to see what would happen if I did try to make a pig with some element of a human brain?”