First human-monkey chimera raises concern among scientists

Researchers reprogrammed human cells before injecting them in the monkey embryo

Efforts to create human-animal chimeras have rebooted an ethical debate after reports emerged that scientists have produced monkey embryos containing human cells.

A chimera is an organism whose cells come from two or more “individuals”, with recent work looking at combinations from different species. The word comes from a beast from Greek mythology which was said to be part lion, part goat and part snake.

The latest report, published in the Spanish newspaper El País, claims a team of researchers led by Prof Juan Carlos Izpisúa Belmonte from the Salk Institute in the US have produced monkey-human chimeras. The research was conducted in China “to avoid legal issues”, according to the report.

Chimeras are seen as a potential way to address the lack of organs for transplantation, as well as problems of organ rejection. Scientists believe organs genetically matched to a particular human recipient could one day be grown inside animals. The approach is based on taking cells from an adult human and reprogramming them to become stem cells, which can give rise to any type of cell in the body. They are then introduced into the embryo of another species.

Izpisúa Belmonte and other scientists have previously managed to produce both pig embryos and sheep embryos which contain human cells, although the proportions are tiny: in the latter case, researchers estimate that only one cell in 10,000 was human. Pig-human and sheep-human chimeras are attractive in part because pigs and sheep have organs about the right size for transplantation into humans.

 The human-monkey chimeras have reportedly only been allowed to develop for a few weeks. Photograph: Xinhua/Barcroft Images

Details of the work reported this week are scarce: Izpisúa Belmonte and colleagues did not respond to requests for comment.

However Alejandro De Los Angeles, from the department of psychiatry at Yale University, said it was likely monkey-human chimeras were being developed to explore how to improve the proportion of human cells in such organisms. “Making human-monkey chimeras could teach us how to make human-pig chimeras with the hope of making organs for transplantation,” he said. “It could teach us which types of stem cells we should be using, or other ways of enhancing what’s called ‘human chimerism levels’ inside pigs.”

De Los Angeles pointed out that, as with previous work in pigs and sheep, the human-monkey chimeras have reportedly only been allowed to develop for a few weeks – ie before organs actually form.

Prof Robin Lovell-Badge, a developmental biologist from London’s Francis Crick Institute, agreed. “I don’t think it is particularly concerning in terms of the ethics, because you are not taking them far enough to have a nervous system or develop in any way – it’s just really a ball of cells,” he said.

But Lovell-Badge added that if chimeras were allowed to develop further, it could raise concerns. “How do you restrict the contribution of the human cells just to the organ that you want to make?” he said. “If that is a pancreas or a heart or something, or kidney, then that is fine if you manage to do that. [But] if you allow these animals to go all the way through and be born, if you have a big contribution to the central nervous system from the human cells, then that obviously becomes a concern.”

The news of the monkey-human chimeras comes shortly after it was reported Japanese researchers such as Prof Hiromitsu Nakauchi received government support to create mouse-human chimeras.

In March Japan lifted a ban on allowing such embryos to develop beyond 14 days and being implanted in a uterus, meaning these chimeras can, if permission for an experiment is granted, be brought to term. Nakauchi has said he does not plan to bring the human-mouse chimeras to term yet.

Lovell-Badge said it is very unlikely the animals, if brought to term, would take on human-like behaviour, but said the animals might not behave like “normal” rodents.

“So there are some animal welfare issues as well as the ‘yuck-factor’ ethical issues from making something more human,” he said. “Clearly if any animal born had aspects of human appearance, their faces, their hands, their skin, then I suspect, while scientifically very interesting, people might get a little upset with that.”

De Los Angeles and colleagues have suggested monkey-human chimeras could, in theory, provide new ways to study neurological and psychiatric diseases in humans.

“In theory, for diseases where primate models are not good enough, making human-monkey chimeras could provide a better model of brain diseases,” he told the Guardian, adding that in the case of Alzheimer’s more than 150 trials have failed in 20 years, possibly because of a lack of a good disease model.

One possible approach for brain research is that a monkey embryo could be genetically altered and then injected with human stem cells so that part of the brain, for example the hippocampus, is composed only of human cells. A similar approach has previously been used by Izpisúa Belmonte and colleagues to grow a rat pancreas inside a mouse.

“If you just swap the hippocampus, it doesn’t mean you are now going to have a human-functioning brain,” said Lovell-Badge. “It might have perhaps slightly better memories or slightly different memories … but they are not going to have a human cortex, which is what actually makes us human.”

But such proposals walk straight into the ethical arena others have been at pains to dodge: the possibility of human cells ending up in monkey brains, a development some fear could result in the creatures being human-like. Researchers have previously said they are able to prevent human cells ending up in chimeras’ brains or sex organs.

De Los Angeles said there is still a long way to go before human-monkey chimeras are brought to term.

“The evolutionary distance between humans and monkeys spans 30-40 million years, so it is unclear if this is even possible,” he said. “This difference is greater than 10 million years between mice and rats, and even the efficiency of making mouse-rat chimeras is already quite low.”

While making monkey brains more human is a red line for some, in some ways it has already been crossed. In April scientists in China published a study in which they claimed to have introduced a human brain gene into monkeys, with the animals showing features including better short-term memory and shorter reaction times. These animals are not chimeras, but it is clear that new boundaries are being pushed.

Lovell-Badge said he thought it possible that the development of human-monkey chimeras to study a part of the central nervous system could gain approval, but that it would take a while.

“In the UK, any proposal to make human-monkey chimeras would have to be very well justified, and it would have to get through a very tough review process,” he said. “I am sure that any proposal to go straight to live born chimeras would not get approval in the UK and probably not also in Japan.”

(Source: The Guardian)

Vanished ape found in ancient Chinese tomb, giving clues to its disappearance

Swinging from branch to branch with loud and often melodic calls, gibbons are a dramatic presence in forests they inhabit. Eighth century Chinese poet Li Bai described their haunting voices: "While on the cliffs of the Yangtze Gorges, gibbons ceaselessly cry/Ten thousand folds of mountains, my skiff has slipped them by."

Today, no gibbons live anywhere near the Yangtze River gorges Li traversed, and the apes that remain elsewhere in China have fur patterns different from those often depicted in classical Chinese paintings. But given their prominence in art, researchers assumed the animals must once have swung through the treetops of central China. Now, physical evidence of a vanished gibbon has turned up in an unexpected place: a tomb that may have been built for the grandmother of China's first emperor, nearly 2300 years ago. The skull and jaw found in the tomb are so distinctive that scientists conclude they belonged to a member of a now-extinct gibbon genus.

The skull "is really a fantastic find," says Thomas Geissmann, a gibbon expert at the University of Zurich in Switzerland who was not involved in the research. "I don't doubt for a second that it's a new species, and probably a new genus. … We can assume that this vast area of central China [once] had many other species" of gibbon. With surviving gibbons also facing extinction, the new find could boost motivation to protect them by highlighting how much has already been lost, says Samuel Turvey, a conservation biologist at the Zoological Society of London who, with his colleagues, describes the ancient skull in this week's issue of Science.

Turvey, who studies human-caused extinctions, combs historical records and museum collections for evidence about past biodiversity. In 2011, at the Shaanxi Provincial Institute of Archaeology in Xi'an, China, he came across artifacts from the tomb, which was discovered in 2004 on the outskirts of Xi'an, the capital of Shaanxi province and once a powerful imperial city. Based on the tomb's location and the artifacts it contained, archaeologists Ding Yan and Zhang Tianen of the Shaanxi institute, who helped lead the excavations, dated it to the Warring States period, about 2250 years ago. They concluded it may have been built for Lady Xia, the grandmother of China's first emperor, Qin Shi Huang. Qin ruled from 256 B.C.E. until 210 B.C.E., united much of China and was buried near Xi'an with his famous terracotta army.

Gibbons are a common motif in classical Chinese artworks such as this 15th century painting. FREER GALLERY OF ART AND ARTHUR M. SACKLER GALLERY, SMITHSONIAN INSTITUTION, WASHINGTON, D.C.: GIFT OF CHARLES LANG FREER, F1911.272 (DETAIL)

The collection's primate bones caught Turvey's attention. "Historically there are accounts of gibbons" in central China, he says, "but it is very, very far from any gibbon populations today." The tomb also contained skeletons of leopards, lynx, black bears, cranes, and a range of domestic animals. The wild animals were all from the region, so the gibbon probably also lived nearby, says archaeologist Hu Songmei of the Shaanxi institute. Gibbons were common high-status pets, and burial chambers were often arranged so that the deceased "could continue to enjoy the life they knew when still alive," Hu says. Because the emperor was presumably involved in his grandmother's funeral preparations, Turvey says, "It's not a total flight of fancy to think that he might have seen this specific gibbon."

Chinese authorities did not let the team sample the bone for DNA, which could have helped determine the animal's kinship with existing gibbons. Instead, Turvey worked with Helen Chatterjee, an expert on gibbons at University College London, and colleagues to measure key points on the skull and teeth and compare the dimensions with those of the four living genera of gibbons. Their statistical analysis found both the skull and molars were so distinct from all of today's gibbons that the fossil belonged to a separate genus.

That fits with what we know of gibbons, Chatterjee says. Gibbon populations can easily become isolated from each other because the apes spend their lives in the treetops and can't cross gaps in the canopy created by rivers or other barriers. That has spurred extreme genetic diversity—the four genera alive today have different numbers of chromosomes, she notes.

The team named the new species Junzi imperialis. "Junzi" is a Chinese word for scholar-officials, who were often associated with gibbons because the animals were considered wiser and nobler than mischievous monkeys. The animals' arms were thought to help them channel chi, "a bit like Jedi masters," Chatterjee says.

As for what J. imperialis looked like, classical paintings may hold some clues. They depict gibbons with a wide variety of colors and facial markings, frequently different from any of today's gibbon species. Turvey says J. imperialis "may be the tip of the iceberg," and a whole suite of gibbon species that were common across China in previous centuries have already gone extinct.

The Imperial Chinese reverence for gibbons apparently didn't extend to preserving their habitat. The razing of forests for agriculture in recent centuries, and perhaps the onset of a cooler, drier climate in central China, apparently spelled disaster for J. imperialis. The same dynamic is at play for today's gibbons, says David Chivers, a primatologist who retired from the University of Cambridge in the United Kingdom. One species, on China's Hainan island, has only two dozen individuals left. "Remove the forest and they're gone," he says of the apes. "We've got to stop the forest being cut down. That's the only way to save them."

(Source: Science)

Sword to kill a mosquito?!

After my hubby said one of his family members is eager to crush/kill me like a fly/mosquito with his/her boots, I laughed heartily remembering a Panchatantra story, The Foolish Friend, which I used to hear in our childhood. 

The power given to wrong hands can bring disasters to the very person who has given them. In this case, my hubby had fought with me to buy a pair of boots/shoes nine years ago to that person. And now, unable to face the truth, that person is eager to crush/kill me under the same boots! 

I’m sure all of us have heard that Panchatantra story at some or the other stage in our lifetime. As another year comes to an end, it’s that time to remember the story. Hope you guys will enjoy and laugh as much as I did!   

Once upon a time there was a king who had a monkey as his pet. He kept him constantly close at hand for his amusement. Everybody knows that parrots, partridges, doves, rams, monkeys and such creatures are a king's natural companions.

It goes without saying that the monkey, fed on the various dishes that the king gave him. He grew large and was given respect by all who surrounded the king. Indeed, the king, due to his love and exceeding trust of the monkey, even gave him a sword to carry!

In the vicinity of the palace, the king had a grove artfully planted with many trees of various sorts. Early in the springtime, the king noticed how beautiful the grove was. Its blossoms exuded a magnificent fragrance, filling the whole atmosphere with love. Thus overcome by love, he entered the grove with his favorite wife. He ordered all his servants to wait for him at the entrance.

After having pleasantly strolling through and observing the grove, he grew tired and said to his monkey, "I want to sleep a little while in this arbor of flowers. Take care that nothing disturbs me!" Having said this, the king fell asleep.

Meanwhile, a mosquito flew up and lit on his head. Seeing this, the monkey thought angrily, "What is this? Am I to allow this common creature to bite the king before my very eyes?"

With that he proceeded to drive it away. However, in spite of the monkey's defense, the mosquito approached the king again and again. Finally, blinded by anger, the monkey drew his sword and struck down the mosquito with a single blow. However, the same blow also split the king's head.

The queen, who was sleeping next to the king jumped up in terror. Seeing the crime, she said, "Oh, oh, you foolish monkey! What have you done to the king who placed such trust in you?"

The monkey explained how it had happened, but thereafter he was shunned and scorned by everyone. Thus it is said, "Do not choose a fool for a friend, for the king was killed by a monkey."

And after that incident, I feel, "It is better not to give power to the wrong person, even if it's your own family member!"