Tag Archives: chimera

Chinese scientists engineer monkey-pig chimeras

In a lab in Beijing, two pigs with monkey cells were born — the very first time such a chimeric animal was bred. The monkey-pig piglets lived for only a week before they died of unknown causes. However, the ultimate goal of such research is to one-day grow human organs into other animals for transplants.

This piglet contained monkey cells before it died one week after birth. Credit: Tang Hai.

Chinese researchers at the State Key Laboratory of Stem Cell and Reproductive Biology in Beijing first genetically modified monkey cells in vitro in order for them to produce a fluorescent protein called GFP. This way, the researchers could track the monkey cells in the host animal. Isolated embryonic monkey stem cells were then implanted into pig embryos five days after fertilization.

A total of 4,000 embryos were implanted in female pigs, which gave birth to ten piglets, two of them being monkey-pig chimeras. The resulting animals didn’t look like some weird cross between the two mammals. The piglets looked and behaved like non-chimeras, however, their hearts liver, spleen, and lungs, as well as skin tissue, contained monkey cells — but in very small amounts, between one in 1,000 and one in 10,000.

A week later, all piglets, chimeras and non-chimeras alike, died of unknown causes. The Chinese authors suspect that their deaths are due to defects introduced by the in vitro fertilization process rather than chimerism. It’s well established that in vitro fertilization in pigs isn’t very efficient compared to humans and other mammals.

In the future, the researchers plan breeding chimeras with an even higher proportion of monkey cells. Ultimately, they would like to grow pigs with an entire heart or pair of lungs made of primate cells.

This isn’t some pointless mad science. Ultimately, human-animal chimeras could be bred to supply people who are in dire need of a transplant with fully biocompatible organs. In the United States alone, 22 people on the transplant waiting list die each day because there aren’t enough donors. And even if a patient is lucky enough to access a donor’s organs, life isn’t easy at all following the transplant.

Today, even the most well-matched organs can’t last long because our immune system continuously attacks them, seeing them as foreign bodies that need to be destroyed. That’s what immunosuppressant drugs are for, which transplant patients have to take all their lives. In the worst case, complications can force them to undergo a new transplant surgery or risk death.

The first successful efforts to breed chimeric animals were made in the 1960s when, one by one, scientists managed to give life in the lab to chimeric rats, sheep, rabbits or cattle. These weren’t cross-species chimeras, but rather organisms composed of cells from multiple genetically distinct individuals of the same species. In time, this kind of research proved to be invaluable to scientists’ ongoing stem cell research efforts.

Other cross-species chimeras include pig-human chimeras developed by a team in California in 2017. These chimeras contained about one human cell in every 100,000 pig cells — the embryos were only allowed to develop for a month due to ethical concerns that their brains could be part humans. In 2018, researchers at Stanford made sheep-human hybrids, which contained one human cell for every 10,000 sheep cells.

It remains to be seen whether human chimeras could ever work. The high death rate and low chimeric efficiency reported by studies thus far are no reason to be optimistic, but the prospect of rendering the donor list obsolete may be well worth the pursuit.

sheep

Scientists breed first sheep-human hybrid — but there’s no reason to freak out

It sounds like something out of a bad science fiction novel, but scientists really have produced sheep-human hybrid embryos. Only a tiny fraction of the resulting embryos contains human cells, however. In time, as scientists breed hybrids with a higher and higher fraction of human cells, such chimeras could have their organs harvested for human transplants.

sheep

Credit: Pixabay.

The startling research was carried out by a team led by researchers at Stanford University. This is the second time scientists have successfully created a human-animal hybrid since last year’s breakthrough, when a pig-human hybrid was bred.

This isn’t some pointless mad science. Ultimately, human-animal chimeras could be bred to supply people who are in dire need of a transplant with fully biocompatible organs. In the United States alone, 22 people on the list for organ transplants die each day because there aren’t enough donors. And even if a patient is lucky enough to access a donor’s organs, life isn’t easy at all following the transplant.

Today, even the most well-matched organs can’t last long because our immune system continuously attacks them, seeing them as foreign bodies that need to be destroyed. That’s what immunosuppressant drugs are for, which transplant patients have to take all their lives. In the worst case, complications can force them to undergo a new transplant surgery or risk death.

That’s the end goal but, so far, we’re quite far from attaining it. The sheep-human embryos that Pablo Ross of the University of California, Davis, and colleagues, produced have only about one human cell for every 10,000 sheep cells. Scientists say that for a transplant to work, at least one percent of the embryo’s cells would need to be human. The hybrid embryos were destroyed after 28 days.

To make a chimera, scientists first isolate stem cells from the organisms they want to cross — the kind that can differentiate into any type of cell, i.e. skin, liver, etc. Then, stem cells from one species are inserted into the embryo of another. By hacking the embryo’s DNA, it is theoretically possible to instruct the organism not to grow a particular organ, which offers the interloping cells the opportunity to fill in the gap. This is how scientists hope to ultimately grow functional human organs, such as a heart or liver, inside a pig or other animal.

human pig chimera

Pig-human hybrid embryo from earlier research, in early 2017. Credit: Juan Carlos Izpisua Belmonte. 

Sheep embryos have desirable properties that made them appealing to the American researchers. They can be easily produced by in vitro fertilization (IVF) and require fewer embryos to be transplanted into an adult than pigs. According to Ross, scientists typically transfer 50 embryos to one recipient pig while for a sheep only four embryos per recipient are typically needed. Like pigs, sheep produce organs of about the right size for the human body, such as the heart and lungs.

These most recent developments presented last Saturday at the 2018 American Association for the Advancement of Science annual meeting in Austin, Texas, signify a new step forward in this direction. In the future, the researchers will gradually increase the human cell count in the hybrids, fine tuning the procedure until one day whole organs can be grown and ultimately harvested. But meanwhile, with each new iteration, the ethical debate will only intensify.

“The contribution of human cells so far is very small. It’s nothing like a pig with a human face or human brain,” said Hiro Nakauchi, a Stanford University researcher.

Breeding animals for the sole purpose of harvesting their organs may seem cruel and vile. Then again, some might argue that breeding livestock for food is not all that different, and most people don’t seem to have any qualms there. Certainly, this is no easy discussion.

“All of these approaches are controversial, and none of them are perfect, but they offer hope to people who are dying on a daily basis,” Ross says.

“We need to explore all possible alternatives to provide organs to ailing people.”

 

Artist impression of Halszkaraptor. Credit: Lukas Panzarin.

Newly discovered amphibious dinosaur had swan-like body but killer raptor claws

Paleontologists have discovered a new dinosaur species whose appearance is so strange, they could hardly believe it was real. The 75-million-year-old dinosaur used to feature a bizarre combination of body parts. it had the snout and neck of a goose but the claws of a velociraptor. Such contrast between grace and viciousness has rarely if ever been seen in the same dinosaur.

Artist impression of Halszkaraptor. Credit: Lukas Panzarin.

Artist impression of Halszkaraptor. Credit: Lukas Panzarin.

The creature is called Halszkaraptor escuillie in honor of famed Polish paleontologist Halszka Osmólska, who was preoccupied with studying many Mongolian dinosaurs. It was in Mongolia — in Ukhaa Tolgod, to be more precise — that this strange duck-like dinosaur was unearthed.

Duck, ostrich, swan?! Hmm…

Credit: Paul Tafforeau/ESRF.

This was one of the smallest known dinosaurs, as Halszkaraptor was no bigger than a goose. It mainly ate fish and crustaceans but likely chowed on lizards and insects too, according to lead author Andrea Cau of the Geological Museum Capellini in Bologna.

Cau and colleagues used multi-resolution, X-ray microtomography to study the fossils in their most intimate details, both on the outside and the inside, without risking any damage to these invaluable fossils. The fossil is still partly embeded in rock.

“The first time I saw the fossil I was shocked,” Cau said. “It was so unexpected and bizarre.”

Like today’s ducks, Halszkaraptor must have spent most of its life in water. It had a somewhat bird-like bill that was still not a true beak. The long neck likely enabled Halszkaraptor to dart out and grab prey close to the water’s surface. It had curved sickle-like claw on the second toe of the foot but which wasn’t particularly long and likely didn’t proove much use in hunting. To top things off, this man-bear-pig dinosaur had the teeth of a croc.

Researchers say that this odd-looking dinosaur used its killer claws to tear its prey to shreds. At the same time, it likely was preyed upon itself by the infamous velociraptor with which it was a contemporary and part of the same dromaeosauridae group. The group included feathered theropods which are closely related to birds but aren’t their ancestors.

Besides its staggering appearance, Halszkaraptor is important because it proves that raptorial dinosaurs not only ran and flew but also swam. If anything it shows just how amazingly diverse dinosaurs were.

Illustration: Maggie Koerth-Baker , BoingBoing

The Weird Wold of Parasitic Twins & Twin Chimerism

So you perhaps thought that twins could be either identical or fraternal? But did you know that there are actually other types of twins besides these two mentioned? Of course, identical and fraternal twins are the ones we are more aware of because they are the ones we hear about most and are most likely to encounter.

The chances of having identical twins are of around 3 in every 100 births. When it comes to fraternal twins the chances are higher and are in fact around double. The incidence rate of twin births does vary from culture to culture and country to country. Twin DNA testing, available by a number of laboratories and companies including International Biosciences, is used to confirm whether twins are monozygotic or dizygotic and people sometimes seek a twin zygosity test prior to a blood transfusion or organ transplant (this is because identical twins make ideal donors to each other due to their same antigens). Whichever the case, twin births are far from common. But there are even rarer types of twins that you might not even have ever heard of. Let’s take a look at two very interesting, if not fascinating, twin phenomena.

Twin Chimerism

Illustration: Maggie Koerth-Baker , BoingBoing

Illustration: Maggie Koerth-Baker , BoingBoing

We always think of twins as two separate individuals irrespective of whether they are identical or fraternal; this might seem like stating the obvious. There is however a phenomenon, rare in animals but rarer in a humans, that is called twin chimerism that defies the idea of twins being two separate individuals.

When we look at how twins are brought into the world we probably all know the following two basic facts:

  • Identical twins: these are the result of a sperm cell fusing with an egg. The fertilized egg later divides into two and forms two new individuals. Each of these new individuals came about from the same egg and therefore, each has the exact same copy of genetic material.
  • Non identical twins: These result from two sperm cells fertilizing two eggs resulting in two new individuals. Each individual carries its personal genetic makeup due to the fact that they were formed from a different sperm cell and egg, each carrying its own genetic material.

So what is a chimera? A chimera twin is formed in a way which is analogous to non identical twins but with a curious twist. Two separate eggs are indeed fertilized by a sperm cell each BUT once the two eggs are fertilized they then fuse together. Yes, one individual kind of absorbs its brother or sister into itself. This means that the new individual formed has two copies of genetic material from two different individuals. A chimera twin can have different genetic profiles depending on which sample is collected and from which part of their body.

[ALSO SEE] Chimeric organ harvesting: growing human organs inside pigs

A well known case was that of Lydia Fairchild, who needed to prove her biological relationship to her children to get state benefit in the USA. DNA tests showed her husband was the father of the children but that she was not the mother. Eventually, her agonizing battle came to an end when she was found to be a chimera twin. This came to light when she gave birth to another child. A DNA test was conducted on the spot which showed that she was totally unrelated to the baby she just gave birth to.

So how rare is twin chimerism? The answer is “very” with only about 30 documented cases amongst humans world-wide.

Another rare phenomenon: Parasitic twin

Illustration from the book "Anomalies and Curiosities"

Illustration from the book “Anomalies and Curiosities”

Parasitic twins are conjoined twins (and identical) who share the same heart (or rather the same cardiovascular system). Parasitic twins come about when the fertilized single egg in a monozygotic twin begins splitting in two but does not fully split. One individual fully develops but the other twin, called the parasite, does not. But parasitic twins are not to be confused with conjoined twins. Parasitic twins are characterized by one fully healthy individual with its parasite who is fully dependent on the health twin for substance and survival. Moreover, the parasitic twin can be joined at any part of the healthy twin. In its most extreme and rare case, one can find  fetus in fetu parasitic twining where the parasitic twin actually lives inside the body of its healthy twin without the healthy (and host twin) ever being aware of it. Parasitic twins are very rare with around one in every one million births. Fetus in fetu parasitic twining is even rarer with only around ninety known cases.

Bio

Helen Burns is a qualified nurse working in the prenatal care unit of a private hospital. She has currently put her nursing career on hold to look after her two young kids. In her part time, she works as a writer specializing on topics relating to child birth and pregnancy. Helen regularly contributes articles to a number of info sites and blogs. 

brown pig

Chimeric organ harvesting: growing human organs inside pigs

brown pig

Photo: freefoto.com

Sure to raise a slew of controversy and debate, researchers in Japan are currently investigating the possibility of growing human organs, like kidneys, livers or even hearts, inside pigs. A real life chimeric tale, as if spawned from the Island of Dr. Moreau. The challenges are numerous though, both technical (we’re talking about growing human organs in a foreign host), legal (human-animal hybrids are illegal in Japan) and of course moral (do we want living, breathing, organ farms – how would it be different from meat farms today?). For now, we can only entertain and ponder these questions, but in Japan things are beginning to shape up towards this goal.

The first steps in this direction were made by Hiroshi Nagashima, a professor at Meiji University, who made chimeric pigs – pigs that contain the genetic signature of two different species. A pilot experiment involved the breeding of what’s called an “a-pancreatic” pig. The genes that code the development of the pancreas in white pigs was switched off, then stem cells from a black pig are introduced into the white pig embryo. When the baby pig is born, it will look like a normal white pig, except it will have a black pig pancreas.

[RELATED] First chimera monkeys presented to the world

At Tokyo University, Professor Hiro Nakauchi is taking things further, by using induced pluripotent stem cells (iPS) – adult cell that are culture and hoaxed into behaving like stem cells, without the need to harvest stem cells from embryos. Nakauchi and team cultured iPS cells from brown mice skin cells and introduced these in the embryos of white mice, which similarly to Nagashima’s research had their pancreas development gene turned off. Nakauchi ended up with a white mouse with a brown mouse pancreas. The beauty of iPS cells, however, is that they can be used to develop into any kind of cells, like the constituting tissue that makes up organs. This is the basis for growing human organs in the lab, something that is currently in development with mixed results.

Man and beast

The Japanese researchers hope they can ultimately grow a human organ inside a pig host, or maybe some other surrogate animal model for that matter. If successful, the human organ grown would theoretically be identical to the human organ needing replacement, since it would have been grown from the patient’s iPS cells. The medical implications would be outstanding. Millions of people all over the world require an organ transplant of some kind and for many the waiting list is too long for survival.  Organs grown this way would actually be ideal, since there wouldn’t be a case of biological incompatibility anymore.

Is such a thing possible in the first place?

Black pig pancreas in a white pig host. Brown mouse pancreas in a white mouse host. Human pancreas inside a pig. Obviously, the latter case doesn’t follow the same pattern. We’re talking about extremely distant species. With confidence, however,  Prof Nakauchi  claims it can be done. In Japan human-animal hybrids are illegal and if any of his research can go further, the laws need to be changed. If not, Nakauchi can always move his research to a more permissive country.

Footage from the movie "The Island of Dr. Moreau".

Footage from the movie “The Island of Dr. Moreau”.

Then there’s another concern. In HG Wells’ sci-fi classic, The Island of Dr Moreau, an oddball scientists breeds all sort of chimeric creatures – grotesque beings that are horse, dog and pig at the same time (M’ling). Nakauchi assures that the genetically engineered pigs would still be pigs, it’s just that they’d be carrying human tissue. Anticipating controversy, the Japanese scientist points to In Vitro Fertilisation (IVF) which was invented in Britain in the 1970’s and which at the time sparked a lot of debate. Today, IVF is no longer seen as strange or unethical and in time Nakauchi’s research may also become accepted if the results measure up, he says.

 

The rhesus monkey twins, Roku and Hex ("six" in Japanesse and Greek respectively, since they were made from six distinct genetic entities), in sound health posing for the researchers. (c) OHSU

First chimera monkeys presented by scientists

The rhesus monkey twins, Roku and Hex ("six" in Japanesse and Greek respectively, since they were made from six distinct genetic entities), in sound health posing for the researchers. (c) OHSU

The rhesus monkey twins, Roku and Hex (“six” in Japanesse and Greek respectively, since they were made from six distinct genetic entities), in sound health posing for the researchers. (c) OHSU

In Greek mythology, the chimera is a fire breathing beast composed of several animal parts (lion body, snake-head tail, a goat head hanging from its back and so on), which has spurred the imagination of man for thousands of years. Though it is fairly clear that such an abomination never existed, apart from the infinite recesses of human imagination, scientist at the Oregon National Primate Research Centre have successfully bred, not one, but three chimera monkeys – each of them made up of tissue that came from up to six distinct genetic entities.

Of course, the scientists worked only with a single species, so that means no monkeys with rhino horns or giraffe ears. The three animals, two twins and a singleton, were bred after several different rhesus monkey embryos were stuck together in their early stage of development. These were later implanted in five female rhesus monkeys, all of which became pregnant. Thus, the chimera monkeys had tissue made up of cells that came from each of the contributing embryo.

“The cells never fuse, but they stay together and work together to form tissues and organs,” said Shoukhrat Mitalipov, who led the research. “The possibilities for science are enormous.”

This isn’t the first time a chimeric animal has been bred, far from it. The first successful attempts of this kind were made in the 1960s when one by one scientists managed to give life in the lab to chimeric rats, sheep, rabbits or cattle.  In time, this kind of research proved to be invaluable for scientists’ ongoing stem cell research efforts. Understanding how during embryonic development one particular cell develops into a particular tissue in the organism is crucial.

“If we want to move stem cell therapies from the lab to clinics and from the mouse to humans, we need to understand what these primate cells can and can’t do. We need to study them in humans, including human embryos,” said Mitalipov.