Tag Archives: DNA

Gene-editing technique has been used on human embryos

In what may be a memorably controversial and groundbreaking new research paper, scientists from China describe in detail the way in which they were successful at manipulating the genomes, or genetic blueprints of human embryos for what is the first time in human history, reintroducing all new ethical concerns about what just may be the next frontier for science.

The story was first reported by Nature News this Wednesday, and their paper was originally published by a little known online journal called Protein and Cell.

In their paper, Junjiu Huang, who is a gene-function researcher from Sun Yat-sen University of Guangzhou, and his colleagues describe the way in which they edited the genomes from embryos they received from a fertility clinic.

The embryos were described as non-viable in the paper, ones that would not be capable of resulting in a live birth because a genetic replication error resulted in them containing an extra set of chromosomes from being fertilized by two different sperm.

The researchers “attempted to modify the gene responsible for beta-thalassaemia, a potentially fatal blood disorder, using a gene-editing technique known as CRISPR/Cas9,” according to the report from Nature News.
“The researchers say that their results reveal serious obstacles to using the method in medical applications.”
The researchers injected the CRISPR into 86 different embryos and then they waited another 48 hours for the molecules that would replace any missing DNA to begin their work.

71 of the embryos survived, and 54 out of that number were then tested.

Researchers learned that just 28 of the embryos had been “successfully spliced, and that just a small fraction of these successes contained the necessary replacement genetic material,” read the report.
“If you want to do it in normal embryos, you need to be close to 100 percent,” Huang said in a statement to Nature News.

“That’s why we stopped. We still think it’s too immature.”

What was more concerning, however, is that there were a “surprising number” of unintended mutations that occurred during the process, and accelerating at a speed that was far higher than anything seen in earlier gene-editing studies which used either mice or adult human cells.

Such mutations, moving at an unchecked speed, could be harmful, and they are one of the primary reasons for why people in the scientific community are expressly concerned. It’s a worry that grew when rumors of Huang’s research team began to circulate at the beginning of the year.

“It underlines what we said before: we need to pause this research and make sure we have a broad based discussion about which direction we’re going here,” said Edward Lanphier, president of Sangamo BioSciences in Richmond, California, in an interview with Nature News.

While the gene editing technique has shown some unprecedented success, there is the question of what effect rapid rates of mutation may have – bringing to light some potential disorders that the scientific community is not yet aware of.

George Daley, who is a stem-cell biologist at Harvard Medical School of Boston, Massachusetts, was careful in his praise of the research, describing it as “a landmark, as well as a cautionary tale.”

“Their study should be a stern warning to any practitioner who thinks the technology is ready for testing to eradicate disease genes,” he said to Nature News.

More studies may be coming to light soon. So far, there are rumors of at least four other Chinese research teams also actively working on human embryos, according to the report.

James Sullivan
James Sullivan is the assistant editor of Brain World Magazine and a contributor to Truth Is Cool and OMNI Reboot. He can usually be found on TVTropes or RationalWiki when not exploiting life and science stories for another blog article.

Will the Woolly Mammoth Be the First Animal to Become De-Extinct?

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Over the last decade, there’s been quite a debate about whether or not, and perhaps more importantly whether or not we should, clone the woolly mammoth back to life. So far, researchers have made some progress on the first question at least. Back in 2005, the Mammoth Creation Project suggested that a creature with 88 percent resemblance to extinct species of mammoth could be cloned successfully within the next 50 years. Already, they may have their first major breakthrough in the processes of cloning.

One of the most prominent geneticists in the United States has successfully managed to extract DNA out of the frozen remains of a frozen mammoth discovered at Wrangel Island in the Arctic Ocean. Although the original strands of DNA are long dead, there was enough genetic information on the animal, which was well preserved with skin and hair, to build a synthetic replica which they then implanted inside the cells of an Indian Elephant – the mammoth’s closest living relatives, which are also about the same size. The elephant cells were kept isolated inside a petri dish. With the aid of a revolutionary (and somewhat controversial) DNA splicing technique known as CRISPR that allows for unprecedented accuracy, which allows for editing genes and even spreading them to the next generation. Lead researcher George Church, of Harvard University, has proudly reported that so far the cells are doing quite well.

The woolly mammoth died out some 10,000 years ago on the mainland in North America, roughly two millennia after mammoth species died out in Europe. The smaller ones indigenous to Wrangel Island, however, lived on peacefully without our intervention until about 1650 BC, overlapping with the rise of civilization in ancient Egypt and the construction of the oldest pyramids at Giza. Before then, they had dominated the Earth for 250,000 years during the Pleistocene Age, thriving during the last of Earth’s five major ice ages, when the planet was between nine and eighteen degrees Fahrenheit colder than it is today. This climate is the primary reason that mammoths, mummified under layers of snow and ice are so easy to find in prime condition, particularly as the Siberian permafrost thaws. Some have even revealed what their fur looked like. So plentiful were the carcasses at one point, that the 1951 Explorers’ Club’s annual dinner in Manhattan actually offered small morsels of mammoth meat for appetizers.

As temperatures became warmer and sea levels began to rise once again, life became a bit harder for the woolly mammoth, particularly around 18,000 years ago, when tribes of hunter-gatherers grew bigger and more organized, successfully hunting them down in large numbers. While Church and his team of researchers were not yet able to fully replicate a complete woolly mammoth genome so what they did was make copies of the genes responsible for the ‘mammoth-like’ attributes that we know – like heavy layers of fat to protect against the cold climate, the ears, which are actually shorter than the ones on modern elephants, tusks, and heavy coats of fur.

“We prioritised genes associated with cold resistance including hairiness, ear size, subcutaneous fat and, especially haemoglobin,” Church revealed to Ben Webster of The Sunday Times. Hemoglobin may have been the key genetic ingredient in helping mammoths tolerate extreme winters. Regardless of the temperature, this protein managed to keep oxygen traveling to the muscles at a constant speed, and may have allowed the mammoths to develop cooling systems for their limbs. By comparison, the hemoglobin in modern elephants, like humans, functions better in warm weather.

While there are samples of flesh and hair that would seem like natural reservoirs for DNA, the trouble is that the meat that has been found is thoroughly rotten, and while the fur shows an orange color, paleontologists have had to adjust the colors they’ve found for what may have been damage to the pigments from being trapped for so long under the ice. Another problem is that many of the mammoths born later clearly suffered birth defects. Cervical ribs that appear in some of the later females may have led to reproductive stress, joining overhunting and climate change as a possibility for their gradual decline.

While people have certainly played at least a partial role in the animal’s disappearance, our technology may eventually bring them back. According to Church: “We now have functioning elephant cells with mammoth DNA in them. We have not published it in a scientific journal because there is more work to do, but we plan to do so.” If successful, we may soon see the first mammoth in nearly 3,300 years.

The technique that combines elephant DNA with the extinct mammoth genome is CRISPR/Cas9, which has lately been used to develop transgenic organisms with an impressive track record. This marks the first time, however, that the technology has taken on the DNA of an extinct organism.

The researchers will next work to determine the best way to reproduce their work with elephant cells outside of the petri dish. It’s actually quite a tall order, but if they are somehow able to this with the use of elephant eggs, then they just might be able to program an elephant that will grow up to be just like a woolly mammoth. The question, however, is whether doing so would be a good idea. De-extinction is a point of contention among many researchers. Not all of them are quite enthusiastic about the idea. According to biologist Alex Greenwood from the Leibniz Institute for Zoo and Wildlife Research, in an interview with The Telegraph:

“We face the potential extinction of African and Asian elephants. Why bring back another elephantid from extinction when we cannot even keep the ones that are not extinct around? What is the message? We can be as irresponsible with the environment as we want. Then we’ll just clone things back?

Money would be better spent focusing on conserving what we do have than spending it on an animal that has been extinct for thousands of years.”

He certainly raises some good points. There are only a few rhinoceroses and a continuously declining population of iconic wildlife throughout Africa, elephants and even the predators like lions suffering from disease. The woolly mammoth would be returning to the world, entering an ecosystem that has adapted to thousands of years of life without them, and require a specialized diet. If we’re already having problems with spreading populations of invasive species, then bringing back extinct species might create an entirely new headache.

On the other hand, many grasslands in North America are showing the impact of having lost their larger grazers such as the megatherium (a bear-sized sloth), 18,000 years after the fact. Perhaps there is the promise of some ecological stability taking place, or perhaps further cultivating the mammoth genome may lead to further improvements in the technology of gene editing. If not an extinct species, perhaps this experiment might also lead to focusing on the preservation of species that only recently died out or those currently extinct in the wild, such as the black rhinoceros. We might be too late in having a thorough debate on the matter anyway, as Church’s team is only one of three research teams in the world actively at work on bringing back the woolly mammoth, but the fact that the issue has been raised alone is important, if only for bringing to the table new ways to preserve already endangered species.

Neanderthals Had Taste In Jewelry Too

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Yet another discovery has been brought into the growing pile of evidence that suggests Neanderthals were not quite the savage, hairy monsters we often portray them as being. Recently the fossil evidence has shown that they were attentive parents, that they had an appreciation of art – creating cave paintings of their own, and that they held elaborate burials for their dead, but a new study elaborates a bit further on their personal tastes. According to a paper published today in PLOS ONE, the Neanderthal hominids may have developed their own jewelry – necklaces fashioned from eagle talons, that until recently were attributed to modern humans.

They disappeared some 39,000 years ago, shortly after modern humans began to enter Europe – for reasons that are not quite known. For some time before their extinction, the species are believed to have interbred, and perhaps they did not so much die out as become assimilated with homo sapiens. Our DNA is 99.7% identical to theirs, and modern humans who aren’t of African descent share about 2.5% of DNA with Neanderthals. Although this lineage has recently fallen into dispute, both Neanderthals and modern humans did originate in Africa, and may have shared a common ancestor. Not only did they craft jewelry, but their hunting skills may have rivaled those of modern humans as well. In order to craft the talon necklaces which seem like a necessary ingredient in most movies featuring prehistoric cavemen – they may have also been able to fashion traps to catch more than one eagle – at that time the sky’s apex predator.

The evidence came not from a recent archaeological dig, but rather through examining some old articles from a museum collection. (as so much evidence does) from the bowels of a museum collection. At the beginning of the 20th century, Croatian paleontologist Dragutin Gorjanović-Kramberger lead an excavation of a site near the Croatian village of Krapina, which was filled with Ice Age human and animal remains. While you may have never seen Gorjanović-Kramberger’s name in print before, during his career, he used newly invented X-ray machines to look at inner bone structures from his finds and he even developed a way to determine the ages of the skeletons he found, through analyzing their fluorine content, nearly half a century before carbon dating came into existence. The site he uncovered held almost a thousand human bones, the bones of several thousand animals, several thousand animal bones, alongside at least a thousand tools, all of which dated between 120,000 to 130,000 years ago. As a result, the town is now home to a large museum dedicated specifically to Neanderthal culture and evolution.

Like most modern paleontologists, Gorjanovic-Kramberger kept a detailed record of where each skeleton was found, but when it came to discovering the necklaces, he overlooked something rather obvious.

“He found these eagle talons and sent them to a bird specialist in Budapest,” said David Frayer of the University of Kansas, one of the new study’s researchers. “But ironically, even though he was the first person to identify cut marks on human bones, he missed these really obvious signs of cut marks and manipulation on the eagle talons.”

The bird specialist in Budapest also paid little attention to the talons as did the museum curators who kept the specimens stored in their collection for well over a century.

It was not until late 2013, when one of Frayer’s colleagues became curator of the Croatian Natural History Museum and gave the talons a second look. She gave him a call after she suspected that the markings had been made by the Neanderthals they were buried with.

“When I saw them, my jaw dropped,” he said. “The talons were so complete and so beautiful, and the cut marks were so obvious.”

The single most important detail is the age of the necklaces. They are 120,000 or 130,000 years old, when Croatia was occupied solely by the Neanderthals.

Researchers have in the past suspected that Neanderthals did craft the necklaces, but may have learned their trade from what were much more sophisticated homo sapiens. The only prototypes they had for this claim, were more modern necklaces found in France, dating to about 40,000 years ago.

“People often argue that Neanderthals were mimicking modern humans instead of coming up with ornamental things on their own,” Frayer said. “In this case, there’s no doubt: There were only Neanderthals there, and only Neanderthal tools.”

The patterns of wear of the talons have led Frayer and his colleagues to believe that the claws had been strung together and were worn as necklaces. Exposure to sweat as well as other bodily fluids led to a distinct type of polishing which is often found on shell bead necklaces made in the same way.

Eagles would be rare in the mountainous terrain where the Neanderthals lived, and were also highly aggressive, two aspects indicating that these Neanderthals were highly skilled when it came to hunting.

“There are talons from three or four different eagles here, and that represents a lot of planning and skill,” he said. “They’re big birds, and they’re vicious when caught.”

These were not run-of-the-mill prey – they were targets that some of the braver Neanderthals deliberately hunted. It took about three or four birds to make one necklace. Even the decision to use eagle talons as an ornament — if it really was intended for that — may also suggest that the Neanderthals had capacity for abstract thinking.

“When you catch the most powerful aerial predator in your environment and wear it around your neck, that suggests some kind of attempt to get its power,” he said.

Explaining Why We Have Such Big Brains in Just a Few Letters

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G, C, A, T to be exact. Only a slight stretch of our DNA make the difference between us and our chimpanzee cousins. When embedding the bit of genetic information into mice, scientists found that the rodents’ brains grew significantly larger than usual.

“It’s likely to be one of many DNA regions that’s critical for controlling how the human brain develops,” says Debra Silver, on the region they chose. Silver is a neurobiologist at Duke University Medical School.

It is likely that this accounts for the massive difference in brain size between humans and our closest living relative, the chimpanzee – a difference of anywhere between two and four times larger by current estimates. While also having larger brains, people also have many more neurons than their simian friends, and many more connections, or synapses, occurring between each.

Scientists have long sought to determine what genetic basis we have for abstract thought as well as valuing logic and complex emotions – our capacity to develop languages and artwork, concepts that have long been associated with larger brain size. Currently, we have a wealth of evidence that our fellow hominids the Neanderthals were also capable of artwork and tool making, presenting a rather different picture than our old stereotypes of mindless barbarians. The Human Genome Project, concluded in 2004, revealed that humans and chimpanzees have DNA approximately 95 percent identical, establishing that we have more in common with chimps than mice do with rats. Silver’s latest interest, however, is to learn more about those regions in the genome that differ. Chimps do have capacity for tool making, using straw to catch termites, but their linguistic capacity, aside from facial reading, is still being explored.

Silver and her researchers isolated a gene that aids in brain development and removed the DNA region near it, which they proceeded to plant into mice. One group received human DNA, and the other received DNA extracted from chimps.

“What we discovered is that the human DNA turned on gene activity in neural stem cells, and these are cells which produce the neurons of our cerebral cortex,” said Silver.

The mice that were born yielded brains 12 percent larger than the brains of mice who received chimp DNA. The findings were published in Current Biology.

Now, Silver’s team will begin an investigation of how differently mice with larger brains will behave as they mature, knowing that they have only begun to scratch the surface. At the same time, they are looking for other genes that are specific to humans.

Of particular interest is within a vestigial genetic region known popularly as “junk DNA,” that which evidences our common descent from other, more primitive lifeforms, but until recently was believed to serve no specific purpose of its own, since this region doesn’t code for any active proteins in the body. Currently, however, researchers suspect that this region is critical for turning on and off genes as new cells are formed. Their ultimate function, if any at all, still remains a mystery.

“We have very little scientific information about the actual functions of those regions,” said Katie Pollard, who researches human and chimp DNA from the University of California, San Francisco, in a recent interview with NPR.

Many of the ways in which we differ from chimps can be found within the junk DNA, and many researchers like Pollard are still looking to meet that gap. As impressive as the results reported in the study may have been, it is difficult to predict what effect it may have on the mice. It’s preferential to see directly how either people or chimps are affected by the region’s presence, but then the research touches on ethical grounds.

“We’re talking about humans and chimpanzees here, and you cannot experiment on either of those,” notes Pollard. “And so it’s very challenging to prove causation.”

Challenging, sure, but not necessarily impossible either. Already, Pollard and her colleagues are experimenting with lab cultivated cells from chimps and humans, raised in Petri dishes.

“We can now actually generate the equivalent of embryonic brain cells and tissues that are human or chimpanzee,” says Pollard. “And, using genome engineering techniques, we can start to study the effects of switching the human and the chimp sequences in these primate cell lines.”

As their work progresses, the team hopes that soon they may find specific sequences in the DNA that are human by their very definition – opening the gateway of questioning precisely what characteristics make us human, and how distinct we really are from our living primate relatives. The difference may be far less than we ever imagined.