Chimeras

Japan: Human-Animal Chimeras On Fast Track

The U.S. is already 4 years ahead of Japan in creating chimeras by injecting human stem cells into animal embryos. Technocrat scientists invent because they can, not because there is a moral imperative to do so. ⁃ TN Editor

Supporters say research could be vital first step towards growing organs that can then be transplanted into people in need

Human-animal hybrids are to be developed in embryo form in Japan after the government approved controversial stem-cell research.

Human cells will be grown in rat and mouse embryos, then brought to term in a surrogate animal, as part of experiments set to be carried out at the University of Tokyo.

Supporters say the work – led by renowned geneticist Hiromitsu Nakauchi – could be a vital first step towards eventually growing organs that can then be transplanted into people in need.

But opponents have raised concerns that scientists are playing God.

They worry the human cells could stray beyond the targeted organs into other areas of the animal, effectively creating a creature that is part animal, part person.

For that reason, such prolonged experimentation has been effectively banned or gone unfinanced across the world in recent years.

In Japan itself, scientists were forbidden from going beyond a 14-day growth period. But those laws were relaxed in March when the country’s education and science ministry issued new guidelines saying such creations could now be brought to term.

Now, Dr Nakauchi’s application to experiment is the first to be approved under that new framework.

“We don’t expect to create human organs immediately, but this allows us to advance our research based upon the know-how we have gained up to this point,” he told the Asahi Shimbun newspaper.

He added that he planned to proceed slowly, and will not attempt to bring any hybrid embryos to term for some years, rather growing the hybrid mouse embryos to 14.5 days, when the animal’s organs are mostly formed, and the hybrid rat embryos to 15.5 days.

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LOCKR

GMO: Move Over CRISPR, Here Comes LOCKR

Scientists have created 100% synthetic proteins that can control how cells behave, including the death of the cell. Since proteins are the building blocks of life, LOCKR sets a dangerous precedent. ⁃ TN Editor

Scientists have invented a synthetic protein designed to control the inner workings of cells. In a pair of papers, published yesterday (July 24) in Nature, the researchers demonstrate how the tool can be used to tweak gene expression, orchestrate protein binding events, and cue functional changes in the cell in response to environmental conditions.

“Cells receive stimuli, then have to figure out what to do about it. They use natural systems to tune gene expression or degrade proteins, for example,” says Bobby Langan, a coauthor of both studies and a former graduate student at the University of Washington in an announcement. The newly designed tool—named LOCKR for Latching, Orthogonal Cage/Key pRotein—fiddles with these inbuilt systems by introducing bioactive peptides in their circuitry. The peptides only pop out when released by specific molecular “keys.”

LOCKR consists of six helixes, tightly bound to form a cage. One of the helical structures, bound more loosely than the others, can be displaced by a specific molecule, the key. When the key clicks into place, the helix moves aside and reveals a peptide customized to perform a particular function.

In their demonstrative studies, the researchers used LOCKR to trigger cell death, degrade specific proteins, and direct the movement of materials through living cells. Individual LOCKR proteins can also be connected to form circuits, systems able make changes within the cell in response to internal and external stimuli. The researchers first tested their tool in yeast, then successfully designed a modified version that works in lab-grown human cells.

“It signals the dawn of de novo designer proteins,”

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Technocrat Scientists Look To Create Human-Monkey Chimeras

Technocrats who believe that humans are just animals like every other animal, see no problem in crossing species by genetic modification. Transhumans go one step further by claiming to control evolution, creating Humans 2.0. ⁃ TN Editor

The monkeys in Douglas Munoz’s Kingston lab look like other monkeys.

They socialize and move around and eat and drink in the same way. They don’t fall over or stagger around. In fact, the only thing separating the macaques from their unaltered lab mates is the elevated level of a specific human protein implanted inside their brains — proteins that accumulate in the brains of humans with Alzheimer’s disease.

The monkeys have been injected with beta-amyloid, a molecule that, in high-enough amounts, is toxic to human brain tissue.

Munoz and collaborators are studying the earliest changes in those monkey cerebrums. Normally it takes several decades for Alzheimer’s to unfold in human brains. The researchers don’t have that kind of time. The injections speed things up.

If left alone, eventually the monkeys will start to show signs of Alzheimer’s. They make more mistakes on memory tasks and their reaction time slows.

Alzheimer’s research relies heavily on rodents. Munoz is trying to develop a monkey model of Alzheimer’s, because one of the biggest reasons for the staggering string of flops in the search for an effective treatment for the brain-ravaging disease is the species gap. The rat brain is a long way away from the human brain. Not so much a monkey’s.

Munoz, Canada Research Chair in neuroscience at Queen’s University, has reported his work using brain molecules. Others are implanting monkeys with fragments of human brain tissue extracted from people who died with Alzheimer’s.

Now, however, some are going further, and proposing the creation of human-monkey chimeras — part-human beings with entire portions of the brain, like, say, the hippocampus, entirely human derived.

For Munoz, the idea of biologically humanizing large portions of a monkey’s brain is  seriously unnerving. “To be honest, it just really ethically scares me,” he said. He believes in animal research as a fundamental way of understanding how the brain works. However, “For us to start to manipulate life functions in this kind of way without fully knowing how to turn it off, or stop it if something goes awry really scares me.”

However, in a new book on the science and ethics of chimeras, Yale University researchers say it’s time to explore, cautiously, the creation of human-monkey chimeras.

“The search for a better animal model to stimulate human disease has been a ‘holy grail’ of biomedical research for decades,” they wrote in Chimera Research: Ethics and Protocols.

“Realizing the promise of human-monkey chimera research in an ethically and scientifically appropriate manner will require a co-ordinated approach.”

To some, that may seem all fine and good. However, some scientists aren’t waiting for the ethics to be worked out.

In April, Chinese researchers announced they had inserted  a human brain gene into monkey embryos, a gene critical for human brain development.The experiment provoked revulsion, and fascination. Ethicists and philosophers condemned it as hugely morally risky, while the scientists behind the work are said to be keen on implanting even more human genes into monkey embryos, including one presumed to play a role in human intelligence.

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First China, Now Russia To Create Gene-Edited Babies

The cat is out of the bag with human genetic engineering. Once the human germline is modified, those changes will be permanently inherited by future generations, mixing with other DNA to produce unknown results. ⁃ TN Editor

A Russian scientist says he wants to create more genetically modified babies, flouting international objections that such a step would be premature, unethical and irresponsible.

Denis Rebrikov, a molecular biologist who heads a gene-editing lab at the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology in Moscow, claims he has developed a safe — and therefore acceptable — way to create gene-edited babies.

“How it can be unethical if we will make [a] healthy baby instead of diseased?” Rebrikov told NPR during his first broadcast interview. “Why? Why [is it] unethical?”

Rebrikov wants to create babies from embryos whose DNA he would edit to protect the resulting children from HIV. Rebrikov would edit a gene called CCR5 to replicate a naturally occurring variation that protects people from HIV.

“The rationale is to guarantee that the baby will be HIV-negative — that’s it,” Rebrikov says.

It’s the same rationale given by a Chinese scientist, He Jiankui, when he created the world’s first gene-edited babies. The birth of the gene-modified twin Chinese girls last year triggered an international firestorm, as well as calls for a global moratorium on creating gene-edited babies until doing so can be demonstrated to be safe and necessary.

Rebrikov says his research has shown that it’s possible to make precise genetic changes in embryos using the gene-editing technique CRISPR. He claims to have verified the safety by comparing the DNA of edited embryos with the unedited DNA of the couples used to create them.

“My experiments show that, yes, it’s safe. We demonstrated it’s safe to use,” says Rebrikov, who is also a researcher at the Pirogov Russian National Research Medical University in Moscow.

The babies created by the Chinese scientist had a father who was HIV-positive. Rebrikov says preventing infection in babies born to HIV-positive women is more justifiable when a woman doesn’t respond to antiviral drugs. Those children are at high risk of becoming infected.

Rebrikov says he plans to confirm his research with additional experiments before proceeding and would move forward only if he won government approval. Rebrikov says he has already identified two HIV-positive women who would be interested in trying to have gene-edited babies, and he plans to apply for approval within months.

Rebrikov’s plans were first reported in the journal Nature. He says he may also try to use his technique to create gene-edited babies for other reasons, such as preventing inherited forms of deafness.

But Sergey Kutsev, the chief geneticist and ethicist at the Russian Ministry of Health, told NPR that he doubts the government would authorize Rebrikov’s experiment.

“I am confident that Denis Rebrikov doesn’t have any chances to get approval from the Ministry of Health as of today,” Kutsev told NPR. He says the safety and usefulness of the technology needs to be proved first.

One concern, Kutsev says, is inadvertently creating mutations that may later lead to cancer or other diseases — changes that also can be passed down through future generations. “Therefore, this is certainly unacceptable at present,” he says.

Other scientists are also deeply skeptical of Rebrikov’s claims.

“The data are weak,” says Shoukhrat Mitalipov, an Oregon Health & Science University scientist who was the first to precisely use CRISPR to edit genes in human embryos.

“The technology is not ready,” agrees Dieter Egli, a Columbia University scientist trying to find safe ways to edit DNA in human embryos.

Many scientists and bioethicists argue that to do what Rebrikov proposes would be unethical and unnecessary because there are other ways to prevent HIV infection, as well as most genetic disorders.

“This is irresponsible,” says R. Alta Charo, a bioethicist at the University of Wisconsin—Madison, who is helping the World Health Organization try to police gene editing. “My biggest worry is that he’s going to bring about the birth of children who are going to suffer because he wanted to play around.”

Someday it may be deemed safe and appropriate to use gene-edited embryos to prevent rare but devastating genetic disorders in babies, Charo and others say.

But it’s far too premature to try that before the science has been tested much more thoroughly and before broad societal debates have been conducted about the ethics and morality, she says.

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Eugenics: Will Gene Editing Make Rich People ‘Superior’

Rich transhumans, many of whom are associated with Silicon Valley and Big Tech, fully expect that gene editing will take over the process of evolution, allowing them to design humanity 2.0. They are wrong, but that won’t hinder their efforts. ⁃ TN Editor

At a time when new technology such as gene editing offers unprecedented control over our own biology, the latest wave of medical advances, including powerful DNA-editing technology like CRISPR/Cas9, is a source of excitement and optimism.

CRISPR works like a genetic scalpel to cut a patient’s DNA, targeting and repairing genes at risk of disease.

This method of gene editing may one day make certain diseases – including Alzheimer’s, sickle cell disease, and some forms of cancer – a thing of the past.

While traditional treatments for chronic illnesses generally address the symptoms, this offers the potential of a permanent cure by attacking the disease at the source. Once genetic mutations are removed from a patient’s cells, the cells can resume normal function for the rest of the patient’s life.

What are the ethical concerns surrounding gene editing?

Gene editing technologies are not without controversy – from ethics to whether it will become a plaything of the super-rich.

One main issue of CRISPR lies in its simplicity, which means it is easier for unauthorised persons to experiment with the technology.

Already, CRISPR has become a favorite of amateur ‘biohackers’, with one man injecting himself with a homemade cocktail in a misguided attempt to boost his biceps. Another tried (and failed) to cure himself of AIDS.

And in late 2018, headlines blared that an ambitious researcher conducted secret gene editing trials in China, making mutations in human embryos to protect against HIV and then apparently turning those embryos into twin babies.

Researchers were aghast at the shoddy science and the premature use of CRISPR in human patients.

While scientists, ethicists, and regulators have called for a ban on gene editing research in human embryos until the risks are better understood, it may be impossible to prevent willing patients and unscrupulous researchers from experimenting with gene editing in humans.

Especially because when cutting-edge therapies do receive official regulatory approval, they often carry eye-popping price tags.

How much will gene editing cost?

Spark Therapeutics plans to charge US patients $850,000 for a gene therapy that treats a rare form of genetic blindness in children.

By some estimates, that’s a bargain: analysts expected a list price as high as $1 million per patient, or a half million dollars per eyeball.

There’s little reason to expect that the next approved genetic therapy will be much cheaper.

In a time when new technology offers unprecedented control over our own biology while global one per cent-ers seem to be the only ones who can afford access, is humanity at a crossroads?

Are we headed for a future where those with the means will be able to purchase genetic superiority, leaving the rest of us behind?

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Scientists: Human-Chimp DNA Hybrids Are Possible?

Dr. Barash’s goal is to convince the world that humans are no different that animals and in particular, monkeys. He thinks it would be good for scientists to use CRISPR and create Chimera ‘Humanzees’. His book’s subtitle says it all: ‘Using science to see our species as it really is.’ ⁃ TN Editor

Our future offspring may be part-human, part-chimp.

At least that’s the nightmarish vision of self-proclaimed expert, David Barash, a professor of psychology emeritus at the University of Washington.

Dr Barash says that not only is the creation of ‘humanzees’ possible using gene editing, but producing such creatures would be a ‘terrific idea’.

He believes it would force humans to acknowledge we are no different to animals and help stop the ‘grotesque abuse’ of the planet’s creatures.

Dr Barash’s remarkable comments – which could lead to a situation resembling Planet of the Apes – were made in his new book titled: ‘Through a glass brightly: Using science to see our species as it really is’.

They follow recent claims by evolutionary psychologist, Gordon Gallup, that a ‘humanzee’ was born in an American lab nearly 100 years ago before being killed by panicked doctors

Dr Gallup claims that humans can be crossbred with other apes and not just chimpanzees. Above is a file image of the 1968 movie Planet Of The Apes showing two members of the species kissing one another

In an extract from his book which appears in the magazine Nautilus, Dr Barash describes the belief that we are discontinuous from the natural world as possibly ‘the most hurtful theologically-driven myth of all times’.

Dr Barash believes CRISPR technology could be used to add or delete targeted genes as desired.

This means it might be possible to make precise edits in DNA and ‘silence’ certain genes that are different between the species.

‘It is unclear whether my own imagined chimphuman will be a hybrid (produced by cross-fertilising human and non-human gametes), or a chimera, created in a laboratory via techniques of genetic manipulation. I’m betting on the latter’, wrote Dr Barash.

Creating a hybrid animal would stop people thinking of themselves as apart from the natural world, Dr Barash argues.

‘Such an individual would not be an exact equal-parts-of-each combination, but would be neither human nor chimp: rather, something in between’, he said.

Creating a hybrid animal would stop people thinking of themselves as apart from the natural world, Dr Barash argues. Pictured is a clip from the 2011 film Rise of the Planet Of The Apes

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transgenic

Transgenic: Chinese Scientists Put Human Gene Into Monkeys

Technocrat scientists view humans as an animal species that is on the same level as monkeys – just containers of atoms and molecules –  so there is no ethical problem with inserting human genes into them. ⁃ TN Editor

Researchers from China and the United States have created transgenic monkeys carrying a human gene that is important for brain development, and the monkeys showed human-like brain development.

Scientists have identified several genes that are linked to primate brain size. MCPH1 is a gene that is expressed during fetal brain development. Mutations in MCPH1 can lead to microcephaly, a developmental disorder characterized by a small brain.

In the study published in the Beijing-based National Science Review, researchers from the Kunming Institute of Zoology, Chinese Academy of Sciences, the University of North Carolina in the United States and other research institutions reported that they successfully created 11 transgenic rhesus monkeys (eight first-generation and three second-generation) carrying human copies of MCPH1.

According to the research article, brain imaging and tissue section analysis showed an altered pattern of neuron differentiation and a delayed maturation of the neural system, which is similar to the developmental delay (neoteny) in humans.

Neoteny in humans is the retention of juvenile features into adulthood. One key difference between humans and nonhuman primates is that humans require a much longer time to shape their neuro-networks during development, greatly elongating childhood, which is the so-called “neoteny.”

The study also found that the transgenic monkeys exhibited better short-term memory and shorter reaction time compared to wild rhesus monkeys in the control group.

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GMO

GMO Cooking Oil Quietly Arrives In Restaurants

Flipping logic upside-down, the Technocrats at Calyxt state: “At Calyxt, we believe it is unethical NOT to use our technologies to address these issues head-on.” In reality, GMO is not equivalent to traditional plant husbandry. ⁃ TN Editor

Somewhere in the Midwest, a restaurant is frying foods with oil made from gene-edited soybeans. That’s according to the company making the oil, which says it’s the first commercial use of a gene-edited food in the U.S.

Calyxt said it can’t reveal its first customer for competitive reasons, but CEO Jim Blome said the oil is “in use and being eaten.”

The Minnesota-based company is hoping the announcement will encourage the food industry’s interest in the oil, which it says has no trans fats and a longer shelf life than other soybean oils. Whether demand builds remains to be seen, but the oil’s transition into the food supply signals gene editing’s potential to alter foods without the controversy of conventional GMOs, or genetically modified organisms.

Among the other gene-edited crops being explored: Mushrooms that don’t brown, wheat with more fiber, better-producing tomatoes, herbicide-tolerant canola and rice that doesn’t absorb soil pollution as it grows.

Unlike conventional GMOs, which are made by injecting DNA from other organisms, gene editing lets scientists alter traits by snipping out or adding specific genes in a lab. Startups including Calyxt say their crops do not qualify as GMOs because what they’re doing could theoretically be achieved with traditional crossbreeding.

So far, U.S. regulators have agreed and said several gene-edited crops in development do not require special oversight. It’s partly why companies see big potential for gene-edited crops.

“They’ve been spurred on by the regulatory decisions by this administration,” said Greg Jaffe of the Center for Science in the Public Interest, a health watchdog group.

But given the many ways gene editing can be used, Jaydee Hanson of the Center for Food Safety said regulators should consider the potential implications of each new crop. He cited the example of produce gene-edited to not brown.

“You’ve designed it to sit around longer. Are there problems with that?” he said.

Already, most corn and soy grown in the U.S. are herbicide-tolerant GMOs. Just last week, regulators cleared a hurdle for salmon genetically modified to grow faster. The fish is the first genetically modified animal approved for human consumption in the U.S.

Though regulators say GMOs are safe, health and environmental worries have persisted, and companies will soon have to disclose when products have “bioengineered” ingredients.

Calyxt says its oil does not qualify as a GMO. The oil is made from soybeans with two inactivated genes to produce more heart-healthy fats and no trans fats. The company says the oil also has a longer shelf life, which could reduce costs for food makers or result in longer-lasting products.

Soybean oils took a hit when regulators moved to ban oils with trans fats. Other trans fat-free soybean oils have become available in the years since, but the industry has found it difficult to win back food makers that already switched to different oils, said John Motter, former chair of the United Soybean Board.

Calyxt said the first customer is a company in the Midwest with multiple restaurant and foodservice locations, such as building cafeterias. It said the customer is using it in dressings and sauces and for frying, but didn’t specify if the oil’s benefits are being communicated to diners.

Calyxt is working on other gene-edited crops that it says are faster to develop than conventional GMOs, which require regulatory studies. But Tom Adams, CEO of biotech company Pairwise, said oversight of gene-edited foods could become stricter if public attitude changes.

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CRISPR

CRISPR Scientists Call For Global Moratorium On Heritable Gene Editing

There are non-Technocrats who see that science must be used responsibly., but once Pandora’s Box has been opened, it is impossible to shut. Rogue scientists will continue to ignore the warnings. ⁃ TN Editor

Some of the biggest names in gene editing want to stop anyone from playing around with cells that pass on changes to the next generation.

After the first International Summit on Human Gene Editing in December 2015, a statement was released. The organizers were unanimous in agreeing that the creation of genetically modified children was “irresponsible” unless we knew for sure it was safe.

Well, a fat lot of good that did. As MIT Technology Review revealed in November last year, Chinese scientist He Jiankui edited embryos to create two genetically engineered babies. Other groups are now actively looking to use the technology to enhance humans.

This has prompted some of the biggest names in gene editing (some of whom signed the 2015 statement) to call for a global moratorium on all human germline editing—editing sperm or egg cells so that the changes are hereditary.

In an open letter in Nature this week, major players in CRISPR’s development, including Emmanuelle Charpentier, Eric Lander, and Feng Zhang, have been joined by colleagues from seven different countries to call for a total ban on human germline editing until an international framework has been agreed on how it should be treated. They suggest five years “might be appropriate.” The US National Institutes of Health has also backed the call.

The signatories hope a voluntary global moratorium will stop the next He Jiankui from suddenly springing another unwelcome surprise.

The group says that this moratorium period will allow time to discuss the “technical, scientific, medical, societal, ethical, and moral issues that must be considered” before the technique can be used. Countries that decide to go ahead and allow germline editing should do so only after notifying the public of the plan, engaging in international consultation “about the wisdom of doing so,” and making sure that there is a “broad societal consensus” in the country for starting on that path, they say.

“The world might conclude that the clinical use of germline editing is a line that should not be crossed for any purpose whatsoever,” the group says. “Alternatively, some societies might support genetic correction for cou­ples with no other way to have biologically related children, but draw a line at all forms of genetic enhancement. Or, societies could one day endorse limited or widespread use of enhancement.”

The letter’s signatories suggest that germline research should be allowed so long as there is no intention to implant embryos and produce children. Using CRISPR to treat diseases in non-reproductive somatic cells (where the changes would not be heritable) should also be fine so long as any adults participating have given their informed consent. Genetic enhancement should not be allowed at this time, and no clinical application carried out unless its “long-­term biologi­cal consequences are sufficiently understood—both for individuals and for the human species,” they write.

We still don’t know what the majority of our genes do, so the risks of unintended consequences or so-called off-target effects—good or bad—are huge. The loss of the CCR5 gene that He was targeting to protect children from HIV, for example, has been implicated in increased complications and death from some viral infections.

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China’s CRISPR Twins Might Have Brain-Enhanced Intelligence

The renegade scientist who edited the gene of twin girls said it was for HIV resistance, but now it is learned that the same gene is directly related to enhanced cognition. This may have been the real goal from the beginning. ⁃ TN Editor

New research suggests that a controversial gene-editing experiment to make children resistant to HIV may also have enhanced their ability to learn and form memories.

he brains of two genetically edited girls born in China last year may have been changed in ways that enhance cognition and memory, scientists say.

The twins, called Lulu and Nana, reportedly had their genes modified before birth by a Chinese scientific team using the new editing tool CRISPR. The goal was to make the girls immune to infection by HIV, the virus that causes AIDS.

Now, new research shows that the same alteration introduced into the girls’ DNA, deletion of a gene called CCR5, not only makes mice smarter but also improves human brain recovery after stroke, and could be linked to greater success in school.

“The answer is likely yes, it did affect their brains,” says Alcino J. Silva, a neurobiologist at the University of California, Los Angeles, whose lab uncovered a major new role for the CCR5 gene in memory and the brain’s ability to form new connections.

“The simplest interpretation is that those mutations will probably have an impact on cognitive function in the twins,” says Silva. He says the exact effect on the girls’ cognition is impossible to predict, and “that is why it should not be done.”

The Chinese team, led by He Jiankui of the Southern University of Science and Technology in Shenzhen, claimed it used CRISPR to delete CCR5 from human embryos, some of which were later used to create pregnancies. HIV requires the CCR5 gene to enter human blood cells.

The experiment has been widely condemned as irresponsible, and He is under investigation in China. News of the first gene-edited babies also inflamed speculation about whether CRISPR technology could one day be used to create super-intelligent humans, perhaps as part of a biotechnology race between the US and China.

There is no evidence that He actually set out to modify the twins’ intelligence. MIT Technology Review contacted scientists studying the effects of CCR5 on cognition, and they say the Chinese scientist never reached out to them, as he did to others from whom he hoped to get scientific advice or support.

“As far as I know, we never heard from him,” says Miou Zhou, a professor at the Western University of Health Sciences in California.

Although He never consulted the brain researchers, the Chinese scientist was certainly aware of the link between CCR5 and cognition.  It was first shown in 2016 by Zhou and Silva, who found that removing the gene from mice significantly improved their memory. The team had looked at more than 140 different genetic alterations to find which made mice smarter.

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