Editing Babies? We Need to Learn a Lot More First

Sooner or later it was bound to happen: A rogue scientist in China claims to have edited a gene in two human embryos and implanted them in the mother’s womb, resulting in the birth of genetically altered twin girls. We’re no longer in the realm of science fiction. If true, this hacking of their biological operating instructions, which they will pass on to their children and generations to come, is a dangerous breach of medical ethics and responsible research and must be condemned.

This is not to say that medicine won’t someday employ gene-editing technologies in similar ways. But that time has not arrived. There are still too many risks, too many unknowns, about tinkering with our heritable genetic blueprints.

In recent years genome editing has been appropriately heralded as the most important advance of biotechnology of our generation, and most likely the past century. Known as Crispr, this technique, and related DNA editing tools, enable their users to cut and paste discrete letters of the genome. This ability has markedly advanced science, shedding new light on the complex human genome with its billions of A, C, T and G letters that are the architecture of who we are.

Already, many clinical trials using this technology are underway involving patients with rare diseases like hemophilia, thalassemia and sickle cell anemia. The difference between these efforts and what reportedly happened in China is that these genome editing trials involve cells from the patient’s body. The manipulations are not transmissible to the next generation.

These trials are in their early stages, and we don’t yet have results to show whether this type of editing is safe or provides effective treatment. But whatever happens, the consequences are confined to a patient who has consented to the experimental treatment.

While there have been reports of human embryo editing experiments in laboratory petri dishes, until now, so far as we know, none of these embryos have been implanted in humans. In such cases, the hazards become markedly amplified because the editing intervenes in so-called germ line cells that are transmitted from one generation to another. Conceivably every cell in the body, some 37 trillion, could be programmed with the edits.

In the Chinese study, led by He Jiankui, a physicist, not a medical doctor, on the faculty of Southern University of Science and Technology in Shenzhen, the targeted gene was CCR5, which helps enable H.I.V. to enter cells. While preventing this intrusion might sound like an advance in the fight against AIDS, it is completely unnecessary and may even carry the hazard of increasing the subject’s susceptibility to other types of infection, such as influenza and West Nile fever. Previous genome editing studies have shown it is possible to disable the CCR5 gene in adults without working at the embryo level.

So the experiment was needless. It had no scientific basis and must be considered unethical when balanced against the known and unknown risks.

He Jiankui, a physicist and researcher, says he edited the genes of twins, a claim that has drawn widespread criticism.CreditVCG/VCG, via Getty Images

 

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He Jiankui, a physicist and researcher, says he edited the genes of twins, a claim that has drawn widespread criticism.CreditVCG/VCG, via Getty Images

The predominant risks are the potential impacts of the editing on other letters of the genome, which could induce diseases. We don’t have the assurance yet that Crispr provides laserlike precision in editing — for example, certain important genes for suppressing cancer are particularly susceptible to unintended editing. The way we assess this risk is to sequence the genome before and after editing, to see whether changes were made in genes other than the target gene.

But our ability to discern these changes is still rudimentary, and it is entirely likely that we will miss something. The fact that we may not have seen unintended mutations brought about by editing is by no means proof of their absence.

With six billion letters in the genome that could be affected, the risk of unintended editing is considerable and requires extensive scrutiny to understand and mitigate. That’s partly why the implantation of edited human embryos has been widely banned.

Even beyond the actual editing, this episode appears to have been marked by breaches of scientific conduct. One issue is informed consent. It is unclear whether the parents were told that there were simple ways to protect the embryos from disease that might have been transmitted by the H.I.V.-infected father. If they had known that, why would they consent to this risky procedure?

Moreover, no report by the researchers has been produced for the biomedical community to review. Through a journalist reporting about this, I had the opportunity to see some of the data, and there’s little question that Dr. He at least attempted to edit the genomes of the embryos. But no sequencing data has been presented or independently assessed.

Nor has data been released to show whether the targeted gene was functionally disabled, which would require cell experiments. Science demands such transparency, but all we have is a YouTube video by the researcher, who makes the bold claim that “the gene surgery was safe.”

Dr. He’s university has disavowed knowledge or support of the research and said an inquiry is underway. It said his “conduct in utilizing CRISPR/Cas9 to edit human embryos has seriously violated academic ethics and codes of conduct.”

We don’t know whether the intended human genome editing was achieved in the twins and have no idea whether it will prove to be safe if it was accomplished.

But we can conclude that this was a misguided, reckless use of powerful gene-altering tools to create edited human beings. We should not proceed down this road until we know far more about the consequences of what we are doing.

 

This article was originally published in The New York Times.  Read the original article.

Chinese Scientist Claims to Use Crispr to Make First Genetically Edited Babies

Ever since scientists created the powerful gene editing technique Crispr, they have braced apprehensively for the day when it would be used to create a genetically altered human being. Many nations banned such work, fearing it could be misused to alter everything from eye color to I.Q.

Now, the moment they feared may have come. On Monday, a scientist in China announced that he had created the world’s first genetically edited babies, twin girls who were born this month.

The researcher, He Jiankui, said that he had altered a gene in the embryos, before having them implanted in the mother’s womb, with the goal of making the babies resistant to infection with H.I.V. He has not published the research in any journal and did not share any evidence or data that definitively proved he had done it.

But his previous work is known to many experts in the field, who said — many with alarm — that it was entirely possible he had.

“It’s scary,” said Dr. Alexander Marson, a gene editing expert at the University of California in San Francisco.

While the United States and many other countries have made it illegal to deliberately alter the genes of human embryos, it is not against the law to do so in China, but the practice is opposed by many researchers there. A group of 122 Chinese scientists issued a statement calling Dr. He’s actions “crazy” and his claims “a huge blow to the global reputation and development of Chinese science.”

If human embryos can be routinely edited, many scientists, ethicists and policymakers fear a slippery slope to a future in which babies are genetically engineered for traits — like athletic or intellectual prowess — that have nothing to do with preventing devastating medical conditions.

While those possibilities might seem far in the future, a different concern is urgent and immediate: safety. The methods used for gene editing can inadvertently alter other genes in unpredictable ways. Dr. He said that did not happen in this case, but it is a worry that looms over the field.

Dr. He made his announcement on the eve of the Second International Summit on Human Genome Editing in Hong Kong, saying that he had recruited several couples in which the man had H.I.V. and then used in vitro fertilization to create human embryos that were resistant to the virus that causes AIDS. He said he did it by directing Crispr-Cas9 to deliberately disable a gene, known as CCR₅, that is used to make a protein H.I.V. needs to enter cells.

Dr. He said the experiment worked for a couple whose twin girls were born in November. He said there were no adverse effects on other genes.

In a video that he posted, Dr. He said the father of the twins has a reason to live now that he has children, and that people with H.I.V. face severe discrimination in China.

Dr. He’s announcement was reported earlier by the MIT Technology Review and The Associated Press.

In an interview with the A.P. he indicated that he hoped to set an example to use genetic editing for valid reasons. “I feel a strong responsibility that it’s not just to make a first, but also make it an example,” he told the A.P. He added: “Society will decide what to do next.”

It is highly unusual for a scientist to announce a groundbreaking development without at least providing data that academic peers can review. Dr. He said he had gotten permission to do the work from the ethics board of the hospital Shenzhen Harmonicare, but the hospital, in interviews with Chinese media, denied being involved. Cheng Zhen, the general manager of Shenzhen Harmonicare, has asked the police to investigate what they suspect are “fraudulent ethical review materials,” according to the Beijing News.

The university that Dr. He is attached to, the Southern University of Science and Technology, said Dr. He has been on no-pay leave since February and that the school of biology believed that his project “is a serious violation of academic ethics and academic norms,” according to the state-run Beijing News.

In a statement late on Monday, China’s national health commission said it has asked the health commission in southern Guangdong province to investigate Mr. He’s claims.

Many scientists in the United States were appalled by the developments.

“I think that’s completely insane,” said Shoukhrat Mitalipov, director of the Center for Embryonic Cell and Gene Therapy at Oregon Health and Science University. Dr. Mitalipov broke new ground last year by using gene editing to successfully remove a dangerous mutation from human embryos in a laboratory dish.

Dr. Mitalipov said that unlike his own work, which focuses on editing out mutations that cause serious diseases that cannot be prevented any other way, Dr. He did not do anything medically necessary. There are other ways to prevent H.I.V. infection in newborns.

Just three months ago, at a conference in late August on genome engineering at Cold Spring Harbor Laboratory in New York, Dr. He presented work on editing the CCR₅ gene in the embryos of nine couples.

At the conference, whose organizers included Jennifer Doudna, one of the inventors of Crispr technology, Dr. He gave a careful talk about something that fellow attendees considered squarely within the realm of ethically approved research. But he did not mention that some of those embryos had been implanted in a woman and could result in genetically engineered babies.

“What we now know is that as he was talking, there was a woman in China carrying twins,” said Fyodor Urnov, deputy director of the Altius Institute for Biomedical Sciences and a visiting researcher at the Innovative Genomics Institute at the University of California. “He had the opportunity to say ‘Oh and by the way, I’m just going to come out and say it, people, there’s a woman carrying twins.’”

“I would never play poker against Dr. He,” Dr. Urnov quipped.

Richard Hynes, a cancer researcher at the Massachusetts Institute of Technology, who co-led an advisory group on human gene editing for the National Academy of Sciences and the National Academy of Medicine, said that group and a similar organization in Britain had determined that if human genes were to be edited, the procedure should only be done to address “serious unmet needs in medical treatment, it had to be well monitored, it had to be well followed up, full consent has to be in place.”

It is not clear why altering genes to make people resistant to H.I.V. is “a serious unmet need.” Men with H.I.V. do not infect embryos. Their semen contains the virus that causes AIDS, which can infect women, but the virus can be washed off their sperm before insemination. Or a doctor can inject a single sperm into an egg. In either case, the woman will not be infected and neither will the babies.

Dr. He got his Ph.D., from Rice University, in physics and his postdoctoral training, at Stanford, was with Stephen Quake, a professor of bioengineering and applied physics who works on sequencing DNA, not editing it.

Experts said that using Crispr would actually be quite easy for someone like Dr. He.

After coming to Shenzhen in 2012, Dr. He, at age 28, established a DNA sequencing company, Direct Genomics, and listed Dr. Quake on its advisory board. But, in a telephone interview on Monday, Dr. Quake said he was never associated with the company.

This article was originally published in The New York Times.  Read the original article.

How Did We Get to Be Human?

I spoke recently to a scientist who was writing up a summary of what we know about human evolution. He should have had a head start, having written a similar article five years ago.

But when he looked at what he had written then, he realized that little of it was relevant. “I can’t use much of any of it,” he told me.

As a journalist, I can sympathize.

In recent years, scientists have offered a flood of insights into how we became human. Fairly often, the new evidence doesn’t square with what we thought we knew.

Instead, many of these findings demand that researchers ask new questions about the human past, and envision a more complex prehistory.

When Science Times debuted 40 years ago, scientists knew far less about how our ancestors branched off from other apes and evolved into new species, known as hominins.

Back then, the oldest known hominin fossil was a diminutive, small-brained female unearthed in Ethiopia named Lucy. Her species, now known as Australopithecus afarensis, existed from about 3.85 million years ago to about 2.95 million years ago.

Lucy and her kin still had apelike features, like long arms and curved hands. They could walk on the ground, but inefficiently. Running was out of the question.

Hominin evolution appeared to have taken a relatively direct path from her to modern humans. The earliest known members of our genus, Homo, were taller and had long legs for walking and running, as well as much larger brains. Eventually, early Homo gave rise to our own exceptional species, Homo sapiens.

Now, it’s clear that Lucy’s species wasn’t the beginning of our evolution; it was a branch that sprouted midway along the trunk of our family tree. Researchers have found fossils of hominins dating back over six million years. Those vestiges — a leg bone here, a crushed skull there — hint at even more apelike ancestors.

All this mixing and experimentation produced as many as 30 different sorts of hominins — that we know of. And one kind did not simply succeed another through history: For millions of years, several sorts of hominins coexisted.

Indeed, our own species shared this planet with near-relatives until just recently.

In 2017, researchers found the oldest known fossils of our species in Morocco, bones dating back about 300,000 years. At that time, Neanderthals also existed. They continued to live across Europe and Asia until 40,000 years ago.

At that time, too, Homo erectus, one of the oldest members of our genus, still clung to existence in what is now Indonesia. The species did not go extinct until at least 143,000 years ago.

Homo erectus and Neanderthals are hardly new to paleoanthropologists. Neanderthals came to light in 1851, and Homo erectus fossils were discovered in the 1890s. But still other hominins, recent research has shown, shared the planet with our own species.

In 2015, researchers unearthed 250,000-year-old fossils in a South African cave. Known as Homo naledi, this new species had a Lucy-sized brain, but it was also a complex structure in ways that resembled our own.

The wrist and other hand bones of Homo naledi were humanlike, while its long, curved fingers seemed more like an ape’s.

While Homo naledi thrived in Africa, another mysterious species could be found on an island now called Flores, in Indonesia. Known as Homo floresiensis, these hominins stood only three feet high and had brains even smaller than that of Homo naledi.

The species may have arrived on Flores as early as 700,000 years ago, and these hominins endured until at least 60,000 years ago. Homo floresiensis appears to have made stone tools, perhaps to hunt and butcher the dwarf elephants that once lived on the island.

Paleoanthropologists today are no longer limited to just examining the size and shape of fossils. Over the past 20 years, geneticists have learned how to extract DNA from bones dating back tens of thousands of years.

In one remarkable discovery in Siberia, researchers examining a nondescript pinkie bone discovered the genome of a separate line of hominins, now known as Denisovans.

As it turns out, we have had the planet to ourselves only in the past 40,000 years — a small fraction of Homo sapiens’ existence. Perhaps we outcompeted other species. Maybe they just had bad luck in evolution’s lottery.

But in one way, we are still living with them. Both Neanderthals and Denisovans interbred with our ancestors some 60,000 years ago, and billions of people today carry their DNA. Still mosaics, after all this time.

This article was originally published in The New York Times.  Read the original article.

The microscopic structure of a cat’s tongue helps keep its fur clean

T.s. eliot’s mystery cat, Macavity, besides being a criminal mastermind able to evade the combined ranks of British law enforcement, had a coat that was “dusty from neglect”. Criminality is one thing, but this truly strains the imagination. Real cats are champion groomers.

Of the ten hours a day that a domestic cat deigns to remain awake, it spends a quarter licking dirt, fleas, blood and loose hairs from its fur. Cats’ tongues, specialised for this task, are covered in hundreds of backward-facing keratin spines. But exactly how these cone-shaped protuberances, called filiform papillae, work to give the animals such mastery over their cleanliness has remained unknown until now.

To crack the mystery Alexis Noel and David Hu, a pair of engineers at the Georgia Institute of Technology, in Atlanta, examined the grooming mechanisms of six feline species—from domestic pets and bobcats to snow leopards and lions. Studying the activity of tongues inside the mouths of living creatures proved tricky, so instead Dr Noel and Dr Hu built an automated grooming machine fitted out with tongues and furs from animals whose lives had ended at places such as the Tiger Haven in Tennessee, a sort of retirement home for rescued big cats. They attached the tongues to a mechanical arm and made them “lick” the furs. High-resolution cameras and scanners took pictures.

The two researchers found that the filiform papillae were shaped not, as had previously been thought, like solid cones. Rather, they resembled tiny scoops. Each had a small groove—named a cavo papilla by the team—at its tip.

This structure permits surface tension to wick saliva from a cat’s mouth and release it into the farthest recesses of the animal’s fur. During each lick, about half of the saliva on the tongue is so transferred. Saliva serves as a multi-purpose cleaning agent and the cavo papillae also assist the absorption, for the return journey, of any dirt or blood that needs removing. The cat’s tongue therefore “acts like a loofah and a sponge at the same time”, says Dr Hu.

The pair’s findings, just published in the Proceedings of the National Academy of Sciences, could inspire new ways to clean complex hairy surfaces. The authors themselves demonstrated one such application, which they call the tongue-inspired grooming (tigr) brush. To make this they employed 3d printing to create structures, shaped like cat papillae, attached to a silicone base. The tigr brush pulled on cat hairs and fur with less force than existing brushes, and was easier to clean. Such a brush could also be used to spread medicines deep into a cat’s fur or onto its skin, without the usual distressing practice of having to shave the animal first.

 

 

This article was originally published in The Economist. Read the original article.

Happy Thanksgiving! You’re about to enjoy one of the most wonderful meals of the year with family and friends. And you’re probably looking forward to a plate full of food that you, or someone you care about, spent a lot of time preparing.

Or maybe they ordered it from a caterer. That’s fine, we don’t judge.

As you give thanks for the bounty of this meal and the company you share it with, spend some time thinking about some of the scientific facts that made your meal possible. Biology. Chemistry. Physics. It’s all there on your plate.

Here are some things we’ve learned about your Thanksgiving meal. If all else fails, these facts might make for nice conversation starters with that step-cousin you only see once a year.


Turkeys were first domesticated in Mexico 1,500 or so years ago, earlier than previously thought.CreditCaitlin Ochs for The New York Times

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Turkeys were first domesticated in Mexico 1,500 or so years ago, earlier than previously thought.CreditCaitlin Ochs for The New York Times

While turkeys share a name with the country at the crossroads of Europe and the Middle East, they originated in the Americas. And people have been raising them for food and other reasons longer than we previously knew.

In 2016, scientists published new research showing that the Zapotec people living in what is now Mexico kept whole turkey eggs in their households as long ago as 400 to 500 A.D., using them for ritualistic purposes. The discovery pushed back the earliest known domestication of turkeys by 100 to 200 years.

“It’s the earliest solid evidence of domesticated turkey in southern Mexico that we have to date,” said Gary Feinman, an archaeologist from the Field Museum in Chicago, in an interview last year. Learn more about the origins of turkeys.

There are many different ways to make good stuffing.CreditKarsten Moran for The New York Times

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There are many different ways to make good stuffing.CreditKarsten Moran for The New York Times

Is it safe to cook stuffing inside your turkey? It’s possible, according to the Agricultural Department, but it’s not without risk. Some years back, a chemist named Robert L. Wolke explained why this was a physics problem:

A turkey is shaped physically like a big round ball, and when you’re roasting it the heat has to come in from the outside. That makes the inner parts of the turkey the last to become hot enough to kill dangerous bacteria; the U.S.D.A. recommends at least 165 degrees.

But by the time the inner thighs get to that temperature, the breast is overcooked. And if the bird is stuffed, the stuffing may never get that hot, and at lower temperatures stuffing is a wonderful growth medium for bacteria.

There are a lot of other good ways to make stuffing, or dressing; perhaps you should try one. Read more of Dr. Wolke’s interview.

Beets get their red color from a different compound than cranberries or other red fruits and vegetables.CreditKarsten Moran for The New York Times

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Beets get their red color from a different compound than cranberries or other red fruits and vegetables.CreditKarsten Moran for The New York Times

You’re probably enjoying some cranberry sauce with your turkey. Perhaps you’re eating roasted beets, too. They’re both red, but the chemical processes that give them their hues are completely unrelated.

Cranberries are made red by pigments called anthocyanins. These compounds are a common source of red coloration in the plant kingdom, from fall foliage to raspberries, apples and cherries.

But beets have something different going on.

Their brilliant reds result from substances called betalains. Scientists recently reported that in their evolutionary history, beets figured out how to harness a surplus of an amino acid called tyrosine. This is the same substance that helps opium poppies produce their narcotic effect. But while most plants switch off the process that yields tyrosine, the beet keeps it going until it becomes such a beautiful shade of red.

Get the full story on the chemistry that makes beets so red.

Brussels sprouts, the most cunning of Thanksgiving vegetables.CreditKarsten Moran for The New York Times

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Brussels sprouts, the most cunning of Thanksgiving vegetables.CreditKarsten Moran for The New York Times

Hopefully you’re eating something green, too. Perhaps it’s a side of brussels sprouts. They may be the craftiest thing on your plate.

Scientists found that when a brussels sprout plant detects eggs laid on its surface by a type of butterfly, it responds by manufacturing a chemical. That chemical sends a signal to parasitic wasps, sort of like a last-minute invitation to a Thanksgiving meal. The wasps lay their own eggs, which eat the growing butterflies, and the brussels sprouts are saved.

Not that we’re saying that digging into those delicious green orbs will attract wasps. Enjoy!

Here’s an overview about that and other surprising things that plants can do.

The pumpkins that fill your pie, and their cousins like squash and cucumbers, share a melon-like fruit as a common ancestor.CreditAndrew Scrivani for The New York Times

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The pumpkins that fill your pie, and their cousins like squash and cucumbers, share a melon-like fruit as a common ancestor.CreditAndrew Scrivani for The New York Times

You shouldn’t? You must. Here’s a nice slice of pumpkin pie. We baked it ourselves.

Instead of the whipped topping, we’ll offer you this fact: your dessert is the product of an evolutionary quirk that transpired some 100 million years ago.

Pumpkins, along with their cucurbitaceae family members like squash, watermelons and cucumbers, were born when the genome of a melon-like fruit duplicated itself. As we explained a couple of months ago in this article, this act of duplication set off a course of adaptations to environmental changes. Millions of years later, the descendants of that fruit ended up in a can that was pried open, poured in a pie crust and baked with love so you’d have something delicious to finish your meal.

There’s still some left. We’ll wrap up a slice for you to take home.

Roaming turkeys in San Rafael, Calif., earlier this month.CreditBill Disbrow/SF Gate, via Associated Press

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Roaming turkeys in San Rafael, Calif., earlier this month.CreditBill Disbrow/SF Gate, via Associated Press

Now that you’ve finished the meal, it’s time to take up one of our most important Thanksgiving traditions: blaming the tryptophan for your drowsiness.

Blame something else.

Tryptophan is one amino acid among many in turkey, and in combination with the others, its soporific effects are constrained.

The real source of your fluttering eyelids? Too many yams. Too many mashed potatoes. Too many brussels sprouts. Too many biscuits. That second slice of pie. Find the full details explaining why tryptophan is not to blame in this quick article.

Better ask for a cup of coffee before you get in the car and go through the woods and over the river to get home.

 

This article was originally published in The New York Times.  Read the original article.