New recipes

Scientists Design DNA Test to Predict Best Steaks Ever

Scientists Design DNA Test to Predict Best Steaks Ever

A team of French (of course) researchers have created a DNA chip that can analyze specific genes in meats to rate the quality

High-tech science may slowly be making its way into our restaurant kitchens and bars, with centrifuges and liquid nitrogen, and it looks like DNA testing might be the next wave.

Science Daily reports that the meat industry may just get a dose of DNA tests to determine the quality of beef you can buy on store shelves. A team of French researchers, led by Jean-François Hocquette at the Herbivore Research Unit of the National Agronomic Research Institute, have sifted through to find more than 3,000 genes that somehow impace a meat's texture, flavor, and juiciness. "These genes belong to different families: those which regulate fat, connective tissue, and protein contents of muscles, respectively," Hocquette said.

After finding these genes, the researchers developed a DNA chip that can analyze the activity of the genes in beef samples, meaning almost any type of beef will get a taste rating. To test, they had a panel taste test the same beef samples and give a score.

When comparing the gene test and the taste test, the researchers found that better gene scores meant better taste scores. In fact, the study reports in the journal Biomed Central Veterinary Research, some of the genes accounted for up to 40 percent for the difference in tenderness in samples. So perhaps better tasting meat has to do with both animal-raising technique as well as heritage? Explains a lot about Kobe beef, then.


Live for ever: Scientists say they’ll soon extend life ‘well beyond 120’

I n Palo Alto in the heart of Silicon Valley, hedge fund manager Joon Yun is doing a back-of-the-envelope calculation. According to US social security data, he says, the probability of a 25-year-old dying before their 26th birthday is 0.1%. If we could keep that risk constant throughout life instead of it rising due to age-related disease, the average person would – statistically speaking – live 1,000 years. Yun finds the prospect tantalising and even believable. Late last year he launched a $1m prize challenging scientists to “hack the code of life” and push human lifespan past its apparent maximum of about 120 years (the longest known/confirmed lifespan was 122 years).

Yun believes it is possible to “solve ageing” and get people to live, healthily, more or less indefinitely. His Palo Alto Longevity Prize, which 15 scientific teams have so far entered, will be awarded in the first instance for restoring vitality and extending lifespan in mice by 50%. But Yun has deep pockets and expects to put up more money for progressively greater feats. He says this is a moral rather than personal quest. Our lives and society are troubled by growing numbers of loved ones lost to age-related disease and suffering extended periods of decrepitude, which is costing economies. Yun has an impressive list of nearly 50 advisers, including scientists from some of America’s top universities.

Yun’s quest – a modern version of the age old dream of tapping the fountain of youth – is emblematic of the current enthusiasm to disrupt death sweeping Silicon Valley. Billionaires and companies are bullish about what they can achieve. In September 2013 Google announced the creation of Calico, short for the California Life Company. Its mission is to reverse engineer the biology that controls lifespan and “devise interventions that enable people to lead longer and healthier lives”. Though much mystery surrounds the new biotech company, it seems to be looking in part to develop age-defying drugs. In April 2014 it recruited Cynthia Kenyon, a scientist acclaimed for work that included genetically engineering roundworms to live up to six times longer than normal, and who has spoken of dreaming of applying her discoveries to people. “Calico has the money to do almost anything it wants,” says Tom Johnson, an earlier pioneer of the field now at the University of Colorado who was the first to find a genetic effect on longevity in a worm.

In March 2014, pioneering American biologist and technologist Craig Venter – along with the tech entrepreneur founder of the X Prize Foundation, Peter Diamandis – announced a new company called Human Longevity Inc. It isn’t aimed at developing anti-ageing drugs or competing with Calico, says Venter. But it plans to create a giant database of 1 million human genome sequences by 2020, including from supercentenarians. Venter says that data should shed important new light on what makes for a longer, healthier life, and expects others working on life extension to use his database. “Our approach can help Calico immensely and if their approach is successful it can help me live longer,” explains Venter. “We hope to be the reference centre at the middle of everything.”

In an office not far from Google’s headquarters in Mountain View, with a beard reaching almost to his navel, Aubrey de Grey is enjoying the new buzz about defeating ageing. For more than a decade, he has been on a crusade to inspire the world to embark on a scientific quest to eliminate ageing and extend healthy lifespan indefinitely (he is on the Palo Alto Longevity Prize board). It is a difficult job because he considers the world to be in a “pro-ageing trance”, happy to accept that ageing is unavoidable, when the reality is that it’s simply a “medical problem” that science can solve. Just as a vintage car can be kept in good condition indefinitely with periodic preventative maintenance, so there is no reason why, in principle, the same can’t be true of the human body, thinks de Grey. We are, after all, biological machines, he says.

His claims about the possibilities (he has said the first person who will live to 1,000 years is probably already alive), and some unconventional and unproven ideas about the science behind ageing, have long made de Grey unpopular with mainstream academics studying ageing. But the appearance of Calico and others suggests the world might be coming around to his side, he says. “There is an increasing number of people realising that the concept of anti-ageing medicine that actually works is going to be the biggest industry that ever existed by some huge margin and that it just might be foreseeable.”

Since 2009, de Grey has been chief scientific officer at his own charity, the Strategies for Engineered Negligible Senescence (Sens) Research Foundation. Including an annual contribution (about $600,000 a year) from Peter Thiel, a billionaire Silicon Valley venture capitalist, and money from his own inheritance, he funds about $5m of research annually. Some is done in-house, the rest sponsored at outside institutions. (Even his critics say he funds some good science.)

Aubrey de Grey is chief scientific officer of his own charity, the Strategies for Engineered Negligible Senescence (Sens) Research Foundation. He funds about $5m of research annually. Photograph: Tim E White/Rex

De Grey isn’t the only one who sees a new flowering of anti-ageing research. “Radical life extension isn’t consigned to the realm of cranks and science fiction writers any more,” says David Masci, a researcher at the Pew Research Centre, who recently wrote a report on the topic looking at the scientific and ethical dimensions of radical life extension. “Serious people are doing research in this area and serious thinkers are thinking about this .”

Although funding pledges have been low compared to early hopes, billionaires – not just from the technology industry – have long supported research into the biology of ageing. Yet it has mostly been aimed at extending “healthspan”, the years in which you are free of frailty or disease, rather than lifespan, although an obvious effect is that it would also be extended (healthy people after all live longer).

“If a consequence of increasing health is that life is extended, that’s a good thing, but the most important part is keeping people healthy as long as possible,” says Kevin Lee, a director of the Ellison Medical Foundation, founded in 1997 by tech billionaire Larry Ellison, and which has been the field’s largest private funder, spending $45m annually. (The Paul F Glenn Foundation for Medical Research is another.) Whereas much biomedical research concentrates on trying to cure individual diseases, say cancer, scientists in this small field hunt something larger. They investigate the details of the ageing process with a view to finding ways to prevent it at its root, thereby fending off the whole slew of diseases that come along with ageing. Life expectancy has risen in developed countries from about 47 in 1900 to about 80 today, largely due to advances in curing childhood diseases. But those longer lives come with their share of misery. Age-related chronic diseases such as heart disease, cancer, stroke and Alzheimer’s are more prevalent than ever.

The standard medical approach – curing one disease at a time – only makes that worse, says Jay Olshansky, a sociologist at the University of Chicago School of Public Health who runs a project called the Longevity Dividend Initiative, which makes the case for funding ageing research to increase healthspan on health and economic grounds. “I would like to see a cure for heart disease or cancer,” he says. “But it would lead to a dramatic escalation in the prevalence of Alzheimer’s disease.”

American biologist and technologist Craig Venter whose company Human Longevity Inc plans to create a database of a million human genome sequences by 2020. Photograph: Mike Blake/Reuters

By tackling ageing at the root they could be dealt with as one, reducing frailty and disability by lowering all age-related disease risks simultaneously, says Olshansky. Evidence is now building that this bolder, age-delaying approach could work. Scientists have already successfully intervened in ageing in a variety of animal species and researchers say there is reason to believe it could be achieved in people. “We have really turned a corner,” says Brian Kennedy, director of the Buck Institute for Research on Ageing, adding that five years ago the scientific consensus was that ageing research was interesting but unlikely to lead to anything practical. “We’re now at the point where it’s easy to extend the lifespan of a mouse. That’s not the question any more, it’s can we do this in humans? And I don’t see any reason why we can’t,” says David Sinclair, a researcher based at Harvard.

Reason for optimism comes after several different approaches have yielded promising results. Some existing drugs, such as the diabetes drug metformin, have serendipitously turned out to display age-defying effects, for example. Several drugs are in development that mimic the mechanisms that cause lab animals fed carefully calorie-restricted diets to live longer. Others copy the effects of genes that occur in long-lived people. One drug already in clinical trials is rapamycin, which is normally used to aid organ transplants and treat rare cancers. It has been shown to extend the life of mice by 25%, the greatest achieved so far with a drug, and protect them against diseases of ageing including cancer and neurodegeneration.

A recent clinical trial by Novartis, in healthy elderly volunteers in Australia and New Zealand, found a variant of the drug enhanced their response to flu vaccine by 20% – our immunity to flu being something that declines with old age.

“[This was] the first [trial] to take a drug suspected to slow ageing, and examine whether it slows or reverses a property of ageing in older, healthy individuals,” says Kennedy. Other drugs set to be tested in humans are compounds inspired by resveratrol, a compound found in red wine. Some scientists believe it is behind the “French paradox” that French people have a low incidence of heart disease despite eating comparatively rich diets.

In 2003, Sinclair published evidence that high doses of resveratrol extend the healthy lives of yeast cells. After Sirtris, a company co-founded by Sinclair, showed that resveratrol-inspired compounds had favourable effects in mice, it was bought by drug giant GlaxoSmithKline for $720m in 2008. Although development has proved more complicated than first thought, GSK is planning a large clinical trial this year, says Sinclair. He is now working on another drug that has a different way of activating the same pathway.

One of the more unusual approaches being tested is using blood from the young to reinvigorate the old. The idea was borne out in experiments which showed blood plasma from young mice restored mental capabilities of old mice. A human trial under way is testing whether Alzhemier’s patients who receive blood transfusions from young people experience a similar effect. Tony Wyss-Coray, a researcher at Stanford leading the work, says that if it works he hopes to isolate factors in the blood that drive the effect and then try to make a drug that does a similar thing. (Since publishing his work in mice, many “healthy, very rich people” have contacted Wyss-Coray wondering if it might help them live longer.)

James Kirkland, a researcher who studies ageing at the Mayo Clinic, says he knows of about 20 drugs now – more than six of which had been written up in scientific journals – that extended the lifespan or healthspan of mice. The aim is to begin tests in humans, but clinical studies of ageing are difficult because of the length of our lives, though there are ways around this such as testing the drugs against single conditions in elderly patients and looking for signs of improvements in other conditions at the same time. Quite what the first drug will be, and what it will do, is unclear. Ideally, you might take a single pill that would delay ageing in every part of your body. But Kennedy notes that in mice treated with rapamycin, some age-related effects, such as cataracts, don’t slow down. “I don’t know any one drug is going to do everything,” he says. As to when you might begin treatment, Kennedy imagines that in future you could start treatment sometime between the age of 40 and 50 “because it keeps you healthy 10 years longer”.

With treatments at such an early stage, guesses as to when they might arrive or how far they will stretch human longevity can only be that. Many researchers refuse to speculate. But Kirkland says the informal ambition in his field is to increase healthspan by two to three years in the next decade or more. (The EU has an official goal of adding two years to healthspan by 2020). Beyond that, what effects these drugs might have on extending our healthy lives is even harder to predict. A recent report by UK Human Longevity Panel, a body of scientists convened by insurer Legal and General, based on interviews with leading figures in the field, said: “There was disagreement about how far the maximum lifespan could increase, with some experts believing that there was a maximum threshold that could not be stretched much more than the current 120 years or so, and others believing that there was no limit.”

Nir Barzilai, director of the Institute for Ageing Research at the Albert Einstein College of Medicine, is one of the pessimists. “Based on the biology that we know today, somewhere between 100 and 120 there is a roof in play and I challenge if we can get beyond it.” Venter is one of the optimists. “I don’t see any absolute biological limit on human age,” he says, arguing that cellular immortality – in effect running the clock backwards – should be possible. “We can expect biological processes to eventually get rid of years. Whether this will happen this century or not, I can’t tell you”. Such ideas are just speculation for now. But John Troyer, who studies death and technology at the Centre for Death and Society at the University of Bath, says we need to take them seriously. “You want to think about it now before you are in the middle of an enormous mess.”

What happens if we all live to 100, 110, 120 or beyond? Society will start to look very different. “People working and living longer might make it more difficult for a new generation to get into the labour force or find houses,” says Troyer. And, with ageing delayed, how many children are we talking about as being a normal family? “There is a very strong likelihood there would be an impact on things like family structures.” A 2003 American president’s Council on Bioethics report looked at some of these issues suggesting there may be repercussions for individual psychology, too.

One of the “virtues of mortality” it pointed out is that it may instill a desire to make each day count. Would knowing you had longer to live decrease your willingness to make the most of life? De Grey acknowledges potential practical challenges but cheerily says society would adapt, for example by having fewer children, and with people able to decide when to end their lives. There are pressing questions too about who would benefit if and when these interventions become available. Will it just be the super rich or will market incentives – who wouldn’t want it? – push costs down and make treatment affordable?

Will Britain’s NHS or health insurers in other countries pay for drugs that extend peoples lives? The medical cost of caring for people in their twilight years would fall if they remained healthier longer, but delayed ageing will also mean more people draw pensions and state benefits. But advocates say these challenges don’t negate the moral imperative. If the period of healthy life can be extended, then doing so is the humanitarian thing to do, says Nick Bostrom, director of Oxford’s Future of Humanity Institute. “There seems to be no moral argument not to,” he says. Troyer agrees but asks whether living longer does necessarily mean you will be healthier – what does “healthy” or “healthier” mean in this context? he asks.

The far future aside, there are challenges for the new tech entrants. Calico may get too side-tracked by basic research, worries de Grey Venter’s approach may take years to bear fruit because of issues about data gathering, thinks Barzilai while the money on offer from the Palo Alto prize is a paltry sum for the demanded outcome and potential societal impact, says Johnson. Still, history reminds us, even if they don’t succeed, we may still benefit.

Aviator Charles Lindbergh tried to cheat death by devising ways to replace human organs with machines. He didn’t succeed, but one of his contraptions did develop into the heart-lung machine so crucial for open-heart surgery. In the quest to defeat ageing, even the fruits of failure may be bountiful.


Discovering the Structure of DNA

The molecule that is the basis for heredity, DNA, contains the patterns for constructing proteins in the body, including the various enzymes. A new understanding of heredity and hereditary disease was possible once it was determined that DNA consists of two chains twisted around each other, or double helixes, of alternating phosphate and sugar groups, and that the two chains are held together by hydrogen bonds between pairs of organic bases—adenine (A) with thymine (T), and guanine (G) with cytosine (C). Modern biotechnology also has its basis in the structural knowledge of DNA—in this case the scientist’s ability to modify the DNA of host cells that will then produce a desired product, for example, insulin.

The background for the work of the four scientists was formed by several scientific breakthroughs: the progress made by X-ray crystallographers in studying organic macromolecules the growing evidence supplied by geneticists that it was DNA, not protein, in chromosomes that was responsible for heredity Erwin Chargaff’s experimental finding that there are equal numbers of A and T bases and of G and C bases in DNA and Linus Pauling’s discovery that the molecules of some proteins have helical shapes—arrived at through the use of atomic models and a keen knowledge of the possible disposition of various atoms.


Treating Disease

Scientists are developing gene therapies - treatments involving genome editing - to prevent and treat diseases in humans. Genome editing tools have the potential to help treat diseases with a genomic basis, like cystic fibrosis and diabetes. There are two different categories of gene therapies: germline therapy and somatic therapy. Germline therapies change DNA in reproductive cells (like sperm and eggs). Changes to the DNA of reproductive cells are passed down from generation to generation. Somatic therapies, on the other hand, target non-reproductive cells, and changes made in these cells affect only the person who receives the gene therapy.

In 2015, scientists successfully used somatic gene therapy when a one-year old in the United Kingdom named Layla received a gene editing treatment to help her fight leukemia, a type of cancer. These scientists did not use CRISPR to treat Layla, and instead used another genome editing technology called TALENs. Doctors tried many treatments before this, but none of them seemed to work, so scientists received special permission to treat Layla using gene therapy. This therapy saved Layla's life. However, treatments like the one that Layla received are still experimental because the scientific community and policymakers still have to address technical barriers and ethical concerns surrounding genome editing.

Technical barriers

Even though CRISPR improved upon older genome editing technologies, it is not perfect. For example, sometimes genome editing tools cut in the wrong spot. Scientists are not yet sure how these errors might affect patients. Assessing the safety of gene therapies and improving upon genome editing technologies are critical steps to ensure that this technology is ready for use in patients.

Ethical concerns

Scientists and all of us should carefully consider the many ethical concerns that can emerge with genome editing, including safety. First and foremost, genome editing must be safe before it is used to treat patients. Some other ethical questions that scientists and society must consider are:

  1. Is it okay to use gene therapy on an embryo when it is impossible to get permission from the embryo for treatment? Is getting permission from the parents enough?
  2. What if gene therapies are too expensive and only wealthy people can access and afford them? That could worsen existing health inequalities between the rich and poor.
  3. Will some people use genome editing for traits not important for health, such as athletic ability or height? Is that okay?
  4. Should scientists ever be able to edit germline cells? Edits in the germline would be passed down through generations.

Most people agree that scientists should not edit the genomes of germline cells at this time because the safety and Scientific communities across the world are approaching germline therapy research with caution because edits to a germline cell would be passed down through generations. Many countries and organizations have strict regulations to prevent germline editing for this reason. The NIH, for example, does not fund research to edit human embryos.

Scientists across the world held a conference to talk about these and similar ethical issues at the International Summit on Human Gene Editing.

Scientists are developing gene therapies - treatments involving genome editing - to prevent and treat diseases in humans. Genome editing tools have the potential to help treat diseases with a genomic basis, like cystic fibrosis and diabetes. There are two different categories of gene therapies: germline therapy and somatic therapy. Germline therapies change DNA in reproductive cells (like sperm and eggs). Changes to the DNA of reproductive cells are passed down from generation to generation. Somatic therapies, on the other hand, target non-reproductive cells, and changes made in these cells affect only the person who receives the gene therapy.

In 2015, scientists successfully used somatic gene therapy when a one-year old in the United Kingdom named Layla received a gene editing treatment to help her fight leukemia, a type of cancer. These scientists did not use CRISPR to treat Layla, and instead used another genome editing technology called TALENs. Doctors tried many treatments before this, but none of them seemed to work, so scientists received special permission to treat Layla using gene therapy. This therapy saved Layla's life. However, treatments like the one that Layla received are still experimental because the scientific community and policymakers still have to address technical barriers and ethical concerns surrounding genome editing.

Technical barriers

Even though CRISPR improved upon older genome editing technologies, it is not perfect. For example, sometimes genome editing tools cut in the wrong spot. Scientists are not yet sure how these errors might affect patients. Assessing the safety of gene therapies and improving upon genome editing technologies are critical steps to ensure that this technology is ready for use in patients.

Ethical concerns

Scientists and all of us should carefully consider the many ethical concerns that can emerge with genome editing, including safety. First and foremost, genome editing must be safe before it is used to treat patients. Some other ethical questions that scientists and society must consider are:

  1. Is it okay to use gene therapy on an embryo when it is impossible to get permission from the embryo for treatment? Is getting permission from the parents enough?
  2. What if gene therapies are too expensive and only wealthy people can access and afford them? That could worsen existing health inequalities between the rich and poor.
  3. Will some people use genome editing for traits not important for health, such as athletic ability or height? Is that okay?
  4. Should scientists ever be able to edit germline cells? Edits in the germline would be passed down through generations.

Most people agree that scientists should not edit the genomes of germline cells at this time because the safety and Scientific communities across the world are approaching germline therapy research with caution because edits to a germline cell would be passed down through generations. Many countries and organizations have strict regulations to prevent germline editing for this reason. The NIH, for example, does not fund research to edit human embryos.

Scientists across the world held a conference to talk about these and similar ethical issues at the International Summit on Human Gene Editing.


The 13 Best Cast Iron Skillets For All Types Of Cooking

This story is a part of Forbes Shopping's 2020 Gift Guide. For more holiday shopping ideas, check out the Forbes Shopping Gifting Hub.

While it can be a bit intimidating to novice cooks, cast iron is often the go-to material for many professional chefs—and for a good reason. Not only is cast iron one of the best cookware materials for heat retention and distribution, but it’s also unbelievably durable, lasting for generations if cared for properly. Whether you’re searing meat or baking cake, the best cast iron skillets deliver consistent and reliable results.

As you cook with your skillet, the metal will develop a natural patina often referred to as “seasoning.” This is essentially just numerous layers of oil that have been baked onto the metal, and it will protect the skillet from rust and create a naturally nonstick surface that makes cooking eggs or sticky sauces a breeze. (Just be sure to go gentle on your cast iron skillet when cleaning—you want to keep the seasoning intact, so steer clear of harsh soaps and abrasive brushes.)

There are a number of standard sizes of cast iron skillet to pick from. Eight or 10-inch skillets are often best for everyday use, as they can easily fit two pieces of protein or a serving of vegetables. Those with larger households may need to size up to a 12- or 14-inch skillet—just make sure your stovetop can accommodate the larger cookware. You’ll also want to consider the depth of your pan, as a skillet with shallow walls isn’t ideal for cooking sauces.

As you shop, you’ll likely encounter the term “enameled cast iron,” which means the metal has been coated with a durable non-porous glaze. Unlike traditional cast iron, enameled cast iron is nonstick right out of the box—no need to build up seasoning—and you can clean it more vigorously without worrying about damage. For these reasons, it’s often a better choice for beginners or anyone who likes lower maintenance pots and pans.

Whether you’re new to cast iron or are looking to grow your collection, here are some of the best cast iron skillets across the board. From the best budget pick to the perfect pan for beginners, any one of them deserves a spot in your kitchen.


Not bot, not beast: Scientists create first ever living, programmable organism

Nanobots are tiny robots that carry out specific tasks. In medicine, they can be used for targeted drug delivery. Credit: shutterstock

A remarkable combination of artificial intelligence (AI) and biology has produced the world's first "living robots".

This week, a research team of roboticists and scientists published their recipe for making a new lifeform called xenobots from stem cells. The term "xeno" comes from the frog cells (Xenopus laevis) used to make them.

One of the researchers described the creation as "neither a traditional robot nor a known species of animal", but a "new class of artifact: a living, programmable organism".

Xenobots are less than 1mm long and made of 500-1000 living cells. They have various simple shapes, including some with squat "legs". They can propel themselves in linear or circular directions, join together to act collectively, and move small objects. Using their own cellular energy, they can live up to 10 days.

While these "reconfigurable biomachines" could vastly improve human, animal, and environmental health, they raise legal and ethical concerns.

To make xenobots, the research team used a supercomputer to test thousands of random designs of simple living things that could perform certain tasks.

The computer was programmed with an AI "evolutionary algorithm" to predict which organisms would likely display useful tasks, such as moving towards a target.

After the selection of the most promising designs, the scientists attempted to replicate the virtual models with frog skin or heart cells, which were manually joined using microsurgery tools. The heart cells in these bespoke assemblies contract and relax, giving the organisms motion.

The creation of xenobots is groundbreaking.

Despite being described as "programmable living robots", they are actually completely organic and made of living tissue. The term "robot" has been used because xenobots can be configured into different forms and shapes, and "programmed" to target certain objects—which they then unwittingly seek.

They can also repair themselves after being damaged.

Possible applications

Xenobots may have great value.

Some speculate they could be used to clean our polluted oceans by collecting microplastics.

Similarly, they may be used to enter confined or dangerous areas to scavenge toxins or radioactive materials.

Xenobots designed with carefully shaped "pouches" might be able to carry drugs into human bodies.

Future versions may be built from a patient's own cells to repair tissue or target cancers. Being biodegradable, xenobots would have an edge on technologies made of plastic or metal.

Further development of biological "robots" could accelerate our understanding of living and robotic systems. Life is incredibly complex, so manipulating living things could reveal some of life's mysteries—and improve our use of AI.

Legal and ethical questions

Conversely, xenobots raise legal and ethical concerns. In the same way they could help target cancers, they could also be used to hijack life functions for malevolent purposes.

Some argue artificially making living things is unnatural, hubristic, or involves "playing God".

A more compelling concern is that of unintended or malicious use, as we have seen with technologies in fields including nuclear physics, chemistry, biology and AI.

For instance, xenobots might be used for hostile biological purposes prohibited under international law.

More advanced future xenobots, especially ones that live longer and reproduce, could potentially "malfunction" and go rogue, and out-compete other species.

For complex tasks, xenobots may need sensory and nervous systems, possibly resulting in their sentience. A sentient programmed organism would raise additional ethical questions. Last year, the revival of a disembodied pig brain elicited concerns about different species' suffering.

The xenobot's creators have rightly acknowledged the need for discussion around the ethics of their creation.

The 2018 scandal over using CRISPR (which allows the introduction of genes into an organism) may provide an instructive lesson here. While the experiment's goal was to reduce the susceptibility of twin baby girls to HIV-AIDS, associated risks caused ethical dismay. The scientist in question is in prison.

When CRISPR became widely available, some experts called for a moratorium on heritable genome editing. Others argued the benefits outweighed the risks.

While each new technology should be considered impartially and based on its merits, giving life to xenobots raises certain significant questions:

  1. Should xenobots have biological kill-switches in case they go rogue?
  2. Who should decide who can access and control them?
  3. What if "homemade" xenobots become possible? Should there be a moratorium until regulatory frameworks are established? How much regulation is required?

Lessons learned in the past from advances in other areas of science could help manage future risks, while reaping the possible benefits.

Long road here, long road ahead

The creation of xenobots had various biological and robotic precedents. Genetic engineering has created genetically modified mice that become fluorescent in UV light.

Designer microbes can produce drugs and food ingredients that may eventually replace animal agriculture.

In 2012, scientists created an artificial jellyfish called a "medusoid" from rat cells.

Robotics is also flourishing.

Robots can incorporate living matter, which we witnessed when engineers and biologists created a sting-ray robot powered by light-activated cells.

In the coming years, we are sure to see more creations like xenobots that evoke both wonder and due concern. And when we do, it is important we remain both open-minded and critical.

This article is republished from The Conversation under a Creative Commons license. Read the original article.


Scientists quash idea of single 'gay gene'

A vast new study has quashed the idea that a single “gay gene” exists, scientists say, instead finding homosexual behaviour is influenced by a multitude of genetic variants which each have a tiny effect.

The researchers compare the situation to factors determining a person’s height, in which multiple genetic and environmental factors play roles.

“[This study] highlights both the importance of the genetics as well as the complexity of the genetics, but genetics is not [the] whole story,” said Dr Benjamin Neale, co-author of the study from the Broad Institute in the US.

Writing in the journal Science, an international team of researchers report how they drew on existing genetic databases to conduct the largest study yet into genetics and same-sex sexual behaviour.

In the first part of the study, they looked at data from about 500,000 individuals collected as part of the UK Biobank project: about 4% of men and nearly 3% of women said they had ever had a same-sex sexual experience. The team stress that they did not focus on identity or orientation, and did not include transgender individuals.

By looking at sexual behaviour and relatedness of individuals, they estimated that about a third of the variation in same-sex behaviour is explained by genetics. That, they say, chimes with previous twin studies that put the figure at about 30% to 50%.

Dr Brendan Zietsch, co-author of the research from the University of Queensland in Australia, said that does not mean the rest is due to upbringing or culture. “For example, it is thought that non-genetic factors before birth, such as the hormonal environment in the womb, also play an important role,” he told the Guardian.

The team then looked at which genetic variants might be behind the link, using data from more than 400,000 participants in the UK Biobank project and more than 68,000 individuals whose data was collected by the company 23andMe.

Researchers found five genetic variants – tiny differences in DNA – that showed a clear link to same-sex sexual behaviour, two in both men and women, two found only in men and one found only in women. The team believe one, found only in men, might be involved in sex hormone regulation, not least because it is linked to male-pattern balding.

Even taken together, though, these five genetic variants explain less than 1% of the variation in same-sex behaviour among participants – suggesting many other variants are involved, each playing a very small role.

Neale stressed that the scale of the influence of non-genetic factors, complexities of sexual behaviour, and difficulties in precisely measuring the size of any variant’s effects, means it is not possible to use genetic information to predict whether an individual will have same-sex partners.

The study provides a number of insights, including that there is overlap between genetic predisposition to same-sex sexual behaviour and traits such as openness to experience, as well as predisposition to mental health problems.

“One possibility is that stigma associated with same-sex sexual behaviour causes or exacerbates mental health issues. This could create a genetic correlation,” said Zeitsch.

The authors also say their findings call into question the idea that sexuality exists on a single scale.

“[There] seem to be genes associated with opposite-sex attraction and other genes associated with same-sex attraction, and these are not related,” added Zeitsch. “These results suggest we shouldn’t be measuring sexual preference on a single continuum from straight to gay, but rather two separate dimensions: attraction to the same sex and attraction to the opposite sex.”

However, the study has limitations including that it is based mainly on people of European ancestry, while the age range of participants does not fully reflect that of the wider population. It also relied on self-reported behaviour.

The idea that genetics might play a role in same-sex attraction was propelled into the spotlight in 1993 when Dean Hamer, a scientist at the US National Cancer Institute, and his team found links between DNA markers on the X chromosome and male sexual orientation.

The findings caused considerable controversy, with the media dubbing the discovery the “gay gene”.


The secret DNA behind bestsellers

Your program can identify, from scanning 20,000 books, ones which made the New York Times bestseller lists with 80% accuracy, and one of your key discoveries was that the topics covered in a novel – marriage, work, technology – are more important than its genre in terms of predicting its success. Why?

JA: If you look at a bestseller list, you might think it was very diverse in genre – a Stephen King alongside a Jojo Moyes. But certain topics were strong indicators of a bestseller, regardless of genre. “Human closeness” came out on top. This doesn’t mean romance – it could be talking with someone you are intimate with or shopping with a parent. It may be to do with pacing – when Dan Brown knows he has to slow his pace down a little bit and let the characters reflect before a big chase scene in the Vatican, his characters talk it out. John Grisham does it perfectly because in all the legal machinations and suspense and back stabbing, there are always scenes where a lawyer gets a bottle of red wine and a Chinese takeaway and sits on the couch with his female counterpart and they chew the cud for a bit. It is almost the opposite of a formulaic how-to make a boy meet a girl, make them fall out.

MJ: You could have a book all about human closeness – but that is too much. What we found in bestsellers was that there was a sweet spot, of a couple of topics, each taking up 30% of the book.

JA: When I worked at Penguin UK, I found that manuscripts by new authors were too ambitious, like a painter who can’t settle on one colour and uses the whole paintbox. We found that having a couple of key topics, and then sprinkling a few smaller ones throughout the rest of the book was perfect. If you look at Danielle Steel or John Grisham, they use the same three topics as their signature then pepper it with other details. Jodi Picoult is an example of an author who has found her sweet spot. She writes “commercial fiction”, and she has her own niche, her own brand. You know what you’ll get with Picoult.

‘She has her own niche, her own brand. You know what you’ll get with Jodi Picoult.’ Photograph: David Levenson/Getty Images

A lot of the authors you identified are series writers, like Grisham: Patricia Cornwell, James Patterson, Lee Child. Should debut writers plan a series?

MJ: In our tests we ensured that when we were testing a particular book, there were no others by the same author available to the machine so it wouldn’t bias against someone who had lots, such as Patterson. But so many serialised books came through in our top 100 list, which signals that is what people like reading.

JA: Series are a very good way to establish your name.

You look at ‘The Girl’ trend in publishing – The Girl with the Dragon Tattoo, The Girl on the Train, Gone Girl. Should writers avoid buying into that?

JA: No, the girl thing still has legs. When I was working in publishing and The Girl with the Dragon Tattoo hit, there were all these acquisitions meetings that focused on finding the secret that we could repeat. Publishers bought thrillers by Scandinavian men. Hundreds came on the market and only one of them got very big: Jo Nesbø. Scandinavian male crime writers were not the right focus – look at Larsson’s plot lines and themes instead.

MJ: I would warn against trying to be a copycat writer. Yes, there is a current fascination with feminine noir but if you don’t have a feminine noir book in you, I don’t think you’re going to manufacture one by piecing together a recipe from topic choices.

Is plot more important than style?

MJ: No. If your style is no good, no one will read it.

JA: Look at Fifty Shades of Grey – some readers complain about the style, but others only notice how effective it is as a page-turner. I don’t think it is EL James’s will to be a stylist, but she’s not making any mistakes either. We found that long sentences are rare in bestsellers – James Joyce might get away with it, but a newbie probably won’t. Same with superfluous adjectives. Exclamation marks don’t go down well. You don’t need all the punctuation on your keyboard. Let the language do the work.

‘long sentences are rare in bestsellers – James Joyce might get away with it, but a newbie probably won’t.’ Photograph: Suki Dhanda/The Observer

You developed a graph of The Da Vinci Code and Fifty Shades of Grey that shows that they are almost exactly matched in terms of fast and slow moments in their pacing.

MJ: Yes we noticed super-bestsellers have symmetrical pacing, and other books that are bestsellers didn’t always have this. It seems there is a marked correlation between this plotting and what we would call a page-turner.

JA: If you think of a plot like a musical beat, James and Brown were the two that had a very fast, consistently even beat, almost like techno – some readers really love this, but some find the fast pace off-putting.

Your program found that bestsellers usually had sex scenes around halfway through. Why?

JA: If you read a romance novel, you get the first kiss or sex scene at a third or halfway in, which drives the plot curve that follows: will they get together? And successful erotic writers know that. But when you know the rules, break them. You could have a sex scene on page one, like a modern crime writer will have a dead body in the first line.

You identified a perfect bestseller, which was The Circle by Dave Eggers, because it was brief, had no signs of superfluous punctuation and three popular topics – technology, jobs and “human closeness”. But other books sold a lot more.

MJ: We’re not claiming it should have been the biggest book ever, but our program found it was the perfect combination. It is the Goldilocks zone – it is just right. It is not a page-turner like The Da Vinci Code, but it is not deeply meditative like Brave New World. It has a plot, but it also has big ideas.


Native American origins: When the DNA points two ways

Scientists are analyzing ancient and modern DNA to learn more about how people first colonized the Americas. Pictured here: tools discovered in 1968 at a Clovis-era burial site in western Montana, alongside remains of a boy who died more than 12,000 years ago, known as Anzick-1. The child’s DNA was used as a basis for comparison in two new genetics studies released on Tuesday.

This week, two teams of scientists released reports detailing the origins of Native American peoples. Both groups looked at ancient and modern DNA to attempt to learn more about the movements of populations from Asia into the New World, and about how groups mixed once they got here. Both discovered a hint that some Native Americans in South America share ancestry with native peoples in Australia and Melanesia.

But the two groups came to different conclusions when it came to how that DNA with ties to Oceania made its way into the Native American genome.

In a wide-ranging paper in the journal Science, University of Copenhagen Centre for GeoGenetics Director Eske Willerslev and coauthors studied genomes from ancient and modern people in the Americas and Asia. They concluded that migrations into the New World had to have occurred in a single wave from Siberia, timed no earlier than 23,000 years ago. They also calculated that any genes shared with Australo-Melanesian peoples must have been contributed through relatively recent population mixing.

In the meantime, Harvard Medical School geneticist David Reich and colleagues, focusing more closely on the Australo-Melanesian genes in a study published in Nature, came to a different conclusion: that the DNA had to have arrived in the Americas very long ago and that founding migrations occurred in more than one wave.

“It was crazy and unexpected and very weird and we spent the last year and a half trying to understand it,” Reich said on Monday. But “it’s inconsistent to a single founding population. People in Amazonia have ancestry from two divergent sources. we think this is a real observation.”

David Meltzer, an archaeologist at Southern Methodist University in Dallas and a coauthor of the Science paper, said that researchers in his field had been wrestling with the early history of the Americas for centuries -- debating when the first settlers arrived here, whether there were pulses of migrations, and so on.

But where archaeologists are very good at dating physical artifacts and using them to figure out that people had to have settled in the Americas by a certain time (around 15,000 years ago), they can’t suss out other details of population history that geneticists are uniquely well-equipped to explore, thanks to recent advances in DNA sequencing and analytics.

The Science paper attempted to pin down some of those details. The team calculated that Native American populations diverged from Asian groups 23,000 years ago, said co-author Yun Song, a computational biologist at UC Berkeley -- making that the earliest time they could have migrated south.

They also estimated that North American and South American populations split between 12,000 and 15,000 years ago, and that there was “evidence of subsequent migrations after the additional wave” -- including the DNA shared with native peoples in Australia and Micronesia.

Song did not think the Science study and Nature studies were necessarily inconsistent, and wondered if one possible scenario in the Nature paper -- “a long drawn out period of gene flow from a structured . source,” amounted to the same thing as his team’s notion of an initial wave with subsequent migrations.

“Maybe the confusion is semantics,” he said.

John Hawks, a professor of anthropology at the University of Wisconsin-Madison who was not involved in either study, agreed that both teams’ data showed a lot of similarities. He was inclined to put more stock in the Science study, he said, because it depended more heavily on ancient DNA sequences in drawing its conclusions. He added that more sampling in the future might uncover evidence of a second ancient migration, however.

Reich, who said his team conducted multiple checks to confirm its hypothesis that there were two founding groups, expected scientists ultimately to confirm the existence of the ancestral group he called “population Y” -- after Ypykuera, the Tupi word for “ancestor.”

“There’s a track record of predicting ghost populations,” he said. “People will find this population Y.”

Meltzer, a self-professed “rocks guy”, said the thought excited him. Scientists don’t have DNA samples from Native Americans dating from around 12,000 to 24,000 years ago. But should they secure a sample, they might be able to sequence it and search for hints of the Australo-Melanesian DNA.

“If we find that [genetic] signal, OK -- there’s our answer,” he said.

For more on science and health, follow me on Twitter: @LATerynbrown


Engineering the Perfect Baby

If anyone had devised a way to create a genetically engineered baby, I figured George Church would know about it.

At his labyrinthine laboratory on the Harvard Medical School campus, you can find researchers giving E. Coli a novel genetic code never seen in nature. Around another bend, others are carrying out a plan to use DNA engineering to resurrect the woolly mammoth. His lab, Church likes to say, is the center of a new technological genesis—one in which man rebuilds creation to suit himself.

When I visited the lab last June, Church proposed that I speak to a young postdoctoral scientist named Luhan Yang. A Harvard recruit from Beijing, she’d been a key player in developing a powerful new technology for editing DNA, called CRISPR-Cas9. With Church, Yang had founded a small biotechnology company to engineer the genomes of pigs and cattle, sliding in beneficial genes and editing away bad ones.

As I listened to Yang, I waited for a chance to ask my real questions: Can any of this be done to human beings? Can we improve the human gene pool? The position of much of mainstream science has been that such meddling would be unsafe, irresponsible, and even impossible. But Yang didn’t hesitate. Yes, of course, she said. In fact, the Harvard laboratory had a project under way to determine how it could be achieved. She flipped open her laptop to a PowerPoint slide titled “Germline Editing Meeting.”

Here it was: a technical proposal to alter human heredity. “Germ line” is biologists’ jargon for the egg and sperm, which combine to form an embryo. By editing the DNA of these cells or the embryo itself, it could be possible to correct disease genes and pass those genetic fixes on to future generations. Such a technology could be used to rid families of scourges like cystic fibrosis. It might also be possible to install genes that offer lifelong protection against infection, Alzheimer’s, and, Yang told me, maybe the effects of aging. Such history-making medical advances could be as important to this century as vaccines were to the last.

That’s the promise. The fear is that germ-line engineering is a path toward a dystopia of superpeople and designer babies for those who can afford it. Want a child with blue eyes and blond hair? Why not design a highly intelligent group of people who could be tomorrow’s leaders and scientists?

Just three years after its initial development, CRISPR technology is already widely used by biologists as a kind of search-and-replace tool to alter DNA, even down to the level of a single letter. It’s so precise that it’s expected to turn into a promising new approach for gene therapy in people with devastating illnesses. The idea is that physicians could directly correct a faulty gene, say, in the blood cells of a patient with sickle-cell anemia (see “Genome Surgery”). But that kind of gene therapy wouldn’t affect germ cells, and the changes in the DNA wouldn’t get passed to future generations.

In contrast, the genetic changes created by germ-line engineering would be passed on, and that’s what has made the idea seem so objectionable. So far, caution and ethical concerns have had the upper hand. A dozen countries, not including the United States, have banned germ-line engineering, and scientific societies have unanimously concluded that it would be too risky to do. The European Union’s convention on human rights and biomedicine says tampering with the gene pool would be a crime against “human dignity” and human rights.

But all these declarations were made before it was actually feasible to precisely engineer the germ line. Now, with CRISPR, it is possible.

The experiment Yang described, though not simple, would go like this: The researchers hoped to obtain, from a hospital in New York, the ovaries of a woman undergoing surgery for ovarian cancer caused by a mutation in a gene called BRCA1. Working with another Harvard laboratory, that of antiaging specialist David Sinclair, they would extract immature egg cells that could be coaxed to grow and divide in the laboratory. Yang would use CRISPR in these cells to correct the DNA of the BRCA1 gene. They would try to create a viable egg without the genetic error that caused the woman’s cancer.

Yang would later tell me that she dropped out of the project not long after we spoke. Yet it remained difficult to know if the experiment she described was occurring, canceled, or awaiting publication. Sinclair said that a collaboration between the two labs was ongoing, but then, like several other scientists whom I’d asked about germ-line engineering, he stopped replying to my e-mails.

Regardless of the fate of that particular experiment, human germ-line engineering has become a burgeoning research concept. At least three other centers in the United States are working on it, as are scientists in China, in the U.K., and at a biotechnology company called OvaScience, based in Cambridge, Massachusetts, that boasts some of the world’s leading fertility doctors on its advisory board.

All this means that germ-line engineering is much further along than anyone imagined.

The objective of these groups is to demonstrate that it’s possible to produce children free of specific genes involved in inherited disease. If it’s possible to correct the DNA in a woman’s egg, or a man’s sperm, those cells could be used in an in vitro fertilization (IVF) clinic to produce an embryo and then a child. It might also be possible to directly edit the DNA of an early-stage IVF embryo using CRISPR. Several people interviewed by MIT Technology Review said that such experiments had already been carried out in China and that results describing edited embryos were pending publication. These people, including two high-ranking specialists, didn’t wish to comment publicly because the papers are under review.

All this means that germ-line engineering is much further along than anyone imagined. “What you are talking about is a major issue for all humanity,” says Merle Berger, one of the founders of Boston IVF, a network of fertility clinics that is among the largest in the world and helps more than a thousand women get pregnant each year. “It would be the biggest thing that ever happened in our field.” Berger predicts that repairing genes involved in serious inherited diseases will win wide public acceptance but says the idea of using the technology beyond that would cause a public uproar because “everyone would want the perfect child”: people might pick and choose eye color and eventually intelligence. “These are things we talk about all the time,” he says. “But we have never had the opportunity to do it.”

Editing embryos

How easy would it be to edit a human embryo using CRISPR? Very easy, experts say. “Any scientist with molecular biology skills and knowledge of how to work with [embryos] is going to be able to do this,” says Jennifer Doudna, a biologist at the University of California, Berkeley, who in 2012 co-discovered how to use CRISPR to edit genes.

To find out how it could be done, I visited the lab of Guoping Feng, a biologist at MIT’s McGovern Institute for Brain Research, where a colony of marmoset monkeys is being established with the aim of using CRISPR to create accurate models of human brain diseases. To create the models, Feng will edit the DNA of embryos and then transfer them into female marmosets to produce live monkeys. One gene Feng hopes to alter in the animals is SHANK3. The gene is involved in how neurons communicate when it’s damaged in children, it is known to cause autism.

Feng said that before CRISPR, it was not possible to introduce precise changes into a primate’s DNA. With CRISPR, the technique should be relatively straightforward. The CRISPR system includes a gene-snipping enzyme and a guide molecule that can be programmed to target unique combinations of the DNA letters, A, G, C, and T get these ingredients into a cell and they will cut and modify the genome at the targeted sites.

But CRISPR is not perfect—and it would be a very haphazard way to edit human embryos, as Feng’s efforts to create gene-edited marmosets show. To employ the CRISPR system in the monkeys, his students simply inject the chemicals into a fertilized egg, which is known as a zygote—the stage just before it starts dividing.

Feng said the efficiency with which CRISPR can delete or disable a gene in a zygote is about 40 percent, whereas making specific edits, or swapping DNA letters, works less frequently—more like 20 percent of the time. Like a person, a monkey has two copies of most genes, one from each parent. Sometimes both copies get edited, but sometimes just one does, or neither. Only about half the embryos will lead to live births, and of those that do, many could contain a mixture of cells with edited DNA and without. If you add up the odds, you find you’d need to edit 20 embryos to get a live monkey with the version you want.

That’s not an insurmountable problem for Feng, since the MIT breeding colony will give him access to many monkey eggs and he’ll be able to generate many embryos. However, it would present obvious problems in humans. Putting the ingredients of CRISPR into a human embryo would be scientifically trivial. But it wouldn’t be practical for much just yet. This is one reason that many scientists view such an experiment (whether or not it has really occurred in China) with scorn, seeing it more as a provocative bid to grab attention than as real science. Rudolf Jaenisch, an MIT biologist who works across the street from Feng and who in the 1970s created the first gene-modified mice, calls attempts to edit human embryos “totally premature.” He says he hopes these papers will be rejected and not published. “It’s just a sensational thing that will stir things up,” says Jaenisch. “We know it’s possible, but is it of practical use? I kind of doubt it.”

For his part, Feng told me he approves of the idea of germ-line engineering. Isn’t the goal of medicine to reduce suffering? Considering the state of the technology, however, he thinks actual gene-edited humans are “10 to 20 years away.” Among other problems, CRISPR can introduce off-target effects or change bits of the genome far from where scientists had intended. Any human embryo altered with CRISPR today would carry the risk that its genome had been changed in unexpected ways. But, Feng said, such problems may eventually be ironed out, and edited people will be born. “To me, it’s possible in the long run to dramatically improve health, lower costs. It’s a kind of prevention,” he said. “It’s hard to predict the future, but correcting disease risks is definitely a possibility and should be supported. I think it will be a reality.”

Editing eggs

Elsewhere in the Boston area, scientists are exploring a different approach to engineering the germ line, one that is technically more demanding but probably more powerful. This strategy combines CRISPR with unfolding discoveries related to stem cells. Scientists at several centers, including Church’s, think they will soon be able to use stem cells to produce eggs and sperm in the laboratory. Unlike embryos, stem cells can be grown and multiplied. Thus they could offer a vastly improved way to create edited offspring with CRISPR. The recipe goes like this: First, edit the genes of the stem cells. Second, turn them into an egg or sperm. Third, produce an offspring.

Some investors got an early view of the technique on December 17, at the Benjamin Hotel in Manhattan, during commercial presentations by OvaScience. The company, which was founded four years ago, aims to commercialize the scientific work of David Sinclair, who is based at Harvard, and Jonathan Tilly, an expert on egg stem cells and the chairman of the biology department at Northeastern University (see “10 Emerging Technologies: Egg Stem Cells,” May/June 2012). It made the presentations as part of a successful effort to raise $132 million in new capital during January.

During the meeting, Sinclair, a velvet-voiced Australian whom Time last year named one of the “100 Most Influential People in the World,” took the podium and provided Wall Street with a peek at what he called “truly world-changing” developments. People would look back at this moment in time and recognize it as a new chapter in “how humans control their bodies,” he said, because it would let parents determine “when and how they have children and how healthy those children are actually going to be.”

The company has not perfected its stem-cell technology—it has not reported that the eggs it grows in the lab are viable—but Sinclair predicted that functional eggs were “a when, and not an if.” Once the technology works, he said, infertile women will be able to produce hundreds of eggs, and maybe hundreds of embryos. Using DNA sequencing to analyze their genes, they could pick among them for the healthiest ones.

Genetically improved children may also be possible. Sinclair told the investors that he was trying to alter the DNA of these egg stem cells using gene editing, work he later told me he was doing with Church’s lab. “We think the new technologies with genome editing will allow it to be used on individuals who aren’t just interested in using IVF to have children but have healthier children as well, if there is a genetic disease in their family,” Sinclair told the investors. He gave the example of Huntington’s disease, caused by a gene that will trigger a fatal brain condition even in someone who inherits only one copy. Sinclair said gene editing could be used to remove the lethal gene defect from an egg cell. His goal, and that of OvaScience, is to “correct those mutations before we generate your child,” he said. “It’s still experimental, but there is no reason to expect it won’t be possible in coming years.”

Sinclair spoke to me briefly on the phone while he was navigating in a cab across a snowed-in Boston, but later he referred my questions to OvaScience. When I contacted OvaScience, Cara Mayfield, a spokeswoman, said its executives could not comment because of their travel schedules but confirmed that the company was working on treating inherited disorders with gene editing. What was surprising to me was that OvaScience’s research in “crossing the germ line,” as critics of human engineering sometimes put it, has generated scarcely any notice. In December of 2013, OvaScience even announced it was putting $1.5 million into a joint venture with a synthetic biology company called Intrexon, whose R&D objectives include gene-editing eggs to “prevent the propagation” of human disease “in future generations.”

When I reached Tilly at Northeastern, he laughed when I told him what I was calling about. “It’s going to be a hot-button issue,” he said. Tilly also said his lab was trying to edit egg stem cells with CRISPR “right now” to rid them of an inherited genetic disease that he didn’t want to name. Tilly emphasized that there are “two pieces of the puzzle”—one being stem cells and the other gene editing. The ability to create large numbers of egg stem cells is critical, because only with sizable quantities can genetic changes be stably introduced using CRISPR, characterized using DNA sequencing, and carefully studied to check for mistakes before producing an egg.

Tilly predicted that the whole end-to-end technology—cells to stem cells, stem cells to sperm or egg and then to offspring—would end up being worked out first in animals, such as cattle, either by his lab or by companies such as eGenesis, the spinoff from the Church lab working on livestock. But he isn’t sure what the next step should be with edited human eggs. You wouldn’t want to fertilize one “willy nilly,” he said. You’d be making a potential human being. And doing that would raise questions he’s not sure he can answer. He told me, “‘Can you do it?’ is one thing. If you can, then the most important questions come up. ‘Would you do it? Why would you want to do it? What is the purpose?’ As scientists we want to know if it’s feasible, but then we get into the bigger questions, and it’s not a science question—it’s a society question.”

Improving humans

If germ-line engineering becomes part of medical practice, it could lead to transformative changes in human well-being, with consequences to people’s life span, identity, and economic output. But it would create ethical dilemmas and social challenges. What if these improvements were available only to the richest societies, or the richest people? An in vitro fertility procedure costs about $20,000 in the United States. Add genetic testing and egg donation or a surrogate mother, and the price soars toward $100,000.

Others believe the idea is dubious because it’s not medically necessary. Hank Greely, a lawyer and ethicist at Stanford University, says proponents “can’t really say what it is good for.” The problem, says Greely, is that it’s already possible to test the DNA of IVF embryos and pick healthy ones, a process that adds about $4,000 to the cost of a fertility procedure. A man with Huntington’s, for instance, could have his sperm used to fertilize a dozen of his partner’s eggs. Half those embryos would not have the Huntington’s gene, and those could be used to begin a pregnancy.

Indeed, some people are adamant that germ-line engineering is being pushed ahead with “false arguments.” That is the view of Edward Lanphier, CEO of Sangamo Biosciences, a California biotechnology company that is using another gene-editing technique, called zinc fingers nucleases, to try to treat HIV in adults by altering their blood cells. “We’ve looked at [germ-line engineering] for a disease rationale, and there is none,” he says. “You can do it. But there really isn’t a medical reason. People say, well, we don’t want children born with this, or born with that—but it’s a completely false argument and a slippery slope toward much more unacceptable uses.”

Critics cite a host of fears. Children would be the subject of experiments. Parents would be influenced by genetic advertising from IVF clinics. Germ-line engineering would encourage the spread of allegedly superior traits. And it would affect people not yet born, without their being able to agree to it. The American Medical Association, for instance, holds that germ-line engineering shouldn’t be done “at this time” because it “affects the welfare of future generations” and could cause “unpredictable and irreversible results.” But like a lot of official statements that forbid changing the genome, the AMA’s, which was last updated in 1996, predates today’s technology. “A lot of people just agreed to these statements,” says Greely. “It wasn’t hard to renounce something that you couldn’t do.”

The fear? A dystopia of superpeople and designer babies for those who can afford it.

Others predict that hard-to-oppose medical uses will be identified. A couple with several genetic diseases at once might not be able to find a suitable embryo. Treating infertility is another possibility. Some men don’t produce any sperm, a condition called azoospermia. One cause is a genetic defect in which a region of about one million to six million DNA letters is missing from the Y chromosome. It might be possible to take a skin cell from such a man, turn it into a stem cell, repair the DNA, and then make sperm, says Werner Neuhausser, a young Austrian doctor who splits his time between the Boston IVF fertility-clinic network and Harvard’s Stem Cell Institute. “That will change medicine forever, right? You could cure infertility, that is for sure,” he says.

I spoke with Church several times by telephone over the last few months, and he told me what’s driving everything is the “incredible specificity” of CRISPR. Although not all the details have been worked out, he thinks the technology could replace DNA letters essentially without side effects. He says this is what makes it “tempting to use.” Church says his laboratory is focused mostly on experiments in engineering animals. He added that his lab would not make or edit human embryos, calling such a step “not our style.”

What is Church’s style is human enhancement. And he’s been making a broad case that CRISPR can do more than eliminate disease genes. It can lead to augmentation. At meetings, some involving groups of “transhumanists” interested in next steps for human evolution, Church likes to show a slide on which he lists naturally occurring variants of around 10 genes that, when people are born with them, confer extraordinary qualities or resistance to disease. One makes your bones so hard they’ll break a surgical drill. Another drastically cuts the risk of heart attacks. And a variant of the gene for the amyloid precursor protein, or APP, was found by Icelandic researchers to protect against Alzheimer’s. People with it never get dementia and remain sharp into old age.

Church thinks CRISPR could be used to provide people with favorable versions of genes, making DNA edits that would act as vaccines against some of the most common diseases we face today. Although he told me anything “edgy” should be done only to adults who can consent, it’s obvious to him that the earlier such interventions occur, the better.

Church tends to dodge questions about genetically modified babies. The idea of improving the human species has always had “enormously bad press,” he wrote in the introduction to Regenesis, his 2012 book on synthetic biology, whose cover was a painting by Eustache Le Sueur of a bearded God creating the world. But that’s ultimately what he’s suggesting: enhancements in the form of protective genes. “An argument will be made that the ultimate prevention is that the earlier you go, the better the prevention,” he told an audience at MIT’s Media Lab last spring. “I do think it’s the ultimate preventive, if we get to the point where it’s very inexpensive, extremely safe, and very predictable.” Church, who has a less cautious side, proceeded to tell the audience that he thought changing genes “is going to get to the point where it’s like you are doing the equivalent of cosmetic surgery.”

Some thinkers have concluded that we should not pass up the chance to make improvements to our species. “The human genome is not perfect,” says John Harris, a bioethicist at Manchester University, in the U.K. “It’s ethically imperative to positively support this technology.” By some measures, U.S. public opinion is not particularly negative toward the idea. A Pew Research survey carried out last August found that 46 percent of adults approved of genetic modification of babies to reduce the risk of serious diseases.

The same survey found that 83 percent said genetic modification to make a baby smarter would be “taking medical advances too far.” But other observers say higher IQ is exactly what we should be considering. Nick Bostrom, an Oxford philosopher best known for his 2014 book Superintelligence, which raised alarms about the risks of artificial intelligence in computers, has also looked at whether humans could use reproductive technology to improve human intellect. Although the ways in which genes affect intelligence aren’t well understood and there are far too many relevant genes to permit easy engineering, such realities don’t dim speculation on the possibility of high-tech eugenics.

“The human genome is not perfect. It’s ethically imperative to positively support this technology.”

What if everyone could be a little bit smarter? Or a few people could be a lot smarter? Even a small number of “super-enhanced” individuals, Bostrom wrote in a 2013 paper, could change the world through their creativity and discoveries, and through innovations that everyone else would use. In his view, genetic enhancement is an important long-range issue like climate change or financial planning by nations, “since human problem-solving ability is a factor in every challenge we face.”

To some scientists, the explosive advance of genetics and biotech means germ-line engineering is inevitable. Of course, safety questions would be paramount. Before there’s a genetically edited baby saying “Mama,” there would have to be tests in rats, rabbits, and probably monkeys, to make sure they are normal. But ultimately, if the benefits seem to outweigh the risks, medicine would take the chance. “It was the same with IVF when it first happened,” says Neuhausser. “We never really knew if that baby was going to be healthy at 40 or 50 years. But someone had to take the plunge.”

Wine country

In January, on Saturday the 24th, around 20 scientists, ethicists, and legal experts traveled to Napa Valley, California, for a retreat among the vineyards at the Carneros Inn. They had been convened by Doudna, the Berkeley scientist who co-discovered the CRISPR system a little over two years ago. She had become aware that scientists might be thinking of crossing the germ line, and she was concerned. Now she wanted to know: could they be stopped?

“We as scientists have come to appreciate that CRISPR is incredibly powerful. But that swings both ways. We need to make sure that it’s applied carefully,” Doudna told me. “The issue is especially human germ-line editing and the appreciation that this is now a capability in everyone’s hands.”

At the meeting, along with ethicists like Greely, was Paul Berg, a Stanford biochemist and Nobel Prize winner known for having organized the Asilomar Conference, a historic 1975 forum at which biologists reached an agreement on how to safely proceed with recombinant DNA, the newly discovered method of splicing DNA into bacteria.

Should there be an Asilomar for germ-line engineering? Doudna thinks so, but the prospects for consensus seem dim. Biotechnology research is now global, involving hundreds of thousands of people. There’s no single authority that speaks for science, and no easy way to put the genie back in the bottle. Doudna told me she hoped that if American scientists agreed to a moratorium on human germ-line engineering, it might influence researchers elsewhere in the world to cease their work.

Doudna said she felt that a self-imposed pause should apply not only to making gene-edited babies but also to using CRISPR to alter human embryos, eggs, or sperm—as researchers at Harvard, Northeastern, and OvaScience are doing. “I don’t feel that those experiments are appropriate to do right now in human cells that could turn into a person,” she told me. “I feel that the research that needs to be done right now is to understand safety, efficacy, and delivery. And I think those experiments can be done in nonhuman systems. I would like to see a lot more work done before it’s done for germ-line editing. I would favor a very cautious approach.”

Not everyone agrees that germ-line engineering is such a big worry, or that experiments should be padlocked. Greely notes that in the United States, there are piles of regulations to keep lab science from morphing into a genetically modified baby anytime soon. “I would not want to use safety as an excuse for a non-safety-based ban,” says Greely, who says he pushed back against talk of a moratorium. But he also says he agreed to sign Doudna’s letter, which now reflects the consensus of the group. “Although I don’t view this as a crisis moment, I think it’s probably about time for us to have this discussion,” he says.

(After this article was published online in March, Doudna’s editorial appeared in Science (see Scientists Call for a Summit on Gene-Edited Babies.) Along with Greely, Berg, and 15 others, she called for a global moratorium on any effort to use CRISPR to generate gene-edited children until researchers could determine “what clinical applications, if any, might in the future be deemed permissible.” The group, however, endorsed basic research, including applying CRISPR to embryos. The final list of signatories included Church, although he did not attend the Napa meeting.)

As news has spread of germ-line experiments, some biotechnology companies now working on CRISPR have realized that they will have to take a stand. Nessan Bermingham is CEO of Intellia Therapeutics, a Boston startup that raised $15 million last year to develop CRISPR into gene therapy treatments for adults or children. He says germ-line engineering “is not on our commercial radar,” and he suggests that his company could use its patents to prevent anyone from commercializing it.

“The technology is in its infancy,” he says. “It is not appropriate for people to even be contemplating germ-line applications.”

Bermingham told me he never imagined he’d have to be taking a position on genetically modified babies so soon. Modifying human heredity has always been a theoretical possibility. Suddenly it’s a real one. But wasn’t the point always to understand and control our own biology—to become masters over the processes that created us?

Doudna says she is also thinking about these issues. “It cuts to the core of who we are as people, and it makes you ask if humans should be exercising that kind of power,” she told me. “There are moral and ethical issues, but one of the profound questions is just the appreciation that if germ-line editing is conducted in humans, that is changing human evolution.” One reason she feels the research should slow down is to give scientists a chance to spend more time explaining what their next steps could be.