2920. Synthetic Biology Gone Out of Control

By Emily Baumgartner, The New York Times, May 14, 2018

Keoni Gandall, in his laboratory at home in Palo Alto, Calif. He barely earned a high school diploma, he said, and was kicked out of a local science fair for reckless genetic engineering. Photo: Erin Brethauer for The New York Times. 

Earlier this year, at Body Hacking Con in Austin, Tex., a biotech executive injected himself with what he hoped would be a herpes treatment. (Verdict: No.) His company already had live-streamed a man injecting himself with a home-brewed treatment for H.I.V. (His viral load increased.)

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Keoni Gandall, in his laboratory at home in Palo Alto, Calif. He barely earned a high school diploma, he said, and was kicked out of a local science fair for reckless genetic engineering.

In a recent interview, Mr. Gandall, now 18 and a research fellow at Stanford, said he only wants to ensure open access to gene-editing technology, believing future biotech discoveries may come from the least expected minds.

But he is quick to acknowledge that the do-it-yourself genetics revolution one day may go catastrophically wrong.

“Even I would tell you, the level of DNA synthesis regulation, it simply isn’t good enough,” Mr. Gandall said. “These regulations aren’t going to work when everything is decentralized — when everybody has a DNA synthesizer on their smartphone.”

The most pressing worry is that someone somewhere will use the spreading technology to create a bioweapon.

Already a research team at the University of Alberta has recreated from scratch an extinct relative of smallpox, horsepox, by stitching together fragments of mail-order DNA in just six months for about $100,000 — without a glance from law enforcement officials.

The team purchased overlapping DNA fragments from a commercial company. Once the researchers glued the full genome together and introduced it into cells infected by another type of poxvirus, the cells began to produce infectious particles.

To some experts, the experiment nullified a decades-long debate over whether to destroy the world’s two remaining smallpox remnants — at the Centers for Disease Control and Prevention in Atlanta and at a research center in Russia — since it proved that scientists who want to experiment with the virus can now create it themselves.

The study’s publication in the journal PLOS One included an in-depth description of the methods used and — most alarming to Gregory D. Koblentz, the director of the biodefense graduate program at George Mason University — a series of new tips and tricks for bypassing roadblocks.

“Sure, we’ve known this could be possible,” Dr. Koblentz said. “We also knew North Korea could someday build a thermonuclear weapon, but we’re still horrified when they actually do it.”

Experts urged the journal to cancel publication of the article, one calling it “unwise, unjustified, and dangerous.” Even before publication, a report from a World Health Organization meeting noted that the endeavor “did not require exceptional biochemical knowledge or skills, significant funds or significant time.”

But the study’s lead researcher, David Evans, a virologist at the University of Alberta, said he had alerted several Canadian government authorities to his poxvirus venture, and none had raised an objection.

Many experts agree that it would be very difficult for amateur biologists of any stripe to design a killer virus on their own. But as more hackers trade computer code for the genetic kind, and as their skills become increasingly sophisticated, health security experts fear that the potential for abuse may be growing.

“To unleash something deadly, that could really happen any day now — today,” said Dr. George Church, a researcher at Harvard and a leading synthetic biologist. “The pragmatic people would just engineer drug-resistant anthrax or highly transmissible influenza. Some recipes are online.”

“If they’re willing to inject themselves with hormones to make their muscles bigger, you can imagine they’d be willing to test more powerful things,” he added. “Anyone who does synthetic biology should be under surveillance, and anyone who does it without a license should be suspect.”

Authorities in the United States have been hesitant to undertake actions that could squelch innovation or impinge on intellectual property. The laws that cover biotechnology have not been significantly updated in decades, forcing regulators to rely on outdated frameworks to govern new technologies.

The cobbled-together regulatory system, with multiple agencies overseeing various types of research, has left gaps that will only widen as the technologies advance.

Academic researchers undergo strict scrutiny when they seek federal funding for “dual-use research of concern”: experiments that, in theory, could be used for good or ill. But more than half of the nation’s scientific research and development is funded by nongovernmental sources.

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In 2013, a quest to create a glowing plant via genetic engineering drew almost half a million dollars through Kickstarter, the crowdfunding website.

“There really isn’t a national governance per se for those who are not federally or government funded,” said Dr. William So, a biological countermeasures specialist at the Federal Bureau of Investigation.

Instead, he said, the agency relies on biohackers themselves to sound the alarm regarding suspicious behavior.

“I do believe the F.B.I. is doing their best with what they have,” said Dr. Thomas V. Inglesby, director of the Johns Hopkins Center for Health Security in Baltimore.

“But if you really want to do this, there isn’t a whole lot stopping you.”

Underground Experimenters

The F.B.I. has befriended many white-hat biohacking labs, among them Genspace in Sunset Park, Brooklyn. Behind an inconspicuous steel door on a gritty, graffiti-lined street, biohackers-in-training — musicians, engineers, retirees — routinely gather for crash courses in genetic engineering.

Participants in “Biohacker Boot Camp” learn basic technical skills to use in homegrown genetics projects, like concocting algae that glows.

“The double helix is the most iconic image of the 20th century, perhaps rivaled only by the mushroom cloud,” the bootcamp’s leader, Michael Flanagan, said to a recent class.

Genspace’s entryway resembles a college dorm room, complete with sagging couch, microwave, mini-fridge. But the lab itself is palatial: two stories of white brick walls, industrial kitchen counters marked with dry-erase notes, shelves towering with glassware and reagents.

It’s a significant upgrade for Genspace. Daniel Grushkin, the co-founder, used to host bacterial experiments in his living room over pizza and beer.

The group later moved into a rental for creatives — roboticists, organic fashion designers, miniature-cupcake makers — and constructed a makeshift lab using old patio screen doors. It was Mr. Grushkin who reached out to the F.B.I.

“People might be calling you because we are nonscientists doing science in a busted-up old building,” he recalled telling bureau agents. “But we aren’t a meth lab, and we aren’t bioterrorists.”

Mr. Grushkin has become a trailblazer in biohacking risk management, in part because he recognizes that letting neophytes manipulate live organisms is “less like a ‘hackerspace,’ more like a pet store.”

He has posted community guidelines, forbidden infectious agents in the lab, and accepted a grant of almost $500,000 to design security practices for some four dozen similar labs across the country.

Most of them report not having heard so much as a greeting from the F.B.I. At many, the consequence for breaking safety guidelines is simply the loss of membership — leaving the perpetrator to experiment in isolation, but still among thousands of enthusiasts huddled online in Facebook groups, email listservs and Reddit pages.

Many find their inspiration in Josiah Zayner, a NASA scientist turned celebrity biohacker who straps a GoPro camera to his forehead and streams experiments on himself from his garage. He’s the man who tried to make his muscles bigger.

“This is just normal Scotch packing tape,” Mr. Zayner, chief executive of a biohacking start-up called The Odin, told his YouTube audience one summer night, muttering expletives as he stripped the top layer of skin from his forearm. “This is Day 1 of my experiment to genetically engineer myself.”

In an interview, Mr. Zayner conceded that among his biohacking followers, an accident — not a premeditated offense — was conceivable.

“I guess I can see why they don’t let the entire public have access to Ebola,” he said. “The risk is, if they’re working with Ebola and their house burns down, the Ebola could somehow get out.”

Even Mr. Zayner is apprehensive of the movement he helped begin; he plans to include live frogs in The Odin’s D.I.Y.-Crispr kits to encourage his followers to experiment on animals instead of themselves — or others.

“I have no doubt that someone is going to get hurt,” he said. “People are trying to one-up each other, and it’s moving faster than any one of us could have ever imagined — it’s almost uncontrollable. It’s scary.”

A Biological Arms Race

If nefarious biohackers were to create a biological weapon from scratch — a killer that would bounce from host to host to host, capable of reaching millions of people, unrestrained by time or distance — they would probably begin with some online shopping.

A site called Science Exchange, for example, serves as a Craigslist for DNA, a commercial ecosystem connecting almost anyone with online access and a valid credit card to companies that sell cloned DNA fragments.

Mr. Gandall, the Stanford fellow, often buys such fragments — benign ones. But the workarounds for someone with ill intent, he said, might not be hard to figure out.

Biohackers will soon be able to forgo these companies altogether with an all-in-one desktop genome printer: a device much like an inkjet printer that employs the letters AGTC — genetic base pairs — instead of the color model CMYK.

A similar device already exists for institutional labs, called BioXp 3200, which sells for about $65,000. But at-home biohackers can start with DNA Playground from Amino Labs, an Easy Bake genetic oven that costs less than an iPad, or The Odin’s Crispr gene-editing kit for $159.

Tools like these may be threatening in the wrong hands, but they also helped Mr. Gandall start a promising career.

At age 11, he picked up a virology textbook at a church book fair. Before he was old enough for a driver’s permit, he was urging his mother to shuttle him to a research job at the University of California, Irvine.

He began dressing exclusively in red polo shirts to avoid the distraction of choosing outfits. He doodled through high school — correcting biology teachers — and was kicked out of a local science fair for what was deemed reckless home-brew genetic engineering.

Mr. Gandall barely earned a high-school diploma, he said, and was rebuffed by almost every college he applied to — but later gained a bioengineering position at Stanford University.

“Pretty ironic, after they rejected me as a student,” he said.

He moved to East Palo Alto — with 14 red polo shirts — into a house with three nonbiologists, who don’t much notice that DNA is cloned in the corner of his bedroom.

His mission at Stanford is to build a body of genetic material for public use. To his fellow biohackers, it’s a noble endeavor.

To biosecurity experts, it’s tossing ammunition into trigger-happy hands.

“There are really only two things that could wipe 30 million people off of the planet: a nuclear weapon, or a biological one,” said Lawrence O. Gostin, an adviser on pandemic influenza preparedness to the World Health Organization.

“Somehow, the U.S. government fears and prepares for the former, but not remotely for the latter. It baffles me.”

2621. CRISPR Gene Editing Can Cause Hundreds of Unintended Mutations

By phys.org, May 29, 2017

CRISPR-associated protein Cas9 (white) from Staphylococcus aureus based on Protein Database ID 5AXW. Credit: Thomas Splettstoesser (Wikipedia, CC BY-SA 4.0)

As CRISPR-Cas9 starts to move into clinical trials, a new study published in Nature Methods has found that the gene-editing technology can introduce hundreds of unintended mutations into the genome.

"We feel it's critical that the scientific community consider the potential hazards of all off-target mutations caused by CRISPR, including single nucleotide mutations and mutations in non-coding regions of the genome," says co-author Stephen Tsang, MD, PhD, the Laszlo T. Bito Associate Professor of Ophthalmology and associate professor of pathology and cell biology at Columbia University Medical Center and in Columbia's Institute of Genomic Medicine and the Institute of Human Nutrition.

CRISPR-Cas9 editing technology—by virtue of its speed and unprecedented precision—has been a boon for scientists trying to understand the role of genes in disease. The technique has also raised hope for more powerful gene therapies that can delete or repair flawed genes, not just add new genes.

The first clinical trial to deploy CRISPR is now underway in China, and a U.S. trial is slated to start next year. But even though CRISPR can precisely target specific stretches of DNA, it sometimes hits other parts of the genome. Most studies that search for these off-target mutations use computer algorithms to identify areas most likely to be affected and then examine those areas for deletions and insertions.

"These predictive algorithms seem to do a good job when CRISPR is performed in cells or tissues in a dish, but whole genome sequencing has not been employed to look for all off-target effects in living animals," says co-author Alexander Bassuk, MD, PhD, professor of pediatrics at the University of Iowa.

In the new study, the researchers sequenced the entire genome of mice that had undergone CRISPR gene editing in the team's previous study and looked for all mutations, including those that only altered a single nucleotide.

The researchers determined that CRISPR had successfully corrected a gene that causes blindness, but Kellie Schaefer, a PhD student in the lab of Vinit Mahajan, MD, PhD, associate professor of ophthalmology at Stanford University, and co-author of the study, found that the genomes of two independent gene therapy recipients had sustained more than 1,500 single-nucleotide mutations and more than 100 larger deletions and insertions. None of these DNA mutations were predicted by computer algorithms that are widely used by researchers to look for off-target effects.

"Researchers who aren't using whole genome sequencing to find off-target effects may be missing potentially important mutations," Dr. Tsang says. "Even a single nucleotide change can have a huge impact.”

Dr. Bassuk says the researchers didn't notice anything obviously wrong with their animals. "We're still upbeat about CRISPR," says Dr. Mahajan. "We're physicians, and we know that every new therapy has some potential side effects—but we need to be aware of what they are.”

Researchers are currently working to improve the components of the CRISPR system—its gene-cutting enzyme and the RNA that guides the enzyme to the right gene—to increase the efficiency of editing.

"We hope our findings will encourage others to use whole-genome sequencing as a method to determine all the off-target effects of their CRISPR techniques and study different versions for the safest, most accurate editing," Dr. Tsang says.

The paper is titled, "Unexpected mutations after CRISPR-Cas9 editing in vivo." Additional authors are Kellie A. Schafer (Stanford University), Wen-Hsuan Wu (Columbia University Medical Center), and Diana G. Colgan (Iowa).

2321. Should We Synthesise a Human Genome?

By Drew Endy and Laurie Zoloth, Cosmos, May 12, 2016

At Harvard today, an invitation-only group of about 150 scientists, lawyers, and entrepreneurs, met to discuss if and how to construct from scratch an entire human genome – the heritable genetic material that in nature is transferred from parents to children.

The meeting was originally organised to focus on “deliverables and industry involvement” with the primary goal of the project being “to synthesise a complete human genome in a cell line within a period of 10 years”.

Such a synthetic genome could then be tested in a laboratory by replacing the existing genome within a human cell. All this would still be far removed from making a synthetic human.

However, the possibility of making a human cell, whose genome is realised from only digital information and raw materials, should trigger broader considerations.  

For context, total synthesis of a human genome is becoming plausible at an accelerating rate. Thanks to new production techniques developed since 2003 the cost of assembling the genetic material encoding genes, the “building blocks” of life, has decreased from $4.00 to just three cents per individual letter, or “base pair” of deoxyribonucleic acid (DNA). 

As a result, the estimated initial cost of printing the DNA fragments encoding a three billion base pair human genome has dropped from $12 billion to $90 million. 

If cost reductions continue in the way they have been, then this price would approach $100,000 within 20 years. However, such dramatic additional cost reductions might never be realised without an overwhelming demand.

Advocates of synthesising a human genome, therefore argue that some open, collaborative “grand challenge” is needed to drive development of such technologies. 

While we strongly agree that sustained improvements in DNA construction tools are essential for advancing basic biological science and improving public health we are sceptical that synthesising a human genome is an appropriate demand driver.

We recall how controversies associated with many of the earliest genome synthesis projects delivered unintended consequences. 

For example, a project that made polio virus from scratch in 2002 generated such fear that public funding for improving DNA synthesis tools was cancelled, unwittingly harming research across diverse and unrelated fields while policy makers struggled to imagine how such tools could ever be controlled.

We argue that the synthesis of less controversial and more immediately useful genomes along with greatly improved sub-genomic synthesis capacities (for example, the real-time printing of plasmids  the casettes that transfer genes between cells) should be pursued instead.

These are alternatives that would deliver broad and diverse public benefits.

Other topics on today’s agenda included changing the human genome itself.  For example, could scientists synthesise a modified human genome that is resistant to all natural viruses? 

They likely could, for purely beneficial purposes, but what if others then sought to synthesise modified viruses that overcame such resistance? Might doing so start a genome-engineering arms race? 

And, what of even greater changes that can be imagined?

In a world where human reproduction has already become a competitive marketplace, with eggs, sperm and embryos carrying a price, it is easy to make up far stranger uses of human genome synthesis capacities. 

Would it be OK, for example, to sequence and then synthesise Einstein’s genome?  If so how many Einstein genomes should be made and installed in cells, and who would get to make them? 

Taking a step back, just because something becomes possible, how should we approach determining if it is ethical to pursue?

Given that human genome synthesis is a technology that can completely redefine the core of what now joins all of humanity together as a species, we argue that discussions of making such capacities real, like today’s Harvard conference, should not take place without open and advance consideration of whether it is morally right to proceed.

When the first people at the table mostly have significant and direct material interests in proceeding, everyone, not just those in the room, risk out-of-control competition between public and private interests, ethical conflicts of interest, and temptations to manipulate human subject consent.

Pluralistic, public, and deliberative discussions are instead the best appropriate way to frame paths forward.

We note that the narrative of creation of the human is the central narrative for many religious communities.

To create a human genome from scratch would be an enormous moral gesture whose consequences should not be framed initially on the advice of lawyers and regulators alone.

The perspectives of others including self-identified theologians, philosophers, and ethicists from a variety of traditions should be sought out from the very beginning.

Critical voices representing civil society, who have long been sceptical of synthetic biology’s claims, should also be included.  

The creation of new human life is one of the last human-associated processes that has not yet been industrialised or fully commodified. It remains an act of faith, joy, and hope. 

Discussions to synthesise, for the first time, a human genome should not occur in closed rooms.   

Drew Endy is Associate Professor of Bioengineering at Stanford University.

Laurie Zoloth is a professor of medical ethics and humanities at Northwestern University, Chicago.

Related post: Synthatic Biology: Making Humans from Chemical?

2320. Synthetic Biology: Making Humans from Chemical?

By Andrew Pollack, The New York Times, May 14, 2016

Sixty trays can contain the entire human genome as 23,040 different fragments of cloned DNA. Photo: James King-Holmes/Science Source

Scientists are now contemplating the fabrication of a human genome, meaning they would use chemicals to manufacture all the DNA contained in human chromosomes.

The prospect is spurring both intrigue and concern in the life sciences community because it might be possible, such as through cloning, to use a synthetic genome to create human beings without biological parents.

While the project is still in the idea phase, and also involves efforts to improve DNA synthesis in general, it was discussed at a closed-door meeting on Tuesday at Harvard Medical School in Boston. The nearly 150 attendees were told not to contact the news media or to post on Twitter during the meeting.

Organizers said the project could have a big scientific payoff and would be a follow-up to the original Human Genome Project, which was aimed at reading the sequence of the three billion chemical letters in the DNA blueprint of human life. The new project, by contrast, would involve not reading, but rather writing the human genome — synthesizing all three billion units from chemicals.

But such an attempt would raise numerous ethical issues. Could scientists create humans with certain kinds of traits, perhaps people born and bred to be soldiers? Or might it be possible to make copies of specific people?

“Would it be O.K., for example, to sequence and then synthesize Einstein’s genome?” Drew Endy, a bioengineer at Stanford, and Laurie Zoloth, a bioethicist at Northwestern University, wrote in an essay criticizing the proposed project. “If so how many Einstein genomes should be made and installed in cells, and who would get to make them?”

Dr. Endy, though invited, said he deliberately did not attend the meeting at Harvard because it was not being opened to enough people and was not giving enough thought to the ethical implications of the work.

George Church, a professor of genetics at Harvard Medical School and an organizer of the proposed project, said there had been a misunderstanding. The project was not aimed at creating people, just cells, and would not be restricted to human genomes, he said. Rather it would aim to improve the ability to synthesize DNA in general, which could be applied to various animals, plants and microbes.

“They’re painting a picture which I don’t think represents the project,” Dr. Church said in an interview.

He said the meeting was closed to the news media, and people were asked not to tweet because the project organizers, in an attempt to be transparent, had submitted a paper to a scientific journal. They were therefore not supposed to discuss the idea publicly before publication. He and other organizers said ethical aspects have been amply discussed since the beginning.

The project was initially called HGP2: The Human Genome Synthesis Project, with HGP referring to the Human Genome Project. An invitation to the meeting at Harvard said that the primary goal “would be to synthesize a complete human genome in a cell line within a period of 10 years.”

But by the time the meeting was held, the name had been changed to “HGP-Write: Testing Large Synthetic Genomes in Cells.”

The project does not yet have funding, Dr. Church said, though various companies and foundations would be invited to contribute, and some have indicated interest. The federal government will also be asked. A spokeswoman for the National Institutes of Health declined to comment, saying the project was in too early a stage.

Besides Dr. Church, the organizers include Jef Boeke, director of the institute for systems genetics at NYU Langone Medical Center, and Andrew Hessel, a self-described futurist who works at the Bay Area software company Autodesk and who first proposed such a project in 2012.

Scientists and companies can now change the DNA in cells, for example, by adding foreign genes or changing the letters in the existing genes. This technique is routinely used to make drugs, such as insulin for diabetes, inside genetically modified cells, as well as to make genetically modified crops. And scientists are now debating the ethics of new technology that might allow genetic changes to be made in embryos.

But synthesizing a gene, or an entire genome, would provide the opportunity to make even more extensive changes in DNA.

For instance, companies are now using organisms like yeast to make complex chemicals, like flavorings and fragrances. That requires adding not just one gene to the yeast, like to make insulin, but numerous genes in order to create an entire chemical production process within the cell. With that much tinkering needed, it can be easier to synthesize the DNA from scratch.

Right now, synthesizing DNA is difficult and error-prone. Existing techniques can reliably make strands that are only about 200 base pairs long, with the base pairs being the chemical units in DNA. A single gene can be hundreds or thousands of base pairs long. To synthesize one of those, multiple 200-unit segments have to be spliced together.

But the cost and capabilities are rapidly improving. Dr. Endy of Stanford, who is a co-founder of a DNA synthesis company called Gen9, said the cost of synthesizing genes has plummeted from $4 per base pair in 2003 to 3 cents now. But even at that rate, the cost for three billion letters would be $90 million. He said if costs continued to decline at the same pace, that figure could reach $100,000 in 20 years.

J. Craig Venter, the genetic scientist, synthesized a bacterial genome consisting of about a million base pairs. The synthetic genome was inserted into a cell and took control of that cell. While his first synthetic genome was mainly a copy of an existing genome, Dr. Venter and colleagues this year synthesized a more original bacterial genome, about 500,000 base pairs long.

Dr. Boeke is leading an international consortium that is synthesizing the genome of yeast, which consists of about 12 million base pairs. The scientists are making changes, such as deleting stretches of DNA that do not have any function, in an attempt to make a more streamlined and stable genome.

But the human genome is more than 200 times as large as that of yeast and it is not clear if such a synthesis would be feasible.

Jeremy Minshull, chief executive of DNA2.0, a DNA synthesis company, questioned if the effort would be worth it.

“Our ability to understand what to build is so far behind what we can build,” said Dr. Minshull, who was invited to the meeting at Harvard but did not attend. “I just don’t think that being able to make more and more and more and cheaper and cheaper and cheaper is going to get us the understanding we need.”

Related post:
Should we synthesise a human genome?

2099. A New Era of Humanity's Dominion: Gene Editing

By Amy Harmon, The New York Times, November 26, 2015

A genetically modified salmon (on the top) and a regular one.

SIOUX CENTER, Iowa — Other than the few small luxuries afforded them, like private access to a large patch of grass, there was nothing to mark the two hornless dairy calves born last spring at a breeding facility here as early specimens in a new era of humanity’s dominion over nature.

But unlike a vast majority of their dairy brethren, these calves, both bulls, will never sprout horns. That means they will not need to undergo dehorning, routinely performed by farmers to prevent injuries and a procedure that the American Veterinary Medical Association says is “considered to be quite painful.”

Instead, when the calves were both just a single cell in a petri dish, scientists at a start-up company called Recombinetics used the headline-grabbing new tools of gene editing to swap out the smidgen of genetic code that makes dairy cattle have horns for the one that makes Angus beef cattle have none. And the tweak, copied into all of their cells through the normal machinery of DNA replication, will also be passed on to subsequent generations.

“It’s pretty cool,” said Micah Schouten, the calves’ caretaker, looking at his charges.

The uproar over the new ease and precision with which scientists can manipulate the DNA of living things has centered largely on the complicated prospect of editing human embryos. But with the federal government’s approval last week of a fast-growing salmon as the first genetically altered animal Americans can eat, a menagerie of gene-edited animals is already being raised on farms and in laboratories around the world — some designed for food, some to fight disease, some, perhaps, as pets.

Just this week, researchers reported having edited mosquitoes so that they will no longer carry the parasite that causes malaria. And the power to reshape other species, scientists and bioethicists say, raises questions that are both unique to animals and may bear on the looming prospect of fiddling with our own.

“We’re going to see a stream of edited animals coming through because it’s so easy,” said Bruce Whitelaw, a professor of animal biotechnology at the Roslin Institute at the University of Edinburgh. “It’s going to change the societal question from, ‘If we could do it, would we want it?’ to, ‘Next year we will have it; will we allow it?’ ”

Animal breeders have for centuries scoured species for desirable traits and combined them the old-fashioned way, by selective mating. But that process can take decades to achieve a particular goal, like cows that are both resistant to disease and produce a lot of milk. And until recently, genetic engineering techniques used to manipulate DNA had been so imprecise as to make them too expensive and difficult to perform in many animals.

But the new techniques, collectively called “gene editing” to reflect the relative ease of their use, have made all manner of previously impossible or impractical goals sufficiently fast and cheap for many to find worth pursuing. Using enzymes that can be directed to cut DNA at specific locations, they allow scientists to remove and replace bits of genetic code more or less on demand. “It’s like a find-replace function in the genome of these animals,” said Scott Fahrenkrug, the chief executive of Recombinetics, based in St. Paul. “It allows us to find the natural variation that exists across a species and quickly bring it under one hood.”

At Roslin, for instance, Dr. Whitelaw has changed three genes in domesticated pigs vulnerable to African swine fever, which can devastate herds, to resemble those from wild pigs that are resistant to the disease. He is now breeding them to put them to the test.

With a tool called Talens, Recombinetics says it has created gene-edited pigs that can be fattened with less food and Brazilian beef cattle that grow large muscles, yielding more meat that may also be more tender. Others are working on chickens that produce only females for egg-laying and cattle that produce only males, since females are less efficient at converting feed to muscle.

Chinese researchers have produced meatier cashmere goats that also conveniently grow longer hair for soft sweaters, miniature pigs lacking a growth gene to be sold as novelty pets and bulky beagles lacking a muscle-inhibiting gene, an edit that could make for faster dogs.

Using the most powerful of the new tools, called Crispr-Cas9, in pursuit of treatments for human disease, researchers are also altering pigs in hopes of making them grow human organs and creating “gene drives” that would ensure that the edit to make mosquitoes malaria-proof, for instance, would spread through the whole population.

An Accelerating Pace

But the rapid advent of gene-edited animals threatens to outstrip public discussion of their risks and benefits, some scientists and bioethicists have warned.

“This essay is, in essence, a plea — let’s not ignore the nonhuman part of the biosphere,” Alta Charo of the University of Wisconsin and Henry T. Greely of Stanford University cautioned in an article titled “Crispr Critters and Crispr Cracks,” to be published in The American Journal of Bioethics next month. “Not only is it much larger than the human part, but it is much more susceptible to unobserved or unfettered — but not unimportant — changes.”

The discussion of gene-edited animals in farming, in particular, will most likely be colored by the existing debate over the merits of genetically engineered food, which for decades has largely centered on corn and soybeans, altered with older technology to resist pests and tolerate herbicides. Opposition to such crops, known as genetically modified organisms, or GMOs, has prompted some retailers to decline to sell food made with them, and efforts to pass legislation to label them, even as farmers have widely embraced them and scientific organizations have said they are as safe for human health and the environment as conventional crops.

Many of the new generation of edited animals do not contain DNA from another species, a frequently cited concern among opponents of genetically engineered foods, which incorporate genes from bacteria. But some consumer advocates say it may be even more difficult to reach consensus on what, if anything, should be done to the DNA of animals.

“Animals on some level will always be more controversial,” said Greg Jaffe, director of biotechnology for the Center for Science in the Public Interest, a nonprofit consumer advocacy group. “If only because people think of them as closer to humans.”

Advocates of the technology argue that it can make farming more efficient to help feed a growing world population with less of a toll on the environment. One projection published in a leading animal breeding journal, Genetics Selection Evolution, suggests that genome-editing could significantly increase the efficiency the livestock industry is able to achieve through conventional breeding within the same time period.

Today’s chickens, for instance, produce nearly 80 percent more meat for the same amount of feed as the chickens of the 1950s; if chicken breeders had had access to genome technology over that time, said John Hickey, a quantitative geneticist and a co-author of the paper, farmers would have been able to achieve that increase and also be able to grow chickens on half the land.

Others say the technology could benefit human health. The National Science Foundation is underwriting an effort to create dairy cattle that can resist a parasite that causes sleeping sickness in sub-Saharan Africa, a blight often treated with an antimicrobial drug that ended up making its way into the meat consumed by humans.

Several projects underway to edit genetic resistance to a variety of diseases in livestock could theoretically reduce the overuse of antibiotics, which has made it harder to treat human bacterial infections. With funds from the United States Department of Agriculture, Bhanu Telugu, a University of Maryland researcher, is trying to design pigs so they can no longer serve as a reservoir for the flu virus. He argues for genome editing on behalf of animal health, too. “If we know we can eliminate the disease and we don’t, it is in my mind animal cruelty,” he said.

Fallout in the Food Chain

Still, some consumer advocates urge caution in applying techniques that are still so new to animals that will be consumed as food. Gene-editing tools are known to sometimes make changes to genes other than their intended targets, raising flags about how the changes might affect an animal’s health or the composition of milk or meat.

“You are reducing the universe of potential risks by moving into these techniques,” said Doug Gurian-Sherman, a senior scientist at the Center for Food Safety, a consumer advocacy organization that has been at the forefront of opposition to genetically engineered plants and animals. “But that is not to say we should not still proceed with great caution.”

And some animal rights advocates say gene-editing is simply a means to prop up an industry that causes animals to suffer.

“Even if they can point to good intentions, it’s just exacerbating the problem,” said David Byer, a spokesman for People for the Ethical Treatment of Animals. The organization, which has urged the dairy industry to stop the practice of dehorning cattle, does not support gene-editing as a solution.

“People should stop consuming dairy or meat or eggs, not further manipulate animals by playing with their DNA,” Mr. Byer added.

The Food and Drug Administration has not said how or whether it will regulate the gene-edited animals to come. But even with the government’s stamp of approval, biotechnology advocates know that farmers are unlikely to embrace technology if they fear consumers will reject it.

And it has not helped the popularity of genetically engineered crops that their chief benefits so far — easier control of weeds and pests for corn and soybean farmers — are not terribly compelling to the eating public.

That is one reason Recombinetics has begun to show off its hornless calves.

Dehorning, which involves burning off horn-buds to stop the flow of blood to the horn tissue, has already garnered a degree of popular concern. Videos of the burning procedure carried out on Holsteins, the black-and-white breed largely responsible for the nation’s milk supply, and circulated by animal rights groups, draw long strings of critical comments.

“We know there’s a negative public perception of dehorning, and it’s certainly not a fun chore for the farmers,” said Lindsey Worden, the executive director for genetics at the Holstein Association.

A small fraction of Holsteins are naturally hornless, and several companies, including General Mills, Dannon and Walmart, have encouraged their dairy suppliers to increase their population through conventional breeding. Farmers have made some headway, with the population of hornless Holsteins climbing to about 4 percent last year from 3 percent in 2013.

But it is slow going. That is why several dairy breeders say they are keeping tabs on Recombinetics’ two hornless calves, which have just been shipped to the University of California, Davis, to be monitored for their health. There, in a few months, their sperm will be harvested, each with edited DNA, which will be used to create a new generation of hornless cattle.

Whether they will become commonplace or remain curiosities may depend largely on how the public comes to view gene editing and its various applications.

“Sometimes you can have nice benefits for animals and farmers and society but still have controversy among consumers,” said Jamie Jonker, vice president for sustainability and scientific affairs at the National Milk Producers Federation. “I think dairy farmers are going to want to see how this is interpreted by the general public.”