Tag Archives: CRISPR (clustered regularly interspaced short palindromic repeats)

Could CRISPR (clustered regularly interspaced short palindromic repeats) be weaponized?

On the occasion of an American team’s recent publication of research where they edited the germline (embryos), I produced a three-part series about CRISPR (clustered regularly interspaced short palindromic repeats), sometimes referred to as CRISPR/Cas9, (links offered at end of this post).

Somewhere in my series, there’s a quote about how CRISPR could be used as a ‘weapon of mass destruction’ and it seems this has been a hot topic for the last year or so as James Revill, research fellow at the University of Sussex, references in his August 31, 2017 essay on theconversation.com (h/t phys.org August 31, 2017 news item), Note: Links have been removed,

The gene editing technique CRISPR has been in the limelight after scientists reported they had used it to safely remove disease in human embryos for the first time. This follows a “CRISPR craze” over the last couple of years, with the number of academic publications on the topic growing steadily.

There are good reasons for the widespread attention to CRISPR. The technique allows scientists to “cut and paste” DNA more easily than in the past. It is being applied to a number of different peaceful areas, ranging from cancer therapies to the control of disease carrying insects.

Some of these applications – such as the engineering of mosquitoes to resist the parasite that causes malaria – effectively involve tinkering with ecosystems. CRISPR has therefore generated a number of ethical and safety concerns. Some also worry that applications being explored by defence organisations that involve “responsible innovation in gene editing” may send worrying signals to other states.

Concerns are also mounting that gene editing could be used in the development of biological weapons. In 2016, Bill Gates remarked that “the next epidemic could originate on the computer screen of a terrorist intent on using genetic engineering to create a synthetic version of the smallpox virus”. More recently, in July 2017, John Sotos, of Intel Health & Life Sciences, stated that gene editing research could “open up the potential for bioweapons of unimaginable destructive potential”.

An annual worldwide threat assessment report of the US intelligence community in February 2016 argued that the broad availability and low cost of the basic ingredients of technologies like CRISPR makes it particularly concerning.

A Feb. 11, 2016 news item on sciencemagazine.org offers a précis of some of the reactions while a February 9, 2016 article by Antonio Regalado for the Massachusetts Institute of Technology’s MIT Technology Review delves into the matter more deeply,

Genome editing is a weapon of mass destruction.

That’s according to James Clapper, [former] U.S. director of national intelligence, who on Tuesday, in the annual worldwide threat assessment report of the U.S. intelligence community, added gene editing to a list of threats posed by “weapons of mass destruction and proliferation.”

Gene editing refers to several novel ways to alter the DNA inside living cells. The most popular method, CRISPR, has been revolutionizing scientific research, leading to novel animals and crops, and is likely to power a new generation of gene treatments for serious diseases (see “Everything You Need to Know About CRISPR’s Monster Year”).

It is gene editing’s relative ease of use that worries the U.S. intelligence community, according to the assessment. “Given the broad distribution, low cost, and accelerated pace of development of this dual-use technology, its deliberate or unintentional misuse might lead to far-reaching economic and national security implications,” the report said.

The choice by the U.S. spy chief to call out gene editing as a potential weapon of mass destruction, or WMD, surprised some experts. It was the only biotechnology appearing in a tally of six more conventional threats, like North Korea’s suspected nuclear detonation on January 6 [2016], Syria’s undeclared chemical weapons, and new Russian cruise missiles that might violate an international treaty.

The report is an unclassified version of the “collective insights” of the Central Intelligence Agency, the National Security Agency, and half a dozen other U.S. spy and fact-gathering operations.

Although the report doesn’t mention CRISPR by name, Clapper clearly had the newest and the most versatile of the gene-editing systems in mind. The CRISPR technique’s low cost and relative ease of use—the basic ingredients can be bought online for $60—seems to have spooked intelligence agencies.

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However, one has to be careful with the hype surrounding new technologies and, at present, the security implications of CRISPR are probably modest. There are easier, cruder methods of creating terror. CRISPR would only get aspiring biological terrorists so far. Other steps, such as growing and disseminating biological weapons agents, would typically be required for it to become an effective weapon. This would require additional skills and places CRISPR-based biological weapons beyond the reach of most terrorist groups. At least for the time being.

A July 5, 2016 opinion piece by Malcolm Dando for Nature argues for greater safeguards,

In Geneva next month [August 2016], officials will discuss updates to the global treaty that outlaws the use of biological weapons. The 1972 Biological Weapons Convention (BWC) was the first agreement to ban an entire class of weapons, and it remains a crucial instrument to stop scientific research on viruses, bacteria and toxins from being diverted into military programmes.

The BWC is the best route to ensure that nations take the biological-weapons threat seriously. Most countries have struggled to develop and introduce strong and effective national programmes — witness the difficulty the United States had in agreeing what oversight system should be applied to gain-of-function experiments that created more- dangerous lab-grown versions of common pathogens.

As scientific work advances — the CRISPR gene-editing system has been flagged as the latest example of possible dual-use technology — this treaty needs to be regularly updated. This is especially important because it has no formal verification system. Proposals for declarations, monitoring visits and inspections were vetoed by the United States in 2001, on the grounds that such verification threatened national security and confidential business information.

Even so, issues such as the possible dual-use threat from gene-editing systems will not be easily resolved. But we have to try. Without the involvement of the BWC, codes of conduct and oversight systems set up at national level are unlikely to be effective. The stakes are high, and after years of fumbling, we need strong international action to monitor and assess the threats from the new age of biological techniques.

Revill notes the latest BWC agreement and suggests future directions,

This convention is imperfect and lacks a way to ensure that states are compliant. Moreover, it has not been adequately “tended to” by its member states recently, with the last major meeting unable to agree a further programme of work. Yet it remains the cornerstone of an international regime against the hostile use of biology. All 178 state parties declared in December of 2016 their continued determination “to exclude completely the possibility of the use of (biological) weapons, and their conviction that such use would be repugnant to the conscience of humankind”.

These states therefore need to address the hostile potential of CRISPR. Moreover, they need to do so collectively. Unilateral national measures, such as reasonable biological security procedures, are important. However, preventing the hostile exploitation of CRISPR is not something that can be achieved by any single state acting alone.

As such, when states party to the convention meet later this year, it will be important to agree to a more systematic and regular review of science and technology. Such reviews can help with identifying and managing the security risks of technologies such as CRISPR, as well as allowing an international exchange of information on some of the potential benefits of such technologies.

Most states supported the principle of enhanced reviews of science and technology under the convention at the last major meeting. But they now need to seize the opportunity and agree on the practicalities of such reviews in order to prevent the convention being left behind by developments in science and technology.

Experts (military, intelligence, medical, etc.) are not the only ones concerned about CRISPR according to a February 11, 2016 article by Sharon Begley for statnews.com (Note: A link has been removed),

Most Americans oppose using powerful new technology to alter the genes of unborn babies, according to a new poll — even to prevent serious inherited diseases.

They expressed the strongest disapproval for editing genes to create “designer babies” with enhanced intelligence or looks.

But the poll, conducted by STAT and Harvard T.H. Chan School of Public Health, found that people have mixed, and apparently not firm, views on emerging genetic techniques. US adults are almost evenly split on whether the federal government should fund research on editing genes before birth to keep children from developing diseases such as cystic fibrosis or Huntington’s disease.

“They’re not against scientists trying to improve [genome-editing] technologies,” said Robert Blendon, professor of health policy and political analysis at Harvard’s Chan School, perhaps because they recognize that one day there might be a compelling reason to use such technologies. An unexpected event, such as scientists “eliminating a terrible disease” that a child would have otherwise inherited, “could change people’s views in the years ahead,” Blendon said.

But for now, he added, “people are concerned about editing the genes of those who are yet unborn.”

A majority, however, wants government regulators to approve gene therapy to treat diseases in children and adults.

The STAT-Harvard poll comes as scientists and policy makers confront the ethical, social, and legal implications of these revolutionary tools for changing DNA. Thanks to a technique called CRISPR-Cas9, scientists can easily, and with increasing precision, modify genes through the genetic analog of a computer’s “find and replace” function.

I find it surprising that there’s resistance to removing diseases found in the germline (embryos). When they were doing public consultations on nanotechnology, the one area where people tended to be quite open to research was health and medicine. Where food was concerned however, people had far more concerns.

If you’re interested in the STAT-Harvard poll, you can find it here. As for James Revill, he has written a more substantive version of this essay as a paper, which is available here.

On a semi-related note, I found STAT (statnews.com) to be a quite interesting and accessibly written online health science journal. Here’s more from the About Us page (Note: A link has been removed),

What’s STAT all about?
STAT is a national publication focused on finding and telling compelling stories about health, medicine, and scientific discovery. We produce daily news, investigative articles, and narrative projects in addition to multimedia features. We tell our stories from the places that matter to our readers — research labs, hospitals, executive suites, and political campaigns.

Why did you call it STAT?
In medical parlance, “stat” means important and urgent, and that’s what we’re all about — quickly and smartly delivering good stories. Read more about the origins of our name here.

Who’s behind the new publication?
STAT is produced by Boston Globe Media. Our headquarters is located in Boston but we have bureaus in Washington, New York, Cleveland, Atlanta, San Francisco, and Los Angeles. It was started by John Henry, the owner of Boston Globe Media and the principal owner of the Boston Red Sox. Rick Berke is executive editor.

So is STAT part of The Boston Globe?
They’re distinct properties but the two share content and complement one another.

Is it free?
Much of STAT is free. We also offer STAT Plus, a premium subscription plan that includes exclusive reporting about the pharmaceutical and biotech industries as well as other benefits. Learn more about it here.

Who’s working for STAT?
Some of the best-sourced science, health, and biotech journalists in the country, as well as motion graphics artists and data visualization specialists. Our team includes talented writers, editors, and producers capable of the kind of explanatory journalism that complicated science issues sometimes demand.

Who’s your audience?
You. Even if you don’t work in science, have never stepped foot in a hospital, or hated high school biology, we’ve got something for you. And for the lab scientists, health professionals, business leaders, and policy makers, we think you’ll find coverage here that interests you, too. The world of health, science, and medicine is booming and yielding fascinating stories. We explore how they affect us all.

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As promised, here are the links to my three-part series on CRISPR,

Part 1 opens the series with a basic description of CRISPR and the germline research that occasioned the series along with some of the other (non-weapon) ethical issues and patent disputes that are arising from this new technology. CRISPR and editing the germline in the US (part 1 of 3): In the beginning

Part 2 covers three critical responses to the reporting and between them describe the technology in more detail and the possibility of ‘designer babies’.  CRISPR and editing the germline in the US (part 2 of 3): ‘designer babies’?

Part 3 is all about public discussion or, rather, the lack of and need for according to a couple of social scientists. Informally, there is some discussion via pop culture and Joelle Renstrom notes although she is focused on the larger issues touched on by the television series, Orphan Black and as I touch on in my final comments. CRISPR and editing the germline in the US (part 3 of 3): public discussions and pop culture

Finally, I hope to stumble across studies from other countries about how they are responding to the possibilities presented by CRISPR/Cas9 so that I can offer a more global perspective than this largely US perspective. At the very least, it would be interesting to find it if there differences.

CRISPR corn to come to market in 2020

It seems most of the recent excitement around CRISPR/CAS9 (clustered regularly interspaced short palindromic repeats) has focused on germline editing, specifically human embryos. Most people don’t realize that the first ‘CRISPR’ product is slated to enter the US market in 2020. A June 14, 2017 American Chemical Society news release (also on EurekAlert) provides a preview,

The gene-editing technique known as CRISPR/Cas9 made a huge splash in the news when it was initially announced. But the first commercial product, expected around 2020, could make it to the market without much fanfare: It’s a waxy corn destined to contribute to paper glue and food thickeners. The cover story of Chemical & Engineering News (C&EN), the weekly newsmagazine of the American Chemical Society, explores what else is in the works.

Melody M. Bomgardner, a senior editor at C&EN [Chemical & Engineering News], notes that compared to traditional biotechnology, CRISPR allows scientists to add and remove specific genes from organisms with greater speed, precision and oftentimes, at a lower cost. Among other things, it could potentially lead to higher quality cotton, non-browning mushrooms, drought-resistant corn and — finally — tasty, grocery store tomatoes.

Some hurdles remain, however, before more CRISPR products become available. Regulators are assessing how they should approach crops modified with the technique, which often (though not always) splices genes into a plant from within the species rather than introducing a foreign gene. And scientists still don’t understand all the genes in any given crop, much less know which ones might be good candidates for editing. Luckily, researchers can use CRISPR to find out.

Melody M. Bomgardner’s June 12, 2017 article for C&EN describes in detail how CRISPR could significantly change agriculture (Note: Links have been removed),

When the seed firm DuPont Pioneer first announced the new corn in early 2016, few people paid attention. Pharmaceutical companies using CRISPR for new drugs got the headlines instead.

But people should notice DuPont’s waxy corn because using CRISPR—an acronym for clustered regularly interspaced short palindromic repeats—to delete or alter traits in plants is changing the world of plant breeding, scientists say. Moreover, the technique’s application in agriculture is likely to reach the public years before CRISPR-aided drugs hit the market.

Until CRISPR tools were developed, the process of finding useful traits and getting them into reliable, productive plants took many years. It involved a lot of steps and was plagued by randomness.

“Now, because of basic research in the lab and in the field, we can go straight after the traits we want,” says Zachary Lippman, professor of biological sciences at Cold Spring Harbor Laboratory. CRISPR has been transformative, Lippman says. “It’s basically a freight train that’s not going to stop.”

Proponents hope consumers will embrace gene-edited crops in a way that they did not accept genetically engineered ones, especially because they needn’t involve the introduction of genes from other species—a process that gave rise to the specter of Frankenfood.

But it’s not clear how consumers will react or if gene editing will result in traits that consumers value. And the potential commercial uses of CRISPR may narrow if agriculture agencies in the U.S. and Europe decide to regulate gene-edited crops in the same way they do genetically engineered crops.

DuPont Pioneer expects the U.S. to treat its gene-edited waxy corn like a conventional crop because it does not contain any foreign genes, according to Neal Gutterson, the company’s vice president of R&D. In fact, the waxy trait already exists in some corn varieties. It gives the kernels a starch content of more than 97% amylopectin, compared with 75% amylopectin in regular feed corn. The rest of the kernel is amylose. Amylopectin is more soluble than amylose, making starch from waxy corn a better choice for paper adhesives and food thickeners.

Like most of today’s crops, DuPont’s current waxy corn varieties are the result of decades of effort by plant breeders using conventional breeding techniques.

Breeders identify new traits by examining unusual, or mutant, plants. Over many generations of breeding, they work to get a desired trait into high-performing (elite) varieties that lack the trait. They begin with a first-generation cross, or hybrid, of a mutant and an elite plant and then breed several generations of hybrids with the elite parent in a process called backcrossing. They aim to achieve a plant that best approximates the elite version with the new trait.

But it’s tough to grab only the desired trait from a mutant and make a clean getaway. DuPont’s plant scientists found that the waxy trait came with some genetic baggage; even after backcrossing, the waxy corn plant did not offer the same yield as elite versions without the trait. The disappointing outcome is common enough that it has its own term: yield drag.

Because the waxy trait is native to certain corn plants, DuPont did not have to rely on the genetic engineering techniques that breeders have used to make herbicide-tolerant and insect-resistant corn plants. Those commonly planted crops contain DNA from other species.

In addition to giving some consumers pause, that process does not precisely place the DNA into the host plant. So researchers must raise hundreds or thousands of modified plants to find the best ones with the desired trait and work to get that trait into each elite variety. Finally, plants modified with traditional genetic engineering need regulatory approval in the U.S. and other countries before they can be marketed.

Instead, DuPont plant scientists used CRISPR to zero in on, and partially knock out, a gene for an enzyme that produces amylose. By editing the gene directly, they created a waxy version of the elite corn without yield drag or foreign DNA.

Plant scientists who adopt gene editing may still need to breed, measure, and observe because traits might not work well together or bring a meaningful benefit. “It’s not a panacea,” Lippman says, “but it is one of the most powerful tools to come around, ever.”

It’s an interesting piece which answers the question of why tomatoes from the grocery store don’t taste good.