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Artemisia – Artemisinin

 

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Farmers Affected: 100,000 [1]
Volume: 200 Metric tonnes/year [2]
Market Value: Artemisinin:$76 million Aretemisinin-based drugs: $340 million [3]
Uses: Malaria Medication
Syn bio Companies: Amyris
Hotspots: China (approx. 10,000ha); Vietnam. (approx. 1000ha); Madagascar.
Also Grown In: India, Nigeria, Mozambique, Kenya, South Africa, Tanzania, Uganda, and Zimbabwe.
Cultural Importance: Use derived from 2000 years of Chinese herbalism.
Biodiversity Considerations: Supplements income of small farmers, acts as a break crop.
Quality Concerns: Artemisinin is a single compound. Excludes other important compounds.Although semisynthetic artemisinin was approved by the World Health Organisation concerns were raised by chemists that WHO changed its standards to allow high levels of additional impurities in the Syn Bio derived version. [4]
Products: Artemisinin Combination Therapies (ACTs)
Feedstock: Sugar
Commercialization: On the market, sold by Sanofi Aventis.

Overview

Artemisinin, the active ingredient from the Chinese herbal shrub Artemisia annua, or sweet wormwood, is the principal ingredient in a range of anti-malarial drugs authorized by the World Health Organization. By 2013, an estimated 100,000 small farmers in Asia and Africa were planting enough artemisia to meet world demand. Artemesia is grown primarily as a cash crop for sale to pharmaceutical companies.

In April 2013 a “semi-synthetic artemisinin” (SSA) entered the market, produced via synthetic biology. This synthetic version was  created by Amyris Biotechnologies in collaboration with Sanofi Aventis using $64 million dollars of philanthropic funds donated by the Bill & Melinda Gates Foundation. [5] It was initially supposed to replace a third to a half of global supply, although key researchers expressed their ambition to take over the entire global market. Suspiciously, the arrival of SSA coincided exactly with a crash in the price of naturally-derived artemisinin. Research suggests that many farmers have since stopped planting the crop in response to this price drop. Sanofi Aventis has shut down its Syn Bio factory for SSA- also because of the low price. The state of the future supply of this important anti-malarial compound is now unclear – and so are the livelihood implications for the farmers that grow it.

What is Artemisinin?

Artemisia annua, or sweet wormwood, has been used by Chinese herbalists to treat malaria for over 2000 years. Since 1967, its active ingredient artemisinin has seen widespread use as the principal ingredient in a range of anti-malarial drugs authorized by the World Health Organization. These drugs are collectively known as Artemisinin Combination Therapies (ACTs), and are currently considered the most effective treatment against this very widespread and dangerous disease. Artemesia is also widely used in herbal tea form as a traditional protection against malaria and whole powdered versions of the leaf also appear to be effective. [6]

Artemisinin as a Natural Product

Until as recently as 2013, natural artemisinin was sourced entirely from an estimated 100,000 small farmers in Asia and Africa, as well as wild harvesters of the crop in China. [7] Currently 80% of all artemisinin derived from artemisia crops is produced in China. Vietnam is a distant second (around 10%), with the remainder coming from Madagascar, Kenya, Tanzania and Uganda. A small amount is grown in India. Farmers have also been growing trial crops of Artemisia in Zimbabwe, South Africa and Nigeria. The average crop area per farmer in China and Africa is around 0.2 hectares. [8]

Cultural and Biodiversity Considerations

Artemesia is  highly prized as a Chinese national treasure for its long history of  use in curing malaria-like symptoms. Although difficult to grow in some areas, Artemesia has been widely adopted by tropical farmers, particularly in malarial regions of East Africa, where it can also be consumed as a herbal tea for medical benefits or transformed into other ‘whole plant therapies’. Artemesia makes a good break or rotation crop for food crops such as rice and potatoes.

Synthetic Biology Production

The production of SSA, Semi-Synthetic Artemisinin, had been presented as a poster child for the field of Synthetic Biology, and is closely associated with Professor Jay Keasling – a serial biotech entrepreneur from the University of California at Berkeley. Artemisinin was chosen by Keasling and his start-up Amyris Biotechnologies as a demonstration molecule for proving out a synthetic biology process to develop isoprenoid chemicals (a class of 55,000 different molecules, many of them valuable). Artemisinin was interesting as a first candidate because its connection to a serious disease could attract philanthropic funds. [9] Supported by a $64-million grant from the Bill & Melinda Gates Foundation, the researchers engineered yeast to produce artemisinic acid (a precursor) and convert that to artemisinin. [10] Sanofi (Sanofi Aventis) announced in April 2013 that they had manufactured 35 metric tonnes (MT) in its first  batch. It indicated plans to annually produce enough Semi-Synthetic Artemisinin (SSA) to meet between a third and a half the global demand. [11]

Although Sanofi’s production was slated to increase to 60 MT per year, it appears that in reality Sanofi were unable to sell this first run of SSA to any ACT (Artemesia Combination Therapies) manufacturer because their price was above market cost; and in 2015 they produced no SSA at all. This was linked to a collapse in artemisinin prices. They have decided to sell the plant to their contractor, HuvePharma. HuvePharma told Nature magazine that they may switch back to botanically-derived artemisinin if they can’t make the process cheaper. [12]

Implications and the Future

A 2006 report from the Netherlands-based Royal Tropical Institute had predicted the effects of introducing synthetic sources of artemisinin: “pharmaceutical companies will accumulate control and power over the production process; artemisia producers will lose a source of income; and local production, extraction and (possibly) manufacturing of ACT in regions where malaria is prevalent will shift to the main production sites of Western pharmaceutical companies.” [13] Additionally, artemisinin experts  warned against the human cost of disrupting the recently stabilized botanical market with a synthetic version. “If it’s brought in too fast it could create huge shortages, because people will stop producing the natural stuff,” [14] said Malcolm Cutler, technical adviser to the A2S2 initiative.

That may indeed have been the initial impact of introducing SSA. Upon the arrival of the syn bio version, 2014 prices of botanical artemisinin dropped to a decade low; and subsequently plantings reportedly fell  by two-thirds. The price fell so low that even SSA was overpriced and that’s the reason Sanofi couldn’t sell theirs. Farmers looked elsewhere for income. Far from calming market volatility, SSA may have helped fuel price volatility and undermined a valuable income source for tens of thousands of farmers.

Worryingly, Jay Keasling meanwhile has indicated that the team behind semisynthetic artemisinin hope to switch entire global production of artemisinin away from botanical artemesia towards syn bio-derived artemisinin. At a conference in Cambridge on the eve of launching SSA commercially, Keasing said “There are moves afoot to replace the entire world supply with this source” adding “Early on, it was not about replacing the agricultural form. In part that was politics too. If I went out into the public and said we are going to replace this they might stop planting and now I think its nearly inevitable that it will shift over”. [15] Switching entire global production to SSA would be a highly dangerous move. If there were to prove a problem with synthetic production, drugmakers would have lost the botanical supply for a needed medication.


[1] Global estimate of 100,000 artemesia growers provided by Charles Giblain, CEO Bionexx, Madagascar. Personal communication Jun 17th 2013

[2] Provided by Charles Giblain, CEO Bionexx, Madagascar. Personal communication Dec 18 2014.

[3] Estimate based on average prices for artemisinin of $380kg – source Charles Giblain, Bionexx – see http://www.a2s2.org/upload/5.ArtemisininConferences/4.2014China/Day1/11.MadAfCountryReportGIBLAIN.pdf

[4] Bhupinder P Kambay, Presentation to A2S2 conference Nairobi, Kenya “proposed Changes to Specifications for Artemisinin as an API and Starter Material” 16th January 2013 – see http://www.a2s2.org/upload/5.ArtemisininConferences/1.2013Kenya/Presentations/Day2/6.ProposedChangesARTSpecificationsKamtech.pdf

[5] Mark Peplow, “Synthetic biology’s first malaria drug meets market resistance” Nature News 23 Feb 2016 – http://www.nature.com/news/synthetic-biology-s-first-malaria-drug-meets-market-resistance-1.19426

[6] Janet Lathrop, “Whole Plant Therapy Shows Promise to Beat Malaria Parasites’ Drug Resistance” jan 5th 2015, UMass Amherst – https://www.umass.edu/newsoffice/article/whole-plant-therapy-shows-promise-beat

[7] Global estimate of 100,000 artemisinin growers provided by Charles Giblain, CEO Bionexx, Madagascar. Personal communication June 17th 2013

[8] Assured Artemisinin Supply System (A2S2), Production Cycle: from Artemisia to ACT, 26 January 2012:
http://www .a2s2.org/index.php?id=50

[9] In person Interview with Vincent Martin, former chief Scientist Amyris Biotechnologies –Montreal, Feb 2 2012

[10] Mark Peplow, “Synthetic biology’s first malaria drug meets market resistance” Nature News 23 Feb 2016 – http://www.nature.com/news/synthetic-biology-s-first-malaria-drug-meets-market-resistance-1.19426

[11] Sanofi news release, “Sanofi and PATH announce the launch of large-scale production of semisynthetic artemisinin against malaria” April 11 2013 – http://www.path.org/news/press-room/422/

[12] Mark Peplow, “Synthetic biology’s first malaria drug meets market resistance” Nature News 23 Feb 2016 – http://www.nature.com/news/synthetic-biology-s-first-malaria-drug-meets-market-resistance-1.19426

[13] Heemskerk, W . et al., The World of Artemisia in 44 Questions, The Royal Tropical Institute of the Netherlands, March 2006, p. i-ii: http://www.kit.nl/health/wp-content/uploads/publications/879_The%20world%20of%20Artemisia%20in%2044%20questions.pdf

[14] Mark Peplow, “Malaria drug made in yeast causes market ferment” Nature News. 13 February 2013 – http://www.nature.com/news/malaria-drug-made-in-yeast-causes-market-ferment-1.12417

[15] Presentation by Jay Keasling at The Future of Nature conference, Cambridge UK April 2013. Partial transcripts provided in presentation by Charles Giblain, Bionexx – see http://www.a2s2.org/upload/5.ArtemisininConferences/4.2014China/Day1/11.MadAfCountryReportGIBLAIN.pdf

Sep 092016
 
Martyn Fletcher via Flickr

Martyn Fletcher via Flickr

by Claire Hope Cummings (Project Syndicate)

HONOLULU – A cynical move is underway to promote a new, powerful, and troubling technology known as “gene drives” for use in conservation. This is not just your everyday genetic modification, known as “GMO”; it is a radical new technology, which creates “mutagenic chain reactions” that can reshape living systems in unimaginable ways.

Gene drives represent the next frontier of genetic engineering, synthetic biology, and gene editing. The technology overrides the standard rules of genetic inheritance, ensuring that a particular trait, delivered by humans into an organism’s DNA using advanced gene-editing technology, spreads to all subsequent generations, thereby altering the future of the entire species.

It is a biological tool with unprecedented power. Yet, instead of taking time to consider fully the relevant ethical, ecological, and social issues, many are aggressively promoting gene-drive technology for use in conservation.

One proposal aims to protect native birds on Hawaii’s Kauai Island by using gene drives to reduce the population of a species of mosquito that carries avian malaria. Another plan, championed by a conservation consortium that includes US and Australian government agencies, would eradicate invasive, bird-harming mice on particular islands by introducing altered mice that prevent them from producing female offspring. Creating the “daughterless mouse” would be the first step toward so-called Genetic Biocontrol of Invasive Rodents (GBIRd), designed to cause deliberate extinctions of “pest” species like rats, in order to save “favored” species, such as endangered birds.

The assumption underlying these proposals seems to be that humans have the knowledge, capabilities, and prudence to control nature. The idea that we can – and should – use human-driven extinction to address human-caused extinction is appalling.

I am not alone in my concern. At the ongoing International Union for the Conservation of Nature (IUCN) World Conservation Congress in Hawaii, a group of leading conservationists and scientists issued an open letter, entitled “A Call for Conservation with a Conscience,” demanding a halt to the use of gene drives in conservation. I am one of the signatories, along with the environmental icon David Suzuki, physicist Fritjof Capra, the Indigenous Environmental Network’s Tom Goldtooth, and organic pioneer Nell Newman.

The discussions that have begun at the IUCN congress will continue at the United Nations Convention on Biological Diversity in Mexico this December, when global leaders must consider a proposed global moratorium on gene drives. Such discussions reflect demands by civil-society leaders for a more thorough consideration of the scientific, moral, and legal issues concerning the use of gene drives.

As I see it, we are simply not asking the right questions. Our technological prowess is largely viewed through the lens of engineering, and engineers tend to focus on one question: “Does it work?” But, as Angelika Hilbeck, President of the European Network of Scientists for Social and Environmental Responsibility (ENSSER) argues, a better question would be: “What else does it do?”

When it comes to the GBIRd project, for example, one might ask whether the “daughterless mouse” could escape the specific ecosystem into which it has been introduced, just as GMO crops and farmed salmon do, and what would happen if it did. As for the mosquitos in Hawaii, one might ask how reducing their numbers would affect the endangered hoary bat species.

Ensuring that these kinds of questions are taken into account will be no easy feat. As a lawyer experienced in US government regulations, I can confidently say that the existing regulatory framework is utterly incapable of assessing and governing gene-drive technology.

Making matters worse, the media have consistently failed to educate the public about the risks raised by genetic technologies. Few people understand that, as MIT science historian Lily Kay explains, genetic engineering was deliberately developed and promoted as a tool for biological and social control. Those driving that process were aiming to fulfill a perceived mandate for “science-based social intervention.”

Powerful tools like genetic modification and, especially, gene-drive technology spark the imagination of anyone with an agenda, from the military (which could use them to make game-changing bio-weapons) to well-intentioned health advocates (which could use them to help eradicate certain deadly diseases). They certainly appeal to the hero narrative that so many of my fellow environmentalists favor.

But the fact is that we have not created the intellectual infrastructure to address the fundamental challenges that gene drives – not to mention other powerful technologies – raise. And now we are supposed to suspend our critical faculties and trust the techno-elites’ promise to use gene drives responsibly in the service of seemingly positive environmental goals. No open public discussion is needed, apparently. But why should we blindly believe that everything is under control?

In my view, the focus on using gene-drive technology for conservation is a ruse to gain public acceptance and regulatory cover. Why expose something to public scrutiny and possible restraints when you can usher it in through the back door by pretending it will do some good? The risks are too obvious for gene-drive advocates to risk talking about them.

In my 20-plus years of researching and reporting on transgenic technologies, I thought I had seen the worst of the false promises and hype that they engender. But gene drives are unlike anything we have witnessed, and amount to the ultimate test of our self-control. Can we really trust science to guide us, or do we recklessly throw in our lot with technological “silver bullets” as the way forward?

Fortunately, we still have a choice. The fact that gene drives can change the basic relationship between humanity and the natural world is both a challenge and an opportunity. We can do now what we should have done a long time ago, with regard to both nuclear and transgenic technologies: start paying more attention to the dangers of human ingenuity – and more respect to the genius of nature.

Genetic “extinction” technology rejected by international group of scientists, conservationists and environmental advocates

 

Posted Sep. 1, 2016

OAHU, HAWAI’I — As thousands of government representatives and conservationists convene in Oahu this week for the 2016 World Conservation Congress, international conservation and environmental leaders are raising awareness about the potentially dangerous use of gene drives — a controversial new synthetic biology technology intended to deliberately cause targeted species to become extinct.

Members of the International Union for the Conservation of Nature (IUCN), including NGOs, government representatives, and scientific and academic institutions, overwhelmingly voted to adopt a de facto moratorium on supporting or endorsing research into gene drives for conservation or other purposes until the IUCN has fully assessed their impacts. News of the August 26 digital vote comes as an important open letter to the group is being delivered.

Scientists and environmental experts and organizations from around the globe have advocated for a halt to proposals for the use of gene drive technologies in conservation. Announced today, a long list of environmental leaders, including Dr. Jane Goodall, DBE, genetics professor and broadcaster Dr. David Suzuki, Dr. Fritjof Capra, entomologist Dr. Angelika Hilbeck, Indian environmental activist Dr. Vandana Shiva and organic pioneer and biologist Nell Newman, have lent their support to the open letter: “A Call for Conservation with a Conscience: No Place for Gene Drives in Conservation.” The letter states, in part: “Gene drives, which have not been tested for unintended consequences, nor fully evaluated for ethical and social impacts, should not be promoted as conservation tools.”

“Gene drives are basically a technology that aims for a targeted species to go extinct,” explains ecologist and entomologist Dr. Angelika Hilbeck, president of the European Network of Scientists for Social and Environmental Responsibility (ENSSER). “While this may appear to some conservationist professionals to be a ‘good’ thing and a ‘silver bullet’ to handle complicated problems, there are high risks of unintended consequences that could be worse than the problems they are trying to fix.”

Both the leading developers of the technology and also those concerned about gene drives will be attending this week’s Congress and holding events to raise awareness, hype promises or highlight the potential hazards of gene drives. One near-term gene drive proposal, promoted by U.S.-based non-governmental organization Island Conservation, intends to release gene drive mice on islands to eradicate them. Another led by the University of Hawai’i would develop gene drive mosquitoes for use in Hawaii to combat avian malaria which affects honeycreeper birds. The debate around gene drives is likely to resurface later this year at the negotiations of the United Nations Biodiversity Convention in Cancun Mexico in December.

“Gene drives, also known as ‘mutagenic chain reactions,’ aim to alter DNA so an organism always passes down a desired trait, hoping to change over time the genetic makeup of an entire species,” explains Dr. Vandana Shiva of Navdanya. “This technology would give biotech developers an unprecedented ability to directly intervene in evolution, to dramatically modify ecosystems, or even crash a targeted species to extinction.”

“Genetic extinction technologies are a false and dangerous solution to the problem of biodiversity loss,” said Erich Pica, president of Friends of the Earth. “There are real, sustainable, community-based conservation efforts that should be supported. We are concerned that genetic extinction technologies will allow new destructive agricultural practices and even use by the military. Speculative conservation claims are at best an unfounded diversion or smokescreen. We support those in the IUCN who recognize the gravity of irreversible and irresponsible technologies such as gene drives.”

Signatories of the letter, which include indigenous organizations and legal experts, raised legal and moral questions, citing an “ethical threshold that must not be crossed without great restraint.”

“From military testing to GMO crops, and now gene drives, Hawai’i should not be treated as a test zone for risky and experimental technologies,” said Walter Ritte, Native Hawaiian activist and hunter. “What happens in Hawai’i must be discussed with residents, not decided from a lab on the other side of the continent. Hawaiians should decide what is best for Hawai’i.”

Some of the signing organizations will be holding a Knowledge Café event as part of the IUCN World Conservation Congress at 8:30 am (HST) on Monday, September 5. The event will be live streamed at www.synbiowatch.org/gene-drives.

In response to upcoming proposals to release gene drive organisms in Hawaii, the local organization Hawai’i SEED will be hosting an educational session on gene drives in the evening on Tuesday, September 6. See http://bit.ly/2bwZEuG for details.

Note to editors:

1. A short briefing outlining concerns about gene drives prepared by the Civil Society Working Group on Gene Drives is available at http://synbiowatch.org/2016/08/reckless-driving/. A copy of the letter “A Call for Conservation with a Conscience: No Place for Gene Drives in Conservation” and a complete list of signatories is available at http://www.synbiowatch.org/gene-drives-letter/.

2. The organizers of the letter are inviting other organizations to join as signatories. Additional organizational signatures can be sent to: genedrives@synbiowatch.org.

3. More details about the Island Conservation Project to release gene drive mice are available in this article: http://baynature.org/article/re-coding-conservation/. Plans to develop gene drives for Hawaii are being developed by the lab of Dr. Floyd A, Reed of Hawaii University: http://hawaiireedlab.com/wpress/?p=2270.

4. The IUCN Motion on Synthetic Biology and Conservation (motion No. 95) was supported by 71 Governments and 355 NGOs (out of a total of 544 votes cast). It includes the following amendment on gene drives: “CALLS UPON the Director General and Commissions with urgency to assess the implications of gene drives and related techniques and their potential impacts on the conservation and sustainable use of biological diversity as well as equitable sharing of benefits arising from genetic resources, in order to develop IUCN guidance on this topic, while refraining from supporting or endorsing research, including field trials, into the use of gene drives for conservation or other purposes until this assessment has been undertaken.” A breakdown of the vote was today made available to IUCN members.

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Expert contacts: Dana Perls, (925) 705-1074, dperls@foe.org; Jim Thomas, (514) 516-5759, jim@etcgroup.org

Communications contacts: Kate Colwell, (202) 222-0744, kcolwell@foe.org; Trudi Zundel, (266) 979-0993, trudi@etcgroup.org

Aug 292016
 

reckless-drivingThis is a new briefing from the Civil Society Working Group on Gene Drives which includes Biofuelwatch, Econexus, ETC Group, Friends of the Earth US, Hawai’i SEED and Navdanya. It can be downloaded as a pdf here (en español).

Imagine that by releasing a single fly into the wild you could genetically alter all the flies on the planet—causing them all to turn yellow, carry a toxin, or go extinct. This is the terrifyingly powerful premise behind gene drives: a new and controversial genetic engineering technology that can permanently alter an entire species by releasing one bioengineered individual.

Gene drives can entirely re-engineer ecosystems, create fast spreading extinctions, and intervene in living systems at a scale far beyond anything ever imagined. When gene drives are engineered into a fast-reproducing species they could alter their populations within short timeframes, from months to a few years, and rapidly cause extinction. This radical new technology, also called a “mutagenic chain reaction,” [1] is unlike anything seen before. It combines the extreme genetic engineering of synthetic biolog y and new gene editing techniques with the idea that humans can and should use such powerful unlimited tools to control nature. Gene drives will change the fundamental relationship between humanity and the natural world forever.

The implications for the environment, food security, peace, and even social stability are significant. Dealing with this run-away technology is already being compared to the challenge of governing nuclear power. [2] Existing government regulations for the use of genetic engineering in agriculture have allowed widespread genetic contamination of the food supply and the environment.

Given the current feeble restraints on existing genetic engineering technologies, how would anyone be able to assess the risks of gene drives? Would the public be informed and have a say in how they would be used? And if an accident were to occur, given that the damage would be massive and irreversible, who would be held accountable?

The ethical, cultural and societal implications of gene drives are as enormous as the ecological consequences. Civil society groups (and even some gene drive researchers) are alarmed by this newfound ability to reshape the natural world. However, such an omnipotent power to control nature is immensely tempting to those who may not be constrained by either common decency or common sense. Gene drive technology is commanding the attention of the world’s most powerful military, agribusiness, and social change organizations. Gene drive technology also appears to be relatively simple and cheap, so it could easily fall into the hands of those, including governments, who might use it as a weapon.

gene-drivesHow does a gene drive work?

A trait is a genetically determined characteristic of an organism (e.g. eye color). In normal sexual reproduction, a trait generally has only a 50% chance of being expressed. With a gene drive, however, that trait is “driven” into the organism’s reproductive cycle so that every single offspring always carries and expresses the specified trait.

Gene drives force an artificially engineered trait to spread through the natural population until it becomes ubiquitous or crashes that population. The first working gene drives were demonstrated at the end of 2014 using a new gene-editing technique known as CRISPR-CAS9. They work by setting up a genetic enforcement mechanism which copies itself from parent to child, cascading from one generation to the next by sexual reproduction.

Gene drives only work in sexually reproducing species. The natural process of inheritance through sexual reproduction is the cornerstone of biological diversity within a species. But gene drives force a species towards uniformity or extinction—a perfectly anti-ecological outcome and a violation of the fundamentals of evolution. For example, when a gene drive commands an organism to glow green, the “mutagenic chain reaction” that follows ensures that all future progeny of that organism, and all its descendants, also glow green. This violates the normal rules of species evolution, which usually limits the passing on of a new trait to only some offspring and limits its survival to those that have a selective advantage.

The implications for natural populations are striking. Figure 1a. shows the normal pattern of inheritance across the generations. Following the established rules of genetics, we can expect roughly 50% of an organism’s offspring to carry a specific gene. Once that altered organism is introduced into a population, the number of affected organisms can dilute through the generations. But with a gene drive (see Figure 1b.) there is 100% inheritance of the new trait enforced among all descendants. Instead of being diluted, the new trait takes over.

If someone wanted to ‘crash’ a species and cause its extinction, they would simply engineer a gene drive that makes all the offspring into males, for instance. This approach is being taken with the so-called ‘daughterless’ mouse gene drive. Any mouse that the daughterless mouse mates with will only give birth to males. In turn, all their progeny will only produce males and they will spread the ‘daughterless’ trait until they overwhelm that mouse species and crash the population. Theoretically, this “male-only” mechanism could be used with any sexually reproducing organism.

Examples of various gene drives

Global drives: a “standard” gene drive that continues to spread, potentially until it takes over the entire species (or causes the entire species to go extinct).
Reversal Drive: a speculative proposal to ‘undo’ the effects of a gene drive by sending a second drive after the first. A recent report from the US National Academy of Sciences was skeptical that this idea would reliably work. [3]
Split drive: a technique where half a gene drive is engineered into an organism’s DNA, and half into a piece of associated virus DNA, so that the organism won’t pass on the full instructions for a new gene drive. [4] This is intended for lab safety but is impractical as a technology in the wild.
Daisy drive: a proposed gene drive that theoretically stops working after a certain number of generations. This is supposed to create ‘local’ gene drives that won’t spread uncontrollably. [5] The inventor, Kevin Esvelt, acknowledges that a daisy drive could mutate into a global drive accidentally.

How can gene drives be used?

1. Industrial Agriculture
Gene drive developers acknowledge that agribusiness is interested in this technology for many uses. These include eradicating weeds (a “sensitizing gene drive” could be released into wild weed species to make it more susceptible to a proprietary herbicide such as roundup), or eliminating pests. For example, gene drive research on fruit flies—specifically on species like Drosophila Suzukii, which attack soft fruit harvests—is intended to eradicate it globally and save on the costs of both pesticides and lost crop damages. [6] Other pests that might be driven to extinction to protect industrial agriculture include mice, moths and locusts. Gene drives may also be used to speed up the introduction of a genetically modified trait into seed harvests.

2. Military
Gene drives are a classic ‘dual use’ technology, meaning that the technology for gene drives developed for one use could also be used as a weapon or biological agent. For example, work is already underway to equip parasitic worms with gene drives in order to eradicate them [7]–the same technology could be used to make them spread disease or toxins. Gene-drive yeasts have been created in the lab and these could be engineered to be harmful to humans. Releasing an engineered gene drive into agricultural fields could attack a country’s food production. And gene drive mosquitos and other insects could be engineered to spread lethal toxins in their bite. [8]

3. Attacking Disease
Much of the hype around pesticides promised that they would safely eradicate pests, but in fact they are, as Rachel Carson called them, “biocides” that kill indiscriminately. While the promised benefits of gene drives are that they will target organisms that carry disease, there is no firm scientific basis for the claim that their impact will not spread beyond the intended target. The following are currently being developed as gene drive organisms under the guise of eradicating disease:
Mosquitos: Several teams are working on gene drives that would eradicate mosquitos or re-engineer them so they are unable to carry malaria. Theoretically the mosquitos that carry Zika and Dengue could also be attacked with gene drive systems.
Parasitic worms: At least one team is working on gene drives to attack the worms that cause schistosomiasis and others propose gene drives for whipworm and threadworm. [9]

4. Artificially Enhancing Conservation
A small group of conservationists argue that tools that cause deliberate extinction could be harnessed for good. A consortium of 5 partners (including two government agencies) led by the conservation group Island Conservation is developing gene drive-equipped mice that will be released on islands ostensibly to kill the mice that harm birds.

They call this the GBIRd project (Genetic Biocontrol of Invasive Rodents) and intend to release these gene drives by 2020. [10] Additionally, there is a highly promoted proposal to develop gene drive mosquitos for release in Hawaii where one species of mosquito carries a form of avian malaria that affects native birds, [11] despite the fact that at least one targeted bird species has developed a natural resistance to avian malaria and there are still disease free areas. [12] This project is being promoted by The Long Now Foundation’s Revive and Restore project. [13]

What are the environmental dangers of gene drives?

Greater threat of unintended consequences
Gene drives carry the same biosafety risks that other genetically engineered organisms carry and more. We know the track record of genetically modified organisms (GMOs) acting in unexpected ways and causing a variety of environmental harms, while not delivering on their promised benefits. Gene drives are designed not only to spread rapidly but also to do it with exponential efficiency. There is nothing in the natural world to compare them to and that limits our capacity to predict their behavior.

Severing a strand in the ecological web
Gene drives are designed to create large-scale changes in populations and intentionally impact entire ecosystems. We know so little about the web of life as it is, are we really ready to take such radical steps to alter the course of evolution? It’s impossible to predict the ecological consequences of such a rapid, massive, unprecedented disruption. Removing a pest may seem attractive, but even pests have their place in the food chain. Additionally, eradicating one species might unpredictably open up space for the expansion of another species which may carry diseases, affect pollination or otherwise threaten biodiversity.

Could gene drives jump species?
Promoters of gene drives present them as precise mechanisms, just as GMO promoters did. But living systems and sexual reproduction processes are messy and unpredictable. We now know there is occasional horizontal gene transfer (movement of genes between different species) and that some genes do cross over into related species.

Applying gene drives to agriculture will intensify existing concerns about the use of genetic engineering and monocultures in industrial agriculture. Gene drive strategies may strengthen the market monopoly of agribusiness giants such as Monsanto and Syngenta, especially if wild weed populations are altered to respond to their proprietary chemicals or wide patent claims are applied. The decision to eradicate wild weed populations may also harm culturally significant crops and indigenous species. For example, proposals to use gene drives against pigweed in North America (Palmer Amaranth) could also eradicate species of amaranth used for food and cultural purposes in Central America. [14]

Dangers to society
The ethical, cultural and societal implications of gene drives are especially complex and challenging. Civil society groups, and even some gene drive researchers, are raising the alarm about the power of this technology. Such a powerful tool may be too tempting to military funding agencies and hi-tech agribusiness who see advantages to exploring this Pandora’s box. This raises the basic question: who will this technology benefit and who decides how it will be used? The potential threat of weaponized gene drives can’t be overstated. While a harmful gene drive could theoretically be engineered into a fast-spreading parasite to ‘wipe out’ a population or used to crash a food harvest, the bigger threat may come from the changing geopolitics and security requirements that the existence of gene drives may unleash.

The need to police gene drives as a potential bioweapon may expand and deepen military control and collusion in biotechnology developments. Proposals to unleash gene drives as a ‘silver bullet’ for health and conservation challenges are highly risky and speculative. But these “technofixes” continue to be over-sold to the public through deceptive media campaigns, corruption of regulatory agencies, and by inflaming the public’s fears and anxieties about disease, climate change, and species extinction. “Silver bullet” technologies distract from, rather than contribute to, the work that needs to be done to root out the systemic causes of these problems – such as providing sanitation, defending human rights, addressing poverty and upholding community land rights and stewardship over nature.

We are walking forwards blind. We are opening boxes without thinking about consequences. We are going to fall off the tightrope and lose the trust of public. – Gene drive developer Kevin Esvelt, MIT, on the current rising interest in gene drive applications. [15]

What should be done?

The Civil Society Working Group on Gene Drives prepared this briefing. [17] We believe that no case can be made for proceeding with gene drive experiments or developments at this time. Moreover, in our view, recent proposals to move ahead with real world gene drive trials (e.g. the GBIRd project led by Island Conservation and the gene drive mosquito in Hawaii) are reckless and irresponsible and do not reflect the essential values of the conservation movement. Such projects should not be funded or promoted by non-profit groups or philanthropic organizations whose social contract and tax-exempt status is founded on the principle that they are doing a public service.

The project of deliberately exterminating species is a crime against nature and humanity… Developing tools of extermination in the garb of saving the world is a crime. A crime that must not be allowed to continue any further. – Dr. Vandana Shiva, India [16]

We recommend:
• An immediate and international halt to gene drive releases and experimentation.
• All existing patents on this technology should be either extinguished as against the public interest or handed to an international agency charged with preventing licensing or use of the technology.
• Scientists, ethicists, environmental groups, civil society groups, lawyers and even artists and poets must speak out clearly against gene drives in a concerted and public way, calling for the withdrawal of support for the funding and continued promotion of gene drive technology.

Footnotes

[1] Gantz VM, Bier E. The mutagenic chain reaction: a method for converting heterozygous to homozygous mutations.Science (New York, NY). 2015;348(6233):442-444. doi:10.1126/science.aaa5945.

[2] Jim Thomas, “The National Academies’ Gene Drive study has ignored important and obvious issues” The Guardian 9th June 2016. https://www.theguardian.com/science/politicalscience/2016/jun/09/the-national-academies-gene-drive-study-has-ignored-important-and-obviousissues

[3] National Academies of Sciences, E ngineering, and Medicine. Gene Drives on the Horizon: Advancing Science, Navigating Uncertainty, and Aligning Research with Public Values. Washington, DC: The National Academies Press, 2016. doi:10.17226/23405.

[4] Safeguarding CRISPR-Cas9 Gene Drives in yeast. James E DiCarlo, Alejandro Chavez, Sven L Dietz, Kevin M Esvelt & George M Church Nature Biotechnology 33, 1250–1255 (2015) doi:10.1038/nbt.3412

[5] Kevin Esvelt, “‘Daisy drives’ will let communities alter wild organisms in local ecosystems.” https://medium.com/mit-media-lab/daisy-drives-will-let-communities-alter-wild-organisms-inlocal-ecosystems-cb626c5a9f38#.91i6eyhc0

[6] Li F. and Scott M. J. (2016). CRISPR/Cas9-mediated mutagenesis of the white and Sex lethal loci in the invasive pest, Drosophila suzukii. Biochem Biophys Res Commun. 469 (4): 911-916. doi: 10.1016/j.bbrc.2015.12.081. web

[7] George Washington University News release” MaxMind gives $100,000 to GW to create Gene Drive to eliminate schistosomiasis” Feb 1st 2016- http://www.eurekalert.org/pub_releases/2016-02/gwu-mg020116.php

[8] Science. 2014 Aug 29;345(6200):1010. doi: 10.1126/science.345.6200.1010-b. Gene Drives raise dual-use concerns.

[9] George Washington University News release “MaxMind gives $100,000 to GW to create Gene Drive to eliminate schistosomiasis” Feb 1st 2016. http://www.eurekalert.org/pub_releases/2016-02/gwu-mg020116.php

[10] GBIRd project (Genetic Biocontrol of Invasive Rodents) led by Island Conservation International – details at http://www.islandconservation.org/program-coordinator/.

[11] Antonio Regalado, “The Plan to Rescue Hawaii’s Birds with Genetic Engineering” Technology Review, May 11th 2016. https://www.technologyreview.com/s/601383/the-plan-to-rescue-hawaiisbirds-with-genetic-engineering/

[12] Samuel, M. D., B. L. Woodworth, C. T. Atkinson, P. J. Hart, and D. A. LaPointe. 2015. Avian malaria in Hawaiian forest birds: infection and population impacts across species and elevations. Ecosphere 6(6):104. http://dx.doi.org/10.1890/ES14-00393.

[13] http://reviverestore.org/case-studies/

[14] Vandana Shiva, “Biodiversity, GMOs, Gene Drives and the Militarized Mind” Common Dreams. July 10th 2016. http://www.commondreams.org/views/2016/07/10/biodiversity-gmos-gene-drivesand-militarized-mind

[15] Kristen V. Brown, “This scientist is trying to stop a lab-created global disaster” Fusion.net 27th June 2016. http://fusion.net/story/317396/kevin-esvelt-gene-drive-responsive-science/

[16] Vandana Shiva, “Biodiversity, GMOs, Gene Drives and the Militarized Mind” Common Dreams. July 10th 2016. http://www.commondreams.org/views/2016/07/10/biodiversity-gmos-gene-drivesand-militarized-mind

[17] The Civil Society Working Group on Gene Drives includes Biofuelwatch, Econexus, ETC Group, Friends of the Earth US, Hawai’i SEED, Navdanya and independent author and lawyer Claire Hope Cummings, M.A., J.D.

Aug 292016
 
International Rice Research Institute via Flickr

International Rice Research Institute via Flickr

by Louise Sales

Last week US biohacker Ellen Jorgensen toured Australia encouraging members of the public to genetically modify microbes prompting the GM Free Australia Alliance to call for a ban on the genetic engineering of microbes outside contained and certified laboratory facilities.

Biohacking generally means genetically modifying a bacteria, yeast, plant or animal to change its function or physical characteristics. Whilst such tinkering currently appears to be legal in Australia, the development of new genetic modification (GM) techniques such as CRISPR [i] have seriously upped the stakes of such experimentation – posing major potential risks to human health and the environment.

Workers in commercial biotechnology labs have already suffered serious health impacts from exposure to genetically modified microbes, [ii] including an Agriculture Department scientist who spent a month in a coma after being infected by the E. coli bacteria her colleagues were experimenting with.

“If you look at pathogenic organisms in nature, they often differ from their nonpathogenic counterparts by very tiny modifications ” Stuart Newman, Professor of Cell Biology and Anatomy at New York Medical College, told Digital Trends. For example, the bacteria that causes the deadly diphtheria infection “was a benign resident of the respiratory system,” he said. “But at some point during evolution…it picked up a protein…which allowed the Bacillus to interact with the human organism and cause horrendous illness.”

Earlier this year the US Director of National Intelligence, James Clapper, added gene editing techniques such as CRISPR to a list of threats posed by “weapons of mass destruction and proliferation” in the annual worldwide threat assessment report of the U.S. intelligence community. “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 concluded. [iii]

In 2001, Australian genetic engineers unintentionally turned a mild mouse pox into a virus that killed every mouse it infected. [iv] The mouse pox experiment was done in a professional lab and the researchers realised they had created a potential disaster. What if the alteration had been done by someone at home who just flushed the experiment down the sink – having no idea of what they had created? If nothing is done to prevent biohacking outside contained and certified laboratory facilities then some form of disaster seems inevitable.

Governments globally have yet to regulate new GM techniques such as CRISPR. This is despite the fact that DIY CRISPR kits are available online now. New GM techniques such as CRISPR are quite clearly gene technology and quite clearly pose potentially serious risks to the environment and human health. Governments need to step up and ban the use of these techniques outside contained and certified laboratory facilities.

Read our factsheet on biohacking

[i] Clustered regularly interspaced short palindromic repeats

[ii] Sandronsky, S. (2012) Biotech Worker’s Illness Raises Worries About the Growing, Largely Unregulated, Industry, http://www.earthisland.org/journal/index.php/elist/eListRead/biotech_workers_illness_raises_worries_about_the_growing_industry/; Pollack, A. & Wilson, D. (2010) Safety Rules Can’t Keep Up With Biotech Industry, New York Times, MAY 27, 2010, http://www.nytimes.com/2010/05/28/business/28hazard.html?src=busln&_r=0

[iii] Regalado, A. (2016) Top U.S. Intelligence Official Calls Gene Editing a WMD Threat, MIT Technology Review, February 9, 2016, https://www.technologyreview.com/s/600774/top-us-intelligence-official-calls-gene-editing-a-wmd-threat/

[iv] Nowak, R. (2001) Killer mousepox virus raises bioterror fears, New Scientist, 10 January 2001, https://www.newscientist.com/article/dn311-killer-mousepox-virus-raises-bioterror-fears/

Aug 192016
 
Aug 082016
 
 Theophilos Papadopoulos via Flickr


Theophilos Papadopoulos
via Flickr

by Almuth Ernsting (Independent Science News)

Subsidies intended for next-generation cellulosic ethanol production are to be applied to a trivial improvement to corn ethanol refining technologies. Since cellulosic ethanol qualifies for much higher subsidies, this will significantly increase corn refinery profits and boost the demand for corn but will do nothing to combat climate change or promote energy independence. This is all thanks to an EPA policy to boost the previously (almost) non-existing cellulosic biofuel production in the US by widening and watering down the definition of that term. Thanks to this policy, cellulosic ethanol subsidies can now go towards biofuels made from the same corn kernels as conventional corn ethanol.

After decades of promises that biofuels derived from cellulosic biomass – i.e. from wood, grasses and crop residues – would replace them, the biofuel market worldwide remains firmly stuck on food crops and plant oils. In 2015, the US produced 16.6 billion gallons of biofuels. Just 2.2 million gallons were classed as ‘cellulosic’, but 98.5% of those came from landfill gas (another questionable definition). Genuine cellulosic biofuels remain where they have been since the 1973 oil crisis, firmly in the research and development stage.

Yet the promise of cellulosic and algal biofuels has helped to legitimise continued government incentives for biofuels made from food. In the US, the main policy instrument has been the Renewable Fuel Standard, enacted under the Bush Administration in 2007. It requires 36 billion gallons of biofuels to be used in the US by 2022, with a maximum of 15 billion gallons coming from corn ethanol, and a minimum of 16 billion gallons from cellulosic biofuels. Both President Obama and his first Secretary of Energy, Steven Chu, have described corn ethanol as ‘transitional’, i.e. a bridge to cellulosic biofuels. Yet while corn ethanol production has greatly expanded and is approaching its ceiling, large-scale cellulosic biofuels remain a remote prospect.

In short, the only ‘achievement’ of cellulosic ethanol has been to boost support for unsustainable conventional biofuel production from food. The same is true in the EU. Greater support for ‘advanced biofuels’ was key to a legislative compromise which capped support for conventional, land-based biofuels at 7% of road transport fuel.

Now, cellulosic ethanol is coming to the aid of corn ethanol refineries once again. For the first time ever, one million gallons of cellulosic ethanol were accredited by the US Environmental Protection Agency (EPA) during one quarter, i.e. between January and March 2016.

Three commercial-scale cellulosic ethanol refineries were officially operational during that period, but those cannot account for it: One was officially opened by DuPont in October 2015, but had still not started production by April 2016. Also in April, INEOS Bio, who own a so far unsuccessful cellulosic refinery, stated that they were still working through ‘mechanical upgrades’ and were hoping to restart later this year. Only in May did the operators of the third, POET and DSM, announce themselves as “ramping up production”, which implies that they had not produced much so far. The latter told Scientific American that sand and gravel mixed with the corn stover had “wreaked havoc on pumps, valves and other equipment”.

This leaves just one potential source: ethanol produced inside a standard corn ethanol refinery but qualifying as ‘cellulosic’. This bizarre possibility goes back to an EPA ruling in 2014, which allowed ethanol made from the fibre contained in corn kernels to be subsidised as ‘cellulosic’. At a stroke, by including a proportion of ethanol made from corn kernels into its definition, EPA turned the conventional understanding of cellulosic ethanol upside down.

A closer look at corn versus cellulosic ethanol

To understand how this is possible, we first need to look at the difference between corn ethanol, cellulosic ethanol, and the new ‘corn fiber ethanol’ technologies which, thanks to the 2014 EPA ruling, now benefit from high cellulosic ethanol subsidies.

Corn ethanol is made from the fermentation of starch. Starches are energy storage molecules consisting of glucose units. Glucose is a sugar that serves as an energy source for most organisms – including yeast cells, which ferment it to ethanol and CO2. Although corn ethanol fermentation is a straightforward process, it does require significant energy inputs, usually from fossil fuels, as well as two different enzymes, which raise the production costs. This is because the starch must be broken into glucose molecules before it can be fermented.

Cellulosic ethanol on the other hand, is far more difficult and expensive to produce, and the energy balances are much worse than those for corn ethanol. The term cellulosic ethanol refers to ethanol made from cellulose and hemicelluloses which are the two main components of plant cell walls. Glucose must be liberated from cellulose before it can be fermented. Hemicelluloses are easier to break apart than cellulose, but their sugars cannot be fermented by the same yeast or any other microorganisms which are used to ferment glucose. There are some microorganisms which can ferment the sugars in hemicelluloses, but none have been found in nature which can efficiently ferment them as well as glucose. Adding to these difficulties, both cellulose and hemicelluloses are intertwined in complex structures which contain various other molecules, of which the best known and usually most abundant is lignin.

These are some of the reasons why efficiently – and affordably – breaking down all the complex cell wall structures and then obtaining a high ethanol yield remains an elusive industry goal.

What is corn fiber ethanol?

Corn kernels consist mainly of starch, but they also contain 10-12% fiber, as well as some protein and fat. The fiber consists of cell walls that contain cellulose and hemicellulose, together with a small amount of lignin. The fibre also contains some starch.  In theory, the ‘cellulosic ethanol’ from the fibre could come from cellulose and hemicellulose.  In fact, hemicellulose accounts for a lot more of the sugar in the fibre than cellulose.  However, no company is currently selling microorganisms capable of fermenting sugars contained in hemicellulose to corn ethanol refiners.  Therefore, such ‘cellulosic ethanol’ originates from the cellulose sugars in the fiber or the starch which adheres to it.

The EPA’s ruling on corn kernel fiber ethanol thus allows ethanol derived from corn starch which adheres to the fiber to be classed as ‘cellulosic’, albeit only in cases where the fiber is processed separately from the bulk of the corn starch. The reasoning given is that it accounts for “typically less than 5 percent of the mass” of the fiber. However, other sources cite much higher figures for the amount of starch that adheres to corn fiber. According to a 2009 presentation by an Associate Professor at the University of Illinois who specialises in corn processing, corn kernel fiber contains on average 25% starch, 40% hemicellulose, and 12% cellulose. If the latter figures are correct then the majority of the ‘cellulosic ethanol’ made from corn fiber in some refineries comes from corn starch. This specifically appears to apply to a corn fiber ethanol technology developed by Quad County Corn Processors and Syngenta.

There are two technologies being commercialised for corn fiber ethanol. One of these, developed by Quad County Corn Processors (QCCP) and Syngenta, would appear to benefit from the EPA’s starch rule. This is because it involves recovering the residues from conventional corn ethanol refining and then pre-treating, fermenting and distilling them to ‘cellulosic ethanol’, i.e. processing the fiber separately from them bulk of the starch.

The other technology (developed by Edeniq—now owned by Aemetis) involves unconventional pre-treatment methods of the whole corn kernels before fermentation. Given that the fiber is not separated from the bulk of the corn starch, companies using this technology cannot benefit from the EPA’s starch rule.

Interestingly, QCCP and Syngenta are claiming far higher ‘cellulosic ethanol’ yields – than Edeniq: QCCP is successfully claiming cellulosic ethanol credits for an additional 2 million cellulosic gallons from their otherwise 35 million gallon a year corn ethanol refinery. On the other hand the first company to commercially employ Edeniq’s process, Pacific Ethanol, claims to be making an extra 750,000 gallons of cellulosic biofuels from a previously 60 million gallon a year corn ethanol plant. This suggests that the amount of starch-derived ‘cellulosic ethanol’ for which QCCP and Syngenta are claiming subsidies could be far higher than the 5% suggested by the EPA.

Obtaining ethanol from cellulose contained in corn kernel fiber bypasses nearly all of the key challenges of cellulosic ethanol production:

  • Obtaining a clean and fairly homogenous feedstock (free from gravel and other impurities) which remains a big challenge for cellulosic ethanol from agricultural residues in particular;
  • The technologies which are now being marketed do not involve fermenting sugars contained in hemicellulose. Only glucose is fermented;
  • Separating cellulose (and hemicelluloses) from lignin is a key challenge of cellulosic ethanol production. Corn fiber, however, contains very little lignin and, according to one article, most of that is “in an immature form”, which presumably means less recalcitrant.

The only innovations, compared to conventional corn ethanol refining are two straightforward ones:

  • Different mechanical processing of the corn kernels at the outset (Edeniq), or processing of the fermentation residues (QCCP), and
  • Addition of enzymes which break down cellulose into glucose. There is no public information available about the enzymes used by Edeniq. However, QCCP uses an enzyme mixture developed by DuPont which was not even developed for cellulosic ethanol but simply for refining conventional starch-based ethanol more efficiently.

What makes corn fibre ethanol attractive to refiners?

According to Edeniq/Aemetis, corn ethanol refiners who use their new technology will raise overall ethanol yields by 7% and produce up to 2.5% cellulosic ethanol. The cellulosic fraction qualifies for much higher subsidies. A gallon of cellulosic ethanol attracts $1.0017 more under the Renewable Fuel Standard than a gallon of corn ethanol, and it also qualifies for an extra $1.01 in cellulosic incentive tax credit. Refiners hope that it will soon qualify for another $0.65 if it falls under the Californian Low Carbon Fuel Standard.

The new processing technique also yields more corn oil, which can be sold as a byproduct. The extra revenues are so high that Aemetis is offering the technology for no upfront cost, merely an obligation to share 50% of the extra revenues.

QCCP’s technology, meantime, promises even higher subsidies, since all of the additional ethanol yield is accredited as ‘cellulosic’ by the EPA. It also results in more corn oil.

Corn fibre ethanol could boost corn ethanol revenues enough to bolster the industry against falling prices

According to a Principal Economist at the University of Illinois, the new technologies could “produce more than 1 billion gallons of cellulosic ethanol at existing dry-grind plants”[1]. Ninety percent of US bioethanol facilities are of the dry-grind type. 1 billion gallons is a modest figure set beside existing corn ethanol production. However, it is a vast amount compared to the cellulosic ethanol sold to date.

Corn fibre ethanol technologies are being rapidly adopted. QCCP inaugurated their bolt-on cellulosic ethanol technology in September 2014. Pacific Ethanol followed suit in December 2015, installing Edeniq’s technology in their 60 million gallon refinery in Stockton, California. They are currently waiting for EPA accreditation of their ‘cellulosic ethanol’, which will clear the way for other refineries which install this technology to also cash in on cellulosic ethanol credits. Pacific Ethanol owns eight corn ethanol refineries in total. Edeniq’s owners Aemetis intend to use the technology at their 60 million gallon plant in Keyes, California later this year. Flint Hills Resources have announced that they will use it at each of their seven corn ethanol refineries, which have a combined capacity of 820 million gallons a year. Siouxland Energy Cooperative has licensed Edeniq’s technology and intends to use it at their 60 million gallon refinery in Nebraska later this year. Syngenta states that they expect the technology used by Quad County Corn Processors to be adopted by two other corn ethanol refineries by 2017.

At a time when revenues are being squeezed by lower oil prices, such higher revenues could well allow some corn ethanol refiners to stay afloat even if oil prices stay low. This would turn cellulosic ethanol subsidies into a lifeline for corn ethanol refineries.

Almuth Ernsting is Co-Director of Biofuelwatch (www.biofuelwatch.net).

Aug 032016
 

Robert Schooler CornellRobert Schooler (Independent Science News)

My name is Robert, and I am a Cornell University undergraduate student. However, I’m not sure if I want to be one any more. Allow me to explain.

Cornell, as an institution, appears to be complicit in a shocking amount of ecologically destructive, academically unethical, and scientifically deceitful behavior. Perhaps the most potent example is Cornell’s deep ties to industrial GMO agriculture, and the affiliated corporations such as Monsanto. I’d like to share how I became aware of this troubling state of affairs.

Throughout my secondary education, I’ve always had a passion for science. In particular, physics and mathematics captured my fascination. My sophomore AP physics teacher, Mr. Jones, became my main source of motivation to succeed. He convinced us students that our generation was crucial to repairing humanity’s relationship to science, and how we would play key roles in solving immense global issues, such as climate change. Thank you Mr. Jones! Without your vision, I would have never had the chance to attend such an amazing university.

I came to Cornell as a freshman, deeply unaware of our current GMO agriculture paradigm, and my university’s connection to it. After two years of school, however, I was reluctant to continue traditional study. I never felt quite at ease, jumping through hoops, taking classes and tests that didn’t inspire me, in exchange for a piece of paper (degree) that somehow magically granted me a superior life. I know many undergraduates fit right in with the university education model, and that’s fantastic. I certainly didn’t, and my mental and physical health began to suffer as a result. I was left with no choice but to take a leave of absence, and pursue another path.

Instead, I began to self-study nutrition out of pure necessity. Luckily, I found Cornell Professor Emeritus T. Colin Campbell’s legendary epidemiological research on nutrition and human disease. His evidence was so clear that I quickly transitioned to a plant-based diet. This personal dietary shift had profound benefits, dispelled my depression, and led me to a deep fascination with the precursor to nutrition: agriculture. I became particularly interested in agroecology. I was astonished to learn that there existed alternatives to chemical-intensive, corporate-controlled models of agriculture, and that they were far safer, more effective, and more sustainable. During my time away from Cornell, I participated in three unique seasons of agroecological crop production, with incredible results. I am immensely grateful for these experiences.

It’s impossible to study and practice agroecology without becoming deeply aware of the other end of the spectrum: the genetic modification of our food supply, ruled by giant agribusiness corporations.

Currently, the vast majority of US commodity crops (corn, soy, alfalfa, sugar beet) are genetically engineered to either withstand Roundup herbicide or produce Bt toxin pesticide. These “technologies” are ecologically damaging and unsafe. The majority of these crops go to feed animals in factory farms. The remainder generally gets converted into corn syrup, white sugar, vegetable oil, or biofuels — you know, good stuff! This combined approach of growing GMO commodity monoculture crops, and feeding them to factory-farmed livestock, is one of the most ecologically destructive forces our planet has ever seen. It’s also a leading contributor to climate change. In fact, some experts believe it to be the leading cause.

As Professor T. Colin Campbell will tell you, the foods that come from this system (animal products and processed foods) are responsible for causing the vast majority of chronic disease. That’s a story for another day.

Cornell’s GMO Propaganda Campaign

I came back to Cornell a changed person, with a drastically different perspective. I was in for quite a shock, however: I sat in on a course entitled “The GMO Debate”. I was expecting members of an intellectual community coming together, with proponents and critics of GMO food each giving the best verified evidence they had to support their cause. Given all that I had learned about GMO agriculture, I was excited to participate for the “GMO skeptic” side.

The GMO Debate course, which ran in the fall of 2015, was a blatant display of unscientific propaganda in an academic setting. There were a total of 4 active professors in the course, and several guest speakers. They took turns each session defending industrial agriculture and biotechnology with exactly zero critical examination of GMOs. In spite of the course’s name, there was a complete lack of actual “debate”. Here are some of the more memorable claims I heard that fall semester:

  • GMO food is necessary to feed the world
  • there is no instance of harm from agricultural GMOs
  • glyphosate, the main ingredient in Roundup, is safer than coffee and table salt
  • if you believe in science, you must believe in GMO technology
  • the science of genetic engineering is well understood
  • “what off-target effects?” … when asked about the proven biochemical risks of GE technology
  • Vitamin A rice is curing children of Vitamin A deficiency (even though the IRRI, the research institute responsible for rolling it out, says it won’t be ready for some years: http://goo.gl/mHcsoJ)
  • Current pesticides and herbicides don’t pose an ecological or human health risk
  • Bt is an organic pesticide, therefore Bt GMO crops are safe and pose no additional risk
  • Bt crops work just fine — but we are now engineering insects as a complementary technology — to make the Bt work better
  • “Are you scared of GMO insects? Because you shouldn’t be.”
  • GMO crops are the most rigorously tested crops in the history of food
  • “If [renowned environmentalist] Rachel Carson were alive today, she would be pro-GMO”

It gets better. During the semester, emails were released following a Freedom of Information Act request, showing that all four of the professors in the class, as well as several guest speakers, the head of Cornell’s pro-GMO group “Alliance for Science, and the Dean of the College of Arts and Life Sciences were all copied in on emails with Monsanto. This was part of a much larger circle of academics promoting GMO crops on behalf of the biotech industry. Jonathan Latham PhD, virologist and editor of independentsciencenews.org, documented this in an article titled The Puppetmasters of Academia. I highly recommend giving it a read, for further context.

Perhaps saddest of all was the inclusion of several visiting African agriculture-academics in the course. They were brought here by the “Cornell Alliance for Science”. This organization was completely funded by a $5.6 million grant from the Bill and Melinda Gates Foundation, and appears to espouse only pro-GMO rhetoric. For those of you who are unaware, Bill Gates is a proponent of using agricultural biotechnology in Africa, India, and other developing regions. So in essence, a group of African representatives got indoctrinated into the industrial and GMO agriculture framework, and were sent home to disseminate this information … after all, who could question the expertise of an Ivy League powerhouse such as Cornell?

I then learned of Cornell’s deep historic ties to the biotech industry, which explained what I witnessed in the “GMO Debate” course. Notable examples include the invention of both the controversial bovine growth hormone, and the particle bombardment (“gene gun”) method of creating GMO crops. Both of these cases are connected to Monsanto.

To say the least, I was completely stunned.

What I’m going to do about all of this

You didn’t think I was just going to complain about a pro-GMO, industry-sponsored Cornell all day, did you? Good, because I have come up with a plan to create actual, lasting change on campus.

A student-led, expert-backed, evidence-based GMO course

I have decided to host an independent course on the current GMO paradigm, in response to Cornell’s course. It will be held on campus, but will have zero influence from Cornell or any biotech organization. Every Wednesday evening, from September 7th to November 16, we will host a lecture. This lecture series is completely free, open to the entire Cornell community and broader public, and will be published online (for free, forever) at my project, gmowtf.com.

There will be several experts and scientists coming in to lecture for this course. Frances Moore Lappé, of “Diet for a Small Planet” and “World Hunger: 10 Myths” fame, will be introducing the course on September 7, via video presentation. She will be speaking on how GMO agriculture is unnecessary to end world hunger.

Steven Druker is a public interest attorney and author of the powerful book “Altered Genes, Twisted Truth: How the Venture to Genetically Engineer Our Food Has Subverted Science, Corrupted Government, and Systematically Deceived the Public”, which Jane Goodall (in her foreword) hails as “one of the most important books in the last 50 years”. He will be giving two lectures that elaborate on the themes in the book’s subtitle and demonstrate that the GMO venture has been chronically and crucially dependent on deception, and could not survive without it.

Jonathan Latham PhD will be giving two lectures, on the dangers of Roundup Ready and Bt crops, respectively. He will also be participating in our special October 5 debate, representing the anti-GMO panel, alongside Michael Hansen PhD, a senior scientist for the Consumers Union. Jonathan has direct experience genetically modifying organisms, so his expertise is guaranteed.

Allison Wilson PhD is a geneticist and editor/science director of the Bioscience Resource Project. She will be giving a lecture on how GMOs are actually created, to dispel any industry myths of precision, accuracy, or deep genetic understanding.

Belinda Martineau PhD is a geneticist with an interesting history — she was on the team of genetic engineers that created the first commercial GM food crop, the Flavr Savr Tomato. She authored a book on her experience, titled “First Fruit: The Creation of the Flavr Savr Tomato and the Birth of Biotech Foods”. Her lecture will be a historical and personal account of the science, regulation, and commercialization of genetically engineered foods, effectively giving context for today’s GMO paradigm.

My personal scientific hero, T. Colin Campbell, who started me on this whole journey years ago, will not be speaking on GMOs per se … but will address some critically important, related topics: academic freedom and scientific integrity. He began his Cornell career over half a century ago, and has “seen it all”. He has fascinating anecdotes that will illuminate these campus-wide issues beautifully.

Jane Goodall, if you’re reading this, you are personally invited to take time out of your busy schedule to come and give the final capstone lecture. I know how passionate you are about saving our species, our planet, and all of its beautiful inhabitants. Your wise presence in this project would take it to the next level. Alternatively, please consider a short video interview. This offer stands indefinitely. Same for you Vandana Shiva!

All in all, our independent GMO lecture series will focus on real threats and real solutions to our current ecological crisis … and perhaps most importantly, will feature 100% less Monsanto influence than Cornell’s course! Sounds good to me.

Taking it further

I’m on my second leave of absence from Cornell to work on this project, and due to my experiences, I have somewhat given up on a Cornell degree … not that I was ever intensely focused on attaining one. This GMO course is by far the most important thing I can do with my Cornell “career”. However, it is just the beginning of my plan.

Remember the $5.6 million Bill Gates gave Cornell through his foundation, to push the pro-GMO propaganda? Well, to coincide with our course, we’re launching an initiative to raise the same amount of money or more to sponsor more appropriate forms of agriculture, educational outreach, and activism. Go to gmowtf.com for more information, but in essence, this would finance:

  • Continued grassroots educational activism at Cornell, and similar programs in other compromised universities (UC Davis and Berkeley, University of Florida, etc.) across the country.
  • A plant-based, NON-GMO independent dining hall for Cornell students. It would source as close to 100% organic and local food as possible. Ideally, it would be cheaper than Cornell’s plan (plant-based eaters won’t subsidize expensive meat and dairy for omnivorous eaters).
  • gmowtf.com as a permanent, free, independent, constantly updated resource for GMO science, policy, news, etc. … also the GMO course would remain online
  • My dream: a research farm focused on rigorous analysis of agroecological practices. There is an infinitum of fascinatingly effective agroecological techniques that are underrepresented in the scientific community (in favor of faddist, ineffective GMO “technology”).
  • Completely paying off student debt for a group of 10-15 undergraduates who are willing to help spread this message to the Cornell community.

Mr. Gates, if you truly care about feeding the world in a safe and sustainable manner, and if you are truly dedicated to science and to the kind of open, fact-based discourse on which it depends, I implore you to learn the important facts about which you have apparently been misinformed — and which are being systematically misrepresented by the Cornell organization you are funding. You can easily gain illumination by reading Altered Genes, Twisted Truthby Steven Druker, one of the key contributors to our independent GMO course. You might find Chapter 11, on the ramifications and risks of altering complex information systems, of particular interest. You are, after all, the world’s most famous software developer!

As the chapter demonstrates, biotechnicians are significantly altering the most complex yet least understood group of information systems on earth — the ones that undergird the development and function of living organisms. Yet, they fail to implement the kind of safeguards that software engineers have learned are imperative when making even minor revisions to life-critical human-made systems. Can this be legitimately called science-based engineering?

Bill, feel free to reach out to any of the experts in our course, and don’t be hesitant to update your views on GMO agriculture in light of new understanding. A genuine scientist lives by this principle.

I Invite you all to go to gmowtf.com and explore my proposals more. Please bear with the construction of the site in the coming weeks, in preparation for our amazing GMO course!

We live in somewhat of a scientific dark age. Our universities have become extensions of corporate power, at the cost of our health, livelihoods, and ecology. This has to stop, yesterday. We cannot afford to spread lies to our undergraduate students. Cornell, please reconsider your ways. Until you do, I will be doing everything in my power to counter your industry GMO propaganda efforts with the facts.

With love,

Robert Schooler

contact (at) gmowtf.com

Jul 272016
 
GMO corn field in Kauai

Photo by Ian UmedaA GMO corn field in Kauai. While a recent National Academy of Sciences study found no evidence that eating genetically engineered food can cause adverse health effects, it also found no evidence that GE traits have provided measureable increases in overall crop productivity.

Unresolved safety questions about gene-editing technologies underscore need for caution

While expressing support for the watered-down GMO labeling bill, which was passed by Congress last week and is now awaiting President Obama’s signature, White House spokeswoman Katie Hill told Bloomberg News: “While there is broad consensus that foods from genetically engineered crops are safe, (emphasis added) we appreciate the bipartisan effort to address consumers’ interest in knowing more about their food….”

Making these kinds of broad statements about all genetically modified foods being “safe” seem to be a common quirk among even among science journalists who write about  GMOs. There is a tendency to describe genetically engineered crops as though they are just one thing. True, GMOs have many traits in common, but so do planes, trains, and automobiles. Writers who lump them together often ignore important subtleties and distinctions between each GMO crop, how they are created and used, as well as the damaging agricultural practices most of the transgenic crops under commercial cultivation promote.

Consider, for example, this story at Slate.com by William Saletan which proclaims that “there’s no good evidence” that GMOs are unsafe. “The deeper you dig,” he writes, “the more fraud you find in the case against GMOs. It’s full of errors, fallacies, misconceptions, misrepresentations, and lies.”

Saletan could find no room for a single mention of the nagging, unresolved safety questions involving new gene-editing biotechnologies like RNA interference or CRISP/Cas9, or to investigate industry claims about increased crop yields, or to note that while less than a handful of GM crops like the ringspot-resistant papaya (engineered to resist a virus that once threatened to wipe out the fruit from the Hawaiian islands) have definitely helped save a fruit crop, biotech corporations have largely focused on commodity crops like corn, soy, and cotton, where the profit margin is higher.

It’s not that he was crimped for space. He rambled on for 10,000 words, or about three times the length of a long-form magazine article. Although such details can annoyingly disrupt a story’s overall arc, they are newsworthy nonetheless. At the time his article was published (June 2015) the safety of these newer technologies was already generating robust debates among scientists.

You can find the same kind of superficial analysis of GMOs in this September 2014 Forbes piece (“The Debate About GMO Safety Is Over”), as well as in this August 2015 Scientific American article (“Why People Oppose GMOs Even Though Science Says They Are Safe. ”)

However, if you are looking for a somewhat more nuanced perspective about this technology, which has been around for only a couple decades, you might want to put aside media reports and official statements, and turn to “Genetically Engineered Crops: Experiences and Prospects,” a study published in May 2016 by the National Academy of Sciences. While many reports about the study claimed that the NAS had concluded that GE foods were “safe,” a fair reading of the NAS study reveals that the safety of GE products is much more complicated than you might think.

The truth is, the NAS study delves into both the benefits and problems associated with the biotechnology. While, as many of the new reports about the study noted, it found no evidence that eating genetically engineered food can cause adverse health effects, it also found no evidence that GE traits have provided measureable increases in overall crop productivity.  “Although emerging genetic-engineering technologies have the potential to assist in achieving a sustainable food system, broad and rigorous analyses will be necessary to determine the long-term health, environmental, social, and economic outcomes of adding specific crops and traits to an agroecosystem,” the report said.

This finding explodes the agrochemical industry’s oft-repeated claim that genetically engineered foods are a key to ending the problem of world hunger.

The NAS found that crop yields for corn, soybeans, and cotton have shown little or no improvements since GE varieties of these crops were first introduced in the early 1990s. Or as the study puts it, nationwide data “do not show a significant signature of genetic engineering technology on the rate of yield increase.”

Doug Gurian-Sherman, a scientist with the Center for Food Safety, said this finding “strongly implies that other factors, such as advances in conventional breeding methods, have played a critical role in raising crop productivity.”

While GMOs may not be a solution to world hunger, they may be a solution to sagging corporate profits.

The academy points out that roughly half of US land in crop production in 2014 was planted with genetically engineered seeds — mainly corn, soybeans and cotton — which command a premium price over conventional seeds. Almost all most of these crops were engineered with the ability to resist herbicides, insecticides, or a combination of the two. The sale of these pesticides is also a source of revenue for Big Ag corporations.

The 407-page study makes clear that there are other potential problems with the biotechnology. For example, it surveys the explosive evolution of herbicide-resistant superweeds and the rise of insecticide-resistant superbugs as a result common GMO cultivation practices that rely heavily on pesticides and herbicides.

It found that in many cases, GE crops that are engineered to include the bacterial toxin Bt are contributing to the evolution of insect pests that are resisting the Bt toxin, eroding the benefits of these crops. It also found that the use of herbicide-resistant crops, such as those that are engineered to withstand applications of the weed-killer glyphosate, “were initially correlated with decreases in total amount of herbicide applied per hectare of crop per year, but the decreases have not generally been sustained.”

Some weed species have even increased in abundance as herbicide-resistant crops have become widely planted, the NAS said.

Unfortunately, there are some significant gaps in NAS’ safety analysis too, such as its failure to mention that GE products have been found to cause harm to farmworkers when they are grown with the aid of synthetic pesticides such as glyphosate and 2,4-D, as they most often are. Both pesticides have been linked to cancer by the World Health Organization.

The academy also considered the potential hazards of emerging “gene-editing” biotechnologies like RNA interference (RNAi, also known as “gene silencing”) and “clustered regularly interspaced short palindromic repeats “ or CRISPR, which the food biotech industry is increasingly turning to. These technologies work by editing or altering certain genes in the crop itself to create traits such as disease resistance and drought tolerance (unlike first-generation GMOs that are created by inserting genes from other organisms into a crop.)

Interestingly, the version of the GMO labeling bill that Obama is scheduled to sign into law makes no mention of gene-editing technologies — an omission that critics say has been pushed by the biotech industry. Which means, as the bill stands now, crops or packaged foods that include gene-edited ingredients wouldn’t require labeling.

Unfortunately, at a time when we need more reliable information about the ramifications of these emerging technologies, the NAS’s discussion of them is rather superficial. For example, its section on RNAi focused almost solely on the findings of a white paper by Environmental Protection Agency scientists that is nearly three years old, but it failed to mention the safety warnings advanced in several newer studies.

These new studies suggest that genetically modified molecules produced by RNAi biotechnology may be reaching the human bloodstream. One controversial study even found they could damage a person’s health by compromising the human body’s ability to neutralize harmful types of cholesterol. This study’s findings have been wholly or partially confirmed by several other studies but have been dismissed here, here and here. The debate rages on.

The NAS believes that other gene-editing techniques, such as CRISPR may be capable to hitting the targeted genes more accurately than RNAi. However, the science is far from settled. Safety reviews of CRISPR technologies have yet to be completed.

Moreover, the NAS neglected to mention that the EPA is far from finished with its own safety review of RNAi technology.

In March 2016, after the agrochemical corporations Monsanto and Dow applied for an EPA permit to release SmartStax Pro, an RNAi-derived pesticidal corn product, the EPA announced it would take a closer look at the product’s safety this fall when it will convene its Scientific Advisory Panel (SAP).

SmartStaxPro corn seeds are engineered to release a toxin that kills the western corn rootworm, one of its main nemeses. It is one of the few RNAi-derived pesticidal products developed so far, but the EPA expects there will be more.

The EPA says it expects to make a decision on the SmartStaxPro application sometime next spring. Of course, if research studies had already proven that all GMOs are safe, there would be no point in conducting these safety reviews.

“This will be the first serious evaluation of agricultural RNAi technology done by the US government,” says Mardi Mellon, a science consultant for the Center for Food Safety, a food advocacy group. “Putting together another SAP to look at a specific RNAi crop suggests the agency is going to thoroughly consider the technologies’ risks.

Mellon notes that a review by of SmartStaxPro by the Food and Drug Administration “barely mentioned risks,” and that a review by the US Department of Agriculture “was superficial and deferred in part to the EPA review, which at the time had yet to be completed.”

Corporations like Monsanto that produce of genetically engineered seeds have responded to herbicide resistant weeds by “stacking” resistance to various combinations of herbicides like glyphosate, glufosinate, 2,4-D, and dicamba in their seeds.

But the NAS said that this strategy appears to be misguided. It recommended that farmers should attempt to delay the evolution of weeds that are resistant to herbicides by avoiding the practice of “simply spraying mixtures of herbicides.”

All of this goes to show that, in the absence of enough, thoroughly researched scientific information on the varied impacts of genetically engineered crops, including crops created using the next generation of genetic manipulation technologies, it’s not too much to want to know whether they are turning up in the food we put on the table.

Sadly, the version of the federal GMO-labeling bill we have now will allow companies to hide this information behind hard to read codes and links to websites that would require shoppers to have smartphones and Internet access. Seems like the “Deny Americans the Right to Know” or DARK Act is living up to its name.

Jul 192016
 

head-in-sandBy Sharon Begley (STAT)

WASHINGTON — At scientific meetings on genome-editing, you’d expect researchers to show pretty slides of the ribbony 3-D structure of the CRISPR-Cas9 molecules neatly snipping out disease-causing genes in order to, everyone hopes, cure illnesses from cancer to muscular dystrophy. Less expected: slides of someone kneeling on a beach with his head in the sand.

Yet that is what Dr. J. Keith Joung of Massachusetts General Hospital showed at the American Society of Hematology’s workshop on genome-editing last week in Washington. While the 150 experts from industry, academia, the National Institutes of Health, and the Food and Drug Administration were upbeat about the possibility of using genome-editing to treat and even cure sickle cell disease, leukemia, HIV/AIDS, and other blood disorders, there was a skunk at the picnic: an emerging concern that some enthusiastic CRISPR-ers are ignoring growing evidence that CRISPR might inadvertently alter regions of the genome other than the intended ones.

“In the early days of this field, algorithms were generated to predict off-target effects and [made] available on the web,” Joung said. Further research has shown, however, that such algorithms, including one from MIT and one called E-CRISP, “miss a fair number” of off-target effects. “These tools are used in a lot of papers, but they really aren’t very good at predicting where there will be off-target effects,” he said. “We think we can get off-target effects to less than 1 percent, but we need to do better,” especially if genome-editing is to be safely used to treat patients.

That, of course, is the hope of companies including Editas Medicine, which Joung cofounded, CRISPR Therapeutics, Caribou Biosciences, and Sangamo BioSciences, which all presented at the ASH workshop.

Off-target effects occur because of how CRISPR works. It has two parts. RNA makes a beeline for the site in a genome specified by the RNA’s string of nucleotides, and an enzyme cuts the genome there. Trouble is, more than one site in a genome can have the same string of nucleotides. Scientists might address CRISPR to the genome version of 123 Main Street, aiming for 123 Main on chromosome 9, only to find CRISPR has instead gone to 123 Main on chromosome 14.

In one example Joung showed, CRISPR is supposed to edit a gene called VEGFA (which stimulates production of blood vessels, including those used by cancerous tumors) on chromosome 6. But, studies show, this CRISPR can also hit genes on virtually every one of the other 22 human chromosomes. The same is true for CRISPRs aimed at other genes. Although each CRISPR has zero to a dozen or so “known” off-target sites (where “known” means predicted by those web-based algorithms), Joung said, there can be as many as 150 “novel” off-target sites, meaning scientists had no idea those errors were possible.

One reason for concern about off-target effects is that genome-editing might disable a tumor-suppressor gene or activate a cancer-causing one. It might also allow pieces of two different chromosomes to get together, a phenomenon called translocation, which is the cause of chronic myeloid leukemia, among other problems.

Many researchers, including those planning clinical trials, are using web-based algorithms to predict which regions of the genome might get accidentally CRISPR’d. They include the scientists whose proposal to use CRISPR in patients was the first to be approved by an NIH committee. When scientists assure regulators that they looked for off-target effects in CRISPR’d cells growing in lab dishes, what they usually mean is that they looked for CRISPR’ing of genes that the algorithms flagged.

As a result, off-target effects might be occurring but, because scientists are doing the equivalent of the drunk searching for their lost keys only under the lamppost, they’re not being found.

One little-appreciated feature of CRISPR’s DNA-cutting enzyme is that it doesn’t stop at one. Even if the enzyme cuts its intended target, the risk of off-target cutting remains. The enzyme “still has energy to bind with off-target sites,” Joung said, so “it can still cleave those sites.”

Scientists from some of the leading genome-editing companies said they are confident they will be able to minimize off-target CRISPR’ing, by picking “high-quality” guide RNAs, among other methods. While “bad” RNAs hit as many as 152 wrong targets, studies show, good ones hit only one, and the algorithms “capture most of” the potential off-target effects, said Dr. Bill Lundberg, chief scientific officer of CRISPR Therapeutics. Still, he conceded, “At the end of the day we’re taking a cell where we can’t predict a priori where the edit has happened.”

Scientists have recently recognized another reason to worry about off-target effects: No two people’s genomes are identical. Off-target-identifying methods, which are based on a composite or “reference” human genome, might indicate that there are no stretches of DNA that CRISPR can mistakenly snip. But because of random mutations and genetic variations, some patients might have additional “123 Main Street”s, attracting CRISPR and its DNA-cutting enzyme where they’re not supposed to go.

“There are a significant percent of sites, more than I would have thought,” where that might happen, said Joung, “and it varies by ethnic group.”

Said Andrew May, chief scientific officer of Caribou: “There is going to have to be some consideration of that” as genome-editors try to bring CRISPR to patients.