Search Results : Search » SynBioWatch » Page 2

Dec 052016
 
Webridge (revised from) CC BY 2.0, via Wikimedia Commons

Webridge (revised from) CC BY 2.0, via Wikimedia Commons

CANCUN, MEXICO – This week, international conservation and environmental leaders are calling on governments at the 2016 UN Convention on Biodiversity to establish a moratorium on the controversial genetic extinction technology called gene drives.

More resources on gene drives and campaigns at CBD COP13

Gene drives, developed through new gene-editing techniques- are designed to force a particular genetically engineered trait to spread through an entire wild population – potentially changing entire species or even causing deliberate extinctions. The statement urges governments to put in place an urgent, global moratorium on the development and release of the new technology, which poses serious and potentially irreversible threats to biodiversity, as well as national sovereignty, peace and food security.

Over 160 civil society organisations from six continents have joined the call. Among them were environmental organizations including Friends of the Earth International; International Union of Food Workers representing over 10 million workers in 127 countries ; organizations representing millions of small-scale famers around the world, such as the La Via Campesina International and the International Federation of Organic Agricultural Movements; the international indigenous peoples’ organization Tebtebba; scientist coalitions including European Network of Scientists for Social and Environmental Responsibility and Unión de Científicos Comprometidos con la Sociedad (Mexico); as well as ETC Group and Third World Network.

“We lack the knowledge and understanding to release gene drives into the environment – we don’t even know what questions to ask. To deliberately drive a species to extinction has major ethical, social and environmental implications,” says Dr. Steinbrecher, representing the Federation of German Scientists. “It is essential that we pause, to allow the scientific community, local communities and society at large to debate and reflect. We can’t allow ourselves to be led by a novel technique. In the meantime, a moratorium is essential.”

“These genetic extinction technologies are false solutions to our conservation challenges,” said Dana Perls of Friends of the Earth. “We want to support truly sustainable and community driven conservation efforts. Gene drives could be co-opted by agribusiness and military interests. We need a moratorium on irreversible and irresponsible technologies such as gene drives.”

“Gene drives will be one of the fiercest debates at CBD this year,” says Jim Thomas of ETC Group. “Gene drives are advancing far too quickly in the real world, and so far are unregulated. There are already hundreds of millions of dollars pouring into gene drive development, and even reckless proposals to release gene drives within next four years.”

“The CBD is the premier international treaty for protecting biodiversity and life on earth from new threats,” said Lim Li Ching of Third World Network. “It is within the mandate of the CBD to adopt this moratorium, and countries that are party to this agreement must act now to avoid serious or irreversible harm.”

A press conference on the Call for a Moratorium will be held on December 5, 2016 at 3pm EST in the Press Conference Room. It can be live-streamed at http://flux.live/cop/coplive/pr.html.

###

Expert contacts:

English: Jim Thomas, (514) 516-5759, jim@etcgroup.org; Dana Perls, +1 (925) 705-1074, dperls@foe.org; Dr. Ricarda Steinbrecher, +44 (776) 973-3594, r.steinbrecher@econexus.info

Spanish: Silvia Ribeiro, +52 55 2653 3330, silvia@etcgroup.org; Veronica Villa, +52 1 55 5432 4679, veronica@etcgroup.org.

Communications contacts: Trudi Zundel, (226) 979-0993, trudi@etcgroup.org; Marie-Pia Rieublanc (se habla español), +52 1 967 140 4432, territorios@otrosmundoschiapas.org.

Note to Editors:

  1. A copy of the Call for a Global Moratorium on Gene Drives is available with a complete list of signatories, and a short briefing outlining the arguments for a global moratorium on gene drives prepared by the Civil Society Working Group on Gene Drives is available at http://www.synbiowatch.org/gene-drives/gene-drives-moratorium
  2. The organizers of the letter are still inviting organizations to join as signatories. Additional organizational signatures can be sent to: trudi@etcgroup.org
  3. The UN Convention on Biodiversity (CBD) is meeting from December 4-17 in Cancun, Mexico. Other synthetic biology topics are being negotiated – more background found in this media advisory: http://www.foe.org/news/news-releases/2016-12-genetic-extinction-tech-and-digital- dna-challenged
  4. In the lead up to COP 13, German Minister for the Environment Barbara Hendricks wrote a statement saying she would not support the release of gene drives into the environment. https://www.testbiotech.org/en/node/1772
  5. In September 2016, the International Union for Conservation of Nature (IUCN) adopted a de facto moratorium on the support or endorsement of research into gene drives for conservation or other purposes. At the same time, 30 leading conservationists and environmentalists called for a moratorium. More information on this moratorium is available at http://www.foe.org/news/news-releases/2016-08-genetic-extinction-technology-rejected-by- international-group-of-scientists.
  6. In June 2016, the US National Academy of Sciences released “Gene Drives on the Horizon,” a report that explored the environmental and social concerns of gene drives, and warned against the environmental release of gene drives. More information on the report can be found at http://nas-sites.org/gene-drives/
Nov 302016
 

gene-drives-image

“Genetic engineering is passé. Today, scientists aren’t just mapping genomes and manipulating genes,
they’re building life from scratch – and they’re doing it in the absence of societal debate and regulatory oversight.”
– Pat Mooney, Executive Director of ETC Group, whose mission is to access the consequences and impacts of new technologies.

Listen to the podcast here: https://www.podomatic.com/podcasts/postcarbon/episodes/2016-11-28T15_39_01-08_00

KWMR Post Carbon Radio:

Our two guests are: Claire Hope Cummings, author of Uncertain Peril: Genetic Engineering and the Future of Seeds. Her concerns are how gene drives are proposed for use in conservation (Island Conservation’s daughterless mouse) and the whole idea of the eradication of the female (daughterless anything) and anything people need to know about the regulatory issues – most notably that there is no regulatory response to these new developments and the response to GMOs was terribly inadequate and facilitated widespread contamination, among other risks which are still a problem.

Jim Thomas is a Research Programme Manager and Writer at ETC Group, located in Ottawa, Canada. His background is in communications, writing on emerging technologies and international campaigning. For the seven years previous to joining ETC Group Jim was a researcher and campaigner on Genetic Engineering and food issues for Greenpeace International – working in Europe, North America, Australia/New Zealand and South East Asia. He has extensive experience on issues around transgenic crops and nanotechnologies has written articles, chapters and technical reports in the media and online.

Nov 212016
 

vat-768x432by Mary Lou McDonald (Safe Food Matters)

New words like “synthetic biology”, “GMOs 2.0”, “CRISPR”, and “new biology” are being heard.  And new compounds are in our fragrances, flavourings, cosmetics and foods.

The new words are for new techniques of genetic engineering. What are the techniques and their products, and should we be concerned?

New Techniques­

The old techniques of genetic engineering (GMOs 1.0) dealt with organisms, and inserted genes by either blasting them into an organism or transferring them via a virus. This was not very precise.

1. Gene Editing. A new technique is called “gene editing”. It is more on target. It can cut the genetic code of organisms with greater precision, insert new code, remove a code and swap out genes with others. Tools used in gene editing include “CRISPR-Cas9”, “Zinc Finger Nucleus” and “TALEN”.

2. Synthetic Biology. Another new technique is the creation of genetic code from scratch, without involving living organisms. This is called “synthetic biology” or “put together life”. It uses computer design technology to engineer and produce new codes in the lab.

Applications and Technologies

These techniques, when applied, have resulted in far-reaching technologies.

a) Applications of Gene Editing

Gene Drives.  A much talked-about technology is “gene drives”.  It drives the particular gene down to the offspring and doesn’t allow space for an alternate to arise, as would occur in natural evolution. Once a trait is forced down at the expense of the alternatives, the extinction of the “alternate” offspring is the ultimate result.

Gene drives have so far been used on yeast, fruit flies and 2 mosquito species, but have not yet been released to ecosystems. There is widespread discussion about using them to eradicate mice on islands, mosquitoes, and pests.

GMOs 2.0.  Gene editing is also used in agriculture, the old domain of GMOs 1.0. With GMOs 2.0, food is being engineered to insert, delete or replace DNA, and entirely new sequences are being created. Gene edited mushrooms (deletions in a gene for non-browning) and canola oil (a gene removed to tolerate herbicide) have both been commercialized. Monsanto in September, 2016 licensed the use of CRISPR to engineer food and Dupont in October 2015 predicted that CRISPR plants would be on dinner plates within 5 years. Proponents of gene editing argue that the resulting organisms are not “GM” or “novel substances”, and therefore aren’t subject to current regulation.

b) Applications of SynBio

Foods, Flavours, Fragrances. The synbio technique has spawned many new applications, including the creation of new compounds in consumer products that are so similar to existing products consumers can’t tell the difference.  The method used is to engineer artificial code into microbes and then ferment them on a large scale in vats. Manufacturers use the word “natural” because fermentation is involved.

Some existing and proposed products resulting from this application are artificial biofuels, vanilla, stevia, ginseng, wine, mint, cocoa, caffeine, scents, cleansers and soaps. (See “Are GMOs 2.0 in your Food and Cosmetics”; “What is Synthetic Biology: The Comic Book”).

New Life Forms. Another application is the engineering of completely new genetic codes and life forms. Current players in this sphere include the “DIY” community, students, and start-ups.  A code can be created on the computer and 3-D printed. The International Genetically Engineered Machine Competition (IGEM) is a university and high school competition for building “biobricks” (like lego) to operate in living cells. A recent commercial example of a new life form is a plant that glows in the dark.

Bio Weapons. A third application is military.  In the US, the Defense Advanced Research Projects Agency (DARPA) provides the most funding for synthetic biology in the US government (although the extent to which this is funnelled to bioweapons is not known). In the US, the Army, Navy and Office of the Secretary of State are also funding synbio. (See Extreme Genetic Engineering and the Human Future, p 31).

What is the Concern?

The concern is we don’t know if the new technologies are safe. Why not? Because we don’t completely understand the interactions that occur in living organisms and ecological systems.

Organisms are complex systems in which chemical reactions “fire” at different times and places along interconnected pathways. They do not behave in linear “cause and equal effect” ways, in either space or time. A gene is part of this system. It is a strand of DNA that messages or “fires” at times (or refrains from “firing”) and brings about an action or change in an organism. Similarly, ecological systems are complex systems.  They rely on species interconnections and interactions which also don’t behave in linear “cause and equal effect” ways.

If a complex system does not behave in a linear fashion, the workings of the systems cannot be known ahead of time and its effects cannot be predicted.  Similarly, the effects resulting from a change to one aspect of a system cannot be predicted. The effects can only be known “after the fact”, and, depending on the system, these effects may vary.

This inability to predict the results of a change in the system was the problem with GMOs 1.0, and is the same problem with these new techniques.  The concern will exist every time one of the new techniques is used in a complex living system. The scientific literature even acknowledges that there are often “unintended” or “unpredicted effects” associated with the products of genetic manipulation.  New substances are often created. Even CRISPR-Cas9 technology admittedly has the problem of being “off-target”.

Historical Examples 

The concern of unpredictability is underlined by historical examples of GMOs 1.0 gone wrong. In the late 1990s and early 2000s several people died as a result of reactions to gene therapy procedures, the most notable of which was 18 year old Jesse Gelsinger.  He died from a severe immune reaction to the viral vector used to transport engineered genes. Another example is the food supplement L-Tryptophan.  Genetic modification of the supplement created a new toxin that is linked to EMS, a disease that killed 80 people and afflicted thousands in the late 1980s, early 1990s.  (See “L-Tryptophan”).

Examples of agriculture GMOs 1.0 gone wrong include the case of canola. In 1995 Canada became the first country to approve commercialization of genetically engineered canola. GM canola has now spread and eliminated natural canola almost everywhere in Canada. Other examples of GM plants that have spread uncontrollably are: creeping bentgrass in the USA; cotton and maize in Mexico; BT poplar in China; Bt rice in China; and canola in Japan, the US, Australia and the EU. (See Transgene Escape by TestBiotech).

Supersized Concerns

The concern of unpredictability is more pronounced with these new synbio and gene editing techniques than with GMOs 1.0. Reason? The applications of these new techniques are very broad in scope, and their effects can be devastating.

Gene Drives. The scope of gene drives is obviously major. It extends to the possible extinction of a species, and resulting degradation of its ecosystem.  Even the National Academy of Sciences of the US, in a June 2016 report (at 86), admits that: “[R]eleasing a gene-drive modified organism into the environment means that a complex molecular system will be introduced into complex ecological systems, potentially setting off a cascade of population dynamics and evolutionary processes that could have numerous reverberating effects”.

GMOs 2.0. The scope of GMOs 2.0 extends to the food humans and animals eat and to the environment. The lack of current regulation and the speed at which the products are being advanced means the GMO 2.0 technologies and products will likely be used before they are assessed. This is even though the effects with GMOs 2.0 are compounded.  Testbiotech indicates that with the new gene editing techniques, a single step can be applied several times, causing large changes; plants and animals with genetic changes can be crossed with each other;  different techniques can be used in combination with each other; and that even small steps, if repeated, enable radical changes in the genome.

Foods, Flavours, Fragrances. The scope of the synbio application is enormous, on many fronts. The flavours and fragrance market is advancing quickly:  it was a US $26.5 billion market in 2016 and is expected to grow to over US $35 billion by 2019. Lux Research indicates synbio will be a “permanent and growing aspect” of the flavours market. A major socioeconomic effect is the displacement of natural botanical farmers: 95% of varieties of natural crops are grown by small-scale farmers, more than 20 million of whom depend on these crops for their livelihood.

The new compounds themselves are pervasive in our consumer products without being identified (except they might be called “natural”).  Common names include:  method, Ecover, patchouli, PeterThomasRoth, Evolva, Clearwood, TerraVia, Neossance Biossance, Eversweet (in Coca Cola Life), Agarwood Oil, Muufri animal free milk, among others.  The effect of these compounds on human beings has not been subject to regulatory assessment, even though they are biologically different than the natural botanical substances.

New Life Forms.  The synbio creation of new life forms in the DIY community is advancing, and there is no way to monitor the proliferation of this technology. The September 2016 report of Genome editing: an ethical review points out that a number of websites provide lab and other support services for amateurs, and DIY CRISPR kits are available on line.  A code can be 3-D printed and Fedexed for less than $100. The seeds and kit for the new glowing plant can be ordered on-line. The potential for intentional and unintentional release obviously exists, again with no regulations in place.

BioWeapons. The scope of the military application of synbio is not known, but appears to be growing as increasing amounts of government funding are directed toward the technology. The obvious risks are the inability to recall a release, and the potential for a release to be off-target.

In Sum

New technologies are advancing quickly and new products and substances are in our world.  Genes can now be created from scratch, a wide array of new products and foods can be created with greater precision, and whole species can be affected. The concerns around safety and unpredictability are the same, but the resulting risk profile has increased dramatically. We would do well to learn the new words.

Oct 202016
 
tobacco

Tobacco plantation. Ikhlasul Amal/Flickr CC

by Chee Yoke Ling and Edward Hammond (Project Syndicate)

AUSTIN, TEXAS – Four hundred years ago, John Rolfe used tobacco seeds pilfered from the West Indies to develop Virginia’s first profitable export, undermining the tobacco trade of Spain’s Caribbean colonies. More than 200 years later, another Briton, Henry Wickham, took seeds for a rubber-bearing tree from Brazil to Asia – via that great colonialist institution, London’s Royal Botanic Gardens – thereby setting the stage for the eventual demise of the Amazonian rubber boom.

At a time of unregulated plant exports, all it took was a suitcase full of seeds to damage livelihoods and even entire economies. Thanks to advances in genetics, it may soon take even less.

To be sure, over the last few decades, great strides have been made in regulating the deliberate movement of the genetic material of animals, plants, and other living things across borders. The 1992 United Nations Convention on Biological Diversity, in particular, has helped to safeguard the rights of providers of genetic resources – such as (ideally) the farmers and indigenous people who have protected and nurtured valuable genes – by enshrining national sovereignty over biodiversity.

While some people surely manage to evade regulations, laboriously developed legal systems ensure that it is far from easy. The majority of international exchanges of seeds, plants, animals, microbes, and other biological goods are accompanied by the requisite permits, including a material transfer agreement.

But what if one did not have to send any material at all? What if all it took to usurp the desired seeds was a simple email? What if, with only gene sequences, scientists could “animate” the appropriate genetic material? Such Internet-facilitated exchanges of biodiversity would clearly be much harder to regulate. And, with gene sequencing becoming faster and cheaper than ever, and gene-editing technology advancing rapidly, such exchanges may be possible sooner than you think.

In fact, genes, even entire organisms, can already move virtually – squishy and biological at each end, but nothing more than a series of ones and zeros while en route. The tiny virus that causes influenza is a leading-edge example of technical developments.

Today, when a new strain of influenza appears in Asia, scientists collect a throat swab, isolate the virus, and run the strain’s genetic sequence. If they then post that strain’s sequence on the Internet, American and European laboratories may be able to synthesize the new virus from the downloaded data faster and more easily than if they wait for a courier to deliver a physical sample. The virus can spread faster electronically than it does in nature.

More complicated viruses and some bacteria are in the range of such techniques today, though wholly synthesizing a higher organism with a more complex genome, such as maize, is many years away. But that may not matter, as new gene-editing technologies, like CRISPR-Cas9, enable scientists to stitch together complicated new organisms, using gene sequence information from organisms to which they do not have physical access.

For example, the key traits of a drought-resistant maize from a Zapotec community in Oaxaca, Mexico, might be reproduced by editing the genes of another maize variety. No major new advance in the technology is needed to unlock this possibility.

What is needed is the genetic sequences of thousands of types of maize. Those data act as a sort of roadmap and resource pool, enabling scientists to compare sequences on a computer screen and identify pertinent variations. The selected adjustments might then be made to, say, the parents of a new Monsanto or DuPont Pioneer maize hybrid.

Managing access to large genomic databases thus becomes critically important to prevent a virtual version of the theft carried out by Rolfe and Wickham. And, indeed, in an unguarded e-mail released under the US Freedom of Information Act, one of the US Department of Agriculture’s top maize scientists, Edward Buckler, called such management “the big issue of our time” for plant breeding.

If agricultural biotechnology corporations like Monsanto and DuPont Pioneer – not to mention other firms that work with genetic resources, including pharmaceutical companies and synthetic biology startups – have free access to such databases, the providers of the desired genes are very likely to lose out. These are, after all, wholly capitalist enterprises, with little financial incentive to look out for the little guy.

In this case, that “little guy” could be African sorghum growers, traditional medicinal practitioners, forest peoples, or other traditional communities – people who have created and nurtured biodiversity, but never had the hubris or greed to claim the genes as proprietary, patented inventions. All it would take is for someone to sequence their creations, and share the data in open databases.

Yet open access is the mode du jour in sharing research data. The US government’s GenBank, for example, doesn’t even have an agreement banning misappropriation. This must change. After all, such no-strings-attached databases do not just facilitate sharing; they enable stealing.

The question of how to regulate access to genetic sequence data is now cropping up in international discussions, including at the World Health Organization and the Food and Agriculture Organization. Perhaps the most important forum for such discussions is the Conference of the Parties to the Convention on Biological Diversity, the main treaty regulating access to biodiversity. The next meeting (COP 13) will take place in Cancún, Mexico, in early December.

Participants at COP 13 must focus on the need to protect the rights of resource providers. To this end, they should pursue a careful assessment of existing policies and craft the necessary changes – before synthetic biology outpaces legal systems and renders them impotent.

Arrangements must be made to supervise access to genetic sequences in a way that ensures fair and equitable sharing of benefits from their use. Otherwise, decades of work to promote conservation and prevent piracy will be undermined, endangering the biodiversity convention – and those it protects

Oct 102016
 

gene-editingby Melody Meyer (Organic Matters)

In an early morning jaunt to Sacramento last week my car was rear ended.  I serve on the California Organic Products Advisory Committee (who by the way are looking for new members), and was on my way to attend a subcommittee meeting when boom—a fine young man rammed me in the rear. As I recuperate from the trauma, I wax philosophical and wonder why this happened and what the long term unintended consequences will be. The same ruminations can be applied to the novel gene editing techniques that are racing towards us with accelerating speed. Are we all on a genetic collision course with unintended consequences? 

As I mull over the details of that 5am departure, I wonder how two strangers woke up, made coffee, and rambled into their cars just to crash into each other at that moment in space and time. What trajectory was I launched on when I circled back and grabbed my lunch bag? What velocity did I drive just so I arrived at that spot for him to anoint me with pounding steel; up the bottom of the carriage so to speak?

The same musings can be mulled over for many of the new gene editing techniques that aren’t classified as GMO’s. From the first time we stood up on the Savanna and picked up that primal tool, were we fatefully launched on a trajectory course that would end in manipulating the very core of life itself? Our propensity for tinkering coupled with our big brains has landed us now in a godlike place where we can alter the very genetic code of life. Will there be unintended consequences?

History (and my sore neck) tells me that there always will be unintended consequences. If you look at the history of DDT, Agent Orange and TNT, they all have had negative accidental aftereffects. We now know that the rise of (traditionally) genetically engineered, herbicide-resistant crops has resulted in a huge increase in herbicide use and the rise of superweeds as a result. Chuck Benbrook has made that point many times.

The hottest and most cutting-edge GMO techniques aren’t even recognized as GMO’s. Scientists can now precisely edit unique traits within one species by using a technique called Crispr-cas9, which works like a pair of molecular scissors, snipping away this trait and inserting yet another. In fact the technology goes so far that it can now force the trait to persist forever more by using “gene drives.” Entire populations can now be genetically altered to always inherit that unique trait or even make the entire species crash. Sound like science fiction? Nope it’s here today and throttling towards us at breakneck speed.

My young driver was good hearted and intended me no harm. Just so the scientists working on these novel techniques are well intentioned mavens of research and genius, hoping to make the world a better place. Gene drives have been proposed as a technique for changing wild populations, for instance to combat mosquitoes that spread malaria and zika, to control invasive species, or to eliminate herbicide and or pesticide resistance in superweeds.

These cutting-edge gene editing techniques could potentially block the inheritance of many diseases such as cystic fibrosis. They could also lead to custom-made children where parents pick and choose the traits of their progeny.

The problem I have is that none of these techniques are regulated or transparently tested for safety. In fact many of these techniques are readily available and easily accessible to anyone who has access to the internet and half a propensity for scientific tinkering. A report by Nuffield Council on Bioethics warns that the simplicity and low cost of tools to edit the genetic code means that “garage scientists” pose a potential risk from the release of GM bugs. Sounds like unintended consequences barreling down upon us.

The report goes on to state and I quote “Genome-edited organisms (as with all genetically modified organisms or GMOs) pose a possible risk of harm to those handling them, and to others or to natural ecosystems if they are released or escape from controlled environments. Most countries have layers of regulation which cover the handling, transport and release of GMOs, but there are concerns about how these can be managed outside of regulated environments.”

Genetically modifying plants is far from harmless as this article points out. “Techniques of genetic modification, old or new, are not fully mastered: if they do allow bringing some new traits to a living organism (such as herbicide tolerance), they also produce unexpected modifications: ‘off-targets’ effects caused by the techniques such as mutations and epigenetic mutations, because of the techniques implemented during the process.”

What do we do now that we are crashing through the penetrable walls of subatomic DNA barriers with no regulation or oversight? Should we step outside the vehicle and access the possible damage? We are no longer messing around with a lone area of our ecosystem but potentially the very building blocks of our genetic heritage and legacy. We can and are impacting life itself on the planet.

The first path to regulations is to become aware of the speeding carriage barreling towards us. Friends of The Earth and ETC Group recently published the Shopper’s Guide to Synthetic Biology to help consumers like you avoid the new wave of GMOs in food and cosmetics, and find truly natural and sustainable options.

The National Organic Program and the National Organic Standards Board are requesting comments on whether these new techniques should be allowed in organic production.

The unintended consequences of this new technological collision course must be explored and challenged. If you need a license to drive a car, shouldn’t you have a license and some rules of the road to do gene editing? Shouldn’t we have safety tests, belts and cameras in place to assure we don’t crash our genetic inheritance?

Let’s urge governments worldwide to put some restraints on these new technologies while putting processes in place to evaluate those we cannot yet dream of. The speeding vehicle is coming.

Oct 032016
 
Waag Society/Flickr CC

Waag Society/Flickr CC

by Eric Meunier (Inf’OGM)

Several new techniques of genetic modification (also called NBT) are currently being discussed worldwide to decide whether to define products obtained from them as GMOs and to regulate them as such, or not. Following a parliamentary hearing in France [1] in April 2016, Inf’OGM tries to figure out some of the potential risks linked to the use of any technique of genetic modification on a plant cells culture.

Techniques of genetic modification, old or new, are not fully mastered : if they do allow bringing some new traits to a living organism (such as herbicide tolerance), they also produce unexpected modifications : ‘off-targets’ effects caused by the techniques of genetic modification themselves as they do not occur in the targeted area of the genome and unintended effects (mutations and epigenetic mutations, also called epimutations) due to other techniques implemented during the different steps of the process.

On April 2016 the 6th, echoing Yves Bertheau’s remarks back in late 2015 (a former member of the French High Council of Biotechnology (HCB) after having resigned), Jean-Christophe Pagès, Head of the HCB’s scientific committee, told the French Parliamentary Office for Science and Technology Assessment about Crispr/Cas 9 that “the difficulties to use it should not be forgotten […] especially regarding in vivo use on animals as you need to provide a matrix and you usually face issues linked to the process of insertion into the cell. In vitro culture is much easier and this is why the majority of its uses are in research and, eventually, organisms are regenerated from in vitro culture. And here, it indeed concerns some plants”… A surprising comment as, after a careful reading, the HCB’s scientific committee document dated from February 2016 the 4th – now downgraded to an interim report status after having been presented by the Scientific Committee as an advice to the French government – do not state such difficulties in vivo, or ease in vitro.

Inf’OGM provides here in a first series of two papers as an overview of the unintended and uncontrolled effects occurring along the steps of a genetic modification process. We will focus in these first paper on the process of insertion step as quoted by Jean-Christophe Pagès, aiming at bringing into a cell the requisite material to generate the intended genetic modification. We will also focus on preliminary steps which are indeed stressful and thus induce mutations and epigenetic mutations (see the box below).

In a next wave of papers we will focus on the unexpected changes called ‘off-targets’ due to the NBT techniques themselves. Several scientific papers will be rapidly cited to help the reader to go more in depth in the details.

Mutation, epigenetic mutation (epimutation) = what is it ?

A mutation is usually defined as a change in the genetic information of an organism, whether it be as DNA or RNA. Mutations are hereditary. They can be “silenced”, meaning without any observable consequences on the organism’s metabolism. They can also change the expression of one or several genes, modifying the metabolism. Epigenetic mutations belong to the class of mutation affecting the expression of a genetic sequence but which are not due to a change in the nucleotide sequence itself. They can be due to a change of the chemical composition of DNA nucleotides or chromatin.

Preparing the cells to be transformed

Before being able to bring some material into the cells (the process of insertion Jean-Christophe Pagès refers to), the first step is to prepare those cells. The lab workers will have to break cells wall, maybe even to remove them entirely. Plant cells without walls – called protoplasts – become transformable and engineers can now bring into those cells tools such as large proteins (such as Cas9), RNAs and/or coding DNAs. But, as Yves Bertheau explains, this creation of protoplasts induces mutations and epimutations, a widely observed phenomenon according to scientific literature [2].

Cell culture induces mutations

The second step is to cultivate those protoplasts. But culturing cells generates also mutations and epigenetic mutations. The scientific literature surprisingly shows that the mechanisms through which those mutations and epigenetic mutations appear is still little-known despite decades of use [3]. This phenomenon, called somaclonal variation, is such that it was previously used by seed companies to create the needed “genetic diversity” to “breed” plants according to the seed companies’ usual language. The French Association for Seeds and Seedlings (GNIS, “a privately funded organization which delivers public services”) points out that “somaclonal variation is the observed modification in some cells after a long cycle of in vitro culture without regeneration. These are therefore no longer identical to the parent plant. This variation can be due to a modification in the nucleus genome or in the genome of cytoplasmic plastids [4].

In other words, plants obtained from those cells have different characteristics. GNIS provides one last interesting detail : “the obtained modifications of traits are barely stable and not always found in the regenerated plant or its progeny”. Why ? The occurrence of other modifications (epigenetic mutations) can make those mutations disappear [5]… As Yves Bertheau tells us, “in such conditions, it looks rather difficult to foresee the impacts this step of cell culture could perform when using a new technique of genetic modification”.

The process of insertion, at last… also called vectorization

Once the cells are prepared and cultivated, we are ready to bring in the biological material to generate the intended modification. Depending on the techniques, this material may be proteins and / or genetic sequences such as RNAs or encoding DNAs (oligonucleotides, plasmids, virus…) – the most frequently used molecules for plants. Bringing this material into the cells needs merely making large holes in the membranes (cytoplasmic and nuclear) of the cell. But, as Yves Bertheau explains us, making such holes induce once again mutations and epimutations [6]. The researcher considers thus impossible to draw a general grid for risk assessment. A choice must be made among several techniques of insertion, different types of material, the genetic sequences to be introduced and the species targeted. Therefore only a case by case analysis for such GMOs would allow the assessment of all the potential risks linked to unintended effects.

HCB’s scientific committee’s interim report says nothing about those mutations

In a scientific paper of 2011, scientists estimated that 35% of all the observed unintended effects following the genetic modification by transgenesis of Senia rice were due to the cells transformation process itself [7]. The phenomenon is therefore not negligible.

Surprisingly, and despite the hearing of its Head in front of the OPECST, the HCB’s Scientific Committee did not deal with those risks in its interim report on risks linked to the new techniques [8]. If the process of insertion is indeed described in the appendix for each technique, it’s only to outline the tools used for a technique and to describe how the material is brought into the cells. Possible mutations and epimutations arising from the different transformation steps are not covered. As the HCB scientific committee is in charge of risk evaluation for the French government, we would have expected this committee to discuss and provide explanations, not to disregard such documented issues. Especially considering that the transformation process – to refer to the only point present in the interim report – doesn’t seem to be fully controlled depending on the techniques. The scientific committee even states that for the oligodirected mutagenesis technique (OdM), “many molecules or molecular mixtures are currently tested to improve the process of insertion which works fairly well in vitro but not well on full organisms (Liang et al., 2012) [9]

 

[2« Stress induces plant somatic cells to acquire some features of stem cells accompanied by selective chromatin reorganization », Florentin, A. et al. (2013), Developmental Dynamics, 242(10), 1121-1133 ;
« Developmental stage specificity and the role of mitochondrial metabolism in the response of Arabidopsis leaves to prolonged mild osmotic stress », Skirycz, A. et al., (2010). Plant Physiology, 152(1), 226-244 ;
« Arabidopsis mesophyll protoplasts : a versatile cell system for transient gene expression analysis », Yoo, S.-D.et al. (2007). Nat. Protocols, 2(7), 1565-1572.

[3« Cell culture-induced gradual and frequent epigenetic reprogramming of invertedly repeated tobacco transgene epialleles », Krizova, K. et al., (2009). Plant Physiology, 149(3), 1493-1504 ;
« Extended metAFLP approach in studies of tissue culture induced variation (TCIV) in triticale », Machczyńska, J. et al., (2014). Molecular Breeding, 34(3), 845-854 ;
« Tissue culture-induced novel epialleles of a Myb transcription factor encoded by pericarp color1 in maize », Rhee, Y. et al., (2010). Genetics, 186(3), 843-855 ;
« Transformation-induced mutations in transgenic plants : analysis and biosafety implications », Wilson, A.K. et al., (2006). Biotechnol Genet Eng Rev, 23(1), 209-238 ;
« A whole-genome analysis of a transgenic rice seed-based edible vaccine against cedar pollen allergy », Kawakatsu, T. et al., (2013).. DNA Research 20, 623-631 ;
« Recent progress in the understanding of tissue culture-induced genome level changes in plants and potential applications », Neelakandan et al.,, 2012,. Plant Cell Reports, 31(4), 597-620

[5« Meiotic transmission of epigenetic changes in the cell-division factor requirement of plant cells », Meins, F. et al., (2003). Development, 130(25), 6201-6208.

[6« Cell biology : delivering tough cargo into cells », Marx, V. (2016). Nat Meth, 13(1), 37-40.

[7« Only half the transcriptomic differences between resistant genetically modified and conventional rice are associated with the transgene », Montero, M. et al., (2011). Plant Biotechnology Journal, 9(6), 693-702.

Sep 302016
 
petri-dish

HCC Public Information Office via Flickr CC

by Ian Sample (the Guardian)

Nuffield Council on Bioethics report finds materials to perform basic experiments are now available to ‘garage scientists’

The simplicity and low cost of tools to edit the genetic code means “garage scientists” – or amateurs with some skill – can now perform their own experiments, posing a potential risk from the release of GM bugs, a new report suggests.

In a report published on Friday, the Nuffield Council on Bioethics said that the rise in precision “gene editing” tools had revolutionised biomedical research over the past ten years and could potentially have a dramatic impact on human society.

But it found that the materials needed to perform basic experiments were available to enthusiasts outside academia and established labs. This year, one firm began to sell a kit for £100 to DIY biology interest groups that allowed them to render the common soil microbe, E coli, resistant to the antibiotic streptomycin.

The report goes on to say that genetic technology has become so powerful that nations need to decide whether or not doctors should ever be allowed to modify the human species.

While the creation of GM humans is not on the horizon yet, the risks and benefits of modifying a person’s genome – and having those changes pass on to future generations – are so complex that they demand urgent ethical scrutiny, the review found.

“This could transform our range of expectations and ambitions about how humans control our world,” said Andrew Greenfield, a geneticist and chair of the Nuffield Council’s working group. “Although most uses so far have been in research, the potential applications seem to be almost unlimited.”

Genome editing has become a common tool in laboratories around the world. The most common technique, called Crispr-cas9, works like a pair of molecular scissors. It is essentially a pair of enzymes that can be designed to find and remove a specific strand of DNA inside a cell, and then replace it with a new piece of genetic material. The procedure can be used to rewrite single letters of genetic code and even whole genes.

The report found that gene editing could potentially block the inheritance of cystic fibrosis and more than 4000 other known conditions caused by single faulty genes. But the technique may also drive profound changes in farming, the report found, where the possibilities range from swine fever-resistant pigs, chickens that only give birth to females, and hornless cows that could be housed in smaller spaces. Because Crispr-cas9 does not leave any traces, meat and other products from GM animals could find its way to market without being labelled. Meanwhile, the simplicity and low cost of Crispr-cas9 means amateurs in the home can now perform their own experiments.

Altering the genetic makeup of a human embryo and transplanting it into a woman is banned in Britain, but there are ethical arguments in favour of the procedure, such as preventing children from inheriting genes that cause fatal diseases. But if the procedure were allowed, some fear it could open the door to what the report calls “consumer” or “liberal eugenics” where children are modified to suit their parents’ preferences.

“We’ve identified human reproductive applications as an area that demands urgent ethical scrutiny and we must consider carefully how to respond to this possibility now well before it becomes a practical choice,” said Karen Yeung, a law professor at King’s College London, and co-author of the report.

Scientists have already begun to edit the genes of human embryos, but only for basic research. Earlier this year, researchers in China tried to add HIV resistance to human IVF embryos which had been donated to science when tests found them to be unviable. The experiments did not achieve their goal, but highlighted how difficult the procedure was likely to be in humans.

In 2015 another Chinese team became the first in the world to edit human embryos, when they tried, and failed, to modify a gene that causes beta-thalassaemia, a potentially fatal blood disorder. Again, the work was performed on abnormal IVF embryos donated to research.

From a purely medical standpoint, there are good reasons to correct faulty genes at the embryo stage, because the defective DNA is then erased from every cell in the body. The risk comes when the modification has unintended consequences. This could harm not only the child, but their future children, because the altered gene would be in their sperm or eggs.

In light of the report, the Nuffield Council has set up two new reviews to look specifically at the ethics of gene editing in human reproduction and livestock. One major question will be where to draw the line on what is acceptable if gene editing is approved in humans, in principle. It may be morally acceptable to correct a faulty gene that will definitely pass on a fatal disease to a child. But what about a gene that has a chance of raising by 10% a person’s risk of heart disease or Alzheimer’s? The report notes that in the future, it may be possible to enhance people with genes from other organisms, for example to improve night vision and sense of smell.

“It is only right that we acknowledge where this new science may lead and explore the possible paths ahead to ensure the one on which we set out today is the right one,” said Yeung.

Intro to syn bio flavors and fragrances

 

intro

A fundamental shift is underway in how food, flavor, cosmetic and fragrance ingredients are being produced for global markets. The new game in town is biosynthesis – the artificial production of key compounds by synthetically engineered organisms. While consumers, farmers and the natural world have already had to grapple with the impacts of the last synthetic revolution (synthetic chemistry), which has created many toxic, harmful or noxious substances and polluted systems, this next synthetic revolution (synthetic biology) is set to have equally disruptive effects. These impacts range from safety and environmental concerns to very profound social and economic upturning of livelihoods and landscapes.

At the sharpest end of this disruption are the farmers, growers, pickers and harvesters, particularly in the tropics, who provide the natural products that make up the ingredients in our foods, cosmetics, soaps, textiles and more. Consumers and workers will also be affected.

In this report ETC Group presents a series of case studies outlining ways that specific products are being bio-synthetically created, and how current livelihoods from traditional agricultural production may be adversely affected as these synthetic biology-based substitutes for high value commodities enter the market. Several of these synthetic substitutes are already in commercial use; some taking major market share already; and many more are rapidly headed towards commercialization, potentially displacing the work of already marginalized peoples in their wake.

What is Synthetic Biology?

Synthetic biology, dubbed “genetic engineering on steroids,” broadly refers to the use of computer-assisted, biological engineering to design and construct absolutely novel synthetic biological segments, devices and systems that do not and never have existed in nature; it also refers to the redesign of existing biological organisms using these techniques. Synthetic biology attempts to bring a predictive engineering approach to biological genetic engineering using genetic “parts” that are thought to be well characterized and whose behavior can in theory be rationally predicted.

“The overall aim of synthetic biology is to simplify biological engineering by applying engineering principles and designs—which emanate from electronic and computer engineering—to biology.” [1]

The Switch to Ingredient Markets

Over the past decade, before world oil prices plunged, fledgling syn bio start-ups (with the financial backing of fossil fuel corporations) made grandiose claims about using designer microbes to produce plentiful, low-cost biofuels in giant fermentation tanks. Manufacturing petrochemical substitutes at commercial scales proved elusive, however. Now with energy markets sputtering, most syn bio companies are giving up on biofuels and turning to high-cost, low volume flavor and fragrance molecules that can be economically produced in smaller batches. [2]

Biodiversity – especially exotic plants and animals – has been the source of natural flavors and fragrances for millennia. Plants, animals and microorganisms are prolific generators of bioactive flavor/fragrance compounds, known as secondary metabolites, that, once extracted, are widely used in food, feed, cosmetics, chemicals and pharmaceuticals. The world’s largest flavor and fragrance corporations are eager to partner with synthetic biology companies because of increasing production uncertainties caused by climate change, as well as the alluring potential of securing cheaper, uniform and more accessible sources of economically desirable natural ingredients.

The world’s largest flavor and fragrance corporations are eager to partner with synthetic biology companies because of increasing production uncertainties caused by climate change, as well as the alluring potential of securing cheaper, uniform and more accessible sources of economically desirable natural ingredients.

With synthetic biology, the goal is to produce high-value flavors and fragrances by using engineered microbes instead of relying on expensive botanical imports or conventional chemical synthesis. The biosynthetic manufacturing platform involves engineering genetic pathways in microorganisms. Scientists and software engineers are tweaking the DNA of existing microorganisms as well as designing new ones from scratch. In the words of one industry analyst: “There is potential for biosynthetic routes to completely replace any natural sources.” – Kalib Kersh, Lux Research,  quoted in Chemical & Engineering News. [3]

Metabolic Pathways to Everything

Even though plant product metabolism is extremely complex, with advances in molecular biology and engineering, researchers are attempting to pinpoint the precise biochemical instructions in the cells of a living organism that result in the production of bioactive molecular compounds. In one well-studied plant, Arabidopsis thaliana (a.k.a. mouse-ear cress or thale cress), at least 20% of the genes are thought to play a role in the biosynthesis of secondary metabolites. [4] The complex interaction of genes and enzymes in their natural context all play a role in the plant’s “metabolic pathway” – the means by which it produces a useful chemical compound.

Using “metabolic pathway engineering,” synthetic biologists are turning microbial cells into “living chemical factories” that can be induced to manufacture substances they could never produce naturally. To date, synthetic biology firms are honing in on the best-known metabolic pathways such as terpenoids, polyketides, alkaloids – these pathways are the keys to producing tens of thousands of natural product families at the molecular level.

biochem_gloves_vb_cc_by_rdecomTo scale up the production of a desired compound, the novel biosynthetic pathway (constructed with synthetic DNA) is inserted into a microbial host (yeast, bacteria, fungi or algae strains, for example) that feed on plant sugars in giant (e.g., 200,000-litre) fermentation tanks. In the words of synthetic biologist Jay Keasling: “We ought to be able to make any compound produced by a plant inside a microbe.” [5]

The engineering of microbes for industrial purposes is nothing new, but synthetic biology start-ups are accelerating the process with computer engineering principles and highly automated, robotic systems. In a mostly random process, software-directed robotic systems design, build, test and analyze DNA sequences and active compounds to identify promising candidates and optimize biomolecular pathways in microbes. Despite the staggering complexity of biological systems, synthetic biologists compare themselves to industrial product designers: “This design strategy can be likened to building millions of variants of a chemical factory, selecting or screening for control system variants that yield the most product and discarding all but one or two of the most productive designs.” [6] One synthetic biology company refers to its employees as “organism designers” who work in a “foundry,” not at a lab bench. [7]

In the words of one venture capitalist, Bryan Johnson, founder of the OS Fund, the ultimate goal of syn bio is
to control biology and make it predictable: “We aren’t there yet with biology… I can’t just sit down and program
biological code to create a particular outcome on a more complex scale. What’s standing between us making good
use of that is our ability to make it predictable.” [8]

Despite the techno-rhetoric, the design and control of synthetic organisms is far from routine, simple or inexpensive. Biosynthetic pathway engineering is highly complex. Just two examples:

  • Researchers at Amyris, Inc. (California) successfully engineered the metabolic pathway of yeast to produce artemisinic acid, a precursor of artemisinin, an effective drug to treat malaria, which is typically sourced from
    the Chinese wormwood plant. [9] The biological engineering involved at least 12 new synthetic genetic parts [10] (and more than $53 million in research grants [11]).
  • Evolva (Switzerland) commercialized a proprietary yeast biosynthesis platform for the production of vanillin – a key flavour compound in natural vanilla. In 2009 researchers disclosed that construction of the denovo pathway in yeast incorporates bacterial, mold, plant and human genes. [12]

Both products are now commercially available and intended for human ingestion.

Industry’s Synbio Advantage

For the industrial flavor / fragrance industry, the synthetic biology platform could offer two major
advantages:

  1. The potential to secure more uniform, uninterrupted supplies of high-value raw materials in factory-based fermentation tanks. In other words, companies would be unencumbered by climate, weather, crop failure, price and political volatility or the logistical complexity of sourcing raw materials from farmers and other suppliers in remote locations.
  2. The ability, under current regulations in the USA and Europe, to market biosynthesized flavors and aroma compounds as “natural” products. [13] In other words, biosynthetic products manufactured via microbial fermentation are deemed “natural” or “substantially equivalent” to a botanically-derived product. In contrast, chemically synthesized flavors/fragrances derived from petroleum cannot be labeled “natural.” [14] Research shows that consumers have a strong preference for the “natural” label – despite the murkiness that surrounds it. One survey indicates that almost 60% of consumers in the United States look for the word “natural” when they shop for food products. [15] Because regulations governing “natural” products specifically permit “fermentation” and “microbiological” processes, the biosynthesis of flavor/fragrances in engineered microbes is not only positioned to compete with natural, botanically derived counterparts – they will also have an advantage over synthetically derived flavors/fragrances. [16] The bottom line: consumers will have no way of knowing if a “natural” flavoring or scent is derived from industrial, genetically engineered microbes or from a traditional botanical source.

Answering the Hard Questions on Synthetic Biology

Do synthetic biology-derived ingredients pose a threat to human health or the environment?

Synthetic biology techniques are more powerful than previous genetic engineering techniques, but threats will depend on each specific application. There is little or no data on long-term impacts (including health risks) from various applications of these techniques, as well as no regulations. Synthetic biology organisms may produce novel contaminants and could have significant implications for ecosystems if they are released or escape into an ecosystem and continue to multiply. There are also overall impacts on farmers, land use and concerns about the consolidation of corporate power over so many commodities.

If the production is contained in vats, are there safety risks? There is insufficient understanding about synthetic biology techniques or about how to contain the engineered organisms. Although some production of synthetic biology organisms (algae and yeast) is done in factory fermentation vats, organisms and viruses even from high containment laboratories routinely escape through human error. Commercial synthetic biology facilities are not necessarily containment facilities, and synthetic biology facilities have already experienced spills and escapes of synthetic biology organisms. These organisms are alive and can evolve, recombine, or change.

Is synthetic biology more “sustainable” because it’s “natural” and “bio-based”?

Several synthetic biology companies are misleadingly marketing their ingredients as “sustainable,” “natural” and “bio-based.” For example, although the synthetic biology-engineered organisms carry out fermentation, a natural process, the organisms themselves are highly unnatural and synthetically constructed.

The term “bio-based” refers to the sugars – including cellulose – that synthetic organisms consume. However, bio-based does not always mean “sustainable” or ecologically responsible. Debates over biofuels and bioenergy have shown that the chemical and water-intensive agriculture used to grow the plant sugars (such as sugar cane or GMO corn) are not sustainable. In addition to their significant ecological impacts from chemical contamination, these feedstock industries are associated with destructive forestry operations, land grabs and land clearances.

Some synthetic biology companies claim that the ingredient synthesized replaces one that would have been unsustainably extracted from the wild – e.g. palm oil. However, these claims are questionable and do not consider existing alternatives; they need to be carefully scrutinized.

gran_sundae_vb_cc_by-nc-sa_hazelisles

Consumer demand shapes industry – (cc) Hazel Isles

If the synthetic biology-derived ingredient is “nature-identical” to the botanical version, what are the concerns?

Most of the synthetic biology-derived ingredients currently being produced are for single flavor, fragrance and cosmetic compounds such as vanillin (vanilla flavor), nootkatone (grapefruit flavor) or squalane (moisturizing oil). Natural products will usually have a much more complex array of compounds and so the quality is quite different. Synthetic biology companies argue that the final compound produced is “nature-identical” (chemically similar) to the naturally-derived version and therefore does not need any additional assessment. However, the synthetic biology processes themselves may create unexpected contaminants, toxins or allergens that may be hard to control for. In addition, the process of replacing natural commodities with unnatural ones raises significant environmental dangers, and concerns about the impacts on small farmers’ livelihoods, cultures, and national economies, as shown in these case studies.

Disrupting Who?

Putting Synthetic Biology Developments in Historic Perspective: Technology, Livelihoods and Commodity Trade In
Botanical Product

History shows that the introduction of new technologies can have profound and devastating impacts on the livelihoods of farmers, agricultural workers and national economies. In the colonial era, for example, European expansion accelerated the flow of food plants and livestock from their colonies, and Europeans began to largely control the flow of crops and to monopolize production and processing technologies important to commercialization (e.g., cotton, rubber, coffee, tea and spices). These technology transfers created patterns of long-lasting economic dependence and poverty in the colonized countries.

perfume-glass-flasks-on-shelvesDevelopments in chemistry toward the end of the 19th century – particularly in Germany, France and the United Kingdom – propelled a new technology wave that reduced and/or eliminated the demand for a wide array of raw materials once sourced in the global South. Chemically-synthesized dyes from Germany, for example, quickly replaced natural dyes such as the madder root. By 1900 Turkey’s natural dye market disappeared, due to a chemically synthesized substitute. When blue synthetic dyes went into large-scale production in Germany in 1897, Indian farmers were cultivating 574,000 hectares of indigo from a variety of plants. In the 1930s, the plastics ‘revolution’ destroyed many other natural industries as well as creating vast pollution. Then, following World War II, similar market disruptions followed the introduction of synthetic petroleum based fibers.

The first beneficiaries of sudden technology shifts have historically been those who develop and/or control the new technology. The “losers” are the producers of primary commodities who were unaware of the imminent changes or who could not make rapid adjustments in the face of new demands and technologies.

In order to assuage concerns that synthetic biology could result in the same win/lose scenario, some advocates have argued that the transfer of field production to vat production could benefit local ecosystems and local food security. Amyris, Inc. in Berkeley, CA has suggested that the elimination of the field production of the Chinese wormwood shrub for a pharmaceutical compound (artemisinin) could allow farmers to grow more potatoes.

In fact, this is not economically or ecologically plausible; many of these plants grow in difficult environments not suited for other crops. Farmers not only benefit substantially from wormwood shrub production, but also the antimalarial tea they brew at home is directly beneficial to their families and communities. Potatoes, on
the other hand, are notoriously destructive to soils, and farmers are often obliged to make extensive use of crop chemicals with all the attendant economic, health and environmental damages.

In another case, undercutting natural vanilla production in Madagascar (and its replacement with vat production in Switzerland) would immediately damage the livelihoods of family producers and oblige them to cut back the wonderfully diverse and valuable forests that they need to create the conditions necessary for their vanilla plants.

Theoretically speaking, however, synthetic biology could stimulate demand for more of a given natural product. The development of synthetic rubber in the USA during World War II and after led, within a couple of decades, to synthetic rubber occupying more than 60% of the global market.

At the same time, post-World War II affluence and the demand for tires also increased the demand for natural rubber and the producer countries in Southeast Asia have benefited. Likewise, the discovery of a bacterium in Thailand in the 1950s, that led to the introduction of high fructose corn syrup (HFCS), could have been expected to wipe out demand for sugar cane and sugar beet. In reality, the explosion in consumer demand for sweeteners – and cars for ethanol – meant that the demand for both corn and sugarcane boomed, for better or worse. Many scenarios have to be considered in each case. Might this be so for natural flavors and fragrances? 95% of the market has already been lost to chemical synthetics. The remaining 5% still sustains tens of millions of farm families around the world. These natural flavors and fragrances are typically richer and more complex than factory-made versions, and in the past few years major food processors and even fast food companies (including Pizza Hut and Taco Bell) are going back to natural flavors in the face of widespread consumer disaffection. This is a battle that can be won. Schumpeter’s dictum on “creative destruction” still dominates, however. Not just change – but also the threat of change – can be highly destructive, even if it may turn out to be beneficial in the long run. Simply the possibility that a crop could be grown in a vat can disrupt supply chains and damage producer prices, causing farmers to abandon their best opportunities for fear that there will be no one to sell to at harvest time, something which already impacted the supply of artemisium, a valuable medicine. If the competition is frightened into retreat, synthetic biology doesn’t have to be technologically successful to be commercially successful. The bottom line is that industrial “creative destruction” is always devastating to marginalized peoples. These long-term changes shouldn’t be considered before those affected are able to be full participants in the political and economic negotiations involved in any technological change.

The Global Flavor & Fragrance Industry

baskets-of-spices-n-herbsIn 2013 the global flavor and fragrance market was valued at $23.9 billion [17] and is expected to grow to over $35 billion by 2019. [18] This figure reflects the value of ingredients for processed foods and fragrances only, and does not include the value of crops like coffee and cacao beans, which are also commonly used to flavor processed foods. The industry is increasingly concentrated in the hands of four multinational firms [19] which controlled 58% of the market in 2013 – Givaudan, Firmenich, IFF and Symrise. [20] The top 10 companies collectively accounted for an estimated 80% of total industry sales. [21] At least six of these companies have R&D agreements with synthetic biology firms. [22] F&F giants are pursuing every feasible route to secure cheaper and more accessible raw ingredients – both natural (sourced from their natural environment) and synthetic (chemicals synthesized from petroleum). Although the flavor and aroma industry likes to emphasize the use of “natural” ingredients, the vast majority of flavors and fragrances are the product of chemical synthesis: an estimated 95% of the compounds used in fragrances are synthesized from petroleum – not sourced from plants, animals or microorganisms. [23] Even so, the main F&F firms still buy thousands of plant and animal-derived ingredients from dozens of countries.

Flavors and fragrances are essential ingredients in the manufacture of household cleaning products, perfumes, cosmetics, pharmaceuticals, food & beverages, aromatherapy and more. For example, the soft drink industry is the major consumer of natural flavors/fragrances, especially essential oils of citrus origin. [24] In fact, “cola” soft drinks cannot be produced without essential oils like lemon or lime. [25] The F&F industry currently sources 200 to 250 different botanical crops grown on an estimated 250,000 hectares worldwide. Around 95% of these crops are grown by small-scale farmers and agricultural works, mostly in the global South. [26]

An estimated 20 million small-scale farmers and agricultural workers depend on botanical crops grown for natural flavors and fragrances. [27] (This is a low estimate.) Flavor & fragrance industry trade groups do acknowledge that these botanicals are “highly important in terms of their socio-economic impact on rural populations and may also have important environmental benefits within agricultural systems.” [28]

From ETC Group’s research it is clear that the very largest players in the Flavor and Fragrance industry are now investing significant sums in synthetic biology production of key compounds. These are players who routinely source thousands of raw materials from tens of millions of farmers and pickers to transform their products into tens of thousands of consumer ingredients. Those enthusiastically embracing synthetic biosynthesis include DSM, BASF, Givaudian, Firmenich, International Flavors and Fragrances and Robertet. The syn bio ingredients they are switching to range from fragrances such as patchouli, rose oil and ambergris to cosmetic compounds such as squalane and shea butter to food ingredients such as vanillin, stevia and saffron.

Sourcing raw materials from a high tech vat rather than from millions of diverse farmers offers them simpler supply chains and increases corporate control over the production process. This current ongoing switch to syn bio derived-ingredients, which does little to benefit the consumer or the farmer, makes sense only in light of the economic interests of these large and powerful ingredients brokers.


[1] Chris Paddon and Jay Keasling, “Semi-synthetic artemisinin: a model for the use of synthetic biology in pharmaceutical development,” Nature Reviews Microbiology, Vol. 12, May 2014, p. 356.

[2] David Ferry, “The Promises and Perils of Synthetic Biology,” Newsweek, March 11, 2015: www.newsweek.com/2015/03/20/promises-and-perils-synthetic-biology-312849.html

[3] Melody Bomgardner, “The Sweet Smell of Microbes,” Chemical & Engineering News, July 16, 2012, p. 26.

[4] Synthetic Biosystems for the Production of High-Value Secondary Metabolites, PhytoMetaSyn website:
www.phytometasyn.ca/index.php/about-phytometas

[5] Jay Keasling, quoted in Michael Specter, “A Life of its own: Where will Synthetic Biology lead us?,” The New Yorker, 28 September 2009, p59.

[6] Chris Paddon and Jay Keasling, “Semi-synthetic artemisinin: a model for the use of synthetic biology in pharmaceutical development,” Nature reviews. Microbiology. Vol. 12, May 2014, p. 356.

[7] Stephanie Lee, “This Startup Is Designing Yeast To Make Brand-New Scents, Flavors,” BuzzFeed, 18 March 2015: www.buzzfeed.com Brian Gormley, “Ginkgo Bioworks Raises $9M to ‘Engineer’ Food Flavors, Fragrances,” Wall Street Journal, 18 March 2015: http://blogs.wsj.com/venturecapital/2015/03/18/
ginkgo-bioworks-raises-9m-to-engineer-food-flavorsfragrances/

[8] Stephanie Lee, “This Startup Is Designing Yeast To Make Brand-New Scents, Flavors,” BuzzFeed, 18 March 2015: www.buzzfeed.com

[9] Withers, S. and Keasling, J. Biosynthesis and engineering of isoprenoid small molecules. Appl Microbiol Biotechnol. 2007 Jan;73(5):980-90. Epub 2006 Nov 18.

[10] Ibid.

[11] Robert Sanders, “Launch of antimalarial drug a triumph for UC Berkeley, synthetic biology,” UC Berkeley News Center, 11 April 2013: http://newscenter.berkeley.edu/2013/04/11/launch-of-antimalarial-drug-a-triumph-for-ucberkeley-synthetic-biology/

[12] Hansen et al. 2009. De novo biosynthesis of Vanillin in Fission yeast (Schizosaccharomyces pombe) and Baker’s yeast (Saccharomyces cerevisiae). Applied and Environmental Microbiology 75: 2765-2774.

[13] Andy Pollack, “What’s That Smell? Exotic Scents Made From Re-engineered Yeast,” New York Times, 20 October 2013. In the United States, there is no requirement that a product derived from a genetically modified yeast be labeled as “GMO.” That’s because the engineered yeast is considered a processing technique, rather than the source of the flavoring/fragrance product.

[14] Products containing chemically synthesized flavor compounds and the introduction of flavors not occurring in nature are labeled as ‘‘nature identical’’ and ‘‘artificial’’ (EC Flavor Directive 88/388/EEC); (US Code of Federal Regulation 21 CFR 101.22). This has reduced the market value of flavors produced by chemical synthesis. Nethaji J. Gallage and Birger Lindberg Møller, “Vanillin–Bioconversion and Bioengineering of the Most Popular Plant Flavor and Its De Novo Biosynthesis in the Vanilla Orchid,” Molecular Plant 8, 40–57, January 2015. www.cell.com/molecular-plant/pdf/S1674-2052(14)00009-4.pdf

[15] “Say no to ‘natural’ on food labels: Why Consumer Reports is launching a campaign to ban the ubiquitous term,” Consumer Reports, June 16, 2014. www.consumerreports.org/ cro/news/2014/06/say-no-to-natural-on-foodlabels/index.htm

[16] Sabisch, M., and Smith, D. (2014). The Complex Regulatory Landscape for Natural Flavor Ingredients. Sigma Aldrich. www.sigmaaldrich.com, 01 August, 2014. www.cell.com/molecular-plant/pdf/S1674-2052(14)00009-4.pdf

[17] Perfumer & Flavorist, 2014 Flavor and Fragrance Leaderboard, June 2014.

[18] Market Insider, Flavors and Fragrances market projected to grow to US$35 billion by 2020, 27 Jan. 2015. www.intracen.org/itc/blogs/market-insider/Flavors-and-Fragrances-market-projected-to-grow-to-US-35-billionby-2020-/

[19] Tully and Holland. Flavors & Fragrances Industry Update, August 2014. www.tullyandholland.com/tl_files/documents/F&F%20Industry_Note_FINAL.pdf

[20] http://www.leffingwell.com/top_10.htm

[21] Ibid.

[22] These include: Givaudan, Firmenich, IFF, Symrise, Robertet, Takasago.

[23] Charu Gupta, Dhan Prakash and Sneli Gupta. A Biotechnological Approach to Microbial Based Perfumes
and Flavors, Journal of Microbiology and Experimentation, Vol. 2, Issue 1, 2015.

[24] IFEAT Socio-Economic Impact Study, “Naturals – small but vital ingredients in a range of products,” IFEAT World, May 2014, p. 4. www.ifeat.org/wp-content/uploads/2014/05/IFEAT_World_May-2014-.pdf

[25] Ibid.

[26] www.ifeat.org/wp-content/uploads/2014/05/IFEAT_World_May-2014-.pdf

[27] ETC Group’s conservative estimate is based on the fact that over 15 million farmers produce cornmint (source of menthol) in India alone.

[28] www.ifeat.org/wp-content/uploads/2014/05/IFEAT_World_May-2014-.pdf

Sep 162016
 

bulliards_etc_cartoon

by ETC Group

Policymakers could still block the agribiz mergers; peasants and farmers will continue the fight for seeds and rights

Wednesday’s confirmation that Monsanto and Bayer have agreed to a $66 billion merger is just the latest of four M&A announcements, but at least three more game-changing mergers are in play (and flying under the radar).  The acquisition activity is no longer just about seeds and pesticides but about global control of agricultural inputs and world food security.  Anti-competition regulators should block these mergers everywhere, and particularly in the emerging markets of the Global South, as the new mega companies will greatly expand their power and outcompete national enterprises.  Four of the world’s top 10 agrochemical purchasing countries are in the global South and account for 28% of the world market.[1] If some of these throw up barriers, shareholders will rebel against the deals regardless of decisions in Washington or Brussels.

“These deals are not just about seeds and pesticides, but also about who will control Big Data in agriculture,” says Pat Mooney of ETC Group, an International Civil Society Organization headquartered in Canada that monitors agribusiness and agricultural technologies. “The company that can dominate seed, soil and weather data and crunch new genomics information will inevitably gain control of global agricultural inputs – seeds, pesticides, fertilizers and farm machinery.”

Neth Daño, ETC’s Asia Director, continues, “Farmers and regulators should be watching out for the seventh M&A – John Deere and Company’s bid to merge its Big Data expertise with Monsanto-owned Precision Planting LLD. After the Bayer-Monsanto merger, it’s not clear whether Precision Planting will go to Deere and Co. or if Bayer will protect its future in agricultural data.” Daño, based in the Philippines, points out that “Deere started connecting its farm machinery to GPS in 2001 and since then has invested heavily in sensors that can track and adjust seed, pesticide and fertilizer inputs meter by meter. The company has 15 years of historic data as well as access to terabytes of other weather, production and market data. Quite literally, Deere and the other farm machinery companies (the top three account for half of the world market) own the box in which the other input enterprises have to dump their products. That means Deere also owns the information.”

Silvia Ribeiro, Director of ETC’s Latin American office, agrees that the latest news confirming Monsanto agreement has “created alarm throughout Latin America and raised big concerns about increased input prices, more privatization of research and huge pressure from these Giant companies to make laws and regulations in our countries that allow them to dominate markets, crush farmers’ rights and make peasant seeds illegal.”

Although the mergers will be contested at the national level around the world, Neth Daño in the Philippines and Silvia Ribeiro in Mexico see the battle moving to a number of international fora in the weeks and months ahead. Daño will be in Indonesia September 27 – 30 when governments, farmers’ organizations and civil society meet to discuss Farmers Rights as part of a legally binding treaty intended to guarantee farmers access and use of seed. “This is an international seed meeting that can’t avoid addressing these mergers,” she asserts. “The hottest topic on the agenda is a Big Data proposal for seeds being pushed by the companies.”

October 17 – 21, Pat Mooney and Silvia Ribeiro will be in Rome attending the UN’s Committee on World Food Security. “Virtually all of the world’s governments, farmer organizations and many agribusinesses companies will be in the same room for a week, with food security on the official agenda. There are going to be a lot of angry people there wanting to stop these mergers,” Ribeiro insists.

December 4–17, the UN Convention on Biological Diversity will be meeting in Mexico where agricultural biodiversity issues are on the agenda. The Convention is famously proactive on seed issues having already set a moratorium against Terminator seeds (seeds genetically modified to die at harvest time forcing farmers to purchase new seeds every growing season) and, as well, a protocol on the trans-boundary movement of transgenic seeds and another protocol that will soon enter into force related to loss and damages caused by GM contamination. When it meets in December, it will debate the risks of a suite of new plant breeding technologies described as “extreme genetic engineering” (synthetic biology) which is much favoured by all the companies now merging as a strategy to sidestep biotech regulations. “Wherever these companies go in the next few months, they are going to have a fight on their hands,” says Silvia Ribeiro.

For further information:

Pat Mooney, Executive Director, ETC Group: 1-613-240-0045 or mooney@etcgroup.org

Neth Daño, Asia Director, ETC Group: +63 917 532 9369 or neth@etcgroup.org

Silvia Ribeiro, Latin America Director, ETC Group: + 52 1 5526 5333 30 or silvia@etcgroup.org

M&As – Public and Not-So Public

The buying spree started in July 2014 when Monsanto (the world’s #1 seed company; #5 In agrochemicals[2]) launched the first of three runs at Syngenta (#1 in crop chemicals; #3 in seeds[3]).  All offers were rebuffed. Nevertheless, the gambit set all of the Big Six seed/chemical companies in motion…

1.     November 2015 –  ChemChina (who owns the world’s 7th-largest agrochemical company, ADAMA[4]) made a $42 billion bid for Syngenta.[5]  The offer (bumped up to $43 billion) was accepted in February 2016.[6] The deal has passed one of several regulatory hurdles in the USA,[7] but faces challenges in numerous other jurisdictions including, apparently, Canada, Brazil and the EU. It is expected to close by the end of 2016.[8] The merger will give ChemChina “a way to diversify beyond agrochemicals into GM seed technology.”[9]

2.     December 2015 – Dupont (#2 in seeds, #6 in pesticides[10]) and Dow (#5 in seeds, #4 in pesticides[11]) announced their $68 billion merger. It is still pending and under review by antitrust regulators,[12] and the companies optimistically claimed the deal will be done by the end of the year.

3.     May 2016 –  Bayer (#2 in crop chemicals; #7 in seeds[13]) low-balled a bid for Monsanto[14] but the companies eventually reached a deal for $66 billion on September 14 and predict closure by the end of 2017.[15]

4.    August, 2016 – Potash Corp. (#1 in synthetic fertilizers by capacity,[16] #4 by market share[17]) began negotiations with Agrium (#2 in fertilizers by market share[18]).  The deal was agreed September 12, 2016, and was valued at $30 billion. Aside from making the new entity the undisputed No. 1 in fertilizers, it also broadens the base of the enterprise to include seeds and crop chemicals.[19] The deal is expected to close in mid-2017.[20]

As the four negotiations went back and forth, the world’s other significant seed, chemical and fertilizer companies were looking on with a mixture of consternation and anticipation. Since it is highly unlikely that all four mergers can play through without divestitures, ETC predicts that at least two other M&A options are coming down the pipeline…

5.     BASF (#3 in crop chemicals and a modest player in seeds[21]) either has to get bigger or get out, and is undoubtedly calculating the possibility of snapping up any smaller seed and pesticide companies that fall by the wayside if the other mergers proceed. Its second option is to go after the second-string of German, Dutch, US and Japanese seed/pesticide companies to cobble together a larger agricultural footprint.

6.    The same second-string players may be thinking of doing the same thing—either picking up the leftovers or merging themselves. Though alarming to smaller companies, the mashing together of the giant companies also leaves them niches of opportunity.

But a 7th M&A has been playing off stage; important on its own, but also a harbinger of much bigger changes that will impact global agricultural inputs in the months and years ahead…

November 2015 –  Deere & Co. (#1 in farm machinery and nothing much in seeds or chemicals[22]). agreed to buy Monsanto’s Precision Planting LLD.[23] In August 2016, however, Deere was sued by the US Justice Department to block the deal[24] because the merger would allow Deere to “dominate the market for high-speed precision-planting systems and be able to raise prices and slow innovation at the expense of American farmers who rely on these systems”[25]:  Deere and Precision Planting LLD together would account for 86% of the precision planting market.[26]  Deere and Monsanto said they would fight the decision.[27] Bayer may have changed all of this.

References:


[1] Brazil is the world’s largest agrochemical market at US$10 billion, China is the 3rd largest agrochemical market at US$4.5 billion, Argentina is 8th at US$1.5 billion and India is 9th at US$1 billion. Source: ETC Group, “Merge-Santo: New Threat to Food Security.” Briefing Note. March 22, 2016. http://www.etcgroup.org/content/merge-santo-new-threat-food-sovereignty

[2] 2014 data. ETC Group, “Breaking Bad: Big Ag Mega-Mergers in Play.” ETC Group Communique 115. December 2015. http://www.etcgroup.org/sites/www.etcgroup.org/files/files/etc_breakbad_23dec15.pdf

[3] Ibid.

[4] Ibid.

[5] Aaron Kirchfield, Ed Hammond, Dinesh Nair, “ChemChina Is in Talks to Acquire Syngenta.” Bloomberg News, Nov 12 2015 – 5pm EST. http://www.bloomberg.com/news/articles/2015-11-12/chemchina-is-said-to-be-in-talks-to-acquire-syngenta

[6] Anonymous, “ChemChina Offers Over $43 Billion for Syngenta” Bloomberg News, February 3, 2016. http://www.bloomberg.com/news/articles/2016-02-03/chemchina-offers-to-purchase-syngenta-for-record-43-billion

[7] Michael Shields and Greg Roumeliotis, “U.S. Clearance for ChemChina deal sends Syngenta stock soaring.” The Globe and Mail. August 22, 2016. http://www.theglobeandmail.com/report-on-business/international-business/european-business/us-clearance-for-chemchina-deal-sends-syngenta-stock-soaring/article31484832/

[8] Syngenta, “ChemChina and Syngenta receive clearance from the Committee on Foreign Investment in the United States (CFIUS),” Press Release, August 22, 2016. http://www4.syngenta.com/media/media-releases/yr-2016/22-08-2016

[9] Lindsay Whipp and Christian Sheperd, “Takeover green light sparks anger in US.” Financial Times. September 7, 2016. (printed edition).

[10] 2014 data. Anonymous, “Top 20 Global Agrochem Firms: Growth Slowing Down,” Agropages.com. 30 October 2015; company reporting.

[11] Ibid.

[12] Jacob Bunge, “DuPont CEO Says Merger With Dow Still on Track.” The Wall Street Journal. July 26, 2016. http://www.wsj.com/articles/dupont-profit-beats-as-costs-decline-1469529581

[13] 2014 data. Anonymous, “Top 20 Global Agrochem Firms,” Agropages.com

[14] Jacob Bunge and Dana Mattioli, “Bayer Proposes to Acquire Monsanto.” The Wall Street Journal. May 19, 2016. http://www.wsj.com/articles/bayer-makes-takeover-approach-to-monsanto-1463622691

[15] Greg Roumeliotis and Ludwig Burger, “Bayer clinches Monsanto with improved $66 billion bid” Reuters. September 15, 2016. http://www.reuters.com/article/us-monsanto-m-a-bayer-deal-idUSKCN11K128

[16] Reuters, “Agrium and Potash Corp Are Merging to Make a Giant Fertilizing Company.” Fortune. September 12, 2016. http://fortune.com/2016/09/12/agrium-potash-corp-merger/

[17] 2014 Data. ETC Group, “Breaking Bad”

[18] 2014 Data. ETC Group, from publicly available information.

[19] Guy Chazan and James Fontanella-Khan, “Bayer urged by Monsanto shareholders to raise bid further.” Financial Times. September 6, 2016. http://www.ft.com/cms/s/0/9219b46c-7422-11e6-b60a-de4532d5ea35.html#axzz4KGHWYNW5

[20] Rod Nickel and Siddarth Cavale, “Fertilizer majors Potash and Agrium to merge, face tough scrutiny.” Reuters. September 12, 2016. http://www.reuters.com/article/us-agrium-m-a-potashcorp-idUSKCN11I0Z0

[21] 2014 data. Anonymous “Top 20 Global Agrochem Firms.” Agropages.com

[22] ETC Group, compiled from company reports

[23]John Deere & Company, “John Deere and The Climate Corporation Expand Options for Farmers.” Press Release. November 3, 2015. https://www.deere.ca/en_US/corporate/our_company/news_and_media/press_releases/2015/corporate/2015nov03-corporaterelease.page

[24] United States Department of Justice, “Justice Department Sues to Block Deere’s Acquisition of Precision Planting.” Press Release. August 31, 2016. https://www.justice.gov/opa/pr/justice-department-sues-block-deere-s-acquisition-precision-planting

[25] Ibid.

[26] Ibid.

[27] Ibid.

Natural Products Map

 

A fundamental shift is underway in how food, flavor, cosmetic, and fragrance ingredients are being produced for global markets. The new game in town is synthetic biology, or GMOs 2.0—companies are now able to create yeasts, algae and other microbes that secrete artificial compounds that taste or smell like familiar substances but don’t actually come from the natural source.

Several products on the market already contain synthetic biology ingredients—check out this shopper’s guide on synthetic biology to learn more about how to avoid syn bio in your food and cosmetics.

Sneaking syn bio in to products as “natural” is bad news for consumers, and it is also bad news for the farmers, growers, pickers and harvesters who provide the real natural products in our food, cosmetics, soaps, and more. Companies use the excuse of sustainability and local food security to justify the transition from field production to vat production—but many of these natural products grow in difficult environments that are not suited to food crops, so offer very high-value for farmers who may not have other good sources of income. Sourcing raw fragrance and flavor materials from a vat instead of from millions of diverse farmers only offers companies simpler supply chains and increases corporate control over the product process.

In these case studies, ETC Group outlines how 13 specific products are being bio-synthetically created and how traditional livelihoods may be adversely affected as these syn bio substitutes enter the market. This map is for civil society organizations, researchers, and policymakers that want to understand how syn bio flavors and fragrances might affect their work at the country level. You can also download the full report “Synthetic Biology, Biodiversity and Farmers“.