Thursday, February 6, 2014

De-extinction: Extreme GMOs in conversationist's clothing

De-extinction is the name given to several approaches that Biotech Boosters promise will eventually be able to bring back extinct species.

It is offered as a plausible solution for healing what Steward Brand calls "the huge hole" that humans have made in nature over the past 10,000 years.

It is hard to deny we have created a "hole" in nature. Ever since the dawn of agriculture, we certainly have been messing things up, and we sure aren't slowing down. We have now converted most of the world's arable land into farms and fields. We are pushing the rest of the biosphere into fragmented "nature reserves" while we line the Earth with rows and rows of the few dozen species of plants and animals that we've come to depend on. This massive conversion of the world's diversity into human foodstuff created a food surplus that spurred the rapid growth of the human population. Further, it provided the opportunity to specialize human labour: in the past, everyone had to subsist through finding their daily bread. Now, we have food production systems that allow us to become soldiers, scientists, politicians, miners and bankers. Many of these professions devastate the land, air, and sea through feverish cycle of extraction, production, consumption, and waste. And the "hole" gets bigger.

Thousands of species have been driven to extinction, and with accelerating industrialization, hundreds of thousands more are either endangered or vulnerable (Barnosky et al., 2011). Environmentalists have been sounding the alarm for decades but their appeals to change course are hushed by the clamour of progress. Industries are digging their claws ever further into ecosystems that have been until now "off limits" --the steepest mountains, the thickest jungles of the Amazon and Congo basins, the deep ocean waters, the once permanently frozen Arctic-- and an increasing population expects and demands the very lifestyle responsible for ripping the hole Brand claims we've made ever more wide.

In light of this harrowing situation, de-extinction is being tossed around in newspaper articles and magazines, from the New York Times to National Geographic, as a radical and powerful way of healing the wounds we've cut and are cutting still every day. Indeed, Brand himself has claimed that because we have the technology to bring back lost species we may have "the moral obligation, to repair some of the damage." With his wife, he's co-founded a nonprofit organization to get the idea up and running.

Not all are so enthusiastic, however. Perhaps the hesitant tone of many feature articles indicates just how well Jurassic Park's dystopic lesson was burnt into our memory cells with a dire warning as to what could happen if we don't keep our hubris in check.

Of course, few people are intent on bringing back velociraptors or tyrannosaurus (let alone another opportunistic sequel with Goldblum repeating (again!) the lines: life will find a way!). Instead, on the table are what appear to be relatively benign discussions about resurrecting those beings we've personally had a hand wiping off the face of the Earth: the passenger pigeon, the wooly mammoth, the thylacine, to name a few. (Needless to say, however, we shouldn't rule out what they may try to do: scientists are stretching their genome sequencers into the remote depths of the past as best they can and have recently decoded a 700,000 year old horse ancestor's genome (Shapiro & Hofreiter, 2014)). In any case, perhaps the more mouth-watering prospect amongst such conservation-minded technophiles is that of resuscitating species now poised at the edge of the abyss, such as the Javan rhino, with its 40-60 kettled souls, or the Siberian tiger, whose numbers have slunk below 400. Some of these critically endangered species do not breed in captivity and producing these species in labs could protect them from what is otherwise certain annihilation. The World Wildlife Federation has called the possibility "exciting."

But, like every fairy tale, we should know that "happily ever after" is really just a literary device employed to make us feel good, not something that is actually conceivable in a complex, messy and everchanging world. This article's intent is to inject an ounce of sobriety into the discussion. Of course, you may now be thinking that I am making the typical "safe is better than sorry" claim that holds back great ideas. Perhaps you want to quote Goethe at me, reminding me that boldness has genius and power and magic in it. Perhaps you would like to bring to my attention that Jurassic Park's "worst case scenario" is highly unlikely (do we really expect the removable ceiling panels to collapse, only to leave our feet dangling for the vicious fangs of the velociraptor poised below?). Indeed, what do we really have to worry about? That passenger pigeons are going to take over our cities? We already have those spikes on every possible roosting spot to prevent our urban pigeons... surely they will also prevent passenger pigeons from causing similar sorts of mischief?

1. De-extinction may well be just a promissory note for laissez-faire economics
One of the biggest problems with de-extinction is that it keeps us complacent towards the environmental crisis. It helps prop up the attitude that the march of science will essentially guarantee that all of our ills are solved. We will not need to change our lifestyles and can continue existing under the spell of consumerism and infotainment. It is not our responsibility to take personal initiative in helping address issues like "extinction" because we have technical experts working on it.

And yet, one might wonder what would happen if we continue to plunder and destroy while leaving extinction to the experts. The experts may well bring back the Eastern Elk (that disappeared in 1896) or the Newfoundland Wolf (the last one was shot in 1911), and dozens of other species to boot. But in what meaningful way can we be healing the "huge hole" in nature if the habitats that these creatures would live in no longer exist? What is the value of de-extinction if the resurrected species end up in zoos or in the über-affluent's bizarre collection of personal curios to show off with?

Nor should we underestimate the impact that de-extinction technologies could have on pushing ahead the business-as-usual agenda. In a recent interview, Stanford University's Hank Greely warns that in a world where resurrection is a technical possibility, rare species may cease to be a political inconvenience suppressing the free pace of economic development. As he notes: "suppose developers want to build on a last bit of land where an endangered bird lives. And suppose they say, ‘We will be happy to pay for freezing [the DNA or eggs]. Now let us build our golf course’” (link). Like the worthless "fish ladders" and "wilderness corridors" used to squelch out concern over hydro-dams and mining projects, de-extinction could easily become a part of the repertoire of options that corporations have to sway public sentiment. In the simplest terms, we may be trained not fear extinction anymore because the marvels of biotechnology have made extinction itself go extinct!

In a broader sense, de-extinction could thereby functions like advertising for the biotech industry. Like "golden rice" engineered to "cure" vitamin A deficiency in children, de-extinction would be an idea with considerable moral force, useful to compel people that the biotech industry is a beacon of good in the world. This is a particularly important message to promote, considering the scrutinizing public continues to paint the industry as secretly hiding its trident and diabolical horns (Geez, I mean Monsanto has been voted the world's most unethical company for how many years now?). De-extinction can boost the dividends of these companies immeasurably if it is part of an integrated strategy to sway the Average Josephine from reluctantly accepting unlabeled foods (as they do now) to praising the industry for its ethics and responsibility.

2. Hodge-podge biology
Beyond economics, the biology itself turns out to be less promising that it seems. The term "de-extinction" is itself a lie. Scientists are not actually capable of bringing back anything. This is not hyperbole. There are solid genetic, epigenetic, and environmental reasons why current plans to de-extinct a lost species amount to nothing more than risky, transgenic chimera-making; extreme GMOs masquarading as restored species.

First off, it is unlikely that scientists will have access to a full genome of an extinct species. Without this access, they will have to either take the missing genes from a related species or synthesize them in the lab. In both cases, this means that the genetic code is not the genetic code of the extinct species. It is a trans-species hybrid, a genetically modified organism, modified to an extent far surpassing anything that has ever appeared on earth before. If you don't know anything about the risks of GMOs, browse this blog site and familiarize yourself with the subject. I will not repeat the arguments here.

Still, we can ask the question: Is it possible to imagine a scenario where patching together DNA from an extinct species with its closest known relative avoids these risks? Consider humans, chimpanzees and bonobos. We are said to share 99% of our DNA with chimps, and 98.7% with bonobos. And yet, we are widely different from either of them. In turn, chimps and bonobos apparently share over 99% of their DNA with each other, but again, there are significant differences in the physiology, form, and behavior of both these species. The take home message is that small differences in DNA can have huge impacts (especially when multiplied by the effects of epigenetic and environmental factors, see below). If rock pigeons and passenger pigeons differ in 1% of their DNA and we are only missing fragments of the passenger pigeon genome, then the likelihood that the missing DNA is different from a rock pigeon is certainly less than 1%. But it is also certainly more than 0%, and the only way to ascertain with absolute confidence that the difference is 0% is if we had an intact passenger pigeon genome to compare it to. But if we did, then this would make the whole enterprise of substituting rock pigeon DNA for passenger pigeon DNA superfluous. So we are left gambling.

Even if scientists have the entire genome of an extinct organism, they are not out of hot water just yet. In fact, this is where the real problems come in. It is vastly unlikely that the scientists would have the full genome of a sufficiently different number of organisms needed to create a viable population. A minimum amount of genetic diversity is necessary in a population in order for the species to propagate sustainably without entering into an ever-weakening cul-de-sac through interbreeding. To create such a viable population, scientists would have to insert random differences into the genes of the different organisms of the species. This would be to mimic the normal genetic diversity that makes up a healthy wild population of any species. In practice, this implies undertaking hundreds of separate transgenic modifications on hundreds of genomes, or zapping the genomes with doses of radiation to induce mutagenesis, in either case multiplying exponentially the opportunities for something to go wrong by way of disrupting genetic networks, pleiotropic factors, etc. (see my Genetics 101 for details on this).
Beyond the gene, we have epigenetic factors. Epigenetic factors can be thought of as all of the cellular elements that contribute to how a gene is expressed. Now because passenger pigeons died a long time ago, we no longer have access to viable eggs. We have passenger pigeon genome but we do not have a passenger pigeon egg. What we do have are eggs from related species, such as rock pigeons and band-tailed pigeons. We would need to somehow put the passenger pigeon's genome into one of these other pigeon's eggs so to initiate embryological development. The main de-extinction technique to accomplish this would be to take one of the other pigeon species' cells and modify the DNA within to match the cells of the passenger pigeon genome. We would end up with a rock or band-tailed pigeon egg interpreting and expressing a passenger's pigeon's DNA.

Does this matter?
It turns out it does. The cytoplasm, mitochondria, biochemistry, size, temperature, and a host of other factors are all different in the two species. But these factors all influence how the passenger pigeon's DNA will be read. In other words, the context of the genome influences how it is expressed. Genes do not have functions independent of context, their context defines their function. A temperature difference, for example, can turn off certain genes and turn on others, and alter the way that groups of genes interact together. Genetics without epigenetics is just a bunch of inert strings of DNA floating around in a soup. Epigenetics is what activates the genes and plays a strong role in directing what exactly it is that they do. In other words, we may have created some sort of pigeon but it is not a member of either of those two species. We would have created an entirely new species and called it de-extinction just to make ourselves feel better and perhaps to excite the big conservation organizations.

The problems don't end here either. At some point, presumably, the new organism (with its bricolage of a patched-up genome and its cellular structure lifted from another species) is born. What does it do? How does it live? People like to think that animals are unlike people in that the young of our species require an upbringing and initiation into culture by their caregivers, whereas animals can essentially make it on their own. This is increasingly recognized as an anthropocentric illusion. Countless species, from parrots to pumas, depend on interaction with their caregivers and peers to develop in such a way that they can make it in the world. Interestingly, some of this behaviour appears to be handed down, tweaking and adjusting itself generation upon generation, showing evidence of "cultures" or "traditions" in the animal kingdom (Avital and Jablonka, 2000). A human denied contact with other people during its critical early years ends up missing something essential. Its "humanity" is compromised. To some extent, this is true for other species as well. The relationship between organisms and what they pass on through their networks of relations, are all a part of their species just as much as their genes or their epigenetics.

And then there's the ecosystems. Stewart Brand hopes that we may able to produce an organism that is "functionally identical" to how the original organism behaved in its ecosystem, but this is obviously untestable and unverifiable and therefore something that scientists would merely have to take on faith. Nevertheless, his hope is itself shortsighted for the simple reason that ecosystems do not remain static. They evolve so it makes as little sense to try and match an extinct species' DNA to an extinct ecosystem as it does to try and match an extinct species' DNA to a contemporary ecosystem. If, say, 500 years ago we compromised an ecosystem by destroying some species in it, the ecosystem has had 500 years to mend this hole through evolving new interconnections and relations. Because the ecosystem has evolved since that species went extinct, it may not be fair to either the introduced species or the persisting species to mess things up in the name of "healing the wounds."

Stewart Brand: Ecosystems are self-healing if we let them.

Or, dare I say... "life will find a way"?

3. Summary

De-extinction is trying to pull a fast one on us: it is an extreme form of genetic engineering being pushed on the public for what are likely largely economic reasons (I am obviously not denying that there are some scientists that are pursuing this purely because they are interested and think it is "cool" or "ethical"). This does not mean that ethical and sustainable de-extinction is not possible. I could imagine a situation where large quantities of still living populations' DNA (and epigenetic structures) are conserved as a last resort in case their populations started plummeting. Such a bio-bank would provide some insurance in the case of a major catastrophe (human induced, or perhaps from an asteroid, etc.). If done correctly, it would need no transgenic (GMO) technology, no epigenetic cross-species shortcuts (it would be cloning instead of genetic engineering), and could even be part of a program introducing the new organisms into actual biological relationships ecologically established members of its species.

However, I have very little faith that this is how de-extinction is likely to proceed, especially considering its main proponents are also those promoting synthetic biology, geo-engineering, and other extreme forms of human-induced changes to the biosphere (such as Church (2013) and Brand (2013)). It is therefore up to us to foster the dialogue we need to in order to ensure that de-extinction (if done at all) is done safely, humanely, and ethically. If we don't then overzealousness, economic interest, and hubris will continue to run their course and into the tragedy of our age another scene will be written.

References

Avital, E., & Jablonka, E. (2000). Animal traditions: Behavioural inheritance in evolution. Cambridge, UK: Cambridge University Press.

Barnosky, A. D., et al. 2011. Has the Earth's sixth mass extinction already arrived? Nature 471:51– 57.

Brand, S. 2013. The dawn of de-extinction: are you ready? TED 2013. TED, Long Beach, CA. Available from http://www.ted.co/talk/stewart_brand_the_dawn_of_de_extinction_are_you_ready.html

Church, G. 2013. Hybridizing with extinct species. TEDx Deextinction/National Geographic, Washington, D.C. Available from http://longnow.org/revive/tedxdeextinction/

Greely, H. 2013, March 15. De-extinction: hubris or hope. TEDx DeExtinction/National Geographic, Washington, D.C. Available from http://longnow.org/revive/tedxdeextinction/

Shapiro, B., & Hofreiter, M. (2014). A paleogenomic perspective on evolution and gene function: New insights from ancient DNA. Science 343(6169),

Switek, B. 2013. The promise and pitfalls of resurrection ecology. National Geographic. Available from http://phenomena.nationalgeographic.com/2013/03/12/the-promise-and-pitfalls-of-resurrection-ecology/

Tuesday, February 4, 2014

Genetics 101: Why you should be concerned about GMOs.

When genetic engineering hits the news, the headlines are so confusing and contradictory that it is hard for any of us to make sense of it. On the one hand, biotech proponents claim that genetic engineering is just a more precise way of breeding, one that holds great promise for ending malnutrition and alleviating ecological collapse. On the other hand, biotech activists claim that genetic engineering is unnatural, unethical and inherently dangerous. Is this a case of crazy, hypochondriac foodies picking fights they know nothing about with an established and highly regulated science? Or of biotech companies claiming science as their authority in order to force unwanted products on hapless consumers?

As is often the case with polarized issues, each side overstates their own case. The fact is that there are many novel risks associated with genetically modified organisms (“GMOs”), many of which are not adequately acknowledged. This does not mean that every GMO will be perilous to humanity or to life on this planet. Indeed, some of them may turn out to be safe (though still not necessarily desirable). What is not safe is that many governments, regulatory bodies, and citizens are persuaded that the biotech companies' version of the story is the accurate "scientific" version. As it turns out, genetics as a science can hardly condone the haphazard mixing and matching of genes undertaken in company labs. It is simply false for anyone to claim that people concerned about GMOs are anti-science (though many of them do make scientifically questionable claims). To understand why the science of genetics leads to skepticism about genetic engineering, we need to familiarize ourselves with some basics of how genes and genetic engineering work. Doing so will provide the clarity we need to understand the risks of GMOs and enable us to make better choices in maintaining a safe and sustainable food system.

1. How is "genetic engineering" different from "traditional breeding"?
Traditional breeding occurs by having two organisms of a single species mate (see footnote i. below). When they mate, their offspring will have a set of genes, some of which come from the male and others from the female. By controlling which organisms breed, breeders can gradually enable certain traits to get expressed more strongly. For instance, if I wanted to breed cats with longer ears, I would choose a male and female with long ears, create the conditions for them to mate, and wait for the results. Of their children, some in turn will have longer ears than others and I can choose to continue breeding them with other long- eared cats. Eventually, over many generations, the cats’ ears would get longer and longer, (provided, of course, that this trait was able to grow while maintaining the integrity of the rest of the organism's physiology). The point is that what can and cannot be bred is dictated strictly by what is possible for each species based on variations that are already occurring within it.

With genetic engineering, something quite different is going on. A scientist will isolate a specific gene or genes that seem to be responsible for a specific trait and will then insert it into another organism with the aim of getting that trait expressed in the new organism. So, for example, scientists have isolated the genes responsible for making petunia plants resistant to the herbicide known as glyphosate and have inserted the gene into a number of stable crops, such as soy and alfalfa for animal feed, to produce plants that can withstand applications of herbicides. Biotech companies are doing similar experiments on a variety of lifeforms, from bacteria, to trees, to animals. In one particularly shocking experiment, scientists identified the genes that make fireflies glow in the dark and have inserted those genes into the genetic code of cats. As a result, they have now produced cats that glow in the dark (pictures on Google).

While this may seem like a neat sci-fi tricks, and certainly appeals to the tech-geek in some of us, there are a number of well-documented ways in which these sorts of experiments can, and do go wrong. There are certainly ethical issues to be carefully considered when conducting these sorts of experiments too. These issues need to be steadfastly separated from the thrilling power and curiosity some scientists feel at being able to create a seemingly endless number of wild and wacky things simply by combining and recombining genes. Many bioethicists have opened discussions as to whether other species have a right not to be experimented on and modified in these ways (Vorstenbosch, 1993; Oritz, 2004). My purpose here is more modest. I seek simply to outline some of the established reasons why there are real risks associated with the production, release, and consumption of GMOs. Radical and exciting developments in our understanding of the genetic code have emerged in the last decade or so, casting serious doubt on the innocent-until-proven-guilty stance of proponents of GMO technology. At the very least, these developments indicate that a great deal more regulatory scrutiny is necessary than is currently required.

To introduce the reader to how geneticists are now thinking about the behaviour and properties of genes, I will outline the concept of "genetic networks" and "dynamic gene activity." Then, I will discuss the techniques that genetic engineers use in order to create GMOs, showing how these methods contrast with geneticists' emerging understanding of how genes work.

2. Our current understanding: Genetic networks
Biotech proponents usually tell a simplified and mechanical version of how genes work.The story, which some of you may remember from high school biology classes, goes something like this: DNA is a long string of molecules, most of which is random and meaningless. However, there are occasional segments of DNA which produce RNA which go on to produce specific proteins. These active segments of DNA are known as genes, and people generally abbreviate the process by saying that "genes code for proteins". These proteins are extremely varied and extremely important because they are the building blocks of the entire body. Not only do they build organs and tissues but they also metabolize many of the molecules that enable all the physiological processes that regulate the body. In other words, proteins are the stuff that make up both the form and the function of an organism. If the proteins change, the form and/or function of the organism changes as well.

As the story is told, each gene has a specific and discrete role, so a genetic engineer can simply "knock out" a gene that is doing something undesired or insert in another gene that produces a valued protein, and thereby enhance the organism's form or function. The novel gene can come from a number of sources, either from a different location in the organism's own code, from a closely related organism, from a completely different organism, or even from the lab after being manufactured synthetically (see footnote ii below).

The story is widespread in our textbooks, in the media, and on the internet. A part of the reason why it is difficult for people to see the dangers of genetic engineering is because when the process is framed in this way, it seems intuitive and logical. It appeals to our understanding of how machines work, for instance. We can (or should) be able to take out and replace or update parts of our car or computer. So why not bigger mechanical structures, like lifeforms? The problem is that the genome is not really built in the same way as a machine.

Genetic engineering is based on a misleading understanding of what the relationship between genes in the genetic code is like. In fact, "genes" as isolated entities may only very rarely exist. The logic that assumes otherwise long ago fell out of favor with scientists who now prefer to think about "genetic networks" (Dillon, 2003; for a debate on how such networks evolved, see Sansom, 2011). The basic idea of a genetic network is that the behavior of a gene depends on other genes, and that combinations of genes influence each other in complex ways that make it difficult to isolate what a gene "does" except in some rare cases. A gene often has strongest influence (and in turn is most strongly influenced by) the genes closest to it on the genetic code, but this is not always the case. Intricate chain reactions can occur between relatively faraway parts of the code, especially when the code is bent such that certain parts come into closer contact with one another (as occur through what are known as "histone modifications" (Fischle, Wang, & Allis, 2003)).

One way that genes can influence each other is through a process known as methylation. In methylation, a gene can be partially or completely silenced through having parts of its code bound to methyl molecules (Jaenisch & Bird, 2003). There are specific portions of the genetic code known as "regulatory DNA" that control the extent to which various genes are and are not methylated. Genes interact with each other directly but can also interact indirectly through influencing regulatory DNA, which in turn methylate or demethylate other genes. In addition to methylation and histone modifications, there are a number of other ways that genes influence one another, including acetylation, translocation, pleiotropy, and transvection. The field studying these processes is collectively known as "epigenetics" and it is a well-established field of research blossoming strong and fertile research programs (see Jablonka & Lamb, 1995; Francis, 2012, for accessible discussions; see footnote iii below). One of the most unexpected findings in epigenetic was the discovery that knocking out vital genes in animals often does not debilitate them because other genes will become activated to compensate for the loss (Suemori & Noguchi, 2000).

In 2000, entrepreneur Craig Venter's company Celera Genomics mapped the entire genetic code of a human. The news hit headlines worldwide but the excitement faded fast once people realized the limited relevance of what had actually been done. The active coding portions of the DNA (i.e. the genes) had been identified, and many had been assigned specific functions in terms of their role in producing the human organism. But without any mapping of the actual genetic networks, the project ended up being a lot of hot air. Without knowing the relationship between the genes, it was like the company had pulled a bunch of words out of a storybook, produced a crude list of definitions for each word, and were left with little understanding of the story itself. The important point here is that while individual genes may have specific functionality, it’s the interaction of these genes through their specific positions in the genome and their proximity to other genes that really dictates their true nature and consequently, that of the organism. If the genome is a machine, it is quite unlike anything humans have ever built before, its parts threaded together and interacting in complex ways, like how the precise meaning of words and sentences get defined by the paragraphs and stories in which they are found.


3. The dynamic genome: Context matters

But even the storybook metaphor is misleading because it relays the sense that the relationship between the genes are fixed, as are the words in a book. Not so with the genome. The story of the genetic code hasn't been written yet; or rather it gets written and rewritten constantly as an organism interacts in its changing environment. Not only are genes embedded in complex, interconnected networks but the networks themselves are themselves ever changing. For example, one gene will cause another to get expressed, which will down-regulate another, but only as long as a third is still coding for proteins. Whether or not a gene is expressed and what in fact its protein products go on to do are entirely contingent, depending on the state of the rest of the genetic code and of the organism in which the gene is found. In an organism's infancy, a gene may do something quite different than it does in an organism's adulthood, which in turn is different from what that gene might contribute to in periods of environment-induced stress. For example, a recent study found that 86% of a fruitflies' genes change significantly in expression throughout its lifespan (Arbeitman et al., 2002). On the other hand, parts of the DNA thought to be non-coding may activate in certain contexts (Makalowski 2003; Biémont & Vieira, 2006)). In fact, large sections of supposedly random and meaningless portions of the genetic code have turned out to have important roles in the changing behavior of the genome. Normally silent and lurking in the recesses of the genetic code, these genes and other DNA elements can be thought of as part of the built-in resiliency of the system, containing important back-up information and alternative routes and pathways that can kick in when critically needed (for example, Schlesinger, 1994).

The genome is therefore an incredibly complex and responsive system, adjusting itself to changes on multiple levels from changes within the cell, to changes between cells in the organism, to changes in the environment that the organism is continually adapting to. As a result, external changes can modify the way in which genes are or are not expressed. An intuitive way to think about it is to consider how a single fertilized egg cell eventually becomes a fetus and then a baby. That first cell, as we have all seen on TV, splits into two cells, and each of those cells split in turn, producing four cells. This splitting goes on and on until eventually a fetus emerges. But how did certain parts differentiate into separate body parts? The genes and the DNA in all of these cells are, after all, identical. How is it that some of the cells eventually become brain cells and others liver cells or blood cells? All of this happens precisely because of the genetic networks dynamically turning on and off certain genes at specific times, all based on the location of the cells relative to one another (Ridley, 1999). Context matters.

It isn't just the human fetus that bears this complexity. All multicellular organisms do. And because of this complexity, it cannot be stated with any certainty that the genes that a biotech company lodges into a genetic code are benign. It is difficult to know whether or not inserted genes will be interfering with a genetic network, disrupting, upregulating or downregulating other genes, or perhaps even splitting apart an important gene that goes unexpressed until an organism meets some specific stressful or demanding environmental situation. Even the most expensive and thorough current tests, which go far beyond any regulatory requirements for the industry, are not technologically capable of providing this information because we simply do not know the entire genetic networks (nor how they can and do change over time) of the species that we genetically engineer. For example, "OMIC tests", which are more specific forms of gene expression profiling, can catalogue gene products (such as transcripts, proteins, or metabolites) to give more detailed snapshots of some of the physiological changes that occur in the organism (Heinemann, Kurenbach, & Quisr, 2011), but these are themselves limited, difficult to interpret, and not required in any current safety evaluations of GMOs (Lay, & Liyanage, 2006). One of the biggest limitations of OMIC tests is that each test only gives results of changes at one point in time so many tests would need to be taken to understand how the dynamic genome changes during the organism's lifespan.

In the first two sections, I tried to show how the genome is connected in many still unknown ways such that the behavior of a gene depends on the behavior of other genes, its location relative to other genes, and that these connections themselves change over time as the organism adjusts to its internal and external environment. The "one gene, one protein/function" model is not reflective of the way scientist are now thinking about genetic networks and the interactions among them.

An important point here is that genetic networks are only jeopardized by genetic engineering and not by traditional plant or animal breeding. Traditional breeding, which mates organisms of a single species together, respects genetic networks because when the chromosomes of the male and female join, their genes (alleles) are nearly invariably located in corresponding locations and thereby match up. In other words, the gene(s) for eye colour, for example, are located in the same place of the same chromosome for almost all organisms of a given species, so when meiosis occurs in sexual reproduction, the genes are aligned and present no problem in the offspring when some genes come from the male and others from the female. By contrast, genetic engineering does not respect genetic networks but instead inserts genetic material into the genetic networks at random locations. Because context matters within the genetic network, the result of the insertion cannot be known, predicted, or controlled.

4. How do they get the genes in anyway?

For a biotech company to produce a GMO they have to insert genes into an organism's genome and then get them expressed (i.e. coding for the desired protein). As it turns out, this is not an easy task and it is precisely here where many of the most concerning risks of genetic engineering are brought to the fore. In essence, the whole process involves shooting the desired gene randomly into the host organism's code with the hopes that it will get lodged in somewhere where it will not disrupt any genetic network too much. The gene, it should be pointed out, is not fired into the host code on its own. As it turns out, it is actually a part of a patched together assembly of genes from at least multiple different organisms (mostly viruses and bacteria) known as a "vector" or a "genetic cassette" (Ho, 1998). Among these genetic components there is an "origin of replication", which is used to replicate the desired genes in preparation to shoot them into the host code; a "multiple cloning site", which allows the scientists to insert the desired gene into the vector; a "genetic marker", which is used to establish whether or not the vector was successfully inserted into the host code; and a "promoter", which is used to ensure that once the vector is in the host code that the desired gene is being expressed.

The origin of replication, multiple cloning site, and promoters are of particular concern because they can make the desired gene, the vector, and the host organism's code more unstable. They are all acquired from different pathogenic organisms such as viruses, and may have been further altered in the lab through synthetic DNA modification. Viruses replicate by parasitizing host genetic codes to create further copies of the virus. Genetic engineers have isolated various parts of viral DNA in order to make use of these hijacking techniques by taking parts of the viral machinery of different organisms and parceling them together into a vector. So, for example, a viral promoter is a gene that viruses use to ensure that once they got into a host code, the viral genes would be recognized and expressed. This is necessary for genetic engineering because cells usually have mechanisms to ensure that foreign DNA is not continuously planting itself into the cell's genome.

It should be apparent here that genetic engineering is far from being simply a "more precise" way to breed for desired traits. By contrast, it is a technique to insert DNA into another organism through bypassing its own defense system by using DNA from viruses and other pathogens. It should also be noted that viruses insert their DNA into sex cells only very rarely. Why is this important? If a virus inserts itself into any other cell of my body and uses the cell to spread, its genes are not being passed down to my descendants. For example, the rhinovirus, responsible for the common cold, only inserts itself into certain respiratory epithelial cells. Its genes do not travel to my sex cells and therefore have no impact on my future offspring. This minimizes ecological and evolutionary impact. Sex cells are generally well-protected in the body to avoid the risky disruptions that occur through viral infection. When genetic engineers say that GMOs are natural because they are employing a form of gene transfer that viruses and bacteria have been using for eons, we should view their claims in a critical light. In fact, in multicellular organisms such as plants and animals, the body has mechanisms precisely to prevent viral transfer of genetic material into its sex cells. This should warn us of the risks of doing so.

Using promoters to express the desired gene in the host code is especially risky because promoters often overpromote. They upregulate the gene (just like the regulatory DNA discussed earlier) such that it produces far more of its protein products than would be normal in its original context. Further, its capacity to overpromote changes the ways in which the host genes surrounding the vector end up getting expressed. It thereby often ends up promoting unintended genes in the organism (Ho, Ryan, & Cummins, 1999). The concern here is that promoters have a strong capacity to modify the genetic networks of the host organism in unpredictable ways. When these are combined with other elements, such as the "origin of replication" genes, we sometimes find that the desired gene actually gets replicated and reinserted in different places across the genome, functioning like "jumping genes" (or, as they are technically known, transposons (Keller, 1983), see footnote 4, below). This further exacerbates the functional integrity of the genetic networks. Promoters and origin of replication genetic segments may also make the vector (or parts of it) unstable and more likely to jump out of the host's genome and into the environment. This now appears to be an uncommon process (de Vries & Wackernagel, 2004), though researchers point out that the colonization of the soil by bacteria that have incorporated such transgenic material should take much more time than has been assumed by many of these studies (Nielsen & Townsend, 2004). Further research is clearly necessary: if these genetic elements can be taken up by soil and gut bacteria, remaining in these micro-ecosystems indefinitely, they carry the risk that they will in turn incorporate themselves into other organisms at some point in the future (with obvious possible unpredictable results on those organismss genetic function).

5. Summary
The risks of genetic engineering emerge on various fronts. First, the "single gene, single function" model is not appropriate. Indeed it is destructive because it trains us to think of life as a machine made out of isolatable, detachable and replaceable parts. The organism is better thought of as an evolving and interconnected system, where its parts are always defined contextually and contingently. When viewed from the perspective of fluid and dynamic genetic networks, the effects of inserting a gene into a genome are not predictable or easily measurable. This is one clear reason why public concern about GMOs needs to be taken seriously by regulatory agencies. Second, the techniques of genetic engineering are problematic and may exacerbate the problems associated with inserting foreign DNA into organisms. Current biotech techniques, which use DNA material from pathogenic organisms, can make the desired gene, the vector, and the host organism's code unstable, and can cause the promotion of proteins and unintended genes, disrupting genetic networks and sometimes possibly jumping into the environment to get taken up by other organisms.

Although genetic engineering technologies are advancing rapidly, our understanding of the genome is undergoing a significant shift that puts into question many of the premises upon which GMOs are based. We can expect that genetic engineers will attempt to accommodate better the fact the genetic networks and epigenetic dynamics exist and cease to employ some of the riskier techniques described in this article. In any case, we must keep vigilant and continue to update ourselves on these evolving approaches so that we can publicly discuss and critically evaluate the technologies for their potential impacts on our health and on the environment. Above all, we must raise our concerns in a clear and articulate manner to our government officials, who themselves may well need some educating on the science of the genome in the 21st Century.

Footnotes

i. A third approach to breeding is called "mutagenesis" and it involves subjecting cells to high levels of radiation to induce mutations and selecting from the mutated cells those that have desirable traits. Mutagenesis has been around for about 100 years, but should not be considered a form of "traditional plant breeding". In any case, it will not be discussed in this article.

ii. Although these procedures have different technical names (known as cisgenic, linegenic, transgenic, and xenogenic engineering respectively), they are all forms of genetic engineering that rely on essentially the same technologies and bear many of the same risks. The common scientific name for them is usually simply "transgenic" engineering.

iii. Of course, as the science of epigenesis evolves so will the desire to apply the knowledge. Epigenetic engineering seeks to modify the behavior of genes through altering the way in which the genes are read and/or expressed in cells. Epigenetic engineering is not necessarily a benign alternative to genetic engineering because it can instigate many of the same interactional effects as genetic engineering. Consumers should be on the lookout for developments in this new field (will they be called EGMOs, as in "epigenetically modified organisms"?).

iv. Botanist Barbara McClintock discovered the presence of transposons, mobile genetic elements that are a part of an organism's genome and which jump around and can replicate inside that genome. Their evolutionary and immunological functions are a subject of great interest. In some ways, transposons may appear to be similar to the overactive promoters introduced by genetic engineers. Closer inspection reveals that the genome has actually evolved to let certain types of genes jump around while restricting this capacity in others. When genetic engineers add promoters to genes and insert them into the genome, the location of the promoter can create new types of transposons that do not have a history of interaction within the organism's genetic networks.


References

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de Vries, J., & Wackernagel, W. (2004). Microbial horizontal gene transfer and the DNA release from transgenic crop plants. Plant and Soil, 266, 91-104.

Dillon, N. (2003). Gene autonomy: Positions, please... Nature, 425, 457.

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Ho, M.-W. (1998). Genetic engineering: dream or nightmare? Penn Valley, CA: Gateway Books.

Ho, M.-W., Ryan, A., & Cummins, J. (1999). Cauliflower mosaic viral promoter - A recipe for disaster? Microbial Ecology in Health and Disease, 11(4), 194-197.

Jablonka, E., & Lamb, M. J. (1995). Epigenetic inheritance and evolution: The Lamarkian dimension. Oxford, UK: Oxford University Press.

Jaenisch, R.; Bird, A. (2003). "Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals". Nature Genetics. 33 Suppl (3s): 245–254.

Keller, E. F. (1983). A feeling for the organism: The life and work of Barbara McClintock. New York, NY: WH Freeman and Company.

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Makalowski, W. (2003). Genomics: Not junk after all. Science, 300(5623), 1246-1247.

Nielsen, K. M., & Townsend, J. P. (2004). Monitoring and modeling horizontal gene transfer. Nature Biotechnology, 22, 1110-1114.

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Ridley, M. (1999). Genome: Autobiography of the species in 23 chapters. New York, NY: HarperCollins.

Sansom, R. (2011). Ingenious genes: How gene regulation networks evolve to control development. Cambridge, MA: MIT Press.

Schlesinger, M. J. (1994). How the cell copes with stress and the function of heat shock proteins. Pediatric Research, 36, 1-6.

Suemori, H. & Noguchi, S. (2000). Hoc C cluster genes are dispensable for overall body plan of mouse embryonic development. Developmental Biology, 220, 333-342.

Vorstenbosch, J. (1993). The concept of integrity: Its significance for the ethical discussion on biotechnology and animals. Livestock Production Science, 36(1), 109-112.

Thursday, May 30, 2013

Kickstarter's Ill-Conceived Support for Extreme Biotechnology

In late April, a Kickstarter campaign was launched to raise money to produce glowing plants. The venture was plugged as environmental: if trees could glow in the dark, we could save energy and resources because we wouldn't have to line our streets with streetlights.

We could use trees instead.

The project falls under the radar of the typical biotech activist. It is not a food, so the growing number of health-conscious consumers may not care. It is also not being produced by a biotech giant, but rather by a handful of young businessmen/scientists. This might neutralize the concern of those fighting Monsanto because they hate monopolies and big business. Environmentalists may actually find themselves enamoured with the whole idea of "glowing plants": it is purportedly "sustainable", after all, allowing us to reduce our energy usage. Right?

Does this mean we shouldn't be concerned?

No. From what I understand, this initiative is potentially one of the most dangerous yet -not just because of very real ecological risks but also because of the precedence it could set. Even though the trees are not produced by Monsanto or Dupont, nor are they generating their own pesticides (such as some GMO foods), the potential risks are enormous. Let me outline them them briefly:

1) Like all engineered organisms, the glowing plants will have unintended side effects. The inserted firefly genes may well be benign in fireflies, but that does not provide any evidence that they will be harmless in plants. The interactions between the firefly genes and the plant's own genes will cause each to behave in potentially unpredictably ways. This is known as "pleiotropy" and I have written about it before. Even if their are no pleiotropic effects (and this would require extensive study) their may be direct ecological effects. For example, how might glowing trees affect the behavior of moths? Of bats? Of birds and squirrels that build nests in them? Or even of ants? Migrating birds already die in colossal numbers because they get confused at night from the lights in big buildings and fly right into the glass. Note that this was not anticipated (and probably not likely anticipatable!) when we began constructing tall glass buildings. We cannot assume that there will be not behavioral changes and it is easy to imagine some frightening scenarios that might occur.

2) The founder of the glowing plants campaign, Antony Evans (pictured on the left... by the way, don't send them hate mail - it is better to educate him), has a reckless marketing gimmick: they will send 100 free "glowing plant" seeds to anyone who contributes over $40 to their project. To date, over six thousand people have signed on, and so hundreds of thousands of these genetically engineered seeds are set to be distributed across North America to all these funders. The problem is that no government agency is testing, regulating, or overseeing these transactions. Kickstarter is allowing fundraising for a type of technology that no government even knows how to regulate.

3) The project is being fundraised through a crowdsourcing platform. If successful, then others, also intent on creating any number of chimeras and monsters, will be able to raise money as well. We may well see dozens or hundreds of independent biohackers raising money online to reprogram organisms. As Huffington Post writer Jim Thomas points out, in the near future, people may soon be able purchase organisms with designed characteristics off the internet as nonchalantly as we now purchase apps from iTunes. If these are not regulated, hundreds or thousands of novel organisms could flood our ecosystems. Keep in mind that the introduction of novel species into ecosystems is already the second biggest cause of species extinction (behind habitat destruction). If this project sets a precedent and hundreds like it are allowed to emerge, biodiversity and the ecosystems that life produces, are in grave danger. This is not an apocalyptic environmentalist fear-mongering. We have ample evidence that new species make other species go extinct and can destabilize the resilience and functionality of ecosystems.

4) Green-tech solutions often eclipse our vision of what really needs to be done. We spend millions of dollars tinkering in labs when we should be spending that money protecting ecosystems. The cheapest and most effective way of attending to the ecological crisis is by conserving ecosystems, which provide trillions of dollars in services for free every year. Green-tech solutions are often hopelessly misguided anyway. How green are glowing plants really expected to be? Are streetlights really what are draining our energy resources? Seems like the smallest fraction of the problem to me, and new LED streetlights are providing impressive advances in efficiency. Green-tech solutions feed the inner tech-geek in us, but they scarcely provide meaningful solutions to the real problems we face.

5) My fifth point is unabashedly sentimental. I admit, it might be "cool" to see a glowing tree. But I certainly don't want to live in a world where the trees lining the streets are glowing at night. Where the new "normal" is to not have the spontaneous beauty and elegance of a growing tree eclipsed by some nerdy tinkerer's get-famous-quick scheme. There is already far too little 'nature' allowed into our cities and the little that is here provides me with immeasurable peace and solace. Imagine how devastating it would be if, everywhere you turned, you saw just another human creation. In those glowing trees, you might hear chirping birds. Some of the birds were genetically altered to eat some insect pest more efficiently (and the insects themselves are pests because they, too, were an earlier green-tech GMO project gone awry (think: killerbees and superweeds)). Other birds were genetically engineered to produce 'cooler' songs or to have brighter colours (because Kickstarter would be especially appreciative of projects with a 'cool' factor). Everywhere you look, you are reminded of human imperfection, egoism, and greed. Richard Louv has documented the importance of nature for the health, sociality, and intelligence of children. We all need nature. We need life's wild and complex freedom around us. Evolution created us as it created the rest of the biological world, and we must maintain environments where we can witness and appreciate the complex birthing process of the Earth. What little we have left, we need to keep.

In a recent interview, Evans, the project founder, stated that Glowing Plants was "a demonstration project to inspire people to get involved with the amateur DIY Bio movement." This might be the 15 most frightening words I've heard in a long time. Listen up! Ecosystems aren't made of Lego blocks that can be built and rebuilt at will. I suggest that any biotech tinkerer who does not understand the concepts of ecological stability, resiliency, redundancy, or have a basic understanding of how the rate of evolutionary change optimally balances novelty and development, should spend more time learning about the world around them. Leave the childish games inside the game room if you must play them at all.

What you can do.

Kickstarter cannot continue to facilitate the widespread contamination of ecosystems by biohackers. Kickstarter has helped scores of fledging artists and entrepreneurs get off the ground. For this they should be commended. But their support for this project is ill-conceived. Please sign the Avaaz petition immediately to demand that they reconsider providing a platform for projects seeking to engineer and distribute unregulated modified organisms. A project called "Kickstopper" is raising money to stop the release of these untested seeds - well worth it to throw a few bucks at them!! Send a personal email to Kickstarter too. Share the news with your friends.

And, of course, there is always Kickstarter's Facebook page...

It is also worth emailing the USDA's agency that deals with the release of transgenic organisms into the environment. Send a brief, informed and polite email to BiotechQuery@aphis.usda.gov to ensure the most effective response.

We haven't got much time. Kickstarter will release the funds on June 7th unless we let them know loud and clear that this is an unacceptable risk!

JUNE 5th: BREAKING NEWS: Prestigious scientific journal, Nature, comes out with the following warning: "A controversial new project is seeking public donations to develop a glow-in-the-dark version of the thale cress (Arabidopsis thaliana) using genes from fireflies. If the effort succeeds, thousands of supporters will receive seeds to plant the hardy weed wherever they wish." (see full article). This has instigated some serious rhetorical back-peddling from the project founders.

Sunday, December 9, 2012

"Substantial equivalence" - A tricky, misleading term!

The biotech industry argues that genetically engineered organisms do not require labeling, should not be subjected to rigorous testing, and do not warrant careful public scrutiny.

This is because, the industry proclaims, genetically engineered organisms are "substantially equivalent" to their non-engineered counterparts.

Substantially equivalent? Say what??

The concept of "substantial equivalence" like so many words in the biotech industry's vocabulary, reeks of Orwellian Doublespeak. It is their attempt to have their cake and eat it too.

In other words, there is a deceptive ambivalence to "substantial equivalence".

Let's unpack the term.

Of course, the industry could not say that the GMO was "completely equivalent" because then they would have no basis for claiming a patent on the organism.

And they could not claim that it was "substantially different" either, because that would trigger concern that they'd rather not face.

The secret was to find a combination of words that make the invention seem just different enough to merit a patent but not different enough for people to be concerned about. With "substantial equivalence", they landed in a pot of gold.

Of course, the concept is absolutely misleading. But that was why it was valuable. It functions like a slippery snake, evading any attempt to pin down its meaning. When those concerned about GMOs speak out, it slithers over towards "equivalence". When the patent offices inquire, it nests in the serpentine ambiguity of the word "substantial".

(I apologize to the snakes out there for using this metaphor.)

"Substantial equivalence" shares that oxymoronic sneakiness that makes so many other industry concepts so enervating. Think of "sustainable development" or "clean coal" or "ethical oil".

The term "substantial equivalence" originally met with resistance from the Food and Drug Administration (FDA), who had internal documents describing the possible toxins, allergens, and new diseases that might arise from GMOs (Freese and Schubert, 2004).

However, for whatever reason, the documents were ignored and the FDA decided to go along with the term.

So did the FAO.

The FDA also decided that it would be sufficient if the biotech companies conducted the studies by themselves to establish whether or not their GMOs were "substantially equivalent". This would not be considered a conflict of interest.

And the FDA decided that the FDA itself would not need to conduct any testing of these novel organisms. It would just believe the biotech companies' reports.

The FDA's regulation gets even more stringent at this point. Listen up.

The actual experimental write-ups by the companies are classified so no independent scientists can access them. The FDA has no problem with this.

And, as icing for this overly saccharine transgenic cupcake... the biotech companies do not allow external scientists to conduct health or environment tests using their seeds. In fact, when you purchase the seeds, you have to sign a legal document assuring that you will not test them in any way.

They are not merely seeking a monopoly on our food source. They are also seeking a monopoly on the knowledge we can gain about their products.

Let's leave all of this (ahem....) impressively rigorous regulation for a moment, and ask ourselves: what is it exactly that the biotech companies claim to analyze in order to deem their products "substantially equivalent"?

A 2003 review in Trends in Biotechnology identified 7 main research foci. Now, we cannot actually see the studies that Monsanto or Dupont or Dow or Astra Zeneca conduct in these 7 areas because, as I said, they are company secrets. But even if we take their word for it and in good will assume that the reports they issue publicly are not biased, the seven areas themselves are not at all convincing.

In fact, with a little understanding of genetics and ecology, they all seem quite weak.

Allow me to indulge a little bit in each of them. Here is what biotech companies claim to do, and here are my answers:

1. Study the introduced DNA and the new proteins or metabolites that it produces.

Genes make mRNA which produce proteins. Understanding what new proteins are produced is crucial for understanding how the gene is altering the behaviour, physiology and biochemistry of the organism. This is because proteins are the building blocks of processes and products in the body. Of course regulators should be studying the proteins that the introduced DNA produces!

Unfortunately, studying the proteins that the introduced DNA produces is not enough.

Why?

Because the introduced DNA interacts with other genes, switching them on or off, upregulating or downregulating them. For example, in yeast, over 95% of the genes interact with their neighbours (Featherstone and Broadie, 2002). Genes do not behave in isolation, they operate in networks. When we introduce new DNA into an organism, an undefined number of other genes end up producing proteins in unexpected ways too. The same goes for metabolites, which are synthesized in complex networks of co-interacting chemicals.

2. Analyze the chemical composition of the relevant plant parts, measuring nutrients, anti nutrients as well as any natural toxins or known allergens.

The key word in this is "relevant". I assume that for GMOs intended for consumptions, the "relevant plant parts" are those parts which people eat. But the novel genes are not just in those relevant plant parts. They are in every single cell of the organism's body! And even if humans are not eating those other plant parts, SOMETHING is. And it is important to know how that something will react because it is part of a larger ecology and so changes to it could have ecological effects.

Second, it is easy to test for "known" allergens and anti-nutrients. But what about unknown ones? The concern is that novel proteins or novel combinations of proteins or metabolites might trigger some health problem. Given that it is impossible to test for an unknown allergen does not mean that the burden of proof should be placed on those concerned. Yes, it is a scientific problem to figure out how to conduct such tests. But that is the problem of those who produce the technology.

It is not acceptable for them to say (as they sometimes do): It is too complicated! How can you expect us to study each and every one of those unlikely scenarios? Doing so would throw a wrench into the cogs of progress!!

3. Assess the risk of gene transfer from the food to microorganisms in the human gut.

Unsurprisingly, there are problems with this one too. And again, they stem from a refusal of the biotech industry to respect living beings as complex interactive networks.

The quantity and variety of gut micro-organisms is continually shifting across time, is dependent on cultural, environmental and climatic factors, and numbers from 300 to 1000 bacteria species, and fungi and protozoa too. Can we possibly imagine that biotech companies test for all of these possible combinations? It is a permutational nightmare and would be exorbitantly costly. But it gets worse: the gut itself is an environment for the gut organisms, and as the gut changes (from sickness, from exposure to chemicals, etc.) they way the gut microorganism behave changes too. Some genes may switch on, others may downregulate, as the organisms co-evolve with their mini-ecosystem. What about all those factors? Further: considering the biotech companies do not actually conduct tests on humans (PRIOR to release, of course... we all know that they are conducting highly unscientific experiment on millions of us AFTER release!) we cannot assume that the environment within which these microorganisms are being tested for gene transfer is equivalent to the environment in the human gut. Finally, the context of the GMO is not stable. Environmental stressors can switch on certain genes or inhibit others, altering the way that the transgene behaves and potentially making it unstable. Alternatively, changes in the human could modify the degree to which the gene may jump.

Proponents of genetic engineering might say: Lighten up! It's just a gene! Why would it be more likely to jump out of the food and cause a nuisance than any of the other genes? Shut up and eat it, it is the most tested food to ever find itself onto your dinner plate!

Well, the answer, again, is clear: the gene didn't just arrive by some happy coincidence into the host code. It was forced in using viral vectors despite the defence mechanisms within the cell to prevent the invasion of foreign DNA. After in, it was shaken into activity using a viral promotor. These viral genes are aggressive and unpredictable. After all, it is through these genes that viruses can hijack other organisms' genetic codes. Viral genes increase the instability of the other transgenic genes. The same stuff that made it get in can also make it jump out.

4. Study the possibility that any new components in the food might be allergens.

It is interesting to ponder how this could be done without human studies. Anyway, I've addressed the concerns with this point in #2 and #3 above.

5. Estimate how much of a normal diet the food will make up.

How much of it we eat is simply not relevant to answering the question of how similar the novel organism is to its natural counterparts. There isn't much else to say about this one.

6. Estimate any toxicological or nutritional problems revealed by this data in light of data on equivalent foods.

This is potentially useful. The idea is this: suppose the novel proteins are present in some other food. The scientists study that food for toxicity so that they have likely scenarios with respect to their GMO. By all means this sort of analysis should be conducted! But it would be erroneous to assume that a given protein in one context has the same effects as that same protein in another. The other nutritive factors and metabolites in that food work synergistically or antagonistically in complex ways that render the protein's effect "context dependent".

7. Additional animal toxicity tests if there is the possibility that the food might pose a risk."

These are typically 90 day studies and are inadequate to assess health across the lifespan or multi-generationally.

So, what would better "substantial equivalence" look like?

It is possible that a gene might be inserted somewhere such that it did not do anything harmful to the organism, to the one consuming it, or to the surrounding ecology. Of course it is theoretically possible that some GMO is "safe" in these senses. But the point is that no study is anywhere near establishing this and there are sound genetic and ecological reasons to believe that this would be a rare phenomena.

Nevertheless, there are some technologies emerging that can show in much greater detail whether or not a GMO is "substantially equivalent". There are problems with these tests, but it is good for food activists to become familiar with them.

Proteomics, metabolomics, and transcriptomics (often known collectively simply as OMIC studies) provide much greater insight into the effects of transgenic alterations than any of the simplistic and limited biochemical tests conducted. For example, a proteomic study would show how the protein products in the new organism differ statistically from a natural organism of the same species. This would help identify pleiotropic effects. If an inserted gene altered the behaviour of some gene nearby it, this altered behaviour would (theoretically) show up as some change in the protein distribution relative to a non-engineered organism.

These studies are still insufficient due to statistical inadequacies, but also because they only provide snapshots into the behaviour of the GMO. The GMO might be tested in laboratory conditions, where the inserted gene behaves in one way with its neighbours. But in complex field conditions, the gene often behaves differently and its behaviour changes over its lifespan. It would be unrealistic to think that the biotech companies could comprehensively test for protein changes across every likely field condition because there is an enormous variety, dependent on humidity, temperature, interacting organisms, predators, nutrient availability, etc.

Needless to say, most biotech companies and their cheerleaders are arguing that ANY OMIC study is unnecessary and that current substantial equivalence protocols are more than sufficient.

I apologize that this article got pretty technical, but I really think we need to know this stuff. Anyway, my conclusion is simple:

"Substantial equivalence" is a misleading term. Current regulations provide many holes for potentially serious health and environmental effects to slip through. Newer OMIC studies exists, which would provide a finer grained filter to skim out potential problems, but these studies are certainly not foolproof. Activists should understand that this neologism is used for political gain and as a tool for ensuring compliance. It is not a scientific term and it is not likely to be in the near future, given our analytical limitations in understanding the genome.

It is important that we expose the regulation for what it is. The biotech industry constantly accuses those concerned with genetic engineering of ignorant fear-mongering. The techniques that these companies utilize and enthrone with the Godly title, "Science", are neither noble nor ingenious. Behind their cunning words lie a dearth of precision and a surplus of greed.


Wednesday, November 21, 2012

The Powerful Potential of Anti-GMO Cyber-Citizens!

Sometime last night,
with the cold November winds blowing amuck outside his window,
and the naked trees scratching menacing songs on the rooftop,
a man stumbled upon something that warmed his heart.


It was, of all things, a Thanksgiving Survey on Smucker's Facebook page.

The survey asked consumers to vote on their favourite Thanksgiving food. The top choices were (in order of preference): turkey, stuffing, potatoes, ham, and pumpkin pie.

Now, as many of you know, these surveys are designed so that people can participate and add items to the list. The man softly grinned and tapped the words "Non GMO food" into the survey.

Then he voted for it.

Word got around because somebody posted it on a consumer advocacy group's Facebook Page and that group, in turn, posted to someone else.

It went viral.

Many people ended up voting. I surely did.

By the time I had gone to sleep, "Non GMO food" had received twice as many votes as the next highest on the list. When I woke up this morning, I saw that it had received 5 times as many. For those stats hounds out there, here's the current score:

Non-GMO Food 259
Turkey 64
Stuffing 46
Ham 19 (... how ham got ANY votes is beyond me!)
Pumpkin Pie 16


(editor's note: The questionnaire has now been removed)

While people voted, they also voiced their concerns about Smucker's GMO policy on their Facebook page. Dozens of comments filled the page and I am happy to report that no one was tempted by the obvious cheap-shots that Smucker's has heard a million times. There were no "Sucker's" or "Schmucker's" flung about at all!

By and large, people were civil, which is the most effective way to be in situations like this.

(What is Smucker's GMO policy by the way? It is basically this: we will use genetically engineered ingredients and we will pay a lot of money to confuse you into believing that labeling is a bad idea if you ever think to try and push the government for your right to know what is in your food.)

This quick, simple action demonstrates the new power that citizens have in the age of the internet.

It is a wonderful example of "swarm intelligence".

Like bees and ants, concerned citizens who use Facebook, Twitter and other forms of social networking, work in a distributed and de-centralized intelligence that has a power that we are only just beginning to recognize. Through the connections and relations it provides, the system is capable of doing things that any individual one of us is impotent to achieve.

As many of the bigger NGOs lumber about, held back by their own weight and bureaucracy, people networking over computers are spontaneously and dexterously birthing new and exciting actions daily. We still need those NGOs for some functions but there are some things that we can do better than they can.

We are crafters of a Beautiful New World Order and posting, sharing, liking, tweeting, recommending, and commenting are among our most important work tools.

My sense is that if we organized ourselves a little bit, we could increase our effectiveness severalfold.

There are over a hundred anti-GMO groups in North America. Many of these groups are performing redundant activities, posting and reposting the same soundbites and visuals. Of course, swarm intelligence requires some redundancy.

But we could divide our labour in an organized way and increase our impact immeasurably.

How?

Well, we could have a few groups whose specific job is to scour Facebook Pages looking for opportunities for us to act. Along with the Smucker's vote, there are probably hundreds of other important resources for us within Facebook.

But we don't have to stay within the navy blue halls of Facebook either: we could have a few groups that scan the major news networks for food issues related to GMOs and organics. Many of these news agencies provide "comment" sections that are beckoning our delightful responses!

We could have a few groups foraging in the "women's magazines" and a few others in the "men's" ones (I know, I hate the gender division here too).

We could have another group surveying the online science magazines.

And, of course, we'd need some other groups to scope out the smaller newspaper websites too.

And then there's the blogs!

Each time a group finds a relevant article, they would leave their comments, copy the link, and send it off through our networks.

Upon receiving these ACTION ALERTS, we would simply click on the link, read the article or post, voice our comments and go about our day feeling slightly happier. We have contributed a little to a new and powerful form of participatory democracy. That always feels good.

When the Smucker's staff open their Facebook account today, their socks are going to fall off.

Can you imagine if we left as few stones as possible unturned, if virtually every North American media resource was well represented with our messages, if customers ignorant of the issue were continually exposed to our polite and informed, yet firm and resolved voices?

I don't want to lead you into any fantasy utopia. But we can certainly get closer to achieving this by organizing a little and dividing our labor.

So let's start! What is your group going to focus on?

Friday, November 16, 2012

Educating more Effectively about GMOs

I am elated, absolutely elated, that North Americans are becoming more concerned about genetic engineering. This is a wonderful, hopeful time!

When the biotech companies and the food giants threw $45 million into defeating our right to know what is in our food, they had no idea what a silly move that was. Instead of silencing their opponents, they made it clear to those sitting on the fence that they would do anything to maintain their profits. My capitalist and socialist buddies alike, hearing the story, shake their heads. It is a move that will disgrace them for decades to come.

As a result, many of us are now beside ourselves with excitement. The defeat of Proposition 37 did not feel like a defeat because the industry exposed their true nature while bashing us down. We are witnessing thousands of people across the continent rising up and speaking out, initiating boycotts and stickering campaigns, all with a newfound gusto that is rare in the activist world. "Worldchangers" cherish these moments when momentum seems to be on our side.

But I want to ask all of you to conserve your energy.

This will be a long battle. Too many activists burn out because they put all their soul into something and aren't given back results that reward them for their commitment and passion.

We cannot afford to burn out. It is the long haul that matters.

If we can organize people and send ten thousand letters to Nestle or Coca-Cola today, it is less effective than sending those same ten thousand letters spread out over a couple months. If the rate steadily increases over that time, it is especially worrying for the companies. Consider the graph below, with two lines depicting the number of letters received about GMOs over a given period of time. If you were a CEO of Coca-Cola, which trend, A or B, would you be more concerned about?


So... not only is it in the interest of our health and sanity to slow down a little bit, it is likely to benefit our cause as well.

Besides, there are only so many people we can persuade with the frantic, frenetic energy that many of us now feel. But there are many more that we will turn off.

Let's all slow down and breathe here. We have to steer this momentum in a useful direction and not have it burn up like newspaper in a campfire.

As we spread information about genetic engineering through our various forms of social media or through conversations with those around us, we must constantly work at refining what we say and how we say it.

Activists are among the least effective educators. But we really only do our cause a disservice if we do not discriminate between what is educational and what is not.

Here are some criteria to consider:

1. Is your information scientific?

The biotech industry is continuously accusing us of being unscientific. We should learn from this that appearing scientific is important. Is the claim we are making supported by a reliable scientific source? Is the article peer-reviewed or does it authentically state the position of some peer-reviewed article or scientist? Can we openly acknowledge the possible weaknesses of a study so that we can say things like: "While it is true that the sample size of this study was small, it nevertheless indicates the need for precaution and further research because the biotech industry sometimes even uses small sample sizes." Here is an example of a scientifically reliable article and here is one that is surely not. Let's all enrich our understanding of genetics and why exactly there are so many risks to this technology!

2. Are you being preachy?

Why is it that Jehovah Witnesses turn so many of us off? Why is it that Angry Vegans often make meat eaters want to go and eat more meat? It is not because of what they are saying. It is how they are saying it. Are you speaking in a way that will make the average consumer feel like you think you are better than them? When people approach us as if they know everything and as if their life mission is to "save" or "wake up" the masses, they flip a switch in our brains from "receptive and listening" to "ok, I gotta get outta here. This person is too much". People are most open to learning from those who are open to learning from them. Reciprocity builds relationships, trust, and a motivation for both people to develop and grow.

3. Do You Know that Less is Sometimes More?


Too much information shuts people off. It is better to have a few, well-considered and well-delivered sources of information than a deluge of mediocre ones, interspersed with the occasional excellent one. The slurry of average-quality messages will camouflage the great ones. People like diversity. People like new stimulation. People do not like opening their Facebook feeds and seeing 20-30 posts monotonously re-informing them that "GMOs are bad" or are "destroying the world". They already get too much junk, most of which they just pass over. We should strive for optimal quantity not maximum quantity. And if, one day, we feel ourselves just a bit too fired up about our friend chomping down on a GMO cheeseburger? We need to take a moment, stop, and reflect: am I calm enough? Or will my comments deter him from listening to me ever again about this issue? If the latter, then maybe it is better to just keep silent right now.

4. Can you make your Message Pleasing?

Mass advertising works for products that people want to buy. It creates thirst and desire. But what we are selling does not often come across as pleasant or good or desirable. It sucks, but the truth isn't always nice.

There is some basic psychology here and you can bet the marketing firms hired by Monsanto know all about it: drinking a can of Coke makes people feel good. But being told that the Coke they've been drinking for 20 years is killing them (and the planet) makes people feel bad. Humans are simple creatures, attracted to what makes them feel good. They will generally prefer the quality of an immediate pleasure to the promise of a long term one. In fact, studies show that people will actually flock to their temptations precisely when they feel most badly about themselves. Our negative messaging may steer people straight towards their vices and dependencies... No wonder so much activism doesn't work!

A GMO-free world has a lot a beauty, health and magic and we need to show people that taking part in imagining such a world is itself more satisfying than munching Lays' GMO potato chips. It is more satisfying, isn't it? Well, how do we show that without force-feeding it?

In conclusion, I suggest that all of us make a lunch date with a teacher we know so we can ask them about teaching strategies and approaches that work in the class. Good teachers have care and tact and subtlety (in their better moments!) that will be of tremendous value for us in our struggle to improve ourselves and become better activists. To the chalkboards!

Monday, November 12, 2012

Contact Information for the Biotech and Food Companies opposing Labeling of GMOs

I have compiled the contact information for the major biotech companies, organizations, and food companies that launched the $45 million campaign to defeat mandatory labeling of genetically engineered organisms in food.

I urge you to write a brief letter and send it to each of these companies. You can copy and paste the same text if you like. It should take less than an hour to run through this list!
Here are some pointers for writing an effective letter:

1. Be polite (they are less likely to think you are a fanatic and more receptive to your message). It is ESPECIALLY important to be polite when writing messages on different companies' Facebook Pages. Faithful customers will be reading your comments and will not be receptive to insults and polarizing language. If your message is furious and violent, the company may also alert Facebook that you are spamming their page and Facebook may revoke your posting rights. Be nice.

2. Let them know how disappointed you are that they do not support our right to know what is in our food (i.e. Proposition 37).

3. Explain that although you love their products (if you do), you will not be purchasing them anymore.

4. Explain that you will also be talking to your investor/bank because you do not want any of your investments supporting the company.

5. Explain that you will be communicating your reasons for boycotting the company to all of your friends.

6. Ask them to change their policy and support the mandatory labeling of genetically engineered organisms, and that you will reconsider your boycott if they make such changes.

Send this page as a link to everyone who you think might be concerned about GMOs!

NOTE: Alliance for Natural Health has just produced this great page where we can send a letter to all of the companies at once! It is very important to sign on to this and spread it widely. But form letters are really NOT substitutes for individual letters. Do both!

Organic Consumer's Association now has a webpage with the call lines of these companies too, if you'd rather give them a ring!




Biotech Company Contacts:

Monsanto
Dupont
Dow Chemical
BASF
Syngenta
Bayer
Council of Biotechnology Information
Biotechnology Industry Organization


Food Company Contacts:

Pepsico
Pepsi's Facebook Page

Grocery Manufacturers Association

Kraft Foods
Kraft Foods Facebook Page

Coca-Cola
Coke's Facebook Page

Nestle USA
Nestle's Facebook Page

Conagra Foods
ConAgra's Facebook Page

General Mills
General Mills' Facebook Page

Kellogg Company
Frosted Flakes Facebook Page

Smithfield Foods
Smithfield Foods Facebook Page

Del Monte Foods
Del Monte Facebook Page

Campbell's Soup
Campbell's Soup Facebook Page

Heinz Foods
Heinz Facebook Page

Hershey Company
Hershey's Facebook Page

The J.M. Smucker Company
Smucker's Facebook Page

Bimbo Bakeries

Ocean Spray Cranberries
Ocean Spray Facebook Page

Mars Food North America
Mars Facebook Page

Hormel Foods

Unilever
Unilever Facebook Page

Bumble Bee Foods
Bumble Bee Foods Facebook Page

Pinnacle Foods

Dean Foods Company

Bunge North America

McCormick & Company
McCormick Facebook Page

Wrigley Jr. Company
Wrigley's Extra Facebook Page

Abbott Nutrition

Cargill, Inc
Cargill Facebook Page

Rich Products Corporation
Flowers Foods
Dole Packaged Foods
Knouse Foods Cooperative

OK. So those are the bad guys. Now we don't want to just be negative activists and criticism should only ever be a portion of our important work. We must also take time to thank, congratulate, and admire those striving to move humanity towards a sustainable future. There are companies and organizations who have contributed lots of money to support labeling of GMOs. They need to know how much we appreciate them!

Contact these proactive companies too!

Major Companies supporting labeling of GMOs:

Mercola
Nature's Path
Dr. Bronner's
Lundberg Farms
Amy's Kitchen
Clif Bar
Organic Valley
Annie's
Nutiva
Eden Foods


There were many more companies that just these supporting our efforts, and many organizations and citizen groups as well! They all deserve our recognition and support. For a full list of labeling endorsers, visit this link!

New: Organic Consumer's Association now has a form letter to thank all of the supporters. You can reach it here.

Other posts related to taking action against the biotech bullies: 10 Easy Ways, The Next Step after Prop 37, Cyberactivism