Unintended Effects of Genetic Manipulation
A Project of The Nature InstituteProject Director: Craig Holdrege
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Over the next five to ten years, a profusion of new genetically engineered products is likely to emerge, including an increasing number featuring such complex interactions and novel traits that U.S. regulatory agencies may be overwhelmed, in terms of trying to provide timely product review and to protect human health and the larger environment from unintended effects. So suggests a major recent report by a committee of the prestigious U.S. National Academies of Sciences, Engineering, and Medicine.
The March 2017 report, “Preparing for Future Products of Biotechnology,” concludes that the federal agencies that either fund research on biotechnology or that regulate biotechnology products should increase their spending and their focus on advancing the science that regulators need to be able to adequately conduct ecological and other risk analyses before new kinds of such products are approved for release.
Researchers have detected unintended differences in protein expression and in the expression of important plant hormones between genetically modified (GM) maize and non-GM maize, and the pattern of differences varied for normal versus drought conditions. They cite their results in calling for detailed molecular analyses to be added to risk analyses of genetically engineered plants. Risk analyses, they added, should also include studies to identify and compare the particular molecular responses of GM and non-GM varieties to environmental stressors, such as drought. Such studies should also profile the way plants engineered to tolerate an herbicide respond at the molecular level when they are actually exposed to the herbicide under stressed versus normal conditions.
An interesting new paper entitled “The Semiosis of ‘Side Effects’ in Genetic Interventions” was published by a University of Edinburgh scholar in October 2016 in the peer-reviewed journal, Biosemiotics. The author points out that genetic engineers tend to discount the likelihood and importance of unintended effects of their work, or else assume they can manage them. Critics of genetic engineering, on the other hand, often warn that unintended and unpredictable “side effects” from modifying an organism’s genome in the lab could be disruptive. He goes on to say that on both sides of the discussion it is easy to forget that effects not intended by engineers may, at least in part, be “intended” by the organism as it reorganizes itself to accommodate or make use of the new conditions imposed upon it. In other words, we humans are not the only “generators of meaning” at work when we try to genetically manipulate organisms. (As an editorial aside: we might, in fact, reasonably think that this largely accounts for the frequent unexpected results.) And acknowledging that organisms actively respond to novelties has important implications for human relations with other species. Our current naïve understanding of the nature and consequences of genetic interventions suggests the need for both humility and caution.
Download the open-access paper, from the journal Biosemiotics, here.
As soybean farmers in the U.S. between 1998 to 2011 planted ever more land in seeds genetically modified to resist glyphosate (the active ingredient in Monsanto’s Roundup herbicide), their total use of herbicides rose, consistent with growing weed resistance to glyphosate, according to a major new study. In fact, their use of pesticides was higher by 28 percent per hectare of land, averaged over that entire period, than for farmers growing non-GMO soybeans.
The goal of new gene-drive technology – to rapidly “drive” engineered genetic sequences into as much of the population of a species as possible – “makes it especially important to minimize the potential for unintended consequences,” and too little is now known about how to do that to support open environmental releases of gene-drive modified organisms, concludes a major new review of the technology.
It observes that researchers are developing the technology at a “breathtaking” pace and adds: “The considerable gaps in knowledge about potential off-target (within the organism) and non-target (in other species or the environment) effects necessitate a collaborative, multidisciplinary approach to research, ecological risk assessment, development of public policy, and decision making for each proposed application of a gene drive technology.” The report, Gene Drives on the Horizon: Advancing Science, Navigating Uncertainty, and Aligning Research with Public Values, was produced by a committee of the prestigious U.S. National Academies of Sciences, Engineering, and Medicine.
A major new review of the research on genetically engineered crops concludes that there is no significant evidence that genetic engineering technology by itself has increased the rate of yields for the three most frequently planted genetically engineered crops in the U.S. – maize, soybeans, and cotton. Such yields have been increasing, but it’s not possible to determine how much the increases could be due to GE technology, versus other factors, despite the authors’ effort to tease out such a positive effect. The report, “Genetically Engineered Crops: Experiences and Prospects,” was produced by a committee of the prestigious U.S. National Academies of Sciences, Engineering, and Medicine.
The committee called for research to “isolate effects of the diverse environmental and genetic factors that contribute to yield.” It also concluded that despite similar national committees having called since 2000 for U.S. data to be collected to make it possible to trace the impact of GE crops on biodiversity and other measures of environmental sustainability, such databases remain “inadequate.” That limits “the ability to assess effects on abundance of monarchs [monarch butterflies] and many other species.” The report also examines a wide range of other questions about the effects and the future of genetically engineered crops, including pesticide resistance.
New research attempting to attack the HIV virus with the advanced new genetic engineering techniques of synthetic biology — often referred to in general as “gene editing” — indicates that such genetic manipulation can backfire. The engineered break in viral DNA can itself lead to mutations that help the virus replicate and continue to infect host immune cells. Immune cells in one recent study had been engineered to find and disable the HIV virus by making particular cuts in the viral DNA. Usually that leads to mutations that inactivate the viral gene that was cut. But for some of the mutations resulting from such cuts, that did not happen. Moreover, the engineered immune cells were no longer able to recognize these mutated versions of the virus as the target they had been engineered to disable. So the viral replication continued.
A new report by the Testbiotech Institute for Independent Impact Assessment in Biotechnology in Germany summarizes the key advanced new methods for genetically engineering plants and animals used in food production that are referred to as “synthetic biology”, and describes the companies that are now actively patenting animals or plants that have been subjected to such methods. The risks and uncertainties associated with these methods, the report cautions, require a stricter adherence to the precautionary principle than has been the practice so far. The report cites studies indicating that these “gene-editing” methods, while often described as being far more precisely directed than older methods of genetic manipulation, “can lead to a wide range of off-target effects.” It also discusses plans by some companies “to perform multiple genetic manipulations in the animals, which also would render multiple side effects and risks to animals, humans, and the environment.” The report recommends that governments not allow the patenting of synthetically engineered animals and plants used in agriculture and food production, and that such plants and animals be subject to European Union regulations for genetically modified organisms. It also calls for an international ban on genetically engineered organisms that “cannot be controlled in their spatio-temporal dimension.” Download the report here.
Farmers in India who rely on rain, not irrigation, can earn similar net revenues whether they grow a traditional Asiatic cotton species or Bt cotton, the now far more common variety of an American species that has been genetically engineered to resist certain pests, a new study suggests. Yields in the study were higher for farmers growing Bt cotton. But expenses were lower and the sales price was higher for those growing the traditional non-GMO cotton. The researchers, from the University of Oxford, were not able to compare the economic returns when each species was grown under irrigation because they could not identify a group of farmers planting the traditional species who irrigated their fields. In fact, 40 per cent of farmers in the study who did irrigate told researchers that planting the Asiatic species wasn’t an option for them because of the low availability of that seed. However, most farmers in Maharashtra, the Indian state where the study took place, do not irrigate their fields. And researchers found that whether farmers planting Bt cotton relied on rain or irrigation, there was no significant difference in their net revenues. The study focused on farmers with less than 12 acres of land. Read more.
Annual suicide rates for farmers in areas of India where cotton fields are fed by rain, not irrigation, are directly correlated with increases in the adoption of genetically engineered insecticidal Bt cotton, according to an unusually holistic new analysis by researchers in the U.S. and Italy. Read more.
The Bioscience Resource Project has released a draft report, written in 2010 but only now available, that summarizes research indicating diverse unintended effects of RNA interference (RNAi) techniques used to genetically manipulate plants. The authors conclude that “RNAi in agriculture raises a spectrum of important biosafety issues.” The report explores three mechanisms whereby RNAi could lead to toxicological and environmental hazards: potential unintended effects on the plant organism being intentionally modified, on invertebrate species that feed on such plants, and on mammals that feed on the modified crops. The possibility of the last raises especially urgent questions about how dietary exposure to transgenic plants engineered with RNAi would affect mammalian cellular functions, the authors state, but little research had been done on this issue at the time of their research. The report was written by Jonathan R. Latham and Allison K. Wilson, the scientists who co-founded the Bioscience Resource Project, which conducts and provides resources for public-interest science. Download the report here.
In a controversial experiment using so-called gene editing techniques, scientists in China manipulated abnormal human embryos that would have been discarded and were donated from fertility clinics. The aim was to insert a genetic construct to create a break in a key hemoglobin gene and then repair that break. The creation of the break succeeded in 28 of the 54 embryos tested, but only in four had the gene been repaired in the intended fashion. The intended alterations occurred in only some of the cells of the embryos, some embryos had repaired the gene without using the introduced construct, and there were unintended mutations in other genes... Read more.
A recent study concludes that there have been at least 396 incidents worldwide of GMOs contaminating food, animal feed, seed, or non-food crops. These include the contamination of non-GMO crops and fish, the contamination of wild or weedy relatives of GMO crops outside the areas where those crops were planted, and the contamination of food or feed supplies resulting from experiments with genetically modified pigs. The data cover the years 1997 – the year after large-scale commercial planting of GMO crops began – through 2013. The incidents involved a total of 63 countries, with half of the incidents being reported by 11 countries.
However, the authors of the peer-reviewed study, published by the International Journal of Food Contamination, indicate that the reports only establish a minimum for the number of incidents, since “there is no systematic global monitoring or recording of GM contamination incidents.” The study is also limited to incidents involving officially unauthorized contamination – not cases where no regulations were breached. The analysis in the study is based on an online register, maintained by one of the authors, that was begun by two non-profit groups that oppose the environmental release of GM crops and that were concerned about the lack of an official global dataset.
A recent analysis exploring that question by two organizations in India concludes the answer is no. In fact, this 2014 report by The Alliance for Sustainable & Holistic Agriculture, in collaboration with JATAN: A Mission for Organic Farming, cites both scientific and regulatory reasons why the commercial promotion of genetically modified crops threatens the further spread of organic agriculture in India. As an example of the challenge of co-existence, it points to a decline in India’s production and export of organic cotton, which it relates to the lack of availability of non-GMO cotton seeds and the negative effects on the market from incidents of organic cotton in India being contaminated with cotton that had been genetically modified to produce the Bt insecticide. Read more.
A review of studies comparing the yield of herbicide-resistant crops and their non-resistant isogenic counterparts shows that there are often few differences in yield and, if there are differences, then the herbicide-resistant varieties tend to yield less. Read more.
Researchers in Canada bred hybrids between genetically modified (GM) Atlantic salmon and its close relative, brown trout. The GM salmon contain a foreign growth hormone gene that enhances growth. Some of the hybrids carried and expressed the transgene. Along with enhanced growth, the hybrids had unintended effects in conditions that mimic natural stream conditions. The researchers write that their findings “suggest that complex competitive interactions associated with transgenesis and hybridization could have substantial ecological consequences for wild Atlantic salmon.” Read more.
A Russian nonprofit organization recently announced that it will carry out a $25 million study to examine the health effects on rats fed genetically modified (GM) herbicide-resistant maize (corn) and the herbicide glyphosate, with which it is sprayed. The study will follow a “protocol whose scale, rigour and range of measurements will meet and exceed current international standards for testing the toxicity of GM foods, pesticides, and other chemicals,” the organization states. Read more.
A new form of genetic engineering is being developed in which genetically modified plants make a special kind of RNA that, when taken up by insect pests, can induce harmful effects through silencing genes in the insect. Two USDA scientists have written a review article discussing the manifold potential unintended effects of this technology, especially in connection with harming nontarget insects. Read more.
Adverse Impacts of Transgenic Crops/Food is a compilation of over 400 abstracts from scientific articles that discuss adverse effects of genetically modified crops and food. It is available online. The report was produced by the Coalition for a GM-free India. The abstracts are ordered in different categories and subcategories:
- Imprecision and unpredictability of genetic engineering as a technology
- Health impacts (Bt toxin, glyphosate, nutritional composition, etc.)
- Environmental impacts (“super weeds,” pest dynamics, biodiversity, soil, etc.)
- Horizontal gene transfer
- Gene flow and contamination
The compilation is valuable for anyone who would like to study scientific literature on unintended effects. It points to the wide spectrum of effects that we also deal with in our reports.
Synthetic Biology is an effort to change and improve living beings — microorganisms, plants, animals, and eventually human beings — following engineering principles. The strategy is to take machines and devices as the model for organisms and to modify organisms accordingly. Synthetic biologists aim to make their discipline less haphazard than conventional genetic engineering and to elicit more controlled changes in organisms. This article by Craig Holdrege provides an introduction to the topic of synthetic biology and places it into the context of contemporary findings about the non-mechanistic nature of life. He questions the wisdom of an approach that manipulates life based on an inadequate understanding of life itself. Read more.
A long-term study claiming to show toxic effects on rats of the herbicide Roundup and genetically modified (GM) Roundup-tolerant maize (corn) was originally published in 2012. It elicited significant controversy. The journal retracted the article but the authors stood by their findings. In 2014, this study was republished. Read more.
Chinese scientists from the National Key Laboratory of Crop Genetic Improvement at the Huazhong Agricultural University in China have reviewed the performance of different crops that have been genetically modified to produce an insecticidal protein (“Bt” crops). The authors are clearly proponents of genetic engineering, but their review shows how context-dependent and unpredictable the performance of Bt crops is. Read more.
Genetically modified (GM) crops sometimes have higher yields than their non-GM counterparts and sometimes similar or lower yields. Here Chinese researchers report on significant differences in yields in two different insect-resistant Bt rice varieties and their non-GM counterpart. Read more.
There is a major concern that if genetically modified crops pollinate closely related weeds, the crop/weed hybrids will survive and spread in the larger environment. Researchers in China have found that insect-resistant rice/weedy rice hybrids, under conditions of normal pest pressure, show (as intended) less insect damage, but, unexpectedly, produce more seeds than both nontransgenic rice and weedy rice controls. Read more.
The GMO Deception: What You Need to Know about the Food, Corporations, and Government Agencies Putting Our Families and Our Environment at Risk. This new book, edited by Sheldon Krimsky of Tufts University and Jeremy Gruber of the Council for Responsible Genetics, provides a major new resource for individuals and organizations interested in broadly exploring the implications of the commercial rush to genetically manipulate food. The book’s scope includes impacts on the quality, safety, and fair distribution of food; the welfare of farmers; the humane treatment of animals, and sustainable agriculture. Read more.
The paradigmatic idea behind genetic modification is that genes control the formation of an organism’s characteristics, so that by introducing new genes you can alter the organism and it takes on new characteristics. In the 1980s, when genetic modification of organisms was beginning, there were great hopes that GM bacteria—“superbugs”—could be used to break down an array of pollutants in the environment. Many such GM bacteria have been developed in the laboratory, but with few exceptions, the real world applications have not materialized. Why not? Read more.
A recent report funded by the U.S. National Science Foundation highlights the need for a major, coordinated new effort to research the ecological impacts of organisms developed through the extreme form of genetic engineering known as synthetic biology. Read more.
Anyone interested in the assessment of technological solutions to complex problems, as well as the unintended consequences of those solutions, should look at the European Environment Agency’s report, “Late Lessons from Early Warnings: Science, Precaution, Innovation.” You can also read our brief comments on the report.
Researchers investigated whether introducing a gene from soybeans related to the formation of ferritin (a protein that stores and makes iron available) into corn (maize) would in any way alter the formation of other substances in corn. They discovered significant unexpected changes. Read more.
The question of whether genetically modified (GM) crops and food are safe is highly contested. How the research is carried out, what researchers find, and how they interpret their results are influenced by a variety of interests. As a result, each experiment and each assessment has a larger-than-science context that is important to recognize, especially when dealing with the controversial field of research that evaluates GM crop safety. Read more.
The Ministry of Health in Córdoba province, Argentina, released a report, based on data gathered over a five-year period, that found the highest death rates from cancer in areas where genetically modified crops are grown and agro-chemicals are used. Read more.
In a thorough review article, scientists describe the increase in the number of insect species that are becoming resistant to genetically modified, insecticide-producing Bt crops designed to kill those insects. Over a billion agricultural acres have been planted with Bt crops, mainly corn and cotton, since 1996. Ecologists knew that at some point the insects would evolve resistance and no longer be killed by these insecticidal plants. Now it’s happening. Read more.
Researchers in Sweden found that genetically modified Bt aspens producing an insecticide, were — as expected — by and large better protected against damage by certain insects than unmodified aspens. This protection did not mean, however, that the trees were more productive, which is the overall goal of such genetic manipulation. Also, and unexpectedly, the Bt trees were not protected against one target pest species. Read more.
In a field experiment, leaf litter from aspen trees that were genetically modified to produce a toxin to kill insects and leaf litter from unmodified trees were exposed to aquatic insects. Surprisingly, the researchers found an increase in the abundance of aquatic insects in the genetically modified leaf litter. Read more.
Aspen trees that were genetically modified to produce a toxin to kill insects had a different composition of leaf chemicals and the leaves — when old — were more likely to be eaten by slugs than were leaves of non-GM trees. Read more.
While wheat plants usually self-fertilize, they do occasionally cross-pollinate with other wheat plants (“outcrossing”). Researchers in Europe found that GM fungal resistant wheat plants were more likely to outcross with other wheat plants than were non-GM plants of the same variety. The unexpected higher rate of outcrossing by the GM lines increases concern about the likelihood of GM wheat hybridizing with non-GM wheat should the seed supply be contaminated with even small amounts of GM seed. Read more.
While there have been no epidemiological studies assessing whether it is safe for human beings to eat genetically modified (GM) foods, there have been many studies with animals. Some show negative side effects, others don’t. Despite this fact, one often hears that there is scientific consensus that GM food is safe for human consumption. The European Network of Scientists for Social and Environmental Responsibility (ENSSER) published a statement that takes issue with this claim and cites many studies that indicate how little consensus there is within the scientific community about the potential effects of GM food on human health. Read the statement.
An article with this title appeared in the journal Food Chemistry. The researchers investigated soybean batches from three different categories of soybeans: genetically modified (GM) soybeans that are resistant to the herbicide glyphosate; conventional, non-GM soybeans; and organically grown soybeans. They found differences in the nutritional composition profiles. Also, and perhaps most strikingly, the GM soybeans, in contrast to the two other types, contained high residues of glyphosate and its breakdown product AMPA. Read more.
Farmers in Iowa have reported since 2009 that the western corn rootworm, a significant corn pest, has been severely injuring Bt corn. Bt corn has been genetically modified to prevent this insect and other insects from feeding on the crop. But this “solution” to eradicating pests is showing its Achilles heel. Read more.
An article by scientists Jonathan Latham and Allison Wilson describes the discovery by the European Food Safety Authority that a key regulatory sequence in the DNA of many commercial genetically modified crops contains a “significant fragment of a viral gene”. They state: “This finding has serious ramifications for crop biotechnology and its regulation, but possibly even greater ones for consumers and farmers. This is because there are clear indications that this viral gene (called Gene VI) might not be safe for human consumption. It also may disturb the normal functioning of crops, including their natural pests”.
A survey during 2013 by the Food and Agriculture Organization (FAO) of the United Nations revealed a growing problem: countries that import food and feed have been increasingly finding shipments contaminated with small amounts of genetically modified (GM) crops and feed.
Monarch butterflies migrate to Mexico and overwinter there. In recent years their numbers have dropped significantly. One of the reasons, which you can read about in this article, is the widespread spraying of the herbicide glyphosate on genetically modified crops in the Midwestern U.S. This poison kills milkweeds, the main food plant of Monarch butterfly larvae.
Use of the herbicide glyphosate has risen dramatically since the advent of genetically modified crops in 1996. Now many weeds have become resistant to the herbicide and don't die when sprayed. As one expert has remarked, “U.S. farmers are heading for a crisis.”
Cross-breeding of glyphosate-resistant rice with a weedy subspecies of cultivated rice — something that easily occurs naturally — produces offspring that are more fecund than either the commercial species or the weedy subspecies. So farmers growing glyphosate-resistant rice “may unwittingly be helping weedy rice to spread rather than eradicating it”.
USDA Animal and Plant Health Inspection Service, May 29, 2013
Having engineered cows to produce milk without β-lactoglobulin (suspected of being an allergen affecting lactose-intolerant persons), researchers discovered large shifts in the relative amounts of other proteins. They also found themselves looking at cows without tails.
A study shows that genetic material in the food we eat can contribute directly to regulate genetic processes in our own bodies.
Rick Callahan, December 30, 2011
Assessing Developmental Dynamics and Leaf Morphology
by Ruth Richter, Jos van Damme and Johannes Wirz, 2011
The authors profiled the proteome and metabolome of potatoes containing transgenes (from mistletoe and yeast) intended for resistance to late blight (Phytophthora infestans). The genetically modified plants exhibited deviations in developmental dynamics and plant senescence. Changes in plant and tuber shape, leaf metamorphosis, and leaf architecture are reported.
A short piece on the recent ruling and implications of the Court of Justice of the European Union case involving contaminated honey with genetically modified pollen.
Genes to produce an insect-control agent have been altered and engineered directly into crops and approved for general use. But now the inevitable is happening: the destructive pests are becoming resistant.
Andrew Pollack, October 30, 2011, The New York Times
by Mark Q. Benedict and Helen Wallace, October 2011
Two scientists explore the controversies over releasing genetically modified mosquitoes into the wild
by Jennifer L. Tank, Emma J. Rosi-Marshall, Todd V. Royer et al., August 2010
by A. Lang and M. Otto, March 2010
One of the major applications of transgenic crops in agriculture are the so-called Bacillus thuringiensis Berliner (Bt) plants, in particular Bt maizes, which produce insecticidal Cry proteins that target specific orders, such as the Lepidoptera or Coleoptera. We reviewed publications that reported on the direct toxic effects of Bt-maize and/or Cry proteins of current Bt-maize events on larvae of non-target butterflies and moths (Lepidoptera). In total, 20 peer-reviewed publications were identified, of which 16 papers contributed laboratory-based data and seven field-based data. An adverse effect on caterpillars was recorded in 52% of all laboratory-based and in 21% of all field-based observations
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