Archive for April 2015
By: Kimberly Leblanc, PhD
Last month, the Food and Drug Administration (FDA) issued a press release announcing the approval of genetically engineered (GE) apples that have reduced browning and potatoes that exhibit reduced black spots and bruising. There are more of these compositionally changed GE foods awaiting FDA approval — among many others, a pink pineapple that includes lycopene, and a tomato that has high levels of anthocyanins, which could lower the risk of cardiovascular disease and cancer. With the increasing prevalence of GE foods, public concern has risen. An Associated Press-GfK poll last December found that 66 percent of Americans want genetically engineered foods to be labeled. Furthermore, a poll from the New Pew Research Center revealed that only 37% of U.S. adults believing that GE foods are generally safe to eat. The question is, are these concerns warranted? In the same Pew poll, 88% of scientists reported that they believe it is safe to eat GE foods. This is greater than the percentage of scientists who believe that climate change is mostly due to human activity (87%) or that the growing world population will be a major problem (82%). This gap between scientists and the public on the issue of GE foods is the largest gap of all issues studied, greater than the difference for climate change, human evolution, or the use of animals in research. What’s the reason for this dramatic difference? One possibility is that 67% of U.S. adults felt that scientists do not have a clear understanding about the health effects of GE foods. But is the science really still out on the issue?
The recombinant DNA techniques used in genetic engineering involve the modification of a single or a select number of genes, allowing the transfer of desirable traits to occur more rapidly, predictably, and precisely than when using traditional agricultural methods, such as selective breeding. The FDA regulates the safety of foods and food products from all plant sources including GE plants, and GE foods must meet the same safety requirements as foods from traditionally bred plants. The FDA addresses nutritional composition to ensure that the nutrition in GE crops is substantially equivalent to the non-GE crop. This means that there are no significant differences in the levels of nutrients (including fiber, protein, fat, vitamins, and minerals), toxic components, or chemical composition in the new GE plant compared to the range of values found in traditionally bred plants. In addition to this regulatory oversight, studies so far have supported the substantial equivalence of GE foods.1,2 The FDA also assesses the potential toxic or allergenic properties of GE crops, and so far any crops that have been shown to be potentially allergenic have halted development before the crops have made it to market,3,4 or been pulled from the market (in the case of Starlink corn) even though there was no evidence that it caused an allergic reaction. So far, the scientific evidence has largely shown that GE foods are safe to consume. In a review of 1,783 studies on the safety and environmental impacts of GE foods, the researchers concluded that “the scientific research conducted so far has not detected any significant hazards directly connected with the use of GE crops”. This is all the more impressive since the authors of the above mentioned review are from Italy and European Union may have the most stringent GMO regulations in the world. However, even a report from the European commission looking at ten years (2001 – 2010) of GMO research concluded that GE foods are safe. Currently there is overwhelming scientific evidence that GE foods are safe to consume, at least in the sense that they are no more dangerous, toxic, or allergenic than non-GE foods, and they have substantial equivalence in terms of nutrition and chemical composition.
There is also considerable concern over possible indirect health impacts of GE foods through increased exposure to pesticides and herbicide. So, do GE crops increase our exposure to harmful pesticides? Insect resistant crops, produced through the expression of Bacillus thuringiensis (Bt) genes, reduced exposure to pesticides in the first ten or so years. Between 1996 and 2011, Bt crops have reduced insecticide applications by 56 million kilograms (123 million pounds). Insecticide use has also declined for both Bt crop growers and non-Bt crop growers, with essentially no difference in pesticide use between Bt corn adopters and non-adopters as of 2010. However, this is likely due to area-wide suppression of certain insects through the adoption of Bt crops, as has been shown in multiple studies. If anything, GE crops have had a positive impact on reducing the amount of pesticides used.
Herbicide usage is more controversial. Although there were initial decreases in herbicide usage in herbicide-tolerant (HT) crops, herbicide resistance among weed populations may have induced farmers to raise application rates in recent years according to the USDA. One study found that herbicide-resistant crop technology has led to a 239 million kilogram (527 million pound) increase in herbicide use since 1996. This increase is largely due to an increase in the use of glyphosphate, the active ingredient in Roundup®, which is classified as a non-toxic herbicide. The National Research Council and the World Health Organization point out that this may be beneficial because glyphosphate is less toxic and less persistent than traditional herbicides like atrazine. While the International Agency for Research on Cancer proposes that glyphosphate increases the risk of cancer, the Seralini et al. (2012) study that claimed that GE corn could induce tumors in rats has largely been discredited by the European Food Safety Authority. A meta-analysis of human and non-human animal research found no significant effects of glyphosphate on neurotoxicity, immunological diseases, or endocrine disruption, and numerous safety evaluations have concluded that glyphosphate does not pose a health risk to humans. However, the USDA warns that herbicide toxicity may be on the rise (compared to glyphosate) by the introduction of crops tolerant to the herbicides dicamba and 2,4-D.
All of this discussion about GMOs leads to the question: should GE foods be labelled? Or more specifically, should the federal or state governments make laws concerning the labeling of GE foods? Rep. Mike Pompeo (R-Kan.) along with co-sponsor Rep. G.K. Butterfield (D-N.C.) recently introduced the Safe and Accurate Food Labeling Act of 2015 (H.R. 1599), which would create a voluntary federal labeling standard while pre-empting states from passing their own mandatory labeling laws for GE foods. In February, the Genetically Engineered Food Right-to-Know Act was introduced in the House (H.R. 913) by Rep. Peter DeFazio (D-Ore.) and in the Senate (S. 511) by Sen. Barbara Boxer (D-Calif.). Their bill would require labels for all foods produced using genetically engineered ingredients and would prohibit manufacturers from labeling genetically modified foods as “natural.” The FDA has issued draft guidance on voluntary labeling. Essentially, unless there is a “material” fact that is different about GE foods – information that is material in light of statements made or suggested on the label, or material with respect to consequences that may result from the use of the food – the producers don’t need to label it. The American Association for the Advancement of Science (AAAS) has stated that mandatory labeling “can only serve to mislead and falsely alarm consumers”, and the American Medical Association has declared that voluntary labeling is misleading unless accompanied by focused consumer education. It is important to note that environmental and social factors also matter to consumer’s decisions, and so these issues must also be considered when debating labeling.
The basis of the question may come down to whether or not citizens have a right to information on what they consume, even if that information might lead to decisions that are not based on scientific evidence.
- Batista, R., & Oliveira, M. M. (2009). Facts and fiction of genetically engineered food. Trends in Biotechnology, 27(5), 277-286.
- Kuiper HA, Kleter GA, Noteborn HP, Kok EJ (December 2002). “Substantial equivalence–an appropriate paradigm for the safety assessment of genetically modified foods?”. Toxicology. 181-182: 427–31. doi:10.1016/S0300-483X(02)00488-2. PMID 12505347
- Lehrer SB, Bannon GA (May 2005). “Risks of allergic reactions to biotech proteins in foods: perception and reality”. Allergy 60 (5): 559–64. doi:10.1111/j.1398-9995.2005.00704.x. PMID 15813800.
- Key S, Ma JK, Drake PM (June 2008). “Genetically modified plants and human health”. J R Soc Med 101 (6): 290–8. doi:10.1258/jrsm.2008.070372. PMC 2408621. PMID 18515776
By: Thomas Calder, Ph.D.
A new genetic engineering technology, known as CRISPR-Cas9, is allowing scientists to edit the human genome faster and easier than ever thought possible. This technology has the potential to treat and even cure several major diseases such as sickle-cell anemia, HIV, and many forms of cancer. As a result, many labs around the world are rushing to better understand the CRISPR-Cas9 system so they can eventually advance the technology into the clinic. However, such unparalleled potential comes with a risk. CRISPR-Cas9 could be used to alter the genetic code of germline cells, which are reproductive cells that could then pass these alterations onto further generations. This has scientists and the public asking the controversial question: is editing the human germline ethical?
This controversy is not new, as genetic engineering technologies have been around since the 1980’s. Zinc-finger nucleases (ZFNs) were discovered in the 1980’s and were determined to have genome-editing capabilities during 1996-2003. ZFNs are DNA cutting enzymes that can be engineered to target specific segments of DNA, and can thus alter sections of the human genome. Designing ZFNs proved to be difficult, so many scientists were excited when different genome-editing enzymes, TAL effector nucleases (TALENs), were found in 2009-2010 to be easier to engineer than ZFNs. Both ZFNs and TALENs have the same shortcoming though. They require scientists to design proteins specifically for a targeted segment of DNA, which then requires validation of each newly designed protein. Thus, these technologies are highly impractical for editing the genome on a large-scale.
The CRISPR-Cas9 system was first discovered in 1987 by a Japanese lab, but it was not well understood until recent years. Scientists determined in 2005-2007 that bacteria harbor this DNA editing system to digest foreign viral DNA. In 2011-2012, scientists began to understand the basic essentials of this system so they could utilize it for genetic engineering. They discovered that Cas9 is a DNA cutting enzyme that can be targeted to specific DNA fragments with the help of a specially designed guide-RNA molecule. This system proved to be much easier to use that ZFNs and TALENs, because scientists did not have to design different enzymes for each targeted DNA fragment. Instead, they only had to engineer RNA molecules to match with targeted DNA fragments. With this approach, CRISPR-Cas9 can be used to target and alter any gene based on its genetic code, and it can even be used for genome-wide studies.
With the recent characterization of CRISPR-Cas9, a new frontier in science has begun. Scientists have designed guide-RNA molecules for every gene in the genome to determine which genes are essential for various diseases, such as many forms of cancer. This approach is exciting because it may lead to the discovery of new targets for drug-based therapy. Scientists are also creating animal models of various genetic diseases by causing disease-specific alterations in the genome of animals such as mice and monkeys. For humans, this research has focused on non-reproductive cells, but the efficacy of this technology is making the human germline a tempting target. Theoretically, scientists could use CRISPR-Cas9 in an embryo to remove a disease-causing gene and replace it with a healthy version of the gene. This approach has the potential to ward off deadly diseases—but is it ethical? Most importantly, is it safe?
Both questions are controversial. In terms of safety, many scientists currently agree that it is not safe to create a permanent genetic alteration that can be passed onto future children. One concern is that Cas9 could have off-target effects that could damage the human genome in unpredictable ways. Another concern is that scientists do not understand the genome well enough to start making changes to the code. According to a Perspective article in the journal Science, by scientists that attended an ethics discussion in January on the topic of editing the human germline, “there are limits to our knowledge of human genetics, gene-environment interactions, and the pathways of diseases (including the interplay between one disease and other conditions or diseases in the same patient).” Also, side-effects from altering the genetic code of an embryo might not be noticeable until that embryo turns into a grown child, many years into the future. Therefore, more information on the human genome is necessary before genetic engineering of the human germline can be considered safe.
These safety concerns factor into the ethics debate, but other concerns are also drawing attention. While CRISPR-Cas9 is currently being proposed to prevent debilitating diseases, the use of this technology might start a slippery slope that could lead to the creation of “designer-babies.” For example, the genome of an embryo could be altered to impart a different eye color, hair color, or higher level of intelligence. These changes are certainly not worth the risk of side-effects, but some parents might pursue these options to provide their child with a “leg up”. Other ethical questions include:
- Would the use of this technology be regulated?
- Would a child be monitored if he/she was genetically modified as an embryo? Would the child’s future offspring be monitored?
- Which parts of society would have access to this technology? Would use of this technology lead to a greater divide between the poor and wealthy?
The CRISPR-Cas9 technology is advancing quickly, so scientists need to act now to reach a consensus on these ethical issues. Many scientists have already called for a moratorium on editing the human germline in the short-term. This would provide time for scientists to engage with the bioethics community and the public to discuss the ethical, social, and legal implications of altering the human genome.
The genetic engineering capabilities of CRISPR-Cas9 is exciting. Millions of lives could benefit from this new technology. It could cure certain cancers, prevent diabetes, ward of many age-related diseases, and even stop HIV from causing AIDS. But scientists must use extra caution when editing the human germline, because any negative effects that arise could last for many generations into the future.
- Germline editing: time for discussion, Nature Medicine
- Don’t edit the human germ line, Nature Comment
- A prudent path forward for genomic engineering and germline gene modification, Science Comment
- The new frontier of genome engineering with CRISPR-Cas9, Science Review
- Ethics of embryo editing divides scientists, Nature News
- Scientists Seek Ban on Method of Editing the Human Genome, New York Times