by Matthew Niederhuber
figures by Kaitlyn Choi
Summary: Bacillus thuringiensis (Bt) is a common bacteria that has played a very uncommon role in agriculture and the development of genetically modified foods. The natural insecticidal abilities of these bacteria have made them an important pest control tool for nearly a century. While their use as a natural biopesticide is widely accepted and approved for organic applications, the engineering of Bt genes into major crops has been more controversial.
Protecting our food from pests has been an ongoing battle ever since humans began cultivating food. The U.S. Food and Agriculture Organization estimates that some 20-40% of global crop totals are lost annually due to disease and pests, and the Environmental Protection Agency estimates that around 5 billion pounds of pesticides are used globally each year, costing more than 35 billion dollars [1-2].
However, with the advent of genetic engineering, new highly targeted strategies for pest control have become available in the form of transgenic plants that are designed to have insecticidal traits. Specifically, these bug-fighting plants were developed by moving some of the genes from the bacterium Bacillus thuringiensis (Bt) into corn and cotton. So called Bt crops are highly effective at combating pests such as European corn borer, rootworm, corn earworm, tobacco budworm, and bollworm [3-4].
Since the 1990s, corn and cotton with Bt genes have become the predominant varieties planted in North America . Yet despite their long-term usage and widespread presence in the U.S. food supply, there continues to be heated debate and rampant consumer misinformation about the safety of Bt and other genetically modified (GM) crops.
So what exactly do we know about the safety of Bt crops?
A bit of history
Bacillus thuringiensis (Bt) is a very common bacterium found in a variety of distinct environments, from soil, to dessert, to tundra. It was first isolated in 1901 by Japanese biologist Ishiwata Shigetane as he studied the causes of a disease afflicting silkworms. Then in 1911, the German scientist Ernst Berliner re-isolated Bt from flour moth caterpillars that had been collected from Thuringia, Germany (hence the species name). Soon Berliner determined that the Bt bacterium was specifically toxic to certain insect larva and not others. However, it wasn’t until 1928 that anyone attempted to harness Bt as a tool for pest control .
Figure 1. Bacillus thuringiensis has been used to control pests for almost a century, with its first agricultural application dating back to 1928 and first commercialization a decade later.
In this first instance, the bacteria were used to fend off European corn borer (Ostrinia nubilalis), which historically has been a common and very damaging corn pest. This initiated the development of the first commercial Bt based biopesticide, Sporine, which was introduced in 1938 in France . Since then, Bt-based biopesticides have been a significant pest control strategy, and are actually a common pest control strategy in organic agriculture. By the 1990s, tens of thousands of Bt strains had been isolated, with toxicity to a broad range of insect species .
Still, it was a game changer when the first GM corn engineered with genes from Bt became available in 1995. Since then, crops with Bt genes have come to dominate the majority of varieties planted in the U.S., representing 81% of total corn and 84% of total cotton acreage .
The mechanism of Bt toxicity
After Bt was first discovered, the mechanism of its toxicity still remained a mystery for many years. But in the 1950s, scientists discovered that the crystalline proteins that formed in Bt spores, previously observed by Berliner, were responsible for Bt toxicity . These crystal proteins, called Cry proteins, exhibit such a high degree of target specificity because of their mode of action within insect larvae.
Figure 2. The production of Bt toxins is coupled to the organism’s sporulation, and the multi-stage toxic mechanism by which Bt kills insects directly benefits the proliferation of the bacteria.
When the Cry protein reaches the gut, it is partially degraded, releasing a smaller and potentially toxic part of the protein . But this toxin will only be active if it finds the right matching protein receptor sticking off the cells lining the gut of a larval insect. This is the most important aspect of the Cry toxin mechanism. Much in the same way that a certain key will only open a certain lock, the Cry toxin can only exert its toxic effect on a particular cell receptor. Consequently, the toxin tends to only impact insects within a particular taxonomic order.
Once the toxin is bound, the process is fairly straightforward. The toxin recruits other Cry toxins to the same cell and together they form a hole in cell’s membrane that ultimately causes the cell to burst . The cumulative effect of this happening to many cells is the irreversible destruction to the midgut membrane, compromising the barrier between the body cavity and gut. Without this barrier, Bt spores and other native gut bacteria can infiltrate and grow within the nutrient-rich body of the insect [4-5].
What makes Bt such a great candidate for pesticide and GM applications is that while these Cry toxins are highly effective against insects, they have been shown to be safe for consumption by mammals. Tests by the EPA have demonstrated that Cry proteins, like any other benign dietary protein, are very unstable in the acidic stomach environment. Furthermore, an oral toxicity test, which involves giving mice exceptionally high doses of purified toxic Bt proteins, showed no significant health impacts. In their 2001 reassessment of several Bt Cry proteins, the EPA concluded from these findings that “there is reasonable certainty that no harm will result from aggregate exposure to the U.S. population, including infants and children, to the Cry1AB and Cry1F proteins and the genetic material necessary for their production.” Similar conclusions were drawn about the Cry1Ac protein of Bt cotton . Other mouse studies on have shown that even high doses of truncated Cry proteins, such that only the toxic region is conserved, have no deleterious effects . A paper in Annual Review of Entomology from 2002 also makes the strong point that, in addition to no demonstrated toxicity of Bt toxins, their use provides important health benefits to livestock and humans by preventing certain insect-caused crop diseases that produce toxic and carcinogenic compounds .
The environmental safety of Bt
Two major questions about the environmental impacts of Bt crops must be addressed. First, to what extent does the use of Bt crops reduce the application of more harmful pesticides? Second, do Cry proteins have significant off-target effects on other organisms?
Bt crops have enormous potential to reduce the use of both synthetic and organic pesticides (see this article). By relying on their Bt corn or cotton, farmers can decrease pest control-related costs and increase their yield. The USDA reports that “generally, Bt adoption is associated with lower insecticide use,” based on a collection of surveys from1998 to 2007 .
In 2001, Bt adopters were using approximately 36% less insecticide than non-adopters. The major caveat of this data, though, is that over the following decade the use of pesticides, on both Bt and non-Bt crops, has dramatically decreased overall. According to the USDA, between 1995 and 2010, the amount of pesticide used per acre of corn decreased by 99%, while insecticide use on cotton crops decreased by about 95% .What is interesting about these numbers, though, is that some studies have found evidence that the use of Bt corn and cotton is associated with a broad suppression of the overall population of damaging pests like corn borer, bollworm, and aphids [9-10].
One notable example of potential concerns for off-target effects occurred in the late 1990s, when it was widely published that high levels of pollen from Bt crops were toxic to the larvae of Monarch butterflies, commented on by David S. Pimentel and Peter H. Raven in 2000 . While this initially raised concern, it has since been shown that the conditions under which this toxicity was observed do not exist in real-world applications of Bt. Specifically, butterfly larvae are not likely to be exposed to levels of Bt pollen that would be toxic, and are less likely to directly ingest toxic Cry proteins, as they do not feed on corn or cotton . The comparison must be made between plants that have been engineered to produce Bt toxins and the application of Bt-based pesticides. The more targeted and localized action of GM Bt crops appears by all accounts to have less of an ecological impact than non-Bt methods.
Bacillus thuringiensis has a long agricultural history dating back nearly one hundred years. Even within the relatively recent age of genetic engineering, Bt has been one of the longest-running applications and successes of GM foods in the United States. The targeted mechanism of the Bt Cry toxin makes it an excellent pesticide since it has been shown to be safe for human consumption, reduces the use of insecticide application, improves crop yield, and reduces the amount of management crops require . The engineering of Bt insecticidal traits into crops like corn, cotton, and potatoes demonstrates the potential benefits and possibilities that advances in biotechnology are now providing. Perhaps most importantly, the story of Bt spotlights the thorough regulatory oversight that governs the development and application of these GM foods, ensuring their safety and sensible use.
Matthew Niederhuber is a Research Assistant in the Harvard Medical School Department of Systems Biology.
This article is part of the August 2015 Special Edition, Genetically Modified Organisms and Our Food.
1. Food and Agriculture Organization of the United Nations. Keeping plant pests and diseases at bay: experts focus on global measures. (2015). http://www.fao.org/news/story/en/item/280489/icode/
2. EPA. 2006-2007 Pesticide Market Estimates: Sales. (2013). http://www.epa.gov/opp00001/pestsales/07pestsales/sales2007.htm#2_1
3. USDA. Adoption of Genetically Engineered Crops in the U.S.: Recent Trends in GE Adoption. (2015). http://www.ers.usda.gov/data-products/adoption-of-genetically-engineered-crops-in-the-us/recent-trends-in-ge-adoption.aspx
4. University of California San Diego Aroian Lab. Bacillus Thuringiensis: Bt GM (genetically modified) crops. http://www.bt.ucsd.edu/bt_crop.html
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8. Lemaux, Peggy. Genetically Engineered Plants and Foods: A Scientist’s Analysis of the Issues (Part I). (2008) Annual Review Plant Biology.
9. USDA. Genetically Engineered Crops in the United States. (2014). http://www.ers.usda.gov/media/1282246/err162.pdf
10. Hutchinson et al. Areawide Suppression of European Corn Borer with Bt Maize Reaps Savings to Non-Bt Maize Growers. (Oct 2010). Science.
11. Pimentel D, Raven P. Bt corn pollen impacts on nontarget Lepidoptera: Assessment of effects in nature. (July 2000). PNAS.
12. Mendelson M, Kough J, Vaituzis Z, Matthews K. Are Bt crops safe? (Sept 2003). Nature Biotechnology.
13. Shelton AM, Zhao JZ, Roush RT. Economic, Ecological, Food Safety, and Social Consequences of the Deployment of Bt Transgenic Plants. (2002). Annual Review of Entomology.
14. Cover image: BT cotton crop. picture taken on 9.8.13 near nagarjuna sagar by Bhaskaranaidu. From Wikmedia commons: https://commons.wikimedia.org/wiki/File:Cotton_crop_2.JPG