EdG Note: This article has been retitled and substantially edited since 1st publication. See "Updates" for details.
Those who pay even casual attention to The Great GMO Debate are likely aware that one of the three main scientific claims used to show the safety of genetic engineering is that people aren't bugs. In other words, bug stomach pH and human stomach pH are different, so what harms them is safe for us. The three claims are:
- Humans can't be hurt by GMOs because our pH is different
- Safety of sprayed-on Bt proves the safety of GMO Bt
- GMOs won't harm us because we don't have certain receptors
While the 3rd claim has a great deal of solid science behind it, the 2nd claim is only partially true, and the 1st claim is, as this diary will show, untrue. Insects and humans are quite different, but remind yourself that we share a portion of our biology with fruit flies if you're starting to feel any tinglings of anthropocentrism.
Follow me past the orange gypsy moth larva for more.
Claim 1: The pH Argument for Bt Safety
According to an article from Biology Fortified (BF), a pro-GMO group, written to "answer this question: What happens when a caterpillar eats the Bt protein?",
(Joe Ballenger, April 5, 2014) Although I’m not focusing on humans in this post, I would like to compare and contrast the environments of the gut pH between insect and human guts. In humans, the Bt protein is very quickly digested in vitro, and this is due in part to the fact that human and insect stomachs are very different.
Proteins are sensitive to environment, and one very important factor is the pH the protein is in. The pH of human stomach acid is about 2 while the pH of the insect gut is about 10. To give you an idea of how different these environments are, remember that prolonged contact with a highly acidic (pH 2) or a highly basic (pH 10) substance will damage human tissue, which is a pH of about 7. (How does BT work?, emph. added)
BAM!!! Shoots and scores!!! A slam-dunk case if I ever heard one. Bugs are from Mars. Humans are from Venus. This solid, scientific evidence should be more than enough to convince any GMO skeptic beyond a shadow of a doubt that GMO technology is absolutely, positively safe. Until you remember that both humans and bugs are from Earth, not separate planets.
What is Bt?
Bacillus thuringiensis (Bt) is a spore forming, Gram-positive, soil-dwelling bacterium that produces crystals protein (cry proteins), that are toxic to many species of insects. Bt has been used as a sprayed-on biological pesticide for many years, even by some organic farmers. GMO plants have cry proteins inserted that confer pest-resistance to the plant itself.
What GMO Crops Are In Use?
There are currently 29 approved GMO crops, including apple, bean, corn, cotton, eggplant, soybean and others. There are 110 different approved genes used in the various GMO crops. -- International Service for the Acquisition of Agri-biotech Applications
Refutation: The pH Argument for Bt Safety is Faulty
A Brief Review of pH
The pH scale measures how acidic or basic a substance is. It ranges from 0 to 14. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Each whole pH value below 7 is ten times more acidic than the next higher value. Many fruits, such as apples are acidic while milk and water are essentially neutral. Ammonia, on the other hand, is strongly basic. The terms basic and alkaline are synonymous. What is ph?
European Corn Borer
How does Bt kill bugs? Basically, the Bt toxin drills holes in the bug's gut cells, water and bacteria flood into the drilled cells, the cells burst, and bug guts spill into the rest of the bug, causing it to die.
The bug literally spills its guts. If they weren't bugs, I'd feel sorry for them.
So far, this all sounds very good. The goal is to target bugs for extermination by exploiting specific biological characteristics that differ significantly from the related human characteristic. Bug gut pH is 10. Bt is shown to work at pH 10. Meanwhile, human gut pH is 2. Therefore, Bt is proved safe for humans.
Except that human gut pH is not always 2. And bug gut pH is not always 10. In addition, different Bt toxins (more on varieties later) operate at different pH levels, some acidic. The great divide between man and moth is not so great after all. It's possible we're not only on the same planet, but in the same hemisphere.
At What pH Are Bt Toxins Viable?
A 2004 study of Cry1Ab protein, widely used in corn crops, found that the toxin is not destroyed at pH 4.0 but that there may be an inhibitory effect due to limited unfolding of the protein. However, folding and pore formation are equally effective at both pH 7.0 and pH 11.0. Unfolding Events in the Water-soluble Monomeric Cry1Ab Toxin during Transition to Oligomeric Pre-pore and Membrane-inserted Pore Channel
The Cry3A toxin, used in GMO potatoes, is active against Coleopteran insects. The unfolding of this toxin is observed at acidic pH (as low as 3.0) that correlates with the acidic pH found in midgut of susceptible Coleopteran insects. Domain organization of Bacillus thuringiensis CryIIIA delta-endotoxin studied by denaturation in guanidine hydrochloride solutions and limited proteolysis
In the presence of Cry1Ac (used primarily in cotton, but also in corn and other food crops), membrane permeability remained high over the entire pH range tested (6.5 to 10.5) for KCl and tetramethylammonium chloride, but was much lower at pH 6.5 than at higher pHs for potassium gluconate, sucrose, and raffinose. In the other tested strain, Cry1C-induced permeability to all substrates tested was much higher at pH 6.5, 7.5, and 8.5 than at pH 9.5 and 10.5. (Differential Effects of pH on the Pore-Forming Properties of Bacillus thuringiensis Insecticidal Crystal Toxins)
About That Human Gut
What exactly is the gut? By the broadest definition, the gut is the Gastro-Intestinal tract and includes all structures between the mouth and the anus. Popular usage often treats it as synonymous with stomach. In some contexts, it consists only of the small intestine and the colon. As the author of the BF article uses stomach and gut interchangeably, we'll stick with his notion of gut equaling stomach, although technically, the Bt toxin works in the midgut (intestines) rather than the stomach.
Why is the gut important to this discussion? It contain gastric acid.
Gastric acid ... is composed of hydrochloric acid, potassium chloride and sodium chloride. The acid plays a key role in digestion ... and making ingested proteins unravel so that digestive enzymes break down the long chains of amino acids. Other cells in the stomach produce bicarbonate, a base, to buffer the fluid so it doesn't become too acidic. ... The pH of gastric acid is 1.5 to 3.5. (Condensed from WikiPedia)
You'll notice the BF author said stomach pH is 2 while WikiPedia says it ranges from 1.5 to 3.5. I'm sure the author picked 2 for convenience, not as a way to broaden the human to bug gap. But 2 is not the whole story. According to
Dressman et al., the median gastric pH is
1.7 in the fasting state (last meal more than 2 hours ago) and climbs to a median peak value of
6.7 soon after a meal. During the
basal state, pH ranges from
3 to
7.
Hmm. A median (middle number; half are higher, half lower) peak pH of 6.7 was measured in young, healthy adults after they ate a meal. Even so, there is still distance between our gut and that of our 6-legged friends, since 6.7 is less than 10, right? Perhaps humans are from eastern Canada while bugs are from western Mexico.
What About Drugs And Diseases That Affect Stomach PH?
Many Americans use over the counter antacids to combat heartburn symptoms. Millions of others take prescription acid blocker drugs to treat stomach disorders ranging from acid reflux to gastric ulcers.
Some, like my rheumatoid arthritis afflicted wife, take an acid blocker to ease the discomfort (NSAID–induced gastropathy and similar) that those with chronic disease suffer from heavy consumption of prescription and OTC medicines.
How do acid blockers work?
Proton-pump inhibitors (PPIs) are a group of drugs whose main action is a pronounced and long-lasting reduction of gastric acid production. They are the most potent inhibitors of acid secretion available. (Wikipedia)
How much is stomach acid reduced? Quite a bit, as it turns out. In order to successfully treat a stomach disorder like GERD, the stomach must be raised to a
minimum pH of 4 averaged over a 24-hour period. That's more than twice the median pH of young, healthy men and women. At mealtime, PPIs combine with the buffering effect of food to raise pH
well over 7. This matters because increased pH has been linked to allergen sensitization and drug hypersensitivity (see
A Couple of PPI Studies below).
In addition, low or absent acid secretion is found in certain diseases such as pernicious anemia, atrophic gastritis and gastric carcinoma. Also, children do not reach adult level acid production until about age 3, while fetuses and newborn infants have an average gut pH of 6 to 8, which is the same as their mother's placental fluid.
Furthermore, food eaten by people who've had gastric bypass surgery is subjected to a much shorter time in acidic conditions and under certain conditions, they can experience gastric dumping syndrome wherein food is dumped straight to the intestines without being processed very much by the stomach.
Or to put it another way, pH-wise, humans are now from Atlantic City while bugs are from Vegas. Unfortunately, as we'll see in the next section, what happens in Vegas doesn't always stay in Vegas.
A Couple of PPI Studies
Our recent studies revealed that digestion labile allergens can also have sensitizing capacity if gastric digestion is hindered. The increase of gastric pH via acid-suppression by proton pump inhibitors, sucralfate or antacids, interferes with protein digestion, and leads to sensitization and allergic reaction in mouse models as well as in human patients. (Mechanisms and risk factors for type 1 food allergies: the role of gastric digestion, December 2012)
Previous research has shown that gastric acid suppression by antacid drugs can promote allergic reactions to acid-labile food proteins. ... In hospitalized patients, the use of proton pump inhibitors was associated with a significant increase[d] risk of drug hypersensitivity reactions along with a personal history of drug allergies and long hospitalization time. (Proton pump inhibitors are associated with hypersensitivity reactions to drugs in hospitalized patients, March 2013)
Will Bt Spill Human Guts?
Bt Toxin Crystals
Continuing with the BF article,
Bt toxin requires a high (basic) pH to be active, and must be activated by specific protein-cutting-proteins in the insect gut. (ibid.)
(EdG note -- The article is licensed Creative Commons Non-Commercial and DK is a commercial blog, so here's a brief restatement of the author's caveats: There are still a lot of unknowns about Bt. We don't fully understand what happens at certain points in the process. There are other debates and limits to understanding. Bt encodes proteins that are toxic by themselves, but when combined together become more toxic. Genetic manipulation may change toxicity.)
The statement that Bt toxin requires a high pH to be active was shown to be untrue in the sidenote "At What pH Are Bt Toxins Viable?" above. There are many different Bt toxins and the specific conditions needed for activation vary. For example, some toxins work at pH levels as low as 3 while others work at pH levels as high as 12.
The three substances required to turn protein segments into gut-spilling killers (aminopeptidase, alkaline phosphatase, and cadherin) are very common substances on the gut wall in both bugs and humans. However, the specific process that works so well to kill bugs should not work at all in humans even when gastric pH is raised. One example is that human cadherin does not express the BT-R1 protein binding site Cry1Aa, Cry1Ab, and Cry1Ac toxins attach to in some insect guts.
Something else the BF article did not mention is that there are actually two ways to activate Bt toxins. In addition to alkaline activation, applying 158 degree Fahrenheit heat for 20 minutes also activates the toxin. For comparison, the best temperature for perfectly cooked white meat on your Thanksgiving turkey is 155-160 degrees measured internally at the breast.
Does this mean Grandma's GMO cornbread stuffing is a killer? Not at all. Many of us would already be dead if that were true. The salient point should already be apparent to those with a scientific bent: Just because something can theoretically occur doesn't mean it will; just because something that theoretically can occur hasn't, doesn't mean it won't.
There are about 170 varieties of natural Bt toxins (identified by the prefix Cry) and some man-modified version, with varying pH-level activation points and binding sites. While some butterflies, moths and true flies do have high midgut pH, other insect species do not. Yet Bt still kills them. As mentioned earlier, some Bt toxins activate at tested pH levels as low as 3.0. Suddenly, bugs and humans are cruising the Vegas Strip together in a big old '65 Chrysler convertible, although bugs are in the back seat and humans in the front.
Scientific Studies About Safety
A number of laboratory and field experiments have been conducted with Cry proteins, particularly the Cry1Ab toxin that has been engineered into corn and rice crops. The majority of these studies have found that Cry1Ab toxin causes no detectable harm in mice or other tested non-human animals. This is good news, and is the sort that should be used when discussing GMO safety rather than specious claims about bug gut pH.
There have been some 2,000 studies conducted on GMOs worldwide. Many were funded by the GMO industry but a number of others received independent or government funding. The majority found no harm was caused under the conditions tested. Keep in mind, though, that studies involving human subjects are rare.
However, there are other factors to consider about GMO testing. First, the studies are lagging behind the introduction of human-consumed GMO crops, which, in the United States, are self-certified as safe by the manufacturers themselves. Second, and this will prove problematic in future, insects are developing resistance to genetically engineered Bt toxins.
To counter Bt toxin resistance, GMO makers are gene stacking two or more genetic toxins together in hopes this will overcome the resistance. This increases testing complexity and may increase the likelihood of unwanted side effects.
Also, particular toxins are being modified to improve their performance. For example, Cry1AbMod eliminates reliance on cadherin as a step in the activation sequence. What this means is that specific bug receptors such as BT-R1 are no longer relevant. The downside, of course, is that this reduces specificity of action (GMO safety claim 3). See: Bacillus thuringiensis Cry1AbMod toxin counters tolerance associated with low cadherin expression
At this point, you're probably wondering about government regulation. After all, doesn't the U.S. government cripple the economy by imposing draconian regulation on corporations? Not exactly.
EPA [Environmental Protection Agency] does not require long-term studies because the protein’s instability in [human] digestive fluids makes such studies meaningless in terms of consumer health. -- Is the Bt Protein Safe for Human Consumption?
In other words, human and bug pH are different so long-term studies are not needed. Now where have we heard something like that before?
GMO Recalls
Some GMOs have been recalled, but there is considerable dissension about whether the concerns that prompted the recalls were warranted. For example, StarlinkTM corn, a variety engineered to express the Bt Cry9C protein, was removed from the market in 1990 because of concerns about potential allergic reactions in humans. Starlink was approved for animal feed but not human consumption. It had entered the human food supply because of problems encountered with segregating feed and food corn. The allergenicity concerns about Cry9C have since been allayed in further studies.
Other recalls involved soybeans with a Brazil nut gene implanted that could cause an allergic reaction in susceptible people and Quest canola seeds in Canada. In addition, ingestion of products containing genetically engineered L-tryptophan (LT) produced by Showa Denko KK caused the 1989 epidemic of eosinophilia-myalgia syndrome (EMS) in the United States, and Showa Denko recalled all of their bioengineered LT products.
Conclusion
In this article, we examined the claim that Bt cannot possibly be harmful to humans because our acidic gut pH is lower than the alkaline gut pH of insects. As clearly shown in this article, the pH claim is patently false. The presumptive safety arising from human gut pH exceptionalism is vastly overstated.
In fact, various Bt toxins have been shown in laboratory studies to activate at pH levels as low as 3 and as high as 12. Human gastrointestinal (GI) tract pH ranges from a low near 1.5 under certain conditions up to 8.5 under other conditions. Insect GI tract pH ranges from 3 up to about 11, depending on species.
There is more to the story than just pH, of course. But it's time for GMO proponents like Biology Fortified to back away from the pH claim of GMO safety. It's simply not true.
Updates
I've added a few updates inspired by reader comments or required by further research:
- Added link to list of GMO crops and genes
- Added data about Cry1Ab and Cry3A pH viability
- Expanded upon the reason for the Starlink recall
- Added link to study on Cry1AbMod re: cadherin
- Removed crayfish study
- Retitled from "How Science is Used to Overhype GMO Safety"
- Other edits and substantial reformatting of content