Thursday, October 3, 2013

Who let the mites out?

 Allergies.... again


How some GMOs might make them worse



Man....I wish I didn't suck at immunology.  The last time I studied the subject, the Gipper was President.
A one-hit-wonder  was topping the charts having us walk like an Egyptian. The juiciest affair of the era wasn't between a President and an aide wearing a blue dress,  or a Twitter flurry of penis images- it was the Iran-Contra affair involving an exchange of weaponry.  Genesis described the era best-  it really was a land of confusion.

 Needless to say, those long forgotten lessons did not make me an immunologist, and I  hate playing one on the net.   But a  recent Twitter conversation with Nathanael Johnson, a food reporter writing a long series on GMOs on Grist,  prompted me to dig around  for whatever remnants of immunology I've not yet forgotten- to explain the scientific reasons I am seeing allergic reactions to GMO ingredients in my patients, clinically- in real life. 

So, lets review some basics. 

In people atopy causes hay fever, asthma and eczema, while food allergies are an undeclared emerging epidemic.

The job of the immune system is to detect and destroy "bugs" out to kill us while leaving our own tissues alone, known as tolerance.  Allergies are seen when the immune system gets "confused" and overreacts to harmless stuff like pollen or dust mites (allergen/ antigen)  reacting to them as if they were lethal invaders. When the immune system declares nuclear war on the body, the result is a life-threatening anaphylactic reaction. 

An allergic reaction typically occurs when an antibody known as IgE binds the antigen, activating mast cells to release inflammatory chemicals, the most famous of which is histamine.
Common anti-histamines like Benadryl work by preventing their release.  Thus, when testing for allergies is done, what immunologists are usually testing is the antibody IgE.

 Did you know that an allergy to birch tree pollen can cause allergies to apples and other fruits?  It is true. This is due to an antigen is known as bet v 1. And allergy to cockroaches or dust mites could make you more prone to allergies to shrimp due to a shared tropomyosin.   And if you were to develop an allergy to latex you might become allergic to kiwis and chestnuts.

  • Cross-reactivity explains the reasons for the overlap of symptoms between inhalant/contact allergies known as atopy and food allergies 

 Cross- reactivity refers to the ability of the IgE antibody to react with more than one allergen/antigen from different sources due to shared antigenic components, such as those between birch pollen and fruit, or grasses and grains, or dust mites and shrimp. Good list of cross-reacting allergens.

Cross reactions arise because the binding site on the allergen-- known as an epitope-- the business end of the allergen made up of a chain of folded amino acids--fits the IgE antibody,  like a lock and key in three dimensions.

Phew...... not too bad, right?

Now that we have some basic immunology figured out,  what does any of this have to do with GMOs?

We will get to it in just a minute.
First, I'd like to introduce you to some microscopic critters billions of whom share our homes, our beds, couches and live on your pet's kibble. They are known as dust mites. Nasty looking critters, aren't they? Another type of mite called storage mites,  just as ugly as these, also live on cereals and your pets' dry food.

Dermatophagoides pteronyssinus Wikipedia

Because house dust mites are microscopic the general feeling about them among clients could be "How much harm can they cause my pet or me?"
 In fact, the most common allergen in dogs and cats (and in people, too) is dust mites. Anyone who is allergic to dust mites can attest to the miserable symptoms this condition can cause. It seems our domestication of dogs and cats (i.e., bringing them into our households and beds) also succeeded in sensitizing them to this common; they suffer from them just like we do.

  • So, what if.. these mites are not only living on the food but are actually in the food

And this is where genetically modified foods (GMOs) come in. No, I am not saying that eating a genetically modified organism (GMO) means you are eating microscopic mite body parts.

  • But...  there is a distinct possibility that a segment of a dust mite allergen might have been spliced into Round Up Ready GMO foods

And this is why.

The most common commercialized GMOs are Round Up resistant: corn, soy, canola, sugar beets and alfalfa. They were engineered to be herbicide resistant by insertion of a  transgene known as Cp4 EPSPS which produces a protein EPSPS  (Enoyl Pyruvyl Shikimate Phosphate Synthase), isolated from a bacteria found growing in an herbicide waste tank,  which rendered it resistant to the herbicide- Round Up -Agrobacterium CP4.

Insertion of exogenous, new and foreign DNA into plants raises concerns about unintended effects such as the creation of novel allergens.  The World Health Organization (WHO) gathered together global experts in allergies and published guidelines on screening GMOs for known allergens in 2001.

The  very first step in the decision  tree WHO experts established screening GMOs for novel allergens is this fundamental rule.  " if a  new gene product  spliced in shares 6 amino acids ( protein building blocks) with known allergens, such a  match  triggers further allergy testing  on  serum from  25  people with an allergy to that substance."

It turns out that Cp4 EPSPS shares a window of similarity of  7 amino acids with common house dust mites, an allergen known as der. p.7.  ( abbreviation of  Dermatophagoides pteronyssinus).  
It isn't the only one.
If you look at Table 4 and Table 5 in the link below, you will notice other potential allergenic matches between new genes being spliced in and known allergens, which I haven't checked.   The decision tree is also graphically illustrated in the article linked below.

Screening of transgenic proteins expressed in transgenic food crops for the presence of short amino acid sequences identical to potential, IgE – binding linear epitopes of allergens

 This brings me back to the conversation with Nathanael and  a link  he provided to studies on genetically modified foods conducted thus far which  help answer the following question:

"did the companies commercializing these crops conduct proper studies to make sure that the transgene was not allergenic based on the guidelines established by the WHO"?  Did they even perform the most basic preliminary steps to screen out allergens? 

And the answer is: no, not really.

While GMO advocates quote these authoritative bodies to support their safety, as you will soon find out--the basic safety guidelines established by these bodies are not followed! 

Ruling out cross-reactivity between the dust mite allergen and the new protein coded by the transgene, an ELISA inhibition assay is required on 25 serum samples from patients with high titers to dust mites-- according to a global panel of allergy experts assembled by the World Health Organization.  Since allergies to dust mites are so incredibly common, it should be exceedingly easy to locate serum samples.

 Unfortunately, a targeted screen utilizing   inhibition ELISA was performed on a pooled sample of 4  in one of the studies cited by Nathanael. Interestingly, it did show minimal cross-reactivity.  But pooling a sample reduces its accuracy while  a sample of four has a very low probability of detecting cross-reactivity.

Additionally, the studies cited were performed on patients in Korea, Portugal and Japan---countries where GMOs are neither as prevalent as in the US nor sold unlabeled. There is not a single study done on a statistically significant number of samples (>10) from Americans with the longest and highest level of exposure to GMOs. 

Thus,  if you, your child or your pet is sensitized to mites, dust mites or storage mites,   the allergies might be exacerbated by foods containing some or all Round Up Ready crops:  soy, corn, canola, sugar beets ( beet pulp). Remember, with allergies it isn't the quantity or the amount--it is exposure to an allergen.

  • Unfortunately, it takes only a tiny amount of mite allergen to elicit an allergic reaction in our pets and people. 
  • Allergic cross-reactivity is often encountered as a reaction without prior exposure.  A very common public misunderstanding is that people and pets express allergies on the first time they are exposed to an allergen. This is very rare, as normally sensitization over a long period is required to have allergy symptoms. 
If you or your pet are sensitized to dust mites or storage mites, does it mean that they or you will automatically be allergic to these foods?   No, it does not.  Even if there is cross- reactivity between the new gene in these foods and mites, cross-reactivity alone does not mean a clinical allergy. It isn't as simple as that. But being aware will allow you to watch yourself or your allergic pet for exacerbation of allergy symptoms with exposure to these ingredients or improvement when they are eliminated, and acting accordingly.

Oh, and please--  if any real immunologists are reading this I'd   appreciate your help! I hope you've enjoyed this little journey through the land of confusion. 



[1] Email I sent to Nathanael- I never received a response. 

Hello, Nathanael.
I believe that GMOs are allergenic based on seeing patients for many years who improve when they are removed from their diets or deteriorate when added to their diets.Allergies are veterinarians' bread & butter out here in dusty Southern California and after 24years of practicing I think I've gotten pretty good at them.
 As I shared with my friend Kevin Folta, I see a case or two a week, whose allergic flare ups, I suspect, are triggered by GMOs. The last one was 2wks ago--the owner switched food, and the dog broke out on his face and feet within 48hrs. The only difference was that the new food had beet pulp, most likely RR. Someone who isn't aware of GMOs would never notice the connection and most vets are clueless about them.  Plus they are much easier to treat with immunosuppressive drugs, then dig around for the cause.  I suspect, but don't know, that the same level of ignorance is also true of the human medical profession--which is even worse because specialization so compartmentalizes it.
Of course, my observations are anecdotal, but if I am right, there is a whole lot of suffering and pain these foods could be contributing to. The immune system is incredibly complicated, there is more we don't know than we do, and there isn't a fine line between an allergy, seen as a nuisance, and devastating inflammatory/ autoimmune diseases in the genetically-vulnerable.
The studies in your link are a mess. They are not standardized; they are poorly done and hard to follow, and none of them do a serum test on 25 patients with allergies to Dermatophagoides pteronyssinus (der. p.). Some do skin prick tests rather than serum tests; others are made up of small sample sizes (10).  There is no standardization of methodology.
 The safety tests of GMOs are a mess, in general. It is like that example you gave off different people feeling different parts of an elephant. So while you are reading a study that examines the elephant's trunk or his tusk, it says absolutely nothing about the whole darn beast.  
The best that can be said about them is that they are pilot studies and that studies on a much higher number of people need to be done.
The Goodman affair I linked on Genetic literacy was to show clearly that Dr. Goodman, who is the director of the biotech allergy database, as well as the new editor of the journal most of the GMO literature is published in, I believe, could not provide a study which fulfills the WHO-established allergy testing standards. Neither could Rod Herman of Dow, who rewrote the GMO- allergy rules, likewise, in the comments in your series.  Either because they do not exist. Or they do exist, since it is a relatively simple test, and it showed that EPSPS and dust mites do cross react, and these companies know it.

I don't know how journalism works, but you do have two biotech people saying on the internet print "record" that the WHO guidelines for allergy testing are not being followed. Ask yourself if that is good enough considering that CP4 EPSPS is in most of our human and animal food and just about everyone and their aunts, uncles & cousin are allergic to dust mites.

I am not sure whether Grist is really allowing you to do genuine investigative journalism, because I noticed ads for Dows cotton in your series. Don't know, but expect, that media outlets have to pay their expenses with advertisers dollars and the biotech companies are in the midst of a media blitzkrieg.

Having said all that, I hope you are a "good guy", might have some room to maneuver and can do some public good.

If you want to know why I am spending this much time on the subject it is really very simple. I have unique training. As a veterinarian I took an oath which obligates me to prevent pain and suffering and watch out for public health. I don't take oaths lightly, and I feel an allegiance to the taxpayers of the state of California who spent a quarter million to educate me. Besides, if  someone, somewhere, doesn't do something,  Monsanto et. al. will destroy the field of biotechnology--they have already turned it into a dirty word.   
Thanks for listening.
Please do your best to do some good. With all the smoke & mirrors, combined with how very complicated this subject really is, some intelligent dogged reporting is sorely needed.
Thanks very much,

Sadly, for the American public,  there are very few trustworthy  journalists on the GMO beat abiding by the   Journalism Code of Ethics.

Society of Professional Journalists explainer on  journalism Ethics:
Members of the Society of Professional Journalists believe that public enlightenment is the forerunner of justice and the foundation of democracy. The duty of the journalist is to further those ends by seeking truth and providing a fair and comprehensive account of events and issues. Conscientious journalists from all media and specialties strive to serve the public with thoroughness and honesty. Professional integrity is the cornerstone of a journalist's credibility.

[2] Le Monde article on Dr. Goodman in charge of the allergen database.