"Substantial equivalence" - A tricky, misleading term!

The biotech industry argues that genetically engineered organisms do not require labeling, should not be subjected to rigorous testing, and do not warrant careful public scrutiny.

This is because, the industry proclaims, genetically engineered organisms are "substantially equivalent" to their non-engineered counterparts.

Substantially equivalent?

The concept of "substantial equivalence" sounds like an oxymoron. It sounds like an attempt to have one's cake and eat it too. Is there a deceptive ambivalence behind the phrase?

Let's unpack the term.

Of course, the industry could not say that the GMO was "completely equivalent" because then they would have no basis for claiming a patent on the organism.

And they could not claim that it was "substantially different" either, because that would trigger concern that they'd rather not face.

The secret was to find a combination of words that make the invention seem just different enough to merit a patent but not different enough for people to be concerned about. With "substantial equivalence", they landed in a pot of gold.

Of course, the concept is misleading but that is why it is valuable. It functions like a slippery snake, evading any attempt to pin down its meaning. When those concerned about GMOs speak out, it slithers over towards "equivalence". When the patent offices inquire, it nests in the serpentine ambiguity of the word "substantial".

(I apologize to the snakes out there for using this metaphor.)

"Substantial equivalence" shares that oxymoronic sneakiness that makes so many other industry concepts so enervating. Think of "sustainable development" or "clean coal" or "ethical oil".

The term "substantial equivalence" originally met with resistance from the Food and Drug Administration (FDA), who had internal documents describing the possible toxins, allergens, and new diseases that might arise from GMOs (Freese and Schubert, 2004).

However, for whatever reason, the documents were ignored and the FDA decided to go along with the term.

So did the FAO.

The FDA also decided that it would be sufficient if the biotech companies conducted the studies by themselves to establish whether or not their GMOs were "substantially equivalent". This would not be considered a conflict of interest.

And the FDA decided that the FDA itself would not need to conduct any testing of these novel organisms. It would just believe the biotech companies' reports.

The FDA's regulation gets even more stringent at this point. Listen up.

The actual experimental write-ups by the companies are classified so no independent scientists can access them. The FDA has no problem with this.

To make matters worse, biotech companies often do not allow external scientists to conduct health or environment tests using their seeds. In fact, when you purchase the seeds, you often have to sign a legal document assuring that you will not test them in any way.

They are not merely seeking a monopoly on our food source. They are also seeking a monopoly on the knowledge we can gain about their products. Without the capacity to freely inquire into new technologies, we are unable to democratically evaluate them and make informed decisions with respect to the role they play in human societies.

But before we go any further, it is useful to ask: what is it exactly that the biotech companies claim to analyze in order to deem their products "substantially equivalent"?

A 2003 review in Trends in Biotechnology identified 7 main research foci. Now, we cannot actually see the studies that Monsanto or Dupont or Dow or Astra Zeneca conduct in these 7 areas because, as I said, they are company secrets. But even if we take their word for it and in good will assume that the reports they issue publicly are not biased, the seven areas themselves are not entirely convincing.

In fact, with a little understanding of genetics and ecology, they all seem quite weak.

Allow me to indulge a little bit in each of them. Here is what biotech companies claim to do, and here are my answers:

1. Study the introduced DNA and the new proteins or metabolites that it produces.

Genes make mRNA which translate into proteins. Understanding what new proteins are produced is crucial for understanding how the gene is altering the behaviour, physiology and biochemistry of the organism. This is because proteins are the building blocks of processes and products in the body. Of course regulators should be studying the proteins that the introduced DNA produces!

Unfortunately, studying the proteins that the introduced DNA produces is not enough.

Why?

Because the introduced DNA interacts with other genes, switching them on or off, upregulating or downregulating them. For example, in yeast, over 95% of the genes interact with their neighbours (Featherstone and Broadie, 2002). Genes do not behave in isolation, they operate in networks. When we introduce new DNA into an organism, an undefined number of other genes end up producing proteins in unexpected ways too. The same goes for metabolites, which are synthesized in complex networks of co-interacting chemicals.

2. Analyze the chemical composition of the relevant plant parts, measuring nutrients, anti nutrients as well as any natural toxins or known allergens.

The key word in this is "relevant". I assume that for GMOs intended for consumptions, the "relevant plant parts" are those parts which people eat. But the novel genes are not just in those relevant plant parts. They are in every single cell of the organism's body! And even if humans are not eating those other plant parts, SOMETHING is. And it is important to know how that something will react because it is part of a larger ecology and so changes to it could have ecological effects.

Second, it is easy to test for "known" allergens and anti-nutrients. But what about unknown ones? The concern is that novel proteins or novel combinations of proteins or metabolites might trigger some health problem. Given that it is impossible to test for an unknown allergen does not mean that the burden of proof should be placed on those concerned. Yes, it is a scientific problem to figure out how to conduct such tests. But that is the problem of those who produce the technology.

If industry responds that such studies are unnecessarily complicated, the public should be able to evaluate whether not engaging in thorough research is a necessary risk for our current social and ecological needs.

3. Assess the risk of gene transfer from the food to microorganisms in the human gut.

Unsurprisingly, there are problems with this one too. And again, they stem from a refusal of the biotech industry to respect living beings as complex interactive networks.

The quantity and variety of gut micro-organisms is continually shifting across time, is dependent on cultural, environmental and climatic factors, and numbers from 300 to 1000 bacteria species, and fungi and protozoa too. Can we possibly imagine that biotech companies test for all of these possible combinations? It is a permutational nightmare and would be exorbitantly costly. But it gets worse: the gut itself is an environment for the gut organisms, and as the gut changes (from sickness, from exposure to chemicals, etc.) they way the gut microorganism behave changes too. Some genes may switch on, others may downregulate, as the organisms co-evolve with their mini-ecosystem. What about all those factors? Further: considering the biotech companies do not actually conduct tests on humans we cannot assume that the environment within which these microorganisms are being tested for gene transfer is equivalent to the environment in the human gut. Finally, the context of the GMO is not stable. Environmental stressors can switch on certain genes or inhibit others, altering the way that the transgene behaves and potentially making it unstable. Alternatively, changes in the human could modify the degree to which the gene may jump.

Proponents of genetic engineering might say: Lighten up! It's just a gene! Why would it be more likely to jump out of the food and cause a nuisance than any of the other genes?

Well, the answer, again, is clear: the gene didn't just arrive by some happy coincidence into the host code. It was forced in using viral vectors despite the defence mechanisms within the cell to prevent the invasion of foreign DNA. After in, it was shaken into activity using a viral promotor. These viral genes are aggressive and unpredictable. After all, it is through these genes that viruses can hijack other organisms' genetic codes. Viral genes increase the instability of the other transgenic genes. The same stuff that made it get in can also make it jump out.

4. Study the possibility that any new components in the food might be allergens.

It is interesting to ponder how this could be done without human studies. Anyway, I've addressed the concerns with this point in #2 and #3 above.

5. Estimate how much of a normal diet the food will make up.

How much of it we eat is simply not relevant to answering the question of how similar the novel organism is to its natural counterparts. There isn't much else to say about this one.

6. Estimate any toxicological or nutritional problems revealed by this data in light of data on equivalent foods.

This is potentially useful. The idea is this: suppose the novel proteins are present in some other food. The scientists study that food for toxicity so that they have likely scenarios with respect to their GMO. By all means this sort of analysis should be conducted. But it would be erroneous to assume that a given protein in one context has the same effects as that same protein in another. The other nutritive factors and metabolites in that food work synergistically or antagonistically in complex ways that render the protein's effect "context dependent".

7. Additional animal toxicity tests if there is the possibility that the food might pose a risk."

These are typically 90 day studies and are inadequate to assess health across the lifespan or multi-generationally.

So, what would better "substantial equivalence" look like?

It is possible that a gene might be inserted somewhere such that it did not do anything harmful to the organism, to the one consuming it, or to the surrounding ecology. Of course it is theoretically possible that some GMO is "safe" in these senses. But the point is that no study is anywhere near establishing this and there are sound genetic and ecological reasons to believe that this would be a rare phenomena.

Nevertheless, there are some technologies emerging that can show in much greater detail whether or not a GMO is "substantially equivalent". There are problems with these tests, but it is good for food activists to become familiar with them.

Proteomics, metabolomics, and transcriptomics (often known collectively simply as OMIC studies) provide much greater insight into the effects of transgenic alterations than any of the simplistic and limited biochemical tests conducted. For example, a proteomic study would show how the protein products in the new organism differ statistically from a natural organism of the same species. This would help identify pleiotropic effects. If an inserted gene altered the behaviour of some gene nearby it, this altered behaviour would (theoretically) show up as some change in the protein distribution relative to a non-engineered organism.

These studies are still insufficient due to statistical inadequacies, but also because they only provide snapshots into the behaviour of the GMO. The GMO might be tested in laboratory conditions, where the inserted gene behaves in one way with its neighbours. But in complex field conditions, the gene often behaves differently and its behaviour changes over its lifespan. It would be unrealistic to think that the biotech companies could comprehensively test for protein changes across every likely field condition because there is an enormous variety, dependent on humidity, temperature, interacting organisms, predators, nutrient availability, etc.

Needless to say, most biotech companies and their cheerleaders are arguing that ANY OMIC study is unnecessary and that current substantial equivalence protocols are more than sufficient.

I apologize that this article got pretty technical, but I really think we need to know this stuff. Anyway, my conclusion is simple:

"Substantial equivalence" is a misleading term. Current regulations provide many holes for potentially serious health and environmental effects to slip through. Newer OMIC studies exists, which would provide a finer grained filter to skim out potential problems, but these studies are certainly not foolproof. Activists should understand that this neologism is used for political gain and as a tool for ensuring compliance. It is not a scientific term and it is not likely to be in the near future, given our analytical limitations in understanding the genome.

It is important that we expose the regulation for what it is. The biotech industry constantly accuses those concerned with genetic engineering of ignorant fear-mongering. The techniques that these companies utilize and enthrone with the Godly title, "Science", are neither noble nor ingenious. Behind their cunning words lie a dearth of precision and a surplus of greed.