US-based systems biologist Shiva Ayyadurai created a controversy recently by claiming that his studies had found that genetically modified soya bean plants had less capacity to get rid of toxins such as formaldehyde compared to non-GM counterparts. The idea that GM technology disrupts a plant’s natural metabolism was seized upon as vindication by anti-GM activists even as it came under criticism from others. In a wide-ranging interview, BusinessLine spoke via conference call to Shiva Ayyadurai, whose current research focuses on developing systems biology methods to understand bio-molecular phenomena, and three other scientists who make a strong pitch for increased regulation and transparency in GM foods — Michael Hansen, senior scientist at the non-profit Consumer Union working on consumer-related policy issues; Ray Seidler, a former senior scientist at the US Environmental Protection Agency (EPA); and Hema Yadav, an agricultural expert who has worked on capacity-building for farmers and managers in India and Africa. Excerpts:

In a nutshell, the essence of your hypothesis seems to be: Like all plants, genetically modified soya bean produces formaldehyde, a carcinogen; but unlike non-GM soya bean, it depletes glutathione, a key anti-oxidant that helps plants remove formaldehyde and other toxins from their cells. As a result, it is wrong to suggest that GM soy is equivalent to non-GM soy and, by implication, that GM plants are equivalent to non-GM plants. Does this make for a fair description?

Shiva Ayyadurai: Yes, our systems analysis shows that GM soy is substantially different from non-GM soy. The critical point is that we used a systems biology approach — the first of its kind — to look at a critical molecular system called C1 Metabolism, which occurs in all plants, bacteria and fungi. In that molecular system, there are three sub-systems: methionine biosynthesis, methylation and formaldehyde detoxification. The goal of this systems approach was to explore if GM plants are the same as, or “substantially equivalent” to non-GM plants. We based the study on integrating molecular pathway information from 6,497 wet lab experiments done in 184 institutions, across 23 countries, on what occurs from genetic engineering to produce Roundup Ready Soy (RRS), the GM soy, and whether such GM causes disruption to C1 Metabolism. We found that there is a significant disruption, particularly to formaldehyde detoxification, following insertion of the foreign gene.

Our analysis concludes that, in GM soy, oxidative stress is caused by the GM, resulting in glutathione, a natural anti-oxidant, being depleted and formaldehyde accumulating. Formaldehyde does exist in all plants, at various levels, and detoxification occurs at different stages. However, in the GM soy, since the formaldehyde detoxification pathway is perturbed, this analysis shows that the levels of formaldehyde and glutathione will vary between GM soy and non-GM soy.

Your research did not involve testing actual plants. So why rely wholly on a ‘systems biology’ approach? Why didn’t you bother to validate this by testing a few transgenic and non-transgenic varieties of soy? Wouldn’t that have strengthened your hypothesis?

Michael Hansen: Clearly, such testing needs to be done and that will be in a forthcoming paper. By the way, this series of four papers is based on thousands of wet lab tests and is not “just a model”. This paper is focused on using modern systems biology methods to provide a foundation, at the molecular level, for all researchers to understand, with full transparency, how GM may perturb complex molecular systems. There is an active effort towards conducting wet lab tests on the results indicated from this systems biology analysis. However, conducting such experiments is extremely difficult, given the lack of transparency from those who own, manufacture, and control those GM seeds, be it soy or others. For example, there are legal constraints in the US to even obtain the seeds to conduct such testing.

Ayyadurai: The systems biology approach is the most important contribution of this series of four papers, and aims to advance the scientific method in a far more transparent and integrative manner to get an accurate view of what is going on in GM versus non-GM. Today, scientists primarily do individual, single experiments using the scientific method, where they first begin with a hypothesis, then do a single experiment, and then gather and organise the data from that experiment. The data is then analysed to build a model, which makes a prediction. The predictions are published, which motivates others to do more experiments, and this cycle of the scientific method is repeated to generate more data and new predictions, until there is consensus on the predictions.

The biggest breakthrough in biology took place after the human genome project ended in 2003, where biologists realised that humans have the same number of genes as a worm, motivating biologists to recognise that the complexity of an organism is not a function of the number of genes, but can only be understood by interconnecting the complexity of molecular pathways derived from multiple experiments, and recognising the need to interconnect molecular pathway information, so we move away from what is called reductionist biology to a systems biology. Reductionist biologists are like guys looking at pieces of an elephant (just the trunk, the ears, tusk, and so on) and each making assumptions on what they think it is, leading them often to erroneous and biased conclusions. Systems biologists attempt to look at the connections across the whole organism, and put it all together to get a more accurate, unbiased view. So, that’s what we did across the series of four papers, step-by-step:

Paper I: Aggregates over 11,000 papers to identify the fundamental molecular pathways of C1 Metabolism (published in Agricultural Sciences).

Paper II: Interconnects the molecular pathways of C1 Metabolism, in normal condition, using a systems approach. This paper shows that formaldehyde is detoxified, and glutathione is maintained in normal plants (published in American Journal of Plant Sciences).

Paper III: Identifies the molecular pathways of oxidative stress in plants, connects them and integrates them with the C1 Metabolism system of Paper II. Oxidative stress occurs when plants experience “stress” such as a drought or weather changes. This integration shows that under stress, plants deplete glutathione, resulting in the accumulation of formaldehyde (published in American Journal of Plant Sciences).

Paper IV: Shows that GM soy is different from non-GM soy based on the differences in the levels of glutathione and formaldehyde. We found in the GM soy, the Roundup Ready version, five molecules are disturbed, based on data from actual wet lab experiments. This molecular disturbance causes oxidative stress, which (as shown from Paper III) results in C1 Metabolism (from Paper I and II) being disturbed, resulting in glutathione being depleted, and formaldehyde accumulating (published in Agricultural Sciences).