Thursday, September 30, 2010

The CWG Syndrome in the Bt Brinjal: Part II. The Indian Trans-Academy Game

In Part I, I had semi-seriously discussed the criticism of the way the Common Wealth Games was being run. I called it the CWG syndrome which has implications of the functioning in a hierarchical society that could lead to self-defeating decisions that betrays society’s (country’s) interests.

In a hierarchical society like that of the monkeys (from which we, as humans, are not far away from although we may not know in which direction on the evolution line) the monkey king is not very stable on his throne. The people who bow most before the king are those that resent the king most. Their main interest is to dethrone.

Kalmadi had to be the monkey king to be dethroned.

The screeching anchors of our television stations got down to the lowest level of investigations that they seem to be at home with. They literally focused on the same filth and kept showing the same “horror” images without any comment on how general it is and what the redeeming features could have been.

As viewers, we are not shocked by that kind of filth that is mass-communicated on our TV stations. Instead, we look forward to more filth that will sock us more. Because it is pure gossip and malice, we accept whatever is said for our own time-pass malicious gossip.

A far more dangerous affair is the attitude of Indian media (and our indifference) on the responsibility of Indian Scientists to the Bt brinjal problem. The outcome of this problem involves important decision-making processes of the science academies of India. Messing up on this one will affect the way we would like to live.

Here there may not be evidence for a monkey king as yet. But the monkey culture, with the CWG syndrome, could prevail.

This blog and the one following this is aimed at showing an interest in the problem and at expressing a studied opinion of a serious kind.

What stirred up my interest is the notice I got recently from one science academy --- the only one which mistakenly made me a member --- which has been founded by an Indian Nobel Scientist of whom I am proud of.

The notice I got by email was about an “Inter-academy report on GM crops” in which they present “… a report on GM crops … at the request of Shri Jairam Ramesh, Minister of Environment & Forests and Dr. K. Kasturirangan, Member of Planning Commission. The way the document has been prepared is detailed in the report itself. The report also contains an appraisal of the issue and a set of recommendations. We hope that this document would be useful to decision makers.” The report was written after “… a brain storming meeting was held at INSA on June 1, which was attended by a cross section of Fellows and nominees of the Academies. “ It was not a brainstorming involving only specialists on GM crops!

For a very happy and welcome change, the involved union minister, Jairam Ramesh, has shown more than his share of enthusiasm in trying to frame a government policy. If anything he can only be said to have been over sincere and gullible in trusting the Indian scientist’s word in a matter which is indeed very complex.

He did meet a range of people (Fig 1, taken from the report which is on the net) who were evidently not back scratchers, except for some obvious front-benchers. In the top centre inset of Fig 1 (click to expand) the minister and the obvious intellectual are sitting with a posture indicating that they are paying close attention. The person on the minister’s right has thick gold rings on his right hand, clutches a ready mobile with his right hand and has a wary look that matches that of a powerful personal assistant to somebody or something far more powerful.

Simply going by a head count of the people seemingly opposed to the scheme the Bt brinjal scheme should have folded up. But because the hierarchical society is in place, the voice of the upper monkey class will prevail because of their short-lived crocodile concerns for the poor.

The CWG had definite deadlines to meet. It is easy to focus and communicate on the goings-on by the way anticipated deadlines have been met or not and the way international standards have not been met or been met. There is no complex scientific or management issues involved in the CWG games.

The Bt brinjal problem is a far more serious one. One is afraid that the CWG syndrome of mismanagement of objectives and covering-up of filth would have far more serious consequences when extended to our food and agriculture.

For one, Sharad Pawar is now the minister of food and agriculture. He makes the decisions. He has made up his mind. “After the environment ministry’s approval, the agriculture ministry will have no hesitation to extend its support. So far such a clearance for Bt Brinjal from the environment ministry is awaited.” What Pawar forgets is that as an agricultural minister he must decide what the outcome of an agricultural policy on a particular crop has on other food crops. He has to worry about it more than the environment ministry. Further, he has to worry about the way the Bt brinjal policy impacts the attitudes of other countries in buying our farm products because of their own environmental concerns.

Pawar had some basis for his confidence in getting an approval from the environment ministry. Their scheme for consideration has only provisions for approval (Fig 2, click to expand) even though the double-headed arrows have sufficient ambiguity. The all-important nodal point in the scheme is the GEAC (Genetic Engineering Approvals Committee) which is again pre-disposed towards approvals. However, GEAC decided to pass the buck onto the Government (capital G as in God) since the “… decision of the GEAC has very important policy implication at the national level…” The GEAC happens to be located in the ministry of Environment and Forests (MEF), so that the concerned minister (Jairam Ramesh) had to take it up even if it is not clear how a GEAC in an MEF would have the required GE expertise to make a decision unless it is fed by a pre-disposed GE lobby with approval written all over it.

The GEAC report may be compared with a UNEP-ILO-WHO report more than a decade earlier (1999) on Microbial Pest Control Agent, BACILLUS THURINGIENSIS. That was what it should have been, just a report. This report was prepared by Task group members and observers from Departments of Biology, Structure and Function, Institute of Terrestrial Ecology, Département des Biotechnologies, Microbiological Institute, Department of Veterinary Pathobiology, Chemical and Agricultural Products, Animal Health Products, and Centre for Pesticide Safety from various countries. It started in 1993 and the report was published in 1999. There is no ‘A’ for approval in this report!

This is why, perhaps, the MEF wanted a trans-academy report preferably without a pre-determined ‘A-for-approval on it.

The academies of science and engineering are now sustained by people who shine best in borrowed protocols. One of these protocols is to advise the government as quickly (and, consequently, as vaguely) as they can. No wonder there is a multiplication of academies in our version of the monkey culture! There are six varieties of national academies of science and engineering. It could be a world record for any country. Knowing our record on population control, this should not surprise us at all.

There is all the marks of disinterestedness in the trans-academy report perhaps because the dadas (big daddies) in the field seemed to be already committed favourably to the Bt-ology that they had submitted earlier to the minister. The A(pproval)-disease persisted. These dadas were probably annoyed that they had to go through the justification process again.

Out of the ~ 60,000 words in the INTER-ACADEMY REPORT ON GM CROPS there was less than 9000 words on Bt Brinjal specifically and hardly any commitment to issues at hand. The report could have been written almost by anybody with an ability to download from the net. The first lines of the paragraphs in the section on Bt brinjal are
Brinjal (Solanum melongena L.), commonly known as eggplant, aubergine or guinea squash, is an important vegetable crop of tropical and temperate parts of the world. … (900 words)
Brinjal has been cultivated for the last 4,000 years in India. … (500 words)
Brinjal cultivars as well as modern varieties have been shown to be susceptible to a variety of stress conditions, which limits crop productivity significantly. … According to a study by Indian Chemical Industry (2007), brinjal is the second largest vegetable crop after Chillies that is sprayed with insecticide. (1700 words)
Early efforts were made at IARI to develop transgenic brinjal expressing insecticidal protein (Cry1Ab) of Bt way back in mid 1990s … . Multi-location research trials and Large scale trials (2004-2008) conducted by Mahyco, … insecticide requirement for Bt brinjal hybrids was on average 80% less than that for the non-Bt counterpart, which translated into a 42% reduction in total insecticide usage. ... (1500 words)
Thus, in brinjal cultivation, there is an urgent need to reduce dependence on pesticides … (1200 word)
Bt brinjal being a transgenic food crop requires environmental clearance under Rules 8 … (1200 words)
Bt brinjal ‘Event EE-1’ has been subjected to a rigorous biosafety regulatory process … (~ 600 words)
Two expert committees, Expert Committees I and II … confirm the safety and utility of Bt brinjal, especially considering the fact that his gene has been in use globally for over 15 years (~ 1100 words)

There is nothing in the trans-academy or report that improves (except for the inclusion of Bt brinjal) upon the UNEP-ILO-WHO report written a decade earlier.

Compared to the effort of the CWG in planning and organizing (not executing) the games, there has been so little evidence for a professional pride that comes from completing a job well done in this trans-academy report.

I try to distance myself from Indian Scientists, especially those of an administrative bent of mind. To our mutual benefits, I am sure. I cannot understand why a good scientist should take time out of his science to become an administrator, the necessary politics of which they should really know little about. However, as one listed in (not belonging to the) “scientist” community of India, I am more than a little concerned about the adverse impact such an insensistively (sorry, Mr. Chips, the word 'insensitively' is not even in Webster) written report could have on future generations.

The “trans-academy” scientists have now the infection arising from bacteria of the Bt kind and are showing all signs of the CWG syndrome --- a coordinated drive to patch-work and push before deadlines set by the tenure of a minister, and the profit schemes of multinationals. This makes them purposefully oblivious of sincere concerns of the diminishing tribe of ordinary people who speak their mind as they see it.

I am writing this blog and the next one with the intention of making comments that I think should be made. I am no expert.

I have exercised caution and have tried to make in it as apolitical statements as one can consciously. After writing the major part of the blog, the newspapers inform me that Jairam Ramesh (Jai Ram, thank you Ram) has rubbished the trans-academy report. This is an welcome Ram Ram in this Ayodhya times.

I have garnered little bits of information from the internet more than the trivial kind that decision making ministers such as Sharad Pawar or corporate honchos such as Kiran Shah Majumdar usually cite while announcing their decisions. This is presented in the next blog

The basic information that I can produce now is the following.

Bt is an acronym for the bacteria bacillus thuringiensis.

Now! Do we know what it is all about?

The first points are simple, but fundamental and is easily found in the net. The most important point about Bt that could allow us not to show concern is that it is found naturally in soil that has been farmed successfully over thousands of years. It has also been used as sprays as "microbial insecticide" before Bt GMO food became known. Indeed it is used to coat seed for preservation against insecticides for long times.

Bt produces intracellular protein crystals toxic to a wide number of insect larvae. Its toxicity depends on it breaking down of the crystal protein on digestion. Insects have alkaline stomach digestive juices while mammals like us have acidic juices so that one assumes that the Bt toxins would not affect humans of the normal healthy otherwise un-medicated kind.

So! Why is this concern now?

For a novice in the area, the possible problems associated with the use of Bacillus thurigiensis in genetically modified foods are many. One would have liked to have seen some definite laws and rules which allow one to judge inputs and outcomes like stoichiometry in chemistry or equations of motion in physics. Unfortunately there are so many ifs and buts in biotechnology that one can only say “maybe” or “hopefully” after giving the matter deep consideration from a non-financial angle.

I have tried to give some of the points that could cause concern, They, I think, require definite responses from experts of the academic kind. They could have been asked by self-appointed experts of the genuine kind. My description in this and the next blog is not exhaustive nor is it expected to be given my background. It is any case another Bt acronym, BTN (better than nothing). Its also a bit BTTAR (better than trans academy report) but then that’s trivial.

One requires a slightly higher level of knowledge to make comments on the Trans-Academy report. At a somewhat minimally higher level (computer-generated meanings or quotations in brackets are given in italics) Bacillus thuringiensis (Bt) is a facultative (in biology it means “able to live or take place under a range of external conditions”) anaerobic (not requiring oxygen for metabolism), Gram-positive (describes bacteria that retain the color of a gentian violet stain of crystal violet when subjected to Gram's method of classifying bacteria; Gram-positive bacteria have only one membrane layer instead of the usual two in Gram-negative bacteria) bacterium that forms characteristic protein inclusions adjacent to the endospore (the inner layer of the wall of a spore). Bt is a member of the group Bacillus cereus (Bc) from which it is genetically indistinguishable except for the genes coding for insecticidal toxins (poison produced by a living organism that accumulates in the body and causes it harm) that is present on plasmids (small circles of DNA that replicates itself independently of chromosomal DNA, especially in the cells of bacteria. Plasmids often contain genes for drug resistance and are used in genetic engineering, since they can be transmitted between bacteria of the same and different species) in the former.

ONE HAS TO WORRY ABOUT THE ENTIRE BACILLUS CEREUS SPECIES OF BACTERIA AS WELL AS DETAILS OF GENETIC ENGINEERING INVOLVED IF ONE IS TO MAKE A SAFETY ASSESSMENT THAT IS OF USE TO A CONCERNED MINISTER WHO WOULD NOT WANT TO BE A MONKEY KING.

In a review in 1998 by Schnepf et al it was stated “We are not aware of any critical experiments directed towards understanding bacterial toxin gene expression within the gut of a susceptible pest.” Later in 2008 in an article on Rules of Engagement: Interspecies Interactions that Regulate Microbial Communities by Little et al it is written in the abstract “little is known about their structure and function, and predictive modeling is limited by a dearth of comprehensive ecological principles that describe microbial community processes.

From the above uncertainties it could seem Bt technology is a case of fools rushing in (in generation time scales) where angels fear to tread. There seems to be little evidence to the contrary.

The genomic data so far available does not reveal “ … the genetic relationships of the species themselves …” even if there “… is a very clear division of the virulence (the quality of being extremely poisonous, infectious, or damaging, or the extent to which a disease or toxin possesses this quality) characteristics and the known virulence genes.” It has also been pointed out that “… genomic relationship between the B. thuringiensis strains is not necessarily defined only by their toxic specificity, but by a series of attributes, such as cry gene content, crystal morphology, and plasmid pattern.” Distinguishing unequivocally between the various phenetic (a system of biological classification based on overall similarities between organisms) and genetic traits is a problem that persists.

No assessment of Bt (Bacillus thuringeinsis) can be considered complete unless unequivocal answers are obtained for some niggling doubts as in some of the above questions have been conveniently answered, The literature has its doubts. The MEF need not feel embarrassed if they have their own doubts and are unconvinced.

So! Why should there not be a concern now?!!

The chief well known concern is that for the first time, there will be mass use of a trans-genic (A transgenic species is an organism that has had part of another organism's DNA transferred into it using recombinant DNA technology.) manipulation when a section of this insecticide will be transplanted into the seed of a plant that we eat. That is also not too much of an unmanageable thing.

Perhaps a little more detail about the way the Bt bacteria acts could provide some more food for introspection and revision. The Bt bacteria, like other bacteria form spores (dormant resistant forms taken by some bacteria in response to adverse conditions) during the dormant stage of the bacterial life cycle especially when it is under environmental stress. Unlike many other bacteria, the spores of Bt are accompanied by protein crystals which are the toxic components of Bt. When the insect’s guts are infested by Bt, the crystal dissolves in the guts. The high pH and reducing environment in the insect midgut helps in dissolving the crystal into prototoxin subunits of ~130,000-Da (Dalton ~ the weight of one hydrogen atom). The prototoxin is then digested by pancreatic (from pancreas : a large elongated glandular organ lying near the stomach. It secretes juices into the small intestine and the hormones insulin, glucagon, and somatostatin into the bloodstream) trypsin-like proteases (enzymes that break down proteins and peptides by catalyzing the hydrolysis of peptide bonds) to form the activated toxin which is half the size of the prototoxin and is resistant to further trypsin digestion. This trypsin-resistant core binds to specific receptors on the insect midgut (the central section of the digestive tract in which the processes of digestion and absorption take place) and forms a pore by the lysis (destruction of cells by disruption of the bounding membrane, allowing the cell contents to escape) of epithelial (describes tissue that forms a thin protective layer on exposed bodily surfaces and forms the lining of internal cavities, ducts, and organs) cells in the midgut. These membranes maintain the gut’s ion balance. Because of this midgut disruption the ion balance is destroyed; the insect is paralyzed and soon dies. This is the direct action.The Bacillus thuringiensis germinate and grow in the midgut of the dead insect. When the direct action fails, the Bt continues with its vegetative growth, when spores germinate to make more spores. This infects the whole body and kills the insect.

There is a line in the UNEP-ILO-WHO report which says “However, it should be noted that vegetative Bt has the potential for the production of Bc-like toxins, the significance of which as a cause of human disease is not known.”

Sticking to the point of crystallization under stress it should be mentioned that the Nobel prize for chemistry on the crystal structure of ribonuclease was partly possible because large crystals are obtained from organisms (bacteria) living in extremely hot or saline conditions. Living organisms seem to crystallize under stress. In the case of the Bt bacteria the crystals yield the poisonous insecticidal toxins.

The production of crystals is not so for some insects such as butterflies themselves. For them crystals add to their colours. I knew about it first from the laboratory in Bologna headed by Carlo Taliani. The laboratory was taking its first steps then in nano-structured materials for photonics and butterfly wings were being studied in Fabio Biscarini’s group. Butterfly wings have nano structures with sizes close to the wavelength of light; they act as diffraction gratings allowing light with a single color to be reflected depending on the crystal size. A Yale team found “… that the outer membranes of the butterfly wing scale cells grow and fold into the interior of the cells. The membranes then form a double gyroid — or two, mirror-image networks shaped by the outer and inner cell membranes. … Chitin is then deposited in the outer gyroid to create a single solid crystal. The cell then dies, leaving behind the crystal nanostructures on the butterfly wing.

Butterfly crystals is certainly little more to be cherished than the Bt protein crystals, which serve their own purpose in a larger ecosystem of the Gaya kind.

An article by Schnepf et al on Bacillus thuringiensis and Its Pesticidal Crystal Proteins in Microbiol Mol Biol Rev. 1998 that has been cited more than 1300 times has statements such as “… mutations in different … regions, sometimes involving the same type of amino acid residue, can have a different effect on binding. … same mutation in a toxin can have quite different results on different insects.
… a lack of correlation between receptor binding affinity and insecticidal activity—are now known
… while … the affinity of Cry1Ab was not directly related to toxin activity, they did observe a direct correlation between the irreversible binding rate and toxicity.
Different toxins may have the same amino acid sequence in the loops of domain II (e.g., Cry1Ab and Cry1Ac) yet bind to different receptors”.

Such statements should have alerted the scientific academies to dangers of genetic manipulations and (at least, in my opinion) extreme caution should have been advised. According to a report by Prof. Gilles-Eric Séralini (commissioned by GreenPeace India) of Committee for Independent Research and Information on Genetic Engineering (CRIIGEN), France, crystal protein for Bt brinjal is a chimeric transgene that is modified to produce a chimeric insecticide toxin containing Cry1ab and Cry1Ac sequences. Earlier, it has always been referred to as Cry1Ac (a protein) in every regulatory document. This chimeric toxin was not used for toxicity tests on target and non-target insects but an improper Cry1Ac toxin was used because this control was easier.

I think Séralini’s point is perfectly valid.

Professor Padmanabhan (a scientist I regard highly) writes in response that the chimeric transgene is 99.4% identical to cry1Ac gene and the 0.6% difference is due to replacement of one amino-acid in the entire sequence. Padmnabhan further adds a personal note by saying that “... every parameter assessed from gene flow in non-target organisms to duration of the animal experimentation studies has been questioned, revealing a mind set to oppose anyway.”

Seralini asserts as a response to this defence about the chimeric transgene in capital that THIS TOXIN IS NOT EXACTLY CRY1Ac AND SHOULD BE REASSESSED PROPERLY, THIS IS CRUCIAL. I will agree with Seralini’s statement that “… only one amino-acid change in a protein may have a folding and a pathological incidence, like in pathogenic prion or several genetic diseases.” The activity of a protein is determined, I learn, more by the nature of the folded state that is very sensitively dependent on the actual sequence and not in the similarity of the sequence.

As Seralini says (in a bad translation of his French, I am sure) : “We are not in an approximate proof of a research but in common life potentially feeding billions of humans and animals!!”. I am sure we know what Seralini actually said.

Pushpa Bhargava would say on the same point “… they said, there is a 99.4% homology to Cry 1 Ac, so they are calling it Cry 1 Ac, only 1 amino acid is different. Now if it is 99.4% homology then 6 amino acids have to be different. It doesn't need too much knowledge of biochemistry to understand that.” Bhargava would add “So they are telling lie after lie everywhere.”

Objectivity is lost in such subjective innuendos. Scientific subterfuge of the CWG kind is revealed. Pawar adds to such malice-mongering by criticizing the critics of Bt brinjal with “India imports 40 per cent of its edible oil requirement and that is largely produced through genetically-modified soyabean. It’s quite ironical that when NGOs from the edible oil producing countries are quiet on this issue, they are providing feed to the NGOs in the country against Bt Brinjal.

The point to note here is that if Bt Brinjal is in cold storage, why is Bt soya oil not? Instead the Government (read Pawar) has lifted all restrictions such as GM certification for import of soya oil from Brazil and Argentina where there is no restriction on the use of the GM seeds. Where was the Minister for Environment and Forests? It is not sufficient to say that “… oil extracted from GM soya seeds does not contain traces of proteins which are harmful to human beings.

Once we go through the above, the possible ill effects of the CWG syndrome on our life itself start bothering me.

We don’t have to know who said: “Who can believe that a new genetically engineered fruit producing an uncharacterized insecticide may be given to millions without being tested more than three months on rats?

Only a monkey king would be allowed to give such a fruit?.

Will we as scientists act responsibly and make a good and competent world class statement that is clean at every nook and corner? Or will we , like the CWG, be monkeys (only from a monkey culture point of view without any disrespect intended either to the monkeys or their descendants) comfortable in the hierarchical culture that will throw a blame on some monkey king?

The trans-academy report has all the signature of doing so. Jairam Ramesh deserves a little better.

The Bt problem is a complex one in which many parameters are involved. There are many things that we require worrying about, even if we may think we have other future happier lives. The damage that may be caused could end the way we like to live forever. We can safely come to this conclusion going by the way we have handled global warming (including taking credit for Pachuri’s Nobel), dengue epidemic, city planning and so on.

With Bt brinjal in the air we can’t look at a brinjal in the eye anymore.

Intensive versus Extensive Knowledge

It does not mean that being an expert in a small aspect, even if it is a fundamentally important aspect, implies that one can apply this intensive expertise correctly to more complex extensive systems.

One may say, like Weisskopf did “… intensive research goes for the fundamental laws, extensive research goes for the explanation of phenomena in terms of known fundamental laws.” To this Nobel Laureate extraordinaire, P. W. Anderson, puts the rejoinder (in More than Matter, Science, 177, 393, before his Nobel Prize) “… The ability to reduce everything to simple fundamental laws does not imply the ability to start from those laws and reconstruct the universe. In fact, the more the elementary particle physicists tell us about the nature of the fundamental laws, the less relevance they seem to have to the very real problems of the rest of science, much less to those of society.

Anderson was cautioning against the intensive-extensive reductionist approach. It is perhaps pertinent in the context of living systems that he starts this article with “The workings of our minds and bodies, and of all the animate or inanimate matter of which we have any detailed knowledge, are assumed to be controlled by the same set of fundamental laws, which except under certain extreme conditions we feel we know pretty well.” The difficulty is that we acknowledge this part as scientists but hesitate to acknowledge exceptions; this is so especially if one is a professional scientist or environmentalist.

The title of a report containing the words "trans-academy report" sounds as if it is a learned report written by experts with good intensive knowledge.

The minister finds it not so, as any interested person should find.

When one is considering the Bt problem, one should not camouflage the social concerns by putting on a mask of high-sounding technical cacophony in place of extensive knowledge.

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