The graph above shows the relative production of these major US row crops comparing the years 1993-1995 (just prior to the introduction of biotechnology enhanced crops) and 2008-10 (the most recent available data which covers a a span which comes 12-15 years after biotech.  Soybean production has expanded 47% in this time-frame while corn is up 58% (far more than the quantity now being diverted for biofuel).  Both of those crops are predominantly planted to “GMO” varieties, while the various segments of the wheat crop remain non-GMO.  Until 2004 it looked as if North American growers would also get to plant biotech wheat, but a vigorous campaign led by Greenpeace succeeded in blocking the technology.  Many major European and Japanese grain buyers were concerned about potential consumer push-back (based on Greenpeace efforts), so they made a coordinated threat to boycott all North American wheat exports if any commercial GMO wheat was planted in the US or Canada.  This was based on the “precautionary principle.”

The wheat industry, particularly the Canadian Wheat Board, asked Monsanto and Syngenta not to go ahead with their plans to sell the improved wheats, and so those often vilified companies put their programs on the shelf at the request of their customer base.  GreenPeace then declared Victory.

The Traits That Didn’t Happen

Monsanto had been developing a “Roundup Ready” version of wheat which would have helped the wheat growers who have grass weed issues.  It was also shown to increase yields and it would have aided in conversion to no-till, and  increased genetic purity for specialty uses.  Syngenta was developing wheat with resistance to a disease called Fusarium Head Scab.  That particular fungus is difficult to control with fungicide sprays, but it can severely hurt yields, and it can diminish the value of what grain is harvested by contaminating it with the mycotoxin, DON or “vomitoxin.”  A major reason that farmers include less wheat in their crop rotations than would be optimal is because of the risks associated with this disease.  The fact that these traits would have increased grower income and reduced a dangerous toxin in the food supply were listed in the Greenpeace internal literature of the day, not as “pros,” but as “campaigning challenges.”

What The Farmers Thought

In the late 1990s, I had the opportunity to sit down with dozens of wheat farmers in Kansas, North Dakota, Minnesota, Indiana and Kentucky to talk about these coming traits.  These growers had experience with GMO soy and corn and were very much looking forward to these new products.  I was testing various “business models” for how the traits would be made available because, like soybeans, much of the wheat crop is planted with “Farmer Saved Seed.”

With non-hybrid crops, farmers have the option to simply save some of their previous grain harvest to use as seed.  Typically they buy new, “certified” seed every few years.  With Soybeans, Monsanto took the risky and controversial step of getting growers to sign a “technology agreement” in which they promised not to save the biotech seed but rather to purchase it new every year.  I, and many in the industry doubted that growers would be willing to do this or that the system could be enforced well enough to prevent free-loaders.  After a few, high-profile lawsuits, the new system was widely accepted and no mainstream soybean farmer even questions it today.

Much More Was Lost Beyond The Traits

Before biotech, the soybean seed industry existed mainly as a “price of doing business” for corn seed companies.  Much of the breeding advancement was still happening in Universities (though with precarious funding).  When soybeans became an every-year purchase, the overall investment in the improvement of that crop went up dramatically.  This helped extend the range of the crop into colder Northern regions and dryer Western areas.  We are also now beginning to see the pay-off of the investment in genomics and Marker Assisted Selection – biotechnology enabled updates on “traditional breeding.”  Roundup Ready soybeans were not a “yield trait” as such, but they were far more convenient for busy farmers and easier to “no-till” farm.  So now both soybeans and corn had become much more attractive options for farmers, and in many regions the “loser” has been wheat.

The Wheat That Was Not To Be

The expansion of corn and soy production in the first chart represents a combination of factors.  Growers planted more of their land to those crops, often using their better fields.  They often grew these crops with greater inputs of fertilizer, water because the economic risk was smaller.  In most areas there was a distinct change in the long term trends for these crops that corresponds to the pre-biotech era (before 1996) and the post-biotech era (after 1996).

One way to calculate the real “cost” of the Greenpeace wheat victory is to extrapolate what would have been the production of wheat if the earlier trend lines are extrapolated to 2010.  To do this I took the data from the USDA-NASS at the Crop Reporting District level (usually 9 districts per state) from the years 1984 to 2010.  This allowed me to fit lines for each crop/district covering the Pre-biotech years of 1984-1995 and then a similar 12 year time frame from 1999-2010 as a Post-biotech era.  By comparing what level of production each trend for predicted for 2010, the impact of the non-biotech nature of wheat in a biotech world could be estimated.  Example trend comparisons are shown below for single district examples of corn, soybeans and winter wheat.  Finally those differences are summed for all the districts where data is available over the 27-year time span (238 for corn, 173 for soybeans, 191 for winter wheat, 39 for spring wheat and 6 for durum wheat).

An example of one of many areas where corn productivity increased faster after the introduction of biotechnology through a combination of more acreage being planted and yield progress increasing.

A very typical example of an area where farmers began to plant a great deal more soy when it was improved through biotechnology.

An example of an area where wheat planting and intensity dropped in the biotech era relative to earlier trends.

Many Variables but Major Overall Outcomes

Exactly how trends changed for each crop and region varied widely, but in very few cases did the pre-biotech trend continue unchanged. For every crop some areas were up and some down, but the net effect was an overall shrinkage of US wheat production at a time when global wheat demand is constantly increasing.  The chart below shows that the biotechnology enhanced crop options saw substantial production increases vs earlier trends, + 437 million bushels/year for soy and a whopping + 4.03 billion bushels for corn. Winter wheat overall declined slower than it had prior to biotechnology for a net trend change of +35 million bushels.  Spring wheat, which was much more in the geographic path and time of year of the soy and corn “locomotives,” lost 315 million bushels of “potential” production.

Would Things Have Been Different With Biotech Wheat?

Would that have been different if Greenpeace didn’t “win?”  It is difficult to know because there were other factors in that time frame such as the Freedom to Farm Act of 1996 which changed the nature of government crop subsidies and set-aside programs.  Delays in biotech trait approvals for import to the EU and Japan altered global market dynamics as did the wide-spread pirating of Roundup Ready soybeans by South American farmers.

Would Monsanto and Syngenta have cross-licensed their wheat traits to allow an attractive package for farmers?  Would the transition away from a “saved seed” market for wheat have offset the declining public breeding support which continues even today?  It is impossible to know, but the wheat industry has now decided that they don’t want to be denied a technological advantage again.  National wheat grower associations in the US, Canada and Australia agreed to a simultaneous launch of any future GMO wheat so that the Europeans and Japanese could not blackmail them again.  Even so, it is likely to be at least a decade until that happens because the other thing that was lost in 2004 was the continuous years of breeding effort that it takes to incorporate a biotech trait in the complex world of wheat (winter, spring, red, white, hard, soft…..).

How Much Lost Wheat Is That?

The theoretical 315 million bushels of wheat not being produced as of 2010 represents 8.6 million metric tons (in the units of global trade).  That is roughly equivalent to the crop in each of the wheat producing countries Argentina, Egypt, or Italy.  It is more than the total wheat imports that go to each of these major, net wheat importing countries (Japan 5.8MMt, Algeria 6.9MMt, Egypt 8.3MMt, Italy 5.4 MMt, Indonesia 4.5 MMt, Brazil 6 MMt, Iran 5.2 MMt).

Putting This In The Context Of The Current Global Food Price Spike

We just finished seeing a severe spike in prices on the global food trade scene in 2007/8 and a new spike is underway and appears to be continuing - particularly for cereals like wheat which is now within 3% of the previous record (see chart below).  India is considering a wheat export ban this year.  Global wheat demand is expected to double by 2050.

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Then, just to add insult to injury, the US congress cut funding for the Global Wheat Genomics Center at Kansas State .  That happens as a new strain of the dreaded Wheat Stem Rust pathogen is threatening wheat crops in more countries every year.

We probably won’t ever be able to make up for what has been lost for one of the world’s most important human food crops.  The catch-up on biotechnology will not be in time to help many poor people survive or to prevent the political instability implications of food shortages.  These are the true “Costs of Precaution,” but they will not be borne by the Greenpeace activists in rich nations.  These very real costs will be borne by poor families in places where wheat can’t be successfully grown.  Greenpeace was happy to take credit for stopping this technology.  I wonder if they are willing to take credit for these consequences.

Norm Borlaug said:  ”If you desire peace, cultivate justice, but at the same time cultivate the fields to produce more bread; otherwise there will be no peace.”

I’d go with Norm’s “Peace” agenda, not that of Greenpeace.

What substantial equivalence can do is give us a starting point.

We know that there is variation in amounts and types of proteins and metabolites, gene expression, and other parameters from variety to variety, from environment to environment, and from plant to plant. For example, if I use a microarray to find similarly and differently expressed genes in two genetically identical plants grown in slightly different environments, such as different temperatures, I will find some genes that have significantly different expression. Similarly, plants of different varieties grown in the same environment will have different gene expression profiles and even two identical plants in the same environment will have some differences.

The first step in a comparative assessment is to test and compare the genetically engineered variety to a genetically similar variety that doesn’t have the trans- or cis-gene. Tests can include gene expression, metabolic profiles, feeding studies, and more. If differences aren’t found in a reasonably wide panel of tests, then the genetically engineered variety can be called substantially equivalent to the genetically similar variety.

If differences are found, two questions need to be asked. First, does the change fall within the natural variation found among different varieties of the same species? For example, some varieties of corn with the Bt gene have been found to contain more lignin than genetically similar varieties without the Bt gene, but the amount of lignin falls within the normal range of lignin content for corn plants. Second, is there a scientific explanation for each change? For example, a transgene that causes higher calcium uptake from the soil is expected to result in higher amounts of calcium.

If there is a change that doesn’t fall within the natural variation for that species, especially if there isn’t an obvious scientific explanation for the change, then more testing needs to be done to determine safety with regard to environment and human health.

What substantial equivalence does not do is give license to make assumptions. The process of genetic engineering does have the potential to cause unintended changes in the resulting organism. That’s why a comparative assessment needs to be conducted before a plant, animal or microbe that has been genetically engineered can be deemed substantially equivalent to a non-genetically engineered but genetically similar organism.

One major problem with determining substantial equivalence is that it is hard to know which tests are appropriate. This problem has improved greatly as “omics” type tests have become more widely used. Tests for macronutrient content could be expected to miss small but significant changes but wide screens for changes in the transcriptome, proteome, or metabolome could be expected to find those small changes.

The metabolome seems to hold the most promise because it effectively tests the end product of gene expression and enzyme activity. Owen Hoekenga presented metabolomics in an excellent 2008 paper as a method that could be used to help determine substantial equivalence.

Hoekenga OA (2008). Using metabolomics to estimate unintended effects in transgenic crop plants: problems, promises, and opportunities. Journal of biomolecular techniques : JBT, 19 (3), 159-66 PMID: 19137102.

Abstract:  Transgenic crops are widespread in some countries and sectors of the agro-economy, but are also highly contentious. Proponents of transgenic crop improvement often cite the “substantial equivalence” of transgenic crops to the their nontransgenic parents and sibling varieties. Opponents of transgenic crop improvement dismiss the substantial equivalence standard as being without statistical basis and emphasize the possible unintended effects to food quality and composition due to genetic transformation. Systems biology approaches should help consumers, regulators, and other stakeholders make better decisions regarding transgenic crop improvement by characterizing the composition of conventional and transgenically improved crop species and products. In particular, metabolomic profiling via mass spectrometry and nuclear magnetic resonance can make broad and deep assessments of food quality and content. The metabolome observed in a transgenic variety can then be assessed relative to the consumer and regulator accepted phenotypic range observed among conventional varieties. I briefly discuss both targeted (closed architecture) and nontargeted (open architecture) metabolomics with respect to the transgenic crop debate and highlight several challenges to the field. While most experimental examples come from tomato (Solanum lycoperiscum), analytical methods from all of systems biology are discussed.

“Omics” studies that have been conducted on the substantial equivalence of genetically engineered plants to their non-genetically engineered counterparts have found that there are differences but those differences fall within the range of differences found within different varieties of the same species. Below are some such studies.

Kogel KH, Voll LM, Schäfer P, Jansen C, Wu Y, Langen G, Imani J, Hofmann J, Schmiedl A, Sonnewald S, von Wettstein D, Cook RJ, & Sonnewald U (2010). Transcriptome and metabolome profiling of field-grown transgenic barley lack induced differences but show cultivar-specific variances. PNAS, 107 (14), 6198-203 PMID: 20308540

Baker JM, Hawkins ND, Ward JL, Lovegrove A, Napier JA, Shewry PR, & Beale MH (2006). A metabolomic study of substantial equivalence of field-grown genetically modified wheat. Plant biotechnology journal, 4 (4), 381-92 PMID: 17177804

Coll A, Nadal A, Collado R, Capellades G, Messeguer J, Melé E, Palaudelmàs M, & Pla M (2009). Gene expression profiles of MON810 and comparable non-GM maize varieties cultured in the field are more similar than are those of conventional lines. Transgenic research, 18 (5), 801-8 PMID: 19396622

Lehesranta SJ, Davies HV, Shepherd LV, Nunan N, McNicol JW, Auriola S, Koistinen KM, Suomalainen S, Kokko HI, & Kärenlampi SO (2005). Comparison of tuber proteomes of potato varieties, landraces, and genetically modified lines. Plant physiology, 138 (3), 1690-9 PMID: 15951487

Gregersen PL, Brinch-Pedersen H, & Holm PB (2005). A microarray-based comparative analysis of gene expression profiles during grain development in transgenic and wild type wheat. Transgenic research, 14 (6), 887-905 PMID: 16315094

Another problem with comparative assessments is that each genetically engineered trait may require different types of testing, depending on what the trait is. For example, a drought tolerant crop may need to be tested under wet and dry conditions while a nutritional trait may not need to be tested under different environmental conditions.

An alternative view to substantial equivalence and comparative assessment is the precautionary principle. Instead of starting  by looking for differences between a genetically engineered organism and a non-genetically engineered but genetically similar organism as we find in a comparative assessment, the precautionary principle requires us to start with the assumption that there are differences and enough studies must be conducted to determine that something is completely safe before release. The precautionary principle is an important enough idea that it deserves its own post, but I will say here that it has some problems, the biggest of which is that the amount of testing that is deemed to be “enough” is rarely defined, so the amount of tests that “need” to be conducted can always be made larger, which may actually be the point.

She felt terrible, with a horrible pain in her gut that cut like a knife, and nausea and fever to match. Usually stoic in the face of pain, my daughter was doubled over and gasping.

When we took her to the hospital, the doctor took one look at her and immediately ordered a scan. Within hours she was in the operating room to have her ruptured appendix removed.  After the operation, the surgeon showed us pictures of the process, including a glossy photo of the inflamed appendix and the staple he had used to close off the end from which it had been removed.  Almost immediately after surgery, my daughter’s fever diminished. Her post-surgical pain was minimal compared to the searing pain that brought us to the hospital in the first place. As I write this, she is still in the hospital where she will remain for a few more days. But the crisis is over and there is improvement by the hour. By the time you read this, she will probably be home again in her own bed.

In the May 2009 issue of Bioethics in Brief, I discussed the fear of novelty that often leads to skepticism about new technology. I urged that moderate skepticism may be appropriate if it leads us to logically weigh the risks involved in new technologies, and that caution may be appropriate when we are unsure how to evaluate the risks we face.

The other side of this equation, of course, is the benefit that technological advances bring. In my grandparents’ generation, people often died from a ruptured appendix, and surgery was a far less certain undertaking.  Today, an appendectomy is a relatively minor procedure. When the surgery is uncomplicated, patients may leave the hospital within a day or so of surgery.

We are grateful for life-saving technologies when we experience their benefits firsthand, and people are typically much less wary of technology—including biotechnology—when their most central interests hang in the balance.

The danger of adopting a technology that is unproven is the difficulty in weighing the involved risks.  Since it is not possible to predict every eventuality, we may not understand how to weigh the risk until it’s too late.  But the alternative danger— the danger involved if new technologies are not adopted—may also involve serious risks. We may not give proper weight to those risks until we experience the benefits first hand. Today as I write this, I am vividly aware of the benefits associated with the surgical technologies that saved my child’s life.

Precautionary Principles

How should we evaluate unproven technologies?  It is sometimes recommended that we adopt a precautionary approach.  The precautionary principle offers a general recommendation that we should be cautious when risks are unknown.  Those who dislike the principle often recommend it as a general, blanket condemnation of any new technology simply on the basis of its novelty.  In a 2003 New York Times editorial, Clyde Prestowitz memorably represented the precautionary principle as a recommendation that “If we can’t prove absolutely that [a new technology] is harmless, let’s ban it.” (Prestowitz, 2003)  Stated in this way, the principle becomes an unfortunate decision criterion.  It is neverpossible to prove absolutely that a novel technology is harmless.  If we are entirely ruled by our fears we will miss the benefits that new technologies offer.

Often, these benefits can be measured in the same terms of life and death, happiness and misery that we may use to weigh risks and costs. Prestowitz is not a fan of the precautionary principle, so his statement of it is intended to make the principle appear ridiculous. While this may make a successful rhetorical point, his argument would have been more interesting and significant if he had re-presented the principle.

A more moderate version of the precautionary principle found its way into international law in the 1992 Rio Declaration. That agreement states “Where there are threats of serious or irreversible damage, lack of full scientific certainty shall not be used as a reason for postponing cost-effective measures to prevent environmental degradation.”  (Rio Declaration, 1992, Article 15) If Prestowitz’s statement of a precautionary principle is absurdly strong, so that it would prevent acceptance of any new technology, then perhaps the Rio statement is absurdly weak.  Of course “lack of full scientific certainty” should not constitute a reason to postpone “cost effective measures” to prevent harm (or degradation).  Empirical science never provides certainty.  While one precautionary statement seems to rule out acceptance of any technology at all, the Rio statement is too weak to motivate caution even in cases where caution would be fully justified.

Confusion about the precautionary principle has resulted in the existence of opposing rhetorical camps.  Some people reject the principle as obviously excessive while others extol it as a minimal and obviously justified principle for policy choice.  If those involved in this discussion have different principles in mind, they may both be correct.  But they are talking past each other.

Risky Decisions and New Technologies

I am overwhelmingly grateful to the people who developed and employed the surgical procedures that saved my daughter’s life recently. But the first time these procedures were used, the risks involved were unknown, and there must have been a reasonable expectation that they could fail.  In the case of a ruptured appendix, the expected cost of doing nothing is high.  Left to follow its natural course untreated, a ruptured appendix can be expected to lead to pain and death.  In some cases, new technologies leave us with less dire alternatives than this.  The cost of caution is often (though perhaps not always) less immediate and extreme for technologies in agricultural biotechnology.

The question whether we should chose to err on the side of caution or optimism will not be solved by reference to either of the simple principles articulated above.  We need rationally to consider all of the risks involved in our choices, including the opportunity cost of proceeding with an abundance of caution.  These costs are difficult to measure, since they are reflected in the foregone benefits that technologies might have brought.  To see that these costs are very real, we would do well to consider the loss we would have experienced if past technologies had not been developed.  In some cases, these opportunity costs are reflected in the lives of people who might have been positively affected by the adaptation of the new technology, even to the extent of dramatically extending the lengths of their lives.

References

Gardiner, S. 2006.  A Core Precautionary Principle. J. Pol.Phil. 14(1):33-60.

Prestowitz, Clyde. 2003. Don’t Pester Europe on Genetically Modified Food. New York Times, January 25.

Stich, S. 1978. The Recombinant DNA Debate. Philosophy and Public Affairs. 7(3) Spring 78, pp. 187-205.

Clark Wolf is the Director of Bioethics and a Professor in the Department of Philosophy at Iowa State University. He is a faculty member in the Graduate Program in Sustainable Agriculture and has a cortursey appointment in the Department of Political Science. He teaches and co-teaches a variety of courses, including Foundations of Sustainable Agriculture, Environmental Ethics, and Bioethics and Biotechnology. Clark gives and organizes thought-provoking talks to diverse audiences at Iowa State, including talks on biotechnology and intellectual property.*

Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the ISU Office of Biotechnology or Iowa State University.

Wolf, Clark. Precautionary Principles and the Cost of Caution. Bioethics in Brief, a Publication of the Iowa State University Office of Biotechnology. May 2010. Volume 12, Number 2.

* Biography composed by Anastasia Bodnar.