Monday, October 7, 2013

The People Side Of GMO Crops: Part I

As with any new technology, the development and commercialization of biotech crops is a story about people.  Its a story about people with ideas and vision; people who did hard and creative work; people who took career or business risks, and people who integrated this new technology into the complex business of farming.  By various artifacts of my educational and career path, I've been in a position to know many of these people as friends and colleagues over the last 36 years.  Their story is important, but it tends to get lost in much of the conversation about biotech crops.

Many narratives about "GMOs" leave out the people side, presenting it instead as some faceless, monolithic phenomenon devoid of human inspiration, intention and influence. Thats not how it happened.  Other narratives about "GMOs" demonize those who made biotech crops a reality. Such portrayals are neither fair or accurate.  The real stories of these people matter, because trust in a technology is greatly influenced by what people believe about those behind it.

That is why I'd like to write about what I have observed about these real and trust-worthypeople over the years. I'll start with the period 1976-1982.

It Started On "The Farm"

Stanford has the nickname, "the farm" but its no Ag School!

I first heard of genetic engineering in 1976 while a senior at Stanford University in a graduate level biochemistry class. The professors lecturing on the exciting new science of molecular biology were Paul Berg, Stanley Cohen and Herbert Boyer.  These basic researchers were doing purely lab work with no commercial motivation, but in the process, they ended up inventing "recombinant DNA technology." At the point of my introduction, the science was still young (key experiments started in 1971).  The Stanford researchers discovered the enzymatic "tools" to cut and paste genes and other key pieces of DNA.  From the beginning it was clear that these discoveries had a huge range of potential applications in basic research, medicine, pharmaceuticals, bio-materials and bio-processing.  It also had potential for agriculture. It was an exciting time, but it took many years for all this to unfold in practical applications.  Berg later received the Nobel Prize for his work and the patents that came from the work of Cohen and Boyer became some of the most widely licensed in history (they became a huge source of research dollars for Stanford).  Genetic engineering, GMO if you will, started in the labs of people who were focused on academic research.

Safety First

The setting for the first conference on biotech safety

It is significant to note that these and other early genetic engineering researchers took special precautions from the very beginning to make sure that they were not creating something in their labs which could be dangerous.  Paul Berg was instrumental in organizing the 1975 Asilomar Conference, a gathering of scientists designed to carefully consider all the ramifications of this new science of "genetic engineering." The outcome of that conference helped guide the NIH (National Institutes of Health) to set guidelines for lab safety regarding biotechnology.  The original rules were severely restrictive, and were only relaxed a bit after much experience and increased understanding.  I'd be interested whether any of my readers are aware of other technologies for which such precautions were taken at such an early a stage?  This standard of thoughtfully trying to anticipate any risks or issues carried forward as the science developed.

Off To Davis To Become An Aggie

The iconic water tower at Davis

Many biology students from my generation went on to pursue the various applications of genetic engineering.  Although I was fascinated by what I had learned about this basic science, I was interested in a much more applied science called Plant Pathology - the study of diseases of plants.  So, in 1977 I started graduate work at the University of California, Davis - an actual ag school.  My research was field oriented and I got my first exposure to farming and farmers.  However, one aspect of my project involved lab work, and the particular equipment I needed was in the adjoining labs of Dr. Robert Shepherd and Dr. Tsune Kosuge.  Both labs worked on topics which were of great importance to the brand new science of plant genetic engineering.  So, my education about biotech continued.

My lab-mates at Davis were pursing very basic research needed to answer two key questions:  "How can we get new genes into the nucleus of a plant cell?" and "How will we get those genes to express" - to be turned on in the cells of the plant as desired?  

A Virus Disease of...Cauliflower?

My little bit of bench space was in Shepherd's lab which worked on virus diseases including Turnip Mosaic and Garlic Mosaic Virus (the smell of the later often permeated the lab as samples were ground up for analysis).  The lab was also one of a few around the world that worked on CaMV (Cauliflower Mosaic Virus).  That is a rather minor disease, but it was of interest because it is a DNA plant virus while most plant viruses are RNA viruses.  Several of my lab mates were "sequencing" that virus, meaning that they were figuring out the pattern of A,T,G and C bases in its genetic code.  The methods they used are humorously crude by modern standards and it took them more than a year to get the sequence - something that would probably take less than a day with modern equipment.  In any case, there was a hope that once the genetic code of CaMV was understood, it might be possible to use that virus as a way to move a new, desired gene into a plant.  After all, the virus manages to do that for its own purposes.  That goal never materialized because the virus protein capsule was too small to "package" a useful gene, but CaMV turned out to be important for a different reason.

You can't fit much DNA in these little virus particles

A gene "promoter" is a part of the DNA sequence that sits in front of a gene and tells tells cells how and when to express that gene - usually meaning to have the cell make the protein for which it codes.  It turned out that a promoter from CaMV called "35S" eventually became the most widely used promoter for transgenic crops of the first generation - both in research and commercial use. At the time, however, the team in the Shepherd lab was just doing basic research, mainly with the hope of getting out some good publications.  35S was actually first described and patented by a group at Rockefeller University.   

Nature's Genetic Engineer

Graphic about how Agrobacterium works, now that we understand 

The neighboring lab (Dr. Kosuge's) also had equipment I needed.  The graduate students, technicians and post-docs there all worked on a soil microbe called Agrobacterium tumifaciens which causes a disease of many plants called "Crown Gall."  Agrobacterium is nature's "genetic engineer."  When it gets into a plant injury it is able to inject a circular piece of its DNA (a plasmid) into the exposed cells.  Then, the genes from the bacterium start functioning in the plant.  The bacterium "engineers" the plant to provide itself with both a protective home and an exclusive food supply based on two unique amino acids only it can use.
A crown gall on a grapevine "engineered" by Agrobacterium

Many labs were trying to figure out the details of how Agrobacterium does that, and Kosuge's group was one of them.  The goal was to "disarm" that "Ti Plasmid" so that it would no longer make the plant sick, but maintain its natural function of inserting genes. Only by understanding the detailed regions of the Ti plasmid would it be possible to only insert desirable genes.  Other approaches were being tried in other labs.  Ultimately, a tamed version of Nature's genetic engineer became the most desirable way to put new traits into a plant.   The researchers in Kosuge's lab were all just making small contributions to that ultimate development.  Many labs around the world were working on the same thing. 

The atmosphere in both of these labs was one of excitement about a distant goal of making a positive contribution to the future food supply, but it was also a group of people excited about being on the cutting edge of a field of science.  Commercial applications were a distant concept at that point.  As with those at Stanford, these researchers were concerned about making sure their work was safe.  Dr. Kosuge was instrumental in convening a major conference of "Risk Assessment in Biotechnology" that was held in Davis in 1988 and which I'll describe later.  Most of the people coming out of these labs went on to the sort of academic jobs all of us were shooting for at the time, but some moved on into the next chapter of plant biotechnology which began in the very early 1980s - the small, start-up companies.  I hope to write about that phase sometime soon.

You are welcome to comment here and/or to write me at

Image of the Stanford Quad in 1978 from Wikimedia Commons
Asilomar State Beach image from Wikipedia
UC Davis water tower image from the UC Davis website
Agrobacterium graphic from Nature
Grape crown gall image from Bill Moller of UC Davis (he was one of my advisors there)