Genetic Maize

Biopharma is such a strange word. To me it sounds sort of sci-fi, evoking images from the 1950s of a future where everything will be high-tech but beautiful and simple at the same time. Of course, not everyone has such positive thoughts about this potentially dangerous yet potentially lifesaving application of technology.

“Scientists Worry Over GM Drug Crops“, posted on Environmental Graffiti, briefly covers the news that crops engineered to express pharmaceutical proteins will be field tested this growing season, concentrating on the Union of Concerned Scientists’ reaction. Apparently UCS is taking their typical anti-tech stance, asking the USDA to require all such crops to be grown in greenhouses or underground. I was not able to find any record of UCS’s recent comments. (more…)

In a sentence: Researchers at Boston Children’s Hospital are inducing fluorescent cancer in transparent zebrafish in order to study the spread of the cancer cells. Now for a little background info to help that sentence make sense!
Zebrafish are one of the so-called “model organisms” because they fit a list of criteria that make them easy to study: fast growth, prolific reproduction, easy to keep in a lab, small genome without too much “junk DNA”, and so on. They are transparent during development, so we can see how their organs take shape over time. As vertebrates, their bodies aren’t all that different from human bodies, so they can give us valuable information about human disease and developmental problems
Once the fish get to be about 4 weeks old, their scales darken, closing the “window” into the fish. Richard White, one of the researchers, said they solved the problem “by mating two existing zebrafish breeds, one that lacked a reflective skin pigment and the other without black pigment. The offspring had only yellow skin pigment, essentially appearing clear [LiveScience].”
What do you do with a transparent fish? White put a fluorescent tumor in the fish’s abdomen. Unfortunately, my university does’t have access to Cell Stem Cell, but the abstract says: “transplantation of GFP-labeled marrow cells allowed for striking in vivo visual assessment of engraftment from 2 hr–5 weeks posttransplant… both transparent and wild-type fish had equal engraftment, but this could only be visualized in the transparent recipient.” In other words, the clear skin of the new breed of fish allowed the researchers to actually watch the cancer spreading. “Viewing the fish under a microscope, White saw the cancer cells begin to spread within five days. He even saw individual cells metastasize, something that has not been observed, so readily and in real-time, in a living organism [EurekAlert].”
So, what’s GFP? Green fluorescent protein occurs naturally in some species of jellyfish. The molecule produces a green glow when exposed to certain wavelengths of blue light. It’s completely non-toxic, so can be used to illuminate living organisms. It sounds strange, but GFP has allowed researchers to view biological processes that would not otherwise be visible. When tissue specific promoters (like light switches for genes) are used to drive expression of the gene for GFP, only that type of tissue glows green. In the picture, zebrafish embryos are expressing GFP controlled by a promoter for a circulatory system gene. A video showing a zebrafish heartbeat, visible via GFP, can be seen here. Now, imagine how much the researchers were able to learn from watching a tumor spread in real time.

As discussed in “Farming in Utopia“, one of the benefits of modern farming is that it requires fewer people to produce more food. This benefit is ignored by those who wish to eschew technology in farming. People who have the luxury of choice shouldn’t force their choices on those with no choices at all. A prime example of this behavior can be found in Jose Bove. The actions and words of people like him mean that people in places like Africa haven’t been allowed to choose what types of farming are best for them.

Poor farmers all over the world are battling drought, insects, fungi… with their bare hands. They may have access to some pesticides and fertilizers. If they are lucky, their inputs are the right ones, and not too toxic. The farmers certainly aren’t stupid, but they haven’t had access to all the bells and whistles that farmers in the US, Europe, and Australia can choose.

There are many reasons for the disparity, including socio-political problems. The Gates Foundation is funding a new Green Revolution, with the goal of ending hunger in Africa, that includes a build-up of infrastructure with a healthy dollop of plant breeding. They recognize that a one-size-fits-all approach won’t work in Africa, so they are “developing appropriate seeds to attain the best yields in the diverse environments of Africa and working to make sure these high-quality seeds are delivered to farmers who need them most.”

The Gates’ program has many facets, but the absence of one is striking. Bowing to efforts of anti-technology activists, the Alliance for a Green Revolution states: “Our mission is not to advocate for or against the use of genetic engineering.” They “will consider funding the development and deployment of such new technologies only after African governments have endorsed and provided for their safe use.” This is sad, because the African governments are held hostage by the same activists on the subject of GMOs. Genetic engineering could bring critical crop adaptations to the people who need them very quickly, much more quickly than depending on traditional breeding or mutation via radiation.

Some people, such as those at Food First, cringe at the mention of the Green Revolution, but I challenge their opinions on the subject. It is unethical to condemn Norm Borlaug for the Green Revolution that he brought about. His calling was to end hunger, using the methods he had. It is unfortunate that he bred lines that are dependent on fertilizer inputs, but the environmental consequences were not known at the time. Regardless, the impetus was to feed the hungry. Today, our knowledge is much greater, so we can do much better – especially with engineered crops that require little-to-no pesticide and fertilizer.

Can we, who enjoy the spoils of technology, prevent that very technology from getting into the hands of the poor?

What farming is today, what it should be, and what people think it should be are very different things. Pro-organic, pro-biointensive mini- and maxi-activists have a distinct idea of what they think farming should be, but don’t quite understand all of the ramifications. For the most part, I heartily agree with them, but I do understand (at least some of) the ramifications for our society and our food supply.
The industrial revolution brought people away from their fields and into the cities. More and more mouths need to be fed, but fewer people want to farm. There are a few ways to solve this problem. One is our current system – larger and larger monoculture farms, with every aspect (from seed to grocery store) controlled by fewer and fewer corporations, and farmed by fewer people. In this system, the need to achieve higher and higher yields of a few main crops has caused increased dependence on chemical inputs. These crops aren’t even considered food anymore, having moved to commodity status.  There are, of course, numerous well-known problems with this system. What are the alternatives?
In the dreams of activists, all farms would be small, perhaps 50 acres or less. Farmers would use as little technology as possible in farming (only “natural” pesticides, no fertilizers besides manure and compost, no tilling of the soil, etc) so as to be more “natural”. The crops would be heirloom varieties, with much genetic diversity and never altered with technology. Monocultures would not exist, with plants grown together in systems designed to help keep the soil healthy and share nutrients. Farms would distribute their produce no more than 100 miles from where it was grown.
For example, the gold standard of bio-intensive farming was pioneered by certain Native American tribes. They planted the “three sisters” – corn, squash, and beans. In this ingenious system, the plants deter each other’s pests and fertilize each other.
This system is so great that farmers is the US and other developed countries should be using it, right? Not having to use fertilizer or pesticides would save money, and be better for the environment, right? The activist’s dream seems to be perfect, until we look a bit deeper.
Unfortunately, things just aren’t that simple. As depicted in the picture to the right, a larger square footage needs to be devoted to this style of farming. The crops must be planted, tended to, and harvested by hand because farming equipment would squish the squash. Fertilizer is still needed for all but the most perfect soils, irrigation remains necessary, and pests are still a constant threat. In other words, this method is great for hobbyists or subsistence farmers who have the time to care for their plants by hand. It might even work for CSAs or other small vegetable farms that can use volunteer labor or charge a premium for their produce. It won’t work, however, to feed the millions of people that live nowhere near farms.
So-called organic farming won’t feed the world either. It’s great for many reasons, but is inherently more risky than conventional farming. Recent studies have shown that organic can compete with conventional farming for yield, but that’s in ideal conditions. We have to consider temperature fluctuations, droughts, insect infestations… problems that can be best solved with technology.
Organic farming also requires more labor to produce the same amount of food. Modern society simply is not prepared to have large proportions of the population employed by farming.  Less than 1% of Americans make their living as farmers. With the price of food being so low and the price of land being so high (even before corn ethanol), it is impossible to recruit enough people to become farmers to feed every person with this type of farming method. I don’t forsee huge numbers of people deciding to farm, or forsee the population getting any smaller.
Another problem is that few people eat squash and beans. Unfortunately, food is subject to the laws of supply and demand. Consumers in the US, and increasingly in the rest of the world, want convenience more than they want fresh vegetables. Although things are getting better, Americans in particular still choose grain-fed beef and fried potatoes over whole grains and leafy greens. Huge fields of corn, soy, rice, wheat, and a few other crops are simply a fact of life.
Does that mean we should give up and accept factory farming, row after row of environment and health damaging monocultured crop? Of course not, but there is a way between the ideal organic and ideal corporate farms. Last week, in a wonderful lecture about her small farm in Iowa, Laura Krouse said something profound: her farm is “as organic as it needs to be”. Using ideas from all types of farming is the only way we can meet the demands of the future.
I propose that we find a happy median – intelligent use of technology combined with stewardship. We need to find the best ways to grow enough food without irreversibly damaging our land and water. Genetic engineering can solve many of our problems, but it needs to be carefully applied. I’ll discuss how in future posts.

Once a transgene is designed and created, getting it into plant cells is surprisingly simple. There are two main ways to transform plants: the gene gun and Agrobacterium tumifaciens. The gene gun literally shoots tiny gold particles coated in DNA into cells. Agrobacterium is a natural soil bacteria that incorporates some of its genes into a plant’s genome so the plant will become a helpful host to the bacteria. For more information on both methods, click on this diagram from ND State Ag Extension.
If the process is so simple, why don’t we see more transgenes, more transformed plant species? BT and RoundUp Ready certainly aren’t the only possibilities!
Regulation isn’t really the issue, as a lot of genetic modifications (such as nutrient enhancement) are safe. Patenting of individual genes could be a problem, but there are many undiscovered genes out there. Patenting of techniques is the biggest issue. I don’t claim to understand the complexities of patent law, but I can report what understand as a young scientist.
“Are university researchers at risk for patent infringement?” in the 1 Nov 2007 issue of Nature Biotechnology describes how innovation in biotechnology has been halted by patents, especially in the case of plant transformation technologies.

Monsanto’s patent on the process of transforming plants through the use of Agrobacterium tumefaciens is claimed so broadly that it could exclude all plant transformation processes that use any engineered bacteria to transfer foreign DNA into plant genomes. The other method, biolistics-mediated transformation, was developed by Cornell University but licensed exclusively to DuPont, which has blocked commercial competitors from accessing the technology.

Any research that includes use of any method covered by currently held patents may not be taken to market or distributed in any way. Researchers can ignore patents and continue their work, but they are technically breaking patent law.

Although the patent statute contains a clearly stated research exemption, the 2002 court decision in Madey v. Duke limits the scope of the research exemption to experiments done “solely for amusement, to satisfy idle curiosity, or for strictly philosophical inquiry”. Madey was not a company but a disgruntled ex-faculty member, but the case has important implications for universities and their researchers. The court found that the precedent did “not immunize any conduct that is in keeping with the alleged infringer’s legitimate business, regardless of commercial implications.” Essentially, major research universities often conduct research projects without commercial application, but that research still advances the institution’s educational mission to “increase the status of the institution and lure lucrative research grants, students and faculty.” It is hardly for amusement.

In other words, university researchers can not use any patent-protected technology unless they can prove that their research has no point. They “can be sued for making, using, selling or importing patented technologies, even if they have no intention of commercializing the fruits of the research.”
All of this means that the problems faced by the developers of Golden Rice, the first GMO specifically designed to help the poor, still exist. The following excerpt is from “The IP Handbook of Best Practices” article on biopharming:

An FTO [freedom-to-operate] assessment revealed that Golden Rice was related to over 70 patent applications and issued patents, most notably in the United States and Europe, and that patent applications were owned by over a dozen institutions. Few patents were applied for or issued in developing countries. However, because the material was developed in Europe, it could not be transferred for use in developing countries without proper licenses. There were a few reasons for this, not the least of which was that several material transfer agreements were limited to research use only.

The patent holders did eventually permit Golden Rice to be distributed without licensing fees for humanitarian reasons, but only after a media storm. The final result: Golden Rice still hasn’t been widely distributed, and laypeople the world over don’t trust genetic engineering or the companies involved. The researchers didn’t consider how many patents they might infringe upon, they just wanted to solve a global nutritional problem.
Corporations conduct a FTO analysis before moving forward with research. Can university researchers be expected to do the same? According to The IP Handbook of Best Practices, FTOs can cost $20,000 to $100,000 to conduct. I can’t imagine adding tens of thousands of dollars to already tight grant proposals. No research would ever be funded!
One alternative to patent battles is to develop new techniques that aren’t covered by patents. The non-profit CAMBIA seeks to create open-source alternatives to Agrobacterium. Their work is promising, as reported by BBC News back in 2005 in “Plant biotech goes open-source“, but not mainstream, and still isn’t widely used. Regardless, scientists shouldn’t have to reinvent things before they move forward.
As I’ve shown in this post, patenting prevents GMOs from being created or distributed, unless they have enough market potential for corporations to create them. I’ve always thought that the dearth of intelligently designed genetically engineered organisms was the fault of activists, that public misunderstanding prevented funding of research. Now that I’ve investigated things further, it’s clear that intellectual property law plays a huge part. In fact, the problem of biotechnology lying solely in the hands of corporations is one of the few things that the activists understand.