Biopharma

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.

Farming in Utopia

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.

Patents prevent development of GMOs

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.

Mini-chromosomes

Where a transgene incorporates into a plant’s chromosomes can not be controlled. So, scientists have to transform many plants, and hope that at least one individual didn’t have the transgene interrupt a native gene. One solution to this problem is called a mini-chromosome. This technique uses the natural centromere sequence of an organism to build an entirely new chromosome that would be passed on to successive generations. The mini-chromosome can then be filled with a combination of genes, knowing that no native genes will be interrupted. Plants could be transformed with entire pathways, using this technology. The applications include improving field traits and nutrition, as well as things like making biofuels and bioplastics.
This research has been going on for a while, but the newest publishing shows that the mini-chromosome can be passed on to the next generation as a normal chromosome. From SD, Transgenics Transformed:

The maize mini-chromosome, once introduced, behaves much like an ordinary chromosome. It remains distinct from the other chromosomes. Its gene cassette is structurally stable from generation to generation. The genes it carries are expressed and it is transmitted through mitosis and meiosis.

The scientists started a company called Chromatin, which sold non-exclusive rights to Monsanto in May. Other companies are looking to get involved.
I’m really excited about this idea. One of the problems with genetic engineering is our inability to control where a gene inserts into the genome. Mini-chromosomes eliminate that problem and allow the scientist to add many genes instead of just one. It would be nice if they were still hiring when I am ready to graduate!

World Food Prize Day

Today was the World Food Prize Symposium, where policy makers from around the world meet to discuss world food problems. The prize was started by Norman Borlaug. His took the idea of hybrids from corn production in Iowa (where he grew up), applied them to rice, and effectively ended hunger in Asia. The main topic today was recreating his “Green Revolution” of the 60s in an “Evergreen Revolution” today, with the goal of creating sustainable agriculture in Africa and eliminating hunger in our lifetimes.
Dr. Swaminathan from India spoke about organic farming. In sumary, the ideas of organic farming are good, but they are non-sustainable and will not feed the world. The idea of green farming is to use crop lines that have been responsibly modified in a farm setting with Integrated Pest Management (using biological methods over chemicals, but chemicals when absolutely necessary), and responsible fertilization and crop rotation to avoid depleting the soil. To me, this approach is ideal. Mixing traditional farming methods with state-of-the-art technology is the only way we can feed the world
A great statement made this morning by Sir Gordon Conway was that the greatest accomplishments of our time were achieved by non-violent methods. This worked to stop racism in America and apartheid in South Africa. Why can’t it work for Iraq? Or North Korea? If we poured money into agriculture, self-sustainment, and education (instead of war) then maybe something positive would actually happen! I truly believe in the power of agriculture to empower people in a positive way. Happy people don’t wage wars.
Other people seem to be seeing this idea in the same light, such as Bill and Melinda Gates. Dr. Shaw is their representative on agricultural initiatives, working towards the same goals as the World Food Prize people. Hearing him talk was amazing. Bill Gates may not be perfect, but his organization may singlehandedly eliminate malaria, and is working to do other great things too.
I had to leave right after Dr. Shaw’s talk, drive back to Ames, and run to a talk by Dr. Kathy Swords of Simplot. This company is working on a lot of awesome things that boils down to making genetically modified crops with no foreign DNA. In other words, instead of a gene from a fish in your tomato, it will be a gene from another type of tomato or from a related plant. It’s much less likely to cause allergic reactions in people, and results in no new novel proteins. The result of the modification could be achieved naturally, but it would take decades of breeding instead of a few years of development. The company voluntarily tests all of their crops, making sure that there are no differences from a naturally bred crop. It sounds like they have much more responsible business practices than Monsanto, with less objectionable results. One frustrating part is that I’ve been talking about this idea for at least a year now. I can be satisfied knowing that someone’s doing it.