Genetic Maize - Navigating the maze 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.

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I was very young when I first read Copernick’s Rebellion by Leo Frankowski. It captured my imagination, and is directly responsible for my thoughts on genetic engineering and my desire to become a genetic engineer. The author was ahead of his time, taking the (then fictional) idea of manipulating genomes to fantastic conclusions. The characters turn our dismal world into something beautiful, a utopia that provides food and shelter for everyone.

Of course, some of the organisms in the book are more likely than others, but the idea holds true. So many things could be accomplished with biotechnology, from feeding the world to cleaning up pollution… but regulatory, financial, and social issues are preventing the most interesting and promising work from being done.

The main character in the book took some extreme measures to get his creations to the people who needed them most, but I think we have some better options. One of those is make genetic engineering accessible to more people.

Software has improved by leaps and bounds because so many people have contributed. Big companies like Microsoft and Google don’t have the desire to make every function that people might want to use. However, people who have time and knowledge can create helpful applications and share them, Open Source, for the good of the community. The code can be tweaked by others, shared, and tweaked further, until some highly useful items come about.
How could this idea apply to genetic engineering?

Over 180 genomes have been sequenced to date, according to Craig Venter’s Genome News Network, and we can expect to see more and more. Within these genomes are the genes we need to solve problems, if only there were enough people working on them. There are relatively few hands working on genetic engineering right now, so most of the treasure remains hidden. If more people had access to the genomes, along with basic knowledge of how genes work, they could apply their time and creativity to designing new solutions. A whole new industry could develop, providing the tools people would need to bring their ideas into reality.

I personally would like some cold-tolerant basil and late-flowering cilantro for my herb garden. Various genes for cold-tolerance and flowering are known, but certainly haven’t been applied in this way. One roadblock to long-lasting cilantro in my garden is patenting of genes. I can’t just use a previously described gene without dealing with intellectual property law.

As of 6 December 2007, Nature has opened all papers reporting genome sequences to the public, under a Creative Commons license. This is a step in the right direction, but doesn’t affect the patenting of individual genes. Patents are necessary to drive innovation - they allow the patent holder to recoup the cost of development or discovery.

A modified patent would allow only the patent holder to use the gene for profit, but freely allow non-profit use of the gene. I could design and create my cilantro, as long as I don’t sell it, and give credit to the person who developed the gene. If I do develop something with market potential, I could negotiate with the patent holder, perhaps to pay royalties for the duration of the patent.

Of course, we can’t ignore the negative aspects of the accessibility of technology. There will always be those who use technology to harm others. Harmful organisms certainly pose a special problem because they can replicate. Strict regulation of harmful organisms and genes would certainly be necessary, and not impossible.

This post was inspired by “The Open Organism: Genetic Engineering in the Open Source Era“.

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Fish as human food present a unique problem. The protein they provide is high quality and low in fat. People all over the world enjoy fish as a staple of their diet. Unfortunately, the demand for fish has overtaxed natural populations. Regulation has been successful in some areas (Alaskan salmon), yet failed miserably in others (Mediterranean tuna). The big question is: how can humans continue to enjoy eating fish but avoid the extinction of popular species?

Aquaculture is one solution. Farming has been especially successful with vegetarian fish like tilapia and catfish, because they can be fed grain based meal. It hasn’t been as sucessful with carnivorous fish because they require a high protein meal that is typically made from smaller fish like anchovies. Overfishing of the smaller fish has negative effects on wild ecosystems. Researchers at Mississippi State may have found the solution. Feed made from insects contains high quality protein and is cheap to produce. Excerpts from the press release are below the cut.

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The review article “Transgenic strategies for the nutritional enhancement of plants” (to be published in vol 12, issue 12 of Trends in Plant Science) discusses each of the methods used to improve nutrition for human populations that depend on one grain as their primary food source (the conclusions of the paper are after the cut). Simply introducing a varied diet, fortified foods, or supplements would solve malnutrition, but these are not options for poor populations in areas with unstable governments. They need a self sustaining way to improve the food that is available to them (i.e. that doesn’t need additional monetary input).

The ’simplest’ or most obvious way to solve malnutrition, then, would be to improve the crops that the people eat. For those people who eat only maize or rice, a change in the nutritional profile of the grain would have a huge effect. Traditional breeding has been less than successful, and can take decades before a noticeable difference is achieved. Some improvements are not even possible with traditional breeding, if the desired trait does not exist in the gene pool of the species.

Enter genetic engineering. Humans now have the capability to improve the nutritional profile of a plant by adding genes that code for the desired trait. One example is the famed golden rice. Rice contains no beta-carotene, the precursor of vitamin A. Vitamin A deficiency is the leading cause of blindness in children, and leaves the children susceptible to disease such as malaria and measles (UNICEF). While the regulatory hurdles of getting golden rice into the bowls of those who need it are enough to fill a whole series of blog posts, the important part is that the levels of beta-carotene in this rice has been improved to high enough levels that the recommended daily value can be fulfilled by consuming a typical day’s servings of rice (goldenrice.org). Imagine that: millions of children who are no longer suffering from the lack of this important vitamin. The only work to be done is to plant and harvest the rice.

Across the world, malnourished children have little chance to better their situation. The lack of nutrients is a barrier to proper brain and body development. We can not expect so-called third-world nations to improve until they have enough people with strong minds and bodies to improve them. In the quest to solve world hunger, the development and deployment of crops with improved nutrients should be our primary concern.

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Nanobots and nanodevices are fully formed in concept, but some of the pieces are harder than others to actualize.

“One of the major limitations in making implantable, nanomedical devices is providing power to them,” said Travis, … of Cornell’s College of Veterinary Medicine. [In Tethered To Chip, Energy Supply That Drives Sperm Could Power ‘Nanobot’ from SD]

Recent work at Cornell has found a candidate motor: sperm! A glycolytic enzyme pathway attached to the solid tail structure converts sugar to ATP. Researchers connected the enzymes to a substrate, and found that they still worked. Since sugar is plentiful, this could be the perfect way to provide ATP to a nanobot. Biological nanotech has a huge advantage because most of the parts already exist!

I’m really interested to see what comes of this reasearch. There are a few interesting medical applications such as targeting drugs to tumors, where the nanodevice needs to “swim” to the appropriate site. Medicine is the most commonly discussed application, but I can think of a few more… nanobots covering plant roots that dispatch harmful nematodes and other parasites, environmental clean-up nanobots that deactivate toxins…

I read “Engines of Creation” by Eric K. Drexler as a child, and have been fascinated with the idea of molecular engineering ever since. It’s not as exciting as genetic engineering, but has huge potential. I especially enjoy it when the two intersect, such as enzymes produced with genetic engineering that are effectively used as tiny machines.

When I use restriction endonucleases to cut specific DNA sequences, I’m employing nanobots to do something that would be impossible without them. Rennet is a food enzyme that immediately comes to mind. It has been used by humans to coagulate milk proteins since animal agriculture began. Can we call enzymes such as these anything but machines? They are certainly devices that assist in useful work. Public perception of science would certainly change if we taught children about enzymes as machines.

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