Australia's Commonwealth Scientific and Industrial Research Organization said last week that it has granted a free non-exclusive license for its hairpin RNAi technology to BioCassava Plus, a global consortium of plant science researchers using biotechnology to improve the nutritional value of cassava, a plant whose leaves and roots are a major food source in sub-Saharan Africa.
According to Bill Taylor, CSIRO Plant Industry's business development manager, the license is the first of its kind his organization has granted. "I wouldn't say it is a formal policy" to provide free licenses to humanitarian groups, he told RNAi News this week, "but we didn't have to think very hard about it [when BioCassava Plus] came to us."
BioCassava Plus was officially launched last year after it received funding from the Bill and Melinda Gates Foundation under the philanthropic organization's Grand Challenges in Global Health initiative. In late 2003, the foundation set aside $200 million to fund research into 14 key scientific challenges facing disease control in developing nations, including the creation of "a full range of optimal, bioavailable nutrients in a single staple plant species."
According to Richard Sayre, a professor in the department of plant cellular and molecular biology at Ohio State University and the principal investigator at BioCassava Plus, cassava accounts for about 40 percent of calories consumed by roughly 250 million people living in sub-Saharan Africa.
"I wouldn't say it is a formal policy [to provide free licenses to humanitarian groups], but we didn't have to think very hard about it [when BioCassava Plus] came to us."
"In some areas, it's nearly 100 percent," he added. "And if you look at cassava as a food being directly consumed by people, rather than feed to animals [that are consumed], it ranks in the top four of all plants consumed globally."
The plant, however, is far from a perfect food. While high in starch, it provides less than 30 percent of the amount of protein needed for a healthy diet, and between 10 and 20 percent of the required amounts of vitamins A and E, iron, and zinc, according to the Bill and Melinda Gates Foundation. Additionally, cassava can be toxic if not prepared properly due to low levels of naturally occurring cyanide, the foundation said.
One group seeking to address this and other causes of malnutrition in developing nations is the Cassava Biotechnology Network.
Sayre told RNAi News this week that it was during a meeting of CBN members, of which he is one, that the idea for BioCassava Plus was born. Key members put together a plan to identify researchers from various scientific disciplines such as human nutrition "that we thought would complement our own programs and bring added strength to the process" of improving cassava using biotechnology, he said.
Following the announcement of the Grand Challenges in Global Health initiative, this core group of CBN researchers submitted a grant proposal for BioCassava Plus, which received its 5-year grant worth $7.5 million from the Bill and Melinda Gates Foundation.
Specifically, the BioCassava Plus effort aims to increase the content and bioavailablity of zinc, iron, protein, provitamin A, and vitamin E in the plants. The group is also working to decrease the cyanogen content in cassava, delay the rapid post-harvest physiological deterioration of the plant, and develop virus-resistant cassava varieties.
According to Sayre, BioCassava Plus' viral control group identified RNAi as a promising technology to help reach three of these goals. CSIRO's technology involves the knocking down of gene expression using DNA that transcribes double-stranded RNA, which makes it ideal for the continuous knock down of gene expression.
Describing RNAi's potential effect on improving iron availability in cassava, Sayre said that "plants sequester a lot of iron as phytates, and phytate is a myo-inositol sugar with phosphates on all six carbons. It binds iron so tightly that it's actually unavailable for human or animal nutrition, so one strategy is to reduce the phytate content [by targeting an] enzyme in that pathway [with] RNAi."
"We feel that if we go into the US first we'll demonstrate to the international community that these [plants] aren't dangerous. We think it will be more acceptable when we go to Africa to do it here first."
The second area where RNAi may prove useful is in the control of a virus common in Africa and Southeast Asia called cassava mosaic virus, which is one of the biggest constraints to cassava production. "The strategy there is to use RNAi technology to inhibit [the virus'] replication," Sayre said.
Finally, RNAi may help BioCassava Plus' researchers better understand and prevent post-harvest deterioration, Sayre said.
Sayre noted that after cassava is harvested, it rots within 48 hours. "We know that enzymes involved in reactive oxygen species metabolism play a key role in that process — at least we think they do. Part of what we're trying to do is some basic molecular biology to understand the roles of those ROS-metabolizing enzymes in the process of post-harvest deterioration," he said.
"There is some basic biology we need to work on, as well, and so part of our efforts will focus on regulating certain gene expressions to understand their roles in various metabolic pathways … in particular … post-harvest deterioration."
In 2000, a team of researchers from Switzerland and Germany unveiled golden rice, a genetically modified variety of rice that produces provitamin A, which is converted by the body into vitamin A, in the edible parts of the plant. Relying on patented technology owned by various companies and institutes, the rice was developed for use in poorer nations where vitamin A deficiency is a primary cause of childhood blindness. Free licenses to the intellectual property, similar to the one CSIRO granted BioCassava Plus, were provided to the rice's developers for humanitarian purposes.
But concerns over the safety of genetically modified foods prevented golden rice, as well as a newly developed version called golden rice 2, from ever making its way to the developing world.
Sayre said that BioCassava Plus anticipates meeting the same kind of resistance from people doubtful about the safety of genetically altered cassava — so much so that the group has three members working full time on establishing and implementing bio-safety programs in African nations by the time improved versions of the plants are ready to go into field trials.
BioCassava Plus also plans on conducting field trials in Puerto Rico before moving on to Africa in order to demonstrate the safety of the plant.
"We feel that if we go into the US first we'll demonstrate to the international community that these [plants] aren't dangerous," Sayre said. "We think it will be more acceptable when we go to Africa to do it here first."
Additionally, "it's easier to get into Puerto Rico because it's a US territory, we're more familiar with the rules and regulations, and the bureaucracy works fairly well," he said. "We'd also like to do a pre-screening there to identify the best performing plants among the multiple transgenics, and then take those to Africa."
Plants incorporating CSIRO's RNAi technology, however, will take some time to develop. The first round of Puerto Rican field trials, which are expected to begin in the coming weeks, "are targeted toward the removal of cyanogenic glycoside, and these turned out to be plants we already had in the lab," Sayre said.
— Doug Macron ([email protected])