Dr Julian Ma believes the silence on the plant biotechnology front over the past couple of years has been intentional. “Every time we do raise our heads above the parapet you do get shot down” he claims. As the head of Pharma-Planta, a Europe wide consortium of plant scientists devoted to developing plant-produced treatments and vaccines, he feels this was partly to do with the media coverage of the subject, “it was very antagonistic, so a lot of people kept their heads low.”
Back in 2004 when Pharma-Planta was launched the possibility of growing pharmaceuticals in genetically engineered crops was greeted with a lukewarm reception from the public. €12 million was pumped into a consortium of labs across Europe to produce plant crops which could be used for ‘pharming’. Clinical trials were due to start this year, in 2009.
However, progress has been rapid during these past four years with a number of new technologies about to enter clinical trials. Ma also thinks the silence has given the group some time for a shake up. “Plant scientists have little commercial nouse with no idea what it takes to get these technologies onto a commercial platform.” he says. “It’s taken a couple of years to get rid of that mindset.”
After years of low expression levels, rows about patents and mixed opinion on the commercial viability of genetically engineering novel plants crops, pharmaceutical crops appear to be overtaking food crops on most counts. Notable food crops engineered to improve nutritional value of the plants like golden rice, failed to produce high enough levels of these substances to be of any use. This has not been a great concern for pharmaceutical crops. The levels of expression required to be financially profitable are lower than is needed for genetically modified food crops.
Cheaper and quicker
Last year researchers Charles Arntzen and Richard Levy released results for the first commercial plant-derived vaccine. They had produced a vaccine for non-Hodgekins lymphoma which had successfully completed phase one of its clinical trial. Their success came from a new approach. After isolating antigens from a lymphoma patient, tobacco mosaic virus was used to infect tobacco plants. A week later the plants were harvested, the antigen was purified and a vaccine was produced. The study started after Levy became frustrated with the time it was taking to produce vaccines through conventional animal cell cultures. Then he found the total time taken to produce a vaccine from biopsy to treatment was three or four months: half the time it takes to produce a vaccine from animal cell cultures (Proceedings of the National Academy of Sciences, vol 105 p 10131).
Ma agrees the use of viral expression systems like tobacco mosaic virus offers hope, “Currently the most promising systems are transient expression systems, driving expression from a virally derived plasmid.” He explains, “This infects the plant cell [where] it divides like a virus inside the cell, so we get multiple copies.”
The plant species used are also important, though currently a diverse number of plants are being used. This is due to the growing number of patents on plant technologies. Around the time of the launch of Pharma-Planta, Ma and his lab looked at which plants were best for their technologies, “We ignored freedom to operate – we took the patent situation out of it. We found tobacco and maize were the best plants to use as they offered the highest expression of the products we were trying to produce.
“But a number of plants are currently being used. Carrot cells are being used by a company in Israel. That’s about to complete its final phase three trial. Human insulin grown in safflower is also close to a commercial lease right now.”
Sembiosys the biotechnology company behind the insulin producing safflower crop highlight the fact that growing human insulin in a safflower crop will reduce manufacturing costs by up to 70 percent, and product cost by 40 percent. This also means just one acre of safflower is needed to produce enough insulin to treat 2,500 patients for a year. A figure not to be sniffed at considering insulin use has tripled in Europe in the last 12 years.
Though it is more than four years on, opposition hasn’t changed much. GeneWatch and other environmental groups including Greenpeace are still opposed to any GM technology on the grounds using food crops for non-food products is high risk. Ma does not agree with their conclusions saying that the tiny scale on which pharmaceutical crops are grown compared with genetically engineered food crops means a lot of their risk assessment is outdated. He notes, “Pharmaceuticals are high value, they are for a very tiny niche market that will use specialist growers on a low acreage. The value of these crops is so high we need to protect against pest and failure, so we would have to grow in greenhouses rather than in open fields. It’s not a worry about the pharmaceutical crops getting out, the problem is stopping the food crops getting in.”
Claire Oxborrow, senior food campaigner for Friends of the Earth claims the risks involved in human error are high, but appreciates these can be reduced. She says, “If things are being contained and they do prevent it happening we still wouldn’t say we were in favour of them, but we would be less opposed. There is always going to be human error and where this involves food crops this is unacceptable. However, if you are talking about tobacco and you are going to grow them in containment then it is going to be further down the risk scale for us.”
The choice of disease targets is also an area which is ripe for controversy. It has been shown costs of drug production can be dramatically reduced, but diabetes and cancer are diseases of Europe and not of the third world. Ma notes that encephalitis is an important disease but as it is not present in the UK there is little research surrounding it. “You have to be careful with your targets. We have always done diseases which affect the developing world like HIV and tuberculosis, but those are pretty important in the UK and Europe as well.”
Staunch opposition may still be the case from some areas of society but in these stretched times, cheap pharmaceuticals should be welcomed. As other strains of biologically engineered plants, currently being developed, start to enter clinical trials we will be able to see their possible impact and the effect this may have on any public opposition.
(NB this is the box out from the copy)
Plants have been used since the dawn of civilisation to create medicines, so the ideas behind growing our own drugs isn’t anything new. One of the most notable modern plant derived drugs is Tamoxifen, a drug derived from the Pacific Yew which is used to treat breast cancer and increasingly to prevent it in high risk women as well.
Extraction of taxol which is used to produce Tamoxifen from the plant is often expensive and time consuming as it exists in such low quantities. In the Pacific Yew, taxol is only produced in the bark of the tree and the tree grows extremely slowly. There is also the added problem of the numerous similar compounds which are present and need to be separated from the taxol: a long and expensive process.
Bioengineering of taxol is a possibility, but is hindered by the complicated genetic pathway which controls the production of taxol. There are fifteen genes which control this pathway and have so far been successfully transformed into yeast, but there is still a long way to go.
Previously genetically modified crops have failed to produce the substances they were engineered to provide, because the host plant they were being grown in was too unlike the original organism. The hunt is on to find a fast growing tree which can be engineered to produce taxol in its bark.