How a tobacco farm in Kent could provide a life-saving drug for millions
· Genetic tweak allows HIV drug to be harvested
· Environmentalists fear cross-contamination
In the perfectly controlled atmosphere of a brick-proof, hermetically sealed greenhouse deep in the Kent countryside, a fresh crop of tobacco plants is beginning to flourish.
There is nothing unusual about the plants' appearance, but they are nonetheless extraordinary. A genetic tweak ensures that every cell of every plant churns out tiny quantities of an experimental drug. When harvested, they could bring cheap medicine to millions.
Scientists say the £8m project could provide a powerful weapon against Africa's HIV pandemic.
The process is called pharming, and to many it is both the future of GM crops, and the future of the drugs industry. If the tobacco plants in Kent are a success, each one will provide 20 doses of an anti-HIV drug - enough to protect a woman from infection for up to three months.
Pharming is a marriage of high and low technology that capitalises on the advantages of both. Instead of needing a $500m drug manufacturing facility that takes five years to pass regulatory approval, pharming uses simple crop-growing practices that have been honed over centuries.
Like other GM technologies, pharming is not without its risks. Pressure groups such as Friends of the Earth fear that if food crops such as maize or tomatoes are adopted to grow drugs in some regions, there is a risk of their contaminating maize or tomato crops elsewhere that are intended for consumption. Clare Oxborrow, FoE's GM campaigner, said: "We wouldn't want to see this done in food crops and certainly not in field trials."
Professor Julian Ma, who leads the tobacco plant project at the Centre for Infection at St George's hospital in south London, acknowledges that the plants, and more importantly their pollen, have to be well contained. It is why the plants are being grown in £35,000 high-security Unigro
greenhouses which normally house experiments on plant viruses. Designed to withstand a lobbed brick, the greenhouses are twin-skinned plastic. Rupture either skin and the entire greenhouse is immediately flooded with formaldehyde, keeping everything inside.
At his labs at St George's, Prof Ma and his PhD student Amy Sexton have been producing the genetically modified tobacco plants and perfecting techniques to boost the amount of drug each plant makes. They take a common tobacco plant, Nicotiana tabacum, and punch small holes from the leaves. The circles of leaf are placed in a petri dish and then squirted with a liquid containing a genetically modified bacterium.
When the bacterium infects a plant leaf, it inserts some of its own genes into the plant's DNA, in effect hijacking its cellular machinery, and fooling the plant to produce new proteins.
In the wild these proteins cause tumours that kill the plant. But in the laboratory, the bacterium is made safe and doctored with different genes that fool the plant into making cyanovirin-N.
The researchers believe that cyanovirin-N could become a powerful new weapon in the fight against HIV, as it prevents the virus from infecting human cells. They are keen to make a microbicide cream for women in Africa and other developing countries where many have little or no control over their partner's use of a condom. The evidence so far is that a microbicide cream could dramatically cut down the spread of HIV through sexual activity. Experiments with rhesus macaques, which have similar reproductive physiology, have shown the microbicide protected 15 out of 18 monkeys from infection with a variant of the HIV virus, while all of eight control animals were infected.
To produce enough cyanovirin to make any significant impact on the HIV pandemic will take a lot of plants. The team calculates that 5,000kg of cyanovirin would be needed for 10 million women to have two doses a week - a scale of production that is far beyond the capabilities of conventional drug manufacturing. Each plant grows to a final weight of around 1kg.
Already the team is working on ways to maximise the amount of drug it can extract from a plant. Instead of growing the plants in soil, Prof Ma is experimenting with hydroponics, where the plants are grown in a nutrient-rich liquid. "The beauty of this is that the roots of the plant can be made to secrete the cyanovirin-N into the water they are grown in. That's a much simpler and cheaper way to extract the drug than having to grind the plants up," he says. "You can think of it as molecular milking."
If the plants continue to grow well in Kent - at the home of the East Malling Research facility - Prof Ma hopes to have enough drug to conduct human clinical trials of the microbicide within three years.
"After the GM food debate, everyone was wondering, is this technology going to fly? We have here a potentially important intervention against HIV, but one that needs enormous production capacity if it's going to make an impact globally on health. GM plants could provide the solution," says Prof Ma.
FAQ: Pharming HIV treatments
How many people have HIV?
Globally, 40m people are believed to be infected with HIV, 25m of whom live in sub-Saharan Africa. More than 40,000 people in the UK are receiving treatment for HIV. However, it is estimated a further 20,000 are infected but do not know it.
What treatments are there?
In developed countries, expensive cocktails of drugs are used to stop HIV becoming Aids. The treatment is scarce in countries most in need of it.Condoms are the most effective barriers to sexually transmitted HIV, but in many countries, women may not be able to insist on their use.
So far, none of the 90 or so experimental vaccines against HIV have proved successful, but there are high hopes for microbicide creams, which women can apply before sex. Trials of anti-HIV creams are continuing in South Africa and Uganda.
How does cyanovirin-N work?
To infect a human immune cell, the HIV virus has to latch on to the cell in a specific way. A protein on the HIV virus surface locks on to what is called the CD4 receptor on the immune cell, and from there, the virus can infect the cell. Cyanovirin works by latching on to the HIV virus, making it unable to stick to human cells.
What are the risks of pharming?
Tight controls are needed to ensure that GM crops do not contaminate natural plants. Growing in airtight greenhouses prevents pollen escaping, but an alternative is to grow GM crops that have no relatives they can pollinate. Scientists are also working on infertile GM crops that do not flower.
Ian Sample, science correspondent
Tuesday July 4, 2006
· Genetic tweak allows HIV drug to be harvested
· Environmentalists fear cross-contamination
In the perfectly controlled atmosphere of a brick-proof, hermetically sealed greenhouse deep in the Kent countryside, a fresh crop of tobacco plants is beginning to flourish.
There is nothing unusual about the plants' appearance, but they are nonetheless extraordinary. A genetic tweak ensures that every cell of every plant churns out tiny quantities of an experimental drug. When harvested, they could bring cheap medicine to millions.
Scientists say the £8m project could provide a powerful weapon against Africa's HIV pandemic.
The process is called pharming, and to many it is both the future of GM crops, and the future of the drugs industry. If the tobacco plants in Kent are a success, each one will provide 20 doses of an anti-HIV drug - enough to protect a woman from infection for up to three months.
Pharming is a marriage of high and low technology that capitalises on the advantages of both. Instead of needing a $500m drug manufacturing facility that takes five years to pass regulatory approval, pharming uses simple crop-growing practices that have been honed over centuries.
Like other GM technologies, pharming is not without its risks. Pressure groups such as Friends of the Earth fear that if food crops such as maize or tomatoes are adopted to grow drugs in some regions, there is a risk of their contaminating maize or tomato crops elsewhere that are intended for consumption. Clare Oxborrow, FoE's GM campaigner, said: "We wouldn't want to see this done in food crops and certainly not in field trials."
Professor Julian Ma, who leads the tobacco plant project at the Centre for Infection at St George's hospital in south London, acknowledges that the plants, and more importantly their pollen, have to be well contained. It is why the plants are being grown in £35,000 high-security Unigro
greenhouses which normally house experiments on plant viruses. Designed to withstand a lobbed brick, the greenhouses are twin-skinned plastic. Rupture either skin and the entire greenhouse is immediately flooded with formaldehyde, keeping everything inside.
At his labs at St George's, Prof Ma and his PhD student Amy Sexton have been producing the genetically modified tobacco plants and perfecting techniques to boost the amount of drug each plant makes. They take a common tobacco plant, Nicotiana tabacum, and punch small holes from the leaves. The circles of leaf are placed in a petri dish and then squirted with a liquid containing a genetically modified bacterium.
When the bacterium infects a plant leaf, it inserts some of its own genes into the plant's DNA, in effect hijacking its cellular machinery, and fooling the plant to produce new proteins.
In the wild these proteins cause tumours that kill the plant. But in the laboratory, the bacterium is made safe and doctored with different genes that fool the plant into making cyanovirin-N.
The researchers believe that cyanovirin-N could become a powerful new weapon in the fight against HIV, as it prevents the virus from infecting human cells. They are keen to make a microbicide cream for women in Africa and other developing countries where many have little or no control over their partner's use of a condom. The evidence so far is that a microbicide cream could dramatically cut down the spread of HIV through sexual activity. Experiments with rhesus macaques, which have similar reproductive physiology, have shown the microbicide protected 15 out of 18 monkeys from infection with a variant of the HIV virus, while all of eight control animals were infected.
To produce enough cyanovirin to make any significant impact on the HIV pandemic will take a lot of plants. The team calculates that 5,000kg of cyanovirin would be needed for 10 million women to have two doses a week - a scale of production that is far beyond the capabilities of conventional drug manufacturing. Each plant grows to a final weight of around 1kg.
Already the team is working on ways to maximise the amount of drug it can extract from a plant. Instead of growing the plants in soil, Prof Ma is experimenting with hydroponics, where the plants are grown in a nutrient-rich liquid. "The beauty of this is that the roots of the plant can be made to secrete the cyanovirin-N into the water they are grown in. That's a much simpler and cheaper way to extract the drug than having to grind the plants up," he says. "You can think of it as molecular milking."
If the plants continue to grow well in Kent - at the home of the East Malling Research facility - Prof Ma hopes to have enough drug to conduct human clinical trials of the microbicide within three years.
"After the GM food debate, everyone was wondering, is this technology going to fly? We have here a potentially important intervention against HIV, but one that needs enormous production capacity if it's going to make an impact globally on health. GM plants could provide the solution," says Prof Ma.
FAQ: Pharming HIV treatments
How many people have HIV?
Globally, 40m people are believed to be infected with HIV, 25m of whom live in sub-Saharan Africa. More than 40,000 people in the UK are receiving treatment for HIV. However, it is estimated a further 20,000 are infected but do not know it.
What treatments are there?
In developed countries, expensive cocktails of drugs are used to stop HIV becoming Aids. The treatment is scarce in countries most in need of it.Condoms are the most effective barriers to sexually transmitted HIV, but in many countries, women may not be able to insist on their use.
So far, none of the 90 or so experimental vaccines against HIV have proved successful, but there are high hopes for microbicide creams, which women can apply before sex. Trials of anti-HIV creams are continuing in South Africa and Uganda.
How does cyanovirin-N work?
To infect a human immune cell, the HIV virus has to latch on to the cell in a specific way. A protein on the HIV virus surface locks on to what is called the CD4 receptor on the immune cell, and from there, the virus can infect the cell. Cyanovirin works by latching on to the HIV virus, making it unable to stick to human cells.
What are the risks of pharming?
Tight controls are needed to ensure that GM crops do not contaminate natural plants. Growing in airtight greenhouses prevents pollen escaping, but an alternative is to grow GM crops that have no relatives they can pollinate. Scientists are also working on infertile GM crops that do not flower.
Ian Sample, science correspondent
Tuesday July 4, 2006
Guardian Unlimited
© Guardian Newspapers Limited 2006
© Guardian Newspapers Limited 2006
