Fighting HIV with tobacco doesn’t sound like something a doctor would normally recommend. Condoms and/or abstinence are the two standardly recommended methods of avoiding infection, but both clearly have inherent drawbacks.
“Condoms work well, but they also prevent fertility, so if you want to have children and you’re part of a community where there’s high risk of HIV infection, you’ve got a problem,” points out Professor Julian Ma, of St George’s, University of London. “Also, in sub-Saharan Africa, it’s very difficult for a woman to insist on condom use”.
With no cure or vaccine for HIV yet available, Ma and his collaborator, Professor Rainer Fischer, are co-ordinating a team of researchers across 39 European institutes who are now focused on neutralising the virus before it can cause infection – and this is where a soupy green sludge of pulverised tobacco leaves might provide an answer.
The idea of using plants to create antibodies to disease was initially mooted in the late 1980s, says Ma.
“You had flights of fancy where people were talking about growing fruit that would contain vaccines, the idea being that you could give a banana to a child and they’d be immunised against a particular disease,” he explains.
“It’s very attractive at first glance, but people have pulled back from that because dose control is very important, and also control of administration. The concept, however, of growing plants containing useful substances – which you could process, extract and freeze-dry, then have administered by a medical professional – still remains.”
As Ma points out, the ravages of infectious diseases are borne most heavily by poor people in developing countries who can’t afford to buy medicines, and where safe and reliable methods of distribution can be hard to ensure.
His aim, therefore, is to come up with an HIV neutralising agent that can be made cheaply, on a large scale, and where production can be easily carried out in developing countries themselves.
The delivery method for the antibody he’s intending to use is a topical microbicide – put simply, a gel, like a spermicide, that would be inserted vaginally or rectally, and so would be under the complete control of women. It would neutralise the HIV virus, but would have no effect on sperm, so fertility wouldn’t be affected.
Interestingly, antibodies that neutralise the HIV virus have already been identified and can be made to order. The problem is that creating such highly virus-specific antibodies – monoclonal antibodies – is expensive. The anti-cancer drug Herceptin, for instance, uses monoclonal antibodies and its prohibitive cost has made it a controversial drug for prescription even in some developed countries.
Ma, moreover, says that because viruses mutate, any microbicide would ideally be a cocktail of two or three antibodies. This makes the medicine twice or three times more expensive.
Enter the tobacco plant. Plants can grow proteins – which is what antibodies are – and if they’re genetically modified, they can grow specific proteins that scientists know will act on the HIV virus (though diseases such as rabies could also be targeted).
“Common sense tells you plants are going to be cheaper,” says Ma. “You could eventually grow them in fields on a large scale, but there are environmental issues that mean this is unlikely to be acceptable in the short term. Pollen from our tobacco plants might get released, or you could get animals eating them.”
The solution currently is to grow the tobacco plants in glasshouses. This is being done in compost in Germany, and in a special hydroponic solution in Kent. Both will go through clinical trials.
The most advanced part of the project to date is the compost-grown tobacco. But soil as a growing medium is hard to control in the way that pharmaceutical regulators need – in different parts of the world it would be made up of different components, for instance.
On the other hand, if antibodies from soil-grown tobacco are proved to be safe and effective, it may be that the issues of standardised soil composition can be overcome, enabling developing countries to grow the raw materials for an effective HIV microbicide easily and cheaply.
Once the plant is mature, the leaves are harvested, ground up and purified to extract the antibody. This is currently being done in the Fraunhofer Institute for Molecular Biology and Applied Ecology in Germany, and first-stage trials to check on the safety of a topical gel are, subject to regulatory approval in the UK, about to begin. Getting this permission has been a hard slog, says Ma.
Approval for the trial production process has just been granted in Germany and an application will be made to the UK regulators in the new year. The German decision is helpful to the project’s case, Ma says, but there are no guarantees that the UK will take the same view.
Getting the pharmaceutical industry to take the research seriously has also proved tricky, says Ma. At this stage in a drugs research project, it would be normal to expect some serious industrial investment, but nobody’s been willing to cough up. “There’s been some disbelief that plants would be viable,” he explains. “Plus, it would be a push to makepharmaceutical companies switch their production methods, because they’ve invested so much in existing systems.”
Ma also points out that pharmaceutical companies’ priorities are not to produce drugs for developing-world problems, because, presumably, there isn’t any money in it. The final nail in his hopes of investment at this stage has been corporate wariness around genetically modified products.
He’s optimistic, however, that “once through this trial, if we can demonstrate that plants are acceptable as a clinical product and we show that it’s a scaleable method, I do think many will come in.”
It’s likely to take about five or six years to reach that stage. In the long term, Ma would like to see pharmaceutical production as an industry that could provide an alternative income for farmers both in Europe and in developing countries.
“It couldn’t be a field of food and a field of pharma sitting side by side,” he says. “It would need to have a dedicated farmer with expertise.”
The debate raging around GM food hasn’t yet been comprehensively won by either side: now that GM pharmaceuticals are a real prospect, it will be interesting to see if the debate is waged with equal vigour when the potential beneficiaries are poor people who disproportionately bear the ravages of disease.
The Guardian
