Sunday, August 14, 2011

Julian Ma: I growing antibodies in tobacco plants to prevent HIV

Julian Ma amid GM tobacco plantsProfessor Julian Ma is pharming tobacco to locate an antibody against HIV. Above, surrounded by GM plants at the medical school in St. George's Hospital, London. Photograph: Frank Baron to the guardian

Julian Ma is the leader of infection and immunity Research Centre in St George's Hospital Medical School in London. He specializes in genetically modifying plants of to produce drugsuseful, a process called pharming, which he hopes will bring cheaper medicines for developing countries. His Pharma-Planta project was recently given permission by UK medical regulator, the medicines and Healthcare products Regulatory Agency, to carry out human trials of a monoclonal antibody, is grown in tobacco plants that can be used to prevent HIV infection.

How a regular drugs?

The class of drugs we treat is called recombinant proteins. What does a kind of protein that is made in a system that is not hosting the original protein. Recombinant proteins have done for decades with the help GM of technologies – it started with GM bacterium e. coli, which was used to make human insulin. We then moved to GM yeast (an example is the vaccine against hepatitis B). Gold standard for making recombinant proteins, especially monoclonal antibody (Herceptin is a good example), more recently, using mammalian cells. The most commonly used is a cell derived ovaries of a Chinese hamster (CHO). These cells are grown in large fermenters as a liquid culture.

Why would use plant cells must be better than these traditional methods?

These fermentation containers must be kept completely sterile and the manufacturing facilities that are involved are very expensive. The thinking behind the whole plants were: here we have a very simple and effective protein-manufacturing system, which simply uses sunlight, water and soil to make proteins. It is no coincidence, plants are at the bottom of the food chain, because it is the cheapest and most economic way to make proteins on a large scale.

How pure the protein that comes out of your experimental installations?

There are many potential variables. The conditions under which you grow the facility inherently have some variability; daylight affects it, and there are variations in the environment surrounding the greenhouse gases. And you got land in your greenhouse gases growing medium. What we have shown in our work is that despite all the variations, what comes out of the installation can be made very high quality; in fact, the quality, we reached even higher than it had gained earlier user CHO-system.

You can use any installations for pharming?

There are some other species, such as maize, which would work very well – any facility that produces a seed would be a good target for us, because the seeds are primarily dehydrated protein-storage bodies. We have selected tobacco for several reasons: the most important thing is that it is not a part of the food chain, and we were very conscious that we should find a species that would not give us the environmental question as to whether we may disclose our product in the food chain. Tobacco is a major crop in the world, so if you're looking at non-food crops, tobacco is a best-esta established. And thirdly, it produces a huge amount of biomass – if you want to create a very comprehensive system of production, biomass levels are important.

Where will this go in the future?

One of the major areas for potential growth of the plants is to make not only very complex molecules but also combinations of complex molecules like antibodies. The product we are working on, anti-HIV antibody, eventually will be used in combination with one or two antibodies: it is very unlikely it will be used by itself. The reason is that HIV is very good for mutation, so you must specify two or three antibodies to prevent viral escape. This concept is applicable across the board for infectious diseases. Plants allows you to make many molecules to add to a cocktail of drugs, because the potential costs of making the molecules is much lower than conventional systems. You can now afford to do cocktails of two to three antibodies, whereas until now, we have not been able to afford to.

You could one day eat plants for extracting drugs, instead of processing them?

This proposal has been around for quite a long time now, and it is attractive, but there are some difficulties with that. The early proposal of growing banana plants or tomato plants and garden fresh produce as a tool for delivery have been discarded, mainly because you can't control the dosage of your medicines very easily. This does not mean you can take the kind of system and combine it with some simple food processing technology. If you were able to produce a medicine in an edible fruit, like a tomato, you can make a simple food processing steps to stabilise the albuminoidal substances in the product's tomato and also standardize the dose. There could be delivered by the oral route.

Deliver vaccines by the oral route has been the Holy Grail of vaccinologists in decades. There are some technical difficulties with this: some people not good answer oral vaccines, and there are some immunological questions. But the potential is there ... I think it is some way off, but, and what we have done at this stage – demonstrated that plants are a viable manufacturing system for vaccines or antibodies — is the first step on a very long road, will ultimately lead to an edible vaccine. In the meantime, it will give us many other valuable products, which looks much more like conventional medicines.

Your technique makes drugs more cheaply?

Real cost of medicines is not down to the cost of the goods themselves, this is due to the many years it takes to develop a drug, and many other steps. Which I think cost will, however, is in the very early stages of drug development. In a plant system is the investment you need to make early to test a new drug is much lower than if you wanted to do it by conventional systems. It could be 10 to 100 times cheaper. We know that many drug fails in the first few years of development, but if the costs of the importance of each of these drugs is very high, very few people are able to enter the field. If you make the cost of entry into service, look at the new drugs are much lower, can use plant technologies, what you bring underdeveloped countries to look at the drug, as you may find very important.

You can hear Professor Julian Ma of the latest edition of the guardian's Science Weekly per podcast


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