Tobacco plants being used to produce human albumin

Human serum albumin (HSA) is the intravenous protein most commonly used in the world for therapeutic ends. It is employed to stabilise blood volume and to avoid risk of a heart attack, its administration in operating theatres being almost a daily occurrence.

It is used for haemorrhages, burns, surgical operations or when the patient shows symptoms of malnutrition or dehydration, chronic infections and renal or liver illnesses. The annual consumption in Spain is about 10 tons but, at a worldwide level, the demand exceeds 500 tons.

Agricultural engineer, Alicia Fernandez San Millan, has developed a novel technique in Spain - plastidial transformation, in order to produce, in a recombinant form, human albumin from tobacco plants. According to her PhD thesis, plastidial transformation is an economically viable alternative, as it enables increasing the levels of HSA by between 10 and a 100 times, compared to levels obtained by nuclear transformation.

The title of the PhD is: "Production of human serum albumin in tobacco plants by means of plastidial transformation". It should be added that this novel technique, fruit of Ms Fernandez San Millan's PhD, has been patented at a world level and there is already a company interested in marketing it.

An efficacious and cheap alternative

Commercial albumin is currently extracted from blood, but the lack of sufficient reserves to cover all worldwide needs has instigated researchers to look for new formulae to multiply this protein. One of the methods most used has been the obtention of HSA from yeasts and mammal cells. However, their high market-place costs have meant that these methods are not competitive. While the price at the pharmacy of albumin produced using plasma is 4 euros per gram, that obtained from yeasts or mammal cells costs between 300 and 4,000 euros per gram. Another option worked on over recent years has been the production of albumin from vegetables, always using nuclear transformation.

The novelty in this research arises from the method of obtention of the HSA. The plastidial system enables the extraction of great quantities of albumin. With nuclear transformation, the maximum level obtained is 0.5% of the total soluble protein of the plant, while application of the plastidial system multiplies this percentage by fourteen (to 7%), reaching an average of 0.9 milligrams of HSA per gram of fresh leaf weight.

The key is the place where the gene in question is deposited. With the nuclear transformation method, it integrates into the DNA of the cell nucleus of the leaf and, thus, can only manage a small number of copies of the gene. With the plastidial system, on the other hand, the gene is introduced into the chloroplast, where photosynthesis takes place and where the genomes can multiply up to 10,000 times.

A property highly valued by the experts has to be added to these positive results: the production of albumin from plants using this technique does not involve the escape of genes through pollen transmission given that, with most crops under cultivation, the genome of the plastids is inherited maternally.

More biomass in tobacco plants

The tobacco plant is very easy to handle genetically and also it is great generator of biomass. The authoress of the thesis says that up to 100 tons of biomass per hectare can be obtained in optimum growth conditions. "Given that the protein is produced in the chloroplasts, the more the leaf biomass we have, the more albumin we can get".

To date all the trials undertaken with tobacco plants have been with laboratory varieties. The aim is to do tests with commercial varieties. Laboratory plants are very small and, as a result, the quantity of albumin extracted is not sufficient. However, the commercial varieties of tobacco are some 30 times more productive in terms of biomass.

Despite the advantages demonstrated by the experts, there is still a long way to go. Involving, as it does, a protein that is intravenously injected into patients, it has to be thoroughly purified to eliminate any kind of contaminant. Moreover, it is necessary to assure that the protein obtained has an identical structure to the human one to guarantee that its functioning will be 100%.