Producing therapeutic proteins in tobacco — Tobacco can be good, after all

For smokers, tobacco is a blessing; for the health conscious, it is a curse. Today, modern biotechnology has given tobacco a new application that is beneficial to both smokers and the health conscious as well, giving it a new and better image. Studies on the production of therapeutic proteins in plants like tobacco are now ongoing and are at various stages of development.

Plants as manufacturers of therapeutic proteins — biopharming

Since the 1980s, the manufacture of proteins to cure human diseases constitutes a significant sector in the pharmaceutical industry and is worth billions of dollars. A $90-billion sale of therapeutic proteins is expected by 2010.

Before the mid-1980s, insulin was isolated and purified from the pancreas of slaughtered pigs and cows. Presently, most therapeutic proteins in the market are produced using microbes through fermentation. Certainly, the production of therapeutic proteins in microbes is already a big improvement from their purification from conventional sources. Human insulin is an example of a therapeutic protein produced in microorganisms through modern biotechnology or recombinant DNA technology. Through this method, the human insulin gene is incorporated in a carrier DNA that is introduced to bacteria which then are allowed to multiply and produce the human insulin protein.

However, this fermentation process is still relatively low yielding and expensive. For instance, according to Dr. Henry Daniell, former professor of Auburn University, Auburn, Alabama and founder of Chlorogen Inc., “the requirement for Insulin Growth Factor I (IGF-I) to treat patients with liver problems per year is 600 mg but the cost per mg is $30,000. However, the best yield for IGF-I using bacterial culture was 5 mg/L.” Therefore, the need to produce human therapeutic proteins in larger quantities and lower cost is imperative.

Scientists have turned to plants to produce health products such as human therapeutic proteins. This new wave of modern biotechnology is called biopharming and through this method, the gene for the therapeutic protein is introduced into the plant genome through high pressure or biolistic means or through a bacterial symbiotic process. A major advantage of using plants as biofactories is the estimated lower cost of production (e.g., $80–250/g using corn versus $350–1200/g using mammalian cell culture). Secondly, plants offer a large production capacity. Thirdly, plants do not carry potential harmful human or animal viruses which are a concern when using mammalian cell culture or animals as biofactories.

Many studies are ongoing in the United States at the laboratory and field stages to produce pharmaceuticals such as antigens, antibodies, growth factors, hormones, enzymes, blood proteins and collagen in plants such as corn, soybean, rice, tomato, barley, safflower, peas and tobacco. These plant-made pharmaceuticals address various diseases like cancer, kidney disease, HIV, heart disease, diabetes, Alzheimer’s disease, cystic fibrosis, multiple sclerosis, spinal cord injuries, hepatitis C, obesity, arthritis and others.

For this purpose, tobacco is a good plant of choice because the pharma product can be expressed or produced at a high level. The practices of planting and managing tobacco as a crop are also well established. Tobacco can grow in areas with less water. Hence, it is not only economically friendly but environmentally friendly as well. Moreover, tobacco is not a plant food. Thus, the therapeutic protein- or pharma-containing tobacco will not go to the food chain. Many of the ongoing researches in developing plant-made pharmaceuticals are therefore using tobacco as biofactory.

To address the potential mixing of pharmaceutical plants with food crops, biotech companies are adopting production strategies that involve confined facilities (greenhouses and isolated fields), the use of self-pollinated crops (like tobacco) and a technology that prevents transfer of the introduced trait by pollen called chloroplast transformation technology. This new technology allows the stable integration of the introduced gene (called the transgene) in the chloroplast genome, which is transferred only through cytoplasmic inheritance and not through the pollen. Interestingly, the pollen has no or limited chloroplast DNA and limited amount of cytoplasm. On the other hand, the egg cell in the female flower or pistil has chloroplast DNA and a large cytoplasm. Thus, through chloroplast transformation technology, the transgene, which is in the chloroplast genome and is located in the egg cell, cannot be transferred to another plant via pollen but only through cytoplasmic inheritance. Therefore, therapeutic genes introduced in tobacco (or another plant) through the chloroplast transformation technology cannot be transferred to other tobacco plants. Moreover, by nature, the tobacco plant is self-pollinating, hence, the spread of pollen is also limited.

This new wave of modern biotechnology promises the production of more affordable human therapeutic proteins.

The use of tobacco as pharma-plant producing proteins that have therapeutic applications can be a boon to our tobacco farmers and industry. Tobacco will then lose its bad image and be considered beneficial, after all.

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Rowena H. Oane and Emeru L. Bool, MS students in Molecular Biology and Biotechnology (MBB) and Genetics, respectively, at the University of the Philippines Los Baños, wrote this science article for the Special Topics course under Prof. Evelyn Mae Tecson-Mendoza. E-mail them at [email protected] and [email protected].