Pharming: Merging Pharmaceuticals and Agriculture

By: Oriel Schmulevich  |  August 29, 2016

AgroinfiltrationTo most people, medicine and crops may seem like two unrelated industries, but in fact the two have a very special relationship, and I am not talking about herbal supplements. More than just a portmanteau, pharming is a promising biotechnological innovation propelling us into the future. Scientists working for biotech companies have applied recombinant DNA technology to the production of plant­-made pharmaceuticals (PMP). They have transformed an ordinary tobacco plant into a drug producing factory that can produce vaccines, antibodies, and other therapeutic proteins, on mass scales.

This technology is not new however: it has been around since the 1980s with experiments that never made it through phase 1 of clinical trials. In recent years though, several drugs have inched their way through phase 2 of clinical trials and have shown much promise.

The advent of transgenic crops solves a critical issue in the public health arena. According to the World Health Organization (WHO), it takes anywhere between 10­-15 years for a vaccine to become available to the public. This can lead to disastrous effects when no treatment is available during an epidemic. According to the CDC, the 2009 H1N1 pandemic took more than 150,000 lives. A severe shortage of the swine flu vaccine largely contributed to that death toll. With the recent Ebola epidemic killing over 11,000 people, the need to manufacture massive quantities of the drug in a short amount of time was greater than ever.

Plants are the most efficient organisms for producing proteins. The turnover rate by which plants can make proteins is faster than bacterial or mammalian cell cultures. Additionally, using plants to produce antibodies eliminates the harmful byproducts associated with traditional bacterial, fungal, and mammalian cell cultures.

One application of PMP is the experimental Ebola drug ZMapp. ZMapp is derived as a PMP from the tobacco plant Nicotiana benthamiana. The bacteria Agrobacterium tumefaciens is genetically modified to express the genes for those antibodies specific to Ebola. The plants are then infected by this genetically modified bacteria by dipping their leaves in the bacterial solution. These transgenic plants then respond by expressing the desired antibodies. Cultures are retrieved, purified, and then used for treatment.

ZMapp is composed of 3 monoclonal antibodies. Antibodies are found in the serum, or non-­blood component, of the circulatory system. This falls under the category of a type of passive immunity called heterologous hyperimmune serum, or antitoxin. This is useful in fighting infections once the person is already infected by a virus, unlike vaccines, which teach the body how to identify and fight infections before exposure occurs. Antibodies for a specific antigen are transferred from a donor to a host (from the plant to a human in this case) which helps activate the immune system and fight the infection.

According to WHO, it costs hundreds of millions of dollars to produce a vaccine. Harvesting plant based vaccines and proteins reduces the cost of production by 10 percent, and also reduces water by 10 percent compared to conventional production. This cost effective operation means that it will be accessible to lower income peoples as well. Additionally, edible vaccines are a possibility with PMPs which could allow people in developing nations to get access to previously inaccessible immunity.

With the emerging field of personalized medicine, PMPs may play a crucial role in providing efficient therapies. Doctors and scientists are hopeful that certain cancers, HIV, heart disease, diabetes, and many more debilitating diseases will soon benefit from the specialized proteins that are customized to each individual patient using PMPs.

Although not proven to be safe and effective yet, doctors are hopeful that ZMapp was responsible for curing two U.S. aid workers, Dr. Kent Brantly and missionary Nancy Writebol, of their Ebola infections. It is important to note, unfortunately, that a third Ebola victim receiving ZMapp did not survive.

Of course, as with all medical discoveries, there is a long way to go. The process of production is still not streamlined enough in order to reach numbers in the millions in the event of a future epidemic. The tobacco leaves which store the antibodies need to be painstakingly ground up, purified, and extracted. Only a dozen or so people can be treated by each plant. Additionally, the effectiveness of ZMapp on Ebola is still uncertain, and it is still being tested to ensure that it is safe for humans.

With transportation making it easier for viruses and bacteria to spread, it is critical that we are prepared to deal with health crises in a timely manner. Perhaps we can look to PMPs for the answer.