How can we use nature’s poisons to our benefit?
Ricin is a protein toxin that is extracted from the castor bean. Photo: Agricultural Reasearch Service, USDA.
Vitetta: Most people know that ricin is a potential biological weapon, but it can also be harnessed for biomedicine. My research involves using a portion of the ricin toxin to develop a new class of therapeutics, called “immunotoxins.” Over the past few decades, immunotoxins have been taken from discovery to clinical trials in patients with a variety of cancers. In addition, emerging from this medical work was the development of a new and effective vaccine against ricin, which completed its first successful clinical trial in 2005. The vaccine was safe and induced antibody production in human volunteers.
Ricin, a natural toxin, is a byproduct of castor oil production. Ricin is very easy to obtain, with an estimated 50,000 tons available in the world today. Castor beans grow wild everywhere, and you don’t really need a whole lot of expertise to purify it. In fact, you don’t even need to purify it. If you mash up castor beans you basically get a crude toxin powder that is very stable. Ricin can be used to contaminate food, water, or air and in high enough levels is fatal when ingested or breathed in. Anyone can pull up information on the Internet about ricin production—sad but true. The fact that it is easy to get, easy to work with, and so toxic makes it very worrisome. It is quite different from something like anthrax, where you must have the scientific know-how to make it.
Immunotoxins are made by linking a tumor-seeking antibody to a portion of the ricin toxin. [An antibody is a protein molecule that defends the body against germs or harmful compounds; some antibodies are synthetic]. Once bound to the cancer cell, it is internalized and kills it, but because the antibody targets only cancer cells, it spares normal cells. When you think of the damaging side effects of current cancer therapies and other therapies for viral disease, such as HIV, immunotoxins offer a promising alternative. They are the “magic bullet” immunologist Paul Ehrlich envisioned in the 1900s, where a therapeutic agent could be delivered directly to abnormal cells without much effect on healthy cells.
We can find sources for immunotoxins in nature. In addition to the castor bean, there are other plants, such as pokeweed. Bacterial toxins are also known. Our lab chose ricin, not only because it’s easy to obtain, but also because the structure is easy to work with. We knew we could separate the A and B chains of the protein to get a very toxic subunit A chain that we could manipulate to attach to an antibody and create a specific delivery system.
Have any of your experiments proven successful?
Vitetta: They have been very successful, in mice and in humans. We can cure mice with tumors by using the appropriate dose and dose regimen of immunotoxins. Clinical studies in human cancer patients are ongoing and encouraging. But it will take time to realize the full potential of immunotoxins and get them FDA approved.