Ricin and Immunotoxins

There are very few substances in this world that have both the ability to give life, as well as take it away. Since, September 11, 2001, the world as we once knew it has changed forever. Terrorist attacks using biological weapons/substances are a growing concern. One likely candidate for use in these kinds of attacks is a protein called ricin. Ricin is a toxin that can be extracted from the castor bean plant (Ricinus Communis) and can be found in the oil left behind from smashing the beans and leaves of the plant ( Layton). As an extremely effective toxin, ricin’s main function when released into the human body is to enter cells and prohibit the ribosomes from producing proteins (Layton). Nicknamed RIP, or Ribosome Inactivating Protein, ricin kills off all the ribosomes in the cytoplasm and terminates any chance of future protein synthesis (CDC). Proteins perform just about every function in a cell and a human’s health quickly deteriorates as their manufacturers are intoxicated and killed one by one.

New discoveries and innovative ideas in science and medicine are leading scientists to believe that ricin’s function can be used to kill specifically targeted cancer cells. Obviously, this toxin has the ability to kill humans, but in the near future it may ironically be a molecular machine used to breathe life into cancer patients, having the largest impact on developing countries.

Everyone is susceptible to cancer. In the United States, cancer accounts for one in every four deaths (ACS). Second only to heart disease, cancer kills more people in the United States over any other cause. In 2007, it is estimated that 564,830 people in America will die from cancer, which is about 1,500 people every day (ACS). As world population is increasing exponentially, these statistics illuminate a deadly disease that will continue to plague a larger world population in the future.

Not surprisingly, cancer affects people all over the world. Cancer took the lives of 6.7 million people worldwide in 2002 and this number is estimated to jump to 10.3 million deaths by the year 2020 (ACS). As Americans, we are fortunate to have access to such advanced healthcare. However, in many developing countries, the term healthcare is virtually non-existent. The main problem with healthcare in most developing nations is the lack of doctors and medicines able to adequately diagnose and treat people with this disease. Death rates from cancer in developing countries are much higher for these reasons.

Cancers of the liver, stomach, and cervix are the biggest threat to developing countries, second only to tobacco, which is the leading cause of cancer in the world (ACS). About 85% of the world’s population lives in developing countries and it is estimated that by the year 2010 these countries will consume 71% of the world’s tobacco (ACS). Clearly, cancer will continue to devastate millions of people in these developing nations as they will increasingly put themselves at risk of getting cancer through such high use of tobacco.

In the future, treatment of cancer in developing countries needs to be a global focus in science and medicine. New drugs, more accessible doctors, faster diagnosis, and better technology will be essential to help cut down on the number of deaths related to cancer.

Given the number of deaths related to cancer worldwide, it is obvious that the world needs a more effective and inexpensive way to treat this disease. Actually, the term cancer includes over one hundred separate diseases that are characterized by an abnormal and unregulated growth of cells in the body (Gordon). The cells that are affected by cancer are called malignant cells, which means that they divide at a more rapid pace than normal human cells do (Gordon). As these cells divide more rapidly than the natural rate due to damaged genetics, they begin to form a malignant tumor, which in turn destroys the tissue and organs that are close by (Gordon). In some instances, tumors release millions of malignant cells into the bloodstream which travel to other parts of the body where they form new tumors that further destroy other organs in other parts of the body (Gordon).

Fortunately, new advances in medical science have lead to the development of immunotoxins which are geared to find and eliminate malignant tumors caused by cancer. One of the toxins that researchers are considering using is Ricin.

Ricin may prove useful in cancer treatment because it is one of the most potent cell-killing toxins in existence. In fact, Ricin is so potent that a dose given to a human that is the size of the head of a pin would prove to be deadly (CDC). However, while Ricin is the toxin that is needed stop ribosomes in cells from producing proteins which are essential to cell life, the immunotoxin will not be effective unless it is combined with an antibody that will specifically seek out the unwanted cancer cells (Cornell). The immunotoxin carrying the Ricin must target only the cancerous cells and bind to specific cites on the surface of the cancer cell. Furthermore, the immunotoxin must then be internalized in the cell so that it may reach the cells cytoplasm were it has access to all the cell’s molecules for total destruction (Fitzgerald). Up to 108 ricin molecules can potentially bind to any given cell. Just one of these molecules that reaches the cytoplasm can destroy 1,500 ribosomes per minute and rapidly stops protein synthesis, effectively killing the cancerous cell (Cornell).

Even more interesting is the fact that researchers and scientists have the ability to clone this immunotoxin and make modifications to its genetic structure (Fitzgerald). Put brilliantly by Fitzgerald:

“By deleting the DNA that codes for the toxin binding region and replacing it with various complementary DNA encoding other cell-binding proteins, it has been possible to make chimeric toxins that kill cells on the basis of the newly acquired binding activity. The ability to make these chimeras may be useful in designing future toxin-based anticancer therapies.”

Scientists have found that immunotoxins perform their task very well in in vitro scenarios, like bone marrow transplants for instance by successfully killing T lymphocytes which help the receiver accept the donor’s bone marrow (Cornell). Researchers have yet to have similar success in in vivo applications, such as treatment of solid tumors (Cornell). Problems when attempting this type of treatment through the use of ricin immunotoxins occur because the immunotoxin can not successfully access the entire tumor mass for destruction (Cornell). The most common problem that is observed when treating patients with the ricin immunotoxin is called “vascular leak syndrome”, where fluids leak from blood vessels and cause several unwanted side effects (Cornell).

While finding a cure for cancer is highly unlikely, the future of cancer treatment lies in these immunotoxins. As more work is done on immunotoxins to improve their effectiveness and reduce side effects, they have the most potential for long term constant treatment. Immunotoxins would have the most impact on developing countries as they will likely be administered through pills or injections. Mass screening could also be offered free of charge through organizations to these developing countries in an effort to catch cancer early, which greatly reduces the risk of fatality (Cavalli). People would no longer have to travel to a hospital or pay for radiation and other expensive chemotherapies. Instead, once diagnosed, perhaps patients would be able to take a pill in their own village or home that would regulate and kill their cancer. With time, the pills would also be cheaper and easier to distribute in comparison to today’s leading cancer treatments (Cavalli). The development of effective immunotoxins can change the cancer-world as we know it.