Researchers Devise a Fast and Sensitive Way to Detect Ricin

Newswise — Scientists at Albert Einstein College of Medicine of Yeshiva University have developed a simple, accurate, and highly sensitive test to detect and quantify ricin, an extremely potent toxin with potential use as a bioterrorism agent. The report appears as a featured article in the April 12th issue of Analytical Chemistry. Ricin, a protein extracted from castor beans, can be in the form of a powder, mist, pellet or solution. When injected or inhaled, as little as one-half milligram of ricin is lethal to humans. No antidote is available. The most infamous ricin attack occurred in London in 1978, when Bulgarian dissident Georgi Markov died after being stabbed with an umbrella that injected a ricin-coated pellet into his leg.

The ricin assay described in the journal article was developed in the laboratory of Vern Schramm, Ph.D., professor and Ruth Merns Chair of Biochemistry at Einstein and corresponding author. The assay detects small amounts of ricin more accurately and faster than ever before.

Users of the assay would place samples of potentially adulterated food, or swabs used to wipe potentially contaminated surfaces, into a few drops of a mixture of reagents; the mixture will emit light if ricin is present, with higher luminescence indicating greater concentrations of the toxin.

Dr. Schramm believes the assay's most immediate application is for discovering drugs that could serve as antidotes for ricin poisoning.

"Previously we had to rely on laborious, multi-step methods to see if a compound was preventing ricin from working, which is probably why no antidote to ricin has yet been discovered," explained Dr. Schramm.

After ricin enters cells, it kills them by interfering with their ability to make proteins─a basic cellular function. Ricin does this by disrupting ribosomal RNA (the key component of ribosomes, the cell's protein manufacturing "machines" ). The ricin attack causes ribosomal RNA to release a molecule of adenine. Dr. Schramm's assay detects and quantifies ricin by measuring the amount of adenine released by cells.

"Our lab's expertise is in enzymes," says Dr. Schramm. "One day I realized we could use a specific enzyme to convert the adenine released by ricin into ATP─a molecule whose presence can be easily detected by an already-available assay based on the light-emitting gene from fireflies. In retrospect, like many scientific advances, it's such a simple idea that I'm surprised it wasn't thought of earlier."

Ricin has also been used as an anticancer agent by linking it to antibodies that home to tumors and deliver the ricin 'warhead' to kill cancer cells. Einstein scientists indicate that detection of ricin in cancer trials may be an early use of this technology. While the researchers emphasize that the ricin detection method is now laboratory-based, they also predict that relatively minor changes will be needed to make detection of ricin by light practical for field and clinical applications.

Albert Einstein College of Medicine has filed a patent application on the ricin detection method and is interested in licensing the technology to a company or organization that would develop it further for drug discovery and public health applications.

The paper by Matthew B. Sturm and Vern L. Schramm is titled "Detecting Ricin: Sensitive Luminescent Assay for Ricin A-Chain Ribosome Depurination Kinetics" appears in the April 12th issue of Analytical Chemistry.

About Albert Einstein College of Medicine of Yeshiva UniversityAlbert Einstein College of Medicine of Yeshiva University is one of the nation's premier centers for research, medical education and clinical investigation. It is the home to some 2,000 faculty members, 750 M.D. students, 350 Ph.D. students (including 125 in combined M.D./Ph.D. programs) and 380 postdoctoral investigators. Last year, Einstein received more than $130 million in support from the NIH. This includes the funding of major research centers at Einstein in diabetes, cancer, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Through its extensive affiliation network involving five hospital centers in the Bronx, Manhattan and Long Island " which includes Montefiore Medical Center, The University Hospital and Academic Medical Center for Einstein " the College runs one of the largest post-graduate medical training program in the United States, offering approximately 150 residency programs to more than 2,500 physicians in training. For more information, please visit www.aecom.yu.edu.