Biological Computer Diagnoses Cancer and Produces the Drug -- in a Test Tube

The world’s smallest computer (around a trillion can fit in a drop of water) might one day go on record again as the tiniest medical kit. Made entirely of biological molecules, this computer was successfully programmed to identify - in a test tube - changes in the balance of molecules in the body that indicate the presence of certain cancers, to diagnose the type of cancer, and to react by producing a drug molecule to fight the cancer cells.

The Weizmann Institute of Science team that developed the computer published these results today in Nature. Headed by Prof. Ehud Shapiro, of the Departments of Computer Sciences and Applied Mathematics, and Biological Chemistry, the team included research students Yaakov Benenson, Binyamin Gil, Uri Ben-Dor and Dr. Rivka Adar. Shapiro presented the team’s findings today at the Brussels symposium “Life, a Nobel Story,” in which Nobel Laureates and others addressed the future of the life sciences.

As in previous biological computers produced in Shapiro’s lab, input, output and “software” are all composed of DNA, the material of genes, while DNA-manipulating enzymes are used as “hardware.” The newest version’s input apparatus is designed to assess concentrations of specific RNA molecules, which may be overproduced or under produced, depending on the type of cancer. Using pre-programmed medical knowledge, the computer then makes its diagnosis based on the detected RNA levels. In response to a cancer diagnosis, the output unit of the computer can initiate the controlled release of a single-stranded DNA molecule that is known to interfere with the cancer cell’s activities, causing it to self-destruct.

In one series of test-tube experiments, the team programmed the computer to identify RNA molecules that indicate the presence of prostate cancer and, following a correct diagnosis, to release the short DNA strands designed to kill cancer cells. Similarly, they were able to identify, in the test tube, the signs of one form of lung cancer. One day in the future, they hope to create a “doctor in a cell”, which will be able to operate inside a living body, spot disease and apply the necessary treatment before external symptoms even appear.

The original version of the biomolecular computer (also created in a test tube) capable of performing simple mathematical calculations, was introduced by Shapiro and colleagues in 2001. An improved system, which uses its input DNA molecule as its sole source of energy, was reported in 2003 and was listed in the 2004 Guinness Book of World Records as the smallest biological computing device.

Shapiro: “It is clear that the road to realizing our vision is a long one; it may take decades before such a system operating inside the human body becomes reality. Nevertheless, only two years ago we predicted that it would take another 10 years to reach the point we have reached today.”

Prof. Ehud Shapiro's research is supported by the M.D. Moross Institute for Cancer Research, the Samuel R. Dweck Foundation, the Dolfi and Lola Ebner Center for Biomedical Research, the Benjamin and Seema Pulier Charitable Foundation, and the Robert Rees Fund for Applied Research.

Further information and photos can be obtained online at: www.weizmann.ac.il/udi/PressRoom <http://www.weizmann.ac.il/udi/PressRoom> or by contacting the Weizmann Institute Publications and Media Relations Department at 972-8-934-3856.