Computing Device To Serve As Basis For Biological Computer

Shapiro's mechanical computer has been built to resemble the biomolecular machines of the living cell, such as ribosomes. Ultimately, this computer may serve as a model in constructing a programmable computer of subcellular size, that may be able to operate in the human body and interact with the body's biochemical environment, thus having far-reaching biological and pharmaceutical applications.

"For example, such a computer could sense anomalous biochemical changes in the tissue and decide, based on its program, what drug to synthesize and release in order to correct the anomaly," Prof. Shapiro said.

The Turing Machine Unlike existing electronic computers, which are based on the computer architecture developed by John von Neumann in the U.S. in the 1940s, the new mechanical computer is based on the Turing machine, conceived as a paper-and-pencil computing device in 1936 by the British mathematician Alan Turing. The theoretical Turing machine consists of a potentially infinite tape divided into cells, each of which can hold one symbol, a read/write head, and a control unit which can be in one of a finite number of states. The operation of the machine is governed by a finite set of rules that constitute its "software program." In each cycle the machine reads the symbol in the cell located under the read/write head, writes a new symbol in the cell, moves the read/write head one cell to the left or to the right, and changes the control state, all according to its program rules.

Although the Turing machine is a general-purpose, universal, programmable computer and is key to the theoretical foundations of computer science, it has never before been embodied in an actual computing device. Shapiro's mechanical device embodies the theoretical Turing machine, and as such is a general-purpose programmable computer.

The device employs a chain of three-dimensional building blocks to represent the Turing machine's tape, and uses another set of building blocks to encode the machine's program rules. In each cycle the device processes one "rule molecule." The device is designed so that the processing of the molecule modifies the polymer representing the Turing machine's tape in accordance with the intended meaning of the rule.

At the conference, Shapiro will present a 30-cm high plastic model of his mechanical computer. He hopes that in the future, with the advent of improved techniques for the analysis and synthesis of biomolecular machines, the actual computer could possibly be built from biological molecules, so that it would measure about 25 millionths of a millimeter in length, roughly the size of a ribosome.

The Computer and the Ribosome In fact, Prof Shapiro designed the mechanical computer with the ultimate goal of constructing it from biological molecules. The computer is not more complicated than existing biomolecular machines of the living cell such as the ribosome, and all its operations are part of the standard repertoire of these machines. These operations include the mechanical equivalents of polymer elongation, cleavage and ligation, as well as moving along a polymer and being controlled by coordinated structural changes.

The ribosome is the molecular machine of the living cell that performs the final step of interpretation of the genetic code by translating messenger RNA, which is transcribed from DNA, into protein. A key similarity between Shapiro's mechanical computer and the ribosome is that a "program rule" molecule specifies a computational step of the computer similar to the way a transfer RNA molecule specifies a translation step of the ribosome.

The computer is similar to the ribosome in that both operate on two polymers simultaneously. They function by incorporating incoming molecules into a growing polymer by matching these molecules to the analogous segments on the first polymer. However, unlike the ribosome, which only "reads" the messenger RNA in one direction, the computer edits the tape (first) polymer and may move in either direction.

A Future Interactive Biological Computer The computer design may allow it to respond to the availability and to the relative concentrations of specific molecules in its environment, and to construct program-defined polymers, releasing them into the environment. If implemented using biomolecules, such a device may operate in the human body, interacting with its biochemical environment in a program- controlled manner. In particular, given a biomolecular implementation of the computer that uses RNA as the tape polymer, the computer may release cleaved tape polymer segments that function as messenger RNA, performing program- directed synthesis of proteins in response to specific biochemical conditions within the cell. Such an implementation could give rise to a family of computing devices with broad biological and pharmaceutical applications.

###About Prof. Shapiro Prof. Shapiro received his Ph.D. from Yale University and joined the Weizmann Institute in 1982. During the 1980s he was involved with the Japanese Fifth Generation Computer Project and published numerous scientific papers in the area of concurrent logic programming languages.

In the early 1990s, Shapiro's innovative research in programming languages led to the establishment of Ubique, a company that develops interactive online environments. Shapiro took a leave from Weizmann to establish Ubique, and when the company was bought by America Online, Inc., he moved to the U.S. to assist in incorporating Ubique's Virtual Places technology in America Online's internet services. When America Online sold Ubique to Lotus/IBM in 1998, Shapiro returned to his research post at the Weizmann Institute.

The mechanical design of Shapiro's computer model was performed by K. Karunaratne from Korteks and M. Schilling from Schilling 3D Design, both from San Diego, CA.

The Weizmann Institute of Science, in Rehovot, Israel, is one of the world's foremost centers of scientific research and graduate study. Its 2,500 scientist, technicians, and engineers pursue basic research in the quest for the enhancement of the human condition. New ways of fighting disease and hunger, protecting the environment, and harnessing alternative sources of energy are the Weizmann Institute's highest priorities.

Notes: Photos of Prof. Shapiro and his mechanical computer model are available in color, by e-mail or regular mail.

Additional information on this research can be found on the Web at http://www.wisdom.weizmann.ac.il//~udi