News | July 6, 1999

Prototype Biological Computer Presented

A general-purpose mechanical computer designed for biomolecular and pharmaceutical applications has been developed by Ehud Shapiro of the Computer Science and Applied Mathematics Department at the Weizmann Institute of Science (Rehovot, Israel). This mechanical computer, the first of its kind, was presented last week at the Fifth International Meeting on DNA-Based Computers at the Massachusetts Institute of Technology (Cambridge, MA).

Shapiro's mechanical computer has been built to resemble molecular machines of the living cell, such as ribosomes. Ultimately, this computer may serve as a model for the construction of a programmable computer of subcellular size that can work in the human body and interact with the body's biochemical environment.

"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," Shapiro said.

This machine, unlike existing electronic computers, which are based on the computer architecture developed by John von Neumann in the U.S. in the 1940s, is based on the Turing machine, a paper-and-pencil computing device conceived 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 that can be in one of a finite number of states. The operation of the machine is governed by a 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 presented 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, Shapiro designed the mechanical computer with the ultimate goal of constructing it from biological molecules. The computer is no 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.

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.

Shapiro joined the Weizmann Institute in 1982 and currently is a faculty member of the Mathematics and Computer Science Department. In the early 1990s, Shapiro's innovative research in programming languages led to the establishment of Ubique, a company that develops interactive online environments. After Ubique's Virtual Places technology was purchased by America Online and incorporated into its Internet services, Ubique was sold to Lotus/IBM.

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

For more information: Ehud Shapiro, Faculty of Mathematics and Computer Science, The Weizmann Institute of Science, Rehovot 76100, Israel, 08-934-4506. Email: udi@wisdom.weizmann.ac.il.