A biological computer diagnoses and treats cancer

Computers may come in all shapes and sizes these days, but on the frontiers of research they are becoming more esoteric than is easy to imagine. In 1999, Ehud Shapiro, a researcher at the Weizmann Institute in Israel, suggested a design for a computer built out of nothing more than carefully engineered biological molecules. Two years later Mr. Shapiro, together with a team of other scientists from the Weizmann Institute, built it. It was made of DNA.

The computer was so small that a trillion could exist, and compute in parallel, inside a small drop of water. The hardware of the computer consisted of enzymes that manipulate DNA, the software was the DNA itself. The result was an output molecule. Now, Dr. Shapiro and his colleagues at the Weizmann have taken their research one step further by showing how such work might be useful. This week they claim, in an online paper in the journal Nature, that they have programmed a biological computer to diagnose and treat cancer.

To understand this remarkable feat, a little bit of background is necessary. What the team has built is known as a Turing machine, a notional type of computer first proposed in 1936 by Alan Turing. This British mathematician imagined a general purpose computer that worked by manipulating a paper tape divided into cells. Each cell was either blank or contained a symbol; the machine would move up and down the tape looking at the contents of the cells, checking its own internal state, and then applying a set of rules to this information to decide what to do next. Substitute a molecule for the paper tape, and this design can be adapted to build a biological computer.

Certain diseases, such as cancers, will induce biochemical changes in the body such as changes in the balance of molecules that it produces. Dr. Shapiro’s computer diagnoses an imbalance that indicates the presence of prostate cancer. After diagnosis it releases short strands of DNA designed to kill these cancer cells. The computer works by analyzing levels of a molecule called messenger RNA (mRNA). This is a chemical cousin of DNA that transfers genetic information – in this case for disease related genes – from the cell’s nucleus to the rest of the cell. It is here where the business of using this genetic information to direct living processes is carried out. And after the computer has measured levels of mRNA, the output molecule of the computation is able to affect the levels of expression of the diseased genes.

Dr. Shapiro’s team is interested in applications where direct processing of biological information is needed – such as medicine. In the traditional model of medicine, a doctor takes samples has these analyzed and uses the results to diagnose the presence of a disease. He then administers some kind of treatment. The paradigm that the team is pursuing is in situ detection, analysis and treatment of disease. One day, then, a medical computer might be administered as a drug. At the moment, the computer built by Dr. Shapiro’s team only works in a watery solution inside a test tube. One worry about taking such work forward is that the insides of a cell are far more complicated and unpredictable than the controlled environment of a test tube. The work, nevertheless, is an important step forward. While it is likely that getting such a computer to function inside a living cell remains some way off, the remarkably rapid progress of biological computers in controlled lab conditions means that that distant day looks to be getting closer.

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