April 30, 2004
DNA Nanomachine Computers Against Cancer

Ehud Shapiro and his team at the Weizmann Institute of Science in Israel have published a paper in Nature on a DNA computer that activates in the presence of genes that indicate a cell is cancerous.

Scientists have built a tiny biological computer that might be able to diagnose and treat certain types of cancer. The device, which only works in a test-tube, is years from clinical application. But researchers hope it will be the precursor of future 'smart drugs' that roam the body, fixing disease on the spot.

This work builds on previous work Shapiro did with a simple biological computer in 2001.

Prof Shapiro's device is a development of a biological computer that he first built in 2001. DNA is the software of life: it carries huge quantities of information, programs the operating system of every cell, controls the growth of the whole organism and even supervises the making of the next generation.

The DNA computer is able to use the activity of multiple host genes as input in deciding whether a cell is in a cancerous state.

In one example, the computer determined that two particular genes were active and two others inactive, and therefore made the diagnosis of prostate cancer. A piece of DNA, designed to act as a drug by interfering with the action of a different gene, was then automatically released from the end of the computer.

This ability to use multiple inputs is needed to accurately detect cancers since any one gene can be on or off at different times in normal cells. We need the ability to check many indicators in each cell to decide whether it is a cancer cell. Still more precise activation mechanisms could be constructed using more gene expression levels as inputs and by making yet more complex sensor mechanisms that detect length of activation of genes or ratios of expression of genes.

When one piece of DNA in their DNA program attaches to abnormal messenger RNA characteristic of a cancer that serves as an input to whether to activate a cancer blocking gene.

The software molecules follow a simple computational path. If they attach to normal mRNA, they do nothing; if they attach to abnormal mRNA, indicating the presence of a disease cell, they initiate a process to unleash a DNA treatment molecule modelled on an anticancer drug.

The Weizmann Institute press release provides more details on the DNA computer state machine and its ability to measure concentrations of molecules as inputs to make a decison on whether to activate its treatment.

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.”

I love this approach. Why? Because the use of a treatment that operates as a state machine attempts to solve the problem of cancer on the level that the mechanisms of cancer operate. Cells are really complex state machines. Our genome is a really complex computer program executing with biochemical mechanisms. Cancers result when that state machine becomes damaged in enough places to lose control of the process of cell division. What we need is a smaller state machine to go into cells, recognize which cells have damage to their programs that make them cancerous, and then to either order those cells to die or to fix the damaged pieces of the cellular program that make those cells cancerous in the first place.

Genetic instructions are the right way to develop a complex state machine to use as a cancer treatment. DNA can have far more complex behavior than any conventional drug compound. The DNA can interact with the messenger RNA made by the cells to ascertain a cell's state and to change that state. Genes and other DNA fragments contain far more information than os contained in conventional chemical drug structures. Groups of genes can function as rather complex state machines. Since cancer cells and normal cells have so much in common a high level of sophistication of behavior is needed in order to develop enough selectivity to identify and manipulate cancer cells.

What these Israeli scientists are doing is the future of medicine. There are still many hurdles in the way of making a DNA state machine drug treatment work. Most notably, a lot of scientists have been trying for years to develop gene therapy delivery mechanisms for getting gene therapies into cells and the advances have been slow in coming. A gene therapy approach that delivers a DNA state machine computer would need to be able to get into nearly all the cancer cells in the body. If effetive gene therapy delivery mechanisms can be developed then DNA computer hackers can start hacking the human body to fix what is broken and improve us in numerous ways.

Share |      Randall Parker, 2004 April 30 12:02 PM  Biotech Therapies


Comments
nitish kr mishra said at February 7, 2005 5:06 AM:

please give idea about application of computer in cancer treatment

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