DNA key to in-body device to aid diagnosis, treatment

Scientists have developed what they say could become the world's smallest medical kit: a computer made of DNA that can diagnose disease and automatically dispense medicine to treat it.

The computer, so small that a trillion would fit into a drop of water, now works only in a test tube, and it could be decades before something like it is ready for practical use.

But it offers an intriguing glimpse of a future in which molecular machines operate inside people, spotting diseases and treating them before symptoms appear.

"Eventually we have this vision of a doctor in a cell," said Ehud Shapiro of the Weizmann Institute of Science in Rehovot, Israel, who led the research, whch was published online Wednesday by the journal Nature.

DNA's role is to store and process information, the genetic code. So it is not surprising that DNA can be used for other computing tasks as well, and scientists have used it to solve mathematical problems.

However, the Israeli scientists said theirs was the first DNA computer that could have a medical use.

The computer, a solution of DNA and enzymes, was programmed to detect the kind of RNA (a DNA cousin) that would be present if particular genes associated with a disease were active.

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 computer.

Experts called the work ingenious but pointed out that it had been done in a test tube to which the RNA corresponding to the disease genes was added. It is not clear, they said, whether such a computer could work inside cells, where there would be an abundance of DNA, RNA and chemicals that could interfere with the reactions.

"I think it's very elegant -- it's almost like a beautiful mathematical proof," said George Church, professor of genetics at Harvard Medical School. "But it's not working in human cells yet."

DNA has intrigued some computer scientists since 1994, when Len Adleman of the University of Southern California showed it could be used to solve a mathematical problem.

People in the field then began envisioning billions of pieces of DNA undergoing chemical reactions, solving problems too complex for more conventional computers.

Some scientists have since concluded that it will be difficult to get DNA computers to match the power of electronic computers.

But Shapiro, who is also in the Weizmann Institute's department of biological chemistry, decided to focus on a DNA computer for use in the body, where silicon would have a hard time competing.

And rather than trying to build the DNA equivalent of a supercomputer, or even a wristwatch calculator, he made a device so simple that it can barely be called a computer.

It has two states, "yes" and "no," and changes from one to the other on the basis of a single variable, like the presence or absence of the RNA it is looking for. If at the end of a series of steps it is in the "yes" state, the diagnosis is positive.

The Weizmann DNA computer encodes both the software and the data in the four letters of the genetic code, A, C, G and T.

The "hardware," the part of the computer that does not change, is an enzyme that cuts the strands of DNA in a particular way.

The computer is made of double-stranded DNA with ends that are single-stranded. These so-called sticky ends can bind to specific other strands of DNA or RNA in the solution under the usual rules of DNA pairing.

If binding occurs, the enzyme cuts the DNA a certain distance away, exposing new sticky ends. If those ends find something to bind to, the enzyme cuts in yet another location, and so on.

If the chain reaction proceeds in a certain way, the enzyme eventually slices off the piece of DNA that acts as the drug.

After the DNA encoding the problem is made and put in the test tube, the computer works automatically and arrives at the answer in minutes.

"Basically," Shapiro said, "we just drop everything in solution and see what happens."