cientists 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 one 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 noticeable
symptoms even appear.
"Eventually we have this vision of a doctor in a cell," said Dr.
Ehud Shapiro of the Weizmann Institute of Science, in Rehovot,
Israel, who led the work, published online yesterday by the journal
Nature.
DNA's role is to store and process information, the genetic code.
So it is not surprising that it can be used for other computing
tasks as well, and scientists have in fact used it to solve various
mathematical problems. But the Israeli scientists said theirs was
the first DNA computer that could have a medical use.
The computer, a liquid 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 end of 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 many pieces
of DNA, RNA and chemicals that could interfere.
"I think it's very elegant ó it's almost like a beautiful
mathematical proof," said Dr. 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 Dr.
Len Adleman of the University of Southern California showed that it
could be used to solve a mathematical problem. People in the field
then began envisioning billions of pieces of DNA undergoing chemical
reactions in parallel, solving problems so complex as to stymie
conventional computers.
Some scientists have since concluded that it will be difficult to
get DNA computers to outmuscle electronic computers. But Dr.
Shapiro, an associate professor of computer science and applied
mathematics 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 ó from a computer science standpoint, that is ó 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," Dr. Shapiro said, "we just drop everything in
solution and see what happens."
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