June 22, 1999

he genetic code has been asked to do a lot of things, from insuring that a spider has eight legs to giving Elizabeth Taylor her violet eyes. But as far as is known, it has never been asked to spy.

Now, however, researchers at Mount Sinai School of Medicine in New York have developed a technique for conducting espionage on a molecular level, by hiding a message in human DNA. Using the technique, a sender would create a unique strand of DNA that only an intended recipient could isolate and "read" from millions of similar strands.

It is a modern twist on an ancient art, steganography, the practice of communicating while concealing the communication. In homage to what is perhaps the most famous steganographic technique, the photographic microdot, the researchers have further hidden their message by transferring the DNA onto a tiny printed dot and pasting it over the period in an otherwise innocuous letter that is sent to the recipient.

For Dr. Carter Bancroft, the lead researcher, using the genetic code as a secret code was a sideline to a sideline. Dr. Bancroft, a professor of physiology and biophysics at Mount Sinai, is a molecular endocrinologist by profession. But for the last five years he has become interested in the idea of using DNA as a kind of organic computer. "That got me thinking about ways to use DNA outside the bounds of a living cell," Dr. Bancroft said.

DNA is made up of building blocks, or nucleotides, and while there are only four different ones -- known as A, C, G and T -- they can be arranged in millions of ways, like four colors of beads on a string. This complexity serves well when it comes to genetics, and is also what makes DNA appropriate for passing secrets. "I realized that the human genome is so complex, you could hide a message in it," Dr. Bancroft said.

Coming up with the idea turned out to be the most difficult part. "It is exceedingly simple to carry out," Dr. Bancroft said, in that it uses only standard DNA research techniques.

The researchers, who described the technique in a recent issue of the journal Nature, first came up with a simple encryption code, a unique sequence of three nucleotides for each of the letters of the alphabet, punctuation marks, numerals and a space. The letter R, for example, is denoted by the sequence T-C-A.

They then created strands of DNA, 69 nucleotides long, with the nucleotides arranged according to the key to create a message (their choice was "June 6 invasion: Normandy," a message actually sent by photographic microdot during World War II). They marked each strand by adding "primer" sequences of 20 nucleotides each to the beginning and end.

The manufactured DNA was then mixed with a solution of human DNA, the strands of which were broken up to the approximate length of the coded strands. Because human DNA is incredibly complex, chopping it up creates about 30 million uniquely sequenced strands.

The researchers used the United States mail as a conduit for their message. They piped the DNA onto a piece of filter paper with a tiny dot printed on it, cut out the dot after it dried and taped it over the period in a sentence of a typewritten letter that was then sent to the recipient.

This use of a microdot makes the technique doubly steganographic. "In the first case, we're hiding the message," Dr. Bancroft said. "Then we're hiding the medium that contains the message."

An enemy would first have to discover the microdot to have a chance at intercepting the message. But for anyone lucky or skilled enough to figure out a microdot is present, the difficulties would be just beginning.

The secret DNA's primer sequences, which both the sender and the intended recipient agree on beforehand, are crucial. By knowing the nucleotide sequence in the primers, the recipient can use a common research method, polymerase chain reaction, to isolate the secret strand and produce an exponential number of copies of it. The secret strand then dominates the DNA soup, and it is a simple matter to analyze it, determine the sequence of nucleotides in the message portion and decode it using the key.

An enemy who does not know the primer sequences, on the other hand, is faced with trying to find one strand among 30 million. Even if the enemy knew the sequence of all human DNA (which is currently unknown) and could somehow isolate the manufactured strand by eliminating the natural ones from consideration, the sender could help insure security just by throwing in some DNA from different organisms. It would not affect the recipient's ability to isolate the secret strand.

Dr. Bancroft sees the technique as a potential tool for corporate security. It could become an alternative to cryptographic methods used to send confidential messages within companies. Or perhaps it might be employed to discretely authenticate documents by adding a DNA watermark. The technique seems less likely to be used by a real-life James Bond, unless he has a degree in molecular biology.