Global Challenges/Chemistry Solutions

Promoting Public Health: Redefining DNA: Darwin from the atom up

July 22, 2009

DNA

The Watson-Crick model of DNA, featuring
four chemical "letters" — adenine, thymine,
guanine and cytosine, or A, T, G and C.
Steven Benner's artificial DNA contains 12
letters.
Credit: U.S. National Library of Medicine.
(Click here to download a high resolution
version of this image
)

Summary

DNA — made up of the four chemical letters of life A, T, C and G — is the blueprint for every organism that ever swam, flew, crawled or walked on earth. Now, four billion years of evolution later, a few bold scientists have created a new genetic blueprint — with some profound applications.

 

DNA — made up of the four chemical letters of life A, T, C and G — is the blueprint for every organism that ever swam, flew, crawled or walked on earth. Now, four billion years of evolution later, a few bold scientists have created a new genetic blueprint — with some profound applications.

In a dramatic rewrite of the recipe for life, scientists from Florida have designed of a new type of DNA with 12 chemical letters instead of the usual four. This artificial genetic system already is helping to usher in the era of personalized medicine for millions of patients with HIV, hepatitis and other diseases.

The research may also shed light on how life arose on Earth, by producing a self-sustaining molecule capable of Darwinian evolution and reproduction, much like one that many scientists suggest arose at the dawn of life on Earth nearly four billion years ago.

At the heart of this research is a discipline known as synthetic biology.

“I’m here because the NSF has a special session on a topic called synthetic biology. This is an area of research where one tries in chemistry to reproduce as much of the behavior of natural living systems as we can without actually reproducing the actual molecular systems in living systems. In this way, we set grand challenges which drag chemists across uncharted terrain where we attempt to answer unscripted questions.”

That was Steven Benner, Ph.D. Benner and his team are rewriting the rulebook that Nobel laureates James Watson and Francis Crick started when they described DNA's structure in 1953. One of the crowning discoveries of 20th century science, Watson and Crick's discovery established how the four chemical "letters" of DNA — A, T, C and G — pair up.

These pairing rules, however, make it very difficult for researchers to develop diagnostic tests for viral diseases — tests that require identification and tagging of viral DNA. Old methods used regular DNA to bind and tag foreign genetic material. But natural DNA would often bind with non-disease DNA and generate confusing false positive and false negative results.

Benner’s artificial genetic system does not operate under Watson-Crick rules, so the tagging gives accurate results. Benner’s artificial alphabet already has been applied commercially. It is the basis of a viral load detector, which helps personalize the health care of those 400,000 patients annually infected with hepatitis B, hepatitis C, and HIV.

“In terms of applications, why is this important? This is being built into diagnostic tests today. If you are unfortunate enough to have HIV virus or Hepatitis B or C infections, there is a good chance that your doctor will personalize your medical care using chemicals that we have made as part of this experimental genetic alphabet with 12 letters instead of 4. We’re now involved in a major program with the national institutes of health to try to do rapid genetic sequencing so we know what viruses you have, whether they are resistant to infectious agents… to see whether you’re predisposed to certain diseases and the genetic component of your reaction to a medical treatment. This is a part of a larger program with the NIH’s National Human Genome Research Institute to understand the genetic component of diseases so your doctor can personalize your medical attention.”

The 12 letter system might also shed light on one of most mysterious times in Earth’s history — the dawn of life nearly four billion years ago. Many scientists believe that this might have occurred when DNA’s ancient cousin, RNA, began to act like a living organism.

Benner’s ultimate goal is to synthesize a similar life form in his lab at the Foundation for Applied Molecular Evolution. His 12 letter genetic system is capable of nearly all of the actions that define a living thing — reproduction, growth and response to its environment — all without the benefit of genes refined over billions of years of evolution.

But so far the molecules still isn’t self-sustaining. Benner’s team still needs to come in each morning and feed it. It doesn’t look for its own food. According to Benner, no one has gotten that first step to work. While Benner continues to pursue a chemical system fully capable of Darwinian evolution, he emphasized that their research has helped them better grasp how chemical structure is related to genetic behavior.

Smart Chemists/Innovative Thinking

Smart chemists. Innovative thinking. That’s the key to solving global challenges of the 21st Century. Please check our full-length podcasts on Promoting Public Health. For the American Chemical Society, I’m Adam Dylewski in Washington.

Steven Benner, Ph.D.
Steven Benner, Ph.D., Image courtesy of the Foundation for Applied Molecular Evolution