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SCIENTISTS SYNTHESIZE VIRUS FROM SCRATCH

By: GENE TULMAN
Statesman Editor

Issue date: 8/7/02 Section: Undefined Section
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Dr. Jeronimo Cello, holding a sample of polio virus particles, is flanked by Dr. Eckard Wimmer, left, and Dr. Aniko Paul. 
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Courtesy of www.newsday.com
Dr. Jeronimo Cello, holding a sample of polio virus particles, is flanked by Dr. Eckard Wimmer, left, and Dr. Aniko Paul.
Courtesy of www.newsday.com
[Click to enlarge]
Researchers announced on July 11 that infectious viruses can now be created in the test tube of any modern laboratory. In fact, it has been done most recently at Stony Brook University (SBU), where biochemist Eckard Wimmer’s team has generated active polio virus particles that are capable of infecting living host cells.

According to Wimmer, the viruses were made based on "sequence" information pulled from scientific literature. The word "sequence" refers to the arrangement of chemical base-pairs, which is the chemical spelling of a gene. By getting the "spelling" of each gene in a tiny virus, it is possible to string the genes together in the correct order so they exhibit emergent properties and are fully functional.

Experts can now download a genetic blueprint from the Internet and use mail-order materials to assemble a deadly virus.

At a time when the word "bio-terrorism" is a reality, the consequences of this development are both alarming and encouraging, he added. It means that scientists probably can create and prepare vaccines faster and more precisely to fend off biological attacks.

However, this also means anyone could manufacture viruses, or even alter them, potentially making them more dangerous.

According to Wimmer, ready-made chunks of DNA were purchased from commercial sources, and the researchers took the instructions for piecing them together from literature available on the Internet.

"If someone publishes the sequence of any old virus, you can chemically put together a DNA copy of that, and then create the virus," he said.

"So with enough money, knowledge, and equipment, you can make any virus for which you can determine the sequence."

The chemical instructions, including the DNA sequence information of many disease organisms, are available on the Internet for scientific use, and more are being added as researchers pursue their work against disease.

In the experiments at SBU, Wimmer and co-workers Jeronimo Cello and Aniko Paul ordered small chunks of viral DNA, called oligonucleotides, and strung the chunks together.

"The most important part of this work is the proof of principle," Wimmer said. "This says that you can generate a virus from the written sequence, and that has consequences."

James LeDuc, at the U.S. Centers for Disease Control and Prevention in Atlanta, told the journal Science that "it is a little sobering to see that folks in the chemistry lab can basically create a virus from scratch."

Given the potential for bio-terrorism, Wimmer said government agencies could monitor what chunks of DNA are being ordered from commercial sources. This would allow the appropriate state authorities to keep track of those who are doing research on dangerous organisms capable of being used for bio-terrorism.

In addition, he argued that an increasing ability to build viruses from scratch should be helpful, allowing scientists "to intensify research on disease organisms. Our work makes a safer world because it puts out notice that we can cope with this new danger [from bio-terrorism]."

It should also help with research into various difficult diseases. Scientists may someday want to resurrect disease organisms that have been exterminated, seeking new weapons against disease. "There is a possibility that you could change the genome structure to get a milder virus for use as a vaccine," Wimmer said.

In their research at SBU, he said, that possibility has arisen. As part of their work, Cello, Paul and Wimmer introduced a few changes into polio’s genome. Unexpectedly, these seemed to weaken the virus, slowing its ability to kill laboratory animals. "We discovered that it is much less virulent [compared to the ‘wild type’ polio virus]," Wimmer said. "That was a pleasant surprise."

For now, it is still not possible to create wholly new viruses in the laboratory.

"No one has been able to invent a virus; it’s too complicated," Wimmer added. "There is great complexity in the interactions of genes and proteins."

This technology, too, is not altogether new. As far back as 1981, biologist David Baltimore and his colleagues in Boston replicated a polio virus from a genetic template.

"But we actually didn’t use any template that nature had used before," Wimmer said. "We produced it chemically, without a natural template."

Although this is still far from creating life in the laboratory, it is a step in that direction. Viruses may only be considered living organisms when they interact with living host cells. As a general rule, viruses are considered to be non-living organisms due to their inability to either replicate independently or to synthesize energetic, metabolic molecules.

"Bio-terrorists didn’t learn anything from us," Wimmer said. "Everything we did has been published before. We just put the steps together.

Many laboratories could repeat what we have done."


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