LAB DECODES GENES OF VIRUS TIED TO SARS
14 Apr 2003
Source: New York Times, April 14, 2003
Lab Decodes Genes of Virus Tied to SARS
By DONALD G. McNEIL Jr.
Scientists in Canada announced over the weekend that they had broken the genetic code of the virus suspected of causing severe acute respiratory syndrome.
Sequencing the genome — which computers at the British Columbia Cancer Agency in Vancouver completed at 4 a.m. Saturday after a team slaved over the problem 24 hours a day for a mere six days — is the first step toward developing a diagnostic test for the virus and possibly a vaccine.
The genome appears to be that of a "completely new" coronavirus unrelated to any known human or animal viruses, a scientist at the Canadian agency said.
A competing United States team at the Centers for Disease Control and Prevention in Atlanta is reaching the same conclusion, and scientists from both teams said the virus's startling novelty could make it harder to trace what animal or bird it came from, if it did jump from another species.
A spokesman for the World Health Organization called the speed at which the gene was sequenced "stunning."
"It was just three weeks ago that the coronavirus was identified as the likely cause," said the spokesman, Dick Thompson. "Don't forget that it took several years to find the virus that causes AIDS. The way people worked together is just great."
While no race was declared, many experts had assumed that the C.D.C. would crack the code first.
A C.D.C. spokesman said his team was "just about done" and expected to post its sequence as early as today.
Dr. Marco Marra, director of the Genome Sciences Center at the Canadian cancer agency, said he hoped that "this isn't viewed as 'beating the C.D.C.' — we're trying to help."
Because 13 people in Canada have died of the syndrome, known as SARS, and 274 more are believed to be infected with it, Canadian scientists feel a sense of urgency about the project, he said. No one is believed to have died of the mysterious respiratory ailment in the United States, where 160 people are believed to be infected.
Also, Dr. Marra said, samples should be sequenced in different laboratories so scientists can check one another's work. Cautioning that his lab's work is "a draft — there are probably still errors in it," he said he still expected it to be posted for public use today on the Web site of the National Center for Biotechnology Information in Bethesda, Md., part of the National Institutes of Health.
The virus appears to be unique. "It doesn't look any more like one known coronavirus than another," he said.
With 29,736 base pairs of nucleotides, he said, "it's a biggie for a coronavirus." Viruses usually have thousands of these base pairs, while bacteria have millions and the human genome has over three billion.
The first tentative identification of the cause of SARS was made in March by a laboratory at the University of California in San Francisco. There, a solution of bits of DNA isolated from SARS patients that was poured on a glass slide covered with bits of 1,000 viruses formed partial matches with coronaviruses found in turkeys and cows, making the coronavirus family the prime suspect.
But Dr. Marra said the genome his lab found was "equidistant" from coronaviruses in turkeys, cows and mice.
Ideally, the sequence will make it possible to come up with a rapid test. Right now, there are three different tests for coronaviruses, but they can take days, by which time a patient may have died or recovered.
Because rapid tests for other coronaviruses exist, "our confidence level is quite good," Dr. Marra said.
Knowing the sequence of base pairs will indicate what proteins the DNA will build, which will hint at which protein-blocking drugs might make the virus impotent.
The possibility of a vaccine is more remote. While vaccines have wiped out or slowed smallpox, chicken pox, measles and other viruses, a vaccine against AIDS has eluded scientists for more than a decade.
Scientists are still trying to prove that this coronavirus causes SARS. To that end, a laboratory in the Netherlands is infecting primates with it to see if they become sick and whether particles of the same virus can be found in them.
Dr. James Hughes, director of the national center for infectious disease at the C.D.C., which is working on a sample cultured from a throat swab on a patient who died in Asia, said it was also finding a new, unrecognized virus. Known coronaviruses fall into three groups based on their surface proteins, he said, "and it looks like this is a fourth."
"If it had looked like it came from a turkey or a chicken," he said, "you could have taken steps to diminish the likelihood of exposure." In 1993, he said, the recognition that a fatal disease in the American Southwest was a hantavirus suggested that it had jumped from rodents. It was eventually traced to deer mice; controlling them limited the disease.
It is impossible to know how much having a fully sequenced genome will trim the time it takes to create a diagnostic test or a vaccine, Dr. Hughes said. A test could come rapidly because another preliminary test based on pieces of the genome was created within days, he said, though it is still in trials. He said he did not expect a marketable vaccine within a year.
The Canadian work began after Dr. Marra and the project's leader, Dr. Caroline Astell, volunteered to put aside their cancer research and devote their 20 scientists and 100,000-square-foot lab to the coronavirus.
Last week, the team received material that was isolated from a patient who had died in Toronto and was grown in primate cells at the National Microbiology Laboratory in Winnipeg, Manitoba.
The "sensitive, very delicate" work of converting the sample's RNA into DNA took about five days by a two-person team, Dr. Marra said, while "the rest of us reorganized the laboratory so it could run rapidly."
Dr. Simon Sutcliffe, the cancer agency's president, described the lab scene as "a lot of tired and excited-looking young people standing in front of their machines." Their average age is "probably 23 or 24," he said, and they are "very genome-focused and technologically adept."
A local newspaper's description of the lab as littered with pizza boxes was incorrect, Dr. Sutcliffe said, because food, a potential contaminant, is forbidden. But team members slept on chairs outside the lab and lived on soda, pizza and doughnuts.
On Friday afternoon, the samples were ready for the sequencing computers, which identify the bases in snippets of DNA about 500 bases long, and then sort them, trying to build something like a whole ladder out of hundreds of pieces of a ladder whose rungs have been sawed apart at different lengths.
"We were on pins and needles waiting for data," Dr. Marra said. "It began to appear at around 9 or 10 Friday night, and everything looked promising."
About 4 a.m., the computers finished their draft and before 8 a.m., Dr. Sutcliffe was being called out of the shower and was giving the authorization to make the announcement.