It was 30 years ago in 1981 that the first known case of acquired immune deficiency syndrome (AIDS) was definitively diagnosed. According to last year’s “UNAIDS Report on the Global AIDS Epidemic”, 31.4-35.3 million people around the world were living with AIDS in 2009. The UNAIDS study also estimates that over 25 million people have died of AIDS-related diseases since 1981.
This issue’s article commemorating GEN’s 30th anniversary is reprinted from February 1985. It recounts how two laboratories, for the first time, independently sequenced the virus believed to cause AIDS. The finding opened the door to the development of new AIDS diagnostics and therapeutic strategies for helping to alleviate the suffering of those afflicted with AIDS.
The AIDS story is the latest example of our decision to reprint an article from one of GEN’s early issues in each issue in 2011. All these stories demonstrate a particular significance and relevance for the life science research community.
—John Sterling, Editor in Chief
"As Seen in GEN" Volume 5, Number 2, February 1985
U.S., French Teams Map AIDS-Linked Virus
By Joan Stephenson Graf
Two research groups, one in the United States and the other in France, revealed that they have independently succeeded in sequencing the virus believed to cause acquired immune deficiency syndrome (AIDS). The two reports apparently confirm that the two viruses linked with AIDS, HTLV-III and LAV are, as scientists believed, the same virus.
The accomplishment represents a crucial bench mark in research on the deadly disease, helping researchers to understand how the virus functions and to develop diagnostic tests and a vaccine against the virus.
Moreover, the HTLV family of viruses may represent a new class of retroviruses that are important human pathogens. According to Dr. Mark Pearson of E.I. du Pont de Nemours, “These viruses appear to represent a new type of virus. Other members of this new virus family may be involved in other chronic diseases. We are just beginning to understand these agents and their role in human disease,” he said.
The analysis of the HTLV-III virus was initiated and coordinated by Drs. Robert Gallo and Flossie Wong-Staal of the National Cancer Institute; four other laboratories collaborated with the NCI group, including a second laboratory at NCI (under the direction of Dr. Takis Papas), a team at Harvard Medical School and Dana-Farber Cancer Institute (led by Dr. William Haseltine), a group at E.I. du Pont de Nemours & Co. in Wilmington, Del. (directed by Dr. Pearson), and a team at Centocor in Malvern, Pa. (led by Dr. Nancy Chang). The LAV virus was sequenced by a group of scientists at the Pasteur Institute in Paris, including Drs. Simon Wain-Hobson, Pierre Sonigo, Olivier Danos, Stewart Cole and Marc Alizon.
Knowing the exact sequence will help AIDS research in a number of ways. The protein or nucleic acid products encoded by the viral genome can be synthesized for research and for medical applications. “It will facilitate any recombinant DNA strategy, because it provides information about how and where to cut and splice,” Dr. Wong-Staal told GEN.
“It should bring more people into the field, because now we can make proteins and fragments of proteins,” said Dr. Gallo. Furthermore, the ability to work with selected portions of the pathogen rather than whole virus makes it possible for researchers to conduct research without fear of contracting the fatal ailment.
“One major medical implication [of the sequencing of the virus] is that now we can proceed with much greater precision to make the reagents necessary for unambiguous diagnostic tests,” said Dr. William Haseltine. There appears to be some ambiguity in the current generation of diagnostic tests, leading to false positives and negatives, he said. The sequencing work, however, makes possible the development of a much more precise series of tools to be used not only for screening blood but also for diagnosis in individuals, he added.
According to a statement issued by the NCI, the knowledge of the viral genome is already being used to develop methods for detection of the virus in blood samples. Several companies, including Genentech and Chiron (both of whom are said to be close to mapping the genome of the virus) are racing to develop blood-screening tests.
The sequencing work also represents a crucial point in the long process of developing a preventive vaccine, and perhaps, therapy to alleviate the symptoms of the disease in individuals who become infected with the virus.
The mapping of the viral genome will provide a set of tools for the design of a series of “prototype” vaccines, Dr. Haseltine said.
“We can now take various genes out—particularly the envelope gene, which we suspect will be crucial in making an active vaccine—and manipulate them via recombinant techniques into appropriate vectors that we think will be good for vaccines.”
Although he thinks it unlikely that infected individuals can be cleared of the disease, Dr. Haseltine suggested that the sequencing of the virus has laid the groundwork for the development of therapeutics to reduce the severity of the symptoms.
“In the area of therapy, it offers very detailed information about the structure of the viral proteases, the virus reverse transcriptase, the virus envelope genes—all of which are potential targets for therapy,” he said. “If you can inhibit active virus replication, you may go some way toward alleviating the symptoms of virus infection, perhaps by preventing people who are asymptomatic from becoming symptomatic, or by alleviating the severity of the disease in the symptomatic individual.”