Editor's Note: Luc Montagnier shared the 2008 Nobel Prize in Medicine or Physiology, awarded on October 6. The new Nobel laureate co-authored this article, originally published in the October 1988 issue of Scientific American. We are making it available here due to its historical significance.

As recently as a decade ago it was widely believed that infectious disease was no longer much of a threat in the developed world. The remaining challenges to public health there, it was thought, stemmed from noninfectious conditions such as cancer, heart disease and degenerative diseases. That confidence was shattered in the early 1980's by the advent of AIDS. Here was a devastating disease caused by a class of infectious agents--retroviruses--that had first been found in human beings only a few years before. In spite of the startling nature of the epidemic, science responded quickly. In the two years from mid-1982 to mid-1984 the outlines of the epidemic were clarified, a new virus-the human immunodeficiency virus (HN)-was isolated and shown to cause the disease, a blood test was formulated and the virus's targets in the body were established.

Following that initial burst, progress has been steady, albeit slower. Yet in some respects the virus has outpaced science. No cure or vaccine is yet available, and the epidemic continues to spread; disease-causing retroviruses will be among the human population for a long time. In view of that prospect, it is essential to ask where we stand in relation to AIDS in 1988. How was HN discovered and linked to AIDS? How does the virus cause its devastation? What are the chances that AIDS will spread rapidly outside the known high-risk groups? What are the prospects for a vaccine? For therapy? How can the epidemic most effectively be fought? Those are some of the questions this article and this issue of Scientific American have set out to answer.

Like other viruses, retroviruses cannot replicate- without taking over the biosynthetic apparatus of a cell and exploiting it for their own ends. What is unique about retroviruses is their capacity to reverse the ordinary flow of genetic information--from DNA to RNA to proteins (which are the cell's structural and functional molecules). The genetic material of a retrovirus is RNA In addition, the retrovirus carries an enzyme called reverse transcriptase, which can use the viral RNA as a template for making DNA The viral DNA can integrate itself into the genome (the complement of genetic information) of the host. Having made itself at home among the host's genes, the viral DNA remains latent until it is activated to make new virus particles. The latent DNA can also initiate the process that leads to tumor formation.

Retroviruses and their cancer causing potential are not new to science. At the beginning of this century several investigators identified transmissible agents in animals that were capable of causing leukemias (cancers of blood cells) as well as solid-tissue tumors. In the succeeding decades retroviruses were identified in many animal species. Yet the life cycle of retroviruses remained obscure until 1970, when Howard M. Temin of the University of Wisconsin at Madison and (independently) David Baltimore of the Massachusetts Institute of Technology discovered reverse transcriptase, confirming Temin's hypothesis that the retroviral life cycle includes an intermediate DNA form, which Temin had called the provirus. The details of viral replication quickly fell into place.

In spite of such discoveries, by the mid-1970's no infectious retroviruses had been found in human beings, and many investigators firmly believed no human retrovirus would ever be found. Their skepticism had several grounds. Many excellent scientists had tried and failed to find such a virus. Moreover, most animal retroviruses had been fairly easy to find, because they replicated in large quantities, and the new virus particles were readily observed in the electron microscope; no such phenomenon had been found in human beings. In spite of this skepticism, by 1980 a prolonged team effort led by one of us (Gallo) paid off in the isolation of the first human retrovirus: human T-lymphotropic virus type I (HTLV-I).

HTLV-I infects T lymphocytes, white blood cells that have a central role in the immune response. The virus causes a rare, highly malignant cancer called adult T-cell leukemia (ATL) that is endemic in parts of Japan, Africa and the Caribbean but is spreading to other regions as well. Two years after the discovery of HlLV-I the same group isolated its close relative, HTLVII. HTLV-II probably causes some cases of a disease called hairy-cell leukemia as well as T-cell leukemias and lymphomas of a more chronic type than those linked to HTLV-I. The two viruses. however. share some crucial features. They are spread by blood. by sexual intercourse and from mother to child. Both cause disease after a long latency. and both infect T lymphocytes. When AIDS was first recognized. these properties took on great additional significance.

1 Comments

1. 1. jonathanseer 03:53 AM 5/10/10

   Early on ciclosporin was used to try and save Rock Hudson just before he died. The Doctors treating him apparently thought what was happening to the immune system resembled rejection or allergic response to self.
   
   The response apparently was dramatic. His t-cells skyrocketed in #.
   
   He was too far gone though, for he died very shortly thereafter, and this line of reasoning on how to treat the then unknown viral infection was dropped in favor of pursuing angles the medical establishment favored.
   
   Medical research like all science can be rigid when it comes to trying something new, and trying to re-imagine HIV as a virally induced allergy for experimental treatment's sake just goes against the ingrained accepted notions on what HIV is and how to treat it.
   
   Everything is focused on finding a way to eradicate it from the system or limit its ability to reproduce or a vaccine.
   
   While there were a few incidences of experimentation with ciclosporin beyond Hudson, all were dropped when the patient died. It was considered a "what do you have to lose" option.
   
   Unfortunately, for some odd reason, because ciclosporin did not produce a miracle interested disappeared.
   
   It never was tried in a proper setting where the patients were NOT at death's door, despite evidence that when tried on close to death patients the effects on the immune system was dramatic showing a marked transient jump in T-cells.
   
   Ciclosporin deserves its day in the sun.
   
   Perhaps it can modulate the overactive immune system downward enough so that T-helper cells don't go killing each other confusing each other with HIV, because HIV's coating is a product of the T-Cell outer envelope.
   
   Once slowed down by ciclosporin perhaps the immune system would be more able to appropriately distinguish infected from healthy and properly manage the infection - turning it into a mild chronic infection rather than the killer it still is in many areas.
   
   Of course, the biggest obstacle to even trying this is that ciclosporin is not going to make the big bucks the new anti-virals are, so its in the interest of big pharma to ignore it entirely no matter how positive the evidence is that such medications could play a successful role in managing the HIV infection.

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