When was the last time a scourge that dominated the headlines in the 1980s made front page news? Two come to mind immediately: crack cocaine and HIV/AIDS. While both still have the ability to wreck lives, social changes have buried the fear of crack and, for many, AIDS. Out of sight, out of mind. But while social changes can suppress crack use, AIDS fears nothing. The disease now must compete for attention--and funding--with Alzheimer’s and various forms of cancer. The numbers are stark but abstract: HIV is still a deadly disease that infects more than 33 million people, and kills than 2 million people each year through its effects. But it's hard for the public to keep track when malaria also kills millions and cancer is the leading threat.
For those whose job it is to find a cure, HIV is an everyday presence, and the pressure is intense to make progress. Late last week, the Dr. Paul Janssen Award for Biomedical Research was presented to two prominent HIV researchers, Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Disease and Erik De Clercq, professor emeritus of the Rega Institute for Medical Research, Leuven, Belgium.
The Janssen award honors those scientist who have made a measurable impact on human health, and certainly De Clercq and Fauci have done their part for society by leading and managing high-level research efforts that led to powerful antiretroviral drugs and treatment of immune-system ailments. De Clercq is a pioneer in the antiviral drugs field, and Fauci, as a result of his studies on pathogenesis, fundamentally changed the way we understand immune response. As a result of his nearly three decades, he has become the lead voice in the fight against HIV/AIDS. In 2005, he was named Scientist of the Year by R&D Magazine in recognition of his accomplishments.
But a cure still eludes Fauci, De Clercq, and countless other researchers. Increasingly, government-funded teams throughout the world have been collaborating in this effort. As a result, old rules have been torn down, and new discoveries have spread more quickly. Until January of this year, HIV carriers were not allowed to even enter the U.S. The withdrawal of this rule led the International AIDS Conference to select Washington, D.C. for an upcoming gathering. As recently as the last decade, U.S. participation in international research has been limited by various political interests. And nations who suffer most from AIDS, particularly in Africa, are beginning to take charge of their own anti-HIV efforts.
Moral reservations are fading because, like cancer and malaria, a distinguishing characteristic of HIV is its persistence. The death rate from AIDS has decreased in the last two years--for the first time in decades--thanks to the treatments championed by Fauci, DeClercq, and many other researchers. But as of 2007, new infections outpaced AIDS-related deaths by 700,000.
The decrease in the death rate from this disease is largely due to antiretroviral drugs. Many HIV-infected individuals are living into their 50s and beyond. Unfortunately, the drugs are not a cure, and recent findings show that HIV infection takes its toll even when held in check. Persistant activation of immune cells by the virus cause an exhaustion of the cells. Individuals with HIV can’t fight infections as well, and are more prone to inflammation-induced diseases.
A cure, in the form of a vaccine, will require understanding what happens immediately following sexual exposure to HIV. Unfolding the complex molecular interactions at this level, Fauci hopes, will provide a target for vaccine development. Meanwhile, African nations are taking efforts into their own hands by distributing microbiocide gels and promoting circumcision.
Many are pinning hopes on recent vaccine trials that show promise. One candidate that is a combination of two previously unsuccessful vaccine candidates delivered a 30% reduction in infections in a trial conducted in Thailand. But these vaccines, as well as the gels, provide incomplete protection and their effectiveness depends greatly on the time at which they are administered. And even the best antiretroviral treatments can’t drive the virus away.
Like cancer, the answer for HIV is probably further away than many of us would care to admit, even with funding levels that continue to climb into the tens of billions of dollars. I don’t profess to know what Fauci thinks about the timeline for a cure, but he may realize the effort could very well span his career and then some, just as viral research spanned the careers of those before him. Why? First, we still don’t fully understand many of the cell signaling and pathway mechanics that govern the infection and propagation of the disease. Second, the virus is able to survive the entire DNA transcription and translation routine inside the cell. It’s ability to integrate into the genome requires the development of intracellular treatments that still are in rudimentary stages.
And, most frighteningly, HIV is the poster child of adaptability through genetics. It mutates constantly and replicates to the tune of about 1010 daily.
leaves us hoping for a seredipitous discovery, or the eventual victory
over HIV through diligent R&D. Honors like the Janssen Award can’t
help us celebrate, but they can bring the matter into focus, and
encourage researchers like Fauci and De Clercq to keep moving forward. As Fauci said as
part of accepting the Janssen award: “we know that in many respects, our
work is just beginning.”
R&D Magazine is still accepting nominations for its 2010 Scientist of the Year Award. If you have someone in mind for this honor, or for one of our other two individual awards, please let us know.