How 100-year-old research could help patients with HIV
In his winning article for the Max Perutz Science Writing Award 2014, Dr Christoffer van Tulleken tells us what a chicken has got to do with HIV, and how his research studying how the virus interacts with machinery inside our cells may, or may not, lead to new drugs.
The most important chicken in medical history was a Plymouth Barred Rock Hen from New York. The chicken’s name is not recorded but in 1911 she was brought by her owner to a young pathologist called Peyton Rous because of a large tumour growing out of her neck.
Rous subsequently performed a series of experiments so elegant it is hard to believe he didn’t know what he was looking for. He showed that the filtered extract from the tumour, containing no actual tumour cells, could cause more tumours in another chicken. Rous had discovered a type of virus that can cause cancer called a retrovirus.
At around the same time, in the dense tropical forests of the Congo Basin, another retrovirus managed to cross from a single chimpanzee to a single human and start a journey that would spread to 60 million people. This virus announced itself to science without fanfare: a brief report in 1981 documented five gay men from Los Angeles all with similar and unusual signs of immune system collapse, including cancers.
The paper reads with the dispassionate tone characteristic of medical case reports ― the deaths of two of the men are recorded with minimal eulogy ― but it was to become one of the most significant medical announcements of the century. This was how the epic narrative of the Human Immunodeficiency Virus (HIV) began in our collective psyche.
But, while the virus had been crossing species and continents, science had also been making vast strides without any idea of how important those advances would be. When the epidemic exploded across geographical and social boundaries in the 1980s we had a head start, thanks to the work that started with Peyton Rous. Because we had gained an understanding of the biology of other viruses, highly effective treatments for HIV were developed in less than 20 years from its discovery.
My research aims to contribute to this understanding of HIV biology which has so far been crucial in developing drugs. It takes place in small tubes and dishes in a lab and it’s a long way from patients and from developing treatments.
It revolves around the unanswered question of how HIV destroys the immune system. Considering that HIV is probably the most studied and understood infection in history this is a huge gap in our knowledge.
Like all viruses HIV sits somewhere between a living organism and a collection of chemicals. It is a package of protein with a little bit of genetic code. Viruses can not reproduce by themselves, they infect other living cells and hijack their machinery to replicate. HIV specifically infects certain vital cells in the body’s immune system and, over several years, as these cells die, the immune system weakens and patients succumb to diseases like the rare cancers and pneumonias first noticed in Los Angeles. No one knows exactly how or why these immune cells die, but some preliminary data implicates the involvement of the machinery that human cells have for repairing damaged DNA.
This machinery, made up of proteins, is of great importance to HIV because, along with all other retroviruses, it actually inserts its genes into the DNA of the human cell. The viral genes become part of your own genetic code. In order to do that HIV needs to cut the long chemical string of the cell’s DNA and insert its own. The cut is then repaired using the cells own DNA repair proteins. It may be these same DNA repair proteins which cause the cells to commit suicide leading to a gradual loss of the cells.
I am trying to understand how HIV interacts with these DNA repair proteins by removing them one by one from cells and observing the effects. If by getting rid of a protein interacting with HIV we able to prevent cell death, might it be possible to design a drug that could perform the same task?
Superficially, the value of my research may be that it contributes to drug development which will better treat HIV. But justifying research by presuming the outcome is illogical almost to the point of absurdity. If I knew what was going to happen it would not be research.
I may find that I am using HIV as a tool to better understand DNA repair in human cells and this may help with treating cancer. Or the results may have no applications in HIV or cancer, but prove vital for a new epidemic as yet unimagined ― just as experiments on the filtered extract of a chicken tumour have proved so directly important during the HIV epidemic.