The Nobel Prize in Physiology or Medicine goes to Harald zur Hausen "for his discovery of human papilloma viruses causing cervical cancer" and to Françoise Barré-Sinoussi and Luc Montagnier "for their discovery of human immunodeficiency virus".
The Nobel Prize in Physiology or Medicine was awarded today to three people, in two groups, for the discovery that HPV causes cervical cancer and for the discovery of HIV. This are related discoveries showing the diverse pathological effects that viruses can cause in humans. They highlight how much we have learned: these diseases aren't random events cause by witches, but defined events resulting from infections with various viruses. They also highlight how much further we have to go to deal with these diseases, especially HIV/AIDS.
Harald zur Hausen and HPV
It has long been known that specific viruses can cause tumors. The 1966 Nobel in Medicine or Physiology was shared by Peyton Rous who discovered tumorgenic viruses in chickens. At the time that zur Hausen began his work it was thought that herpes simplex type 2 virus was causal agent of cervical cancer.
Technique Note: in situ hybridization
DNA gets transcribed into RNA. RNA gets translated into protein. This is the so called central dogma of biology. In situ hybridization looks for the presence of specific RNA molecules. You do this by adding a labeled complementary piece of DNA or RNA. Because DNA/RNA binding is sequence specific, only something complementary to the probe will be labeled. This way we can look for a specific RNA transcript, a single gene, or a single variant of a single gene.
zur Hausen didn't seen HSV-2 RNA in in situs. This led him to propose that viral DNA can get integrated into the human genome, but not get expressed. Therefore, people should be looking at the DNA for the presence of viral sequences, rather than in the pool of transcribed RNAs. He thought that genital warts could be sites of viral integration without expression of the genes.
He took extracts of an HPV virus, made labeled RNA from that DNA and tried hybridizing that to extracts from tumors. He discovered that viral DNA was present in various skin warts but not in cancers. This led him to propose that there are multiple variants of HPV, some cause warts and some cause cancers. This led him to identify a number of HPV variants.
Building on this he was able to look for related virus sequences using the known HPV variants. Eventually he reached HPV16 whose DNA was found in ~50% of cervical cancers. Continuing this approach in cancers that did not show any HPV16 led to the discovery of HPV18. DNA from HPV16 and HPV18 are found in 82% of patients with invasive cervical cancers.
Once the cause of these cancers had been identified, researchers can try to treat or prevent the cancers. Something like the HPV vaccine would not be possible without this original ground-breaking research.
Françoise Barré-Sinoussi and Luc Montagnier and "human immunodeficiency virus"
In the early 80s when researchers began looking into HIV seriously, and found it quite confusing. Here was something marked by a loss of certain immune cells and marked by a bewildering variety of infections, tumors and other diseases that attacked all organ systems equally. How could something with so many diverse symptoms be caused by a single factor?
A virus could fit the bill. It was passed between people like a virus, through filtered blood transfusions, sexually, from mother to placenta. The specific loss of CD4 positive T-cells could also be explained by a retrovirus.
To study this, Barre-Sinoussi and Montagnier started culturing lymphocytes from patients in early stages of the disease who still had CD4 T-cells, the supposed target of the virus. From these cultured cells they noted high levels of reverse transcriptase activity (reverse transcriptase takes RNA and turns it into DNA, this enzyme is best studied for its role in RNA viruses and at telomeres) that was dependent on addition of new cells. This suggests that the RT activity is coming from something that is killing cells. Something like a retrovirus. Electron microscopy of these cultured cells exhibited particles budding from cell membranes that looked like retroviruses. Once they knew they had a virus they could purify it by spinning it in a sucrose gradient. Then they could inject viral proteins into mice or rabbits to raise antibodies.
Technical Note: immunofluorescence
Antibodies are proteins made by immune systems that very specifically bind to an antigen. Scientists can make antibodies against a specific protein by injecting the antigen into rabbits, mice or other small mammals. The animal will detect the protein as foreign and make antibodies against it. Their blood serum can be purified to collect antibodies. Now we have a tool to detect the antigen in any condition. We can take cells from a patient, fix them and then add our antibody which will bind to the antigen. We then add a fluorescently labeled secondary antibody. This is an antibody raised against a large class of antigens. For example, anti-rabbit antibodies will recognize any primary antibody made in a rabbit. We add the primary which recognizes our antigen (e.g. HIV virus particles), we add the secondary which recognizes its antigen (e.g. rabbit anti-HIV antibody). Then we look under a microscope to see if our antigen is present.
One they had an antibody they looked in patients and saw reactivity. On the flip side, the antibodies from patients bound to proteins made by the virus (basically, they fed infected cells radioactive amino acids to make virus with radioactive proteins. Antibodies from the patients specifically bound to radioactive proteins from infected cells, but not uninfected cells.)
This virus culture did not react with antibodies raised against any of the previously characterized retroviruses, suggesting that it was an entirely new virus. Because antibodies from patients with AIDS or at risk for AIDS would react with their new viruses, but antibodies from patients with other disease did not, they concluded that their virus was crucial to the disease. Other groups also isolated viruses form AIDS patients that had similar characteristics to their virus, eventually people agreed that it was the same virus causing AIDS.
Once the virus was identified there was an explosion of research. By tracking changes in the virus genome people could track the geographical spread of the virus. People could identify how it acts to infect and kill T-cells. People could begin to understand how the virus leads to AIDS, we can understand HIV's odd behaviors like the long incubation time. People could begin to develop specific treatments.
As with the HPV, this serves to highlight how much we have learned about HIV/AIDS since its discovery but also shows how much more we have to do.
Political Commentary
These are both major public health issues. HPV infects millions of Americans and HIV infects millions worldwide. There is also a great deal that can be done to help people not get infected or to treat those who have been infected. However, these only work if people have access to both knowledge and the necessary tools. Unfortunately the Republican hysteria about abortions and contraception being the same as abortion does a huge amount of harm. If young adults were told that these diseases are sexually transmitted, that proper use of condoms is highly effective at preventing the spread of these diseases (and others) and were given access to those condoms, it would be a start. However, we get abstinence-only education:
Despite the allocation of hundreds of millions of dollars of federal funds for abstinence-only programs over the past decade, at the time Title V was enacted there was little, if any, evidence that such efforts prevented sexual intercourse in adolescence or provided accurate information about reproductive health. Mathematica Policy Inc, a nonpartisan firm that conducts policy research and surveys, was authorized by Congress in 1997 to conduct an evaluation of abstinence-only education programs. Three reports were released, with a final evaluation published in 2007 (http://aspe.hhs.gov/hsp/abstinence07/report.pdf). The firm surveyed more than 2000 elementary and middle school students who were followed up into high school. Approximately 60% of the students were in programs identified by abstinence-only proponents as ideal programs and 40% were controls.
The programs "had absolutely no measurable impact on initiation rates, ages of first intercourse, or numbers of partners, no impact on pregnancies, births, or STDS, and the same rates of condom and birth control use," said Bruce Trigg, MD, of the New Mexico Department of Health in Albuquerque. "And in some of these cases, kids sat through 3 years of mandatory abstinence-only classes," he added.
The Mathematica report also noted that participants in the abstinence-only programs were less sure that condoms would prevent STDs and were less likely to perceive condoms as effective.
Abstinence-Only Programs Under Fire, Tracy Hampton, PhD JAMA. 2008;299(17):2013-2015.
(JAMA=The Journal of the American Medical Association)
Not only our children not getting educated, but this misguided philosophy affects funding of research and of aid to other countries, making it a global issue not just a domestic problem. This has been going on for years 2003, 2005, last week.
Bush and his policies are doing irreparable damage here and abroad by not educating people about risks and solutions, and by putting his own moralistic/religious beliefs/interpretations first and putting science and the health and well-being of people second.
Most information for this came from: http://nobelprize.org/...