Nature Video: Combating cancer with Edmond Fischer

Nobel Laureate Eddie Fischer was born in Shanghai in 1920. Since then, China has emerged as an economic superpower. Now it’s becoming a scientific heavyweight too. Tong Qing belongs to the newest generation of Chinese scientists. She decided to study cancer after a family friend became ill with breast cancer. In this film, she tells Fischer about life and research in China today.

Nature Video: The virus catchers with Harald zur Hausen

Young researchers Jan Gralton and Sven-Eric Schelhorn are fascinated by the minute world of viruses. They have plenty of questions for Harald zur Hausen who won a Nobel Prize for proving that human papillomaviruses (HPV) can cause cervical cancer. All three are worried by public distrust of the HPV vaccine, which was made possible by zur Hausen’s work.

Harald zur Hausen, 2008 Nobel Prize in Physiology or Medicine

Jan Gralton, The University of New South Wales, Australia

Sven-Eric Schelhorn, Max Planck Institute for Informatics, Germany

Infections that cause cancer – Harald zur Hausen

Even if you adore red meat, you’ll put off your big juicy steak by hearing what Harald zur Hausen has to say about it. At the 61st Lindau meeting, the Nobel laureate spoke about his current hypothesis about why beef causes colorectal cancer. He thinks it might contain a nasty pathogen that infects us that then causes the disease but the source hasn’t been discovered yet.

Colorectal cancer has a high incidence among men and women worldwide, and cases are increasing. Researchers blame this on the ‘Westernisation’ of lifestyles, including eating more red meat, in economically transitioning countries, such as China. 

 

zur hausen 

Harald zur Hausen at Lindau, photo: Christine Ottery 

Zur Hausen reached this hypothesis by eliminating possible carcinogenic factors and searching for correlations. First, he looking at the way that food was cooked, and found that it seems implausible to blame the cooking processes for beef-related cancer when eating white meat or fish cooked the same way is safe. He also looked at countries that have high and low incidences of bowel cancer, and found that in countries where red meat is eaten, but predominantly not beef (ie mutton or goat), incidences are still relatively low compared to North America, Europe and Australia, where the incidence is high.

Lastly, zur Hausen considered that beef is often cooked ‘rare’, and that this could affect the ability of viruses to survive cooking. He said that papillomavirus, polyvirus and single strand DNA viruses can endure a roasting at 80 degrees Celcuis for 30 minutes. Much beef is cooked more lightly than this. And zur Hausen’s hypothesis may explain the rise in bowel cancer cases in Japan, where the staple protein is traditionally fish, rather than beef.  

Zur Husen says that if we can find an infection that causes colorectal cancer, then 35 per cent of the world’s cancer cases could be traced back to an infection. At the moment, 21 per cent of cancers are known to stem from infections, including Hepatitis B, Helicobacter, Schistosoma. And, of course, zur Hausen won his Nobel prize in 2008 by proving that high risk HPV virus causes cervical cancer. The cancer of the cervix is the second most frequent cancer in women with 530,000 cases a year, globally – and 86 per cent of these cases are in developing countries. 

The first vaccine to prevent cancer was the Hepatitis B vaccine, developed in Taiwan in 1984. But the vaccine everyone’s talking about is the HPV vaccine, which can protect close to 100 per cent of previously non-exposed women, and likewise prevents the infection of cervical precursor lesions. Zur Hausen said that high risk HPV can be completely eliminated if all girls are vaccinated before reaching sexual maturity – and the vaccination of boys will close the circle of infection. 

He said that we should look for more infections that cause cancer. Could all cancers be linked to an infection? You can watch zur Hausen’s lecture in full, below. As for beef, I’ll be having mine well done in the future.

Mehr als nur HPV: Impfungen gegen Krebs

Der späte Vormittag gehörte in Lindau den Medizinern: Zunächst erzählte Harald zur Hausen von den Zusammenhängen zwischen Infektionen und Krebs, dann legte Luc Montagnier seine Forschungsergebnisse zur Physik und Biologie der DNA vor – böse Zungen behaupteten, der Mann sei nun unter die Homöopathen gegangen. Zuletzt sprach Francoise Barré-Sinoussi über die Entdeckung von HIV und weshalb sie ohne translationale Forschung nie möglich gewesen wäre.

Bezüglich der Geschichte der Zusammenhänge zwischen Infektionen und Krebs hat Martin vor ein paar Wochen schon einen großartigen Artikel geschrieben. Professor zur Hausens Vortrag ließ das Publikum zeitweise vor Ehrfurcht erstarren, als er die Rolle von Infektionen bei der Krebsentstehung auf vielfältigste Weise erklärte. So begann er zwar natürlich mich dem Humanen Papillomavirus (HPV), für dessen Erforschung der 2008 den halben Nobelpreis erhielt (die andere Hälfte ging an Montagnier/Barré-Sinoussi). Darüberhinaus aber zeigte er weitere Beispiele, wie Viren und Bakterien indirekt Krebs auslösen können, so zum Beispiel den Zusammenhang von Helicobacter Pylori und Magenkrebs, Hepatitis B und seine Rolle bei Leberkrebs, HIV 1 und 2, die durch die Schwächung des Immunsystems ebenfalls die Krebsentstehung begünstigen, Tuberkulose, die an der Entstehung von Lungentumoren beteiligt sein kann und Borrelia burgdorferi, das mit der Entwicklung von B-Zellen-Lymphomen assoziiert wird. Insgesamt kommt zur Hausen damit auf 21 Prozent aller Krebserkrankungen, die durch Infektionen ausgelöst werden – wobei viele von ihnen vermeidbar wären.

Außerdem zeigte zur Hausen einen weiteren interessanten Aspekt, der möglicherweise helfen könnte, zukünftige Krebsraten zu senken. Im Vergleich diverser Risikofaktoren für Leukämien im Kleinkindalter ist zwar zu erkennen, dass Infektionen in diesem Alter das Erkrankungsrisiko insgesamt senken. Treten die Infektionen jedoch gehäuft im ersten Lebensjahr auf, erhöht dies die Wahrscheinlichkeit – vermutlich kann das Immunsystem so gar nicht erst ausreifen. Dieses Beispiel zeigte auch wie Kinder mit höherem sozioökonomischen Status – zumindest unter diesem Aspekt – ausnahmsweise benachteiligt sind.

Um solche durch Infektionen ausgelösten Krebsarten zu reduzieren forderte zur Hausen zu mehr Forschung an Impfstoffen auf. Gemeinsam mit seiner Frau Prof. Ethel-Michele de Villiers erforscht er so momentan auch das TT-Virus – ein Virus, das per se zwar “nur” die Leber angreift, zugleich jedoch der Entstehung von Gehirntumoren und Autoimmunerkrankungen wie Asthma oder Multipler Sklerose zugeschrieben wird.

Die vergangenen Jahrzehnte haben eine Vielzahl an Forschungsergebnissen zu den Verknüpfungen zwischen Krebs und Infektionen gebracht. Harald zur Hausen forderte die jungen Forscher nicht nur auf, an Impfstoffen gegen solche Erkrankungen zu forschen sondern auch weitere Viren, Bakterien und Parasiten auf ihre Folgeerkrankungen zu untersuchen.

More than HPV: Vaccines against cancer

The late morning in Lindau was a non-stop marathon of medical researchers – first Harald zur Hausen talked about the links between infections and cancer, then Luc Montagnier gave an insight into his research that analyzes DNA under physical as well as biological aspects – venomous tongues may have linked that talk to homeopathy. At last Francoise Barré-Sinoussi talked about the discovery of HIV and how it was faciliated by global translational research.

Concerning the history of the relationship between infections and cancer, Martin has already written a great article a few weeks ago. Professor zur Hausens lecture let the audience awestruck by the Laureate’s quick and clever demonstration of how much cancer can possibly be caused by infections. As such he mentioned of course the papilloma virus (HPV), for whichs role in cervical cancer he was awarded with half the Nobel Prize in 2008 (the other half went to Montagnier/Barré-Sinoussi). But there are several further viruses and bacterias that can be indirect causes to human cancers, as for example helicobacter pylori is linked to gastric cancer, HIV 1 and 2 increase several cancer risks due to weakening the entire immune system, tuberculosis increases the risk of developing a later lung cancer and borrelia burgdorferi is known to increase the risk of b-cell lymphomas. Zur Hausen explained how many of those viruses even introduct oncogenes into their host cells. In some cases even parasites can lead to cancers, as for example schistosoma is associated with bladder cancer – in Egypt the parasite is one of the main causes of this type cancer. Alltoghether zur Hausen estimated that 21 percent of all global cancer incidents are linked to infections – and many of them are preventable.

And zur Hausen also showed another interesting aspect that might lead to new ways to reduce cancer prevalences. In comparing risk factors for early-childhood leukemia, he pointed out that infections during our childhood in general lower the risk of developing such a cancer. However, if a high number of infections occur in the first year of life, the risk of leukemia is increased – supposedly the immune system can’t mature efficiently. This example also explained how children with a higher socioeconomic status are under this aspect disadvantage.

To prevent such infection-induced cancers he suggested to develop further vaccines so that infections can be prevented. Toghether with Prof. Ethel-Michele de Villiers he currently does research on the TT-Virus – a virus that for itself “just” harms the liver but is linked to causing brain tumours as well as promoting autoimmune diseases such as asthmatic conditions and multiple sclerosis.

The past decades have been filled with discoveries of links between cancer and infections. Not only did zur Hausens lecture encourage young medical researchers to focus on vaccines – but it also showed that there are a lot more viruses, bacterias and parasites to explore.

100 years infection and cancer

There are many reasons to get excited in anticipation of this year’s Lindau Nobel meeting that is now less than two weeks away. One aspect of the meeting I personally enjoy is the appreciation for the historical perspective of science. One recurring theme of many Nobel laureates in Medicine or Physiology during the last 50 years is the fascinating relationship between infections and cancer, and in fact this year marks the 100th anniversary of one of first important discoveries in the field.

Peyton Rous (Nobel Prize for Physiology or Medicine in 1966) in 1910 described a malignant chicken sarcoma which could be propagated by transplanting its cells, forming new tumors in other chicken. He also showed that these tumors were caused by a virus (the Rous Sarcoma Virus), but it took 15 years of discussions before the scientific community unanimously accepted this connection. In the 1930s Rous discovered that the giant warts (benign tumors of the skin that can progress to cancer) of rabbits in the Southwestern US were caused by papilloma viruses.

It took another 30 years until viruses were found to also cause tumors in man. By the late 1960s the first oncogenes were discovered: part of the genetic material of viruses and able to induce tumors in human cells. David Baltimore, Renato Dulbecco and Howard M. Temin (Nobel Prize for Physiology or Medicine in 1975) studied the mechanisms of how viruses transform normal cells into tumor cells, including the enzyme reverse transcriptase that transcribes the genetic information of RNA viruses into DNA.

Michael Bishop and Harold Varmus (Nobel Prize for Physiology or Medicine in 1989) discovered that most oncogenes are in fact of cellular and not viral origin, acquired by viruses during replication in the host cell. 

BaruchBlumberg (Nobel Prize for Physiology or Medicine in 1976) began working on serum protein polymorphisms and inherited susceptibility to disease in the late 1950s. This work led him to the discovery of the Australia Antigen (now called Hbs Antigen) in 1963 and by 1967 the Hepatitis B virus was isolated. By 1969, blood donors were tested for Hepatitis B virus and rates of post-transfusion hepatitis soon soon decline.

After testing for Hepatitis B virus became available, it became obvious that there is a strong the geographical correlation between chronic Hepatitis B infection and liver cancer. A first vaccine against Hepatitis B virus was approved in 1982, and a decrease in liver cancer was first detected in 1990. Since 2003, vaccination for Hepatitis B is in use worldwide.

Harald zur Hausen (Nobel Prize for Physiology or Medicine in 2008) in the late 1960s started to study the role of the newly discovered Epstein-Barr virus in causing Burkitt’s lymphoma. He showed that Epstein-Barr virus DNA was integrated into the genome of these tumors, rather than causing a chronic infection.

In the mid 1970s he switched to searching for an infectious agent causing cervical cancer. Cervical cancer was long thought to be related to an infection, starting with the observation in 1842 by Rigoni-Stern that this cancer is more common in married women, widows and prostitues than in virgins and nuns. After initially trying to detect herpes simplex virus in cervical cancer tissue, zur Hausen switched to studying human papilloma viruses. In 1983 he and his coworkers successfully isolated HPV-16, and later detected DNA from this virus in half of all cervical cancer biopsies. HPV-18 was isolated in 1984 and in the following years his laboratory studied the mechanisms by which human papilloma viruses induce cervical cancer. A causal relationship between human papilloma viruses and a subset of oral cancers was discovered in 2000. The first vaccine against human papilloma virus infection was approved in 2006 with the expectation to decrease the rate of cervical cancer in the coming decades.

Françoise Barré-Sinoussi and Luc Montagnier received the Nobel Prize for Physiology or Medicine in 2008 for their work on the human immunodeficiency virus that is causing the aquired immundeficency syndrome (AIDS). Patients with AIDS have a dramatically increased risk to develop lymphomas associated with Epstein-Barr virus infection. The rare tumor Kaposi sarcoma is also much more common in AIDS patients, but it soon became clear that it is not HIV itself that is causing the tumor – no HIV proviral DNA was detected in Kaposi sarcoma samples, and the risk for Kaposi sarcoma was not the same for every HIV-infected person. This led to the search for another infectious agent, and in 1994 Kaposi-sarcoma associated herpesvirus was discovered by Yuan Chang, Patrick Moore and colleagues. This virus is required for Kaposi sarcoma to develop, and is also responsible for two other rare cancers.

The pathologist Robin Warren was studying gastritis-causing bacteria in the late 1970s, and in 1981 was joined by the gastroenterologist Barry Marshall (shared Nobel Prize for Physiology or Medicine in 2005). Their work not only showed that the bacterium Helicobacter pylori is involved in most cases of gastritis and peptic ulcer, but also that chronic H. pylori infection increases the risk of gastric cancer and lymphoma of the stomach. This makes H. pylori one of the few infectious agents that are not viruses to be implicated in causing tumors in man.