AsianScientist (Jan. 24, 2014) – Speaking at the Global Young Scientists Summit 2014 at Nanyang Technological University, Nobel Laureate Professor Harald zur Hausen had this advice for young researchers: Persevere at developing and testing unconventional scientific hypotheses, and do not be discouraged by skeptics who lack the bravery to do the same.
Prof. zur Hausen was awarded the 2008 Nobel Prize in Physiology or Medicine for the discovery that cervical cancer is caused by human papilloma viruses (HPV). His laboratory also isolated and characterized the two HPV types that are most often implicated in cancer – research that laid the groundwork for the development of the HPV vaccines that are available today.
Effective vaccines have eradicated smallpox and largely eliminated other infectious diseases such as polio, measles, and mumps. Since approximately 21 percent of human cancers have been linked to infectious agents, the identification of these agents and the development of vaccines against them would allow similar progress to be made against cancer, said Prof. zur Hausen.
A new challenge: Unraveling the mechanisms behind colorectal cancer
Prof. zur Hausen has now turned his attention to understanding the development of colorectal cancer, a disease which is on the rise in Europe, Japan and South Korea. Many epidemiological studies, he said, have incriminated the consumption of red meat as a major risk factor for the disease, and the prevailing theory is that the cooking process – broiling, grilling or frying the meat for example – produces carcinogens such as aromatic hydrocarbon molecules. This explanation, however, did not sit well with Prof. zur Hausen.
“The disturbing aspect was that the same chemical compounds arise when you barbecue, grill or fry chicken or fish,” he said.
In fact, the concentration of aromatic hydrocarbons is higher in smoked salmon than in a well-done steak; yet several studies have shown that fish consumption may actually protect against colorectal cancer.
Dig deeper into the epidemiological data, and the plot only thickens. It turns out that the increased cancer risk appears to be associated only with meat from some bovine species. Countries which eat mainly European-Asian domestic species of cattle have higher colorectal cancer rates than countries in which other species such as yak or zebu are more commonly consumed. Mongolians, for example, eat a diet high in yak meat, but have one of the lowest rates of colorectal cancer in the world.
“Over the years I became more or less a specialist in cattle,” quipped Prof. zur Hausen, adding that these observations led him to wonder if there could be species-specific factors in cattle, which increase cancer risk.
An infectious agent in colorectal cancer?
In Japan and South Korea, colorectal cancer rates have increased steadily after World War II, a trend that coincides with an increase in the consumption of red meat. In particular, raw or undercooked meat dishes (red meat sashimi and shabu shabu in Japan for example) have become increasingly popular. These provide the perfect conditions for infectious agents to thrive, said Prof. zur Hausen. In addition, air-drying is a common method of preserving meat in some parts of Europe and Asia.
“If you are a biologist like myself, you should know that air-drying is the best method of conserving infectious agents for long periods of time,” he added. “That led us to postulate that there is a specific bovine factor, probably linked to the European-Asian type of cattle, involved in human colon cancer specifically.”
Prof. zur Hausen predicts that a heat-resistant virus present in raw or undercooked beef may latently infect the intestine. The development of colorectal cancer could then result from a combination of the infection and long-term exposure to chemical carcinogens produced in red meat during the cooking process.
In collaboration with veterinary centers, Prof. zur Hausen’s group has begun the search for infectious agents in the serum of cattle. Thus far, the researchers have identified approximately ten novel single-stranded circular DNA molecules, which they suspect are heat-resistant. They are now in the process of experimentally testing their hypothesis and ruling out contamination from bacterial or other sources.
A world of possibilities
High red meat consumption has also been linked to breast cancer, said Prof. zur Hausen, and in countries such as India where beef is not consumed for religious reasons, the incidences of both colorectal and breast cancer are low. Despite some striking similarities, however, the epidemiological patterns of these two cancers do not overlap completely, perhaps suggesting that different infectious agents are involved, he said.
Prof. zur Hausen added that butchers and slaughterhouse workers have long been known to be at a higher risk of developing lung and pharyngeal cancers, even after the heavy smoking habits of these groups of workers are taken into account. He dangled yet another possibility before the audience: could this stem from airborne exposure to an infectious agent present in meat?
While these hypotheses are tantalizing, the scientific evidence is still lacking, said Prof. zur Hausen, who also emphasized the crucial role of basic research in providing novel approaches to prevent disease.
“I can only stimulate young researchers to look more carefully into this issue; personally I’m convinced that we are in for some surprises, as far as the participation of viruses and other agents in human cancer is concerned.”
The plenary talk titled “Search for infections linked to human cancers” was part of the Global Young Scientists Summit 2014, organized by the National Research Foundation of Singapore and taking place from January 19 to 24, 2014 at Nanyang Technological University.
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