The Cold and A Cold: Do they really go hand-in-hand?

By: Helen Beilinson and Zuri Sullivan

Biology is complex—very, very, very, very, very complex—and because of this, simplification is incredibly important. Many experiments are conducted by breaking down a complex system and studying its constituent parts, manipulating specific components (or “variables,” in science slang) to understand how they impact the system as a whole. For example, to understand how viruses replicate within their animal hosts, scientists often study how the virus replicates in animal cells grown in an incubator, instead of the whole organism. As a consequence, scientific knowledge accumulates in tiny increments—each study answers a small, but specific question. When we amass sufficient answers to simple questions, we learn something new about a complex biological system. 

This strategy of deconstruction and reconstruction has led to a number of important scientific discoveries, but it comes at a cost. Findings made in smaller systems can’t always be extrapolated to the larger system. Sometimes, these findings are really exciting, and they tempt us to jump to conclusions because of their potential impact on the larger system. This presents a major challenge to science reporters: keeping a story exciting at its beginning while resisting the temptation for overstatement. Some stories in the media meet this challenge better than others, but like all news, science news should be taken with a grain of salt—a scientist’s interpretation of his or her findings and their potential impact on society can vary widely from the interpretations of reporters.

As a case study for this idea, we investigated a recent high-profile story about the relationship between temperature and catching the common cold. The original study, published last month in the Proceedings of the National Academy of Sciences by a team of investigators headed by the laboratory of Akiko Iwasaki, an investigator of Howard Hughes Medical Institute and Professor of Immunobiology at Yale University, investigated the effect of temperature on protective immune responses to rhinovirus, the predominant causative agent of the common cold.

“It’s been known since the 1960s that the virus replicates better at nasal cavity temperature, which is around 33 to 35 degrees Celsius,” said Dr. Ellen Foxman, a post-doctoral fellow at Yale University who was the primary author of the study. Core body temperature for humans is 37 degrees Celsius (98.6°F), but inhaling cool air brings the temperature in our noses down to about 33-35 degrees Celsius (91.4-95°F)—the temperature at which rhinovirus grows best. By exploring the role of specific immune responses in a cell system, the study found that the temperature difference in viral replication was caused by a temperature-dependent difference in immune responses. Turns out, key immune responses against rhinovirus don’t work as well at 33-35 degrees as they do at core body temperature, so the virus is able to replicate more.

Given the implications of these findings (particularly that we should always listen to our moms and bundle up in cold weather), this study was covered widely by the media, with such headlines as “Common cold ‘prefers cold noses’” and “Common cold really is triggered by cold weather”.

“Some of the headlines went further than we did in our study,” says Ellen. “We didn’t actually study weather at all. Or people going out in the cold.” This was apparent in the original research findings, but many journalists bit into the cold weather/cold virus relationship. “To really make that claim, in terms of a clinical research study, you’d need to have two groups of people, normalize them, put some people in the cold…all that we didn’t do. So some people took it a bit further than we would have.”

This study wasn’t conducted in humans or in animals for that matter. It was done in a system where cells that live on a dish in an incubator in a lab are infected with the virus and are grown at different temperatures. Organisms are a lot more complicated than cells in a dish, making it difficult to extrapolate the findings from the study to a complex organism like a human. The relevance of these studies in humans is not currently known. This was seen as a limitation in other mainstream articles that covered the study, but was never fully discussed. On another note, the study looked at temperatures of 33-35°C compared to 37°C. The temperature of the human nasal cavity during winter could reach far below 33°C. Studies exploring how the immune responses functions below 33°C have not been done. Far from invalidating their results, however, the controlled system in which the experiments were performed is a major strength of the research. It demonstrated that the slight shift in the temperature dampens the immune response to the virus. Because inhaling cold air results in cooling of the nasal cavity temperature, the study implies that the cold weather could lead to more virus replication in human nose.

“After we isolated the primary cells, everything was identical about them, except for a few hours of incubation at different temperatures. So, it’s not the same as studying it in a person…but in a person, there are so many variables that you can’t control, that you can’t analyze. That’s the advantage of doing something in a laboratory. You can control everything except for one variable at a time and see how this variable affects the immune response, and thereby the infection.” This high degree of control is an indispensable component of the scientific method—without it, results are extremely difficult to interpret because outcomes cannot necessarily be attributed to a single variable. In order to show cause and effect, scientists need to ask straightforward questions under tightly controlled conditions. This control allowed for the discovery of what Ellen sees as the most important implication of the study.

Did someone really prove that eating red meat causes cancer?

By: Ross Federman

One frustration facing many scientists today is the manner in which primary research articles are interpreted by other writers and subsequently reported to the general public.  Often, important subtleties and details regarding the experimental design are disregarded, and while researchers are careful to qualify their conclusions based on this, other writers may not be. The past few weeks has provided a clear example of this.  This research article provides some implications, and promises to guide future research to gain more insight into the question at hand. However, many articles covering the research, such as this one from The Telegraph, are stating these implications as a concept that the article “proved,” in this case, that eating red meat will cause cancer.

First off, it should be noted that there is long standing epidemiological data to show that those who consume meat in their diets, on average, have a higher risk of developing cancer than those who abstain from meat consumption.  It’s also a widely held opinion that this is likely due to increased chronic inflammation that is present in meat eaters.  To date, there was very little mechanistic evidence or insight into why meat eaters suffer from more inflammation and thus higher risk of cancer.  An article published at the end of last year in The Proceedings of the National Academy of Sciences, a very reputable and highly respected journal, provided some a possible mechanism to account for this.  They showed that there is a specific sialic acid molecule (N-Glycolylneuraminic acid or Neu5Gc for short) present in almost all meat consumed by humans, and that this molecule becomes incorporated into the human body after consumption.  The molecule is of course also present in any animal that the meat came from.  To these animals, Neu5Gc is considered “self.” That is, their immune systems are trained to ignore it.  Humans however, do not produce this molecule on their own, so their immune systems likely see it as foreign.  This in theory could lead to an antibody response whereby antibodies specific for the molecule are created, and induce inflammatory conditions wherever it is present. In a meat consumer, this would be all over the place.  The resultant chronic inflammation would thus increase an individual’s risk of cancer.

So what did these researchers actually do?  They used a mouse model in which they deleted the gene in mice that produces Neu5Gc. This deletion essentially made the mice more like humans in the sense that they would now see Neu5Gc as foreign.  They artificially introduced antibodies directed at the molecule, found that these antibodies did indeed promote chronic inflammation, and that mice treated with the antibodies had significantly higher incidence of cancer.  This provides a mechanism whereby a mammal that does not produce Neu5Gc inherently may be able to produce antibodies against it that promote inflammation.

What did they not show?  First off, none of this work was done in humans, and while mice provide a great experimental model, they are different animals, and not all conclusions drawn from mouse work can simply be transferred to our understanding of humans.  But more importantly, the antibodies that mediate this mechanism were artificially introduced into the mice, and without them, there was no response to the foreign meat residue whatsoever, or at least not enough to significantly impact tumor development.  The authors justify this by stating that antibody responses to this molecule have been shown in the past, but that they are quite complex and not easily controlled in an experimental system.  That’s not a major problem in terms of the research itself.  This still provides a model mechanism to explain the increased inflammation caused by meat consumption.  However, this does become problematic in others’ interpretations of the work because it is a subtle distinction that any immunologist would look and therefore take some of these implications with a grain of salt.  Those covering this research for broader scope publications however may have either not picked up on this, or simply chosen to ignore it. 

Thus, while this research is well executed and appropriately interpreted by the authors, the interpretation by some of the writers that have covered this article are really not supported by the work.  The interpretation that this work has “proven that meat eating causes cancer” is far too great of an over-simplification, and not a correct conclusion to draw from this particular study.  Again, the mice and human differences cannot be overlooked.  Hopefully, because of this study, researchers may begin to look at human antibody responses to this particular molecule, but until that is examined, the relevance to human health is merely an implication, certainly not a conclusion.  The other elephant in the room here is that the gene deletion was not enough to induce this mechanism without the artificial addition of antibodies specific for the residue.  This implies that the true mechanism at work in a physiological context is likely far too complex to be easily explained by this particular study.  So while this is great science, and certainly contributes to the story of “cancer from carnivore,” it is not sufficient to prove much other than the fact that this particular mechanism is possible given all the right conditions that may or may not be present in human meat eaters, but they could be, potentially, and that is really the heart of the paper. 

In all reality, very few individual research papers “prove” major concepts such as these.  Rather, each paper contributes in a way that creates a larger and larger foundation for future studies, fills in knowledge gaps in the field, or both.  This paper does both.  It sheds light on the knowledge gap between meat consumption, and cancer promoting chronic inflammation, while guiding efforts to begin to examine the human antibody response to the molecule in question.

At the end of the day, this shouldn’t really change what the average person thinks about meat consumption.  It was already known that this diet habit is linked to higher rates of cancer.  There are many similar associations of this nature.  Pilots and other flight crewmembers have significantly higher risk of developing acute myeloid leukemia likely due to the increased UV radiation exposure that occurs at flying altitudes over accumulated flight hours for example. This has not stopped us from taking full advantage of flight as a convenience of the modern age, and for many to pursue careers as pilots. Most people would be amazed to see the list of materials or conditions that cause cancer. It’s astounding. And based on how long mankind has been consuming meat, it is likely that the impact meat consumption has on cancer development is fairly minimal. The long history of meat consumption (as far as our records can tell) would imply that if meat consumption significantly impacted human cancer development to such a great extent that it impacted our fitness, we likely would have evolved to be strictly herbivores.  The bigger concern should always be for those highly potent carcinogens, materials like asbestos, benzenes, or even gamma radiation, all of which are not nearly as enjoyable as eating a nice delicious steak. If you’re not going to eat meat, do it because you don’t like it, or you care too much about animals, not because you think this particular research article proved that doing so causes cancer.