Gary Perdew, Penn State University
Smoke inhalation would have been a serious threat for early man, due to campfires. But it appears that modern humans have evolved a reduced sensitivity to the chemicals in smoke so that it doesnít trigger so much inflammatory damage to our airways. Looking at the equivalent genes in Neanderthals shows they didnít have this protective change, which is perhaps contributed to their demise, as Gary Perdew, from Penn State Universityís explained...
Gary - We work on receptors called the aryl hydrocarbon receptor or AH receptor that sensors external chemicals in the environment. So, if youíre exposed to smoke from a diesel bus or from a fire, there's many chemical constituents in that smoke that will actually bind and activate this receptor. And the overall idea is that once this receptor is activated it increases the expression of enzymes that will metabolise and help your body get rid of those chemicals.
Chris - Right, so weíre endowed with a system for detecting Ďnastiesí in the environment and dealing with them but, obviously, we didnít evolve in the context of buses spewing out diesel fumes and that kind of thing so why would we have this naturally?
Gary - Probably the most obvious response to that would be this concept that plants have a lot of different chemicals that they express in order to keep animals from eating them. So this system would have evolved, probably, to largely deal with our dietary exposures.
Chris - Whatís the relevance then to combustion?
Gary - Out in the wild you wouldnít be exposed to smoke constituents except for if you started to utilise fire and you stay in close proximity to that fire on a day in, day out basis. Then that would become an issue.
Chris - And what influence might that have had on us genetically then?
Gary - So then, the idea would be that if this receptor was hyper-activated by that exposure, that could lead to toxicity. Itís good to have response to low levels of dietary chemicals so you can get rid of those and deal with them. But if, all of a sudden, youíre exposed to high levels of these compounds in smoke youíre going to breath them in your lungs and itís going to cause lung toxicity.
Chris - It sounds a bit paradoxical then. You detoxify the smoke but, in the process, you do damage! Why would that happen?
Gary - The kinds of chemical reaction that this enzyme catalyses leads to intermediates that are reactive but our body has a way to deal with them effectively at low levels. So itís not a problem except for when you produce them at too high a rate.
Chris - Oh, so if weíre exposed to a lot of smoke then this is overloading the system and, therefore, potentially doing harm and your argument would be have we, therefore, evolved to become less susceptible or less sensitive to these sorts of chemicals compared with other animals because of our use of fire?
Gary - Yes, exactly.
Chris - Right, so if I look at our human ancestors we know that there was Homo erectus that was around a million years ago or so until more recently. It then splits of and you get anatomically modern humans (us), and you also get Neanderthals coming off. So if one compares Neanderthals with anatomically modern humans (us), do both Neanderthals and us have this smoke handling capacity?
Gary - It turns out that the neanderthal sequence for this receptor, they would metabolise these compounds more rapidly than humans.
Chris - How do you know that?
Gary - There are three Neanderthal genomic sequences; the entire genome of the Neanderthals was sequenced. So once we could get the full DNA sequence for this gene we were able to synthesise it artificially - thereís a company that will do this for you now - and so we have the full length sequence for the neanderthal receptor and the human receptor that we can now compare experimentally.
The way we do this is weíll introduce these DNA sequences into a cell line that doesnít express the AH receptor and then these cells will express it. We can expose them to increasing amounts of polycyclic aromatic hydrocarbons and look at the ability of each receptor to increase the level of these metabolising enzymes.
Chris - Wow! So youíre effectively re-creating a fossil gene (a Neanderthal gene) in the modern context and seeing how it changes the behaviour of cells in the presence of these chemicals?
Gary - Yes.
Chris - And youíre saying the Neanderthal equivalent responds very differently than the modern human equivalent?
Gary - Yes. The Neanderthal has 150- to as much as 5,000-fold difference in its ability to increase expression of these enzymes.
Chris - Now one obvious thing about Neanderthals is that they are no longer with us. Would you contend, then, that one factor that might contribute to their disappearance is that they didnít evolve to handle smoke as well as we did and they were possibly being killed off by their own camp fires?
Gary - Yes, that would increase their susceptibility to diseases and infections because of lung toxicity, or even in the gastrointestinal tract. They were eating charcoal broiled food, which Iím sure they weren't the greatest cooks and probably were a bit blackened at times...