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The "Hangover" Gene: Scientific Literature vs. Popular Press
When Scholz, et al (2005) announced the discovery of the hangover gene in August 2005, the press had a field day. Though its catchy name may suggest otherwise, wild-type hangover actually seems to confer ethanol tolerance to Drosophila melanogaster (fruit flies) repeatedly exposed to ethanol vapors. Several popular press sources, including FOX news, the New York Post, and NewScientist.com, attempted to convey this message to the public. These arguably more accessible analyses were brief and basically on target, although occasionally misleading.
While creating mutant flies by performing numerous P-element insertions, scientists at the University of California at San Francisco and the University of Wurzburg isolated one particular strain, AE10. This strain apparently exhibited normal response to one exposure to ethanol, but failed to develop the same level of tolerance relative to the control flies after repeated exposure to ethanol vapors. These scientists reported their findings in a paper entitled, “The hangover gene defines a stress pathway required for ethanol tolerance development,” which appeared in the August 11, 2005 issue of Nature. The article contained five main points.
1) Flies are a good model
In their article, Scholz H, et al. (2005) assert that fruit flies represent a good model organism for studying ethanol tolerance in mammals, namely humans. In particular, flies exhibit many of the same symptoms (loss of coordination, initial hyperactivity, and eventual sedation) during exposure to ethanol vapors as humans who imbibe ethanol. Furthermore, Scholtz H. et al. (2005) cite their previous work that demonstrates that when normal flies are exposed to ethanol 4 hours prior to a second exposure, the flies require more ethanol in repeated ethanol exposures to reach the same effects as compared to the first event (Scholtz H, et al., 2000). In other words, just like humans, Drosophila have the capacity to develop tolerance to alcohol when repeatedly exposed to the drug.
2) Flies lacking hangover are less tolerant to repeated ethanol exposure
Notably, Scholtz H, et al. (2005) claim to have isolated a mutant strain of flies (AE10) through random P-element insertions that lacks the ability to acquire ethanol tolerance. Even when exposed to ethanol 4 hours prior, AE10 flies, referred to as hang, require the same amount of ethanol to become intoxicated as in the instances when they were not previous exposed to ethanol vapors. The scientists determined that in this particular strain of mutant flies, the P-element inserted into gene CG32575 (renamed hangover). Thus, this particular mutant strain apparently fails to produce the protein product of hangover. Scholtz H, et al. (2005) claim that P-element insertion resulted in a null allele because the RNA transcript for hangover is not evident in a Northern blot analysis. Furthermore, the scientists note that the flies’ capacity for tolerance can be rescued when a functional copy of hangover is reinserted into the flies under an appropriate neuronal promoter.
3) Description and localization of hangover
Scholtz H, et al. (2005) continue by briefly characterizing hangover and its protein product. Hangover apparently has eight exons and seven introns in addition to the 5’ and 3’ untranslated regions (Figure 1), The particular P-element insertion in the AE10 mutant flies occurred in the 1st exon.
Figure 1. Schismatic diagram of hangover. The gray boxes represent exons, while the first and second white boxes represent the 5’ and 3’ untranslated regions, respectively. The large triangle depicts where the P-element inserted in the hang mutant flies. (Image courtesy of Henrike Scholz, permission pending).
The protein product of hangover appears to consist of 1901 amino acids, and contains one EF hand and 15 zinc-finger domains (Figure 2). Thus, the hangover protein may function by binding to calcium and/or RNA. This protein is “broadly expressed in the nervous system and localized to the nuclei of neurons” (Scholz H, et al., 2005).
Figure 2. Cartoon of the 1901 amino acid hangover protein product. The ovals represent zinc-finger domains, while the ones marked with asterisks specifically refer to U1-like RNA binding domains. The black box represents an EF hand, which indicates that the protein may have calcium-binding properties. aa = amino acids. (Image courtesy of Henrike Scholtz, permission pending).
4) The hangover pathway has a connection to stress
In their supplementary figures, Scholtz H, et al. (2005) illustrate that the lack of ethanol tolerance in the hang flies is not a result of alterations in the flies' metabolism of ethanol. The scientists did, however, find a relationship between hang and the oxidative stress pathway by two routes. For example, hang flies showed an “increased sensitivity” to paraquat, a chemical, which leads to the creation of damaging reactive oxygen species (Scholtz H, et al., 2005). Thus, hangover appears to be necessary for flies to handle stress at the cellular level. Furthermore, while exposing normal, wild-type flies to heat shock conditions (i.e. inducing stress) 4 hours prior to ethanol exposure conferred the same incidence of tolerance as when the flies were exposed to ethanol 4 hours prior to a second exposure, hang flies exhibited the expected lack of tolerance when pre-treated with heat-shock conditions. Indeed, stressful conditions, such as heat-shock, appear to ramp up tolerance in normal flies, just like pre-exposure to ethanol.
5) At least one other tolerance pathway exists
Finally, Scholtz H, et al. (2005) explained that hangover is involved in one of at least two pathways linked to ethanol tolerance. Monastirioti M, et al. (1996) had previously isolated a strain of mutant flies that lack the gene for Tyramine beta-Hydroxylase, which processes tyramine to octopamine. Octopamine appears to act in invertibrates as noradrenaline acts in mammals (i.e. as a neurotransmitter). Mutant flies lacking Tyramine beta-Hydroxylase, called Tbh, also exhibit reduced abilities to develop ethanol tolerance by an unknown mechanism, unrelated to the cellular stress pathway (Scholtz H, et al., 2000). Tbh flies are not particularly sensitive to treatment with paraquat as the hang flies. In addition, in the most recent article, the scientists show that hang, Tbh double mutant flies still exhibit a minimal level of tolerance, suggesting yet another pathway involved with ethanol tolerance (Scholtz H, et al., 2005).
Probably due in large part to its title, shortly after this scientific paper appeared in Nature, the popular press sources from newspapers, to television stations, and even internet sites eagerly reported on the discovery of hangover to the public. Indeed, I will consider three such reports from The New York Post, FOX news, and NewScientist.com. These articles range in their content and accuracy. Careful analysis reveals that none of these summary articles are complete and---worse--- they are often misleading in some way.
To begin, FOX news’s article has an eye-catching, but accurate title: “Hangover Gene? Alcohol Tolerance May Be Genetic.” The overall point of this article is consistent with the scientific literature. FOX news correctly asserts that 1) “the gene didn’t literally create hangovers” and 2) ”Heberlein, PhD, and colleagues were studying a newfound gene in fruit flies that appears to affect alcohol tolerance” (Hitti M, 2005).
However, I have three main critiques of this article. First of all, this article contains strong language where the scientific journal is less definitive. For example, the article assets that increased consumption of alcohol “leads to physician dependence and addiction over time.” The verb “leads” is too strong given the incomplete scientific evidence. Simple qualifiers like “may” would make the statements in the article less definite, but more accurate. Furthermore, the article leaves out necessary background information and many points included in the original article of which that the average reader probably would not be aware. Indeed, Hitti correctly asserts that “the researchers only tested fruit flies, not people” (Hitti M, 2005). However, Hitti does not add that fruit flies are a model organism, often used to study the function of human genes. This fact is not obvious, because based on appearances alone fruit flies and humans are very different.
Moreover, unlike the scientific article, Hitti only vaguely discusses how the experiments were conducted. She never delves into actual methods to show that these scientists were doing good science. Likewise, Hitti never mentions the composition of hangover, its protein product, or the fact that there was another gene previously linked to alcohol tolerance, although these facts took prominence in the original scientific article. Finally, Hitti only references one source, the original article in Nature. It appears that she may be taking everything these scientists claim at face value. She is not approaching science as a skeptic or being completely unbiased.
On the other hand, the New York Post’s article contains problems of its own. First of all, its very title: “Hangover Gene” Clue in Booze-Woe Puzzle” is not altogether fitting. While “Booze-woe” puzzle could refer alcoholism, this phrase seems to suggest that hangover may be responsible for the hangovers. This title will likely mislead the average reader. Furthermore, although, again, the general gist of this article is in line with the scientific literature, this article leaves much out because it is so short. In fact, this article makes very little reference that scientists discovered hangover in flies. It also immediately generalizes the findings of the study to humans, where the original article only speculated about humans. Indeed, the average reader would likely miss this subtlety. Likewise, the New York Post article leaves out information regarding the methods of the study, the structure of the hangover gene and its protein product, the connection between hangover and the cellular-stress pathway, and the existence of alternative pathways for ethanol tolerance. This article only represents one main point from the scientific article. Finally, this article alludes to other studies, but it does not reference any sources. It only mentions the original article in Nature in passing. The average reader would be left to his or her own devices to find more information on the topic.
Finally, the NewScientist.com’s article represents perhaps the best summary of the original scientific literature, but nevertheless contains some misleading or inaccurate information. To begin, the article’s title is fitting, but too strong. “Hangover gene is key to alcohol tolerance” suggests that the findings are more definite than even Scholz, et al. (2005) assert. Regarding, the actual content of the article, it contains information that other popular press sources left out, including a brief description of the methods. The NewScientist.com article also addresses three main point of the scientific article in easy to understand language: the usefulness of flies as a model organism, the lack of tolerance exhibited in hang flies, and the connection between hangover and the cellular stress pathway. However, this article did leave out important information, such as the description of the hangover gene and its protein product and the fact that other tolerance pathways have been studied before. The article contains only one journal reference to the original article in Nature and does not bolster its information with additional information.
Also, the idea of stress as presented in this article is confusing. The article makes a leap that to the fly studies are applicable to human stress-related alcoholism that the scientific article does not. Vince writes, “prior stress can induce tolerance to alcohol even if a person has never had a drink before” (Vince, 2005). It is unclear whether stress in this case refers to physical or emotional stress. I am not convinced that heat-shock conditions and paraquat forced upon flies directly correlate the psychological stress that human experience.
Nevertheless, this popular press article uses easy to understand language and is generally on target with the original scientific article in Nature. Unlike the other popular press article, average readers would generally gain an understanding of the original scientific article after reading the NewScientist.com. Finally, Vince makes a valid, interesting point to which the scientific article alluded, but did not directly state. Vince writes, “there may be people in the population who have an over-expression of the human equivalent of the hangover gene and who may be especially at risk from developing addition problems” (Vince 2005).
Popular press articles certainly reach a broader audience than scientific journals. Thus, they disseminate scientific discoveries to the public. However, readers must be skeptical and not take popular press articles on scientific articles as scientific authorities. As we have seen in the examples above, it is often best to refer to the original sources cited by the popular press to attain the most complete information. Even the best popular press articles about scientific discoveries are often incomplete, contain overstatements, and can be misleading. Very rarely do popular press articles on scientific findings present information better than the original sources (i.e. contain information that is accurate and complete, yet uses everyday language or containg information about valid applications of findings).
“’Hangover gene’ clue in booze-woe puzzle.” 2005. New York Post. <http://www.nypost.com/news/regionalnews/51772.htm>. Accessed 2005 Sept 1.
Hitti M. 2005 Aug 11. “Hangover gene? Alcohol tolerance may be genetic.” FOX News. <http://www.foxnews.com/story/0,2933,165346,00. html>. Accessed 2005 Sept 1.
Monastirioti M, Linn CE, White K. 1996 Jun 15. Characterization of Drosophila Tyramine b-Hydroxylase gene and isolation of mutant flies lacking octopamine. J Neurosci 16, 3900-3911.
Scholz H, Franz M, Heberlein U. 2005 Aug 11. The hangover gene defines a stress pathway required for ethanol tolerance development. Nature 436: 845- 847.
Scholz H, Ramond J, Singh CM, Heberlein L. 2000 Oct. Functional ethanol tolerance in Drosophila. Neuron 28, 281-271.
Vince G. “’Hangover gene’ is key to alcohol tolerance.” 2005 Aug 22. NewScientist.com. <http://www.newscientist.com/article.ns?id=dn7830>. Accessed 2005 Sept 1.
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