by: Dr. Kathleen S. Matthews

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The nature of science is cumulative, building upon past discovery to open new insights into the natural world. This unique character of the research enterprise demands a high level of trust in the knowledge base upon which the next steps are constructed. As a consequence, the expectation of ethical behavior in the scientific community is very high. If the foundation for an experiment or theory has been flawed by intention, significant effort and expense are wasted, and careers can be compromised. This need for confidence in the work of others and awareness that intentional flaws or deceit are necessarily uncovered in attempts to replicate or expand research findings come together to drive a high level of ethical conduct in the scientific community.

Each individual scientist inevitably brings a set of perceptions with the potential to bias theory/experimental design or even interpretation, but the multiplicity of critiques that any discovery must undergo — from laboratory group discussions to peer review — ensure a wide variety of corrective inputs. Intentional violations of the expectations of accuracy in gathering, reporting, and interpreting data or formulating theories are effectively anti-science. Indeed, the fundamental importance of behavior that aligns with the expectations of the profession is reflected in the institution of systems within federal funding agencies to promote research integrity and, when necessary, to investigate lapses in ethical conduct of research. The Office of Research Integrity at NIH, http://ori.hhs.gov/, provides links to the research misconduct policies for many federal agencies. The emphasis on this issue is also seen in the requirement for instruction in the ethical conduct of research — from how to collect and analyze data and report results to treatment of animal and human subjects — associated with training grants from federal sources.

The challenges become even more complex for research involving human subjects. For example, “informed consent” is required for participation in clinical research trials, and a widespread view is that this consent is sufficient to render clinical research ethical. However, others have argued that “informed consent is neither necessary nor sufficient” [1] to establish an ethical base for research involving humans and that a larger set of questions must be addressed before individuals should be enlisted for clinical studies. Ethical lapses of commission or omission in clinical studies have the potential for dire consequences to the participants.

Beyond the larger issues, including fabrication or falsification of data, plagiarism, and other types of misconduct, ethical questions reach deeply into the scientific process and have been addressed from many perspectives [e.g., 2]. One of the most important concerns regards management of data. Interestingly, the majority of research misconduct findings in the federal review processes involve data falsification and fabrication, some simply as the result of poor data recording and management. For this reason, data management practices are emphasized in training scientists. How data are collected and recorded determine their reliability, and undergraduate teaching laboratories make significant efforts to guide students in developing good habits for the future. Data interpretation is particularly important — all data collected should be utilized in framing interpretations and developing hypotheses. Thus, data “selection” is not acceptable, and data inconsistent with the hypothesis guiding the experiments should never be withheld or ignored.

An area of particular concern in the modern computer age is the capacity to manipulate images and datasets, or even fabricate them to one’s own end. This area is of particular concern as the visual images and data from a variety of sources are digitally recorded and maintained. The conclusions from such fabricated or distorted data can be particularly destructive, both undermining others working in the same area and eroding confidence in the scientific enterprise itself.

The impact of scientific misconduct is reflected in its own entry in Wikipedia (http://en.wikipedia.org/wiki/Scientific_ misconduct), with a section that details this subject further and provides links to renditions of high profile examples of research misconduct. Recent examples include a prominent scientist from Seoul National University (Korea), who was indicted for embezzlement and for fraud based on fabricated data in reports on generating human embryonic stem cells; a research scientist from Bell Labs, who was fired and his doctoral degree revoked by the University of Konstanz for using falsified data in publications reporting single-molecule semi-conductor technology; and a professor at the University of Vermont, who, in 2006, was the first academic ordered to serve federal prison time for falsifying data in a research grant application to the NIH and was also found to have fabricated data in ten different published papers. As is evident, the consequences to the perpetrators, as well as to those attempting to replicate fabricated work, can be disastrous.

The ethical responsibilities of scientists encompass not only exercising a high level of integrity in our work, but also include understanding the social and ethical implications of our research [3]. Sharing our excitement in understanding the world/universe and enticing others to engage in that process are part of helping embed science as a part of our society. In particular, scientists are important players in making new policy, and finding a path that introduces our knowledge base into the complexities of political decision-making must be placed in an ethical framework. Roger Pielke [4] has suggested a variety of ways in which scientists can engage in sharing their experience and insight in creative, ethical, and useful ways. Rice University’s Baker Institute for Public Policy (BIPP) has been active in inviting scientists to share their expertise and in providing a variety of venues for reflection and discussion. Students interested in becoming involved can engage through the student arm of BIPP or contact Kirstin Matthews (krwm [AT] rice dot edu).

Ethical conduct is important in all aspects of our lives, but the very nature of science demands a high level of integrity. Indeed, the essential process of science with its accumulation of knowledge cannot function without honest disclosure. We rely on the honor of our colleagues and their scrupulous efforts to report their observations accurately. Without this element, the structure that we are building will be flawed and eventually collapse. That is not to say that scientists interpret all data correctly or that unintentional mistakes do not occur, but the primary intent required of the scientist is to report what is observed as honestly and completely as possible. What scientists have interpreted incorrectly will be discovered and set right as an integral part of the larger collective process. The necessity for correction because of intentional deceit corrosively undermines the scientific community.

The excitement of science is found in the effort to answer current questions about how things work and then pose new questions unanticipated by present knowledge. Since we often do not recognize what we do not know, a single breakthrough can open unimagined new horizons and render significant change, both in science and society. The discoveries of restriction enzymes, the magnetic properties of atomic nuclei, or Buckyballs (right here at Rice) are examples that have opened whole new territories for investigation and evoked substantial societal change. For example, without our knowledge of the magnetic properties of nuclei, invasive surgery rather than simple MRI scans would be needed to “see” what is happening inside our bodies.

The on-going scientific process of opening and exploring new territory at the frontiers of knowledge is highly robust because the discovery of error — intentional or otherwise — is inherent in the system. Most scientists exercise a high degree of integrity precisely because the journey beyond the far horizons of our current understanding is exhilarating and we wish nothing to impede our pioneering expeditions into the unknown!

Dr. Kathleen S. Matthews is the former Dean of Natural Sciences and a Stewart Memorial professor of Biochemistry & Cell Biology.

References

1. Emanuel, E.J., Wendler, D., Grady, C., What makes clinical research ethical? Journal of the American Medical Association 283, 2701-2711 (2000).
2. Montgomerie, B., and Birkhead, T., A beginner’s guide to scientific misconduct, ISBE Newsletter 17, 16-24 (2005).
3. Beckwith, J., and Huang, F., Should we make a fuss? A case for social responsibility in science, Nature Biotechnology 23, 1479-1480 (2005).
4. Pielke, R.A. Jr., The honest broker — Making sense of science in policy and politics, Cambridge University Press, Cambridge, UK (2007).

by: Tina Munjal, ’12

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The genome is indeed a curious creature. You may find it strange for a set of assorted strings of nucleotides to be referred to as a “creature,” because the implication would be that this collection of macromolecules is somehow alive and capable of self-preservation. Indeed, this is precisely the portrait that author Matt Ridley paints in his novel entitled Genome: The Autobiography of a Species in 23 Chapters.

Evidence for the idea of genomic autonomy can be found in the very origins of life. Ridley ponders these beginnings when he says, “It now seems probable that the first gene, the ‘ur-gene,’ was a combined replicator-catalyst, a word that consumed the chemicals around it to duplicate itself.” Thus, this gene served no higher purpose than to ensure its own survival and propagation. The ur-gene was not a subservient sequence.

If the initial purpose of genes was to attend to themselves, how is it that DNA has, over time, become an instrument of the organisms in which it resides? Or has it? As Ridley explains, it may be quite possible that the genome remains the omniscient executive, and the organism is but its compliant agent. The end goal of the genome-organism system is the proliferation of the genetic material itself, not of the “essence” of the organism in any platonic sense.

The most fundamental display of this phenomenon occurs during bacterial conjugation, in which each bacterium is a “temporary chariot” for the genes it carries. The transfer of genetic material can then be compared to the formation of “transient alliances” between the involved parties. Ridley proposes that, over time, genes “found a way to delegate their ambitions, by building bodies capable not just of survival, but of intelligent behavior as well. Now, if a gene found itself in an animal threatened by winter storms, it could rely on its body to do something clever like migrate south or build itself a shelter.” The author’s choice of words leaves no doubt that the genes, although relatively flexible masters, do indeed hold the reins over the actions of the organism to ensure that they are in agreement with—not in opposition to—the survival of the genetic message.

Extending this notion of genes as active doers rather than passive coders, Ridley offers a plausible explanation for the presence of so-called “junk DNA” in the genome. He likens these seemingly useless sequences, such as retrotransposons, to parasites that, at some point in the distant past, invaded the endogenous DNA. Just as there is war among nations to exert and expand influence, there is “competition between genes using individuals and occasionally societies as their temporary vehicles.” DNA is therefore much like a battle zone in constant evolutionary flux.

Ridley’s novel discussion about the relationship between genome and organism is at once fascinating and humbling. However, it would be insufficient to state that all of the actions of an organism, especially a human, lead so imposingly and inevitably, to nothing more than the proliferation of a collection of genetic material. Further, the image of the genome as the driver of some insentient chariot is not enough to describe the intricate exchanges that occur between genes, mind, body, and environment. Ridley does recognize this fact and even likens the fragile interaction to the workings of a free market. Just as there is no centralized authority in command of making the economy’s decisions, “You are not a brain running a body by switching on hormones. Nor are you a body running a genome by switching on hormone receptors. Nor are you a genome running a brain by switching on genes that switch on hormones. You are all of these at once.” The organism, then, possesses a variety of hierarchical systems that work simultaneously to form a functional whole.

This idea of shared authority smoothly propels Ridley’s discussion into the concluding philosophical treatise on determinism versus free will. On the one hand, there are those who would argue that genes are not what foster the development of behavior and personality—this view would be entirely too deterministic. Instead, proponents of the alternative hypothesis believe that the environment, not an intrinsic genetic factor, shapes individuals. However, as Ridley asks, is this not even more deterministic? He cites the example of Aldous Huxley’s frightening novel, Brave New World, in which “alphas and epsilons are not bred, but are produced by chemical adjustment in artificial wombs followed by Pavlovian conditioning and brainwashing…” In this world, genes factor very little into the equation, and the hellish, deterministic society is created entirely by environmental manipulations. So the essential question remains: do we have conscious control over our fates? The dilemma is not a new one. As Ridley points out, the philosopher David Hume summarized the problem through Hume’s fork, which states, “Either our actions are determined, in which case we are not responsible for them, or they are random, in which case we are not responsible for them.”

Perhaps the best answer comes from chaos theory, which states that a general course of events can be predicted with some certainty, while the finer details of this course remain unknown. As Ridley explains, due to various reasons, an individual chooses whether to eat a particular meal and the time at which the meal is taken. It can be said with confidence, however, that the individual will eventually eat at some point in the day. Eloquently, Ridley begins to close, “This interaction of genetic and external influences makes my behaviour unpredictable, but not undetermined. In the gap between those words lies freedom.” There is indeed flexibility within determinism, and consciousness alongside instinct.
For all of its impossible questions and imaginative answers, Matt Ridley’s book on the self-replicating, autobiographical, living, changing genome is worth its place on any genome-holder’s bookshelf.

Tina Munjal is a freshman double-majoring in Biochemistry & Cell Biology and Cognitive Sciences at Wiess College.

Reference

1. Ridley, Matt. Genome: The Autobiography of a Species in 23 Chapters; Harper Perennial: New York, 1999.

by: Zeno Yeates, ’10

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The increasing prevalence of energy drinks over the past decade is a phenomenon that cannot simply be dismissed as a passing obsession. What began with the advent of Red Bull in 1984 has evolved into a colossus of different brands claiming anything from sharpened mental acuity to enhanced athletic performance. Austrian-born Red Bull founder and CEO Dietrich Mateschitz relies on the younger generation for his sales base, exploiting the teenage drive for risk-taking and adventure using dramatic product names, draconian logos, and sponsorship of extreme sporting events [1]. Predictably, a multitude of competitors have followed suit, introducing similar concoctions with dicey names such as Cocaine, Dare Devil, Pimp Juice, Venom, and Monster. However, none of the claims of enhanced performance have been qualified by the U.S. Food and Drug Administration, thereby conjuring substantial criticism from the media and a variety of third-party organizations [2]. Yet at this point in time, neither advocate nor critic speaks with certainty.

All things considered, the chronicles of Red Bull are more of tenacious entrepreneurship than of science. However, the rationale behind its chemical formula reveals the potentially medicinal properties of its components. While overseas as a traveling toothpaste salesman, Mateschitz discovered the revitalizing effect of a syrupy tonic sold at local pharmacies in Thailand. The mixture, composed of only water, sugar, caffeine, taurine, and the carbohydrate glucuronolactone, soon became a mainstay remedy for his chronic jet-lag. After reading a financial article listing the top ten taxpayers in Japan, he was surprised to learn that a certain Mr. Taisho, who manufactured a similar restorative beverage, was listed among the other entrepreneurs. The ingredients were explicitly listed on the can itself, and neither trademark nor patent existed to protect its formula; hence, Red Bull was born [3].

Careful observation of any university library will reveal the undeniable popularity of iPods and Red Bulls – the arsenal for the true titan of academic endeavor confronting a full night of intellectual tribulation. Nevertheless, some conjecture whether Red Bull’s buzz serves only to distract the active mind in the same way that prolonged auditory stimulation seems to. The most immediate answer is given on the container itself, which specifically claims to improve performance in times of elevated stress or strain, increase endurance, increase reaction speed, and stimulate metabolism [4]. Surprisingly, the only active ingredients aside from water, sugar, and caffeine, are the amino acid taurine and the carbohydrate glucuronolactone [3]. A series of past Japanese studies on taurine had suggested cardiovascular benefits, further convincing Mateschitz of its revitalizing properties. However, taurine is not an entirely unfamiliar biochemical intermediate as some people might imagine. From a human physiological standpoint, taurine (2-aminoethanesulphonic acid, [NH2-CH2-CH2-SO4]) is a major constituent of bile found in the lower intestine [5]. Produced in the liver and brain, taurine plays an important role in the regulation of osmolarity, muscle contraction, and neuroprotection [6]. While technically not considered an amino acid (it conspicuously lacks a carboxyl group), taurine is a derivative of the sulfhydryl amino acid cysteine, and it constitutes the only naturally-occurring sulfonic acid [7]. Human taurine synthesis occurs in the liver, although it is also naturally produced in the testicles of numerous mammals, and urban legends suggest that the commercial sources of taurine are derived from bull urine and semen. Although taurine is found in both of these sources, the pharmaceutical industry actually obtains taurine from isethionic acid, which in turn, is obtained from the reaction of ethylene oxide with aqueous sodium bisulfate. In 1993 alone, approximately 5,000-6,000 tons of taurine were produced [8].

However, it must be noted that taurine is not the only active ingredient among the host of energy drinks on the market today. Generally, a given energy drink will include an amalgamation of caffeine, B-vitamins, and herbal extract. Other common ingredients include guarana, ginseng, L-carnitine, glucuronolactone, and ginko biloba. Many contain high levels of sugar, but many brands also offer artificially-sweetened “low-carb” versions. Nevertheless, the primary ingredient in nearly all energy drinks is caffeine, of which the average 16-fluid ounce serving contains 150 mg [2]. Little is known about the health effects of taurine and glucuronolactone, other than the fact that the given quantities in stimulant drinks are several times higher than that of a normal diet [9].

Nevertheless, taurine plays a major regulatory role within the human body. Found in high concentrations in skeletal muscles, it functions in regulating myofibril contraction. It increases force generation by enhancing the accumulation and release of calcium ions within the sarcoplasmic reticulum. Increasing intracellular taurine levels also augments the mean rate of increase in the force response. It has been suggested that the balance of endogenous myofibril taurine concentrations is critical for maintaining the appropriate force output during muscle contraction. Muscle fibers possibly modulate their contractility by increasing the taurine levels in response to neuronal inputs. Considering taurine’s role in muscle contraction, it may appear that increasing blood taurine concentration through dietary intake could enhance contractile force. However, considering that intracellular taurine concentration is tightly regulated [10], it remains unknown whether an increase in taurine plasma levels following consumption would have any noteworthy effect.

Since taurine exerts neuroprotective activity against excitotoxicity and oxidative stress, it is no surprise that massive amounts are released in the event of an ischemic episode. An in vivo analysis indicated that during ischemia, a seventeen-fold increase in taurine levels is typically observed in the brain. However, one must realize that there are two sources of taurine in the brain; direct synthesis from neurons and transport across the Blood-Brain Barrier (BBB). The Blood-Brain Barrier constitutes the membrane surrounding blood vessels leading to the brain, which regulates the exchange of molecules. The BBB is highly permeable to non-polar compounds but less permeable to polar ones. This regulation prevents harmful substances from entering the brain and only permits the passage of substances necessary for normal brain function. While caffeine can readily diffuse across the BBB, the entry of taurine seems to be regulated more rigidly [11].

Taurine is present in high concentrations throughout the brain, and it has been hypothesized that ingesting taurine in conjunction with caffeine improves concentration and reaction speed while also enhancing emotional status. Seidl et al. performed a double-blinded, placebo-controlled study in which the experimental group ingested a capsule containing caffeine, taurine, and glucuronolactone whereas the control group received a placebo capsule. The authors reported that members of the experimental group had shorter motor reaction times and better overall psychological well-being when evaluated. Hence, they concluded that taurine in conjunction with caffeine and glucuronolactone had positive effects on cerebral function. They also conjectured that taurine might interact with GABAergic, glycinergic, cholinergic, and adrenergic neurotransmitter systems. Nevertheless, they also agreed upon the possibility that such findings on cognitive performance may have been attributable solely to caffeine [12]. Unfortunately, none of the above experiments examined the possibility that caffeine alone could have produced such results. It is widely known that caffeine competitively inhibits adenosine receptors and thereby increases cAMP concentration [13]. This blockade can free cholinergic neurons from inhibitory control, leading to pervasive excitatory responses and the suppression of fatigue. These properties of caffeine alone may explain the favorable cognitive and emotive influences as demonstrated by the experiments [14].

Further refutation of the study by Seidl et al. stems from the fact that sodium and chloride dependent taurine transporters exist in the BBB. The activity of these transporters is closely regulated by transcription of the genes encoding them [16]. Such transcription seems to be dependent on the degree of cell damage, osmolality, and level of taurine in the brain, thereby suggesting that active expression of this gene serves as an acute response to neuronal perturbance or crisis. Hence, it is intuitive that under normal non-ischemic conditions, taurine levels within the brain are maintained at a stable level [15]. Therefore, an increase in the taurine plasma level resulting from dietary supplementation is not likely to cause a sudden influx of taurine into the brain. Furthermore, considering the substantial amount of endogenous taurine already present in the brain, it is questionable whether any entry would make a significant difference to the overall concentration [16].

Taurine itself is naturally present in a variety of meat, seafood, and milk [17]. However, taurine from the consumption of energy drinks is several times higher than that from the intake of a normal diet [5]. Under normal physiological circumstances, taurine is highly-conserved in the adult human body and present in relatively large quantities [9]. It has been estimated that a 70 kg (155 lb.) human is likely to contain 70 g of taurine, and the mean daily intake has been estimated to be somewhere between 40 and 400 mg [5]. In contrast, many energy drinks may contain up to 4,000 mg of taurine. Nevertheless, there is almost no data to suggest that consumption of taurine alone poses any substantial risk to human health. However, Simon, Michele, and Mosher’s study examined the growing trend of mixing energy drinks with alcohol. It was determined that blending energy drinks with alcohol greatly increased the number of energy drinks consumed per session, particularly in males aged 19-24 years. In addition, the data suggests that taurine may somewhat ameliorate the unfavorable effects of alcohol consumption [18]. Conversely, alcohol is known to exercise an inhibitory effect on taurine homeostasis in humans. The implication is that the massive influx of taurine from energy drinks encourages binge drinking. The advent of the Jägerbomb aptly reflects the social understanding of the antagonistic effects of both compounds. To this effect, drinkers attest to more reckless behavior and to a greater overall capacity for consumption. A study conducted in early 2006 concluded that combining energy drinks with alcohol predisposes drinkers to alcohol abuse since the depressant effects of the alcohol are somewhat mitigated by the stimulant effects of the energy drink [19]. Additional concern exists for the havoc that the depressant-stimulant combination wreaks on the heart. Alcohol alone, if abused, has been shown to reduce brain activity, impair cardiac function, and potentially lead to myocardial infarction [20]. In combination with an energy drink, effects on the consumer may include shortness of breath and an irregular heartbeat. Moreover, the body’s defenses are weakened by the dehydration from alcohol and caffeine, both of which are diuretics [21].

Yet despite the injurious social trends that have become associated with energy drinks, many studies have demonstrated the applicative efficacy of the products in their pure form. With regards to the psychological effects of Red Bull Energy Drink, two studies reported significant improvements in cognitive performance in addition to increased mental alertness [22]. Moreover, consumption of energy drinks may induce a mild to moderate euphoria primarily caused by the stimulant properties of caffeine and ginseng [16]. The restorative properties were attributed to a combination of caffeine and sugar in energy drinks, though a concerted effect between glucose and caffeine has also been suggested. Concerning generalized physiological effects, the consumption of Red Bull alone was shown to promote endurance during repeated cycling tests in young healthy adults [23].

The short term physiological effects of energy drinks were most thoroughly examined by Alford, Cox, and Wescott in a series of three studies conducted on a small population of students from the University of Bristol in England. The studies investigated psychomotor performance (reaction time, concentration, and memory), subjective alertness, and physical endurance. When compared with control drinks, containing neither taurine, caffeine, nor glucoronolactone, Red Bull significantly improved aerobic endurance in addition to anaerobic performance in stationary cycling tests. Significant improvements in mental performance were also noted, especially with respect to choice reaction time, concentration, and memory. These consistent improvements in both mental and physical performance were interpreted as reflecting the combined effects of the active ingredients [22]. The same study was conducted based on the fact that Red Bull contains several active components (taurine, glucuronolactone, caffeine, and several B-vitamins), which render a multiplicity of effects on human metabolism. Perhaps more fundamentally, Red Bull also contains glucose, which is metabolized to release energy during both aerobic and anaerobic metabolism and may improve cognitive performance [14].The fact that Red Bull is also endowed with a host of B-group vitamins must not be overlooked however. It is widely known that vitamin B-12 (cyanocobalamin) plays a critical role in human brain function and is intimately associated with energy production [24]. Nevertheless, the most important conclusion drawn from this study is that the anti-hypertensive actions of taurine may oppose increases in blood pressure from caffeine, reflecting that the ingredients act in concert and not independently to achieve the observed effects [14]. Although most improvements in mental acuity are attributed to the caffeine content, it should be noted that energy drinks contain several other biologically-active ingredients that possibly contribute to this effect [15].

Perhaps surprisingly, the biological effects and health consequences of caffeine, despite extensive research, remain the subject of ongoing debate. In the UK, the mean daily caffeine intake from tea, coffee, and carbonated beverages is estimated to be 278 mg/day for a typical 70 kg male [25]. In addition to coffee, tea, and carbonated beverages such as soft drinks, caffeine is present in many medications, headache treatments, and diet pills. In fact, caffeine is an active ingredient in more than 70% of the soft drinks consumed in the United States [12]. However, one must assess not only the quantity ingested but also the rate at which it is metabolized. All of the caffeine contained in a cup of coffee (115-175 mg) is cleared from the stomach within forty-five minutes of ingestion [26]. The caffeine is then absorbed from the small intestine, but does not accumulate in the body as it is rapidly metabolized by the liver, with a half-life of 4 hours for a normal adult [27]. Increased half-life values can be found in women using oral contraceptives (5-10 hrs) and in pregnant women (9-11 hrs) [28]. One review of caffeine dependence studies shows a wide variety of withdrawal symptoms including headache, irritability, drowsiness, mental confusion, insomnia, tremors, nausea, anxiety, restlessness, and increased blood pressure [29]. It is interesting to note that the symptoms of caffeine withdrawal also occur in the case of excess consumption [30]. On the other hand, lower doses of caffeine (20-200 mg per day) have been associated with positive effects on mood, such as perceived feelings of increased energy, imagination, efficiency, self-confidence, alertness, motivation, and concentration. While caffeine is reported to reduce reaction time during simple tasks, the effect is thought to be from enhancing coordination rather than from accelerating mental activity [16].

In contrast to the more detrimental pursuits practiced by consumers, the newest line of energy drinks is marketed with a health component, suggesting benefit to individuals partaking in athletic pursuits. The progeny of this innovation is Free Radical Scavenger Energy (a.k.a. FRS Energy), which constitutes the newest line of energy tonics. Accordingly, Lance Armstrong is already on board for endorsements. The legendary cyclist makes the supportive claim: “With all I have going on, I need a source of sustained energy. FRS fits in line with me wanting to be ninety, wanting to keep running marathons, riding my bike, being fit, and having fun.” Apparently, the marketing angle on energy drinks has progressed from late-night fix to sheer invincibility. The basic premise of FRS energy is that it simultaneously fights fatigue and cancer. FRS differs from its competitors in that it is endowed with a different central component known as quercetin, which plays a dual role in the human body both as a stimulant and as a flavonoid [31]. Flavonoids are typically secondary plant metabolites known to sequester numerous mutagens and carcinogens [32]. But FRS also claims that this plant derivative also combats fatigue by inhibiting the enzyme Catechol-O-methyltransferase (COMT), which is responsible for the degradation of catecholamine neurotransmitters including dopamine, epinephrine, and norepinephrine. These neurotransmitters are largely responsible for the “fight or flight” response generated in times of duress [33]. Contrary to other energy drinks, FRS claims not to have the commonly associated withdrawal and crash effects [32]. This claim is based on the fact that quercetin has a physiological half-life of 16 hours, as compared to the 4-hour half-life of caffeine, thereby extending its window of physiological effects on the body. Quercetin also helps to fight cellular damage and fatigue caused by the oxidants that accumulate from daily activity, exercise, and stress [34].

The mass-manufacture of quercetin might present a temporary loophole in high-powered athletic drug screening. Currently, caffeine use in Olympic sports is a contentious issue, and the International Olympic Committee (IOC) considers a urinary concentration of caffeine of 12 mg/L to be a positive drug test. This is due to the fact that caffeine has been shown to have performance-enhancing effects at concentrations that would result in a urinary excretion below 12 mg/L as set by the IOC [35]. Caffeine is reported to be most beneficial in endurance-type exercise activities [36]. Nevertheless, there is still no consensus on the biological mechanism to explain performance improvements. However, one possibility is that caffeine lowers the threshold for the release of exercise-induced endorphin and cortisol—hormones which may contribute to the reported benefits of caffeine on exercise endurance. Also, there exists no widely-accepted evidence that such performance-enhancing effects increase with additional caffeine doses [26]. On the contrary, the dehydration effects of caffeine and the absorption inhibition effects of glucose pose a serious threat to an athlete training in warm weather conditions [14].

It seems as if the principle concerns regarding energy drinks stem from one of the two associated risks of ingesting something with a high caffeine content. One is the possibility of caffeine overdose that can result in tremors, seizures, or even death [37]. The LD50 for caffeine depends on body mass, but ranges from 13-19 g as the mean lethal dose for a 70 kg (155 lb) male, which equates to approximately 80 cups of coffee [38]. Many deaths have been linked to the excessive caffeine content in energy drinks, which is a consequence of the misleading display of nutrition facts on the container. Manufacturers often limit the serving size to half or even a third of the bottle and do not factor in the hidden caffeine content of the herbal additives such as guarana. Such commercial subterfuge allows for rapid ingestion of large quantities of caffeine under the assumption that you are consuming nothing more than the equivalent of two cups of coffee [21]. The second associated risk is that of dehydration, which also results from excessive caffeine intake [39]. Claims that energy drinks enhance athletic performance have led to consumption both before and after athletic activity. Coupling fluid loss from exercise with the diuretic properties of caffeine facilitates accelerated dehydration rates [26]. Reflecting on the recent proliferation of the energy drinks industry, the Stimulant Drinks Committee of the British Nutrition Committee issued a series of recommendations for the consumer. Primarily, the committee advises discretion in the consumption of stimulant drinks with alcohol. Likewise, it deems energy drinks unsuitable for children under the age of sixteen, for pregnant women, or for individuals sensitive to caffeine. Finally, it recommends that stimulant drinks not be consumed as a thirst quencher in association with sports and exercise [36]. Even so, the true test of the efficacy and safety of energy drinks will only come from decades of widespread consumption by the general populace.

Nevertheless, one must consider the societal ramifications of widespread consumption. Assuming that energy drinks do confer some sort of competitive advantage, whether it be in the athletic or intellectual realm, what are the consequences? This same question was posed by David Eagleman, assistant professor of neurobiology and anatomy at Baylor College of Medicine, during the Rice Scientia lecture last fall. He stressed one factor that must be taken into consideration is the relatively high cost of energy drinks, as most products sell for about $3 a can. Eagleman also made the very apt remark that many gateways to economic success are based on standardized tests mandating a specified degree of mental capability [40]. He went on to insinuate that socio-economic disparities might be exacerbated when the affluent have unrestricted access to such mind-enhancing products. Competition for high-stakes testing such as the SAT is enormous and reports abound of identity fraud and violation of test protocols that are in place to ensure the standardized nature of these monolithic rites of passage into the professional world [41]. Operating under the assumption that energy drinks do confer some real performance advantage, one can only speculate on how the retail of such a competitive edge will influence existing class disparities. In the same light, any student has heard of someone taking self-prescribed Adderall to jack their focus for the next big exam. When school becomes a sport, what will be the next regulatory countermeasure, retinal scans and blood testing before the MCAT? Nevertheless, despite the debatable efficacy of existing energy drinks, their development marks the realization of a concept that will likely be pursued in the future. That is, the idea of biological performance enhancement not for sport, but for academia will be manufactured, marketed, and sold in a diversity of ways.

In sum, what began with the introduction of Red Bull twenty-five years ago has proliferated into an assortment of products that demonstrate short-term physiological benefits. However, the effects of regular long-term consumption have yet to be determined. Although energy drinks have traditionally associated themselves with risk-taking and subversive behaviors, the consolidation of various stimulant and focus-enhancing substances into one beverage represents an effort to maximize productivity. Not surprisingly, new product lines supported by world-class athletes claiming added health benefits constitute the newest progression for the energy drink enterprise. Finally, one must question the socio-economic ramifications of widespread use of legalized performance enhancers. Nevertheless, for now at least, the buying and selling of human energy remains caveat emptor, though there is no better remedy for the infamous all-nighter.

Zeno Yeates is a junior double-majoring in Biochemistry & Cell Biology and English at Sid Richardson College.

References

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I was walking across campus one day when a guy with a voice recording device stopped me and asked if I’d be willing to talk for thirty seconds about Rice student life. I must not have seemed very enthusiastic because he insisted I could talk about “anything that mattered to me.” I accepted. When he asked, “What has been the most memorable part of your undergraduate experience?” I started talking about zebrafish and fluorescently labeled embryos, hands-on experience and great mentors, and – “Um, is there anything other than research that you’d like to mention?” I blinked. “Well, yeah, there’s the college system and classes, all that, but – ” “Yeah, that’d be great, can you talk about that, please?”

So for everyone who already knows about the college system and classes, or for anyone who wants to know what it’s like to try research as an undergrad, here is my story. Naturally, there is no single ‘Undergraduate Research Experience at Rice.’ It will depend both on the lab and on the student. Many undergrads probably find it difficult to balance lab with classes, college life, sports, and other hobbies. In the end, though, it all comes down to a conscious decision. We distribute our time according to what matters to us. If you ask any undergraduate researcher what his or her experience is like, the specifics will change, but all of them will agree that they get out as much as they put in. So I can only speak for myself when I say that joining my lab was probably the best academic decision I made while in college. It’s been a lot of fun, and it’s helped me figure out what to do after I graduate, but what I really want to talk about here are the ways in which I have been challenged, and the things that I have learned. Research is hard, but all of the things that make it hard are the things that make it worth it.

I joined Dan Wagner’s lab at the beginning of the second semester of my freshman year. He and Mary Ellen Lane are the two Rice faculty members who work with the zebrafish as a model organism for embryonic development. I started looking for a lab with the idea that I wanted to work on development, a topic that strongly appealed to me even though I knew very little about it. All I knew was that every cell in my body contained the same DNA, and the process by which all of these cells came to be different seemed like a huge, exciting mystery.

From the beginning, I found my research topic fascinating. We try to identify genes that are important for cell and tissue movements during development. I’ve worked on several different projects over the last two years, and I’ve learned more than I ever would have expected. I learned a handful of technical skills, sure, like how to inject embryos at various stages with RNA, how to navigate the compound microscope, or how to tell adult male and female zebrafish apart. I developed more intellectual skills, like how to think of ways to answer a specific question by using the tools available, how to succinctly summarize my data for a group, or how to fit what I was doing into the bigger picture. I also learned a fair amount of developmental biology itself, just by exposure through background reading and lab meetings. But honestly, the biggest revelation, for me, was discovering what science is truly like.

I’d had no prior research experience, and even though I loved biology, I wasn’t initially convinced that I would actually enjoy research. I had always been slightly dysfunctional with school-related labs. They seemed boring and pointless, and I’d always end up knocking a beaker over or forgetting to add HCl at some critical point. But I soon realized that research was nothing like any prior educational experience I’d had. It is a very different way of learning; it has a different final goal. In many introductory science classes, we spend a lot of time taking in massive amounts of very detailed information. This is fine, since in the end we manage to avoid nervous breakdowns and we retain a sense of the bigger picture. In teaching labs, most of us are just doing the work so that we can get the expected result and get out of there (go eat dinner, pass the course, get on with our lives). That’s fine too, since those classes still provide a structured, straightforward introduction to basic experimental procedures and theory.

But when we do research, we’re a part of something much bigger. We can have various motivations for doing the work: 1) it’s a much more entertaining way to spend the afternoon than studying, 2) it will help us learn new skills that will open up doors for the future, 3) we’re so engrossed by the research question that we lose sleep over failed experiments and we want to know if it works this time, 4) we feel valued by a team that we have somehow become a part of, and contributing to something bigger than ourselves gives us a sense of purpose, or 5) all of the above. In any case, the nature of the investment is very different than for schoolwork, and perhaps this is why it comes as a bit of a shock when things don’t run smoothly.

Science is slow, and failure is normal. I was surprised, at first, by how often my experiments didn’t work, but after a while I realized that I’d get there in the end. I just had to keep trying. Patience and perseverance are almost always rewarded. True, luck will come into play, but it’s like everything else in life: there are so many things outside of our control, but we can’t focus on those. We’ll go crazy if we do. We need to focus on what’s in our power. Analyze our options, pick one, and keep going. Sooner or later we run into that beautiful day when everything goes right and we get so much done and something really exciting happens, and then it’s all worth it.

Another major thing that surprised me was the extent to which research is based on human interactions. It is an amazing feeling to be surrounded by people who are eager to share their passion, to answer my questions, to listen to ideas – it is difficult to explain the extent to which this has transformed my academic life. Without the others to guide me and make me think deeper, go farther, push my own intellectual limits, I wouldn’t have grown or learned nearly as much.

I have decided to go to graduate school, because I cannot imagine not being able to do this after I graduate from Rice next year. I know that my experience is not everyone’s, but I think that many types of students can get a lot out of research. I have heard pre-meds comment that it has helped them learn “how to think”, as well as how to keep trying. And it’s good for any science major to get a glimpse into how the process of knowledge actually happens. Again, I can only speak for myself when I say that I don’t regret the time and energy I’ve committed to research. I think that people from any discipline can relate to the importance of finding one’s passion. It doesn’t have to be your career–I know a friend who lives for music even though she is a Bioengineer–but somehow, I stumbled upon mine here.

Celine Santiago is a senior Biochemistry & Cell Biology major at Martel College and the recipient of the 2008 Barry M. Goldwater Scholarship.