If you were to hear the words ‘opioid peptides’, they might not trigger much within your brain, other than that the former sounds a bit like opium and together they sound quite scientific. Opium (also known as poppy tears) is a dried substance or latex that originates, as the alternative name suggests, from the opium poppy. Beautifully intricate pipes of bamboo, ivory, silver, jade and porcelain have been carved over the centuries and used to vaporise and inhale the latex traditionally obtained by scratching immature poppy seed pods by hand. Numerous Empires including the Egyptian, Greek, Roman, Persian and Arab made widespread use of the drug, which was then the most potent form of pain relief available. This analgesic property is conferred by morphine, which constitutes approximately twelve per cent of opium and is chemically processed to produce heroin. Commonly known by the street names H, smack, horse and brown, among others, the effects of heroin will be well known by any ‘Trainspotting’ fans. What writer Irvine Welsh did not reveal, however, is that opiates such as heroin mimic the effects of naturally occurring molecules that can be generated inside our own bodies.
Opioid peptides are small molecules that are produced in the central nervous system (the brain and spinal cord) and in various glands throughout the body such as the pituitary and adrenal glands. These peptides can be divided into three categories (enkephalins, endorphins, and dynorphins), depending on the type of larger precursor molecule from which they are derived. Opioid peptides function both as hormones and as neuromodulators; the former are secreted in the blood system by glands and are delivered to a variety of target tissues where they induce a response, while the later are produced and secreted by nerve cells (or neurons) and act in the central nervous system to modulate the actions of other neurotransmitters.
Neurons are electrically excitable cells that process and transmit information through electrical and chemical signals that travel via synapses, specialised connections with other cells. These signals are transmitted across a synapse from one neuron to another by neurotransmitters. By altering the electrical properties of their target neurons and making them difficult to excite, opioid peptides can influence the release of various neurotransmitters.
Through these two different mechanisms, opioid peptides can produce many effects including pain relief, euphoria and altered behaviour such as food and alcohol consumption. The apparent connection between exercise and happiness has been explained at least somewhat by the release of endorphins, for example. Exercise is commonly recommended as a strategy for stress-relief and mood improvement, but less widely accepted forms of therapy might also be connected to opioid peptides. Evidence suggests that pain relief induced by acupuncture results from stimulation of opioid peptides – these peptides act through receptors on their target neurons, and chemicals that inhibit opioid receptor function have been found to reverse acupuncture-induced analgesia. Painful, stressful or traumatic events or stimuli can induce the release of opioid peptides, with the resulting euphoria and pain relief making the sufferer less sensitive to noxious events. Opioid peptides have been reported to affect the release of specific neurotransmitters such as dopamine and serotonin, but the response of the neurons that receive opioid-peptide stimulation depends on their excitatory versus inhibitory nature, making the outcome difficult to predict.
The words ‘opioid peptides’ may not have left a dazzling feeling of recognition within your memory upon first encounter, but these peptides act within the brain and wider body to influence a number of important functions. Although it is not easy to predict the effect of neuromodulators that alter the release of other neurotransmitters, there is little question that opioid systems play a critical role in modulating a large number of sensory, motivational, emotional and cognitive functions. Alterations in opioid peptide systems may contribute to a variety of clinical conditions, including alcoholism, obesity, depression, diabetes and epilepsy. Many questions still remain, particularly those concerning the exact role of opioid peptides produced within the body in relation to addictive and emotional behaviour and psychiatric disorders. Since these disorders are typically of a complex nature, seeking the answers to these questions is not a simple feat. Advances in genetics and genomics research that aim to explain function by studying our DNA are helping to pave the way. But perhaps if there is one thing that can help motivate our talented scientists to reach their challenging goals, a healthy dose of opioid peptide might be just the thing.
Emily Brown PhD
Google the words ‘protein supplements for athletes’ and a number of links will appear in your browser. While apparently just a click away from learning the ‘truth’ about these dietary additions, it is advisable to consider the nature of whichever website you fall upon before hollering hallelujah. Company websites marketing protein supplements claim to give athletes the ability to ‘beat their best competition’ and to ‘get bigger and/or stronger’. Promasil, ‘the athlete’s protein’, for example, features seven of the world’s most powerful proteins. Imagine the industrial strength containers needed to keep these key ingredients from escaping. No more five dozen eggs a day to grow biceps the size of barges (the strategy adopted by Disney’s Gaston), a more palatable and practical solution is delivered in the form of a delicious flavoured powder. Since proteins are a major component of muscle, it surely makes sense that consuming more would result in extra bulk. But protein supplementation is not only about bodybuilding. For those more concerned about beating personal bests and leaving the competition trailing behind, protein supplements are also argued to directly enhance endurance performance and to optimise recovery of muscle function following exercise.
So how does it work? Naming a chocolate bar after a long-distance running event (and later rebranding using a word that sounds like underwear in British vocabulary – ‘Snickers’), no doubt taught the importance of carbohydrate as an energy source. Through reduced breakdown of carbohydrate during prolonged exercise, protein supplements are thought to enhance performance and to more quickly replete muscle glycogen (a specific type of carbohydrate) during recovery. By stimulating muscle protein synthesis, protein supplementation is also theorised to reduce muscle damage and speed up the recovery of muscle function. If you recently ran down a hill or lifted some weights, ideally not at the same time, you may later have felt soreness in your muscles, caused by damage to proteins that are required for muscle contraction. In such circumstances, rates of muscle synthesis and degradation are increased, and without sufficient protein intake, rates of degradation exceed synthesis and a negative net protein balance results. Consuming protein supplements during recovery from exercise should, however, promote the production of skeletal muscle (muscle that is attached to bones and contracts on demand).
Despite the logic behind these claims, a systematic assessment of the evidence to support or refute the relationship between the use of protein supplements and exercise performance, muscle damage and soreness, and recovery of muscle function has until recently been lacking. Earlier this year, Pasaikos, Lierberman and McLellan addressed this dearth by publishing two review articles in the journal Sports Medicine. Examining publications reporting findings from ‘healthy human adults’ (no chimpanzees thankfully) between 18 and 50 years of age, they found no apparent relationship between recovery of muscle function, muscle soreness and muscle damage when protein supplements were consumed prior to, during or after a bout of endurance or resistance exercise. If supplemental protein was consumed after daily training sessions, however, beneficial effects such as reduced muscle soreness and damage became more evident. They also found that when carbohydrates were at optimal levels during or after exercise, protein supplements provided no performance enhancing effects. In particular, sparing of muscle glycogen stores was not supported as a mechanism leading to enhanced endurance performance.
Pasaikos et al. warned, however, that small numbers of participating adults and lack of dietary control limited the effectiveness of several of the investigations they examined. Since studies did not measure the effects of protein supplementation on direct indices of muscle damage or muscle glycogen, for example, the interpretation of the data was often limited. What does seem clear, however, is that if athletes maintain a healthy diet, by consuming enough protein and carbohydrate through traditional means (for example regular food), protein supplements are unlikely to generate record breaking results. Only when the healthy human adults involved in the studies examined by Pasaikos et al. were lacking in nitrogen (found in amino acids that make up proteins) and/or energy balance were performance enhancing effects of protein supplements found to be greatest. Endurance is of course built by training and not protein alone. Whilst Pasaikos et al. demonstrated the need for further high quality research on the potential benefits of protein supplements, a healthy diet, sufficient rest and undeterred dedication seem to be best recipe for success.
Emily Brown PhD
An apple a day may keep the doctor away and is a good idea title for a book, but it’s probably a bad premise for a scientific study. The other day, a friend of mine drew my attention to a headline in the UK Telegraph “Eating an apple a day improves women’s sex lives, study shows.” Bad grammar not withstanding, I defied my better judgment and decided to read the article. The Telegraph doesn’t have the best track record of health reporting. Recently they wildly misreported a study about edible flowers and true to form they botched this one as well.
The article makes a number of claims. It says that that apples have “been show to be an aphrodisiac,” that “an apple a day can improve the sex lives of women” and that they “boost sexual pleasure in healthy women.” These are impressive attributes for a simple fruit, so I decided to read the actual study this report was based on.
The study was published in the Archives of Gynecology and Obstetrics. Essentially researchers took 731 women and asked them how many apples they ate every day and then asked them to fill out a questionnaire about their sex lives in areas such as desire, arousal, satisfaction, pain, etc. Researchers found an improvement in lubrication and consequently in the total score, but not in any other area of the questionnaire. Here is an actual quote from the study, “No significant differences between the two study groups were observed concerning desire, sexual arousal, satisfaction, pain and orgasm.” (Interestingly, the group that ate less apples had a slightly higher satisfaction score 4.5 vs. 4.3). This strikes me as fairly convincing that apples are don’t affect the quality of women’s sex lives at least in terms of the metrics that actually matter. Having read this study, I cannot for the life of me figure out how the Telegraph could have generated their headline. I can only assume they didn’t actually read it and just parroted the press release.
Even if you accepted their one single positive finding, the study has a lot wrong with it. First off, it is not a randomized clinical trial. Even though the newspaper story seemed to imply that it was, here researchers simply asked women how many apples they ate and did not actually conduct an experiment. It is easy to image why women who ate apples on a daily basis would be different than women who did not. They were likely more health conscious, probably exercised more, and probably had a better diet overall. Those who ate more apples probably ate more bananas, more oranges, more pears and more fruits in general. Researchers did not ask about other fruits and they likely could have just as easily shown an association with kiwis or pomegranates. So why apples? I guess the link to the biblical story of Adam and Eve was too good to pass up. Of course, the fruit of the tree of knowledge wasn’t actually an apple but why quibble on details.
The newspaper article also then makes a number of claims that the benefits of apples are due to phloridizin and polyphenols. This is pure speculation. This study, as I mentioned, did not measure any hormone levels or perform any tests on the apples themselves. It was purely the analysis of questionnaire sent out to women. Clearly, throwing in a few “sciency” terms (and adding the requisite photo of an alluring women biting into an apple) made the article more appealing to the newspaper editors.
Apples are unlikely to improve your sex life and, while we’re at it, neither will oysters, chocolate, or ginseng. An overall healthy lifestyle with regular exercise and a balanced diet is probably your best bet (but admittedly this would make for a lousy headline). So what can we conclude overall about eating an apple day? No effect on sexual desire or satisfaction, great title for a book, and (from my point of view) it’s bad for business.
MD CM FRCPC
I get a surprisingly large amount of hate mail when I advocate for such “radical” things like vaccinations, water fluoridation, and suntan lotion (yes even suntan lotion). Some people just flat out insult me but some try to re-educate me with their version of the “evidence.”
A similar thing happened this week with the release of a document from an organization called Action on Smoking and Health, which has as its main goal to lobby for tighter restrictions on cigarette sales. Their report focused on the growing use of electronic cigarettes in the UK, which has tripled from 700,000 to about 2 million in the past 2 years. It has shown that electronic cigarettes are a very popular product in the UK and that most people are trying them as a means to quit smoking.
I had several problems with these assertions. Firstly, the sheer popularity of a product doesn’t make it a good idea. There was of course a time when combustible cigarettes were very popular too. So I got on Twitter and pointed out that this report doesn’t actually provide any new evidence on the long term safety or effectiveness of this product from a medical standpoint.
What happened next was quite amazing. A flurry of e-cig supporters descended upon my post and started offering up “evidence” that e-cigs will “millions of lives” and that I was in the pocket of the big tobacco companies and wanted people to keep smoking. I calmly pointed out that the two biggest manufacturers of e-cigarettes, blu and Vuse, are owned by Lorillard and Reynolds, two of the biggest tobacco companies. Consequently the biggest promoter of e-cigarettes is the tobacco industry (note that Jenny McCarthy, the great luminary of our generation, has become the spokesperson of blu). This sparked apoplectic rage on Twitter where many claimed that what I said wasn’t true and that they were “fighting 4 lives now & future.”
I was then presented with a reference that the Royal College has stated “E-cigarettes will save lives, and we should support their use.” I looked up the reference and pointed out that it was actually an editorial written by a single person not a professional endorsement from the medical community. I was told in response, “What ever you wish to call it, the meaning is plain, Huge Health dividends can be had with Ecigs.” At this point I realized that I was wasting my time and that logic can seldom overcome this degree of idolatrous zealotry.
I remembered a quote that I heard a while back. It is attributed to Scott Weitzenhoffer in a review on Amazon of Eugenie Scott’s book “Evolution vs. Creationism: an introduction.” The quote was “Debating creationists on the topic of evolution is rather like trying to play chess with a pigeon — it knocks the pieces over, craps on the board, and flies back to its flock to claim victory.” Numerous versions of the quote now exist and is often applied to Internet trolls and most other groups who can never change their minds despite evidence to the contrary.
The astute reader will realize that I’ve never actually said what I think about e-cigarettes. I am reserving final judgment on the products, but I have some concerns. First, the widespread marketing so clearly aimed at children (why else would you make the product in cotton candy and bubble gum flavour) is unsettling. Second, while everyone is talking about these products as smoking cessation one company states “blu eCigs® electronic cigarettes are not a smoking cessation product … nor are they intended to treat, prevent or cure any disease or condition.” The companies have to state this in order to be able to market and sell their product without restrictions or governmental oversight. They let Twitter make the health claims for them.
Sadly, it may take over 10 years before we have enough data to see if e-cigarettes actually do make people quit smoking, reduce cancer incidence, or have any health benefits. Until then I will remain cautiously skeptical, as all good scientists should.
Although I suspect my new found friends on Twitter, (who are seldom right but never in doubt, as Joseph Dobrian put it) will not be so circumspect in their assumptions and continue to claim that their product is the greatest thing since sliced bread. So as they fly back to their flock to claim victory and I pick up the dropping covered chess pieces lying on the floor, I have learned a valuable lesson about arguing with people on the Internet: you can’t win against someone who doesn’t understand the rules.
Christopher Labos MD CM FRCPC
Division of Epidemiology, Biostatistics and Occupational Health
The most recent Spider-Man film grossed nearly $800 million worldwide, and cinemas are set to unleash a new and improved Spider-Man 2 this May. Whilst the great charm and beauty of actors Tobey Maguire and Kirsten Dunst most likely helped fuel the initial success of the film series, our fascination with the part-man-part-beast concept has spanned far beyond the glitter of Hollywood. Peter Parker’s DNA may have flashed before our eyes as his body assimilated superhuman powers, but the idea of genetic modification existed in both the fantasy and real worlds long before the advent of such impressive computer generated images. Wikipedia, arguably the source of all valuable knowledge, lists 85 characters, comics or films that involve some form of genetic engineering. Ranging from the less suspecting (Tracy Strauss, Madelyn Pryor, Julian Bashir) to the more ridiculous (Shaggy Man, Venus Bluegenes, The DNAgents), these characters share in common a possession of extraordinary powers, and sometimes the adoption of highly colourful and figure-hugging body suits.
But how exactly is the acquisition of such power explained by the respective literary proponents? Peter Parker’s body-wide changes are initiated by radioactive mutagenic enzymes present in the venom of the lethally irradiated spider un(fortunate) enough to bite him. Not long after this bite does Parker start to display spider-like characteristics -superhuman strength (the jumping spider can for example hold 170 times its own body weight), reflexes, balance, a subconscious sense of danger (the so-called ‘spider-sense’) and the ability to cling to any surface. No doubt all highly desirable traits. But as unlikely as this might sound, the suggestion that enzymes can alter DNA is not such a wild idea. Genetic modification, the direct manipulation of an organism’s DNA, requires the DNA to first be cut so that it can then be joined or spliced together with DNA from another source. A restriction enzyme is an enzyme that cuts DNA at or near specific recognition nucleotide sequences, known as restriction sites. These ‘molecular scissors’ are routinely used for DNA modification in laboratories and are a vital tool in molecular cloning.
Over 3000 restriction enzymes have been studied in detail, and more than 600 are available commercially. Whilst the idea of an irradiated spider might seem far-fetched, restriction enzymes are naturally found in bacteria and archaea (a group of single-celled microorganisms). Here they provide a defence mechanism against invading viruses; the foreign viral DNA is cut up by the restriction enzymes, while the host DNA is protected by an enzyme that modifies the DNA and blocks cleavage. The term restriction enzyme originates in fact from the studies of phage l (a virus that infects the bacteria Escherichia coli, better known as E. coli). In the early 1950s, in the laboratories of Italian scientists Salvador Luria and Giuseppe Bertani, it was discovered that a phage could grow well in one strain of bacteria, yet fare significantly worse in another. In the latter case, the bacterial host cell was evidently capable of reducing the biological activity of the virus (in a process known as restriction), although the exact mechanism remained unclear. This mystery was solved in the 1960s, this time in the laboratories of Werner Arber and Matthew Meselson, where it was shown that the restriction is caused by enzymatic cleavage of the phage DNA. Unsurprisingly, the enzyme involved was termed a restriction enzyme.
The restriction enzymes studied by Arber and Meselson were type I restriction enzymes that recognise a restriction site, but cleave the DNA at a non-specific point located some distance away. Another decade later, in 1970, Hamilton O. Smith, Thomas Kelly and Kent Welcox isolated and characterised the first type II restriction enzyme, HindII, found in the bacteria Haemophilus influenzae. This type of restriction enzyme differs in that it cleaves DNA at the restriction site, and in doing so serves to be much more useful in the laboratory. Cohesive end cutter type II restriction enzymes cut the two DNA strands (most DNA molecules are double-stranded helices) at different points within the restriction site. The result is a staggered cut that generates a short single-stranded sequence or overhang, known as the sticky or cohesive end. These overhangs become very useful in genetic engineering, since the unpaired nucleotides that make up the sticky end can pair with other overhangs made using the same restriction enzyme. If DNA from two different sources are cut with the same enzyme, it is highly probable that the two DNA fragments will splice together because of the complementary overhang. The product is a recombinant DNA molecule, composed of DNA from two different origins, created by DNA technology.
Since the first discovery of restriction in the 1950s, the use of recombinant DNA technology has become commonplace, as new products from genetically altered plants, animals and microbes have become available. In 1997, Dolly the sheep dominated the headlines as the world’s first animal to be cloned from an adult cell. Whilst her early death may have left some scientist ‘wooly’ on the cloning issue (thanks to Jim Giles and Jonathan Knight for this clever pun), the technology has since gone on to bring advances to various areas of life, from treatments for cancer to transgenic insect-resistant crops. As far as is known however, we are yet to see the technology confer super-human strength and power. Thankfully we are not currently at risk of encountering deadly villains and their counterpart heroes on a daily basis, sporting their ridiculous costumes and egos. Instead, we are surrounded by the unseen heroes, the special enzyme molecules that battle to fight invading viral villains, and the scientific geniuses that brought them to light. Mr Muscle may argue that bacteria are best destroyed, but we should also thank these microorganisms for opening a whole new realm of our world, whatever that world may hold.
Emily Brown, PhD
The nurse paged me about a patient with high blood pressure; I asked my second-year which medication I should dispense. A patient complained of shortness of breath; I asked my second-year what to do. My prescriptions wouldn’t print; I asked my second-year what was wrong with the printer. It felt ironic to me how one day I was nothing but an annoying medical student, and the next day everyone was calling me “doctor,” and yet I didn’t feel any different.
This time, however, I do feel different. In a few days, on that notorious first day of the month of July, a new batch of Interns will come in, and I will be that second-year that they come to for answers.
Unlike in Canada or other countries where first-year residents are merely called “R1”, the hierarchy in the American medical field is further underscored by the terms “Intern” and “Senior.”
“Internship” is often said to be the toughest year of residency, during which the young doctor with her newly donned white coat has to prove to the world that she is tough enough to be a doctor. And of course, being at the very bottom of the feeding chain (because medical students aren’t even on the radar), interns, or first-years, are given all the “scut work.”
Scut work is basically tedious and what one might consider menial tasks that no one likes to do but which have to be done. Common scut work includes calling a patient’s primary care physician to obtain their background information, faxing papers, waiting for papers to be faxed back, drawing blood, bringing the blood sample to the lab, filling out paperwork, running around the hospital looking for a cane because the patient cannot be discharged without one… the list is endless, and so are the hours.
I remember being awakened in the middle of the night by interminable pages. Feeling frustrated over a dispute with a nurse; angry because of a rude and aggressive patient; incompetent about not being able to figure out what was wrong with a patient and discouraged about just being a cog in the wheel.
And then one day, recently, I heard a code. A patient had crashed. I ran to the scene where my co-intern Dr. Aaron Pickrell was already giving chest compressions to a patient who had collapsed on the floor, and giving nurses orders. In that split second, I felt pride for my colleague and friend. I rushed to his side and took over the chest compressions. We asked the nurses to get the patient’s finger stick to check her blood sugar level, checked the patient’s blood oxygen level with a pulse oximeter, ordered dextrose, glucagon, epinephrine, ordered the respiratory therapist to administer oxygen… Of course it was not perfect, and it was messy, but there we were, “little interns”, acting like doctors.
More experienced residents and attendings arrived shortly, and guided us in our efforts to save this woman’s life.
Yes, this time, I do feel different. I feel like a doctor.