By Sonia Vohra While middle school children across the world were singing along to the catchy narwhal song that went viral in 2015, marine mammal biologists were journeying to Nunavut, Canada to study narwhals alongside the Inuit people [12]. Despite the captivating YouTube video, many individuals today still do not believe in the existence of narwhals, which are commonly referred to as the “unicorn of the sea.” In fact, many people equate this legitimate sea creature with the mythical magical horse. In reality, the only mystery surrounding the narwhal is not it’s existence, but the purpose of its identifying tusk. This article seeks to illuminate the unparalleled structure of the narwhal tusk and to explore the current state of nature surrounding its function. Since the early Middle Ages, narwhal tusks were prized as valuable commodities because their tusks were associated with the myth of the unicorn. Viking traders could often sell the tusks for their weight in gold. In the sixteenth century, Queen Elizabeth I paid a sum of money equal to the price of the castle for an ivory narwhal tusk [7]. However, despite its association with unicorns, a narwhal tusk is not a horn, but a tooth. Narwhals are genetically capable of producing sixteen teeth, but genetic factors immediately silence the expression of fourteen of them, leaving narwhals with two teeth. In male narwhals, the left tooth becomes an approximately eight-foot long tusk, while in females, both teeth remain embedded in the upper jaw. Occasionally, a female narwhal will grow a single tusk or a male narwhal will grow two tusks, although the latter is extremely rare [9]. A narwhal tusk is incredibly unique in many ways. It is the only helical tusk in nature, characterized by a left-handed counterclockwise spiral. It is also the only tusk placed asymmetrically on an animal: it always appears on the left side and defies the mirror image mammalian requirement of teeth. Finally, it is the only flexible tusk in nature, as it is capable of bending up to twelve degrees in any direction without breaking. despite all of the physical information scientists have collected about narwhal tusks, they are still unsure of the tusk’s function [6]. A common misconception about the tusk is that narwhals use it to spear fish. However, this theory has been disproven a number of times as the tusks do not seem appropriately suited to this task. The flexible nature of the tusk would prevent or at least weaken a “spearing” function, and, some scientists argue since both male and female narwhals consume the same diet, it would not make sense if the tusk played a prominent role in feeding. Recent drone video footage appears to show narwhals stunning their prey, but this function has not yet been experimentally proven [2]. Other proposed functions for the tusk include being used to break through ice and to dig for food in the ocean floor [1]. One of the most common theories circulating throughout the scientific community is that the narwhal tusk plays an important role in sexual selection. On the one hand, some researchers believe that male narwhals engage in combat to demonstrate dominance. A 1985 study showed that scarring on males’ foreheads correlated with broken tusks, suggesting combat [4]. Perhaps the combat occurs in the winter, when scientists are unable to properly study narwhals in the Arctic. On the other hand, a 2014 study found a statistical link between the length of a male narwhal’s tusk and the size of its testes, suggesting that females might choose a mate based on the size of its tusk [5]. Both theories are supported by the fact that generally, only males narwhals have a tusk. A recent theory about the narwhal tusk comes from Dr. Martin Nweeia, whose fascination with the narwhal tusk stems from his experience as a dentist. In 2014, Dr. Nweeia proposed that the narwhal tusk serves a sensory function. Teeth often have sensory capabilities in many mammals, so Dr. Nweeia believes that the narwhal tusk might also play a sensory role. For example, the tusk might be able to detect changes in temperature or salinity in the Arctic waters that the narwhal resides in. Dr. Nweeia presents a variety of structural evidence, including the presence of dentinal tubules that communicate with the surrounding environment through open channels. He has also found that there are significant changes in heart rate when the tusk is exposed to differing levels of salinity [8]. His work has shown that a variety of sensory functions have allowed for the tusk’s evolutionary development and persistence. Many of Dr. Nweeia’s collections and much of his research are currently on display at the Smithsonian Museum of Natural History in its new Narwhal Exhibit, which is open until August 2019 (10th St. & Constitution Ave. NW, Washington, DC) [11]. Ultimately, the narwhal is not a mythical figure but simply a toothed whale shrouded in mystery. Thankfully, the increased prevalence of genetic testing will likely lead researchers to discover why evolution has allowed the unique narwhal tusks to persist. References
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By Alexandra Bunjes The global contraceptives industry earns approximately $20 billion per year and is expected to increase to $33 billion by 2023 [7]. The majority of this money goes towards female-targeted methods of pregnancy prevention such as oral contraceptives, intrauterine devices (IUDs), condoms, implants, and injectables. Ninety-eight percent of women in the United States have used contraception at some point in their lives and 62% of women in the US of reproductive age are currently using birth control methods [4]. Due in part to the efficacy of female contraception and its widespread nature, women carry much of the responsibility for pregnancy prevention and there isn’t much research incentive to explore methods that are targeted to men.
Currently there are no prescribed hormonal methods of birth control for men, but why? It may seem to be a normative standard that women bear the brunt of the responsibility for pregnancy prevention, but why is this? Why does female-geared contraception dominate the market? Why isn’t male birth control as prevalent as female birth control? The answers to these questions ultimately boil down to two problems: the biological difficulty of creating male birth control and the lack of incentive of pharmaceutical companies to sell it. Contraception was initially created for women because they were typically the ones who bore the responsibility for childrearing. However, research has since indicated another reason why today more contraception is still targeted toward women: female reproductive biology leaves more room for interference. Since women have a regulated monthly cycle, small doses of hormones each day – through oral contraception, arm implants, or injections – can be very effective in altering the process to decrease chances of pregnancy. Additionally, IUDs can either release hormones or be made of materials that divert sperm. IUDs are placed in in the uterus, so even if pregnancies do implant, it is difficult for them to progress. Male biology is much different: each month, a female only produces one mature egg, but men produce millions of sperm. Since women cyclically release one product, it is easier to influence this process than continual male spermatogenesis [8]. Hormonal pills would also take weeks to affect sperm count [8] and previous clinical studies have shown that in order to have contraception in men of comparable efficacy to that in women, large amounts of hormone must be administered, which often causes long-term adverse effects [2]. Many male hormonal studies up until this point have caused acne and mood disorders, which has discouraged participants from wanting to continue. There is also no simple way to directly interfere with the male reproductive organs in a manner similar to that with an IUD. Nonetheless, many researchers have remained committed to exploring the potential for male contraceptives with the hope of shifting some of the responsibility. In 2016, an experiment was done in which healthy men between the ages of 18 and 45 were injected with hormonal birth control every eight weeks [2]. Couples participating in this study were in monogamous and had an average coital frequency of twice per week [2]. The hormone injection involved a mix of the sex hormones progestogen and testosterone. This caused suppression of sperm production and a decreased number of pregnancies. By 24 weeks into the experiment – after 3 rounds of injections – participants showed a significant decrease in sperm concentration [2]. Additionally, there was a 95% rate of recovery after 54 weeks, which means that sperm production returned to normal. Of the 266 male participants in this experiment, four of their partners became pregnant, yielding an overall failure rate of 1.57% [2]. Side effects included acne, mood changes, increased libido, and injection site pain – circumstances not dissimilar to what women experience each month on their periods or while taking oral birth control [2]. This experiment was terminated early due to the frequency of mood disorders, but it nonetheless demonstrated the potential for hormonal male birth control to become a viable method of contraception. Arguably, the most promising method is the gel injections developed by 76-year-old biomedical engineer Sujoy Guha. These injections are quick, reversible, and have demonstrated 98% effectiveness in preventing pregnancy with no major side effects [1]. The procedure is simple: the sperm-carrying tubes in the scrotum are injected with a polymer gel that damages the heads and tails of the sperm, effectively disabling them and thus preventing them from being able to swim to the egg and fertilize it. This gel was injected into 540 men in India 13 years ago, and none have had pregnancies since their injection. This contraceptive effect lasts until reversed by a second injection, which breaks down the gel and allows normal reproduction to continue. The U.S. nonprofit Parsemus Foundation is working to establish a market for the gel outside of India with the goal of selling the injections for as low as $10 in poorer countries and for a few hundred in richer ones [1]. The foundation is currently raising funds to conduct human trials [1]. Since this gel is cheap, unlike IUDs, and does not require constant administration, such as birth control, it could be revolutionary for the 225 million women in developing countries that do not have access to contraception [1]. Worldwide projections estimate that putting this gel on the market would result in a $10 billion drop in the female contraception market and $3.2 billion overtaking of annual condom sales. The current issue that Guha faces with his injections is finding a company to sell them – Big Pharma is not interested in male contraception [1]. This is an example of the social problems that underlie male contraceptive development: the success of female contraception and the frustrating prevalence of reproductive inequality has caused there to be little incentive for male birth control to be developed and marketed. The prevalence of female birth control has normalized female responsibility, and despite the research being done surrounding male contraception, most men are wary of taking control of pregnancy prevention. Since the market for female contraception shows no signs of diminishing and most of the leaders in pharmaceutical companies are men, male birth control has been given little attention. Nonetheless, the results of these the gel and hormone therapy studies indicate that progress is being made toward a more equal balance of reproductive responsibility. Since there are many steps to be taken between creation and implementation, the success of this research does not mean that other studies have stopped; researchers are continuing to find new ways to address the topic of male reproduction. Some studies are taking a closer look at sperm production and trying to stop it at its source. When sperm are released during ejaculation, they use a corkscrew-like motion to drill into the egg and inject genetic material [6]. This is made possible by an ion channel called Catsper, which is only found in sperm [6]. One potential method of future birth control could be looking for ways to block up this channel and thereby prevent sperm from drilling into eggs. Another way of exploring this issue is by learning about the mechanisms underlying male infertility and then finding ways to apply this knowledge for contraceptive use. For example, about 10% of infertile men have disruption in the fertility-causing genes of their Y chromosomes [5]. Since it is known that deletion in any of three specific regions leads to infertility, exploring the roles of these genes could lead us to back-solving for contraception; if we know exactly what the genes do – and thus why their absence is leading to infertility – we could potentially develop targeted drugs that inhibit the sperm, thus blocking pregnancy [5]. This ties into another concept being explored in male birth control: the notion of turning the “switch” of contraception on and off. The ideal circumstance for birth control would be to find a reliable, reversible way to turn off sperm production or prevent sperm activity. One proposed method for doing this is to try to block the gene that prevents sperm from being damaged during production. In a study with mice, it was shown that the lack of this protective gene can lead to infertility because sperm production comes to a halt [5]. If scientists could find ways to control this, it is another potential avenue for pregnancy prevention [5]. There are clearly many exciting areas of research being explored when it comes to male contraception, but there aren’t many pharmaceutical companies willing to invest in distribution. The hope is that in the coming years, demand will increase, and the responsibility for contraception will shift from women to become more of a shared undertaking. This would be a big step toward not only reducing the instances of unplanned pregnancy, but also reaching a state of increased reproductive equality. References 1. Altstedter, A. (2017, March). A New Kind of Male Birth Control Is Coming: Novel treatment may be submitted for Indian approval this year. Bloomberg. Retrieved from https://www.bloomberg.com/ 2. Behre, H. M., Zitzmann, M., Anderson, R. A., Handelsman, D. J., Lestari, S. W., McLachlan, R. I., ... & Festin, M. P. R. (2016). Efficacy and safety of an injectable combination hormonal contraceptive for men. The Journal of Clinical Endocrinology & Metabolism, 101(12), 4779-4788. 3. Jegalian, Karin & Lahn, Bruce. (2001). Why the Y is so Weird. Scientific American - SCI AMER. 284. 56-61. 10.1038/scientificamerican0201-56. 4. Jones, J., Mosher, W., & Daniels, K. (2013). Current contraceptive use in the united states, 2006-2010, and changes in patterns of use since 1995. In Sexual Statistics: Select Reports from the National Center for Health Statistics. Nova Science Publishers, Inc.. 5. Michigan State University. (2017, October 10). Genetic advance for male birth control.ScienceDaily. Retrieved October 16, 2017 from www.sciencedaily.com/releases/2017/10/171010124108.htm 6. Molteni, Megan (2017, May). Scientists Found Sperm’s Power Switch – And a Way to Turn It Off. Wired Magazine. Retrieved from https://www.wired.com/ 7. Nasdaq GlobeNewswire (2016, September 27). Contraceptives Market size to exceed $33 Billion by 2023: Global Market Insights Inc. Retrieved from https://globenewswire.com/ 8. Smith, B. C. (2017, August). Here’s Where We’re at With the ‘Male Pill’ – ‘We’ve been 5 years from male contraception for 50 years.’ Mel Magazine. Retrieved from https://melmagazine.com By Angela Lu Although the Human Genome Project is a great breakthrough to knowing about human genetics and to better addressing genetic complications, it also fostered the increase of bioethics debates regarding research and procedures in the field of genomics. This field has been growing with unprecedented speed as more genomes are being understood, sequenced, and even manipulated. Among all the bioethics issues raised regarding development of genomics, family planning has always attracted public attention and political involvement about how appropriate it is to incorporate genetic screening, treatment, and alteration as part of the process. With increasing knowledge about the causes of various genetic diseases, we continue to discover possible mechanisms to prevent them particularly through genetic engineering. Just like any other natural science advancements that interfere with social decisions, the role of genomics in family planning is worthy of discussion with the aim to design and implement better policies which genetic practices can be as beneficial as possible. One popular issue about genomics in family planning is the maternal inheritance of mitochondria, the powerhouse for cells that produces the energy molecule ATP. Offspring get their mitochondrial circular DNA (mtDNA) only from their mothers, unlike autosomal chromosomes which are inherited in pairs with one chromosome from the mother and one from the father. This means all affected females with diseases related to mtDNA mutations will almost most certainly have affected offspring. Maternal inheritance pattern of mtDNA is often used in forensics to find related individuals and there continues to be an interest in what else mtDNA can help with. Although only accounting for a small number of genetic diseases, mitochondrial mutations tend to result in rather large phenotypic variability due to its unique inheritance characteristics. Some of the reasons include mutation rate in mtDNA being 10 times higher than nuclear DNA because of lack of repair mechanisms, more exposure to free oxygen radicals, and the presence of not one but a population of mitochondria in each cell; only some carry mutations, resulting in various degrees of disease expression depending on the proportion of mutant mtDNA [3]. Mutations and diseases related to mtDNA are important because ATP (produced in the mitochondria) fuels normal functions of most tissues. Cells in tissues often start to degrade and even die with insufficient ATP. Therefore, consideration of mtDNA mutations is important in the attempt to prevent adverse genetic consequences in offspring, potentially through genetic engineering. The possibility of three-parent baby therefore stems from this concern and the maternal inheritance pattern of mtDNA. Three-parent is termed to describe embryos that have the DNA of three individuals; the creation of these embryos is accomplished through replacing the mutated maternal mtDNA with a donor mtDNA with genetic engineering technology. The offspring will have DNA from the father, mother, and the donor of mtDNA. With the donor’s mtDNA, the offspring ideally would not have the mtDNA mutation inherited from the mother and would therefore be free from any clinical symptoms associated with it. The critical understanding to this seemingly easy-fix process is that the whole maternal mtDNA is replaced. This includes the mutated region, no matter how small it might be, and all the other genetic material that functions normally. Here arises the discussion of whether or not the prevention of a disease that has varying levels of symptom severity is worth the artificial exchange of the entire mtDNA, which will give the offspring a different set of mitochondrial functionalities from an individual that is not related to him or her at all. This essentially boils down to a risk evaluation upon whether manipulating genetic information at the germline level is worthwhile to prevent children both with devastating and life-threatening diseases [4]. In this evaluation, there are both biological and social concerns. The new donor mtDNA runs the risk of being incompatible with the maternal nuclear DNA, which could be problematic due to the “constant conversation between the genes in the mitochondria and the genes in the nucleus... that’s especially critical during embryonic development” [5]. The technology itself for this procedure is also another concern, which at its current state still cannot guarantee that there would be no carry-over of the original mtDNA mutation. The inherent biological risk of having maternal genetic materials from two women in an offspring has not studied enough. The basis of this risk assessment is then explored again: if the purpose of this treatment is decreasing the risk of disease caused by these mutations, how much of the argument is changed when the technology itself is not developed enough yet to guarantee a decrease in risk? And even with an optimistic belief that the biomedical technology will develop and become confident in preventing mtDNA mutation diseases without severe side effects, the risk also includes social implications, as well as the biological and technical aspects. The Novel Tech Ethics article “The Ethics of Creating Children with Three Genetic Parents” breaks down the ethical concerns of this new procedure into four main categories. The first is related to the harm-benefit ratio associated with the donor who has to go through physical and potentially mental pain in order to donate the mtDNA through her egg. The argument here is that the in vitro fertilization (IVF) patient (the birth mother) attains most of the benefit at the end and although the donor gets certain emotional benefit of performing a good deed or financial reward if she was paid, the harm-benefit ratio is still unfavorable to the donor. This is a potentially serious issue, considering that impoverished women being could be excessively targeted as potential egg donors because of their financial need. Sometimes the real willingness of these women to contribute time and effort to donate eggs is unclear when the monetary benefit is presented as their largest motivation. In those cases, some people worry about the impact of emotional consequences post-donation. The ethical concerns regarding egg donation is a complex issue on its own, but it certainly has to be incorporated into the three-parent baby discussion. The second ethical conundrum is related to the unknown consequences of having an offspring with a mixture of genetic material and the risk assessment against other alternative options that are less risky and more well-developed such as adoptions and preimplantation genetic diagnosis. The core of the argument is the distinction between a preferable wish and a necessary need. This ethical concern is important when considering whether or not to make this procedure more widely available, presumably starting by lifting the current ban for the procedure in the U.S. Cost-benefit analysis and other important utility and resource management considerations are needed for a better understanding of the procedure’s necessity and net benefit before considering it a plausible medical practice and viable option for family planning. This argument also alludes to the concern for future generations if this genetic alteration becomes more available as procedures such as mtDNA replacement becomes widely accepted [1]. The further mingling of genetic materials between individuals is inevitable and with more artificial intervention, there are legitimate concerns about the unpredictable consequences of such genetic interplay. The third ethical consideration involves the use of mtDNA information to trace ancestry for social studies and, more importantly, identification. As mentioned, the unique maternal inheritance pattern of mtDNA is used in forensics and other identification techniques; therefore “mitochondrial replacement technology represents a potential threat to genealogical research using mtDNA analysis, as it would obscure the lines of individual descent, thereby providing a false or confusing picture” [2]. The social application should be treated with equal importance as the science itself because it is the link between science, society, and policy. This again highlights the multidisciplinary impacts generated by any major advancement or change. The fourth ethical question is an interesting discussion about non-therapeutic intents of human enhancement as a purpose for this procedure. One example the article mentions is a scenario in which: “a lesbian couple where both partners wanted a genetic link to the children they intend to parent” [6]. This raises the bigger and more commonly discussed concern of whether or not our growing ability to control natural sciences, in this case genetics, provides us the right to interfere with the natural gene pool. The ethical concerns of mtDNA gene replacement procedure or any other genetic engineering methods go far beyond the four identified categories. Obviously the discussion so far is not to negate the main therapeutic purpose of preventing mitochondrial genetic diseases; however, a more comprehensive and extensive understanding about the social implications is needed before before any genetic engineering methods like this one becomes a real practice that affects real people. The questions surrounding mtDNA gene replacement highlight the multitude of effects generated by genetic research, be they immediate or lasting, domestic or global, and biological or social. References: [6] Baylis, F. (2013). The ethics of creating children with three genetic parents. Reproductive biomedicine online, 26(6), 531-534. [2] Baylis, F., Robert, J.S. (2004). The inevitability of genetic enhancement technologies. Bioethics 18, 1–26. [4]Baylis, F., Robert, J.S. (2006). Radical rupture: exploring biological sequelea of volitional inheritable genetic modification. In: Rasko, J.E.J., O’Sullivan, G.M., Ankeny, R.A. (Eds.), The Ethics of Inheritable Genetic Modification. Cambridge University Press, Cambridge, 131–148. [5]Bredenoord, A. L., & Braude, P. (2010). Ethics of mitochondrial gene replacement: from bench to bedside. BMJ: British Medical Journal (Online), 341. [3]Jorde L, Carey J, and Bamshad M. (2016). Medical Genetics (5th ed.). Philadelphia, PA: Elsevier. Kazdin, C. (2016, November 08). When Three Become One: The Ethical Dilemma of the 'Three-Parent Baby'. MEL Magazine. Retrieved from: https://melmagazine.com/when-three-become-one-the-ethical-dilemma-of-the-three-parent-baby-a04366868c1b [1] Roccella E, Buttiglione R, Picchi G, et al. (2015, February 20th). Three-person DNA. The Times letter. Retrieved from: http://www.thetimes.co.uk/tto/opinion/letters/article4360729.ece Figure 1 Jorde L, Carey J, and Bamshad M. (2016). Medical Genetics (5th ed.). Philadelphia, PA: Elsevier, 92 Figure 2 CBS News (2016, September 28). Genetically modified baby born with DNA from 2 women. Retrieved from: http://www.cbc.ca/news/health/3-parent-baby-birth-1.3781026 Figure 3 Kazdin, C. (2016, November 08). When Three Become One: The Ethical Dilemma of the 'Three-Parent Baby'. Retrieved from: https://melmagazine.com/when-three-become-one-the-ethical-dilemma-of-the-three-parent-baby-a04366868c1b |
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