Good morning all, As our term comes to a close, I'll use my last news message to send along the latest news from on ongoing story in exercise physiology that raises interesting, and difficult, questions about sex differences in physiology and the regulation of sporting events. As we have described in class, both males and females have circulating testosterone, with males generally having much higher levels than females, on average. But, like all aspects of physiology, there is a wide range of what constitutes "normal" values, and there is overlap between the ranges of naturally-occurring male and female levels. The science of testosterone is fairly well-understood in terms of its anabolic effects. Testosterone enables muscle fiber development to a larger size, and facilitates its maintenance at that size. Testosterone supplements have been used (both knowingly and unknowingly) for decades to help athletes build muscle, and its use was the primary factor which led to the formation of the World Anti-Doping Agency (WADA) and the associated regulations restricting the use of chemicals to enhance the physiology and performance of athletes, especially those competing in sanctioned (e.g., large, high-profile, big money) events. Over the last few years in particular, however, we have gained an understanding that much of what makes us male or female is not always so perfectly discrete, so categorical. For some aspects of our genetics, anatomy, physiology, and performance, male and female traits are most often clearly binary (e.g., one way or the other). But other of our traits, especially some of our physiology, is not so dimorphic or discrete, and circulating testosterone levels fit into this category. Males and females generally compete only within same-sex sporting events because, for most events, males hold a competitive advantage. This is certainly true for track-and field race events, which place emphases on speed and endurance. This is not to say that female athletes are in any way unimpressive or not elite - they certainly are, and many would leave male competitors 'in the dust'. But, in general, males outperform females in foot races, and testosterone seems to provide at least some of that advantage, through enhanced muscle size and performance. Recent analyses have shown that the top female athletes in female track events have testosterone levels higher than the average woman. This is perhaps not a surprise, as these elite female athletes carry more muscle than the average woman as well. We must ask - which came first? Did higher testosterone promote more muscle, which led to racing success? Or does intense training lead to muscle development and an altered hormonal profile? Probably some of both. This situation has reached a peak in recent years over the case of Caster Semenya, an Olympic medalist who hails from South Africa. By all published accounts, Caster is genetically and physically female, but exhibits hyperandrogenism, a state of producing greater than the normal amount of androgens (male hormones). She is the most-accomplished middle-distance female athlete of the last decade, to the point at which protests against her have been raised, and regulations put in place to prevent her from racing unless she takes medications to reduce her androgen levels. She has appealed those decisions, to no avail. This issue raises many difficult considerations, from the personal (is this athlete being singled-out? Has her privacy been unfairly invaded?), to the social and political (is this another, familiar case of racism in sport?), to the athletic (is Caster really benefiting from her androgen levels?). As such, it seems unlikely to be settled easily, or soon. Nonetheless, it serves as a useful reminder that natural variability is, well, natural - it is an essential part of what allows us to exist as 7 billion different individuals. There are those among us who are short or tall, thick or thin, slow, - or very fast. Can we really regulate or legislate ourselves into categories, for competition, or for other reasons? Most of our physical and physiological traits vary broadly over a continuum, which means that drawing categorical boundaries may be somewhat artificial. In this case, we seem to have a single physical trait, with a well-understood connection to physical performance, that has become exposed in the very high-profile (and big-money) world of competitive sporting. https://www.nytimes.com/2019/05/01/health/caster-semenya-testosterone.html As we learn more about physiology, we are likely to revisit this issue many times again, and in new ways. How long will it be before we hear "Is it fair for me to compete against someone who has a better genetic profile than I do?". I suspect that, in the coming decades, we will be discussing less the physiological and hormonal aspects of physical and mental performance, but rather the genetic bases for them instead. I'm signing off for the term now. I hope that these weekly news messages have been useful to you. This is the first semester that I have used them to this extent, and it has been a learning experience for me. In particular,
In the end, though, I remain very optimistic. Science is "mankind's organized quest for knowledge" (Floyd Bloom), and we already know that "knowledge is power" (Francis Bacon). It is science that offers us the best hope to deeper understanding, new therapies and treatments, new cures, and new adventures. We will encounter many speed-bumps along the way, to be sure. I hope that our course has inspired you to be a part of this quest, and to make the best use of the knowledge that you gain while on it. Have a great weekend, and best of luck with all of your exams next week. Dr. Nealen
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Good morning all, As our term comes to a close, I'll use my last news message to send along the latest news from two ongoing news stories in genetics: The first bit of news is about a newly reported fossil find, from a branch of ancestral hominins known as the Denisovans. While scientists and anthropologists have been studying our Neanderthal relatives for decades, Denisovans are only recently discovered. They are thought to have represented a 3rd lineage of ancestral hominin, that co-existed with and likely inter-bred with both Neanderthals as well as early humans. Until very recently, all information on Denisovans came from fossils collected from a single location, the Denisova cave in modern Siberia (Russia). This new report describes a Denisova fossil from much farther south, in modern Tibet, which suggests that Denisovans were more broadly distributed, expanding the ranges of times and locations over which they may have interacted with modern humans. We know so little about Denisovans that this new information has been described as 'game changing'. If you recall the patterns of early human migration we considered, the first humans may well have had opportunity to interact with the last Denisovans. We all likely have some 'Neanderthal DNA' in us; we may come to realize that we all have a little 'Denisovan DNA', too. https://www.nytimes.com/2019/05/01/science/denisovans-tibet-jawbone-dna.html The second news story I will send here relates to the promise, and difficulty, of genome editing. We've discussed a number of times the concept of genes and alleles, and we've considered both gene therapy as well as some of the news related to human genome editing. Recently, a group of prominent scientists has argued that, given our current state of knowledge, the use of gene editing to produce 'designer babies' is more fiction than fact. Even apart from the difficulty of successfully edited the human genome, they suggest that the likelihood of finding individual genes with pronounced effects is very, very low. If you remember, genome-wide association studies (GWAS) can be used to identify genes associated with particular aspects of our physiology and health, but the strength of these associations normally is very low (e.g., often <1%). As such, we may not yet have good, individual targets for gene manipulation. https://www.npr.org/sections/health-shots/2019/05/02/719665841/why-making-a-designer-baby-would-be-easier-said-than-done That said, it is very likely that both our gene-editing as well as our genome evaluation skills are going to improve over time, so perhaps the current limitations on the likelihood of 'designer genome editing' are just that: current, but not permanent. It seems impossible that this topic, or interest in it, is going away any time soon. I'm signing off for the term now. I hope that these weekly news messages have been useful to you. This is the first semester that I have used them to this extent, and it has been a learning experience for me. In particular,
In the end, though, I remain very optimistic. Science is "mankind's organized quest for knowledge" (Floyd Bloom), and we already know that "knowledge is power" (Francis Bacon). It is science that offers us the best hope to deeper understanding, new therapies and treatments, new cures, and new adventures. We will encounter many speed-bumps along the way, to be sure. I hope that our course has inspired you to be a part of this quest, and to make the best use of the knowledge that you gain while on it. Have a great weekend, and best of luck with all of your exams next week. Dr. Nealen |
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