Your Environment Is Cleaner. Your Immune System Has Never Been So Unprepared. - The New York Times9/19/2019 Good evening everyone, At the end of this week we find ourselves in the midst of a discussion of immune function, first with our lecture yesterday on the immune system (Chapter 7), to be followed by our next lecture on infectious disease (Chapter 8), scheduled for next Monday. Recall that for tomorrow's class (Friday 20 Sept), we will not meet in person. Instead, I'd like you to read/digest a news article on a current and very relevant immune topic, that of environmental exposure to antigens. For much of the history of our species, human life and society was based around agriculture, including exposure to domesticated animals. In the last hundred years, of course, that has changed for many, as populations became more urban. During this same period, the use of cleansing and sanitizing products in the household has increased dramatically, culminating recently in the explosion of "anti-bacterial" products, such as soaps, wipes, and tissues. Most immunologists believe that we have taken cleanliness a bit too far. According to the "hygiene hypothesis", natural exposure to antigens keeps the immune system primed for action, and enables it to make robust responses to actual disease agents. In our ultra-clean worlds, however, many (especially the young children of cleaning-obsessed parents) are coming into contact with fewer and fewer natural antigens, and increasingly their immune systems are ill-equipped to respond to them when they do, leading to a rash (no pun intended) of allergies, sensitivities, or, at worst, autoimmune disorders. This article explores the "hygiene hypothesis" and some of its implications. As you go through it, I'd like you to consider a few key questions: - what happens to our immune system when we are exposed to naturally-occurring antigens? - why should exposure to non disease-causing antigens enable us to better respond to more serious antigens? - do you personally use anti-bacterial products in your household? - does this article make you want to reconsider their use, in any way? https://www.nytimes.com/2019/03/12/health/immune-system-allergies.html?searchResultPosition=19 Our immune system is wonderfully complicated and powerful, but some think that our social behaviors have evolved faster than is good for it. Perhaps a nice walk outdoors, a swim in a lake, or a picnic in the grass is just what we need... #ReturnToNature Have a great weekend - see you on Monday. Dr. Nealen
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Good morning everyone, We soon will be discussing the brain and nervous system, and our discussions will include the concept of 'body maps' in the brain. These represent areas of the brain that contain neurons that are spatially arranged to correspond to particular areas of our bodies (like our fingers and faces). We all have them, and they make some of the computations required by our brain a bit easier. Specialized training (such as the playing of a musical instrument) can modify these maps, making them (in some case) larger and more sensitive. In the science news this week is a report about these brain maps, but in an unusual way. This news describes brain maps that represent the fine motor skills one develops as a painter, but with a catch: these are painters who use their feet, rather than their hands. In these subjects, the 'brain maps' for their feet have been come elaborated, much like what happens to the brain maps for fingers when highly trained to perform a skill like a painting. This story reminds us of a number of important features about the brain: even in adults, much of the brain is 'plastic', or modifiable - that is the secret to our ability to learn new things. This story also demonstrates the old saying the 'nature abhors a vacuum' - if part of the brain is not being used a its normal task, in some cases that task can be shifted elsewhere, and parts of the the brain 'reassigned' (to some degree) to new responsibilities. This flexibility is also a hallmark of our brains, and is an important one, for it contributes to recovery from brain injuries, like stroke. When areas of brain tissue are damaged, in some cases nearby areas can be trained to take over those functions that are no longer being served. So, even if you find that painting is not something you are good at (as I have), don't despair! You have plenty of brain tissue ready and waiting for your hidden talents to emerge... https://www.sciencenews.org/article/artists-paint-feet-toe-maps-brain Have a great weekend - Dr. Nealen Good morning everyone, In my scans of the science news, I often come across articles that overlap with our course topics. I'll share some of these with you, in the hopes that you find them interesting, and with a goal of broadening our conversations. Today's news comes from a report about animal-based espionage, via training programs conducted by the CIA during the height of the Cold War. Animals are often highly adept at trained behaviors, and instinctual behaviors (like homing) can be co-opted for specialized tasks. Still, this report suggests that there was little direct benefit from these programs - or, perhaps they are not telling us everything, as much remains classified. So, the next time you see a pigeon, cat, or dolphin(!) nearby, remember: they may be watching you as well... https://www.bbc.com/news/world-us-canada-49692534 Have a great weekend - Dr. Nealen Good morning all, As a follow-up to the news article I last sent, here are a couple of updates on this developing story: Severe illness and unexplained deaths associated with vaping have continued to occur, and, while no definitive cause has been identified, the majority of cases seem to be linked to the inhalation of vaping substances that are coating or irritating the lining of the lungs, preventing proper gas exchange. Vaping materials often have additives, such as flavorings or oils, that are the prime target. A number of persons suffering respiratory distress after vaping seem to have oils lining their lung surface. As one researcher put it, 'The lungs are designed to encounter gases only. Inhalation of other substances is inherently risky'. https://www.nytimes.com/2019/09/07/health/vaping-lung-illness.html https://www.washingtonpost.com/health/2019/09/07/what-we-know-about-mysterious-vaping-linked-illnesses-deaths/?tid=pm_national_pop I understand that vaping is quite popular, and I worry (a lot) about how dangerous it is. It is trendy and new, but not well regulated, and too recent to have been well studied. I suspect there will be much more news on this topic, and likely soon many more regulations about what can or cannot be included in vaping materials. I hope that you do not vape - but if you choose to do so, please be informed, for your own safety. Sincerely, Dr. Nealen Good morning all, Just passing along here an interesting news article, linking behavior and conservation. Human have long associated with animals, and in doing so have shaped many of their behaviors. Here's an example of a detrimental effect: a semi-domestication that changes foraging behavior and seed dispersal in endangered New Zealand weka: https://www.nytimes.com/2019/08/29/science/weka-birds-seeds-new-zealand.html This kind of change illustrates the behavioral flexibility many species employ, particularly for adapting their own ecology to exploit the humans around them. In the long run, these sorts of associations can cause evolutionary change in brain and behavior (https://www.nationalgeographic.com/animals/2019/09/humans-shaped-dog-brains/), in ways that can dramatically alter the natural ecology of species. This is also an important reminder that interacting too much with endangered species can endanger them ever more if they imprint too strongly on humans - hence the need for 'panda suits' (https://www.youtube.com/watch?v=GaLP6S9ZHQ4 - how's that for a day job?). See you tomorrow for review of the material for our first exam. I'm not planning a formal lecture; instead, I will review any material on which you have questions. Sincerely, Dr. Nealen First Death in a Spate of Vaping Sicknesses Reported by Health Officials - The New York Times8/29/2019 Good evening all, As I mentioned in lecture on Wednesday, we are still on track schedule-wise, and do not have a chapter planned for Friday of this week. Thus, let's not meet in person for class tomorrow. Instead, I'm passing along (below) a link to a recent news article that I would like you to read, about some of the dangers associated with vaping, a topic that is certainly of the latest health issues of concern. As a former smoker, I know first-hand the 'rush' associated with nicotine; as a physiologist, I know too well the dangers associated with inhaled substances. To me, vaping seems to present dangerous levels of both. I will occasionally pass along science and health news articles of this type during the semester. My purpose in doing so is to help you to become more aware of topics at the interface of biology and society, and also to help you assess how you obtain your science and health news. Those of us working in science obtain our scientific news, quite often, directly from the original sources: the people conducting the studies and reporting the results. They publish their findings in science journals, or present them at conferences. Most people do not obtain science news directly, but hear news via secondary sources, such as news releases from scientific organizations, or news stories from the major news outlets. These secondary reports often are then carried by tertiary outlets (smaller/other reporting sources, including news aggregators and media feeds). Along the way from source to audience, science news is normally distilled (a lot) - much of the detail is excluded or simplified, and the reports often are boiled-down to singular take-home messages, which may (or may not) be good representations of the original work. When you browse the links that I will forward, or when you access science and health news on your own, I'd encourage you to delve a little bit deeper into them, to read more than just the summaries, and to follow links back to original sources when possible. I'd also encourage you to think a little about the translation of news from source to consumer, and the reputability of the news outlets that you use. You will not be formally tested on any of the material in the news stories that I will send you, but I do hope that the material in them makes its way into our conversations. This first link is from the New York Times, which provides one of the best (e.g., best funded and most reliable) secondary sources of science and health news. They do limit access to only a handful of free articles each month, so I will use them sparingly. https://www.nytimes.com/2019/08/23/health/vaping-death-cdc.html Here's wishing you all a safe and enjoyable Labor Day weekend - see you next week. Sincerely, Dr. Nealen 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 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 Good morning all, As we head into warmer weather, thoughts inevitably turn to outdoor activities. With them comes, of course, exposure to sunlight and its radiation. Natural light offers us warmth, pleasurable sensations, and stimulates vitamin D production. As we have been discussing in lab, sunlight also contains dangerous levels of UV radiation. One of the safety concepts we hear reported related to outdoor activities is the "UV index". This is a scale meant to represent the relative degree of exposure risk posed by harmful UV radiation. The World Health Organization, in partnership with other health agencies, promotes the use of this index as a way to keep the public quickly and easily informed of their exposure risk. The index is fairly easy to interpret: low index numbers, relatively low risk; higher numbers, more risk. https://www.who.int/uv/intersunprogramme/activities/uv_index/en/ Behind the index is a fair amount of science, in which measured amounts of UV exposure were assessed for their ability to cause cell and tissue damage. Many of the initial studies were done without direct knowledge of what was changing in cells, or what was driving tissue damage. Now, health scientists are able to marry environmental exposure studies to genetic studies, leading to genetic profiles for many of our genes. For example, we now know that the gene responsible for directing production of the melanocortin 1 receptor (gene MC1R) is often mutated by UV radiation; its mutation is one of the leading agents of skin cancer. The normal role of the MC1R gene product is to regulate the production of melanin (eumelanin) in our skin cells, the same melanin which gives us a 'tan' after UV exposure. We all have different levels of melanin production; those of us with lighter skin produce relatively less of it and are at higher risk of UV damage. https://ghr.nlm.nih.gov/gene/MC1R#conditions Our lab exercise of the past two weeks demonstrated how even short durations of UV exposure can mutate DNA, and also showed how critical DNA monitoring/repair is to continued health. The plate coverings that we used all provided some degree of protection from radiation. While it may be impractical to cover ourselves with tin foil when we venture outside, sunscreen or even thin cloth provided very useful protection. Remember those plates which were empty of yeast the next time you think about spending long hours in the sun - be sure to use sunscreen! Have a great weekend - Dr. Nealen Good morning all, As you know, I try to send you an article from the science news each week that is relevant to a recent topic we have considered in our class. Some weeks, that requires a little bit of digging, a little reading beyond my usual outlets for science news. This week, however, there is no need to look far, or wide. Our most recent lecture was on immunity, and the science news has been FULL of stories about the immune system, nearly the entire semester. This week, there are two major news stories related to immune system function. The first of these is just breaking, and will surely be followed by more news to come: the first widespread use of a vaccine against malaria in Africa. We do not hear much about malaria in this country (even though several thousand cases occur in the U.S. every year), but it is a tropical scourge across much of the globe. It is caused by the malarial parasite Plasmodium falciparum, carried by mosquitoes and transferred between human hosts by their bites. It is very infectious - estimates suggest that more than 200,000,000 (that's 200 million) cases occur each year. It's also very deadly, causing >400,000 deaths per year. Children are especially vulnerable. I heard a news report this week that estimated that every 2 minutes, an African child dies of malaria. As a disease, malaria is very problematic. Its mosquito hosts are very numerous, widespread, difficult to control, and difficult to avoid. The parasite passes directly into the human host circulatory system during a mosquito blood meal, where it takes up residence inside of red blood cells. Remember that disease agents that get inside of our cells are hard to combat - they are at least partially hidden/protected from immune surveillance, and should they be detected and their host cell destroyed, it results in the net loss of functional host cells, potentially even releasing more parasites to infect other cells. Persons suffering from malaria have symptoms ranging from mild (tiredness, chills, aches) to severe (high fevers, blood clots, kidney damage), and aggressive treatment with anti-parasitic drugs (such as Chloroquine) is normally required. Anti-parasitic drugs can also be used prophylactically (e.g., to prevent infection before it happens), but their efficacy is not perfect and varies considerably against the different strains of the malarial parasite. For all of these reasons, an effective vaccine would be a great benefit. In the news this week is report of the first widespread use of a moderately-effective, inexpensive, anti-malaria vaccine. It was developed over the last 30 years, following promising laboratory studies (the development of a pharmaceutical, from lab bench to use in human populations, can be VERY long). It is suggested to be only ~30% effective in protecting against malaria. But, if 30% of the hundreds of thousands of deaths that occur each year can be prevented, it will be very worthwhile - imagine being able to create a vaccine that prevents 100,000 deaths each year! In addition, much will be learned from this first really large human trial of the vaccine, and the data that will be collected on its efficacy will likely lead to improvements in the vaccine itself. https://www.nature.com/articles/d41586-019-01342-z https://www.who.int/news-room/detail/23-04-2019-malaria-vaccine-pilot-launched-in-malawi https://www.cdc.gov/parasites/malaria/ The other big story related to immunity this week also relates to infectious disease and immunizations, this time for measles. Measles is a very highly infectious disease caused by the measles virus. It causes rashes, aches, and often dangerously-high fevers, and can be fatal to vulnerable subjects. In most developed parts of the world, measles has largely been eradicated, through successful development and use of the measles vaccine, commonly given as one part of the MMR (measles-mumps-rubella) vaccine. Very recently, however, there are severe outbreaks of measles in several locations in this country (including New York City). These recent outbreaks in the U.S. have been caused by a combination of two factors. The first is a reduced number of parents having their children vaccinated against measles, in large part due to false information about the potential harm caused by vaccines. Over the past decade, several widely reported (but now discredited) stories have circulated about the use of the preservative thimerosol in vaccines, which has led some to believe that the vaccines themselves are more dangerous than the diseases they are designed to prevent. In addition, the vaccine is so effective that measles is rarely reported, so many believe that it is no longer even necessary. Together, these cause lower rates of vaccination in some populations. The other causative agent is the introduction of the disease from elsewhere, in these cases from travelers who visited areas in the Middle East, picked-up the virus, and brought it back to their U.S. communities. The symptoms of measles may not appear for weeks after exposure, so persons who carry the virus but do not yet realize it can very easily pass it unknowingly to others. Vaccinations protect individuals if they encounter an agent of disease, because it primes their immune systems (remember those memory cells?) to make rapid and robust responses upon subsequent exposure to an antigen, such as that of the measles virus. Vaccinations also work at a population level, by reducing the likelihood of encountering a disease in the first place. This is the concept of "herd immunity" - if everyone in a population is vaccinated, the chances of encountering someone who could pass on the disease is very low. Measles is extremely infectious (via sneezing/coughing), such that ~95% vaccination rates are necessary for "herd immunity" against measles to be available. In select populations, immunization rates have fallen well below this level. This combination of factors (reduced immunization rates, highly infectious virus) leads to disease outbreaks. In addition to large outbreaks in New York and Washington state, several college campus in California began quarantining personnel, in an attempt to control measles outbreaks. https://www.sciencenews.org/article/us-measles-cases-record-high-disease-eliminated-2000 https://www.washingtonpost.com/national/health-science/over-1000-quarantined-in-measles-scare-at-la-universities/2019/04/26/79e29cdc-6881-11e9-a698-2a8f808c9cfb_story.html https://www.cdc.gov/measles/index.html https://www.cdc.gov/vaccinesafety/concerns/thimerosal/index.html Just as our immune systems are wonderfully adapted to protect us from agents of disease, so too are those same agents of disease evolved to evade our immune defenses. It's an evolutionary 'arms race', and, left on its own, would continue that way. Vaccinations give us a terrific advantage against some infectious diseases - but only if those vaccines are safe, available, and accepted. Are they perfect? Of course not - but the scientific community is very much in agreement that they are better than facing the risks without them. If you hear of anyone near you having measles, make sure that you and your family are protected. Have a great weekend - Dr. Nealen |
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