We've Sequenced the Human Genome. So Why Haven't We Cured More Diseases? | Discover Magazine2/24/2020 Good evening all,
In class, we have talked a number of times about how our phenotype (our physical appearance and characteristics) stems from our genotype (the particular set of alleles that we have in our genome). We've also considered how phenotype and genotype are related, by examination of a handful of traits which are influenced (all, or mostly) by individual genes (such as the trait for freckles, or attached earlobes). These examples allow us to evaluate the relationship between alleles (such as dominant and recessive forms), to consider patterns of gamete formation and potential crosses (via Punnett squares), and to assess familiar patterns of inheritance (via pedigrees). These relatively straightforward examples suggest that other aspects of our genetic health, such as disease risk for a variety of conditions, might also be similarly simple: easy to diagnose, and potentially easy to fix, if problematic. Alas, this is not the case for most traits of human disease concern. I'm forwarding here a link to an article which nicely describes why the genetic basis of our health is not so straightforward, or easy to manipulate. In reality, most of our important human diseases are only very weakly linked to individual genes, which themselves may play only a very small role in influencing our individual disease risk or expression. https://www.discovermagazine.com/health/weve-sequenced-the-human-genome-so-why-havent-we-cured-more-diseases So, of what value then is this massive Human Genome Project, this effort to sequence, and understand, every single one of our genes? Well, in short, we do not yet know its full value, as we are still learning how to mine this enormous database. It seems very likely to yield important insights into our genetic disease risks, but it has not led to the immediate creation of a broad spectrum of ready, easy-to-use, off-the-shelf treatments for our human diseases. That day of individualized, genetic approaches to health is coming, though - the first individually-based genetic treatments are now in use. They are as yet not broadly proven, and they remain enormously expensive. But, they represent proof-of-concept types of studies, which suggest that, as our knowledge and technology improve, the days of the 'genome card' are coming. Save some space in your wallets... Have a great evening - Dr. Nealen
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Good evening all,
Week after recent week, the global spread and impact of the new 'Wuhan' coronavirus continues to dominate our science and health news. Most health experts appear to have underestimated how easily this virus would spread, how long it it would persist, and how damaging it would be for global functions like travel and commerce. In terms of its lethality, this coronavirus is far less dangerous than the seasonal influenza (the "flu") that we experience each winter here in the U.S., which typically is associated with 3-10x as many deaths annually in this country alone than have been attributed to the Wuhan coronavirus worldwide. Still, this Wuhan coronavirus (more specifically, Covid-19 coronavirus) is a very good demonstration of the fact that infectious diseases do not have to be especially lethal to be very problematic. Given the scale of disruption this virus has caused, it is no surprise that a variety of treatment and preventative efforts are underway, including attempts to develop effective screens for infected persons, as well as tests of potential immunizations to prevent the contraction of the disease. One of the less well-publicized efforts is the attempt to identify "patient 0" - the first human to "catch" the virus. Of what value would it be to find this first human subject? In theory, this would allow scientists their best hope of finding the original source of the virus, the animal species from which the virus made its leap to human hosts. Identification of the animal host reservoir (be it bat, snake, pig, or other) could help limit future spread of the virus, and may also inform biological efforts to combat it. The more we know about the virus, the better our chances to counter it. But, there may be drawbacks to finding "patient 0", as outlined in this recent article: https://www.bbc.com/future/article/20200221-coronavirus-the-harmful-hunt-for-covid-19s-patient-zero Is there more harm to be done, or more gain, in finding this first human subject? Experts disagree, but not yet to the point at which the search for this first subject will cease. Finding the original subject in a disease outbreak is a standard epidemiological technique, and there are plenty of examples (including several described in this article) in which finding that first human host of a new disease agent was helpful. Still, the article also describes the risk of stigmatization, and error - what if someone is wrongly identified as the starting point for an epidemic? In this country, and in other developed nations, there are relatively standardized procedures for dealing with newly emerging diseases. When a new pathogen or new disease begins to spread that eclipses scientific expectations, however, some of the cracks in our defenses begin to show, and efforts to combat the new condition often become less uniform than would be ideal. We are seeing exactly this in recent weeks: there is open debate about how to count the number infected by this virus, continued uncertainty over its origins, and newly emerging evidence of how spectacularly unsuccessful quarantine efforts can be. We still have much to learn, it seems. The good news is that the virus really is of relatively minor risk to healthy individuals. We've no nearby cases here in Western PA, but should it appear, remember that the best defenses are surprisingly simple: avoid contact with infected individuals, and wash your hands well with soap after public forms of contact. Common sense is equal to best practice, in this case. Have a great evening - Dr. Nealen Good morning all,
I'm passing along here (at page bottom) a link to a recent news article about genetic sleuthing of the source for the 'Wuahn coronavirus', the virus that appears to have made its first appearance in humans and now is causing tens of thousands of infections, and perhaps >1,000 deaths, worldwide. As you now, this has been the top genetics and health news story for several weeks now. Viruses are a bit of an evolutionary quandary. They are tiny objects, composed of protein and nucleic acid. They are not considered to be cells, and they are not considered to be 'alive'. They are parasitic 'replicating devices' - they can only replicate when they have successfully infected the cell of a host species. And, they are designed to take-over the protein machinery of their host's cell, causing it to make many more virus particles, and to spread them. https://en.wikipedia.org/wiki/Virus Mammals have evolved with viruses throughout our history, and our immune systems contain some viral defenses, just as our genomes contain bits and pieces of DNA that may have been viral in origin. In recent years and decades, we have increasingly been aware of 'new' viruses, not previously seen in humans, that are suddenly causing human disease. Swine flu, avian flu, MERS, SARS, and others - and now, the Wuhan coronavirus. Why are viruses so common in mammals? Because we are really good hosts for them - lots of cellular protein machinery, warm-blooded cells which promote high rates of viral replication, dense social structure which promotes transmission. From rats to cats, bats, camels and more, each mammalian group bears its own viral load. Why do viruses move between mammal species? Two words: mutation and opportunity. As viruses mutate, they can gain or lose features that make them better, or worse, suited for particular host species (e.g., cats versus dogs). As species co-mingle, the odds improve that a virus can successfully 'make the leap' to a host of a different species, one to which it is newly well-suited. Why are so many of these novel viruses originating in Asia? Population density and food production practices. On the global scale, the U.S. is relatively sparsely populated (save our largest cities). Across the globe, it is very common for population densities to be much higher than those found here. And, high human densities require ramped-up food production. Much of food production here is commercialized and removed from the public, but again, this is a global exception. Across most of the world, food production tends to be on a smaller scale, and it tends to be much more personal - individuals tending their own animals, working with their tissues and bringing their own products to open market. Together, this density and close contact ups the risk of transmission of animal viruses to human hosts. This article describes genetic efforts to identify the original animal source of the human virus, as well as to characterize the virus more fully. The more we know about the virus, the more likely we can stop the spread of infections and develop effective preventatives (such as a vaccine) and treatments. https://www.sciencemag.org/news/2020/01/mining-coronavirus-genomes-clues-outbreak-s-origins I will occasionally pass along 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 their 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). 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 classroom conversations. Have a great weekend - Dr. Nealen Avian flu! Swine flu! Now, bat flu? Last week I sent you a news article on the recent coronavirus, first described in Wuhan, China, that was emerging as a 'new' human virus, one not previously detected in humans or known to cause human disease. A week later, as you know, this remains the top health news story, and rightly so - the virus has now killed many dozens, and infected many thousands, around the globe. Viruses are a bit of an evolutionary quandary. They are tiny objects, composed of protein and nucleic acid. They are not considered to be cells, and they are not considered to be 'alive'. They are parasitic 'replicating devices' - they can only replicate when they have successfully infected the cell of a host species. And, they are designed to take-over the protein machinery of their host's cell, causing it to make many more virus particles, and to spread them. https://en.wikipedia.org/wiki/Virus Mammals have evolved with viruses throughout our history, and our immune systems contain some viral defenses, just as our genomes contain bits and pieces of DNA that may have been viral in origin. In recent years and decades, we have increasingly been aware of 'new' viruses, not previously seen in humans, that are suddenly causing human disease. Swine flu, avian flu, MERS, SARS, and others - and now, the Wuhan coronavirus. https://www.bbc.com/news/health-51237225 Why are viruses so common in mammals? Because we are really good hosts for them - lots of cellular protein machinery, warm-blooded cells which promote high rates of viral replication, dense social structure which promotes transmission. From rats to cats, bats, camels and more, each mammalian group bears its own viral load. Why do viruses move between mammal species? Two words: mutation and opportunity. As viruses mutate, they can gain or lose features that make them better, or worse, suited for particular host species (e.g., cats versus dogs). As species co-mingle, the odds improve that a virus can successfully 'make the leap' to a host of a different species, one to which it is newly well-suited. Why are so many of these novel viruses originating in Asia? Population density and food production practices. On the global scale, the U.S. is relatively sparsely populated (save our largest cities). Across the globe, it is very common for population densities to be much higher than those found here. And, high human densities require ramped-up food production. Much of food production here is commercialized and removed from the public, but again, this is a global exception. Across most of the world, food production tends to be on a smaller scale, and it tends to be much more personal - individuals tending their own animals, working with their tissues and bringing their own products to open market. Together, this density and close contact ups the risk of transmission of animal viruses to human hosts. What can we do? Addressing the inequities of education and opportunity that put some more at risk of public health diseases than others is a global problem, one that is daunting in scale. Can we immediately correct it? No, of course not. We can, however, be careful consumers, paying attention to the kinds of products we purchase, their degree of commercialization, the level of exploitation that may be attached to them. We can pay attention to climate issues, which seem to exacerbate many emerging diseases. And personally, we can practice good public health ourselves - stay up-to-date with vaccinations, follow good hand hygiene protocols, cover our coughs and our sneezes. And, we can stay informed, and help others to be informed - that is perhaps the best defense of all. I hope that, by this time next week, the spread of this coronavirus has been contained. Sincerely, Dr. Nealen Scientists Predict Fish Behavior from Real-Time Brain Monitoring | The Scientist Magazine®1/27/2020 Good evening all,
I read a lot of science each week. More accurately, I scan a lot of science journal Tables of Contents, and science news headlines, and I select articles to read from them. Throughout the term, I will occasionally send you links to articles, along with a short 'blog' about why I think the article is worth sharing. The article whose link I am forwarding below describes a recent study, whose primary finding may seem, at face value, insignificant. In this study, scientists monitored multiple (several thousand) neurons in the brains of fish, which they had trained to left, or right, in response to a sensory cue. Then, analyzing the neural recordings they had obtained, they could predict (from the neural data they collected) which direction the fish would turn, up to 10 seconds before the turn. Wow, right? They can predict whether a fish turns one way, or the other. It doesn't sound like much. But, it is a useful result, for a number of reasons. Experiments like this are designed to assess decision-making, something that our brains have to do an incomprehensible number of times each day. Sure, we make many 'big' decisions, conscious ones, including many with life-altering consequences (like staying in our lane on the freeway). But, we make untold more smaller decisions, many unconsciously, steadily throughout the day. Think of something like typing, or writing - each letter requires a series of motor actions, in order, that have to planned and executed, against a background of many alternative movements that are possible. That's a lot of decision-making, even just to write or type a single word. How do our brains accomplish it? What can go wrong to impair decision-making? What can we do when that happens? Each of these 'big questions' must be addressed in tiny pieces, like in the study described here. In the neuroscience research community, there are lots of different experimental models for decision-making. Larval zebrafish do not seem like an obvious choice, but they offer several specific advantages. They are small, easy to breed and house. They are relatively low on the 'scale' of vertebrate animals, such that their use raises relatively little ethical concern. Importantly here, they (1) readily learn this simply task, (2) reliably report their decision, and, (here's the big one) have brains that are small and nearly transparent. This allows researchers to monitor essentially every neuron at once, which is quite remarkable. (Remember - these are free-swimming animals, less than a cm in length, with *tiny* brains.) Most studies of decision-making in mammals focus on the frontal cortex. Neurons there are engaged in decisional tasks, and damage to this cortex impairs decision-making (causing slower, and often faulty, performance). This new study suggests that decision-making activates neurons across the entire brain, including in areas thought to be primary reflexive, or involved in motor coordination (like the cerebellum). It's an interesting result, and one that will cause those who focus narrowly on one region or another to take a step back, and evaluate their scope of investigation. The second primary advantage of a model system such as this is that a system of only 5,000 neurons is one that can be computer-modeled in its entirety. We may not have all of the information about how these neurons are connected, or their individual biophysical characteristics, but we definitely have the computing power to incorporate all of them into a single model. They are multiple, ambitious projects to map and model the human brain, but they remain limited both by data as well as by computing power. The more we learn about the brain, the more we realize that neurons across the brain seem to be involved in collective networks. That's a much harder nut to crack than a group of neurons in one location being solely responsible for some singular function. So, the next time you see even the simplest of organisms behave, such as a fly taking-off or landing, recognize that its nervous system is performing functions very analogous to our own! ------------------- I will occasionally pass along articles of this type during the semester. My purpose in doing so is to help you to become more aware of current neuroscience topics, 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 their science news directly, but hear news via secondary sources, such as news releases from scientific organizations, or as science news stories from the major news outlets. These secondary reports often are then carried by tertiary outlets (smaller/other reporting sources). I'd 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. 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 (like this one: https://www.cell.com/cell/fulltext/S0092-8674(19)31380-7). Some of these ultimate sources will be behind paywalls, but others will be accessible, especially if accessed via an IUP campus computer. If you ever really want to chase down one of the source articles and cannot, let me know and I can help you get to it. Some of the science and news sources whose links I will forward allow only a handful of free articles each month; I will try to use them sparingly. I also will generally send reports only from sources (professional societies and reputable science and news outlets) that I trust. The material that I send you as science news will not specifically be represented on our course exams, but I do hope that the material in them makes its way into our conversations. Have a great rest of the weekend - Dr. Nealen Coronavirus Live Updates: Wuhan May Have 1,000 More Cases, as Death Toll Rises - The New York Times1/27/2020 Good evening all,
As I scan the science news each week, I very often encounter science news reports that are worth sending to you. Some of them are timely matches to our course content, some of them are just plain interesting, and still others are just too important to ignore. This one may fall into the last category. There is an epidemic of the 'Wuhan coronovirus' in China. And, infected individuals are known to have traveled to a large number of places outside of China, such that infections are now being detected in other countries, including here in the U.S. Worldwide, many thousands are known to be infected, and the number of deaths attributed to this virus, while still low, is rising. This is a new virus, not seen previously in humans. As viruses go, this one is not especially lethal. But, like may other viruses, it appears to be able to spread reasonable easily from person to person. And, persons infected with the virus can be asymptomatic (e.g., show no outward signs of illness) for some time, allowing them to come into contact with others before they are aware of the need to limit their exposure to others. Is there a vaccine? No, it is not possible to create a vaccine to a new virus in such short time. From where has this virus come? It has been suggested to have originated in reptiles (possible snakes), and then made the jump to human hosts. This is not completely novel, as other viruses which cause human disease (such as the HIV virus, or those causing 'swine flu' or 'avian flu') also originated in animals. Why are humans at risk from these new viruses? Because we have no prior exposure, our medical community has no ready defenses (such as vaccines). Because this virus may be appearing in humans for the first time, our immune systems have not evolved any natural defenses, either. Should you panic? In short, no. Many more people die because of the seasonal flu virus each year than are likely to suffer death from this one. What should you do: Most importantly, pay attention to the news, stay informed, and be cognizant of anyone in your circle of interaction who may recently have traveled from an area in China experiencing an outbreak. Only if cases are detected in our community will specific calls to action be issued. So, if the lethality of the virus is low, and the risk of infection is low, why should you care? It's worth paying attention because this is just the latest in a series of 'new' viruses that have emerged (most in the Asia or the Middle East, including SARS and MERS) that, while of relatively little consequence here, are severely problematic there. Imagine entire cities on lock-down, quarantine. Imagine all of the work, school, and travel that has been disrupted. And, remember, there is still much we do not know about this virus, of its origins, its ability to mutate, and spread. Ask yourself: what if it happened here? Would our U.S. health agencies be ready and able to combat the emergence of a new virus? Many feel that the answer is 'no'... The best individual defense is information, and awareness - that is why I am sending this along today. https://www.nytimes.com/2020/01/26/world/china-coronavirus.html --------------- I will occasionally pass along articles of this type during the semester. My purpose in doing so is to help you to become more aware of current physiology and health topics, 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 their science news directly, but hear news via secondary sources, such as news releases from scientific organizations, or as science news stories from the major news outlets. These secondary reports often are then carried by tertiary outlets (smaller/other reporting sources). 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. None of these news links that I send you will be represented on our course exams, but I do hope that the material in them makes its way into our physiology conversations. I'm sending this link to both my BIOL 240 lecture and lab sections, so my apologies if you receive this message twice. 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. Have a great rest of the weekend - Dr. Nealen Good evening all, We've made it a point several times during class this term to highlight how behavioral knowledge could be applied to conservation efforts. Here's a link to a recent (and lengthy) discussion of how captive breeding in cheetahs has been enhanced by applying more-naturalistic methods than simply pairing together single males and females. It's quite striking the lengths to which breeders have gone in order to improve the success rate of their breeding programs! https://www.pnas.org/content/116/50/24911 Dr. Nealen Good morning all, Hot off of the presses - new information on the genetic basis of avian migratory behavior, a topic we have considered in class. Here, researchers believe that they have identified a single gene on one of the avian sex chromosomes that is linked to specific migratory targeting in warbler species of conservation concern. Interestingly, this avian gene is related to a human gene thought to be associated with movement. This is a good example of the current state of much of the study between genetics and behavior. Through large-scale genomic analyses, it is possible to identify associations (correlations) between individual gene variants and particular aspects of behavior, but there is much to be learned "in the middle" - how does any one gene, and its gene product, mechanistically contribute to behavior? Or is the association identified in first-order analyses spurious, or non-causal? There is plenty of room for further work, as these researchers note. https://news.psu.edu/story/585429/2019/08/28/research/new-insights-genetic-basis-bird-migration Good luck with all of your remaining exams - Dr. Nealen Good morning all, Hot off of the presses this morning is a news report about sustainable "forest farms", efforts to use environmentally-friendly propagation methods, in naturalistic-type settings, to commercially produce native plants that are of economic value. It's an interesting idea, and one that is quite different (by necessity) from the mass-production, highly-intensive, large-scale format of most of our modern agricultural production. https://news.psu.edu/story/599492/2019/11/25/research/forest-farms-could-create-market-ginseng-other-herbs Many find these small scale, low-impact 'farming' methods attractive for their reduced reliance upon chemicals and their shortened supply chains, with products often moving from producer to consumer with few or no intermediaries. As these authors note, these practices may provide a bit of 'social justice' as well, by providing more-direct benefits and controls to producers. As such, these methods could represent a 'win-win' situation: valued and sustainable production, and well-served consumers. This ties in very nicely with the concepts in our last chapter, including the adoption of sustainable agricultural practices. Dr. Nealen Nitrogen crisis from jam-packed livestock operations has ‘paralyzed’ Dutch economy | Science | AAAS12/9/2019 Good morning all, In the news this weekend is a report about nitrogen pollution from farming and industrial activities, topics we discussed just this past week. These are global problems, but the problems are worse in some areas than in others. And, the political will to address them is equally uneven in its distribution. I suspect that we will see more of these 'crises', as industries are shut down or face temporary moratoriums when pollution reaches dangerous levels. These are not easy problems to fix - it's very hard to change communities that have been operating in a given way toward newer/better methods, especially when much has been invested in current technologies and practices. Big solutions, integrating social reform, advanced engineering, and education are likely to be required. https://www.sciencemag.org/news/2019/12/nitrogen-crisis-jam-packed-livestock-operations-has-paralyzed-dutch-economy See you this afternoon for review - Dr. Nealen |
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