Good evening all, As I indicated during class on Wednesday, we will not meet for lecture tomorrow (Friday 22 Nov), but instead will consider some topical science news: We finished one of our recent lectures by introducing the concepts of gene therapy and cloning. Both of these stem from the application of modern genetic methods, and both exist already - but not without controversy. As described in your text, gene therapy is an attempt to correct defective or missing genes, by using viruses to insert them into a person's cells. It remains very controversial and of relatively limited use, because many of the risks and complications of the technique have yet to be overcome. Indeed, some human gene therapy trials have resulted in patient deaths, and few would say that the technique has been proven to the point at which broad use is possible. Still, for some people with very specific types of genetic defects, gene therapy has proven to be a lifesaver (literally). We can expect to continue to hear much about gene therapy in the years to come. Related to gene therapy is the concept of gene editing. The goal of this technique is not to replace defective genes with normal copies, but rather to use enzymes to edit (correct) the defective genes in place (e.g., within the cells of the organism). Gene editing utilizes techniques more recent than those employed in gene therapy, so it has been tested, and used, relatively less. Thus, it was of great surprise to the scientific community last Fall when a Chinese scientist (He Jiankui) claimed to have performed gene editing on several artificially (in lab) created human embryos, and then to have implanted those embryos into female surrogates to carry the developing embryos until birth. The technique of gene editing is new enough that, one year ago, the ethical guidelines governing its use had not been fully developed. Nonetheless, there was a general understanding that the technique was not to be used in human embryonic tissue, that would result in *all* cells in the body inheriting the edited gene. This understanding was very broad, but was not universal, and scientists in several countries did use (or attempt to use) the technique on human embryos, in the hopes of creating a gene-edited person - a "designer baby". The scientific backlash against this first report of human embryonic (germline) gene editing was relatively swift, and relatively severe. The scientist who conducted these first trials has been stripped of his research position, and charged with violating his country's biomedical research laws. The infants (twin girls) were reported to have been born, but little is known about their condition. Some researchers have suggested that they are at risk of a shortened life expectancy because of the gene editing. The gene that was edited in these now-children is thought to promote resistance to HIV infection, but also seems to play other roles in cells. The article I am forwarding here comes from a few months ago, when the investigations into this researcher and his colleagues was still in process. In particular, there were a number of scientists here in the U.S. who were implicated as having supported this work. The researchers here have generally been cleared of any wrongdoing, but significant questions remain about who knew what, and the motivations (money? fame? patent-able technology?) for their involvement. This article also includes links to a number of related stories, of which there are many. https://www.nytimes.com/2019/04/14/health/gene-editing-babies.html It is worth noting that somatic (non-germline gene editing) is gaining ground as a very powerful and promising technique. This variant of gene editing does not change the DNA in every cell in one's body, but only in focal tissues (such as a single organ) that may be malfunctioning due to a defective gene. Indeed, news reports of the promise of this (more-limited) application of gene editing are also prominent in the recent news, including: https://www.forbes.com/sites/leahrosenbaum/2019/11/19/human-crispr-trials-promising/#340301322daa I suspect that your generation will be forced to come to terms with the promises and perils of gene editing - it seems both incredibly promising, and incredibly dangerous at the same time. Having a robust set of regulations and ethical guidelines will be very important. If you were faced with the opportunity to correct a gene in yourself, in a loved one, would you? That's a very difficult question to answer a the moment, as we do not yet have enough experience with the pros and cons of these techniques. But, the evidence is beginning to accumulate... Here's wishing you all the very best Thanksgiving break - please be safe, rest, relax, eat, and enjoy. Sincerely, Dr. Nealen
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Good morning all, As I noted on Tuesday, we will not meet for lecture today. We have only one textbook chapter remaining, which we will save for our first meeting after the Thanksgiving break. Instead of lecture today, I'll offer you a reading instead, one that encompasses several of our recent topics. In recent classes, we have considered the degree of cooperation and conflict between reproductive partners, as well as the signaling that occurs to influence each other. When sexual investment is strongly different between the sexes, we expect that sexual selection can drive exaggerated displays, enhance female 'choosiness' of mates, and promote unequal reproductive tactics. But, curiously, sexual displays also are common within pair-bonded species, in which males and females have equal (or nearly equal) roles and should be in cooperative agreement over parental investment, rather than in conflict. An explanation for this paradox has been lacking. A very recent paper sheds some light on this problem, and present a mathematical model which supports the idea that inter-sexual signaling displays which originate to exploit a sensory bias in the signal receiver can evolve into a cooperative exchange, suggesting that sexual conflict can morph into sexual cooperation. This has significant implications for parental investment and care, as we've noted that the degree of sexual conflict is one of the primary drivers of sexual dimorphism in parental investment. https://www.pnas.org/content/116/46/23225.abstract?etoc This paper was published in the Proceedings of the National Academy of Science (PNAS), our national body of 'science experts'. Election to the Academy is reserved for the top thinkers in one's field, and is a prestigious badge of honor. Their Proceedings journal publishes papers submitted by Academy members, as well as those that Academy members recommend for publication. If you access this link from an IUP campus computer, you can obtain access to the full article and its associated material, through IUP library subscription. If you try to access the article from off-campus, you will be blocked. I've attached the PDF of the article, just in case. The math of the authors' model is well beyond us. If we accept their model as being sound, it suggests that, instead of females being 'lured' into over-investment in their offspring by male displays, females instead evolve to require (or at least benefit from) the male display in terms of stimulating female condition/motivation to a level of investment which is optimal for the female (but less than that which is maximally optimal for the male). This causes males to remain invested in the pair-bond and their role in parental investment, and reinforces the pair-bond between mating partners. In a sense, the females are now requiring the males to remain present, remain attentive, and to offer displays, in order to ensure that their female partner is providing enough investment of her own. As do many science journal, PNAS occasionally offers peer commentary on papers which are especially important, or especially difficult (this one is perhaps both). The associated commentary on this paper (link below, PDF attached), describes this result in the context of dove mating pairs, for which male stimulation of female reproductive condition is a well-understood and very necessary component to the reproductive cycle. Interestingly, as the commentary notes, the capitulation of this male-female exchange may ultimately be female self-stimulation of reproductive condition, a result which has been suggested to occur in doves. That may be the current evolutionary end-point to this exchange, but it also has the potential to serve as a type of an "escape clause", which males may now be selected to exploit. It would be interesting to see how much variation exists in this end-point, and whether males can benefit from females which perform more of their own reproductive stimulation. https://www.pnas.org/content/116/46/22899?etoc= I hope that you find this article interesting - it represent a nice, theoretical treatment of a difficult (= interesting) problem, and should set the stage for experimental work to come. I hope that you all have an excellent Thanksgiving break - please be safe, rest, relax, eat, and enjoy. See you early in December for our last chapter. Sincerely, Dr. Nealen Good morning all, As we remain on-schedule, we will not meet in-person for lecture on Friday (15 Nov). I'd like instead to offer you several pieces of recent science news: We have considered issues surrounding vaping several times this terms, most recently the alarming and poorly-understood severe respiratory distress that has developed in otherwise healthy individuals who vape. After several months of investigation, our CDC (Centers for Disease Control and Prevention) have released a report that appears to identify the likely cause of his distress syndrome: vitamin E acetate, and oily compound used as a additive in some vaping products. https://www.cdc.gov/mmwr/volumes/68/wr/mm6845e2.htm?s_cid=mm6845e2_w Vitamin E and its derivatives are lipophilic (fat soluble), which allows them to interact with cell membranes more easily than most biological compounds (which are hydrophilic, or lipophobic). Multiple samples of lung tissue from persons afflicted with vaping-associated respiratory distress have revealed this compound adhering to the lung surface. If you remember our discussions on lung structure/function, we described the exchange surface between the alveoli and the capillaries of the lungs as being as thin as possible (essentially, two single-cell layers of epithelium), to allow as much gas diffusion across them as possible. Now, imagine that same surface covered with a sticky, oily residue - it's easy to see that gas exchange could be severely impaired. There may be other substances contributing to this distress syndrome, and not all experts are convinced that vitamin E acetate is the culprit. But, the evidence is accumulating, and it appears likely to be the primary cause of the cases investigated so far. https://www.nytimes.com/2019/11/08/health/vaping-illness-cdc.html If you do vape, check your products - do they list this as an additive? Can you select other materials that do not? Juul, one of the largest companies producing vaping products, recently agreed to stop making some kinds of flavored vaping products, as they and others in the industry were being accused of improper marketing toward minors: https://www.cnn.com/2019/11/07/health/juul-mint-pods-bn/index.html One young person with vaping-associated respiratory distress recently was forced to undergo a double lung transplant: https://www.reuters.com/article/us-health-vaping-transplant/michigan-boy-17-gets-double-lung-transplant-after-damage-from-vaping-idUSKBN1XN04R Vaping seems like a habit to be avoided at all costs, in my view. Our lung tissue is simply not designed to handle contact with things other than atmospheric gases. In a few years, we may look back at this as a trend that appeared, and briefly flourished, before its significant health implications were well-understood. I suspect that regulations around vaping will get tighter and tighter, and the available evidence suggests that our public health would be best served by limiting access to vaping materials and more carefully regulating their contents. Have a great rest of the week - see you on Monday for Chapter 22 (DNA Biology and Technology). Sincerely, Dr. Nealen Good morning all, As I noted in lecture on Wednesday, we remain caught-up with our lecture schedule and do not have chapter assigned for today. So, we will not meet in person for class today; instead I will offer this reading which I would like to you to consider. In our last lecture, we identified the "cell cycle" as a way to describe the normal lifespan of a cell, from its formation, through its functional life, and then its eventual end. All of our body cells are formed from mitotic cell division to begin their life, and, at the end of their functional lives, many of our cells undergo division themselves, essentially being reborn as two new daughter cells. We also identified important "checkpoints" in the cell cycle, to prevent cells from speeding through the cell cycle too rapidly. Many of our cells have functional lives of months to years, and without these checkpoints, they would otherwise just divide rapidly into new cells. As we noted, failure to stop at these cell cycle checkpoints can lead to tumors caused by uncontrolled growth; some tumors can become cancers, invading otherwise normal tissues and causing them to become cancerous as well. As you know, cancer is one of the primary causes of human mortality. We experience a variety of cancers: some are slow to progress, others very rapid; some are essentially benign while others are very deadly; some are highly invasive and others less so. The diversity if cancers we experience and the diversity of tissues that they strike represents one the of the primary difficulties in treating cancer: there is no single cure, for cancer is very diverse in its many forms. That's not to say that there aren't standardized treatments. Most hospitals have oncology boards that carefully document each occurrence of cancer, and they typically made treatment decisions based upon consultation among a team of physicians, including oncologists, radiologists, surgeons, and others. Much of their decision-making is based upon care standards that have been developed by national and international cancer agencies, such as our own American Cancer Society, which suggests treatment guidelines for the different forms of cancer. Still, we know all too well that curing cancer is difficult, and sometime impossible. The best one can hope for is to eliminate the cancerous tissue to the point at which is cannot be detected, but that is no promise that every cancerous cell has been removed, nor that it cannot re-appear. Because of the burden cancer poses to society, there are many federally-funded research groups investigating potential treatments. These include
Of course, many of the latest treatments combine multiple approaches, such as using immune cells to target delivery of cytotoxic drugs directly to cancer cells. In the news this week is report of a promising new approach to treating some kinds of cancer, based upon a metabolic starving of cancer cells. Cells that are rapidly dividing (such as those within a tumor or a cancer) are metabolically very demanding, needing large amounts of fuel. Scientists have developed methods to prevent cells from using glutamine (a glucose-like fuel source), to successfully prevent cancer growth. But, earlier formations of this treatment caused widespread side effects, because the cancer cells were not the only ones being starved of fuel. In this latest test, the scientists successfully "handcuffed" an inactive form of their drug to allow its focal delivery to cancer cells, where it was "unhandcuffed" into an active form by cancer cell enzymes. There it successfully prevented cancer growth. Even better, this new treatment actually improved immune T-cell function, providing an immunological boost to cancer elimination as well. These initial studies, done in mice, were very promising. While the road from animal studies to human uses is often long and unsure, this could mark the beginnings of a new generation of cancer treatments that are improved in their focused targeting as well as in their effectiveness at cancer elimination. https://www.sciencemag.org/news/2019/11/revamped-cancer-drug-starves-tumors-mice We'll talk more about cancer in our upcoming lectures, and I hope that this article will put some of the lecture material into practical context. Cancer touches many families, and does not discriminate by race, class, knowledge, or upbringing. May your generation be the one that finally reduces the impact that it has on our individual and our public health. Have a great weekend - see you on Monday. Sincerely, Dr. Nealen Good morning everyone, Last week I sent you a news report about the prospect of "sugar taxes", extra monetary tax levied against sweetened drinks as a way to reduce their consumption and to (hopefully) induce some improved health in the persons who might normally consume too much sugar in their diets. The article that I sent you last week considered some of the potential benefits, and potential difficulties, of implementing such taxes. It also described the limited amount of data available thus far, suggesting that it is still too early to know whether these kinds of taxes lead to health improvements. In this news this week is report of a newly-released study on this very topic. Here, researchers followed the health of a focal group of 200+ people at the University of California-San Fransisco medical school, where a full ban on the sale of sweetened drinks has been in effect. Researchers report improvements in several subject health measures, including reduced waist size, less belly fat, and improved response to insulin. They suggest that these changes were directly a function of reduced sugary drink consumption in these subjects. https://www.nytimes.com/2019/10/28/well/eat/sugary-drink-soda-ban-health-medical-center.html Note that this study described subjects under a workplace ban on the sale of sweetened drinks, not those under a "sugar tax". Here, subjects could purchases sweetened drinks elsewhere, or bring them from home, but could not purchase them at their workplace. This is likely to have a larger effect on consumption than a sugar tax itself, but it does suggest that the benefits of lowering the consumption of sweetened drinks is a very worthwhile goal. The available data suggests that most of us consume too much refined sugar (in some form), which suggests that most of us would benefit by reducing our sugar intake. As we have seen many times during the term, our health depends heavily on the choices we make. Hope that you are enjoying the weekend - see you tomorrow. Dr. Nealen |
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