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.
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.
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 -
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.
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.
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 -
Good morning everyone,
Our lecture on Tuesday of this week described the essentials of digestion, and Thursday's topic followed with consideration of metabolism and energy balance as a whole. In the science news this week is a new study on these very topics, with description of a genetic mutation that influences both.
During our digestion lecture, I noted that much of its function is regulated autonomically, by local reflexes mediated in the ENS. That is to say, the digestive tract functions more or less on its own when food is presented to it. By inference then, regulation of food acquisition controls the overall amount of digestion we perform, and the number of calories we have available to use or store.
Regulation of hunger, food-seeking, and feelings of satiety (satisfaction of hunger, or "fullness") occur largely through the hypothalamus, where a variety of chemical signals are known to promote either orexigenic (food-seeking) or anorectic (satiety) states. These include a number of cryptically-named chemicals such as CART, alpha-MSH, agouti-related peptide (AgRP), and melanocortin (MC), each acting at hypothalamic cells bearing specific receptors for them. A great deal of experimental work over the last several decades (mostly in mouse models) has demonstrated that disruption of their signaling (via increased activation of their receptors, or blockade of them) can cause food consumption and body mass to either increase, or decrease.
Abnormally-elevated body mass to the point of obesity has reached critical levels in this country. Depending upon the guidelines one uses, it has been estimated that 30-40% of adults in this country are obese, with another substantial proportion of the population classified as overweight. Extra body mass is a significant health complication, raising one's risk of a number of diseases (including hypertension and diabetes) and complicating treatment and prevention of many others. As such, there is an enormous research effort underway to explore the roots of obesity. We know for certain that the issue is complex - socioeconomic status, willpower, behavior, access to high-quality foods, and sociality influence our food choices, eating habits, and body mass, in ways that are both many and complicated. Increasingly, there is growing appreciation of genetic components to obesity as well.
Modern genetic assessments of health have benefited by technological advances that allow sequencing of individual genomes, resulting in large databases of genetic information. When these are paired with health profiles and lifestyle data, they make possible genome-wide association studies (GWAS). GWAS represent a powerful way to take two very large sets of data (gene sequences and health/lifestyle data) and see how/where they intersect. In contrast to the twin study I described to you in my science news email last week, GWAS are useful only when based upon thousands (usually, hundreds of thousands) of individuals. These are not experimental methods, so they cannot provide definitive proof of anything, but they can reveal interesting "associations" - places where genetics and health vary in consistent ways.
This new study describes a GWAS that sought genetic bases for obesity. In a very large sample of human subjects (500,000 individuals), the researchers looked for consistent genetic mutations in people who were, or were not, obese. They found evidence for specific genetic variation in the MC4R gene (melanocortin receptor 4) that was associated with obesity: persons whose MCR4 gene was mutated (causing reduced function) were much more likely to be obese that those who carried the 'normal' version of the gene. To some extent, this finding was not new - this effect of MCR4 mutation had been described previously, in smaller studies. Here, though, the researchers also found evidence that if mutations in the gene(s) that regulate MCR4 cause it to be 'turned on' all of the time (instead of occasionally, such as after eating), it causes chronic satiety, or "fullness". Persons with this form of mutation are much less likely to be obese, so the researchers interpret this alteration of MCR4 function as protective, and preventive of obesity.
Thus, we may have a single gene, which if mutated in one fashion can contribute to obesity, and if dis-regulated in another way can protect against it. A second study described in this same article uses similar data to create a genetic risk assessment for obesity, with the hope of reducing its prevalence, potentially by intervening before it reaches criticality.
The genetic associations described in this study are not enormous, just a few percent (perhaps 6%). Still, they represent the largest known genetic association for obesity, and that in and of itself is a very worthwhile finding. Many persons who are obese suffer from anxiety, depression, and feelings of low self-worth, thinking (and too-often being told) that they are 'fat', or overweight, because of their behavior and lack of willpower. What if the problem lies in their genes, and not in their self-control? We all know how difficult it is to resist food when we are hungry - what if that feeling never goes away?
Like most science, these studies raise more questions than they answer. Obesity and weight control are such significant problems, though, that their investigation is crucial to improved public health. Here's to more studies and more information on these topics - they are likely to benefit us at a variety of levels: individually, via our loved ones, or as part of society as a whole.
Have a great weekend -
Good morning all,
In lab recently, we have been considering some of the aspects of personalized genetics, with particular reference to genetic ancestry and the use of DNA databases in forensic and criminal investigations. During our introduction to this topic of personalized genetics, I noted that there also are significant interests in using personalized genetics as a way to assess health. Indeed, many of the commercial entities that offer to analyze an individual's DNA also offer to provide some estimate of their health risks for a variety of conditions. I also said at the time that, in our discussions, we would largely stay away from the health aspects of these services, as they are much less well-established than are the ancestry ones.
I described to you recently how using DNA in criminal investigations relies upon combining two large databases (of individual genomes, and police records) to look for intersections, in order to highlight potential crime suspects or their relatives. Using DNA to assess health risks works in a very similar way, this time by evaluating databases of individual gene sequences against databases of individual health and lifestyle records. These types of tests are called genome-wide association studies (GWAS). GWAS are useful only when based upon thousands (usually, hundreds of thousands) of individuals. These are not experimental methods, so they cannot provide definitive proof of anything, but they can reveal interesting "associations" - places where genetics and health vary in consistent ways.
There are lots of large databases of public health records and DNA sequences, and many researchers and even some governments are using them to investigate public health. The commercial operatives also offer to do the same for their subscribers. In the news this week is a reminder that simply claiming that such a service is available does not mean that it is a complete or accurate one. Researchers at not-for-profit health institutions are warning that those who use 23andMe health assessments of genetic risks for breast cancer (the leading type of cancer in women) are potentially being misinformed of their genetic risks. This is a big deal - many people make dramatic decisions about their health and life when learning of their genetic risks for breast cancer, such as undergoing mastectomy (breast removal). At the opposite extreme, what if a person has a substantial risk, but is told that they do not?
The federal Food and Drug Administration (FDA) has given its approval for 23andMe (and other commercial) genetic health assessments, and this is an important reminder that FDA approval is not meant to imply that the services are the best available, more so that the services are generally safe and perhaps useful. Anyone who is using a commercial service to evaluate their genetic health risk should follow-up with their physician if they have any concerns - the better hospitals can perform some of these tests on their own. "Caveat emptor", or "buyer beware" - commercials services, by design, place emphases on their interests, first. When in doubt, a second opinion from an independent health professional is the best course of action.
Have a great weekend -
Good morning everyone,
As we enter the last quarter of out term, we soon will be considering the remaining chapters in our text, on topics including digestion, immunity, metabolism, and reproduction. These are relatively 'integrated' phenomena - complex and intertwined with other of our physiological systems and processes.
In the science news this week is a report that is similarly integrated, on simultaneously both a larger scale (the entire body) and a smaller one (examination of just one person, relative to one other).
Nearly all quality research in physiology (like that of other fields) relies on large sample sizes - studies of hundreds, thousands, or even millions of individuals. The larger the sample, often the greater the statistical power of the comparisons, the ability to detect tiny effects. Does this drug lower blood pressure? How does a vegan diet influence sleep habits? What are the genetic components of immunity? Studies like these would never evaluate one or two subjects, because the ability to generalize the results would be very low. And, studies employing few subjects would be very unlikely to be funded or pursued, for exactly that reason.
But, NASA's study of astronaut Scott Kelly (and comparison to his Earth-bound twin Mark) is quite unique, in many ways: how many of us will ever spend (nearly) a year in space? So, far, perhaps just a handful of people. How many of these individuals have an identical twin? Just one.
Scott and Mark were subjected to a battery of tests before, during, and after Scott's 340 day long space aboard the International Space Station. How does a life in space influence the body? Well, in many ways, as it turns out. Why do we care? Because, as a society, we continue to push the boundaries of space travel, and long journeys in space (to Mars, or other places) are surely on the horizon. What will happen during those trips? Scott and Mark Kelly offer a useful, and unique window into this problem. Because they are genetically identical, in theory, any differences between them should be due to their environments. If they were carefully evaluated before, and then after, Scott's year in space, it should allow us to see what space travel does to the body, by comparing Scott and Mark.
If Scott Kelly is a useful model, life in space will be very challenging, physiologically. Among the largest changes noted upon his return to Earth were cognitive deficits, colonization of his body by different kinds and numbers of bacteria, indicators of high stress levels (no surprise), many genetic mutations, and, surprisingly, longer telomeres on his chromosomes. This last finding was unexpected - telomere length is a sign of cell age, and long telomeres are normally interpreted as a sign of youth. Does space travel reverse aging? Probably not! It's more likely that the rigors of space life (especially the radiation exposure) triggered lots of repair and replacement of damaged cells, and newly created cells may have higher levels of telomere maintenance.
In many ways, Mr. Kelly has offered himself as a 'guinea pig' for these studies - even now, back on Earth for years, many of his symptoms and genetic mutations remain. Was it worth it? His answer is an unequivocal 'yes'. Like other astronauts before and after him, his experiences were literally other-worldly. Our technological advances toward space may be outpacing our physiological ones, however. If Mr. Kelly's response is typical of what will happen to the human body in space, we have much to learn, and much work to do, before long-term stays in space will become feasible.
Not to say that all of the news is negative: he took some amazing photos while he was there:
Have a great weekend -
Good morning all,
In lab this past week, we considered some of the aspects of personalized genetic testing, including the ability to estimate one's genetic heritage and family history through evaluation of genetic dissimilarities to others. Fresh on the heels of that discussion is another news report of more decades-old crimes being solved by similar kinds of genetic comparisons.
When a person offers their genetic information to 23andMe, Ancestry.com, or other of the genetic history services, their DNA sequence and its identified markers are entered into massive databases. It is only against these databases that useful comparisons can be made - we can't learn much about our genetic history by comparing our DNA to that of one or two others.
Remember that these DNA sequences can be compared for similarities and dissimilarities, and they also can be clustered into haplotypes - groups that share some common ancestry. Haplotypes are the basis for construction of genetic pedigrees, or genetic 'family trees'.
How can we solve crimes using this information? Imagine that 5 or 10% of the population of a city have their DNA stored in one of these databases. If a crime (new or old) is committed, investigators can
1) collect DNA evidence from a crime scene (easy to do, as we leave hair and cells everywhere we go)
2) compare the DNA from the crime scene to that of the collected database
3) Evaluate whether there is a direct DNA match to someone in the database. If so, that person may be the culprit! Well, if only 10% of a population has been genetically profiled, the odds of that are low. It's also likely that that people who commit crimes are not likely to freely offer their DNA to public databases.
4) But, we all have relatives. Investigators can often find similarities between the DNA collected at a crime scene, and the DNA of some family group within a database. Then, they look at the personal and family backgrounds of just those individuals. Are any of those people in the DNA database related to someone who has committed other crimes, and has a criminal history already in the police records?
This represents a very powerful way to quickly sort through a lot of information. One the one hand is a large database of genetic information. On the other hand is a large database of police records of crimes and criminals. Finding out specifically where they intersect is the key, and such a comparison often produces leads to a small number of individuals as suspects.
5) Suspects can then be watched/followed, and their DNA then sampled (for example, by collecting from the trash a drinking cup they had used). If this new DNA sample matches that collected at the crime scene, the crime may be solved.
It is exactly these methods which are being used in many cases, both new and old. Notice that they rely very heavily on personal genetic data, and, importantly, notice that suspects can be identified even if they don't offer their own DNA, as long as someone related to them already has. This is a challenge for the courts, too - what is an individual's right to privacy and protection from suspicion when your relatives implicate you, just by being related?
It's exciting to think of the possibilities for learning about one's self through DNA. It's equally important to remember that these are discoveries that we cannot make on our own - we are relying upon public and commercial databases, that can be used in ways we may not have intended or not even thought about. Science is about progress - new ideas, information, and abilities. Even as we reap the benefits of these advances, it is important that, as a society, we stay abreast of the social and ethical challenges that come with them.
Have a great weekend -
Good morning all,
We've talked about genes, and modifications of gene structure (gene editing) or use (gene expression) a number of times this term, and I am sure that you understand both the power and peril that these methods embody. Editing DNA is, at its most basic level, very profound: it really is the 'stuff' that defines us.
In the science news this week comes a recent report, that at first glance, seems unimportant: scientists have performed gene editing, and made an albino lizard. But, this simple summary doesn't quite capture the importance of this work.
For most of its history, molecular biology (and its recent growth into genomics) have focused upon a few model organisms, chosen for their practicality of study. These have included bacteria, yeast, roundworms, fruit flies, zebrafish, and mice, to name a few. Much has been learned from these models, and most of what we know about molecular biology and genetics comes from work on them. But, their use excludes several prominent groups of organisms, including birds and reptiles. That may be coming to an end.
One research group recently employed a modern gene-editing technique (CRISPR) to modify gene expression in Anolis lizard eggs to produce albino offspring. This, in and of itself, is not necessarily an earth-shattering result. What is new is the fact these researchers were able to use CRISPR on a new family of vertebrates, suggesting that it really is going to be a general and powerful technique. Even more importantly, however, these researchers were able to edit the genome of immature eggs, which means that the effects they caused were then propagated throughout the entire organism that resulted from those eggs.
Remember when we talked about gene therapy, and introducing new genes into specific tissues (only)? Here now is a more powerful technique: performing targeted gene editing on the whole-organism genome.
Stay tuned: this gene (and now genome) editing ride is going to be a wild one for a few years, until our understanding of it, our ethical evaluations, and our regulations mature.
Have a great weekend -
Good morning all,
In our last two lectures of this third unit of the course, we are considering renal function and the often overlooked role of the kidneys in our health and well-being. During lecture on Thursday, I mentioned several facts related to kidney disease and failure that some recent science news can inform.
We discussed conditions such as diabetes and hypertension that can induce kidney damage and failure, and the third items on that list was genetic bases for kidney ailments. One of the reasons that we did not elaborate on the topic is that the specific genetic causes of kidney disease (like that of so many other of our diseases) is very nebulous - there are many genes involved, often with very weak effects, and their interactions with each other and with environmental influences are poorly understood. In these situations, patients often recognize that they are part of a family history of disease (suggesting its genetic basis), but typically the genes involved are not identified, or their function is not characterized.
Recently, several research teams have made progress on this issue. Using exome sequencing (a DNA sequencing method that focuses only upon the protein-coding regions of our DNA), researchers recently have described with greater detail the number of different genes involved in a small sample of patients with chronic kidney disease. They identify over 60 different genes, some with identified roles as membrane transporters or regulators of gene expression. Most of these were associated with a tiny number of disease cases.
As is often the case, studies like this are useful if only because they reveal how much we have yet to learn, and offer a potential method forward. It's a very long (and expensive) pathway from gene identification, to functional investigation, to testing of therapeutics, to useful treatments, and most avenues of exploration do not yield breakthroughs. But, we now know more than we did, and there is great interest in finding ways to abate kidney disease. There are still a great number of people awaiting kidney transplants, and many die while they wait. Inequities of access to donated organs may be part of the problem. Perhaps we should pay people for organ donation - or would that be more problematic than useful?
Have a great weekend -