Friday, April 24, 2015

Gulp - Mary Roach documents her travels on the alimentary canal

Gulp: Adventures on the Alimentary Canal is Mary Roach's 2013 release about food and its journey from start to finish. Here, Roach brings her trademark style combining interviews and site visits with interesting vignettes. She is never afraid of the taboo (Ed Yong has said he has the "wow" beat in science writing; I think Mary Roach has the "ick" beat) and the subject of the physical process of eating and digestion is rife with such topics. Roach states that books about cuisine and food have eclipsed books about the process of eating, which serves her well because most of the interesting stories about digestion are untold.

One of these strange tidbits is that different animals perceive tastes differently. Catfish have taste receptors all over their skin, effectively making them "swimming tongues"; this also makes catfish a popular model organism for taste researchers. Flies taste with their feet. Humans have taste receptors in the gut and the esophagus as well as the tongue; luckily, only the receptors on the tongue are transmitted to the brain. Animals also have different preferences for tastes: rodents love sweetness, but cats cannot perceive sweet tastes. Dogs' tastes are driven by their sense of smell and they show a strong preference for things that smell like cadaverine or putrescine, odors emitted by decaying meat. Dog food manufacturers often use these scents in concentrations perceptible to your dog but not to you to increase a dog's interest in the food. Roach visits a pet food manufacturer and watches dogs taste testing dog food, which gives a fascinating behind-the-scene glimpse of the industry.  

Beaumont studying the digestion of his patient, St. Martin
Roach digs into the tale of scientific obsession at the heart of the relationship of William Beaumont and his patient and experimental subject, Alexis St. Martin. Over the course of thirty years, Beaumont performed hundreds of experiments into digestion via a fistula in St. Martin's stomach. These experiments did yield the first information about the function and contents of the stomach. However, the mental cost to the patient was likely very high. St. Martin eventually escaped Beaumont for his native Canada, but the doctor was constantly pursuing him. (For more on this strange tale, check out the Radiolab episode Guts.) 

I also learned some surprising facts about saliva. For one, the main digestive enzyme in saliva is amylase, which breaks down starches into simple sugars. This activity makes amylase an excellent way to treat food stains on clothing. Laundry detergents often contain at least three digestive enzymes: amylase to break down starchy stains, lipase for greasy stains, and protease to break down protein. It's good to know that there is a scientific basis to my instinct to spit on food stains.

The other interesting elements in the book are learning the techniques that scientists are using to study eating, digestion, and defecation. Roach visits labs that study topics like the function and components of saliva, the process of chewing, and the chemical composition of flatulence. Unfortunately, I felt that these serious topics were often glossed over for the sake of a punchline. I do find Roach's work easy to read, but her sense of humor does not always mesh with mine. I knew that talking about the journey that food takes from beginning to end would bring out her obsession with the scatological and yet I plowed through. I suppose I'm glad I did, as the penultimate chapter discussed Elvis Presley's digestive troubles; Elvis suffered from mega-colon, which was likely a confounding factor in his death. It's funny that my favorite Mary Roach book is Stiff: The Curious Lives of Human Cadavers (I admit to reading it after seeing it on Six Feet Under), which somehow seems less gross than this one. In the end, I would only recommend reading Gulp if you like Mary Roach's approach to science writing.

Thursday, April 9, 2015

Inheritance by Sharon Moalem: an excellent new perspective on human genetics and epigenetics

Inheritance: How Our Genes Change Our Lives
and Our Lives Change Our Genes, by Sharon Moalem, offers a unique perspective on the subject of human genetics. Moalem is a physician-scientist who specializes in rare diseases; his specialty has given him a keen eye for discerning subtle physical differences (phenotype) that are frequently linked to genetic differences (genotype). In some cases, the differences are insignificant. For example, if you have an extra row of eyelashes, you share something with Elizabeth Taylor, specifically a mutation in a gene called FOXC2. Other differences can serve as a diagnostic for rare genetic conditions. In one chapter, Moalem describes being at a dinner party when he noticed several physical traits that suggested that his hostess may have Noonan syndrome, which can be associated with heart disease and blood clotting. Another example is orbital hypertelorism, where the space between the eyes is large enough to accommodate another eye. This trait can be associated with Fanconi anemia, a blood disorder linked with an increased incidence of cancer. Wide-set eyes are commonly found in actresses and models (famous examples include Jackie Onassis and Michelle Pfeiffer). Our preference for certain physical traits may be explained by our interest in ensuring a good developmental and genetic history in our mates; Moalem suggests that facial features are an obvious indicator that brain and body development occurred properly.

Inheritance also highlights how minor differences in the sequence of our DNA can cause major differences in phenotypes. For example, congenital polycythemia (PFCP) is a genetic condition caused by a mutation in the EPOR gene that results in a greater number of red blood cells. This mutation gave Finnish athlete Eero Mäntyranta a distinct advantage in aerobic competition because his blood can carry more oxygen (essentially it's like he always has doped blood). However, PFCP can also lead to an increased risk of stroke. Thus, evolution took a different approach to solving the low oxygen problem for Sherpas: a mutation in the EPAS1 gene causes lower production of red blood cells, but increases the efficiency of oxygen delivery.  Interestingly, this mutation fixed in the population relatively quickly: Sherpas moved into their current low altitude environment around 1500. (This is a really fascinating story; if you want to read more, I recommend this Ed Yong piece.) These examples also underscore that while humans are ~99% similar, there is still a lot of variability in DNA sequence. In fact, in the 14 years since the first human genome was sequenced, we have learned that there really is no average genome. As I highlighted in my previous post on genomics, large-scale genomics projects (e.g., The 1000 Genomes Project) aim to get samples from a highly diverse set of people to remove the background noise so that significant differences can be identified.

Moalem also has an informative discussion of epigenetics (i.e., changes to DNA that do not occur at the sequence level). A great example in the book is the queen bee. Every bee in a colony is completely identical in their DNA sequence. How then does a queen bee become so different in size and function? Larval queens are fed royal jelly, which changes their DNA to allow them to express queen-specific genes. The protein DNA methyltransferase (Dnmt3) can methylate DNA and change its expression. In fact, if you shut down Dnmt3 in bee larvae, all of them become queen bees. The field of epigenetics is relatively young. However, there are already many fascinating ways in which our daily activities can alter the expression of our genes. The epigenome is dynamic and can be impacted by the things we eat and drink, the exercise we do, and, most surprisingly, the experiences we have. Accumulating evidence suggests that stress can alter your genome; in some cases, these changes can be inherited. The Radiolab episode Inheritance highlights a Swedish study that suggests that the eating habits of your grandfather could have an effect on your longevity. Geneticists are just beginning to find ways to track these changes and, more importantly, how to reprogram the methylated genes. As you can imagine, methylation is a very useful way for a cell to alter its gene expression. However, methylation can also mean the difference between a benign growth and a malignancy, making it an attractive target for therapeutic development.

Moalem makes an excellent argument for the support of the study of rare diseases. Most funding bodies think that funding diseases where many people are affected (e.g., cardiovascular disease, Alzheimer's) is the most cost-effective approach. However, studying the mutations and physiology of people with rare diseases can often shed light on the basic underpinnings of how normal cells work. For example, the study of familial hypercholesterolemia (FH) gave us insights into the function of LDL and HDL ("bad" and "good" cholesterol); these results facilitated the development of Lipitor, which has helped many people with elevated levels of LDL who do not have FH.

In short, Inheritance is immensely readable. The author uses clever and pertinent analogies. For example, he compares our cells to the production style of Toyota and Apple in that they stock only the supplies they need to avoid waste (an approach called production leveling). Another great example is when he is explaining a genetic condition that turns muscle into bone; he writes, "Osteoclasts are the Wreck-it Ralphs of the skeletal system. Osteoblasts are the Fix-It Felixes." Overall, the book is very topical and up to date; it would be an informative read for those who are well versed in genetics as well as those who are just becoming interested in the subject. Inheritance is definitely one of the best books I have read on the subject (a close second to Sam Kean's The Violinist's Thumb) and will be added to my list of great science reads.