Thursday, March 13, 2014

My Favorite Science Reads - updated

Here is a running list of my favorite science reads (in no particular order), which I will attempt to keep updated. I have included links to the Amazon page as well as the related post from my blog.








The Immortal Life of Henriette Lacks - Rebecca Skloot (my post here)

The Violinist's Thumb - Sam Kean (my post here); The Disappearing Spoon was also excellent (my post)

The Philadelphia Chromosome - Jessica Wapner (my post

Lab Girl - Hope Jahren (my post at CrossTalk)

Inheritance: How Our Genes Change Our Lives and Our Lives Change Our Genes - Sharon Moalem (my post)

The Panda's Thumb - Stephen Jay Gould (all the books I have read by Gould have been excellent)

The Shadows of Forgotten Ancestors -  Carl Sagan and Ann Druyan

The Selfish Gene - Richard Dawkins (The Blind Watchmaker is also great)

Radioactive - Laura Redniss (my post

Blueprint for a Cell - Christian DeDuve 

The World Without Us - Alan Wiesman (my post here)

Stiff - Mary Roach (I review Packing for Mars here, but it wasn't as good)

Tuesday, March 4, 2014

Matt Ridley's Genome - 14 years later

Genome - The Autobiography of a Species in 23 Chapters  by Matt Ridley came highly recommended on Amazon. Despite the fact that the book was published in 2000, I decided to read it. The structure of the book is rather clever: each chapter focuses on one chromosome. This format allows Ridley to expand the metaphor that the human genome is a book: each chromosome is a chapter; the genes are the sentences; the codons (the three letter DNA sequences that the cellular machinery reads) are the words; and the DNA nucleotides are the letters. This kind of metaphor can help non-scientists visualize and remember the organization of the genome. Unfortunately, Ridley eschews the proper scientific terminology, calling codons "words" and nucleotides "letters". Science writing should teach people more about the subject matter; to eliminate the use of fundamental terminology seems a folly.

In each chapter, the author highlights one gene of interest on the chromosome. For example, the chapter on chromosome 13 introduces BRCA2. Like the Jeff Wheelwright book I reviewed previously, Ridley discusses the population genetics of BRCA2. In some chapters, he writes about genetic lessons from a particular chromosome. In some cases, the conceit works brilliantly (e.g., the chapter on the X and Y chromosomes examines sexually antagonistic genes), but other times, it was not as successful. Ridley uses Chapter 21 to discuss eugenics. While the history of the topic is interesting, the connection to chromosome 21 seems a bit tenuous. Parents are increasingly using prenatal screening to detect chromosomal abnormalities, the most common of which is Down syndrome, which is caused by an extra copy of chromosome 21. I found the book worked best when there was an obvious candidate gene to discuss on the chromosome.


It is amazing to consider how much the field of genomics has changed since the publication of Ridley's book (February 2000). In June of that year, the initial rough draft of the human genome was published. When the sequence was officially completed in April 2003, the final cost was estimated to be $2.7 billion; the project took more than a decade. Today, we are approaching the benchmark of the $1000 genome (discussed here and here). The next step is to improve the speed and portability of sequencing equipment as well as the ability to process and analyze the data.

The human genome project has been considered a success in terms of yields for basic research. However, there has been some disappointment that the completion of the project hasn't led to more clinical applications (for more specifics, see these editorials from Francis Collins and Craig Venter, the heads of the Human Genome Project). One problem is that very few diseases are caused by a single gene. Another confounding factor is that there is 1-3% difference between any two individuals' genome sequences. These variations can complicate genomic analyses. To perform a genomic study of a population with a genetic condition, knowing the differences that are normally present in the genome can help narrow down the possible regions that are linked to the condition of interest. Thus, having more complete sequences available will allow scientists to connect DNA sequences with genetic conditions. The 1000 Genomes Project plans to identify all the genetic variations present in the human population. The initial phase of this project was completed in just over four years with the publication of 1,092 complete human genome sequences from 14 populations across the globe. In the coming years, the project plans to complete a total of 2,500 genome sequences to improve the representation of various human populations across the globe. 

Another major change in the genomic landscape is the advent of personal genomics, such as 23andme. These companies offer DNA analysis service that supplies information on your possible ancestry as well as information about other genetic markers. These markers include both the innocuous ones, like whether you can detect a terrible smell in your urine after eating asparagus, and genes linked to possible health risks (e.g., BRCA, Huntington's disease). After intervention by the FDA, the service is now limited solely to ancestry. Scientific American had a fascinating piece about why we should really be concerned about companies like 23andme (TLDR: they are collecting and storing your most personal data
your DNA).

I would not recommend this book to a non-scientist. If you want to learn more about the human genome and DNA, look elsewhere. I highly recommend The Violinist's Thumb by Sam Kean; the recently updated Double Helix by James Watson and the newest book from Craig Venter are likely to be good reads. 

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Want read more?  
* The Human Genome at 10 Special Issue in Nature covers the changes in the genomics landscape with editorials and articles by a number of major players in the field.
* There is also abundant information on other "big science" approaches to genomics, such as  the HapMap, the ENCODE project, and The Cancer Genome Atlas [TCGA]. I have not explored these for the sake of brevity.

Wednesday, January 29, 2014

The Drunken Botanist - lessons from Amy Stewart's exploration of the plants that intoxicate

I love a good cocktail. The rise in the popularity of cocktail culture and craft cocktails has made me very happy. As with professional chefs, I find it amazing that people can still come up with unique creations. Our last dinner out included the Nasturtium (citrus vodka, St. Germain, and aperol - served down) for me and an Algonquin (rosemary-infused rye, fresh pineapple, dolin dry vermouth, and orange bitters - served up) for my husband. I admit that I rarely know much about the particulars of these beverages that have become an integral element of dining out. Thinking that it might be fun to learn more about the components that create these little glasses of deliciousness, I picked up The Drunken Botanist: The Plants That Create the World's Great Drinks from my local library. 
Like Wicked Bugs, The Drunken Botanist is written as a compendium of sorts with accompanying pen and ink illustrations of the plants described. Here, Stewart focuses on the plants that people have used throughout history to create alcoholic beverages. There is good coverage of both the classic ingredients (e.g., rye, wheat, hops, and grapes) and the plants used for the mixers and garnishes that are essential to create the perfect cocktail. In the spirit of the book, here is a litany of things that I learned:


  • The invention of the Moscow Mule highlights the kind of story I love. The drink was first created in 1941 through the collaboration of a vodka distributor, who hoped to introduce Americans to vodka, and a bartender, who had extra ginger beer in stock. Because the bartender's girlfriend owned a company that manufactured copper mugs, these became an element in the recipe. A recent rise in the cocktail's popularity has led to an increase in thefts of the distinctive copper mugs. (In the course of my research, I noticed that Wikipedia has a slightly different version of the story of the invention of the drink, which is to be expected.)
  • The distinctive smell of the dentist office is caused by the use of clove extract as a dental anesthetic.
  • The fragrance of jasmine flowers is due to several compounds, including phenyl-acetic acid. Based on genetic differences, some people find that jasmine flowers smell like honey, while others compare the scent to urine. This is similar to the small genetic differences that cause some people to perceive a horrible smell in urine after eating asparagus or to find that cilantro tastes like soap (Julia Child and I share that one).
  • Some figs must be pollinated by a wasp in order to reproduce. The wasp then lays its eggs inside the fig and dies there. Those figs would contain little bits of wasp carcass. Most figs in use today can bear fruit without pollination. This tidbit makes me love figs just a little bit more.
  • I was surprised by the number of stories about the link between alcoholic beverages and scurvy. For example, in the 1500s, the British navy included beer in their fleet's rations, both because water would spoil at sea and to keep the sailors happy. Unfortunately, beer also went bad on longer voyages, which led to the use of grog (rum mixed with water, lime juice, and sugar). The lime juice was initially added to make the drink palatable, but it had the indirect result of improving the sailors' health. In some cases, the vitamin C deficiency was combated with spruce beer; spruce trees produce ascorbic acid to help them survive the cold. Spanish explorers used bitter orange as a treatment for scurvy.  In the course of their travels, they left seeds on an island called Curaçao, where the bitter oranges are the ingredient in the eponymous liqueur.
  • Initial attempts to make wine from grapes grown in America were abject failures; both native and imported vines were unsuccessful. One problem was an aphid called phylloxera; the American grapevines were resistant to the pest, but European vines were not. Unfortunately, Americans sent infected grapevines to France, where the aphids quickly devastated the wine industry there. The solution: grafting American vines onto old European vines. The second problem was that the American grapes had undergone natural selection by birds, while the European vines had been subjected to hundreds of years of artificial selection by humans. Even today, researchers are working on making palatable wines from the grape vines native to America. 
  • There were numerous mentions of the Dogfish Brewery, who are resurrecting old approaches to making beer. In collaboration with a molecular archeologist, they have recreated several ancient beers based on the discoveries at dig sites.
There are probably other fascinating stories that I am missing, but I think I need to go make a cocktail.

Wednesday, January 15, 2014

Why I can't go to SeaWorld again: a comment on the movie Blackfish

Growing up in Florida, my interest in science was spurred by my love of the ocean. I decided I wanted to be a marine biologist at a very young age. Later, I thought that becoming a trainer at SeaWorld would be the perfect job. My subsequent interest in animal rights and environmentalism made me lose my fondness for SeaWorld.


My dolphin encounter.
When I visited my family in Florida in 2012, my mother suggested that we go to SeaWorld. I figured it was a good compromise as I certainly did not want to go to Disney and I did feel some obligation to let my son experience the place that once brought me such joy. We had a nice day in the park. I touched a dolphin for the first time and got so excited that I flashed back to my younger self. At the end of the day, we went to see the orca show. In past visits, this was always my favorite part, but it had been the better part of 20 years since my last trip to SeaWorld. During the show, I started crying; I eventually realized that I was crying for these poor whales, who were stuck inside this relatively small tank in an overly warm tourist attraction. After that experience, I concluded that I would probably not come back to Sea World.

Last week I watched Blackfish on Netflix, which solidified my opinion. The documentary explores the story of the killer whale Tilikum, who has been linked to the deaths of three individuals during his time in captivity. The documentary is based primarily on interviews with former SeaWorld trainers as well as killer whale experts. The main complaint against SeaWorld Orlando (SWO) in the film is that they did not accurately represent the threat that Tilikum, who had killed one trainer before arriving in Orlando in 1992, might pose to the trainers there. According to the trainers interviewed in the film, SWO never made that history or the incidents that may have precipitated that event known to the trainers. Later, Tilikum was involved in the strange death of a tourist who allegedly wandered into the tank. SWO claimed that hypothermia killed the man, rather than by an attack by the killer whale.





In February 2010, trainer Dawn Brancheau was killed by Tilikum. SWO claims that Brancheau's death was due to trainer error. The other trainers in the film argue that this was not the case. A lawsuit by OSHA eventually forced SeaWorld to remove the trainers from the tanks with the animals. SWO isolated Tilikum and kept him from performing, as least until until 2011. However, Tilikum is not likely to leave the park as he has been incredibly profitable as a breeder: the bull orca has sired 21 offspring during his time in captivity. According to the film, Tilikum is frequently found nearly immobile for hours at a time in his tank. They speculate that his large size and his treatment while in the Sealand park in British Columbia may be the reason for his erratic behavior. 

In addition, the film charges that SeaWorld does not accurately present scientific facts about killer whales. Science education and species preservation has always been a strong defensive point for the park. However, comparing the talking points of the former and current trainers and tour guides with the facts, it seems that teaching people the science of killer whales is not a priority for the park, especially if the facts can make the organization look bad. For example, whales in captivity frequently have a dorsal fin that is flopped over. SeaWorld claims that this is common in the wild as well. However, the killer whale expert interviewed states that this is only observed in about 1% of whales in the wild. The park also claims that the whales in captivity have a similar lifespan to those in the wild; in fact, captive whales live 30-50 years while those in the wild live 50-90 years. In the end, the film confirmed my view that SeaWorld is just another theme park, which puts its own interests above both those of its animals and its workers.

The film ends with a powerful scene, as the former trainers go on a whale watching cruise; they all seem emotional as they observe a pod of killer whales in their natural habitat, jumping and swimming in the open ocean with their family intact. The film succeeded in making its case against the capture and captivity of whales. It convinced me that I should never go back to SeaWorld. Now I just have to break the news to my mom.

Sunday, December 1, 2013

The Wandering Gene: BRCA1 mutations and population genetics

For some time I have been searching for a book similar to Rebecca Skloot's book about Henrietta Lacks. After some searching on Amazon, I found The Wandering Gene and the Indian Princess: Race, Religion, and DNA, which a number of review suggested was just as good. Because it was on the shelves of my local library, I picked it up immediately. Jeff Wheelwright's book examines the population genetics of a particular BRCA1 mutation. The BRCA1 and BRCA2 (breast cancer 1 and 2) genes were first linked to heritable breast and ovarian cancer (HBOC) in the early nineties. Since the initial discovery of the genes, scientists have identified many mutations in BRCA1 and 2 that are linked with HBOC as well as other cancers.

When functioning properly, the BRCA tumor suppressor genes produce proteins (breast cancer type 1/2 susceptibility protein) that are primarily involved in DNA repair. These proteins ensure that cells with errors in their DNA sequence either fix the mistakes or are destroyed. When a BRCA mutation is present, there is still a wild type ("normal") copy of the BRCA gene on the matching chromosome. Thus, the presence of a BRCA mutation is not necessarily an assurance of getting cancer (cancer risk rates for BRCA mutation carriers range from 35-80%, depending on the study and the type of cancer). If something occurs to alter the function of the wild type copy of the gene, then the cell is left with no functional BRCA1 or 2. Thus, DNA errors become more prevalent, which makes it more likely that a healthy cell will become a cancer cell. BRCA mutations account for only 10% of breast cancers; the majority of cancers are sporadic, caused by random rather than inherited mutations.  

The Wandering Gene focuses on the BRCA1 185delAG mutation; this mutation is due to the deletion (del) of two DNA residues (A and G, or adenine and guanine) at position 185, which results in a frame shift (or misreading) in the DNA sequence and ultimately the sequence of the protein that the DNA encodes**. This particular BRCA1 mutation has been linked to Ashkenazi or Eastern European Jews. Here, the author meets the Medinas, an Hispano family from New Mexico, as they receive genetic counseling and testing for the 185delAG mutation. The family is descendants of Native Americans and Spanish Catholics; thus, they were surprised to learn that they carry a mutation that has been linked to Ashkenazim. Geneticists and historians think that the 185delAG mutation in this group likely arose from a population of Jews from Spain, who were persecuted during the inquisition, converted to Catholicism, and then established themselves in the Americas.




The most interesting element of the book examines where the 185delAG mutation arose and how it became fixed in one particular population. There is evidence that a 2500-year-old Jewish founder could be the source of the mutation. Two particular characteristics of Jewish history (the cultural isolation and the large losses of population, such as from pogroms, forced relocation, and mass murders) led to frequent genetic bottlenecks. Bottlenecks occur due to the loss of genetic variability in a population; dramatic losses of population size can cause deleterious mutations (such as the BRCA1 mutation) to become fixed in a group. The founder effect can also explain the presence of other heritable diseases that are linked to the Jewish population, such as Tay-Sachs disease (carried by one in 25 Ashkenazim) and more than forty other genetic disorders.  It is important to note here that Jews are not more susceptible to genetic mutations; it is simply that, for a variety of reasons, they have been studied more thoroughly than other population groups. There are other examples of founder effects in small, isolated populations, including the Amish and fundamentalist Mormons.

The book also discusses the rise in genetic screening in certain populations where BRCA mutations are more common. Interestingly, such large-scale screening programs began in an effort to control Tay-Sachs disease as early as the 1980s. A group called Dor Yeshorim  screens Orthodox Jews for the most common genetic disorders and informs couples looking to wed whether or not they are a good genetic match. This approach has decreased the incidence of Tay-Sachs disease. The blood samples from Dor Yeshorim were useful for determining the prevalence of the 185delAG mutation in the Jewish population (1%). A recent story in the New York Times highlights the efforts in Israel, where one in 40 women carry a mutation in BRCA (compared to one in 100 women in the population as a whole), to begin universal screening for the mutations. The June 2013 Supreme Court decision, which ruled that naturally occurring human genes and mutations cannot be patented, should decrease the cost of the test in the United States. Prior to that decision, Myriad Genetics held patents on BRCA1 and 2, which led to high costs (more than $3000) for the test.

The subtitle of the book is definitely a good representation of what is inside; each of these topics seemed to get equal treatment. When the focus was on the DNA or race, the book held my interest. However, when the focus was more on religion, I found myself skipping pages. I didn't see how the history and beliefs of the Jehovah's witnesses helped the reader understand the genetics of this mutation. There were some surface similarities with Rebecca Skloot's book, as both have a very strong human angle. The book was a quick read, it taught me some new things about population genetics and BRCA mutations, and it served as an excellent jumping-off point for me to learn more.


**Footnote: If you imagine DNA as a sequence of three letter words, the phrase "The fat cat has the hat" becomes a very different sentence if two letters (at of cat) are eliminated and the spacing stays the same: "The fat cha sth eha t".

Sunday, November 17, 2013

Oh, the places I go! Another reason I love being a Scientific Editor

My job as a Scientific Editor gives me the opportunity to read much more broadly than I did when I worked in the lab. While researching manuscripts for suitability for the journal or while trying to find reviewers, I sometimes end up in very unexpected places. I discussed this briefly in my post about the book Elephants on Acid and Other Bizarre Experiments. I often find myself reading abstracts for papers that sound like fodder for Seriously, Science (formerly known as NCBI ROFL). The premise of this site is simple: post abstracts from PubMed with a simple description of the work. Of course, they tend to choose papers that sound pretty ridiculous on the surface. These are typically the types of papers that would garner criticisms about why such research should be funded. Here are some recent examples: "Study proves 'old person smell' is real"; "Curvy vs. straight - which glass ups your drinking rate?"


As a graduate student I studied the motility of the sperm from Ascaris, an intestinal parasite from pigs; we affectionately called our system "worm sperm". Thus, I understand the appeals and perils of working with an offbeat system. These unusual systems actually have important applications (otherwise they would not likely be funded). For example, worm sperm has a novel machinery for cell motility (more specifically, it uses a completely unique protein to power the movement of its amoeboid sperm), which could help us understand how more traditional cells crawl. Studying simple cells to understand more complex ones is a common approach in cell biology. The idea is that there should be conserved elements that should be comparable between the different cell types; such an approach can allow scientists to generate a minimal parts lists for a cellular process of interest. Thus, brewer's yeast can be used as a model system for a surprising number of cellular processes, even neurodegenerative diseases like Huntington's and Parkinson's.

A few weeks ago, I was looking for reviewers for a paper about protein stability during cryopreservation of heart tissues (now available in BBA - Proteins and Proteomics). The work could eventually have an impact on how tissues are stored prior to tissue transplants.  I found myself reading title after title about the stability of proteins after cryopreservation of semen of various types, especially boar and horse semen. The funny thing was -  I was not surprised to stumble upon these papers because I had seen them before. On the previous occasion, I was researching a paper on the proteomics of horse semen. These areas of research might elicit some giggles even from the seasoned scientist, but the work could have important implications for animal husbandry.

I recently evaluated a paper that described the protein in Venus fly traps responsible for digesting arthropods. Interestingly, it is a chitinase, an enzyme that can break down the chitinous exoskeleton of the fly trap's lunch (now published in BBA- Proteins and Proteomics). While searching for reviewers, I found a plethora of interesting papers, such as the mechanics of the opening and closing of Venus fly traps and proteomics to identify the components involved in digestion in a variety of carnivorous plants. I also see a lot of papers about insect venom. For example, we recently received a paper about the proteomics of fishing spider venom. As I learned in the book Wicked Bugs, insects and spiders have some pretty amazing (and terrifying) ways of attacking their prey. Some recently published papers demonstrate that understanding how the venom works can be useful for developing new pain killers as well as novel pesticides.

Every week I seem to find a new and strange corner of PubMed to explore. Sure, I still have some knee-jerk reactions and giggle when I read some of the titles. Generally, though, once I dig deeper to understand what the long-term goal of the work is, I tend to be amazed at the boundlessness of scientific curiosity and the ingenuity of scientists for finding new ways of solving problems.

Monday, October 14, 2013

The Poisoner's Handbook and my idea for a new tv show

I just finished reading The Poisoner's Handbook: Murder and the Birth of Forensic Medicine in Jazz Age New York. Similar to Sam Kean's book about the periodic table (The Disappearing Spoon), this book focuses on stories about some rather dangerous and fascinating chemistry. Here, author Deborah Blum culls stories from the Prohibition Era in New York City. Before that time, New York City's police department was poorly run. Then in 1918, Charles Norris was appointed as chief medical examiner (M.E.); Norris was the first M.E. who actually had suitable credentials for the position. Once in the department, Norris brought toxicologist Frank Gettler on board. Together, they helped to establish the role of forensic medicine in the investigation of crimes. Both Gettler and Norris worked countless hours in the laboratory to establish tests for the lethal doses of various poisons; they also investigated some of the more notorious crimes of the Prohibition Era.

Each chapter is focused on a different poison (e.g., radium, methyl alcohol). Blum chooses stories that are all linked to Gettler and Norris and the development of forensic medicine. A few of the chapters focus on what are likely seen as standard poisons, cyanide and arsenic. These poisons were readily available at pharmacies and hardware stores; thus, murders by these methods were almost commonplace. The work of Norris and Gettler established tests to help police convict poisoners who decided to use rat poison to get rid of an irksome husband or mother-in-law.

Of course, because the book focuses on the Prohibition Era, many stories described the effects of methyl alcohol and ethyl alcohol. When alcohol was outlawed in the US, the government decreed that industrial alcohol should increase the percentage of methyl alcohol. This was intended to decrease the chance that the alcohol would be imbibed. Instead, there was a sharp increase in the number of alcohol-related fatalities; these were mostly poor folks who couldn't afford safer alcohol. Blum discusses the chemists who were involved in bootlegging during this time period, which gave me an excellent idea for a new show: Breaking Bad meets Boardwalk Empire. Imagine the mild-mannered chemists like Walter White who found themselves in league with the unscrupulous bootleggers like Nucky Thompson!



from Wikipedia
The poor policy decisions behind prohibition were responsible for an increasing number of deaths; in addition, the lack of federal oversight of industry was also proving dangerous. For example, one company sold hair depilatories that included thallium; while the product did fulfill its promise of removing unsightly hair, it often made the users blind and eventually killed them. Another heart-breaking story, which I first read about in Radioactive, was that of the radium dial painters. In 1917, the Radium Corporation in Orange, New Jersey employed several young women to paint the faces of watches and other radium-dial instruments for the military. The employees shaped the tips of the paintbrush with their lips to produce the fine point necessary to make the small numbers on the dials. None of the employees found this behavior risky because radium was a popular panacea, which was present in a number of health tonics and spa treatments. Unfortunately, the women all became very ill; by 1924, nine of the dial painters died. The medical examiner in New Jersey (Harrison Martland) consulted with the NYC M.E.s to investigate these illnesses. They found that the living dial painters, called the "Radium Girls" by the press, were exhaling radon gas. The bones of the deceased dial painters were radioactive enough to generate an image on X-ray film and set off a radiation detector. The data gathered by the two groups of medical examiners were critical for the case brought by five of the Radium Girls, who were asking for a settlement from their former employer to help pay their medical bills. In the end, the women received a very small settlement ($10,000 in cash and complete medical care); while it was much less than they originally sought, they were happy to have any money while they were still living. Interestingly, the dial painters all died of aplastic anemia, which was also the cause of Marie Curie's death in 1934. 

Despite the amount of press that the case of the Radium Girls received, products containing radium were still on the market. It wasn't until the death of millionaire Eben Byers in 1931 that the safety of these products was called into question. On the advice of a physician, Byers was regularly drinking a product called "Radithor" for the treatment of an arm pain. The state of Byers' body was similar to those of the Radium Girls. Shortly after Norris and Gettler released the results of their autopsy, the government issued a warning regarding the safety of drugs like Radithor. In 1932, the products were officially banned by the government.

In the final analysis, The Poisoner's Handbook was interesting and included lots of off-beat stories from a strange time. However, its focus is more on history and forensics than chemistry. Thus, I slightly preferred The Disappearing Spoon.