Dinosaur Aunts, Bacterial Stowaways, & Insect Milk

Today’s guest post (originally posted here) is from Katie Hinde, an Assistant Professor in Human Evolutionary Biology at Harvard University.  Katie studies how variation in mother’s milk influences infant development in rhesus monkeys.  You can learn more about Katie and mammalian lactation by visiting her blog, Mammals Suck… Milk!.  Follow Katie on Twitter @Mammals_Suck.




Dinosaur Aunts, Bacterial Stowaways, & Insect Milk


Milk is everywhere. From the dairy aisle at the grocery store to the explosive cover of the Mother’s Day issue of Time magazine, the ubiquity of milk makes it easy to take for granted. But surprisingly, milk synthesis is evolutionarily older than mammals. Milk is even older than dinosaurs. Moreover, milk contains constituents that infants don’t digest, namely oligosaccharides, which are the preferred diet of the neonate’s intestinal bacteria (nom nom nom!)  And milk doesn’t just feed the infant, and the infant’s microbiome; the symbiotic bacteria are IN mother’s milk. 

Evolutionary Origins of Lactation
The fossil record, unfortunately, leaves little direct evidence of the soft-tissue structures that first secreted milk. Despite this, paleontologists can scrutinize morphological features of fossils, such as the presence or absence of milk teeth (diphyodonty), to infer clues about the emergence of “milk.” Genome-wide surveys of the expression and function of mammary genes across divergent taxa, and experimental evo-devo manipulations of particular genes also yield critical insights. As scientists begin to integrate information from complementary approaches, a clearer understanding of the evolution of lactation emerges.
 

In his recent paper, leading lactation theorist Dr. Olav Oftedal discusses the ancient origins of milk secretion (2012). He contends the first milk secretions originated ~310 million years ago (MYA) in synapsids, a lineage ancestral to mammals and contemporaries with sauropsids, the ancestors of reptiles, birds, and dinosaurs. Synapsids and sauropsids produced eggs with multiple membrane layers, known as amniote eggs. Such eggs could be laid on land. However, synapsid eggs had permeable, parchment-like shells and were vulnerable to water loss. Burying these eggs in damp soil or sand near water resources- like sea turtles do- wasn’t an option, posits Oftedal. The buried temperatures would have likely been too cold for the higher metabolism of synapsids. But incubating eggs in a nest would have evaporated water from the egg. The synapsid egg was proverbially between a rock and a hard place: too warm to bury, too permeable to incubate. 

Ophiacodon by Dmitri Bogdanov

Luckily for us, a mutation gave rise to secretions from glandular skin on the belly of the synapsid parent. This mechanism replenished water lost during incubation, allowing synapsids to lay eggs in a variety of terrestrial environments. As other mutations randomly arose and were favored by selection, milk composition became increasingly complex, incorporating nutritive, protective, and hormonal factors (Oftedal 2012). Some of these milk constituents are shunted into milk from maternal blood, some- although also present in the maternal blood stream- are regulated locally in the mammary gland, and some very special constituents are unique to milk. Lactose and oligosaccharides (a sugar with lactose at the reducing end) are two constituents unique to mammalian milk, but are interestingly divergent among mammals living today. 

Illustration by Carl Buell
Mammalian and Primate Divergences:  Milk Composition
         
Among all mammals studied to date, lactose and oligosaccharides are the primary sugars in milk. Lactose is synthesized in mammary glands only. Urashima and colleagues explain that lactose synthesis is contingent on the mammalian-specific protein alpha-lactalbumin (2012). Alpha-lactalbumin is very similar in amino-acid structure to C-type lysozyme, a more ancient protein found throughout vertebrates and insects. C-type lysozyme acts as an anti-bacterial agent. Oligosaccharides are predominant in the milks of marsupials and egg-laying monotremes (i.e. the platypus), but lactose is the most prevalent sugar in the milk of most placental (aka eutherian) mammals. Interestingly, the oligosaccharides in the milk of placental mammals are most similar to the oligosaccharides in the milk of monotremes. Unique oligosaccharides in marsupial milk emerged after the divergence of placental mammals. 

Marsupial and monotreme young seemingly digest oligosaccharides. Among placental mammals, however, young do not have the requisite enzymes in their stomach and small intestine to utilize oligosaccharides themselves. Why do eutherian mothers synthesize oligosaccharides in milk, if infants don’t digest them?

In May, Anna Petherick’s post “Multi-tasking Milk Oligosaccharides” revealed that oligosaccharides serve a number of critical roles for supporting the healthy colonization and maintenance of the infant’s intestinal microbiome. Beneficial bacterial symbionts contribute to the digestion of nutrients from our food. Just as importantly, they are an essential component of the immune system, defending their host against many ingested pathogens. The structures of milk oligosaccharides have been described for a number of primates, including humans, and data are now available from all major primate clades; strepsirrhines (i.e. lemurs), New World monkey (i.e. capuchin), Old World monkey (i.e. rhesus), and apes (i.e. chimpanzee). 

        
Among all non-human primates studied to date, Type II oligosaccharides are most prevalent (Type II oligosaccharides contain lacto-N-biose I). Type I oligosaccharides (containing N-acetyllactosamine) are absent, or in much lower concentrations than Type II(Taufik et al. 2012). 

In human milk, there is a much greater diversity and higher abundance of milk oligosaccharides than found in the milk of other primates. Most primate taxa have between 5-30 milk oligosaccharides; humans have ~200. Even more astonishingly, humans predominantly produce Type I oligosaccharides, the preferred food of the most prevalent bacterium in the healthy human infant gut- Bifidobacteria (Urashima et al 2012, Taufik et al. 2012).

         
Human infants have bigger brains and an earlier age at weaning than do our closest ape relatives. Many anthropologists have hypothesized that constituents in mother’s milk, such as higher fat concentrations or unique fatty acids, underlie these differences in human development. But only oligosaccharides, a constituent that the human infant does not itself utilize, are demonstrably derived from our primate relatives (Hinde and Milligan 2011). At some point in human evolution there must have been strong selective pressure to optimize the symbiotic relationship between the infant microbiome and the milk mothers synthesize to support it. The human and Bifidobacteria genomes show signatures of co-evolution, but the selective pressures and their timing remain to be understood.

Vertical Transmission of Bacteria via Milk
In the womb, the infant is largely protected from maternal bacteria due to the placental barrier. But upon birth, the infant is confronted by a teeming microbial milieu that is both a challenge and an opportunity. The first inoculation of commensal bacteria occurs during delivery as the infant passes through the birth canal and is exposed to a broad array of maternal microbes. Infants born via C-section are instead, and unfortunately, colonized by the microbes “running around” the hospital. But exposure to the mother’s microbiome continues long after birth. Evidence for vertical transmission of maternal bacteria via milk has been shown in rodents, monkeys(Jin et al. 2011), humans(Martin et al. 2012), and… insects. 

Yes, INSECTS!

A number of insects have evolved the ability to rely on nutritionally incomplete food sources. They are able to do so because bacteria that live inside their cells provide what the food does not. These bacteria are known as endosymbionts and the specialized cells the host provides for them to live in are called bacteriocytes. For example, the tsetse fly has a bacterium, Wigglesworthia glossinidia,* that provides B vitamins not available from blood meals. Um, if you are squeamish, don’t read the previous sentence.     
 *I submit the tsetse fly and its bacterial symbiont (Wigglesworthia glossinidia
for consideration as the number one mutualism in which the common name of the host 
and the Latin name of the bacteria are awesome to say out loud! 
Bring on your challenger teams.
Hosokawa and colleagues recently revealed the Russian nesting dolls that are bats (Miniopterus fuliginosus), bat flies (Nycteribiidae), and endosymbiotic bacteria (proposed name Aschnera chenzii)(2012). Bat flies are the obligate ectoparasites of bats (Peterson et al. 2007). They feed on the blood of their bat hosts, and for nearly their entire lifespan, bat flies live in the fur of their bat hosts. Females briefly leave their host to deposit pupae on stationary surfaces within the bat roost. 

Bat flies are even more crazy amazing because they have a uterus and provide MILK internally through the uterus to larva! Male and female bat flies have endosymbiotic bacteria living in bacteriocytes along the sides of their abdominal segments (revealed by 16S rRNA). Additionally, females host bacteria inside the milk gland tubules, “indicating the presence of endosymbiont cells in milk gland secretion”. 

The authors are not yet certain of the specific nutritional role that these bacterial endosymbionts play in the bat fly host. The bacteria may provide B vitamins, as other bacterial symbionts of blood-consuming insects are known to do. My main question is what is the exact role of the bacteria in the milk gland tubules? Are they there to add nutritional value to the milk for the larva, to stowaway in milk for vertical transmission to larva, or both?  

Conclusions
The studies described above represent new frontiers in lactation research. The capacity to secrete “milk” has been evolving since before the age of dinosaurs, but we still know relatively little about the diversity of milks produced by mammals today. Even less understood are the consequences and functions of various milk constituents in the developing neonate. Despite the many unknowns, it is increasingly evident that mother’s milk cultivates the infant’s gut bacterial communities in fascinating ways. A microbiome milk-ultivation, if you will, that has far reaching implications for human development, nutrition, and health.  Integrating an evolutionary perspective into these newly discovered complexities of milk dynamics allows us to reimagine the world of “dairy” science.

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Hinde & Milligan. 2011. Primate milk synthesis: Proximate mechanisms and ultimate perspectives. Evol Anthropol 20:9-23.
Hosokawa et al. 2012. Reductive genome evolution, host-symbiont co-speciation, and uterine transmission of endosymbiotic bacteria in bat flies. ISME Journal. 6: 577-587
Jin et al. 2011. Species diversity and abundance of lactic acid bacteria in the milk of rhesus monkeys (Macaca mulatta). J Med Primatol. 40: 52-58
Martin et al. 2012. Sharing of Bacterial Strains Between Breast Milk and Infant Feces. J Hum Lact. 28: 36-44
Oftedal 2012. The evolution of milk secretion and its ancient origins. Animal. 6: 355-368.
Peterson et al. 2007. The phylogeny and evolution of host choice in the Hippoboscoidea(Diptera) as reconstructed using four molecular markers. Mol Phylogenet Evol. 45 :111-22
Taufik et al. 2012. Structural characterization of neutral and acidic oligosaccharides in the milks of strepsirrhine primates: greater galago, aye-aye, Coquerel’s sifaka, and mongoose lemur. Glycoconj J. 29: 119-134.
Urashima, Fukuda, & Messer. 2012. Evolution of milk oligosaccharides and lactose: a hypothesis. Animal. 6: 369-374.

Biology Explainer: The big 4 building blocks of life–carbohydrates, fats, proteins, and nucleic acids

The short version
  • The four basic categories of molecules for building life are carbohydrates, lipids, proteins, and nucleic acids.
  • Carbohydrates serve many purposes, from energy to structure to chemical communication, as monomers or polymers.
  • Lipids, which are hydrophobic, also have different purposes, including energy storage, structure, and signaling.
  • Proteins, made of amino acids in up to four structural levels, are involved in just about every process of life.                                                                                                      
  • The nucleic acids DNA and RNA consist of four nucleotide building blocks, and each has different purposes.
The longer version
Life is so diverse and unwieldy, it may surprise you to learn that we can break it down into four basic categories of molecules. Possibly even more implausible is the fact that two of these categories of large molecules themselves break down into a surprisingly small number of building blocks. The proteins that make up all of the living things on this planet and ensure their appropriate structure and smooth function consist of only 20 different kinds of building blocks. Nucleic acids, specifically DNA, are even more basic: only four different kinds of molecules provide the materials to build the countless different genetic codes that translate into all the different walking, swimming, crawling, oozing, and/or photosynthesizing organisms that populate the third rock from the Sun.

                                                  

Big Molecules with Small Building Blocks

The functional groups, assembled into building blocks on backbones of carbon atoms, can be bonded together to yield large molecules that we classify into four basic categories. These molecules, in many different permutations, are the basis for the diversity that we see among living things. They can consist of thousands of atoms, but only a handful of different kinds of atoms form them. It’s like building apartment buildings using a small selection of different materials: bricks, mortar, iron, glass, and wood. Arranged in different ways, these few materials can yield a huge variety of structures.

We encountered functional groups and the SPHONC in Chapter 3. These components form the four categories of molecules of life. These Big Four biological molecules are carbohydrates, lipids, proteins, and nucleic acids. They can have many roles, from giving an organism structure to being involved in one of the millions of processes of living. Let’s meet each category individually and discover the basic roles of each in the structure and function of life.
Carbohydrates

You have met carbohydrates before, whether you know it or not. We refer to them casually as “sugars,” molecules made of carbon, hydrogen, and oxygen. A sugar molecule has a carbon backbone, usually five or six carbons in the ones we’ll discuss here, but it can be as few as three. Sugar molecules can link together in pairs or in chains or branching “trees,” either for structure or energy storage.

When you look on a nutrition label, you’ll see reference to “sugars.” That term includes carbohydrates that provide energy, which we get from breaking the chemical bonds in a sugar called glucose. The “sugars” on a nutrition label also include those that give structure to a plant, which we call fiber. Both are important nutrients for people.

Sugars serve many purposes. They give crunch to the cell walls of a plant or the exoskeleton of a beetle and chemical energy to the marathon runner. When attached to other molecules, like proteins or fats, they aid in communication between cells. But before we get any further into their uses, let’s talk structure.

The sugars we encounter most in basic biology have their five or six carbons linked together in a ring. There’s no need to dive deep into organic chemistry, but there are a couple of essential things to know to interpret the standard representations of these molecules.

Check out the sugars depicted in the figure. The top-left molecule, glucose, has six carbons, which have been numbered. The sugar to its right is the same glucose, with all but one “C” removed. The other five carbons are still there but are inferred using the conventions of organic chemistry: Anywhere there is a corner, there’s a carbon unless otherwise indicated. It might be a good exercise for you to add in a “C” over each corner so that you gain a good understanding of this convention. You should end up adding in five carbon symbols; the sixth is already given because that is conventionally included when it occurs outside of the ring.

On the left is a glucose with all of its carbons indicated. They’re also numbered, which is important to understand now for information that comes later. On the right is the same molecule, glucose, without the carbons indicated (except for the sixth one). Wherever there is a corner, there is a carbon, unless otherwise indicated (as with the oxygen). On the bottom left is ribose, the sugar found in RNA. The sugar on the bottom right is deoxyribose. Note that at carbon 2 (*), the ribose and deoxyribose differ by a single oxygen.

The lower left sugar in the figure is a ribose. In this depiction, the carbons, except the one outside of the ring, have not been drawn in, and they are not numbered. This is the standard way sugars are presented in texts. Can you tell how many carbons there are in this sugar? Count the corners and don’t forget the one that’s already indicated!

If you said “five,” you are right. Ribose is a pentose (pent = five) and happens to be the sugar present in ribonucleic acid, or RNA. Think to yourself what the sugar might be in deoxyribonucleic acid, or DNA. If you thought, deoxyribose, you’d be right.

The fourth sugar given in the figure is a deoxyribose. In organic chemistry, it’s not enough to know that corners indicate carbons. Each carbon also has a specific number, which becomes important in discussions of nucleic acids. Luckily, we get to keep our carbon counting pretty simple in basic biology. To count carbons, you start with the carbon to the right of the non-carbon corner of the molecule. The deoxyribose or ribose always looks to me like a little cupcake with a cherry on top. The “cherry” is an oxygen. To the right of that oxygen, we start counting carbons, so that corner to the right of the “cherry” is the first carbon. Now, keep counting. Here’s a little test: What is hanging down from carbon 2 of the deoxyribose?

If you said a hydrogen (H), you are right! Now, compare the deoxyribose to the ribose. Do you see the difference in what hangs off of the carbon 2 of each sugar? You’ll see that the carbon 2 of ribose has an –OH, rather than an H. The reason the deoxyribose is called that is because the O on the second carbon of the ribose has been removed, leaving a “deoxyed” ribose. This tiny distinction between the sugars used in DNA and RNA is significant enough in biology that we use it to distinguish the two nucleic acids.

In fact, these subtle differences in sugars mean big differences for many biological molecules. Below, you’ll find a couple of ways that apparently small changes in a sugar molecule can mean big changes in what it does. These little changes make the difference between a delicious sugar cookie and the crunchy exoskeleton of a dung beetle.

Sugar and Fuel

A marathon runner keeps fuel on hand in the form of “carbs,” or sugars. These fuels provide the marathoner’s straining body with the energy it needs to keep the muscles pumping. When we take in sugar like this, it often comes in the form of glucose molecules attached together in a polymer called starch. We are especially equipped to start breaking off individual glucose molecules the minute we start chewing on a starch.

Double X Extra: A monomer is a building block (mono = one) and a polymer is a chain of monomers. With a few dozen monomers or building blocks, we get millions of different polymers. That may sound nutty until you think of the infinity of values that can be built using only the numbers 0 through 9 as building blocks or the intricate programming that is done using only a binary code of zeros and ones in different combinations.

Our bodies then can rapidly take the single molecules, or monomers, into cells and crack open the chemical bonds to transform the energy for use. The bonds of a sugar are packed with chemical energy that we capture to build a different kind of energy-containing molecule that our muscles access easily. Most species rely on this process of capturing energy from sugars and transforming it for specific purposes.

Polysaccharides: Fuel and Form

Plants use the Sun’s energy to make their own glucose, and starch is actually a plant’s way of storing up that sugar. Potatoes, for example, are quite good at packing away tons of glucose molecules and are known to dieticians as a “starchy” vegetable. The glucose molecules in starch are packed fairly closely together. A string of sugar molecules bonded together through dehydration synthesis, as they are in starch, is a polymer called a polysaccharide (poly = many; saccharide = sugar). When the monomers of the polysaccharide are released, as when our bodies break them up, the reaction that releases them is called hydrolysis.

Double X Extra: The specific reaction that hooks one monomer to another in a covalent bond is called dehydration synthesis because in making the bond–synthesizing the larger molecule–a molecule of water is removed (dehydration). The reverse is hydrolysis (hydro = water; lysis = breaking), which breaks the covalent bond by the addition of a molecule of water.

Although plants make their own glucose and animals acquire it by eating the plants, animals can also package away the glucose they eat for later use. Animals, including humans, store glucose in a polysaccharide called glycogen, which is more branched than starch. In us, we build this energy reserve primarily in the liver and access it when our glucose levels drop.

Whether starch or glycogen, the glucose molecules that are stored are bonded together so that all of the molecules are oriented the same way. If you view the sixth carbon of the glucose to be a “carbon flag,” you’ll see in the figure that all of the glucose molecules in starch are oriented with their carbon flags on the upper left.

The orientation of monomers of glucose in polysaccharides can make a big difference in the use of the polymer. The glucoses in the molecule on the top are all oriented “up” and form starch. The glucoses in the molecule on the bottom alternate orientation to form cellulose, which is quite different in its function from starch.

Storing up sugars for fuel and using them as fuel isn’t the end of the uses of sugar. In fact, sugars serve as structural molecules in a huge variety of organisms, including fungi, bacteria, plants, and insects.

The primary structural role of a sugar is as a component of the cell wall, giving the organism support against gravity. In plants, the familiar old glucose molecule serves as one building block of the plant cell wall, but with a catch: The molecules are oriented in an alternating up-down fashion. The resulting structural sugar is called cellulose.

That simple difference in orientation means the difference between a polysaccharide as fuel for us and a polysaccharide as structure. Insects take it step further with the polysaccharide that makes up their exoskeleton, or outer shell. Once again, the building block is glucose, arranged as it is in cellulose, in an alternating conformation. But in insects, each glucose has a little extra added on, a chemical group called an N-acetyl group. This addition of a single functional group alters the use of cellulose and turns it into a structural molecule that gives bugs that special crunchy sound when you accidentally…ahem…step on them.

These variations on the simple theme of a basic carbon-ring-as-building-block occur again and again in biological systems. In addition to serving roles in structure and as fuel, sugars also play a role in function. The attachment of subtly different sugar molecules to a protein or a lipid is one way cells communicate chemically with one another in refined, regulated interactions. It’s as though the cells talk with each other using a specialized, sugar-based vocabulary. Typically, cells display these sugary messages to the outside world, making them available to other cells that can recognize the molecular language.

Lipids: The Fatty Trifecta

Starch makes for good, accessible fuel, something that we immediately attack chemically and break up for quick energy. But fats are energy that we are supposed to bank away for a good long time and break out in times of deprivation. Like sugars, fats serve several purposes, including as a dense source of energy and as a universal structural component of cell membranes everywhere.

Fats: the Good, the Bad, the Neutral

Turn again to a nutrition label, and you’ll see a few references to fats, also known as lipids. (Fats are slightly less confusing that sugars in that they have only two names.) The label may break down fats into categories, including trans fats, saturated fats, unsaturated fats, and cholesterol. You may have learned that trans fats are “bad” and that there is good cholesterol and bad cholesterol, but what does it all mean?

Let’s start with what we mean when we say saturated fat. The question is, saturated with what? There is a specific kind of dietary fat call the triglyceride. As its name implies, it has a structural motif in which something is repeated three times. That something is a chain of carbons and hydrogens, hanging off in triplicate from a head made of glycerol, as the figure shows.  Those three carbon-hydrogen chains, or fatty acids, are the “tri” in a triglyceride. Chains like this can be many carbons long.

Double X Extra: We call a fatty acid a fatty acid because it’s got a carboxylic acid attached to a fatty tail. A triglyceride consists of three of these fatty acids attached to a molecule called glycerol. Our dietary fat primarily consists of these triglycerides.

Triglycerides come in several forms. You may recall that carbon can form several different kinds of bonds, including single bonds, as with hydrogen, and double bonds, as with itself. A chain of carbon and hydrogens can have every single available carbon bond taken by a hydrogen in single covalent bond. This scenario of hydrogen saturation yields a saturated fat. The fat is saturated to its fullest with every covalent bond taken by hydrogens single bonded to the carbons.

Saturated fats have predictable characteristics. They lie flat easily and stick to each other, meaning that at room temperature, they form a dense solid. You will realize this if you find a little bit of fat on you to pinch. Does it feel pretty solid? That’s because animal fat is saturated fat. The fat on a steak is also solid at room temperature, and in fact, it takes a pretty high heat to loosen it up enough to become liquid. Animals are not the only organisms that produce saturated fat–avocados and coconuts also are known for their saturated fat content.

The top graphic above depicts a triglyceride with the glycerol, acid, and three hydrocarbon tails. The tails of this saturated fat, with every possible hydrogen space occupied, lie comparatively flat on one another, and this kind of fat is solid at room temperature. The fat on the bottom, however, is unsaturated, with bends or kinks wherever two carbons have double bonded, booting a couple of hydrogens and making this fat unsaturated, or lacking some hydrogens. Because of the space between the bumps, this fat is probably not solid at room temperature, but liquid.

You can probably now guess what an unsaturated fat is–one that has one or more hydrogens missing. Instead of single bonding with hydrogens at every available space, two or more carbons in an unsaturated fat chain will form a double bond with carbon, leaving no space for a hydrogen. Because some carbons in the chain share two pairs of electrons, they physically draw closer to one another than they do in a single bond. This tighter bonding result in a “kink” in the fatty acid chain.

In a fat with these kinks, the three fatty acids don’t lie as densely packed with each other as they do in a saturated fat. The kinks leave spaces between them. Thus, unsaturated fats are less dense than saturated fats and often will be liquid at room temperature. A good example of a liquid unsaturated fat at room temperature is canola oil.

A few decades ago, food scientists discovered that unsaturated fats could be resaturated or hydrogenated to behave more like saturated fats and have a longer shelf life. The process of hydrogenation–adding in hydrogens–yields trans fat. This kind of processed fat is now frowned upon and is being removed from many foods because of its associations with adverse health effects. If you check a food label and it lists among the ingredients “partially hydrogenated” oils, that can mean that the food contains trans fat.

Double X Extra: A triglyceride can have up to three different fatty acids attached to it. Canola oil, for example, consists primarily of oleic acid, linoleic acid, and linolenic acid, all of which are unsaturated fatty acids with 18 carbons in their chains.

Why do we take in fat anyway? Fat is a necessary nutrient for everything from our nervous systems to our circulatory health. It also, under appropriate conditions, is an excellent way to store up densely packaged energy for the times when stores are running low. We really can’t live very well without it.

Phospholipids: An Abundant Fat

You may have heard that oil and water don’t mix, and indeed, it is something you can observe for yourself. Drop a pat of butter–pure saturated fat–into a bowl of water and watch it just sit there. Even if you try mixing it with a spoon, it will just sit there. Now, drop a spoon of salt into the water and stir it a bit. The salt seems to vanish. You’ve just illustrated the difference between a water-fearing (hydrophobic) and a water-loving (hydrophilic) substance.

Generally speaking, compounds that have an unequal sharing of electrons (like ions or anything with a covalent bond between oxygen and hydrogen or nitrogen and hydrogen) will be hydrophilic. The reason is that a charge or an unequal electron sharing gives the molecule polarity that allows it to interact with water through hydrogen bonds. A fat, however, consists largely of hydrogen and carbon in those long chains. Carbon and hydrogen have roughly equivalent electronegativities, and their electron-sharing relationship is relatively nonpolar. Fat, lacking in polarity, doesn’t interact with water. As the butter demonstrated, it just sits there.

There is one exception to that little maxim about fat and water, and that exception is the phospholipid. This lipid has a special structure that makes it just right for the job it does: forming the membranes of cells. A phospholipid consists of a polar phosphate head–P and O don’t share equally–and a couple of nonpolar hydrocarbon tails, as the figure shows. If you look at the figure, you’ll see that one of the two tails has a little kick in it, thanks to a double bond between the two carbons there.

Phospholipids form a double layer and are the major structural components of cell membranes. Their bend, or kick, in one of the hydrocarbon tails helps ensure fluidity of the cell membrane. The molecules are bipolar, with hydrophilic heads for interacting with the internal and external watery environments of the cell and hydrophobic tails that help cell membranes behave as general security guards.

The kick and the bipolar (hydrophobic and hydrophilic) nature of the phospholipid make it the perfect molecule for building a cell membrane. A cell needs a watery outside to survive. It also needs a watery inside to survive. Thus, it must face the inside and outside worlds with something that interacts well with water. But it also must protect itself against unwanted intruders, providing a barrier that keeps unwanted things out and keeps necessary molecules in.

Phospholipids achieve it all. They assemble into a double layer around a cell but orient to allow interaction with the watery external and internal environments. On the layer facing the inside of the cell, the phospholipids orient their polar, hydrophilic heads to the watery inner environment and their tails away from it. On the layer to the outside of the cell, they do the same.
As the figure shows, the result is a double layer of phospholipids with each layer facing a polar, hydrophilic head to the watery environments. The tails of each layer face one another. They form a hydrophobic, fatty moat around a cell that serves as a general gatekeeper, much in the way that your skin does for you. Charged particles cannot simply slip across this fatty moat because they can’t interact with it. And to keep the fat fluid, one tail of each phospholipid has that little kick, giving the cell membrane a fluid, liquidy flow and keeping it from being solid and unforgiving at temperatures in which cells thrive.

Steroids: Here to Pump You Up?

Our final molecule in the lipid fatty trifecta is cholesterol. As you may have heard, there are a few different kinds of cholesterol, some of which we consider to be “good” and some of which is “bad.” The good cholesterol, high-density lipoprotein, or HDL, in part helps us out because it removes the bad cholesterol, low-density lipoprotein or LDL, from our blood. The presence of LDL is associated with inflammation of the lining of the blood vessels, which can lead to a variety of health problems.

But cholesterol has some other reasons for existing. One of its roles is in the maintenance of cell membrane fluidity. Cholesterol is inserted throughout the lipid bilayer and serves as a block to the fatty tails that might otherwise stick together and become a bit too solid.

Cholesterol’s other starring role as a lipid is as the starting molecule for a class of hormones we called steroids or steroid hormones. With a few snips here and additions there, cholesterol can be changed into the steroid hormones progesterone, testosterone, or estrogen. These molecules look quite similar, but they play very different roles in organisms. Testosterone, for example, generally masculinizes vertebrates (animals with backbones), while progesterone and estrogen play a role in regulating the ovulatory cycle.

Double X Extra: A hormone is a blood-borne signaling molecule. It can be lipid based, like testosterone, or short protein, like insulin.

Proteins

As you progress through learning biology, one thing will become more and more clear: Most cells function primarily as protein factories. It may surprise you to learn that proteins, which we often talk about in terms of food intake, are the fundamental molecule of many of life’s processes. Enzymes, for example, form a single broad category of proteins, but there are millions of them, each one governing a small step in the molecular pathways that are required for living.

Levels of Structure

Amino acids are the building blocks of proteins. A few amino acids strung together is called a peptide, while many many peptides linked together form a polypeptide. When many amino acids strung together interact with each other to form a properly folded molecule, we call that molecule a protein.

For a string of amino acids to ultimately fold up into an active protein, they must first be assembled in the correct order. The code for their assembly lies in the DNA, but once that code has been read and the amino acid chain built, we call that simple, unfolded chain the primary structure of the protein.

This chain can consist of hundreds of amino acids that interact all along the sequence. Some amino acids are hydrophobic and some are hydrophilic. In this context, like interacts best with like, so the hydrophobic amino acids will interact with one another, and the hydrophilic amino acids will interact together. As these contacts occur along the string of molecules, different conformations will arise in different parts of the chain. We call these different conformations along the amino acid chain the protein’s secondary structure.

Once those interactions have occurred, the protein can fold into its final, or tertiary structure and be ready to serve as an active participant in cellular processes. To achieve the tertiary structure, the amino acid chain’s secondary interactions must usually be ongoing, and the pH, temperature, and salt balance must be just right to facilitate the folding. This tertiary folding takes place through interactions of the secondary structures along the different parts of the amino acid chain.

The final product is a properly folded protein. If we could see it with the naked eye, it might look a lot like a wadded up string of pearls, but that “wadded up” look is misleading. Protein folding is a carefully regulated process that is determined at its core by the amino acids in the chain: their hydrophobicity and hydrophilicity and how they interact together.

In many instances, however, a complete protein consists of more than one amino acid chain, and the complete protein has two or more interacting strings of amino acids. A good example is hemoglobin in red blood cells. Its job is to grab oxygen and deliver it to the body’s tissues. A complete hemoglobin protein consists of four separate amino acid chains all properly folded into their tertiary structures and interacting as a single unit. In cases like this involving two or more interacting amino acid chains, we say that the final protein has a quaternary structure. Some proteins can consist of as many as a dozen interacting chains, behaving as a single protein unit.

A Plethora of Purposes

What does a protein do? Let us count the ways. Really, that’s almost impossible because proteins do just about everything. Some of them tag things. Some of them destroy things. Some of them protect. Some mark cells as “self.” Some serve as structural materials, while others are highways or motors. They aid in communication, they operate as signaling molecules, they transfer molecules and cut them up, they interact with each other in complex, interrelated pathways to build things up and break things down. They regulate genes and package DNA, and they regulate and package each other.

As described above, proteins are the final folded arrangement of a string of amino acids. One way we obtain these building blocks for the millions of proteins our bodies make is through our diet. You may hear about foods that are high in protein or people eating high-protein diets to build muscle. When we take in those proteins, we can break them apart and use the amino acids that make them up to build proteins of our own.

Nucleic Acids

How does a cell know which proteins to make? It has a code for building them, one that is especially guarded in a cellular vault in our cells called the nucleus. This code is deoxyribonucleic acid, or DNA. The cell makes a copy of this code and send it out to specialized structures that read it and build proteins based on what they read. As with any code, a typo–a mutation–can result in a message that doesn’t make as much sense. When the code gets changed, sometimes, the protein that the cell builds using that code will be changed, too.

Biohazard!The names associated with nucleic acids can be confusing because they all start with nucle-. It may seem obvious or easy now, but a brain freeze on a test could mix you up. You need to fix in your mind that the shorter term (10 letters, four syllables), nucleotide, refers to the smaller molecule, the three-part building block. The longer term (12 characters, including the space, and five syllables), nucleic acid, which is inherent in the names DNA and RNA, designates the big, long molecule.

DNA vs. RNA: A Matter of Structure

DNA and its nucleic acid cousin, ribonucleic acid, or RNA, are both made of the same kinds of building blocks. These building blocks are called nucleotides. Each nucleotide consists of three parts: a sugar (ribose for RNA and deoxyribose for DNA), a phosphate, and a nitrogenous base. In DNA, every nucleotide has identical sugars and phosphates, and in RNA, the sugar and phosphate are also the same for every nucleotide.

So what’s different? The nitrogenous bases. DNA has a set of four to use as its coding alphabet. These are the purines, adenine and guanine, and the pyrimidines, thymine and cytosine. The nucleotides are abbreviated by their initial letters as A, G, T, and C. From variations in the arrangement and number of these four molecules, all of the diversity of life arises. Just four different types of the nucleotide building blocks, and we have you, bacteria, wombats, and blue whales.

RNA is also basic at its core, consisting of only four different nucleotides. In fact, it uses three of the same nitrogenous bases as DNA–A, G, and C–but it substitutes a base called uracil (U) where DNA uses thymine. Uracil is a pyrimidine.

DNA vs. RNA: Function Wars

An interesting thing about the nitrogenous bases of the nucleotides is that they pair with each other, using hydrogen bonds, in a predictable way. An adenine will almost always bond with a thymine in DNA or a uracil in RNA, and cytosine and guanine will almost always bond with each other. This pairing capacity allows the cell to use a sequence of DNA and build either a new DNA sequence, using the old one as a template, or build an RNA sequence to make a copy of the DNA.

These two different uses of A-T/U and C-G base pairing serve two different purposes. DNA is copied into DNA usually when a cell is preparing to divide and needs two complete sets of DNA for the new cells. DNA is copied into RNA when the cell needs to send the code out of the vault so proteins can be built. The DNA stays safely where it belongs.

RNA is really a nucleic acid jack-of-all-trades. It not only serves as the copy of the DNA but also is the main component of the two types of cellular workers that read that copy and build proteins from it. At one point in this process, the three types of RNA come together in protein assembly to make sure the job is done right.


 By Emily Willingham, DXS managing editor 
This material originally appeared in similar form in Emily Willingham’s Complete Idiot’s Guide to College Biology

Why blueberries won’t turn you blue and other blueberry facts

Blueberries. Credit.


by Adrienne Roehrich, Chemistry Editor

Blueberries in the Northwestern semisphere are the fruit of several shrubs in the genus Vaccinium L.  They grow in all provinces in Canada and all but two of the United States (Nebraska and North Dakota). In the Northwestern semisphere, one can find 43 species of blueberries, depending on the region. Blueberries are found and produced in all hemispheres of the world. However, the species can vary by region.

Taxonomy:
Kingdom: Plantae (Plants)
Subkingdom: Tracheobionta (Vascular plants)
Subdivision: Spermatophyta (Seed plants)
Division: Magnoliophyta (Flowering plants)
Class: Magnoliopsida (Dictyledons)
Subclass: Dilleniidae
Order: Ericales
Family: Ericaceae
Genus: Vaccinium

There are 43 species and 46 accepted taxa overall. Some of the species include fruits we do not necessarily recognize as blueberry, including farkleberry, bilberry, ohelo, cranberry, huckleberry, whortleberry, deer berry, and lingonberry.  (Source

Blueberries are a very popular fruit in the U.S., and is consumed in fresh, frozen, and canned forms. While blueberries are a great fruit to eat to meet your suggested fruit intake, it also is one of the foods that are purported to have properties that it just does not have. This undeserved reputation results from the high levels of anti-oxidants, leading those predisposed to looking for “super foods” to classify blueberries into the anti-oxidant super food category. While eating more healthy foods is always a good idea, no food has curative effects all on its own.

Other aspects of blueberry nutrition includes it as a source of sugar. One cup (148 g) of blueberries contains about 15 g of sugar and 4 g of fiber, a single gram of protein, and half a gram of fat. If you are counting carbs, this cup has 21 g of them. That one cup of blueberries averages about 85 calories, which is approximately the same as a medium apple or orange. While almost all the vitamins and minerals nutrition gurus like to report on are present to some amount, for the 2000-calorie diet, that one cup of blueberries will provide the recommended daily value of 24% of Vitamin C, 36% of Vitamin K, and 25% of manganese. The remaining values range from 0-4%. (Values obtained from Nutrition.com and verified through multiple sources.)

The Wikipedia entry is quite good and well researched (as of August 18, 2012). 

The photo above shows all of the life stages of a blueberry. Berries go from the little red nub at the end of the branch to round and juicy blueberries through fertilization of the ovary, which swells rapidly for about a month, then its growth ceases. The green berry develops with no change in size. The chemicals responsible for the blue color, anthocyanins, begin to turn the berry from green to blue as it develops over about 6 days. The volume of the berry increases during the change in color phase.

Will blueberries turn you blue? In short, no. You can achieve blue skin through the ill-advised practice of drinking silver or you can achieve orangish-yellow skin by eating a large number of carrots. This is because the chemicals causing the skin color are fat soluble and are present in a large quantity in the fat just under the skin, giving the skin those colors. Anthocyanin, the primary chemical causing the blue color in blueberries, is not fat soluble and will not reside in the fat under your skin.

Anthocyanins is a class of over 30 compounds. The chemical structure is generally as shown below. They are polyphenolic, which indicates the 3 ring structures. The “R” indicates different functional groups that change depending on which anthocyanin the structure represents. 


Interestingly, anthocyanins are also pH indicators because their color ranges from yellow to red to blue depending on the local pH. The blue color indicates a neutral pH. The wikipedia page on anthocyanins is also informative (as of August 18, 2012). 

As mentioned before, blueberries are a popular fruit. Recipes abound, but here is one from my own Recipe Codex for Surprise Muffins with blueberries:

Ingredients
  • 6 Tbsp. butter
  • 3/4 cup sugar
  • 2 eggs
  • 1/2 cup milk
  • 1/2 – 1 pint blueberries, fresh or frozen (defrosted)
  • Food coloring, optional
  • 2 cups all-purpose flour
  • 1/4 tsp. salt
  • 1 Tbsp. baking powder
  • Your favorite mini-treat (Hershey’s Kisses, Hugs, Reese’s Mini Cups, strawberry jam, etc.)
Directions
  1. Preheat the oven to 350º. In a large bowl, cream the butter and sugar. You can use a wooden spoon, a potato masher or handheld electric mixer. Mix in the eggs, one at a time, and add the milk.
  2. Rinse the strawberries and cut off the green stem. Mash the berries with a potato masher or puree in a blender. Then stir the berries into the butter and milk mixture. TIP: For muffins with a more blue color, add a few drops of blue food coloring.
  3. In a separate bowl, sift the flour, salt and baking powder. Stir well. Add the flour mixture to the berry mixture. Use a wooden spoon to stir until all the white disappears.
  4. Line the muffin tin with paper liners. Drop the batter from a tablespoon to fill the cups halfway.
  5. Add a surprise: an unwrapped mini treat or 1/2 teaspoon of jam. Then spoon more batter to fill almost to the top.
  6. Bake until the muffins begin to brown and a toothpick inserted near the center (but not in the mini-treat) comes out clean, about 20-25 minutes.
  7. Remove the muffins from the tin and cool.
Or perhaps you are in less of a cooking scientist mood and more in a home lab mood. Try this at-home lab with blueberries about dyes. Adapted from the Journal of Chemical Education.

Items You Need
  • 4 microwavable/stove top staff glasses, pots, or containers at least 1/2 cup in volume
  • tablespoons or 1/4 cup measuring cup
  • water
  • spatula
  • alum (available in the grocery store spice aisle)
  • cream of tartar (available in the grocery store spice aisle)
  • hot pads and tongs
  • at least four small (1-2 in.) squares of white cotton cloth
  • yellow onion skins
  • blueberries
  • spoon
  • paper towels
  • vinegar
  • baking soda
  • a dropper
  • notebook for experimental observations
Procedure
In each step, you will want to record your observations, paying special attention to colors.
  1. Pour 4 tablespoons (1/4 cup) into container 1. Add a pea-sized scoop of alum and about half that amount of cream of tartar and stir. Bring the solution to a boil on the stove top or by microwaving for about 60 seconds. (Your microwave may vary.) Add two small squares of white cotton cloth and boil for two minutes. Set the container aside. The squares will be used in steps 4 and 6.
  2. Tear the outer, papery skin from a yellow onion into pieces no more than 1 inch square. Place enough pieces in a second container to cover its bottom with  2 or 3 layers of onion skin. Add about 4 tablespoons of water to the container. Bring the solution to a boil on the stove top, continuing to boil for 5  minutes.
  3. Wet a new square of cloth with water. Place it in container 2 so it is completely submerged and boil for 1 minute. Using tongs, remove the cloth and rinse it with water. Place the cloth square in the appropriate area on a labeled paper towel.
  4. Use tongs to remove one of the cloth squares from beaker 1. Repeat step 3 using this square. Compare to the dyed cloth square from step 3.
  5. Pour 4 tablespoons of water in a third container. Add 4-5 blueberries to the container and mash them with a spoon. Bring the solution to a boil on the stove, and continue to boil for 5 minutes.
  6. Repeat steps 3 and 4 substituting the blueberry mixture in container 3 for the onion skin mixture in container 2.
  7. Mix a small scoop of baking soda with a tsp of water in a clean container. With a dropper, place 1-2 drops of the baking soda solution in one corner of each cloth square. What happens? Rinse the dropper thoroughly, then place 1-2 drops of vinegar on the opposite corner of each square. What happens? Rinse the fabric squares under cool running water. Is there a change? Allow the squares to dry overnight. Is there any change of the cloth dries?
Optional: Try variations in the procedure such as changing the amount of dye source, the length of time the cloth spends in the dye solution, and the temperature of the dye solution.

Questions to consider
The solution in step 1 is called a mordant. Based on your observations, what is the purpose of a mordant?
Is the dye produced by blueberries really blue? Why might some people not want to wear clothes dyed with blueberries?

———————-
All in all, enjoy your blueberries. As a shrub, it is quite pretty. As a fruit, it is quite yummy. And as the tool in an experiment, it is quite fun.

These views are the opinion of the author and do not necessarily reflect or disagree with those of the DXS editorial team.

Freezing Point: Science never tasted so good!

Learning about freezing point can lead to a tasty reward!

When trying to devise cool activities for my kids, I generally stick with either a culinary or a scientific theme.  This is mostly because cooking and science are what I know best.  But when the opportunity arises to combine the two in a fun-filled, hands-on, and awesomely secret educational activity, I do my best to keep from micturating in my undergarments. 

In my experience, the best example of culinary science fusion involves a lesson on the concept of freezing point, mainly because the end product of this stealth lesson can be topped with whipped cream and a cherry.  That’s right, I’m talking about teaching science while making ice cream.

To fully appreciate the culinary chemistry behind this frozen delight, it’s important to understand the concept of freezing point and melting point.  Simply put, the freezing point is the temperature at which a liquid freezes and the melting point is the temperature at which a solid melts.  For most substances, the melting point and the freezing point are the same. 

Let’s use water as an example.  If water is cooled below 0°C (32°F), it will transform into ice.  Therefore, the freezing point of water is 0°C.  However, if the temperature of ice is raised above 0°C, it will melt.  Therefore, the melting point of water is also 0°C. 

HOWEVER, these points can be manipulated.  For anyone who lives in an area where winter happens, you’ve probably seen the massive seasonal salt inventory at The Home Depot.  The idea is that by putting salt on walkways, usually in the form of either rock salt (NaCl) or calcium chloride (CaCl2), you will prevent the build up of ice and snow and thus prevent any nasty slips.  This is because salt will lower the freezing point of water, thereby helping to keep it from turning into an icy mess, even when temperatures are below freezing.  But, it will only work if the walkway is warmer than -9°C (or 15°F). 

How does this relate back to ice cream?  Well, we can use the same idea of lowering the freezing point of water and apply it to making cream freeze.  The set-up involves two resealable plastic bags (one quart-sized and one gallon-sized), ice, lots of salt, cream, milk, sugar, vanilla, and your flavoring of choice. 

Into the quart-sized resealable plastic bag, combine the cream, milk, sugar, vanilla, and flavoring (follow the recipe below and ensure that the bag is fully sealed).  Fill the second resealable plastic bag about halfway with crushed ice and all of the salt.  Place the cream-filled bag into the ice-filled bag and seal.  Then…shake! 

When salt is added to the ice water, the temperature of the mixture drops.  Because the temperature of the ice-salt mixture is lower than the cream mixture, a temperature gradient is created and the cream mixture easily freezes.  After about five to ten minutes of shaking, you will have yourself some fresh-churned sciencey deliciousness!  Enjoy!


Science Experiment Ice Cream:

½ Cup Heavy Cream

½ Cup Milk

¼ Cup Sugar

¼ Tsp. Real Vanilla Extract

Crushed or Shaved Ice

1 Cup of Table Salt or Sea Salt

1 Quart-Sized Ziploc Bag

1 Gallon-Sized Ziploc Bag

Here is a video of my and a few of my pals doing this experiment with my daughter.  We did this last year and my daughter STILL talks about it!  



The set-up:

Shakin’ it up:

The big reveal: 


For more information check these out:

General Chemistry Online Why does salt melt ice?


Jeanne Garbarino, Double X Science Editor

From spiders to breast cancer: Leslie Brunetta talks candidly about her cancer diagnosis, treatment, and follow-up

According to Leslie Brunetta, she now has much more hair than she had last July.
We became aware of Leslie Brunetta because of her book, Spider Silk: Evolution and 400 Million Years of Spinning, Waiting, Snagging, and Mating, co-authored with Catherine L. Craig. Thanks to a piece Leslie wrote for the Concord Monitor (and excerpted here), we also learned that she is a breast cancer survivor. Leslie agreed to an interview about her experience, and in her emailed responses, she candidly talks about her diagnosis, treatment, and follow-up for her cancers, plural: She was diagnosed simultaneously with two types of breast cancer. 
DXS: In your Concord Monitor piece, you describe the link between an understanding of the way evolution happens and some of the advances in modern medicine. What led you to grasp the link between the two?

LB: I think, because I’m not a scientist (I’m an English major), a lot of things that scientists think are obvious strike me as revelations. I somehow had never realized that the search for what would turn out to be DNA began with trying to explain how, in line with the theory of evolution by natural selection, variation arises and traits are passed from generation to generation. As I was figuring out what each chapter in Spider Silk would be about, I tried to think about the questions non-biologists like me would still have about evolution when they got to that point in the book. By the time we got past dragline silk, I realized that we had so far fleshed out the ways that silk proteins could and have evolved at the genetic level. But that explanation probably wouldn’t answer readers’ questions about how, for example, abdominal spinnerets—which are unique to spiders—might have evolved: the evolution of silk is easier to untangle than the evolution of body parts, which is why we focused on it in the first place.

I decided I wanted to write a chapter on “evo-devo,” evolutionary developmental biology, partly because there was a cool genetic study on the development of spinnerets that showed they’ve evolved from limbs. Fortunately, my co-author, Cay Craig, and editor at Yale, Jean Thomson Black, okayed the idea, because that chapter wasn’t in the original proposal. Writing that chapter, I learned why it took so long—nearly a century—to get from Darwin and Mendel to Watson and Crick and then so long again to get to where we are today. If we non-scientists understand something scientific, it’s often how it works, not how a whole string of people over the course of decades building on each other’s work discovered how it works. I knew evolution was the accumulation of gene changes, but, until I wrote that chapter, it hadn’t occurred to me that people began to look for genes because they wanted to understand evolution.

So that was all in the spider part of my life. Then, a few months into the cancer part of my life, I was offered a test called Oncotype DX, which would look at genetic markers in my tumor cells to develop a risk profile that could help me decide whether I should have chemotherapy plus tamoxifen or just tamoxifen. The results turned out to be moot in my case because I had a number of positive lymph nodes, although it was reassuring to find out that the cancer was considered low risk for recurrence. But still—the idea that a genetic test could let some women avoid chemo without taking on extra risk, that’s huge. No one would want to go through chemo if it wasn’t necessary. So by then I was thinking, “Thank you, Darwin!”

And then, coincidentally, the presidential primary season was heating up, and there were a number of serious candidates (well, serious in the sense that they had enough backing to get into the debates) who proudly declared that they had no time for the theory of evolution. And year after year these stupid anti-evolution bills are introduced in various state legislatures. While I was lying on the couch hanging out in the days after chemo sessions, I started thinking, “So, given that you don’t give any credence to Darwin and his ideas, would you refuse on principle to take the Oncotype test or gene-based therapies like Gleevec or Herceptin if you had cancer or if someone in your family had cancer? Somehow I don’t think so.” That argument is not going to convince hard-core denialists (nothing will), but maybe the cognitive dissonance in connection with something as concrete as cancer will make some people who waver want to find out more.

DXS: You mention having been diagnosed with two different forms of cancer, one in each breast. Can you say what each kind was and, if possible, how they differed?

LB: Yes, I unfortunately turned out to be an “interesting” case. This is one arena where, if you possibly can, you want to avoid being interesting. At first it seemed that I had a tiny lesion that was an invasive ductal carcinoma (IDC) and that I would “just” need a lumpectomy and radiation. Luckily for me, the doctor reading my mammogram is known as an eagle eye, and she saw a few things that—given the positive finding from the biopsy—concerned her. She recommended an MRI. In fact, even though I switched to another hospital for my surgery, she sent emails there saying I should have an MRI. That turned up “concerning” spots in both breasts, which led to more biopsies, which revealed multiple tiny cancerous lesions. The only reasonable option was then a double mastectomy.

The lesions in the right breast were IDCs. About 70% of breast cancers are diagnosed as IDCs. Those cancers start with the cells lining the milk ducts. The ones in the left breast were invasive lobular carcinomas (ILCs), which start in the lobules at the end of the milk ducts. Only about 10% of breast cancers are ILCs.

Oncologists hate lobular cancer. Unlike ductal cancers, which form as clumps of cells, lobular cancers form as single-file ribbons of cells. The tissue around ductal cancer cells reacts to those cells, which is why someone may feel a lump—she’s (or he’s) not feeling the cancer itself but the inflammation of the tissue around it. And because the cells clump, they show up more readily on mammograms. Not so lobular cancers. They mostly don’t give rise to lumps and they’re hard to spot on mammograms. They snake their way through tissue for quite a while without bothering anything.

In my case, this explains why last spring felt like an unremitting downhill slide. Every time someone looked deeper, they found something worse. It turned out that on my left side, the lobular side, I had multiple positive lymph nodes, which was why I needed not just chemo but also radiation (which usually isn’t given after a mastectomy). That was the side that didn’t even show up much on the mammogram. On the right side, the ductal side, which provoked the initial suspicions, my nodes were clear. I want to write about this soon, because I want to find out more about it. I’ve only recently gotten to the place emotionally where I think I can deal with reading the research papers as opposed to more general information. By the way, the resource that most helped us better understand what my doctors were talking about was Dr. Susan Love’s Breast Book.  It was invaluable as we made our way through this process, although it turned out that I had very few decisions to make because there was usually only one good option.   

DXS: As part of your treatment, you had a double mastectomy. One of our goals with this interview is to tell women what some of these experiences with treatment are like. If you’re comfortable doing so, could you tell us a little bit about what a double mastectomy entails and what you do after one in practical terms?

LB: A mastectomy is a strange operation. In a way, it’s more of an emotional and psychological experience than a physical experience. My surgeon, who was fantastic, is a man, and when we discussed the need for the mastectomies he said that I would be surprised at how little pain would be involved and how quick the healing would be. Even though I trusted him a lot by then, my reaction was pretty much, “Like you would know, right?” But he did know. When you think about it, it’s fairly non-invasive surgery. Unless the cancer has spread to the surrounding area, which doesn’t happen very often now due to early detection, no muscle or bone is removed. (Until relatively recently, surgeons removed the major muscle in the chest wall, and sometimes even bone, because they believed it would cut the risk of recurrence. That meant that many women lost function in their arm and also experienced back problems.) None of your organs are touched. They don’t go into your abdominal cavity. Also, until recently, they removed a whole clump of underarm lymph nodes when they did lumpectomies or mastectomies. Now they usually remove just a “sentinel node,” because they know that it will give them a fairly reliable indicator of whether the cancer has spread to the other nodes. That also makes the surgery less traumatic than it used to be.

I opted not to have reconstruction. Reconstruction is a good choice for many women, but I didn’t see many benefits for me and I didn’t like the idea of a more complicated surgery. My surgery was only about two hours. I don’t remember any pain at all afterwards, and my husband says I never complained of any. I was in the hospital for just one night. By the next day, I was on ibuprofen only. The bandages came off two days after the surgery.

That’s shocking, to see your breasts gone and replaced by thin red lines, no matter how well you’ve prepared yourself. It made the cancer seem much more real in some way than it had seemed before. In comparison, the physical recovery from the surgery was fairly minor because I had no infections or complications. There were drains in place for about 10 days to collect serum, which would otherwise collect under the skin, and my husband dealt with emptying them twice a day and measuring the amount. I had to sleep on my back, propped up, because of where the drains were placed, high up on my sides, and I never really got used to that. It was a real relief to have the drains removed.

My surgeon told me to start doing stretching exercises with my arms right away, and that’s really important. I got my full range of motion back within a couple of months. But even though I had my surgery last March, I’ve noticed lately that if I don’t stretch fully, like in yoga, things tighten up. That may be because of the radiation, though, because it’s only on my left side. Things are never quite the same as they were before the surgery, though. Because I did have to have the axillary nodes out on my left side, my lymph system is disrupted. I haven’t had any real problems with lymphedema yet, and I may never, but in the early months I noticed that my hands would swell if I’d been walking around a lot, and I’d have to elevate them to get them to drain back. That rarely happens now. But I’ve been told I need to wear a compression sleeve if I fly because the change in air pressure can cause lymph to collect. Also, I’m supposed to protect my hands and arms from cuts as much as possible. It seems to me that small nicks on my fingers take longer to heal than they used to. So even though most of the time it seems like it’s all over, I guess in those purely mechanical ways it’s never over. It’s not just that you no longer have breasts, it’s also that nerves and lymph channels and bits of tissue are also missing or moved around.

The bigger question is how one deals with now lacking breasts. I’ve decided not to wear prostheses. I can get away with it because I was small breasted, I dress in relatively loose clothes anyway, and I’ve gained confidence over time that no one notices or cares and I care less now if they do notice. But getting that self-confidence took quite a while. Obviously, it has an effect on my sex life, but we have a strong bond and it’s just become a piece of that bond. The biggest thing is that it’s always a bit of a shock when I catch sight of myself naked in a mirror because it’s a reminder that I’ve had cancer and there’s no getting around the fact that that sucks.    

DXS: My mother-in-law completed radiation and chemo for breast cancer last year, and if I remember correctly, she had to go frequently for a period of weeks for radiation. Was that you experience? Can you describe for our readers what the time investment was like and what the process was like?

LB: I went for radiation 5 days a week for about 7 weeks. Three days a week, I’d usually be in and out of the hospital within 45 minutes. One day a week, I met with the radiology oncologist and a nurse to debrief, which was also a form of emotional therapy for me. And one day a week, they laid on a chair massage, and the nurse/massage therapist who gave the massage was great to talk to, so that was more therapy. Radiation was easy compared to chemo. Some people experience skin burning and fatigue, but I was lucky that I didn’t experience either. Because I’m a freelancer, the time investment wasn’t a burden for me. I’m also lucky living where I live, because I could walk to the hospital. It was a pleasant 3-mile round-trip walk, and I think the walking helped me a lot physically and mentally.
DXS: And now to the chemo. My interest in interviewing you about your experience began with a reference you made on Twitter to “chemo brain,” and of course, after reading your evolution-medical advances piece. Can you tell us a little about what the process of receiving chemotherapy is like? How long does it take? How frequently (I know this varies, but your experience)?
LB: Because of my age (I was considered young, which was always nice to hear) and state of general good health, my oncologist put me on a dose-dense AC-T schedule. This meant going for treatment every two weeks over the course of 16 weeks—8 treatment sessions. At the first 4 sessions, I was given Adriamycin and Cytoxan (AC), and the last 4 sessions I was given Taxol (T). The idea behind giving multiple drugs and giving them frequently is that they all attack cancer cells in different ways and—it goes back to evolution—by attacking them frequently and hard on different fronts, you’re trying to avoid selecting for a population that’s resistant to one or more of the drugs. They can give the drugs every two weeks to a lot of patients now because they’ve got drugs to boost the production of white blood cells, which the cancer drugs suppress. After most chemo sessions, I went back the next day for a shot of one of these drugs, Neulasta.

The chemo clinic was, bizarrely, a very relaxing place. The nurses who work there were fantastic, and the nurse assigned to me, Kathy, was always interesting to talk with. She had a great sense of humor, and she was also interested in the science behind everything we were doing, so if I ever had questions she didn’t have ready answers for, she’d find out for me. A lot of patients were there at the same time, but we each had a private space. You’d sit in a big reclining chair. They had TVs and DVDs, but I usually used it as an opportunity to read. My husband sat through the first session with me, and a close friend who had chemo for breast cancer 15 years ago sat through a few other sessions, but once I got used to it, I was comfortable being there alone. Because of the nurses, it never felt lonely.

I’d arrive and settle in. Kathy would take blood for testing red and white blood counts and, I think, liver function and some other things, and she’d insert a needle and start a saline drip while we waited for the results. I’ve always had large veins, so I opted to have the drugs administered through my arm rather than having a port implanted in my chest. Over the course of three to four hours, she’d change the IV bags. Some of the bags were drugs to protect against nausea, so I’d start to feel kind of fuzzy—I don’t think I retained a whole lot of what I read there! The Adriamycin was bright orange; they call it the Red Devil, because it can chew up your veins—sometimes it felt like it was burning but Kathy could stop that by slowing the drip. Otherwise, it was fairly uneventful. I’d have snacks and usually ate lunch while still hooked up.

I was lucky I never had any reactions to any of the drugs, so actually getting the chemo was a surprisingly pleasant experience just because of the atmosphere. On the one hand, you’re aware of all these people around you struggling with cancer and you know things aren’t going well for some of them, so it’s heartbreaking, and also makes you consider, sometimes fearfully, your own future no matter how well you’re trying to brace yourself up. But at the same time, the people working there are so positive, but not in a Pollyannaish-false way, that they helped me as I tried to stay positive. The social worker stopped in with each patient every session, and she was fantastic—I could talk out any problems or fears I had with her, and that helped a huge amount.

DXS: Would you be able to run us through a timeline of the physical effects of chemotherapy after an infusion? How long does it take before it hits hardest? My mother-in-law told me that her biggest craving, when she could eat, was for carb-heavy foods like mashed potatoes and for soups, like vegetable soup. What was your experience with that?

LB: My biggest fear when I first learned I would need chemo was nausea. My oncologist told us that they had nausea so well controlled that over the past few years, she had only had one or two patients who had experienced it. As with the surgeon’s prediction about mastectomy pain, this turned out to be true: I never had even a single moment of nausea.

But there were all sorts of other effects. For the first few days after a session, the most salient effects were actually from the mix of drugs I took to stave off nausea. I generally felt pretty fuzzy, but not necessarily sleepy—part of the mix was steroids, so you’re a little hyped. There’s no way I’d feel safe driving on those days, for example. I’d sleep well the first three nights because I took Ativan, which has an anti-nausea effect. But except for those days, my sleep was really disrupted. Partly that’s because, I’m guessing, the chemo hits certain cells in your brain and partly it’s because you get thrown into chemical menopause, so there were a lot of night hot flashes. Even though I’d already started into menopause, this chemo menopause was a lot more intense and included all the symptoms regularly associated with menopause.

By the end of the first session, I was feeling pretty joyful because it was much less bad than I had thought it would be. By the second week in the two-week cycle, I felt relatively normal. But even though it never got awful, the effects started to accumulate. My hair started to fall out the morning I was going to an award ceremony for Spider Silk. It was ok at the ceremony, but we shaved it off that night. I decided not to wear a wig. First, it was the summer, and it would have been hot. Second, I usually have close to a buzz cut, and I can’t imagine anyone would make a wig that would look anything like my hair. My kids’ attitude was that everyone would know something was wrong anyway, so I should just be bald, and that helped a lot. But it’s hard to see in people’s eyes multiple times a day their realization that you’re in a pretty bad place. Also, it’s not just your head hair that goes. So do your eyebrows, your eyelashes, your pubic hair, and most of the tiny hairs all over your skin. And as your skin cells are affected by the chemo (the chemo hits all fast-reproducing cells), your skin itself gets more sensitive and then is not protected by those tiny hairs. I remember a lot of itching. And strange things like my head sticking to my yoga mat and my reading glasses sticking to the side of my head instead of sliding over my ears.

I never lost my appetite, but I did have food cravings during the AC cycles. I wanted sushi and seaweed salad, of all things. And steak. My sense of taste went dull, so I also wanted things that tasted strong and had crunch. I stopped drinking coffee and alcohol, partly because of the sleep issues but partly because it didn’t taste very good anyway. I drank loads of water on the advice of the oncologist, the nurses, and my acupuncturist, and I think that helped a lot.

During the second cycle, I developed a fever. That was scary. I was warned that if I ever developed a fever, I should call the oncologist immediately, no matter the time of day or day of week. The problem is that your immune response is knocked down by the chemo, so what would normally be a small bacterial infection has the potential to rage out of control. I was lucky. We figured out that the source of infection was a hemorrhoid—the Adriamycin was beginning to chew into my digestive tract, a well-known side effect. (Having to pay constant attention to yet another usually private part of the body just seemed totally unfair by this point.) Oral antibiotics took care of it, which was great because I avoided having to go into the hospital and all the risks entailed with getting heavy-duty IV antibiotic treatment. And we were also able to keep on schedule with the chemo regimen, which is what you hope for.

After that, I became even more careful about avoiding infection, so I avoided public places even more than I had been. I’m very close to a couple of toddlers, and I couldn’t see them for weeks because they were in one of those toddler constant-viral stages, and I really missed them.

The Taxol seems to be much less harsh than the AC regimen, so a lot of these side effects started to ease off a bit by the second 8 weeks, which was certainly a relief.

I was lucky that I didn’t really have mouth sores or some of the other side effects. Some of this is, I think, just because besides the cancer I don’t have any other health issues. Some of it is because my husband took over everything and I don’t have a regular job, so I had the luxury of concentrating on doing what my body needed. I tried to walk every day, and I slept when I needed to, ate when and what I needed to, and went to yoga class when my immune system was ok. I also went to acupuncture every week. I know the science is iffy on that, but I think it helped me with the side effects, even if it was the placebo effect at work (I’m a big fan of the placebo effect). We also both had extraordinary emotional support from many friends and knew we could call lots of people if we needed anything. That’s huge when you’re in this kind of situation.

Currently, I’m still dealing with some minor joint pains, mostly in my wrists and feet. I wasn’t expecting this problem, but my oncologist says it’s not uncommon: they think it’s because your immune system has to re-find its proper level of function, and it can go into overdrive and set up inflammation in the joints. That’s gradually easing off, though.

Most people don’t have it as easy as I did in terms of the medical, financial, and emotional resources I had to draw on. I’m very mindful of that and very grateful.

DXS: You say that you had “few terrible side effects” and a “very cushy home situation.” I’m sure any woman would like to at least be able to experience the latter while dealing with a full-body chemical attack. What were some factors that made it “cushy” that women might be able to talk to their families or caregivers about replicating for them?

LB: As I’ve said, some of it is just circumstance. For example, my kids were old enough to be pretty self-sufficient and old enough to understand what was going on, which meant both that they needed very little from me in terms of care and also that they were less scared than they might have been if they were younger. My husband happens to be both very competent (more competent than I am) around the house and very giving. I live in Cambridge, MA, where I could actually make choices about where I wanted to be treated at each phase and know I’d get excellent, humane care and where none of the facilities I went to was more than about 20 minutes away.

Some things that women might have some control over and that their families might help nudge them toward:

  • Find doctors you trust. Ask a lot of questions and make sure you understand the answers. But don’t get hung up on survival or recurrence statistics. There’s no way to know for sure what your individual outcome will be. Go for the treatment that you and your doctors believe will give you the best chance, and then assume as much as possible that your outcome will be good.
  • Make sure you talk regularly with a social worker or other therapist who specializes in dealing with breast cancer patients. If you have fears or worries that you don’t want to talk to your partner or family about, here’s where you’ll get lots of help.
  • Find compatible friends who have also had cancer to talk to. I had friends who showed me their mastectomy scars, who showed me their reconstructions, who told me about their experiences with chemo and radiation, who told me about what life after treatment was like (is still like decades later…). And none of them told me, “You should…” They all just told me what was hard for them and what worked for them and let me figure out what worked for me. Brilliant.
  • Try to get some exercise even if you don’t feel like it. It was often when I felt least like moving around that a short walk made me feel remarkably better. But I would forget that, so my husband would remind me. Ask someone to walk with you if you’re feeling weak. Getting your circulation going seems to help the body process the chemo drugs and the waste products they create. For the same reason, drink lots of water.
  • Watch funny movies together. Laughter makes a huge difference.
  • Pamper yourself as much as possible. Let people take care of you and help as much as they’re willing. But don’t be afraid to say no to anything that you don’t want or that’s too much.

Family members and caregivers should also take care of themselves by making some time for themselves and talking to social workers or therapists if they feel the need. It’s a big, awful string of events for everyone involved, not just the patient.

DXS: In the midst of all of this, you seem to have written a fascinating book about spiders and their webs. Were you able to work while undergoing your treatments? Were there times that were better than others for attending to work? Could work be a sort of occupational therapy, when it was possible for you to do it, to keep you engaged?

LB: The book had been published about 6 months before my diagnosis. The whole cancer thing really interfered not with the writing, but with my efforts to publicize it. I had started to build toward a series of readings and had to abandon that effort. I had also started a proposal for a new book and had to put that aside. I had one radio interview in the middle of chemo, which was kind of daunting but I knew I couldn’t pass up the opportunity, and when I listen to it now, I can hear my voice sounds kind of shaky. It went well, but I was exhausted afterwards. Also invigorated, though—it made me feel like I hadn’t disappeared into the cancer. I had two streams of writing going on, both of which were therapeutic. I sent email updates about the cancer treatment to a group of friends—that was definitely psychological therapy. I also tried to keep the Spider Silk blog up to date by summarizing related research papers and other spider silk news—that was intellectual therapy. I just worked on them when I felt I wanted to. The second week of every cycle my head was usually reasonably clear.

I don’t really know whether I have chemo brain. I notice a lot of names-and-other-proper-nouns drop. But whether that’s from the chemo per se, or from the hormone changes associated with the chemically induced menopause, or just from emotional overload and intellectual distraction, I don’t know. I find that I’m thinking more clearly week by week.

DXS: What is the plan for your continued follow-up? How long will it last, what is the frequency of visits, sorts of tests, etc.?

LB: I’m on tamoxifen and I’ll be on that for probably two years and then either stay on that or go onto an aromatase inhibitor [Ed. note: these drugs block production of estrogen and are used for estrogen-sensitive cancers.] for another three years. I’ll see one of the cancer doctors every three months for at least a year, I think. They’ll ask me questions and do a physical exam and take blood samples to test for tumor markers. At some point the visits go to every six months.

For self-care, I’m exercising more, trying to lose some weight, and eating even better than I was before.

DXS: Last…if you’re comfortable detailing it…what led to your diagnosis in the first place?

LB: My breast cancer was uncovered by my annual mammogram. I’ve worried about cancer, as I suppose most people do. But I never really worried about breast cancer. My mother has 10 sisters and neither she nor any of them ever had breast cancer. I have about 20 older female cousins—I was 50 when I was diagnosed last year–and as far as I know none of them have had breast cancer. I took birth control pills for less than a year decades ago. Never smoked. Light drinker. Not overweight. Light exerciser. I breastfed both kids, although not for a full year. Never took replacement hormones. Never worked in a dangerous environment. Never had suspicious mammograms before. So on paper, I was at very low risk as far as I can figure out. After I finished intensive treatment, I was tested for BRCA1 and BRCA2 (because mutations there are associated with cancer in both breasts) and no mutations were found. Unless or until some new genetic markers are found and one of them applies to me, I think we’ll never know why I got breast cancer, other than the fact that I’ve lived long enough to get cancer. There was no lump. Even between the suspicious mammogram and ultrasound and the biopsy, none of the doctors examining me could feel a lump or anything irregular. It was a year ago this week that I got the news that the first biopsy was positive. In some ways, because I feel really good now, it’s hard to believe that this year ever happened. But in other ways, the shock of it is still with me and with the whole family. Things are good for now, though, and although I feel very unlucky that this happened in the first place, I feel extremely lucky with the medical care I received and the support I got from family and friends and especially my husband.
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Leslie Brunetta’s articles and essays have appeared in the New York Times, Technology Review, and the Sewanee Review as well as on NPR and elsewhere. She is co-author, with Catherine L. Craig, of Spider Silk: Evolution and 400 Million Years of Spinning, Waiting, Snagging, and Mating (Yale University Press).

Organic versus conventional foods–no winner?

A strawberry. Can you tell
if it is organic or not?
[Photo credit:  Rasbak from nl.]
By Emily Willingham

A report on organic foods has just come out from a Stanford University team, and the headlines, such as this one from the New York Times, pretty much say what everyone’s saying about it: Organic foods aren’t any better for you, nutritionally, than conventional foods. 

According to the NYT report, the Stanford researchers spent four years looking over more than 200 studies, evaluating various aspects of research findings about organic versus conventionally farmed or ranched plants and meats. The kind of analysis they did is called a “meta-analysis” because it goes beyond–or “meta”–a single study and looks at a pile of existing data to analyze. 

The NYT piece and a lot of what I’ve been seeing on Twitter gives the impression that people buy organic foods because they think these foods are nutritionally superior to conventionally produced foods. In that context, according to the NYT piece, the researchers

concluded that fruits and vegetables labeled organic were, on average, no more nutritious than their conventional counterparts, which tend to be far less expensive. Nor were they any less likely to be contaminated by dangerous bacteria like E. coli.

The researchers also found no obvious health advantages to organic meats.

The problem? This is purely anecdotal (although at least one poll supports it), but the people I know who buy organic don’t do it because they’ve got some idea that an organic strawberry’s got more vitamin C than a non-organic one. They do it because of the rules governing the production of organic fruits and vegetables and organic meats. Their reasoning is that these processes will result in foods with less pesticide residue and less contamination with antibiotic-resistant bacteria. Guess what the Stanford team found? Again, from the NYT:

Conventional fruits and vegetables did have more pesticide residue, but the levels were almost always under the allowed safety limits, the scientists said

and

Organic produce, as expected, was much less likely to retain traces of pesticides….Organic chicken and pork were less likely to be contaminated by antibiotic-resistant bacteria.

That finding for pesticides alone is one reason many people I know who buy organic do so. 

One of the Stanford researchers acknowledged as much in the NYT piece:

Dr. Bravata agreed that people bought organic food for a variety of reasons – concerns about the effects of pesticides on young children, the environmental impact of large-scale conventional farming and the potential public health threat if antibiotic-resistant bacterial genes jumped to human pathogens. “Those are perfectly valid,” she said.

Indeed, the piece does include an observation from an analyst with the Environmental Working Group noting that the “more nutritious” concept has “never been a major driver” in people’s decision to buy–and pay more for–organic food. That said, organic producers do tend to emphasize the “nutritional superiority” of organically produced foods. Perhaps their advertising is poorly targeted.
Oddly enough, the researchers did find some potentially higher nutritional benefits of some organic foods, such as more “heart-healthy” omega 3 fatty acids in organic milk compared to conventionally produced milk.
What about you? Do you buy organic? If so, what are your reasons? 
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For further reading, check out the online brouhaha that blew up last summer, ignited by this article from Christie Wilcox, writing at Scientific American blogs. 
These views are the opinion of the author and do not necessarily reflect or disagree with those of the DXS editorial team.