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.

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.


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

HPV and cervical cancer don’t care what month it is

Young love. Like older love, it too can spread HPV.
Image via Wikimedia Commons, public domain image.

January was Cervical Cancer Awareness Month, but we’d like to note that sexually active people should be aware of cervical cancer in any month and continue the recommended preventive and early detection measures for it, which includes keeping up with Pap tests. To maintain awareness, we’re kicking off the month for lovers–February–with a post about cervical cancer and the human papillomavirus (HPV). 

One thing that cervical cancer awareness overlooks is that HPV causes not only that cancer but also can play a role in penile, vaginal, urethral, anal, and head and neck cancers. In fact,  a recent study found that about 1 in 10 men and almost 4 in 100 women are orally infected with HPV, the most common sexually transmitted virus in the United States, and HPV-related head and neck cancer rates are higher among men. Further, HPV-related oral cancers have been on the rise for about two decades now, and HPV is now responsible for about 50% of oral cancers today.

Research also shows that about 50% of college age women acquire an HPV infection within four years of becoming sexually active. In addition, an infected mother can pass HPV to her baby during childbirth, and the virus can populate the child’s larynx, causing recurrent growths that block the respiratory tract and require surgical removal.

The remainder of this post appeared initially on the Parents of Kids with Infectious Disease site, which provides information for preventing infectious disease in addition to supporting parents whose children have them. As insidious as HPV is, the vast majority of HPV infections can be prevented now with a vaccine.

Have you or a loved one ever had an abnormal Pap test result? If precancerous cells were identified, the cause was almost undoubtedly infection with human papillomavirus (HPV). Almost all cases of cervical cancer arise because of infection with this virus. Yet a vaccine can prevent infection with the strains that most commonly cause cervical cancer.

A vaccine against cancer. It’s true.

For the vaccine to work, though, a woman must have it before HPV infects her. You may find it difficult to look at your daughter, especially a pre-teen daughter, and think of that scenario. But the fact is that even if your daughter avoids all sexual contact until, say, her wedding night, she can still contract HPV from her partner. As we noted above, it happens to be the most common sexually transmitted infection.

About 20 million Americans have an HPV infection, and 6 million people become newly infected every year. Half of the people who are ever sexually active pick up an HPV infection in a lifetime. That means your daughter, even if she waits until her wedding night, has a 1 in 2 chance of contracting the virus. Unless it’s a strain that causes genital warts, HPV usually produces no symptoms, and the infected person doesn’t even know they’ve been infected.

Until the cancer shows up.

And it can show up in more places than the cervix. This virus, you see, favors a certain kind of tissue, one that happens to be present in several parts of you. This tissue, a type of epithelium, is a thin layer of the skin and mucous membranes. It’s available for viral invasion in the cervix, vagina, vulva, anus, and the mouth and pharynx. In fact, HPV is poised to replace tobacco as the major cause of oral cancers in the United States.

The virus can even sometimes pass from mother to child, causing recurrent respiratory papillomatosis, the recurrent growths in the throat that must be removed periodically and can sometimes become cancerous. It strikes about 2000 children each year in the United States.

How does a virus cause cancer? To understand that, you must first understand cancer. You may know that cells reproduce by dividing, and that cancer occurs when cells divide out of control. Behind most cancers is a malfunction in the molecules that tell cells to stop dividing. These molecules operate in a chain reaction of signaling, like a series of well-timed stoplights along a boulevard. If one starts sending an inappropriate “go” signal or fails to send a “stop” signal, the cell divides, making more cells just like it that also lack the right signals. If your body’s immune system doesn’t halt this inappropriate growth, we call it cancer.

The blueprint for building these “stop” molecules is in your genes, in your DNA sequences. As a virus, HPV also requires a blueprint to make more viruses. Viruses use the division machinery of the host cell—in you—to achieve reproduction by stealthily inserting their own DNA blueprint into the host DNA.

Sometimes, when it’s finished with the host, a virus leaves a little bit of its DNA behind. If that leftover DNA is in the middle of the blueprint for a “stop” molecule, the cell won’t even notice. It will use the contaminated instructions to build a molecule, one that no longer functions in stopping cell division. The result can be cancer.

Of the 150 HPV types or strains, about 40 of which pass through sexual contact, two in particular are associated with cancer, types 16 and 18. They are the ones that may persist for years and eventually change the cellular blueprint. The vaccines developed against those two strains are, therefore, anti-cancer vaccines.

Without a successful viral infection, viral DNA can’t disrupt your DNA. That’s what the HPV vaccine achieves against the two strains responsible for about 70% of cervical cancers. Recent high-profile people have made claims about negative effects of this vaccine, claims that have been thoroughly debunked. The Centers for Disease Control and Prevention as always offers accurate information about the side effects associated with available HPV vaccines.

This achievement against cancer, including prevention of almost 100% of precancerous cervical changes related to types 16 and 18, is important.

Worldwide, a half million women receive a cervical cancer diagnosis each year, and 250,000 women die from it. These women are somebody’s daughter, wife, sister, friend. Women from all kinds of backgrounds, with all kinds of sexual histories.

Women whose precancerous cervical changes are identified in time often still must undergo uncomfortable and sometimes painful procedures to get rid of the precancerous cells. These invasive procedures include cone biopsies that require shots to numb the cervix and removal of a chunk of tissue from it. Cone biopsies carry a risk of causing infertility or miscarriage or preterm delivery. A vaccine for your daughter could prevent it all.

HPV doesn’t care if your daughter has had sex before. It’s equally oblivious to whether the epithelium it infects is in the cervix or in the mouth or pharynx or in an adult or a child. What it does respond to is antibodies that a body makes in response to the vaccine stimulus.

Even if your daughter’s first and only sex partner passes along one of the cancer-associated strains, if she’s been vaccinated, her antibodies will take that virus out cold. It’s a straightforward prevention against a lifetime of worry—and a premature death.

For more info: Facts about the HPV vaccine from the National Cancer Institute.

By Emily Willingham, DXS managing 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.
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).

Biology Xplainer: Evolution and how it happens

Evolution: a population changes over time
First of all, in the context of science, you should never speak of evolution as a “theory.” There is no theory about whether or not evolution happens. It is a fact.

Scientists have, however, developed tested theories about how evolution happens. Although several proposed and tested processes or mechanisms exist, the most prominent and most studied, talked about, and debated, is Charles Darwin’s idea that the choices of nature guide these changes. The fame and importance of his idea, natural selection, has eclipsed the very real existence of other ways that populations can change over time.

Evolution in the biological sense does not occur in individuals, and the kind of evolution we’re talking about here isn’t about life’s origins. Evolution must happen at least at the populationlevel. In other words, it takes place in a group of existing organisms, members of the same species, often in a defined geographical area.

We never speak of individuals evolving in the biological sense. The population, a group of individuals of the same species, is the smallest unit of life that evolves.

To get to the bottom of what happens when a population changes over time, we must examine what’s happening to the gene combinations of the individuals in that population. The most precise way to talk about evolution in the biological sense is to define it as “a change in the allele frequency of a population over time.” A gene, which contains the code for a protein, can occur in different forms, or alleles. These different versions can mean that the trait associated with that protein can differ among individuals. Thanks to mutations, a gene for a trait can exist in a population in these different forms. It’s like having slightly different recipes for making the same cake, each producing a different version of the cake, except in this case, the “cake” is a protein.
Natural selection: One way evolution happens

Charles Darwin, a smart, thoughtful,
observant man. Via Wikimedia.
Charles Darwin, who didn’t know anything about alleles or even genes (so now you know more than he did on that score), understood from his work and observations that nature makes certain choices, and that often, what nature chooses in specific individuals turns up again in the individuals’ offspring. He realized that these characteristics that nature was choosing must pass to some offspring. This notion of heredity–that a feature encoded in the genes can be transmitted to your children–is inherent now in the theory of natural selection and a natural one for most people to accept. In science, an observable or measurable feature or characteristic is called a phenotype, and the genes that are the code for it are called its genotype. The color of my eyes (brown) is a phenotype, and the alleles of the eye color genes I have are the genotype.

What is nature selecting any individual in a population to do? In the theory of natural selection, nature chooses individuals that fit best into the current environment to pass along their “good-fit” genes, either through reproduction or indirectly through supporting the reproducer. Nature chooses organisms to survive and pass along those good-fit genes, so they have greater fitness.

Fitness is an evolutionary concept related to an organism’s reproductive success, either directly (as a parent) or indirectly (say, as an aunt or cousin). It is measured technically based on the proportion of an individual’s alleles that are represented in the next generation. When we talk about “fitness” and “the fittest,” remember that fittest does not mean strong. It relates more to a literal fit, like a square peg in a square hole, or a red dot against a red background. It doesn’t matter if the peg or dot is strong, just whether or not it fits its environment.

One final consideration before we move onto a synthesis of these ideas about differences, heredity, and reproduction: What would happen if the population were uniformly the same genetically for a trait? Well, when the environment changed, nature would have no choice to make. Without a choice, natural selection cannot happen–there is nothing to select. And the choice has to exist already; it does not typically happen in response to a need that the environment dictates. Usually, the ultimate origin for genetic variation–which underlies this choice–is mutation, or a change in a DNA coding sequence, the instructions for building a protein.

Don’t make the mistake of saying that an organism adapts by mutating in response to the environment. The mutations (the variation) must already be present for nature to make a choice based on the existing environment.

The Modern Synthesis

When Darwin presented his ideas about nature’s choices in an environmental context, he did so in a book with a very long title that begins, On the Origin of Species by Means of Natural Selection. Darwinknew his audience and laid out his argument clearly and well, with one stumbling block: How did all that heredity stuff actually work?

We now know–thanks to a meticulous scientist named Gregor Mendel (who also was a monk), our understanding of reproductive cell division, and modern genetics–exactly how it all works. Our traits–whether winners or losers in the fitness Olympics–have genes that determine them. These genes exist in us in pairs, and these pairs separate during division of our reproductive cells so that our offspring receive one member or the other of the pair. When this gene meets its coding partner from the other parent’s cell at fertilization, a new gene pair arises. This pairing may produce a similar outcome to one of the parents or be a novel combination that yields some new version of a trait. But this separating and pairing is how nature keeps things mixed up, setting up choices for selection.

Ernst Mayr, via PLoS.
With a growing understanding in the twentieth century of genetics and its role in evolution by means of natural selection, a great evolutionary biologist named Ernst Mayr (1904–2005) guided a meshing of genetics and evolution (along with other brilliant scientists including Theodosius Dobzhansky, George Simpson, and R.A. Fisher) into what is called The Modern Synthesis. This work encapsulates (dare I say, “synthesizes?”) concisely and beautifully the tenets of natural selection in the context of basic genetic inheritance. As part of his work, Mayr distilled Darwin’s ideas into a series of facts and inferences.

Facts and Inferences

Mayr’s distillation consists of five facts and three inferences, or conclusions, to draw from those facts.
  1. The first fact is that populations have the potential to increase exponentially. A quick look at any graph of human population growth illustrates that we, as a species, appear to be recognizing that potential. For a less successful example, consider the sea turtle. You may have seen the videos of the little turtle hatchlings valiantly flippering their way across the sand to the sea, cheered on by the conservation-minded humans who tended their nests. What the cameras usually don’t show is that the vast majority of these turtle offspring will not live to reproduce. The potential for exponential growth is there, based on number of offspring produced, but…it doesn’t happen.
  2. The second fact is that not all offspring reproduce, and many populations are stable in size. See “sea turtles,” above.
  3. The third fact is that resources are limited. And that leads us to our first conclusion, or inference: there is a struggle among organisms for nutrition, water, habitat, mates, parental attention…the various necessities of survival, depending on the species. The large number of offspring, most of which ultimately don’t survive to reproduce, must compete, or struggle, for the limited resources.
  4. Fact four is that individuals differ from one another. Look around. Even bacteria of the same strain have their differences, with some more able than others to with stand an antibiotic onslaught. Look at a crowd of people. They’re all different in hundreds of ways.
  5. Fact five is that much about us that is different lies in our genes–it is inheritable. Heredity undeniably exists and underlies a lot of our variation.
So we have five facts. Now for the three inferences:

  1. First, there is that struggle for survival, thanks to so many offspring and limited resources. See “sea turtle,” again.
  2. Second, different traits will be passed on differentially. Put another way: Winner traits are more likely to be passed on.
  3. And that takes us to our final conclusion: if enough of these “winner” traits are passed to enough individuals in a population, they will accumulate in that population and change its makeup. In other words, the population will change over time. It will be adapted to its environment. It will evolve.
Other mechanisms of evolution

A pigeon depicted in Charles Darwin’s
Variation of Animals and Plants
Under Domestication
, 1868. U.S.
public domain image, via Wikimedia.
When Darwin presented his idea of natural selection, he knew he had an audience to win over. He pointed out that people select features of organisms all the time and breed them to have those features. Darwin himself was fond of breeding pigeons with a great deal of pigeony variety. He noted that unless the pigeons already possessed traits for us to choose, we not would have that choice to make. But we do have choices. We make super-woolly sheep, dachshunds, and heirloom tomatoes simply by selecting from the variation nature provides and breeding those organisms to make more with those traits. We change the population over time.

Darwin called this process of human-directed evolution artificial selection. It made great sense for Darwinbecause it helped his reader get on board. If people could make these kinds of choices and wreak these kinds of changes, why not nature? In the process, Darwin also described this second way evolution can happen: human-directed evolution. We’re awash in it today, from our accidental development of antibiotic-resistant bacteria to wheat that resists devastating rust.

Genetic drift: fixed or lost

What about traits that have no effect either way, that are just there? One possible example in us might be attached earlobes. Good? Bad? Ugly? Well…they don’t appear to have much to do with whether or not we reproduce. They’re just there.

When a trait leaves nature so apparently disinterested, the alleles underlying it don’t experience selection. Instead, they drift in one direction or another, to extinction or 100 percent frequency. When an allele drifts to disappearance, we say that it is lost from the population. When it drifts to 100 percent presence, we say that it has become fixed. This process of evolution by genetic drift reduces variation in a population. Eventually, everyone will have it, or no one will.

Gene flow: genes in, genes out

Another way for a population to change over time is for it to experience a new infusion of genes or to lose a lot of them. This process of gene flow into or out of the population occurs because of migration in or out. Either of these events can change the allele frequency in a population, and that means that gene flow is another was that evolution can happen.

If gene flow happens between two different species, as can occur more with plants, then not only has the population changed significantly, but the new hybrid that results could be a whole new species. How do you think we get those tangelos?

Horizontal gene transfer

One interesting mechanism of evolution is horizontal gene transfer. When we think of passing along genes, we usually envision a vertical transfer through generations, from parent to offspring. But what if you could just walk up to a person and hand over some of your genes to them, genes that they incorporate into their own genome in each of their cells?

Of course, we don’t really do that–at least, not much, not yet–but microbes do this kind of thing all the time. Viruses that hijack a cell’s genome to reproduce can accidentally leave behind a bit of gene and voila! It’s a gene change. Bacteria can reach out to other living bacteria and transfer genetic material to them, possibly altering the traits of the population.

Evolutionary events

Sometimes, events happen at a large scale that have huge and rapid effects on the overall makeup of a population. These big changes mark some of the turning points in the evolutionary history of many species.

Cheetahs underwent a bottleneck that
has left them with little genetic variation.
Photo credit: Malene Thyssen, via
Bottlenecks: losing variation

The word bottleneck pretty much says it all. Something happens over time to reduce the population so much that only a relatively few individuals survive. A bottleneck of this sort reduces the variability of a population. These events can be natural–such as those resulting from natural disasters–or they can be human induced, such as species bottlenecks we’ve induced through overhunting or habitat reduction.

Founder effect: starting small

Sometimes, the genes flow out of a population. This flow occurs when individuals leave and migrate elsewhere. They take their genes with them (obviously), and the populations they found will initially carry only those genes. Whatever they had with them genetically when they founded the population can affect that population. If there’s a gene that gives everyone a deadly reaction to barbiturates, that population will have a higher-than-usual frequency of people with that response, thanks to this founder effect.

Gene flow leads to two key points to make about evolution: First, a population carries only the genes it inherits and generally acquires new versions through mutation or gene flow. Second, that gene for lethal susceptibility to a drug would be meaningless in a natural selection context as long as the environment didn’t include exposure to that drug. The take-home message is this: What’s OK for one environment may or may not be fit for another environment. The nature of Nature is change, and Nature offers no guarantees.

Hardy-Weinberg: when evolution is absent

With all of these possible mechanisms for evolution under their belts, scientists needed a way to measure whether or not the frequency of specific alleles was changing over time in a given population or staying in equilibrium. Not an easy job. They found–“they” being G. H. Hardy and Wilhelm Weinberg–that the best way to measure this was to predict what the outcome would be if there were no change in allele frequencies. In other words, to predict that from generation to generation, allele frequencies would simply stay in equilibrium. If measurements over time yielded changing frequencies, then the implication would be that evolution has happened.

Defining “Not Evolving”

So what does it mean to not evolve? There are some basic scenarios that must exist for a population not to be experiencing a change in allele frequency, i.e., no evolution. If there is a change, then one of the items in the list below must be false:

·       Very large population (genetic drift can be a strong evolutionary mechanism in small populations)

·       No migrations (in other words, no gene flow)

·       No net mutations (no new variation introduced)

·       Random mating (directed mating is one way nature selects organisms)

·       No natural selection

In other words, a population that is not evolving is experiencing a complete absence of evolutionary processes. If any one of these is absent from a given population, then evolution is occurring and allele frequencies from generation to generation won’t be in equilibrium.

Convergent Evolution

Arguably the most famous of the
egg-laying monotremes, the improbable-
seeming platypus. License.
One of the best examples of the influences of environmental pressures is what happens in similar environments a world apart. Before the modern-day groupings of mammals arose, the continent of Australiaseparated from the rest of the world’s land masses, taking the proto-mammals that lived there with it. Over the ensuing millennia, these proto-mammals in Australiaevolved into the native species we see today on that continent, all marsupialsor monotremes.

Among mammals, there’s a division among those that lay eggs (monotremes), those that do most gestating in a pouch rather than a uterus (marsupials), and eutherians, which use a uterus for gestation (placental mammals).

Elsewhere in the world, most mammals developed from a common eutherian ancestor and, where marsupials still persisted, probably outcompeted them. In spite of this lengthy separation and different ancestry, however, for many of the examples of placental mammals, Australiahas a similar marsupial match. There’s the marsupial rodent that is like the rat. The marsupial wolf that is like the placental wolf. There’s even a marsupial anteater to match the placental one.

How did that happen an ocean apart with no gene flow? The answer is natural selection. The environment that made an organism with anteater characteristics best fit in South America was similar to the environment that made those characteristics a good fit in Australia. Ditto the rats, ditto the wolf.

When similar environments result in unrelated organisms having similar characteristics, we call that process convergent evolution. It’s natural selection in relatively unrelated species in parallel. In both regions, nature uses the same set of environmental features to mold organisms into the best fit.

By Emily Willingham, DXS managing editor

Note: This explanation of evolution and how it happens is not intended to be comprehensive or detailed or to include all possible mechanisms of evolution. It is simply an overview. In addition, it does not address epigenetics, which will be the subject of a different explainer.

Drill, baby, drill — microbial-style

Could the oil energy needed to light up this drill
come directly from soil bacteria instead of the soil?
Image credit: Obakeneko; via Wikimedia Commons

By Jeffrey Perkel, DXS tech editor

It’s no secret that America’s petroleum addiction is a problem in need of a solution. “Drill, baby, drill” notwithstanding, this country eventually will have to find a way to survive without low-cost oil – or at least, find another way to make it.

A recent MIT press release suggests one route to energy independence: soil bacteria. The release, Teaching a microbe to make fuel,” details a recent study from MIT graduate student Jingnan Lu, research scientist Christopher Brigham, and their lab director, Anthony Sinskey.

What Brigham, Lu, and their colleagues did was convince a soil bacterium called Ralstonia eutropha to turn carbon into gasoline –- specifically, the four-carbon molecules iso-butanol and 3-methyl-1-butanol.

Ralstonia eutropha bacteria in culture
How’d they do that? It was a simple matter of microbial engineering. As detailed in MIT’s description:
… in the microbe’s natural state, when its source of essential nutrients such as nitrate or phosphate is restricted, “it will go into carbon-storage mode,” [Brigham says,] essentially storing away food for later use when it senses that resources are limited. 
 “What it does is take whatever carbon is available, and stores it in the form of a polymer, which is similar in its properties to a lot of petroleum-based plastics,” Brigham says. By knocking out a few genes, inserting a gene from another organism and tinkering with the expression of other genes, Brigham and his colleagues were able to redirect the microbe to make fuel instead of plastic.

That last sentence makes the process sound easier than it was. It took a full year of work to effect that transformation, Brigham tells me, and no wonder: Bacteria don’t normally make gasoline. But they do make amino acids, the protein building blocks that all living things need to survive. The team realized that Ralstonia bacteria create one particular group of amino acids (the so-called branched-chain amino acids) using chemical intermediates that they could coopt to turn sugar into fuel.

To realize that potential, Brigham and his colleagues first had to get Ralstonia to refocus its energies, literally. When stressed, the bacteria store carbon in a polymer–a chain of molecules–called PHB. The bacterium executes this particular biochemical program extremely effectively, cranking out enough polymer to account for more than 80% of the cell’s mass. Brigham and Lu had to redirect that enzymatic zeal towards gasoline instead. So, they knocked out the genes involved in building PHB.

Next, they added some missing chemical pieces. I said earlier that the branched-chain amino acid pathway includes an intermediate that could be used to make gasoline. To do that, the cells need a missing bit of hardware — specifically, an enzyme to convert that chemical intermediate into something the gasoline-making enzymes can use. That enzyme is called KIVD, and Ralstonia does not make it. But another bacterium, Lactococcus lactis, does make it. Brigham and Lu borrowed the related bit of genetic material from Lactococcus lactis, expressed it in Ralstonia, and –- not much happened.

As University of California, Berkeley, biochemical engineer Jay Keasling explained to me, the cell in such situations is literally a chemical factory. For the factory to run smoothly, all the factory workers –- the enzymes -– need to be fully engaged at the right time. That won’t happen if one enzyme is cranking out lots of its product but others are not. Intermediate products will start piling up, reducing efficiency and potentially poisoning the cell.

In this case, with KIVD, the cells had all the necessary pieces to make gasoline. But they weren’t producing them at the same levels. In other words, the factory had more workers at one part of the assembly line than at others. As a result, productivity was relatively low (about 10 mg isobutanol per liter of culture). To boost that output, the researchers dialed up expression levels of several proteins to get them all in sync. They also shut down a handful of other chemical assembly lines, too, “carbon sinks” that could siphon off intermediates.

When all was said and done, the cells could produce about 310 mg of gasoline per liter of culture. That gas conveniently drifts into the culture medium surrounding the cells, from which it is easily extracted. Now, says Brigham, the trick is optimizing the process.

In the meantime, others are working towards the same goal. Researchers have considerable experience getting bacteria and yeast to produce compounds they don’t normally make — the antimalarial drug artemisinin, for instance -– and microbial biofuel development is a research target at the Joint BioEnergy Institute (headed by Keasling), Synthetic Genomics, and LS9, among other places.

Often, those biofuel strategies rely on plants to produce their starting materials. And that’s the really cool part about Sinskey’s work: Ralstonia can eat almost anything, Brigham says, from carbon dioxide and organic acids to fatty acids and sugar. Brigham envisions coupling these organisms to waste streams, such that they can suck out the nutrients and turn them into fuel, no plants required.

Garbage in, fuel out: Now that’s a microbial trick I can get behind. 

(If you’re interested, you can read Brigham and Lu’s work here.)

Image: Christopher Brigham /

Miscarriage: When a beginning is not a beginning

The “Pregnant Woman” statue
at Ireland Park, Toronto, by Rowan Gillespie

Photo credit: Benson Kua.
[Editor's note: We are pleased to be able to run this post by Dr. Kate Clancy that first appeared at Clancy's Scientific American blog, the wonderful Context and Variation. Clancy is an Assistant Professor of Anthropology at the University of Illinois. She studies the evolutionary medicine of women’s reproductive physiology, and blogs about her field, the evolution of human behavior and issues for women in science. You can follow her on Twitter--which we strongly recommend, particularly if you're interested in human behavior, evolutionary medicine, and ladybusiness--@KateClancy.]
Over the course of my training to become a biological anthropologist with a specialty in women’s reproductive ecology and life history theory, or ladybusiness expert, I have learned a lot about miscarriage. Only it wasn’t miscarriage, it was spontaneous abortion. Except that some didn’t like the term spontaneous abortion and used intrauterine mortality (Wood, 1994). Or fetal loss. Fetal loss is probably the most common.
There is also pregnancy loss (Holman and Wood, 2001). You can use that term, too. Oh, or a Continue reading