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25 myths about the flu vaccine debunked

Setting the record straight on the flu vaccine

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

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

                                                  

Big Molecules with Small Building Blocks

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

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

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

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

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

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

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

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

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

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

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

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

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

Sugar and Fuel

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

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

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

Polysaccharides: Fuel and Form

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

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

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

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

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

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

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

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

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

Lipids: The Fatty Trifecta

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

Fats: the Good, the Bad, the Neutral

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

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

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

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

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

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

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

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

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

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

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

Phospholipids: An Abundant Fat

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

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

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

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

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

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

Steroids: Here to Pump You Up?

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

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

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

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

Proteins

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

Levels of Structure

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

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

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

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

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

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

A Plethora of Purposes

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

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

Nucleic Acids

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

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

DNA vs. RNA: A Matter of Structure

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

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

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

DNA vs. RNA: Function Wars

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

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

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


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

Pertussis: Get the vax or at least listen to why you should

by Tara Haelle, DXS contributor

The past few weeks have seen big news for vaccines. A bill related to vaccine exemptions was signed into law, a court ruled against a parent’s refusal to vaccinate and a recent study points out the value of vaccinating a household — especially mom — to protect a young infant from pertussis (whooping cough).


The latest news is that Governor Jerry Brown in California signed a bill last Sunday that had been sitting on his desk since September 6 and was the target of a number of rallies by parents who didn’t want to see it pass. Among those fighting the bill was Dr. Bob Sears, who says he walks a middle ground with vaccine policy but in reality tends to flirt with those who fear vaccines and rely on misinformation. Although some parents claimed the bill took away their right to choose whether their children get vaccinated, it actually just ensures they get good medical information before they make that choice.

Photo by Dave Gostisha at sxc.hu.
The bill-now-law, AB 2109, proposed by a pediatrician, requires parents to get a statement signed by a health care practitioner that the parents/guardians have received accurate, evidence-based information about the risks and benefits of vaccines before they can use a personal belief exemption to prevent their children from being vaccinated. This law is a tremendous triumph both for informed consent in medical decisions and for the public health of children in California, which saw a considerable outbreak of pertussis (whooping cough) in 2010. Washington state passed a similar law last year and saw 25 percent drop in exemptions filed. Other states are considering similar laws in a nationwide overall shift toward strengthening exemption requirements.


Why are these laws so important? In short, they kill two birds with one stone: They make it more difficult for parents to casually opt out of vaccines on philosophical grounds (as opposed to religious or medical reasons), and they require parents who want to opt out to at least hear out a pediatrician on accurate information about the actual risks (which do exist) and benefits (there are so many) of immunizations. Parents who are determined not to vaccinate their children can still refuse, but many parents who might have signed those forms out of convenience — it can be easier to sign than to get to the doctor’s office for the shot — will now at least hear the impact a decision not to vaccinate can have on the community. (Hopefully, they go to a health care practitioner other than Dr. Sears, whose stances have gradually been moving further and further toward unscientific and misinformation of those who oppose vaccines.) 

It’s also particularly notable that California and Washington are the most recent states to tighten opt-out procedures for parents because they are home to some of the more recent pertussis outbreaks. More on that in a moment.

First, a bit of background on vaccine exemptions: Only 20 states have personal belief exemptions, and until last year, eight of these simply require nothing more than a parent signature. Now that number is down to six. (Other types of requirements for philosophical exemptions include writing out your reasons for exemption, requiring the forms to be notarized, requiring education on the risks/benefits, direct involvement from the state or local health department or renewals.)


All states have medical exemptions for patients who have auto-immune disorders, have proof that their bodies do not respond to immunization, have documented allergic reactions or have other circumstances which make it too risky for them to be immunized. In fact, these are the very people that the rest of the population protects through herd immunity when vaccination rates are up where they should be. All but two states have religious exemptions (Mississippi and West Virginia are the exceptions).


And that brings us to some less covered but still significant news about one state’s ruling on a particular case involving religious exemption. Last week, the U.S. district court in Ohio ruled that one woman’s claim of religious objection was insufficient for her children to be exempted from being vaccinated. Read the whole story here. To be fair, this is a complex case involving far more than vaccines; the mother is clearly neglectful and the overall situation is pretty crappy. However, the fact that the court found “the mere assertion of a religious belief … does not automatically trigger First Amendment protections,” and that “it has long been recognized that local authorities may constitutionally mandate vaccinations” is significant in a state that offers both religious and personal belief exemptions.


Because of the danger to public health when clusters of kids are not vaccinated, my personal opinion on this issue is that “personal belief” exemptions should not be offered in any state, and religious exemptions should be extremely difficult to get, if they are offered at all (which may be the best overall route). Some cite the Amish, Mennonite and Christian Scientists, though actually the majority of Amish children, at least, are vaccinated, and it doesn’t appear that any Amish objections to vaccines are for religious reasons. Christian Scientists have successfully been convicted of neglect in other incidents where their children died from inadequate medical care, though their religion is the only one I’m aware of that vaccination actually, explicitly violates. 

The constitutionality of religious exemptions is dubious as well. At the very least, however, anyone seeking any exemption should certainly to see a doctor first to be sure they have accurate information and not simply what they have seen online or heard at the playground. Those who absolutely will not vaccinate in states without exemptions may also opt to home school or send their children to private schools that don’t have requirements. But considering the increasing rates of measles and the increasing epidemics of pertussis, the need for high vaccination coverage in communities is more important than ever.

It is true that the pertussis vaccine is not as effective as the old one used to be, something I wrote about a few weeks ago.  It’s also true that pertussis peaks every five years or so, but even taking into account the peaks, the overall rate of cases has been steadily on the move upward. Dr. Offit, the chief of the Division of Infectious Disease at Children’s Hospital of Philadelphia and a very vocal advocate of vaccines, said he believes that parents’ refusals to vaccinate are playing their own small part in the increase.


“The major contributor is waning immunity. The minor contributor is the choice not vaccinate,” he said. He noted that there are researchers working on the problem, as this Nature article notes (paywall), including attempts to make a better vaccine with more adjuvants, the additives that enhance the body’s immune response to a vaccine. While vaccinated children and adults have been high among the numbers of those getting whooping cough, getting the vaccine remains among the best ways to reduce your risk of contracting it — or of having less rough of a time with it if you do get it. Dr. Offit also pointed out that pregnant women in particular should be sure they get their booster.


Which brings us to the study published last week that relates to the most important reason to get vaccinated, at least from the perspective of preventing deaths — to protect the babies who are too young for the vaccine but most likely to contract it and die from it.

The study, published in the journal Epidemiology last week, looked at how frequently pertussis was transmitted to others within the same household and how effective “cocooning” is. Cocooning is vaccinating all the household members who can get the vaccine for the purpose of protecting young babies who can’t yet be vaccinated for the disease.


They found that transmission rates within the home are high, especially for mothers passing the illness on to their children. Therefore, making sure all pregnant women are vaccinated before their baby arrives would, according to their calculations, cut the risk in half that a baby would contract pertussis. The evidence for sibling vaccination, though weaker, still points to the value of overall cocooning: “Vaccination of siblings is less effective in preventing transmission within the household, but may be as effective overall because siblings more often introduce an infection in the household.”


Indeed, this year, siblings’ bringing home the disease appears more likely than ever in the states experiencing big outbreaks this year. Just how bad are the numbers? Well, 2010 was the last five-year peak, which totaled 27,550 cases. It’s currently September of 2012, and the numbers last reported to the CDC were at 29,834, and that doesn’t even include over 3,700 cases in Minnesota that haven’t been officially reported to the CDC yet. These numbers, which include 14 deaths (primarily of babies under 3 months), may very well end up doubling the 2011 total of 18,719 if they continue at the current rate through the end of the year. It’s the biggest pertussis outbreak since 1959.


Not surprisingly, the majority of the states leading in pertussis cases are also among those that offer personal belief exemptions. Washington, despite their new law, is sitting at 4,190 cases, quadrupling their 2011 count of 965. This is the state where 7.6 percent of parents opted for exemptions (among all grade levels, not just kindergarten) in 2008-09, more than four times the national rate of about 1.5 percent. Minnesota and Wisconsin have similarly high rates and both have personal belief exemptions. The most recent numbers out of Minnesota are 3,748 — they had just 661 cases last year. Wisconsin is leading the nation with 4,640 cases, up from 1,192 in 2011, at last report in the Sept. 28 Morbidity and Mortality Weekly Report (pdf) at the CDC.


But the increases are being seen across the nation, as this CDC map shows. Texas (1,287 cases to date this year), Pennsylvania (1,428 cases) and Colorado (897 cases, though they averaged 158 over the past four years) are among other states with personal belief exemptions (though the Texas one has significant restrictions and hoops to jump through). But it’s clear the decreased effectiveness of the vaccine is playing the biggest role, especially in places like Iowa (1,168 cases) and New York (2,107), neither of which offer personal belief exemptions.


Again, though, a less effective vaccine does not mean a worthless vaccine. It still offers 85 percent protection when you get the shot or the booster, and even as it loses some effectiveness as the years go by, you’re far less likely to have a severe case if you do get the disease. And you’re protecting those around you, including the babies who have only been here a few months and are the most susceptible to catching and dying from the disease.


Bottom line — it’s worth it to get the shot, and to make sure your kids do too.


Opinions expressed in this article do not either necessarily reflect or conflict with those of the DXS editorial team or contributors.
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[Tara Haelle (www.tarahaelle.com) is a health and science writer and a photojournalist based in Peoria, IL after years as a Texan, where she earned her undergraduate degrees and MA in journalism at UT-Austin. She’s the mental health editor for dailyRx.com in addition to reporting on pediatrics, vaccines, sleep, parenting, prenatal care and obesity. Her blog, Red Wine & Apple Sauce, focuses on health and science news for moms, and you can follow her on Twitter at @health_reporter and @tarasue. She’s also swum with 9 different species of sharks, climbed Kilimanjaro and backpacked in over 40 countries, but that was in the years of B.C. (Before Children). She finds that two-year-olds are tougher to tussle with than tiger sharks.]

Leaky gut and wonky immune response might be double whammy leading to inflammatory bowel disease (in mice)

A case of ulcerative colitis, a form of inflammatory bowel disease.
Photo via Wikimedia Commons. Credit: Samir.

A two-hit punch in the gut might explain why some people find themselves alone among their closest relatives in having inflammatory bowel disease (IBD). The double gut punches come in the form of a compromised intestinal wall coupled with a poorly behaved immune system, say Emory researchers, whose work using mice was published in the journal Immunity. IBDs include ulcerative colitis and Crohn’s disease, the latter of which is slightly more common in women.

An inflamed gut is the key feature of IBD, which affects about 600,000 people in the United States each year. Typical symptoms include bloody diarrhea, fever, and cramps, which can come and go with bouts of severe inflammation punctuating relatively calm periods. The going explanation for these disorders is a wonky immune system, but some breach of the barrier that keeps your gut contents in their place is also implicated. Researchers also have identified a link between bouts of gastroenteritis–known around my house as “throw-up” illnesses–and development of IBD. What’s remained unclear is how people who have these so-called “leaky guts” don’t develop a disease like Crohn’s when a close family member with a leaky gut does.

These hints in humans led the Emory investigators to examine the interaction of a compromised gut and the immune system in mice. The mice in the study had ‘leaky’ gut walls because they lacked a protein that usually ties cells together into water-tight sheets. Without these proteins sealing up the intestinal lining, bacteria and other components can make their way their deeper into the intestinal wall, triggering chronic inflammation.

The thing is, these mice with their leaky guts don’t develop colitis spontaneously, a situation, the investigators hypothesized, that  reflects families full of people with leaky guts but rarely IBD.  Permeable intestines alone aren’t enough. Some other dysfunction related to the immune system, they figured, must pile onto that leakiness and bring on the inflammatory disorder.

If you’re an immunologist–which I am not–an obvious choice for investigation is a class of immune cells called T cells. These cells come in a dizzying array of types, but one way to narrow them down relies on a protein that some but not all of them make. Pulling out the T cells that make this protein, says Timothy Denning, PhD, a mucosal immunologist at Emory and study author, is “the simplest way” to start examining the immune system involvement because these cells play a ton of roles in balancing different immune responses. So, they first collected the T cells carrying this protein from the mouse intestines.

“There are good and bad” versions of T cells carrying these identifier molecules, though, says Denning, so the next step was to find the “good” ones that might be protecting mice in spite of their sieve-like intestinal linings. To achieve that goal required some fancier lab moves. “We stimulated the cells and looked at the cytokines (immune signaling molecules) they make,” explains Charles Parkos, MD, PhD, an experimental pathologist and mucosal immunologist at Emory and also a paper author. “We found that the cells in the mice that were better protected predominantly secreted TGF-beta, a prototypic marker for ‘good’ cells.”

One of the things T cells do with TGF-beta is to talk to B cells, another class of immune cell. B cells take responsibility for remembering what’s attacked you in the past and marshaling forces if it attacks again. Also, when B cells are stimulated, explains Parkos, one way they respond is to release proteins–antibodies–that target the offending invaders. In the gut, the kind of antibody the B cells make in response to the TGF-beta message is immunoglobulin A, or IgA. This antibody “keeps bacteria in check,” says Denning, and also probably “broadly neutralizes lots of different microorganisms” in the intestines, adds Parkos.

The Emory-based team found that when the leaky-gut mice also had an IgA deficiency, they became more open to the types of immune cells that cause gut inflammation. The animals also were far more susceptible to colitis triggered by a chemical treatment in the lab and had much worse disease. Without the IgA, the mice couldn’t dampen inflammation triggered by bacteria slipping through the intestinal breaches. The results of this two-step physiological fail, in mice, at least: severe inflammatory  gut disease.

Denning cautions that these results in mice don’t suggest a rush to TGF-beta or IgA treatment for inflammatory diseases. “TGF-beta has many effects and on many different cell types, and too much is not a good thing because it’s known to play a role in fibrosis and cancer,” says Denning. “If your child had IBD, the last thing you’d want to do is to give TGF-beta.” Much more work has to be done, he adds, for a better understanding of the implications of these results before anyone starts talking about therapies. Parkos agrees. “To our knowledge, administration of TGF-beta is not a viable therapy.”

The same applies for IgA, Denning says. “We couldn’t just take any old B cells and get them to make IgA and put it in and hope that it would do something,” he says. The reason, he explains, is because B cells make many different types of IgA molecules specific to foreign invaders they encounter, a process that happens on the spot, not in a lab dish. “We need to understand much more about the basic mechanisms, but we do believe that these pathways would be critical to induce in people who are more susceptible to IBD, such as first-degree relatives.”

Some research groups are conducting trials to treat IBDs with helminth worms–intestinal parasites–on the hypothesis that their presence would induce a balance in the immune system and tamp down an overactive inflammatory response. The balance in this case is supposed to be between two competing aspects of the immune system, called Th1 and Th2. But one issue in these intestinal inflammatory disorders, says Denning, is that Crohn’s is linked to Th1 hyperactivity while ulcerative colitis is associated with Th2.

Yet the worms appear to show some beneficial effects in both disorders, in spite of the different involvement of Th1 and Th2. The TGF-beta signaling effect on IgA that the Emory group identified operates by a third component, tentatively identified as Th3. Both Denning and Parkos are intrigued by the possibility that the presence of helminths might trigger this pathway, rather than influencing Th1 or Th2, explaining why worm treatment has sometimes proved useful for both Crohn’s and ulcerative colitis.

As for why IBD arises, the researchers hope their findings answer some questions. “There are different camps in the IBD community,” says Parkos. “Some say immune system, some say barrier, others say genetics or environment.” What they have with their results, he says, is evidence showing that a leak alone is not enough and that a wonky immune system alone is not enough. But the double-whammy of a leaky gut and an absence of immune protection “dramatically increase susceptibility to disease, and that helps explain why diseases are so complicated,” he says.

The use of parasitic worms for these inflammatory diseases arose from the concept of the hygiene hypothesis, the idea that we’re too clean in the modern developed world, leading to an immune imbalance that can include chronic inflammation and autoimmune disorders. Asked about any links between the hygiene hypothesis and this pathway to IBD they identified in mice, Denning says, “It’s not obviously all about the parasites. That’s just one key thing–it’s probably an exposure to a lot of different types of things in your gut and airways.” He describes the immune system as being a thermostat that registers a specific set-point early on based on these exposures. This set-point, he says, is lower in people who grow up in developed countries like the United States and leads to a “trigger-happy immune system that is ready to fire much more easily.”

That doesn’t mean that a worm infection or just being dirty will prevent your developing IBD. That said, these immunologists both have the same general advice for parents regarding their children. “Being too clean is not a good thing,” they agree. As immunologists, he adds, “We feel exactly the opposite. Go play in the dirt.”

HIV+ doesn’t mean you can’t have children

Prenatal care and treatment access are big factors.

By Laura Newman     

Last week, the media got all excited about the possibility of a cure for HIV perinatal transmission. What was lacking was the recognition that the public remains largely ignorant about HIV in pregnant women. Yet with good wellness care, prevention, HIV testing, and medication,HIV  transmission from mother to child can be close to zero. The public needs to know that women who are pregnant and HIV positive can also live good-quality lives, as can their children.

CDCgraphicHIVThanks to Dr. Judy Levison, an obstetrician/gynecologist whose career centers on caring for HIV-pregnant women, I began to learn how scientific advancements in HIV-care make it possible for pregnant women with HIV and HIV-positive men to have children and not transmit the virus to their newborns. In the midst of this learning experience, I found out that a young woman I know, “Angela*,” was HIV positive and wanted to plan a pregnancy. I was shocked; I knew plenty of gay men with HIV, but rarely had I met a woman who had contracted the virus. Planning a pregnancy while being infected with HIV was something that I couldn’t imagine.

“Angela” is married and has lived with HIV for some years, with a low viral load by taking good care of herself and taking recommended antiretroviral therapy, when needed. She sought artificial insemination, one of several options available to HIV-affected couples. It worked. When she was planning her pregnancy, her parents were resistant. They worried that even though she is healthy now, that might change. They couldn’t imagine being saddled with taking care of a young child. Her parents’ resistance reminded me of the old coming-out stories we used to hear and how parents adapted to learning their child is gay. To their credit, both parents soon rose to the occasion. Angela and her spouse have a healthy toddler, and the grandparents love spending time with him.

Angela’s story isn’t everyone’s story. The hubbub at the recent 20th Conference on Retroviruses and Opportunistic Infections was not on the “functional cure” of the baby born to a pregnant woman with HIV, but on why, in this day and age, the mother doesn’t seem to have received the recommended prenatal care and antiretroviral therapy herself. Under what circumstances did she deliver? How did mom and baby get lost in the healthcare system? It’s far too easy to be captivated by a potential breakthrough and forget that plenty of people don’t get access to basic science-backed care that prevents HIV transmission in the first place.

As I describe below and as Angela’s experience illustrates, a lot of evidence shows that it is very safe for women with HIV to get pregnant, have healthy babies, and not transmit HIV to their children. Unfortunately, for many pregnant women with HIV, harsh judgments and inaccurate assumptions often carry the day. Let’s just say that HIV-positive moms and their kids have not earned the acceptance allotted to, say, a Magic Johnson, who has had HIV for decades, and with good HIV and wellness care, lives a good-quality life.

These inroads in science-based HIV prevention and care that have helped Johnson so much lag behind in poor and minority communities in the United States and low-resource countries around the world. HIV disproportionally affects African-Americans in the United States, and access to care, Medicaid cuts, and poverty reduce the chance that many people in need will receive good state-of-the-art prevention (regular testing, practicing safe sex, not sharing drug needles) and wellness care. Perinatal transmission could well rise in these communities.

Facing down ignorance

At first, being pregnant was not easy for Angela — not because her pregnancy was hard (it was not) — but because of the uneasiness some of her coworkers expressed about her becoming pregnant as an HIV-positive woman. Even though Angela worked in healthcare, some of her coworkers thought she had no business being pregnant. When she complained to her supervisor, the manager urged Angela to take it upon herself to educate staff about scientifically proven treatments for pregnant women with HIV that help moms stay well and prevent transmission to the baby. Angela asked instead for an in-service training, which was scheduled. Her colleagues’ attitudes turned around after the in-service.

It meant a lot to her to change the culture.

Angela had a normal term delivery, gave birth to a healthy baby, who is now a toddler, with no sign of HIV infection. Angela’s viral load remains undetectable. They are living healthy, high-quality lives like many other families, moms, and children.

The parents and prenatal planning

The ideal in the setting of HIV infection is that both partners are involved in preconception planning. Prevention of transmission of HIV from an HIV-positive father to an HIV-negative mom and fetus is now possible. The door is now open to HIV-positive men and women who want families but have HIV. Any plans they had to become parents have not simply vanished.

HIV research has advanced to the point that we now know that if HIV-positive individuals work with knowledgeable medical providers and have good access to proven practices, parents and children do quite well. Essential practices include:

  • Before trying to conceive, people should take antiretroviral drugs and have their infection under control, shown by a low viral load or undetectable levels of the virus (“undetectable” levels vary, depending on the lab) in their blood;
  • Couples are instructed to have unprotected sex only when the woman is ovulating. Current guidelines recommend using an ovulation prediction kit, which you can purchase at most drugstores.
  • Artificial insemination is another option that HIV-affected couples are using, as Angela did.
  • HIV testing is recommended routinely for all pregnant women, as well as for all non-pregnant adults and teens.
  • If a woman learns during her pregnancy for the first time that she is HIV infected, she can work with her healthcare provider to stay healthy, prevent mother-to-child transmission, and prevent passing HIV to her partner.

 

In general, people infected with HIV who are not pregnant begin taking anti-HIV medications when their CD4 counts fall below 500 cells/mm3 (HIV targets these immune cells and destroys them, compromising a person’s immunity). The medication regimen during pregnancy depends on whether or not you are taking medication to improve your own health or just your baby’s. In many cases, healthy women delay starting antiretroviral medication until the second trimester, which is when all women should be on HIV medication. However, HIV medication and interactions with other drugs and the fetus are complicated and require consultation with a physician. If women are diagnosed later in a pregnancy, they should start HIV drugs then. You can find detailed recommendations here.

During childbirth, women whose viral loads are still undetectable can have normal vaginal deliveries. However, according to the National Institutes of Health and other authorities, scheduled cesarean delivery at 38 weeks of gestation is recommended to reduce perinatal transmission of HIV for women with HIV-RNA levels >1,000 copies/mL or unknown HIV levels near the time of delivery, regardless of whether they were taking recommended antiretroviral drugs during pregnancy. The guidelines state that when there is a low rate of transmission (viral loads lower than 1000 copies/mL), the benefits of a scheduled c-section are unclear. Dr. Levison, an obstetrician/gynecologist at Baylor College of Medicine, Houston, TX, says that in her practice, women rarely need a cesarean section.

The newborn child

In the United States, breastfeeding is discouraged because HIV can be transmitted in breast milk. According to the Centers for Disease Control and Prevention (CDC), the risk for HIV transmission goes up as much as 45%. However, the topic of breastfeeding remains controversial. In healthy women with no HIV history, the broad consensus is that breastfeeding is best, giving babies excellent nutrition and helping the infant bond with mom. And many parts of the world have problems with sanitation and dirty water, making breastfeeding preferable to mixing formula. Outside of the US, according to Levison, in the UK, breastfeeding guidelines are more liberal. Furthermore, in some cultures, women are afraid not to breastfeed for fear that they will be outed as having an HIV infection, according to Levison, so many treating physicians adapt practice to the culture, preferences of the mom. Internationally, for example, in Africa, women often breastfeed and remain on antiretroviral drugs during that time. Formula is also costly. In the US, poor moms are eligible for formula through the federal Women’s Infants and Children’s nutritional support program.

Besides breastfeeding, HIV-positive moms need to know that pre-chewing of food before feeding baby is a transmission risk.

As soon as a woman goes into labor and during childbirth, the infantmust begin a six-week course of the antiretroviral medication zidovudine (AZT). Current guidelines also state that the baby should be tested for HIV at 14 to 21 days, at 1 to 2 months, and again at 4 to 6 months. If the viral load remains undetectable after two tests, the baby is considered to not have gotten HIV.

Resolving resource disparities

The moms, dads, and kids with HIV have enormous potential to live healthy lives for decades on proven antiretroviral drugs.

In fact, a December 2012 CDC Fact Sheet states that the number of women with HIV giving birth in the United States increased approximately 30% from 6,000 to 7,000 in 2000 to 8700 in 2006. During that same time frame, the estimated number of perinatal infections per year in all 50 states and 5 dependent areas continued to decline.

It’s not all good news, though, because of marked disparities in resource allocation and pre- and perinatal care. According to CDC data, 63% of perinatal infections were in blacks/African-Americans; 22% were in Hispanics/Latinos, and 13% were in whites. That leaves a lot of work to be done in enhancing targeted prevention programs.

Another recent milestone is that the US Preventive Services Task Force is finally about to endorse universal HIV testing, long after the CDC backed such a move in 2006. This milestone is important to because it is also linked to health reform.  All public and private health plans are required to provide coverage for U.S. Preventive Services Task Force-recommended preventive services without patient copayments.

With this availability, perhaps women might learn about an HIV infection before they become pregnant, giving them time to have their own treatment in place before it is too late to protect the baby. The case report of the baby cured of HIV gives a lot of hope, but even more preferable would be preventing HIV infection in the first place, through safe sex and not exchanging needles. Once people become infected, for whatever reason, their lives should no longer be viewed as if they are at in a holding pattern until death.

The world needs to know that just like every other mom, dads and pregnant women with HIV can parent children, stay healthy, and not transmit the virus to their babies. Paramount in this is universal HIV testing for adults and teens, prevention programs, and ensuring scientifically proven treatment of the mother before, during, and after her pregnancy.

*Named changed to protect identity. Continue reading