Is the bar high enough for screening breast ultrasounds for breast cancer?

The stormy landscape of the breast, as seen
on ultrasound. At top center (dark circle) is
a small cyst. Source: Wikimedia Commons.
Credit: Nevit Dilmen.
By Laura Newman, contributor

In a unanimous decision, FDA has approved the first breast ultrasound imaging system for dense breast tissue “for use in combination with a standard mammography in women with dense breast tissue who have a negative mammogram and no symptoms of breast cancer.” Patients should not interpret FDA’s approval of the somo-v Automated Breast Ultrasound System as an endorsement of the device as necessarily beneficial for this indication and this will be a thorny concept for many patients to appreciate.

If the approval did not take place in the setting of intense pressure to both inform women that they have dense breasts and lobbying to roll out all sorts of imaging studies quickly, no matter how well they have been studied, it would not be worth posting.

Dense breasts are worrisome to women, especially young women (in their 40s particularly) because they have proved a risk factor for developing breast cancer. Doing ultrasound on every woman with dense breasts, though, who has no symptoms, and a normal mammogram potentially encompasses as many as 40% of women undergoing screening mammography who also have dense breasts, according to the FDA’s press release. Dense breast tissue is most common in young women, specifically women in their forties, and breast density declines with age.

The limitations of mammography in seeing through dense breast tissue have been well known for decades and the search has been on for better imaging studies. Government appointed panels have reviewed the issue and mammography for women in their forties has been controversial. What’s new is the “Are You Dense?” patient movement and legislation to inform women that they have dense breasts.

Merits and pitfalls of device approval
The approval of breast ultrasound hinges on a study of 200 women with dense breast evaluated retrospectively at 13 sites across the United States with mammography and ultrasound. The study showed a statistically significant increase in breast cancer detection when ultrasound was used with mammography.

Approval of a device of this nature (noninvasive, already approved in general, but not for this indication) does not require the company to demonstrate that use of the device reduces morbidity or mortality, or that health benefits outweigh risks.

Eitan Amir, MD, PhD, medical oncologist at Princess Margaret Hospital, Toronto, Canada, said: “It’s really not a policy decision. All this is, is notice that if you want to buy the technology, you can.”

That’s clearly an important point, but not one that patients in the US understand. Patients hear “FDA approval” and assume that means a technology most certainly is for them and a necessary add-on. This disconnect in the FDA medical device approval process and in what patients think it means warrants an overhaul or at the minimum, a clarification for the public.

Materials for FDA submission are available on the FDA website, including the study filed with FDA and a PowerPoint presentation, but lots of luck, finding them quickly. “In the submission by Sunnyvale CA uSystems to FDA, the company stated that screening reduces lymph node positive breast cancer,” noted Amir. “There are few data to support this comment.”

Is cancer detection a sufficient goal?
In the FDA study, more cancers were identified with ultrasound. However, one has to question whether breast cancer detection alone is meaningful in driving use of a technology. In the past year, prostate cancer detection through PSA screening has been attacked because several studies and epidemiologists have found that screening is a poor predictor of who will die from prostate cancer or be bothered by it during their lifetime. We seem to be picking up findings that don’t lead to much to worry about, according to some researchers. Could new imaging studies for breast cancer suffer the same limitation? It is possible.

Another question is whether or not the detected cancers on ultrasound in the FDA study would have been identified shortly thereafter on a routine mammogram. It’s a question that is unclear from the FDA submission, according to Amir.

One of the problems that arises from excess screening is overdiagnosis, overtreatment, and high-cost, unaffordable care. An outcomes analysis of 9,232 women in the US Breast Cancer Surveillance Consortium led by Gretchen L. Gierach, PhD, MPH, at the National Institutes of Health MD, and published online in the August 21 Journal of the National Cancer Institute, revealed: “High mammographic breast density was not associated with risk of death from breast cancer or death from any cause after accounting for other patient and tumor characteristics.” –Gierach et al., 2012

Proposed breast cancer screening tests
Meanwhile, numerous imaging modalities have been proposed as an adjunct to mammography and as potential replacements for mammography. In 2002, proponents of positron emission tomography (PET) asked Medicare to approve pet scans for imaging dense breast tissue, especially in Asian women. The Medicare Coverage Advisory Commission heard testimony, but in the end, Medicare did not approve it for the dense-breast indication.

PET scans are far less popular today, while magnetic resonance imaging (AKA MR, MRI) and imaging have emerged as as adjuncts to mammography for women with certain risk factors. Like ultrasound, the outcomes data is not in the bag for screening with it.

In an interview with Monica Morrow, MD, Chief of Breast Surgery at Memorial Sloan-Kettering Cancer Center, New York, several months ago concerning the rise in legislation to inform women about dense breasts, which frequently leads to additional imaging studies, she said: “There is no good data that women with dense breasts benefit from additional MR screening.” She is not the only investigator to question potentially deleterious use of MR ahead of data collection and analysis. Many breast researchers have expressed fear that women will opt for double mastectomies, based on MR, that in the end, may have been absolutely unnecessary.

“There is one clear indication for MR screening,” stressed Morrow, explaining that women with BRCA mutations should be screened with MRI. “Outside of that group, there was no evidence that screening women with MR was beneficial.”

At just about every breast cancer meeting in the past two years, the benefits and harms of MR and other proposed screening modalities come up, and there is no consensus in the field.  It  should be noted, though, that plenty of breast physicians are skeptical about broad use of MR– not just generalists outside of the field. In other words, it is not breast and radiology specialists versus the US Preventive Services Task Force – a very important message for patients to understand.

One thing is clear: as these new technologies gain FDA approval, it will be a windfall for industry. If industry is successful and doctors are biased to promoting these tests, many may offer them on the estimated 40% of women with dense breasts who undergo routine mammograms, as well as other women evaluated as having a high lifetime risk.  The tests will be offered in a setting of unclear value and uncertain harms. Even though FDA has not approved breast MRI for screening dense breasts, breast MR is being used off label and it is far more costly than mammography.

When patients raise concerns about the unaffordability of medical care, they should be counseled about the uncertain benefit and potential harms of such a test. That may be a tall bill for most Americans to consider: it’s clear that the more is better philosophy is alive and well. Early detection of something, anything, even something dormant, going nowhere, is preferable to skipping a test, and risking who-knows-what, and that is something, most of us cannot imagine at the outset.

[Today's post is from Patient POVthe blog of Laura Newman, a science writer who has worked in health care for most of her adult life, first as a health policy analyst, and as a medical journalist for the last two decades. She was a proud member of the women’s health movement. She has a longstanding interest in what matters to patients and thinks that patients should play a major role in planning and operational discussions about healthcare. Laura’s news stories have appeared in Scientific American blogs, WebMD Medical News, Medscape, Drug Topics, Applied Neurology, Neurology Today, the Journal of the National Cancer Institute, The Lancet, and BMJ, and numerous other outlets. You can find her on Twitter @lauranewmanny.]

Ed note: The original version of this post contains a posted correction that is incorporated into the version you’ve read here.

The opinions in this article do not necessarily conflict with or reflect those of the DXS editorial team. 

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

For Dad: A guide on strokes, including a glossary of terms

A scanning electron micrograph of a blood clot.  Image credit: Steve Gschmeissner/Science Photo Library (http://www.sciencephoto.com/media/203271/enlarge#) 


On Monday January 1st, I overheard my dad telling my mom how his left arm was numb and that he had no strength in his left hand.  I immediately ran into the medicine cabinet, grabbed two aspirin, practically shoved them down my dad’s throat, and told him to get his coat.  He was going to the ER. 

As it turns out, my dad was having a stroke, which is basically the cessation of blood flow to an area in the brain.  Luckily, my dad only suffered a very mild stroke, and after several days of monitoring and a battery of tests, he was released from the hospital. 

While we are all relieved that he dodged what could have been a fatal bullet, I came to realize that there was only a superficial understanding of what was actually happening.  So, to help demystify the process for my dad (and anyone else in this situation), I’ve decided to write a mini-guide on strokes.  Below you will find some handy information about strokes, including what they are, as well as a glossary of relevant terms.   

Why we need blood flow in the brain

Before I get into what happens to the brain when a stroke occurs, it is important to first understand why unrestricted blood flow in blood vessels in the brain is important.  The brain is a type of tissue, and like all tissues in our body, it needs a constant access to nutrients and oxygen.  Furthermore, tissues produce waste, and this waste needs to be removed.

The human cardiovascular system. Image Credit: Wikipedia.
Evolution’s solution to this problem is the development of a vast network of blood vessels existing within our tissues.  For instance, take a good look at your very own eyeballs.  Especially when we are tired, we can see tiny blood vessels called capillaries, which help to deliver key nutrients and oxygen, keeping our organs of sight healthy and happy.  Now consider that this type of blood vessel network exists in all tissues in our bodies (because it does).  Depending on the needs of the tissue, these vessels vary in size and number.  Sometimes the blood vessels are large, like the aorta, and sometimes they are super tiny, like the capillaries in our eyes.  However, all serve the same function: to make sure that cells can breath, eat, and get rid of waste.

When blood is prevented from traveling to a specific area within a tissue, the cells in that area will not get enough fuel and oxygen and will begin to die.  For instance, the restriction of blood flow to the heart leads to the death of heart tissue, causing a heart attack.  Similarly, the interruption of normal blood flow within the brain causes the affected cells in the brain to essentially starve, suffocate, and die, resulting in a stroke.  The medical term for a lack of oxygen delivery to tissues due to a restriction in blood flow is ischemia.  In general, the heart, brain, and the kidneys are the most sensitive to ischemic events, which, when occurring in these organs, can be fatal.      

So, what exactly is a stroke?

Some strokes can be categorized as being ischemic.  As mentioned above, an ischemic stroke occurs when blood flow (and the associated oxygen supply) is restricted in an area within the brain, leading to tissue death.  A major cause of ischemic strokes is a progressive disease called atherosclerosis, which can be translated to mean “the hardening of the arteries.” 

Severe atherosclerosis of the aorta.
Image Credit: Wikipedia.
Affecting the entire cardiovascular system, atherosclerosis is the result of cholesterol build-up inside of our blood vessels, causing their openings to become narrower.  These cholesterol plaques can eventually burst, leading to the formation of a blood clot.  Ischemic strokes occur as a result of a blood clot, medically known as a thrombus, that blocks the flow of blood to the brain, a phenomenon often related to complications from atherosclerosis.  A ruptured cholesterol plaque and resulting blood clot can occur in the brain, or it can occur elsewhere in the body, such as in the carotid arteries, and then travel to the brain.  Either way, the blood clot will block blood flow and oxygen delivery to sensitive brain tissue and cause a stroke.           

Strokes that result from the bursting of a blood vessel in the brain can be categorized as being hemorrhagic.  In this situation, there may be a pre-existing condition rendering the blood vessels in the brain defective, causing them to become weak and more susceptible to bursting.  More often than not, a hemorrhagic stroke is the result of high blood pressure, which puts an awful lot of stress on the blood vessels.  Hemorrhagic strokes are less common than ischemic strokes, but still just as serious. 

How do you know if you’ve had a stroke?

The symptoms of a stroke can vary depending on which part of the brain is affected and can develop quite suddenly.  It is common to experience a moderate to severe headache, especially if you are hemorrhaging (bleeding) in the brain.  Other symptoms can include dizziness, a change in senses (hearing, seeing, tasting), muscle tingling and/or weakness, trouble communicating, and/or memory loss.  If you are experiencing any of these warning signs, it is important to get to the hospital right away.  This is especially important if the stroke is being caused by a blood clot since clot-busting medicationsare only effective within the first few hours hours of clot formation. 

Once in the hospital, the caregiver will likely give anyone suspected of having a stroke a CT scan.  From this test, doctors will be able to determine if you had a stroke, what type of stroke you had (ischemic versus hemorrhagic), or if there is some other issue.  However, as was the case with my dad, a CT scan may not show evidence for a stroke.  This issue can arise as a result of timing (test performed before brain injury set in) or size of affected area (too small to see).  When not in an emergency situation, doctors may also or instead choose to prescribe an MRItest to look for evidence of a stroke.    

If a stroke has been confirmed, the next steps will be to try and figure out the underlying cause.  For ischemic strokes, it is important to find out if there is a blood clot and where it originated.  Because my dad had an ischemic stroke, he had to undergo a series of tests that searched for a blood clot in his carotid arteries though ultrasound, as well as in the heart, using both an electrocardiogram(EKG) and an echocardiogram(ultrasound of the heart).  The patient might also be asked to wear a Holter Monitor, which is a device worn for at least 24 hours and can detect potential heart abnormalities that may not be obvious from short-term observations, like those obtained via an EKG.  If a stroke is due to a hemorrhagic event, an angiogramwould be performed to try an pinpoint the compromised blood vessel.  

A stroke you did have.  Now what?

Once a stroke has been confirmed and categorized, the patient will most likely be transferred to the stroke unit of the hospital for both treatment and further observation.  If a clot has been detected, a patient will receive clot-busting medications (assuming this detection occurs within several hours of clot formation).  Alternatively, a clot can be mechanically removed with surgery (animation of clot removal, also known as a thrombectomy).  Patients might also be given blood-thinning medications to either ensure that clots do not increase in size or to prevent new clots from forming.   As for secondary prevention, meaning preventing another stroke from happening, patients might be given blood pressure and cholesterol lowering medications. 

If a disability arises due to stroke, a patient might need to undergo rehabilitation.  The type and duration of stroke rehabilitation is dependent on the area of brain that was affected, as well as the severity of the injury.  

Major risk factors and predictors of stroke

There are many situations that could predispose one to having a stroke, and many of these conditions are treatable.  The absolute greatest predictor of a stroke is blood pressure.  High blood pressure, also known as hypertension, will significantly raise your risk of having a stroke.   Other modifiable stroke risk factors include blood cholesterol levels, smoking, type 2 diabetes, diet, alcohol/drug use, and a sedentary life style.  However, there are also risk factors that you cannot change including family history of stroke, age, race, and gender.  But that shouldn’t stop one from practicing a healthy lifestyle!

In conclusion, strokes are no joke.  I am glad that my dad is still here (yes, dad, if you are reading this, we are in fact friends) and that he escaped with relatively no real consequences.  Let’s just not do this again, ok?  

Stroke Glossary

Anti-coagulants:These are medications that help to reduce the incidence of blood clotting.  The repertoire includes aspirin, Plavix, Warfarin, and Coumadin.  Also called blood thinners.
Atherosclerosis:Literally translated as “hardening of the arteries,” this condition is hallmarked by the build-up of cholesterol inside of blood vessels.  Atherosclerosis can lead to many complications including heart disease and stroke.

Atherosclerotic Plaque: The build of fatty materials, cholesterol, various cell types, and calcium.

Cardiovascular System: The network of blood vessels and heart that works to distribute blood throughout the body. 

Carotid Arteries: Arteries that carry blood away from the heart toward the head, neck, and brain.

CT Scan: Cross sectional pictures of the brain using X-rays.

Echocardiogram:An ultrasound of the heart.  In stroke vicitms, electrocardiography is used to detect the presence of a blood clot in the heart.

Electrocardiogram (EKG or ECG): The measurement of the electrical activity of the heart.  It is performed by attaching electrodes to a patient at numerous locations on the body, which function to measure electrical output of the heart.

Embolic Stroke: A type of ischemic stroke, an embolic stroke occurs when a blood clot forms (usually in the heart) and then travels to the brain, blocking blood flow and oxygen delivery to brain tissue.

Hemorrhagic Stroke: A type of stroke that results form the bursting of a blood vessel in the brain.

Hypertension: High blood pressure, defined as having 140/90 mmHg or above.

Ischemic Stroke: The restriction of blood flow to an area within the brain.

Magnetic Resonance Imaging (MRI): An imaging technique employing a magnetic field that can contrast different soft tissues in the body.

Thrombolytic Medications: Medications that are approved to dissolve blood clots.  Also called “clot-busting” medications.

Thrombus:Blood clot.

Breast cancer screening and treatment, especially in younger women

[Editor's note: I was on Twitter, as usual, a couple of days ago, and started seeing tweets with the hashtag #SSCAbc. They contained information that I, an avid consumer of science and medical information, don't normally see addressed in breast cancer stories, including for young women with breast cancer and how to talk to children about having breast cancer. I've aggregated some of those tweets below, but you can read more at the hashtag here, which represents the Seattle Cancer Care Alliance, whose representatives were conducting the Twitter session.]

[View the story "Seattle Cancer Care Alliance: Talking about breast cancer" on Storify]

Seattle Cancer Care Alliance: Talking about breast cancer

http://www.sccablog.org/2012/10/tweeting-for-breast-cancer-awareness-month/ Twitter handles @SeattleCCA, @UWMedicineNews, and @HutchinsonCtr; also @jrgralow and @SeattleMamaDoc

Storified by Emily Willingham · Mon, Oct 15 2012 13:00:07

“@stales: MT @SeattleMamaDoc: Exercise lowers hormone levels, consequently lowers risk of breast cancer.#SCCAbc #SCCAbc”MESFER AL SHAHRANI
#SCCAbc Topic 3: If your mother or sister had breast cancer, especially < age 40, you may be at increased risk.Julie Gralow
RT @jrgralow: Breast cancer in multiple family members, especially at young age, increases risk. Great info: http://ow.ly/euFq8 #SCCAbcWendySueSwanson MD
THIS IS A TRIPLE WHAMMY: Breast feeding is good for mom, great for baby, & lowers breast cancer risk (less estrogen while nursing) #SCCAbcWendySueSwanson MD
RT @SeattleCCA: Recap T2: earlier age at first #pregnancy, more pregnancies & #breastfeeding can decrease #breastcancer risk #SCCAbcAlicia C. Staley
Tough for many of us—and not necessary–but earlier pregnancies (esp under age 20) dec risk of breast cancer #SCCAbcWendySueSwanson MD
RT @SeattleMamaDoc: Tell your teens. Scream it from the rooftop RT @jrgralow: #SCCAbc Oral contraceptives do NOT increase breast cancer riskDominique B.
TOPIC 4 Q1: What is the recommended age for a #mammogram, and why? #SCCAbcSeattle Cancer Care
RT @jrgralow: We recommend starting age 40 for most women. If you have higher or lower risk than average this will vary. #SCCAbcUW Medicine News
Mammograms can decrease rate of death from breast cancer, especially true in those women over age 50 #SCCAbc http://1.usa.gov/puQ0NcWendySueSwanson MD
RT @seattlecca: T4 Q2: What else can a woman do other than a #mammogram to screen for #breastcancer? #SCCAbcUW Medicine News
RT @jrgralow: #SCCAbc Topic 4: Younger women have denser breasts, making mammos less reliable. Here’s some info: http://ow.ly/euH6tUW Medicine News
RT @jrgralow:Topic 4: Ultrasound is great in young, dense breast when abnormality is noted. So far, not a good screening tool yet. #SCCAbcUW Medicine News
#SCCAbc Topic 4: Breast MRI more sensitive than mammo in young women. For women with strong family history we recommend breast MRI .Julie Gralow
BRCA1 & BRCA2 are genes that can be passed in families & inc your risk of breast cancer. There’s blood tests 4 BRCA1&2 gene changes. #SCCAbcWendySueSwanson MD
#SCCAbc Topic 3: We can test for BRCA1/2, also sometimes PTEN or p53 or other tests may be applicable.Julie Gralow
RT @SeattleMamaDoc If concerned abt costs of genetic test, call ur insurance prior to tests. I also rec genetic counseling visits. #SCCAbcAlicia C. Staley
RT @SeattleMamaDoc Mammos, like most things, arent perfect. Esp in the young. If high risk 2 fam history/genes, ask abt breast MRI #SCCAbcAlicia C. Staley
RT @uwmedicinenews: Topic 5 Q1: how would you recommend speaking with young children about a loved one’s breast cancer? #SCCAbcHutchinson Center
More than anything, take ur time in explaining breast ca diagnosis with children. There isn’t urgent rush for all details at once #SCCAbcWendySueSwanson MD
@jrgralow Children learn fear of cancer from us. Be open/provide info, take them to chemo if they want, helps normalize #gr8 advice #SCCAbcUW Medicine News
RT @jrgralow: SCCAbc Topic 5: I love this book (by one of my patients) on talking about chemo with kids. http://ow.ly/euInm #SCCAbcSeattle Cancer Care
RT @jrgralow: Young Survival Coalition offers great support for young women w breast cancer http://www.youngsurvival.org/ #SCCAbcWendySueSwanson MD
RT @SeattleMamaDoc: Tip: Let people help you on YOUR terms when navigating cancer diagnosis &raising children. #SCCAbcUW Medicine News
#SCCAbc Topic 5: 2 great sets of info on coping and relationships and cancer. http://ow.ly/euITz http://ow.ly/euIUHJulie Gralow
Consider freezing eggs before chemo RT @jrgralow #SCCAbc T2: Chemo can put young women into early menopause, decrease future ferility.Ruth Ann Crystal, MD
RT @jrgralow: #SCCAbc Topic 1: Presidents Cancer Panel report on healthly lifestyles and cancer: http://ow.ly/er0pE #SCCAbcAlicia C. Staley
T4Q1: Thanks to @Safeway for supporting SCCA’s #MammoVan, will be in Safeway parking lots throughout Oct: http://ow.ly/euGjx #SCCAbcSeattle Cancer Care
RT @SeattleMamaDoc: PS– Breast feeding after breast cancer is okay: http://ti.me/coREKR #SCCAbc cc @brochmanSara

How helpful are dense-breast right-to-know laws?

A doctor reviews a digital mammogram, pointing to a possible cancer.
Credit: National Cancer Institute.
By Laura Newman, DXS contributor
In a victory for the dense-breast patient movement, Governor Jerry Brown (D-CA) signed legislation last week requiring that doctors who discover that women have dense breasts on mammography must inform women that:

§  dense breasts are a risk factor for breast cancer;
§  mammography sees cancer less well in dense breasts than in normal breasts; and
§  women may benefit from additional breast cancer screening.

The California law goes into effect on April 1, 2013. It follows four states (Connecticut, Texas, Virginia, and New York) with similar statutes. All have enjoyed solid bipartisan support. Rarely do naysayers or skeptics speak up.
Young women who are leading the charge often bring lawmakers the story of a young constituent, diagnosed with a very aggressive, lethal cancer that was not shown on film-screen mammography. The Are You Dense? patient advocacy group engages patients on Facebook, where women share their experiences with breast cancer, organize events, and lobby for legislation. Individual radiologists work with the advocacy groups, but many radiology groups and breast surgeons do not endorse these laws.


A Closer Look at Breast Cancer Data

Living in an age when information is viewed as an entitlement, knowledge, and power, many physicians find it hard to argue against a patient’s right to know. Can sharing information be a mistake? Some epidemiologists think so. Otis W. Brawley, MD, FACP, Chief Medical & Scientific Officer, American Cancer Society, says: “I really worry when we legislate things that no one understands. People can get harmed.” Numerous issues have to be worked out, according to Brawley. For one, he explains: “There is no standard way to define density.” Additionally, “even though studies suggest that density increases the risk of cancer, these cancers tend to be the less serious kind, but even that is open to question,” Brawley says. “We in medicine do not know what to do for women who have increased density.”

A study of more than 9,000 women in the Journal of the National Cancer Institute revealed that women with very dense breasts were no more likely to die than similar patients whose breasts were not as dense. “When tumors are found later in more dense breasts, they are no more aggressive or difficult to treat,” says Karla Kerlikowske, MD, study coauthor, and professor of medicine and epidemiologist at the University of California San Francisco. In fact, an increased risk of death was only found in women with the least dense breasts.


The trouble is what is known about dense breasts is murky. Asked whether he backs advising women that dense breasts are a risk factor for breast cancer, Anthony B. Miller, MD, Co-Chair of the Cancer Risk Management Initiative and a member of the Action Council, Canadian Partnership Against Cancer, and lead investigator of the Canadian National Breast Cancer Screening Study, says: “I would be very cautious. The trouble is people want certainty and chances are whatever we find, all we can do is explain.”

Women in their forties, who are most likely to have dense breasts (density declines with age) may want to seek out digital mammography. In studies comparing digital mammography to film-screen mammography in the same women, digital mammography has been shown to improve breast cancer detection in women with dense breasts. Findings from the Digital Mammographic Imaging Screening Study, showed better breast cancer detection with digital mammography. But digital mammography is not available in many areas.  Moreover, Miller explains: “We do not know if this will benefit women at all.  It is very probable that removal of the additional small lesions will simply increase anxiety and health costs, including the overdiagnosis of breast cancer, and have no impact upon mortality from breast cancer.”


Additional imaging studies sound attractive to people convinced that there is something clinically significant to find. But as I pointed out in my last post, many radiologists and breast physicians contend that there is no evidence that magnetic resonance imaging or any other imaging study aids breast cancer screening in women with dense breasts. Brawley notes: “These laws will certainly lead to more referral for MRI and ultrasound without clear evidence that women will benefit (lives will be saved.) It’s clear that radiologists will make more money offering more tests.” Miller adds: “A number of doctors are trying to capitalize on this and some of them should know a lot better.”


Many Advocates Question More Tests, Statutes

Even though the “Are You Dense?” campaign has been instrumental in getting legislation on the books across the county, other advocacy groups and patient advocates want research, enhanced patient literacy about risks and benefits of procedures. Many recall mistakes made that led women down the path of aggressive procedures. In that group is the radical Halsted mastectomy, used widely before systematic study, but once studied,  found no better than breast-conserving surgery for many cancers, and bone marrow transplants, also found to be ineffective, wearing, and costly.

Jody Schoger, a breast cancer social media activist at @jodymswho engages women weekly on twitter at #bcsm, had this to say on my blog about the onslaught of additional screening tests:

“What is needed is not another expensive modality… but concentrated focus for a biomarker to indicate the women who WILL benefit from additional screening. Because what’s happening now is an avalanche of screening, and its subsequent emotional and financial costs, that is often far out of proportion to both the relative and absolute risk for invasive cancer. I simply don’t think more “external” technology is the answer but one that evolves from the biology of cancer.”

Eve Harris @harriseve, a proponent of patient navigation and patient literacy, challenged Peter Ubel, MD, professor of business administration and medicine, at Duke University, on his view of the value of patient empowerment on the breast density issue. In a post on Forbes, replicated in Psychology Today, Ubel argued that in cases where the pros and cons of a patient’s alternatives are well known, for example, considering mastectomy or lumpectomy, patient empowerment play an important role. “But we are mistaken to turn to patient empowerment to solve dilemmas about how best to screen for cancer in women with dense breasts,” he writes.


Harris disagrees, making a compelling case for patient engagement:

“I think that we can agree that legislative interference with medical practice is not warranted when it cannot provide true consumer protection. But the context is the biggest culprit in this situation. American women’s fear of breast cancer is out of proportion with its incidence and its mortality rate. Truly empowering people—patients would mean improving health literacy and understanding of risk…”


But evidence and literacy take time, don’t make for snappy reading or headlines, and don’t shore up political points. Can we stop the train towards right-to-inform laws and make real headway in women’s health? Can we reallocate healthcare dollars towards effective treatments that serve patients and engage them in their care? You have to wonder.
[Today's post is from Patient POVthe blog of Laura Newman, a science writer who has worked in health care for most of her adult life, first as a health policy analyst, and as a medical journalist for the last two decades. She was a proud member of the women’s health movement. She has a longstanding interest in what matters to patients and thinks that patients should play a major role in planning and operational discussions about healthcare. Laura’s news stories have appeared in Scientific American blogs, WebMD Medical News, Medscape, Drug Topics, Applied Neurology, Neurology Today, the Journal of the National Cancer Institute, The Lancet, and BMJ, and numerous other outlets. You can find her on Twitter @lauranewmanny.]

The opinions in this article do not necessarily conflict with or reflect those of the DXS editorial team. 

Why Can You Hear Around Corners But Not See?

As I sit and type this in my study, I can hear my cats crashing around the living room, which is around the corner from me. There’s a wall between us, so I can’t see them or shoot them with my water pistol (which I would be tempted to do if they were in the same room, before they knock over something fragile). So, just like in my earlier post on mirrors, we’ll start with a question: why can I hear my cats around the corner, but not see them?

Both sound and light are waves, but the way we perceive those waves are very different. I don’t just mean the organs we use – eyes and ears do have major biological differences – but how the characteristics of those waves differ. We perceive differences in light through color, and differences in sound through pitch, but in the end these characteristics mean the same thing: they’re a measure of how big the wave is. The technical term for this is its wavelength: the distance it takes for a wave to start repeating itself.

For visible light, red has the longest wavelength, while violet has the shortest. In between you get the other colors of the rainbow, and if you mix them all together you get white light. Visible light wavelengths are between 400 and 700 nanometers, which is smaller than bacteria (which themselves are smaller than cells in our bodies)! Wavelengths smaller than 400 nanometers get into ultraviolet, X-ray, and gamma-ray territory; wavelengths greater than 700 nanometers comprise infrared, microwaves, and radio waves.

For sound, the situation is a little messier, since our ears respond to frequency, not wavelength. The specific wavelength of sound depends on the temperature and humidity of the air, but if we assume dry room-temperature air, a low-pitched sound has a wavelength of about 17 meters and high-pitched sounds have wavelengths around 2 centimeters. That’s a big range, and not all those sounds will travel around corners. Shorter wavelengths are ultrasound, which are probably most familiar for tracking the health of fetuses: these sound waves can penetrate or reflect off tissue, and by measuring the waves that bounce back, doctors can track blood flow and other developmental processes inside your body. (X-rays go right through soft tissues, so they’re better for looking at bones.) Longer wavelengths are infrasound; animals like elephants use these very low-pitched sounds for communication across long distances.

When a wave meets an opening like a door, it can experience something known as diffraction: the wave passing through the opening spreads out on the other side. However, the wave doesn’t just come through the center of the door: it makes a bunch of waves along the length of the opening, and those waves actually interfere with each other. The wider the door, the more of these new waves are made.

The image to the right shows the interference pattern from a red laser shining through a very narrow opening (smaller than a millimeter). The central maximum is where most of the light coming through the opening ends up, but you also have dark spots where the light interferes and cancels out. The secondary spots on either side of the maximum are much less bright, and you also get tertiary and smaller spots that are fainter still. You get the same pattern for sound, though for obvious reasons I can’t show you a picture of it! The only difference is you exchange brightness for loudness, and dark spots for places where the sound is silenced.

The width and intensity (brightness or loudness) of the spots depend on the ratio of the wavelength to the size of the opening. If the wavelength is bigger than the opening, there isn’t diffraction; if the wavelength is about the size of the opening, then you get strong diffraction, and the central maximum is a lot wider than the opening. If the wavelength is much smaller than the opening, then the central maximum is quite small, and since the secondaries, tertiaries, and so forth are fainter still, the pattern may be hard to detect.

So there’s our answer! A typical doorway is around a meter wide (a little less, usually), so sound with its relatively large wavelengths will create a big central maximum and sufficiently-loud secondaries. That can be enough to hear even if you aren’t in a straight line with the hooligan cats in the other room. A corner is just a very wide doorway, so everything I’ve said about doorways carries over to them too.

Visible light has very small wavelengths, so while you do get light diffraction through doorways, you’d need a microscope to see the pattern! If you have a strong light shining through the door, you’ll get a nice rectangular blaze of light on the opposite wall, but it’s not much bigger than the door, and doesn’t go around corners. However, if you have a cell phone or a cordless phone, the signal from those definitely can go around corners: those are based on microwaves or radio waves, which have much larger wavelengths than visible light.

Similarly, elephants communicate via infrasound over huge distances because rocks, trees, and other obstacles are smaller than the wavelengths they use, so the sound just diffracts right around them. Very handy! Tigers use roars to establish territories, and since they live in dense forests, again infrasound lets their growls travel around the trees easily. (We humans may not hear the infrasound part of the roar, but we can definitely feel it. The lowest notes from large pipe organs or tubas are below our normal hearing range, but they still can contribute to the overall sensation of a musical piece.)

There is one place where diffraction does play a role in our vision: our eyes themselves. Doorways are too big for diffraction, but the pupil in a human eye is about 2 millimeters across, varying depending on whether we’re in a bright or dark place. The size of the central maximum of light cast on our retina is part of what determines how well we see. Diffraction also is why radio telescopes need to be very large, but why an ordinary visible light telescope you might have doesn’t need to be huge – yet the larger it is, the more clearly you’ll be able to see distant planets and galaxies. The telescope is like a big window, so you want to match the size of the window to the wavelength of the light you’re viewing.

Now if you’ll excuse me, I need to go make sure my cats haven’t wrecked the living room.