Starting with X-rays.  X-rays are a type of invisible radiation, just like infrared, ultraviolet, and radio waves.  X-rays have a very short wavelength and this allows them to pass through objects that are not very dense such as skin and muscle.  Dense objects, such as bone, will reflect X-rays.  By scanning an object with X-rays, one can use the pattern of where X-rays pass unhindered and where they are reflected to create a picture.  The reflected portions are denser material, although an X-ray cannot tell you what that material is.  When imaging a human, it has to be bone because there is nothing denser.  Also, if you take a person apart the X-ray pattern matches the human skeletal pattern.  I don’t advise doing this.

An X-ray produces a two dimensional picture.  A three-dimensional picture, however, provides more diagnostic information.  This 3D picture is a CAT or CT scan.  We can use a computer to combine many 2-dimensional X-rays pictures taken from different angles into a full 3D picture.  Essentially, CAT (computed axial tomography) simply means “computer generated picture (“computed”) created using an X-ray device (“tomography”) rotated around an object (“axial”)”.   It’s simply a three-dimensional X-ray.

An ultrasound is very similar to an x-ray in that it reflects energy waves off of objects and uses the pattern of reflection to create a picture.  Ultrasound waves are much lower in frequency than X-rays.  Because they have a low frequency, they do not penetrate very far into objects.  Thus, they are perfect for imaging things near the skin surface.  Because they are low frequency, they do much less harm to living tissue than X-rays.  The low frequency means they have a low energy content and will interact with tissue in a less destructive manner than X-rays.  This is a major reason why ultrasound is preferred for imaging fetuses.  Like Dave said, this is essentially the same technique used by bats and other critters to echo-locate.  By sending out a sound and listening to the reflection, we (and the bats) can build up a picture of the immediate environment.

Now we get to MRIs.  The true term is NMRI or nuclear magnetic resonance imaging.  The word nuclear was removed due to concerns that the public would be unnecessarily fearful.  This scan relies on the fact that the water molecules that make up the human body can be manipulated with a magnetic field.  No- you cannot be controlled against you will in this manner.  The effect is extremely small, but large enough to use for imaging.  An MRI uses a very powerful magnetic field to line up all of the hydrogen atoms contained in the water molecules the field.  A second magnetic field is then used to push some of the hydrogens out of alignment.  As the pushed hydrogen atoms relax and return to their alignment with the original magnetic field, they release energy in the form of radio waves.  (Radio waves are a very low energy, very long wavelength form of radiation).  The energy pattern given off by the relaxing hydrogen atoms is used to produce a picture (just like the way a picture is formed from reflecting radiation during an X-ray).  The usefulness of an MRI comes from the fact that the pushed hydrogen atoms relax at rates in different body tissues (muscle, fat, cartilage, etc).  This means that different body structures (the brain, joints, kidneys, etc) can be imaged in good detail.

A quick note: Dave mentioned that X-rays are ionizing radiation.  This means that the rays are strong enough to knock electrons off of atoms and molecules to create charged particles (ions).  This is not a great thing since ions react with living tissue, often in very destructive ways.  The occasional dental or medical X-ray is nothing to worry about because it’s a short, one time dose and is not much more than a few weeks of exposure to normal background radiation.  Whenever possible, the least invasive type of scan is used to minimize ionization and other interactions with healthy live tissue.

Pete Wentz would look like a leprechaun if you dressed him in some Irish greenery.  Aside from the cool album title of their last record, I’m not familiar.

Justin Timberlake makes catchy but not very exciting tunes, awesome commercials, weak movies, and great SNL appearances.  I’d totally hang with him in a bar.

yo science bitches! explain to me the following things, comparing and contrasting as you go:

1) CAT scan
2) MRI
3) Ultrasound
4) X-ray
5) Pete Wentz
6) Justin Timberlake

Now, the first few things are all nicely interrelated: The CAT (now more commonly known as a CT) scan is computed tomography (axial is the missing “A” word in the old name) and uses X-rays send at differing angles to create a three-dimensional picture of the scanned object. X-rays alone are useful as a radiography tool. They are an ionizing radiation that can be deflected by dense objects, which is why they are useful for imaging bones. Soft tissues provide little disruption and is usually “invisible” compared to the bones.

MRI (magnetic resonance imaging) uses nuclear magnetic resonance of hydrogen atoms (in most cases) to create a three dimensional picture of a scanned object using a strong magnetic field. It’s more effective at soft tissue scanning than a CT scan and lacks the ionizing radiation as well.

Ultrasound (ultrasonography) uses high frequency sound (2,000-18,000 Hertz) to penetrate into the body and produce an image. There’s a tradeoff between the frequency and resolution. High frequency produces a better resolution but penetrates shallowly into the body. Sonography is useful for soft tissues, looking at lesions (cysts, cancers), and is the common form of imaging for a developing fetus. The technology itself uses, what is essentially echo location. A computer measures the time and intensity of sound echoing off tissues and translates it into an image.

Pete Wentz is a member of the band Fall Out Boy and has little to do with diagnostic imaging. He produces neither a magnetic field (of any useful level) nor ionizing radiation. The band will produce high-frequency sound but the lack of focus and receiving equipment makes FOB a poor choice for sonography.

Justin Timberlake is an unexplanable phenomena.

The structure of Vitamin C is seen to the left. It’s similar in structure to some simple sugars. Of course, none of that is really all that useful, it’s the function of Vitamin C that’s of issue here.

The compound is capable of functioning as an antioxidant and a cofactor in the synthesis of endogenous compounds. See Wiki. Again, I’m not a fan of going to Wikipedia as my major source but the information seems to be useful.

Among the important functions is the stabilization of the formation of collagen. Vitamin C deficiency causes the condition known as scurvy, which is an inability of collagen to function properly. Collagen is one of the major supporting macromolecular structures in the body, produced by cells known as fibroblasts. Loss of collagen in scurvy is seen as:

Scurvy leads to the formation of spots on the skin, spongy gums, and bleeding from all mucous membranes. The spots are most abundant on the thighs and legs, and a person with the ailment looks pale, feels depressed, and is partially immobilized. In advanced scurvy there are open, suppurating wounds and loss of teeth.

Humans are not capable of synthesizing the compound, unlike most other living organisms, which is why an exogenous source is necessary.

The recommended daily intake is centered, at least initially, on dosages that are sufficient to prevent scurvy. The US RDA recommends 75 mg (female) and 90 mg (male) of Vitamin C per day with an upper limit of 2000 mg per day. I knew nothing about the controversy surrounding high-dose Vitamin C until just recently. Some scientists are claiming that the RDA is nothing more than a minimal dose to prevent disease, while a larger dose is capable of providing increased antioxidant protection and a host of other good things.

The problem that I see is twofold: One, doses above the 2000 mg/day upper limit are known to cause diahrrea and intestinal problems (some detractors claim this is how you know it’s working) indicating a deviation of the body away from normal homeostasis. Two, For the most part the body will use what it’s given to the extent that it’s needed. Large doses of Vitamin C are likely to be excreted without being used in any way.

It would seem then, that the RDA for Vitamin C is an effective dose to maintain health and avoid one of the more annoying downsides of life as a pirate. It is possible to take doses at 1000% of the RDA and still be within accepted tolerances for daily dosing without side effects.

As always, feel free to chime in with follow-up questions or corrections.

How do they come up with the recommended daily allowance for the various vitamins and minerals?

I initially tried doing some research and didn’t find much in the way of an interesting answer. Unfortunately in the intervening time I haven’t been able to expand my research on the subject. As a result this is going to be a short answer that mainly comes from Wikipedia.

The RDA was developed during World War II by Lydia J. Roberts, Hazel K. Stiebeling and Helen S. Mitchell, all part of a committee established by the U.S. National Academy of Sciences in order to investigate issues of nutrition that might “affect national defense.”

The allowances were meant to provide superior nutrition for civilians and military personnel, so they included a “margin of safety.” Because of food rationing during the war, the food guides created by government agencies to direct citizens’ nutritional intake also took food availability into account.

The Food and Nutrition Board subsequently revised the RDAs every five to ten years. In the early 1950s, USDA nutritionists made a new set of guidelines that also included the number of servings of each food group in order to make it easier for people to receive their RDAs of each nutrient.

For the current recommendations the following guidelines are used:

• Estimated Average Requirements (EAR), expected to satisfy the needs of 50% of the people in that age group.
• Recommended Dietary Allowances (RDA), the daily dietary intake level of a nutrient considered sufficient to meet the requirements of nearly all (97–98%) healthy individuals in each life-stage and gender group.
• Adequate Intake (AI), where no RDA has been established, but the amount established is somewhat less firmly believed to be adequate for everyone in the demographic group.
• Tolerable upper intake levels (UL), to caution against excessive intake of nutrients (like vitamin D) that can be harmful in large amounts.
• The RDA is used to determine the Recommended Daily Value (RDV) which is printed on food labels in the U.S. and Canada.

This does not really answer the question about how the regulations were developed, but covers the history of the way we came about the guidelines.

I can follow up with information about specific nutrients if desired, but this is well out of my area of expertise and requires some research. I dislike having Wikipedia as my sole reference, but it’s a place to start.

One of the many hurdles in developing a drug is understanding how a drug is metabolized. This is the process by which the body changes the structure of the drug to make it easier to excrete. A drug may be excreted unchanged or may be significantly altered in the process of traveling through the body. None of these things are known ahead of time, but all are determined in the “pre-clinical” phase of drug development. In this phase researchers work on the metabolism problems as well as looking at toxicity, bioavailability (how much of an oral dose will reach the bloodstream unchanged and active), and formulation (the coating and release mechanisms from pill form).

Why is metabolism important? The structure developed may be effective in treating your disease of choice, but it might very well be a metabolite of that structure that is the truly effective compound. Metabolites (and the parent compound) can have inhibitory or stimulatory effects on other enzymes in the body or on ion channels. The Human Ether A-gogo protein (hERG) is an ion channel in the heart that can be disrupted by some drugs and has been linked to deaths. It is vitally important for any new drug to avoid affecting this channel in the course of its action.

One of my favorite examples comes from combinations of drugs. St. John’s Wort is an herbal compound that most people believe has no side effects. This is simply a myth. Any compound you put into your body is a drug and will have an effect. The effect (and side effects) are dependent upon the dose but herbal compound are no more safe than any other drug but because they are regulated differently by the FDA there is little control over their administration.

Now, suppose you are a woman taking birth control pills (which are usually combinations of hormones),  you are sexually active, and you do not want to have children. The normal dosing of The Pill changes the hormone balance in women to prevent ovulation but requires daily dosing to remain effective. The dosed hormones are metabolized to inactive metabolites by an enzyme in the liver: cytochrome P450 3A4 (abbreviated CYP3A4, part of the cytochrome P450 monooxygenase family of enzymes). So, daily dosing infuses the body with hormones and CYP3A4 works to remove those hormones.

Enter St. John’s Wort. This compound induces CYP3A4 by activating cellular receptors and telling the cell to make more enzyme. A woman taking both St. John’s Wort (SJW) and birth control pills is now in trouble. The SJW will increase levels of CYP3A4 in the liver and as a result more rapidly metabolize the birth control hormones. Despite daily dosing, the woman will quickly overwhelm the effects of the birth control pills and (because she is sexually active) become pregnant unless other forms of birth control are used.

The moral of the story is that anything you put into your body will have an effect (pharmacology) on biological systems. When those interactions are deleterious on their own (toxicology) you will see toxic side effects from the compound. Side effects can come from drug interactions (SJW and birth control) or from a compound acting at multiple biological receptors (opioids work on receptors to control pain but also prevent normal muscle function in the intestines and cause severe constipation).

Developing drugs is a difficult and costly process that involves the interaction of organs throughout the body with the drug and its metabolites. It is, however, an area that I find infinitely intersting and will be happy to answer any questions on the subject.

Hormonal therapy has become an integral part of large animal veterinary medicine and livestock production. We use reproductive hormones to manipulate the estrus cycle of females to increase breeding efficiency, give hormones to animals to alter growth and development (largely for economic benefit) and remove naturally occurring hormones from animal to alter behavior and reproductive potential (spaying and neutering animals). So first some background information on growth hormones used in the animal industry:

Growth hormones have one basic principle, to increase production of an economically desirable commodity. Usually this is in the form of meat or milk. We’ll talk about these separately. First, to increase carcass yield from meat animals you must begin with an animal that has the potential to grow to your desired specifications, basically the genetic capability to grow, gain weight and convert feed to muscle mass. Hormonal additives are typically in the form of ear implants composed of estrogens, progesterones, synthetic anabolic steroids or a combination thereof. Estrogen and progesterone stimulate a natural release of growth hormone (GH) in higher levels than would naturally occur. This engages a cascade of metabolic processes that lower overall catabolism and increase the retention of amino acids by the animal’s body, thus leading to a significant gain in muscle mass over the animals life. Anabolic steroids are typically only used just prior to slaughter (if at all) for a short period of time as they create rapid growth but can sacrifice the quality of the meat if overused. So, growth hormone itself is not given, but rather other naturally occurring hormones are used to stimulate to animals body to produce its own GH.

When it comes to using hormonal therapy in increasing milk production the concept is similar. Recombinant bovine somatotropic hormone (rbST) has been widely publicized recently, especially in California where the dairy industry is huge. It is given to cows when they achieve peak lactation, typically about 10-12 weeks post-calving. It is a naturally occurring growth hormone that re-directs the use of absorbed nutrients to increase the milk yield over the course of an entire lactation. The cow does not produce more milk that she would naturally produce in a day at her peak lactation, but rather maintains that peak lactation for a longer period of time, thus increasing yield over the course of a lactation period (about 10 months). The cow isn’t over-milked or worn out as is often perceived, and no studies to this point have shown an increase in mastitis (udder infection) or other health issues.

These hormone supplements are perfectly safe for use and have all been approved by the FDA. When it comes to meat animal “enhancement” the animals receiving the treatment are not going to be used for breeding (and are usually steers or spayed heifers) and thus the effects are terminal and not propagated in the species. If these hormones are given to breeding animals they will usually have deleterious effects on reproductive capability and thus prevent any changes from entering the future gene pool. This is similar to men using anabolic steroids and having reduced testicular capacity due to negative feedback on hormonal regulation.  rbST in dairy cows also does not alter the genetics of the cow or her offspring but may make it more difficult for that particular cow to be re-bred with the efficiency desired on large dairies (studies vary on conception rates in cows using rbST). They still breed back, it can just take longer under normal management practices.

Our interference with these additives is not altering the evolution of these species, but our breeding selections and genetic manipulations are certainly placing pressure on all species to change. This is nothing new and has been ongoing since humans first domesticated animals and sought out desired characteristics. I am not aware of any effects these additives have on behavior but I will look into it. I’m sure Dave will have something to say about the biotechnology and genetic modification of animals lately…

Have there been any significant changes to farm animals’ biology and behavior in the last few decades due to the increased use of growth hormones? Could our interference actually change or speed up their evolution as a species?

I am ill-equipped to answer the first part of that question. The second part I think I can take a stab at.

Our interference in the development of any domesticated species (cats, dogs, cows, pigs, etc.) is affecting the evolution of those species. Dogs are an excellent example of what selective breeding and isolate populations can produce. While all dogs are still technically the same species, it is physically impossible for some breeds to reproduce (think St. Bernard and Chihuahua).

The increased use of growth hormones (and I assume you were thinking of cows in this example) can have an effect on the development of the species. Again, I’ll have to defer to Bret to talk about significant changes in the animals themselves. From a moelcular biology perspective (which is where I usually sit) the addition of an exogenous hormone will change gene expression and protein production in the cows. The intended consequence is increased milk production or better quality beef. Because of the complexity of the systems and the uncertainty of long-term effects on the animals, there may be additional changes that we are unaware of.

Biological systems like to find an equilibrium. When something is added (external hormone, genetic activation) or knocked out (gene knockout animals are common in research) there are compensatory changes in the animal. Other pathways, genes, and proteins will be activated/deactivated in unexpected ways to attempt to create a “normal” functioning animal.

Cows injected with hormones will almost certainly develop a resistance to the chemcial (regardless of whether it is a normally-occuring hormone or not) and will find a balance of self-regulation that will try to keep the cow in “cow form” as much as possible.

If this is extended over may generations and in an isolated population, it may begin to select for genes and pathways that are not normally expressed in cows. So, yes, there is the potential for accelerating the evolution of animals through these treatments.

The Center for Severe Weather Research at the National Center for Atmospheric Research reached the same conclusion. In the U.S., the area known as Tornado alley stretches from Colorado and Wyoming in the west to Ohio in the east, North Dakota in the north to Texas and Louisiana in the South (see map here). There are roughly two dozen major metropolises in this area, but they make up only a small fraction (less than 1%) of the total area. Thus, it is more likely a tornado will strike an area that does not contain a major city.

Dr. Fujita at the University of Chicago (for whom the tornado intensity scale is named) suggested that urban heat island effects may have an impact on small tornadoes. His thinking was that the increased heat levels in the center of major metropolises may disrupt the formation of small tornadoes (which make up the majority of tornado strikes). This assertion has not been proven or disproven and weather researchers continue to investigate the impact of cities on tornado formation.

What would you say is the most promising research going on in your field today, both with respect to technological advancements (which will eventually affect the general public) and with respect to broadening our general knowledge of science (which the general public probably doesn’t care about)?

This was a little difficult to answer at first because my field of expertise (if you can call me that) is in pharmacology and toxicology. I deal with the way drugs and toxicants interact with biological systems. From this field I reach into metabolism, physiology, neurology, and most other biologic sciences. It leaves me in a position where I know a little about a lot of fields and a lot about a few smaller fields.

To me the most exciting prospects are in the “-omics” areas: genomics, transcriptomics, and proteomics. Genomics is a term that most people know, dealing with the study of the genome. Projects to decode the human genome have been completed and many other animals and microbes are underway. This is not news though. The biggest difficulty in genomics is the vast amount of data. It only gets more complicated. Even when we reach the point where we can look at the entire genome of an individual it does not tell us the whole story: just because the “code” is built into the DNA does not mean that we know anything about the use of it. The central dogma of molecular biology is:

DNA –> RNA –> Protein

While there are exceptions to this rule, the central dogma leads us from genomics to transcriptomics looking at the expression of mRNA from the coding regions of DNA. Understanding the expression of mRNA adds a level of context to the DNA code. No longer is it simply potential, but the DNA has actually “produced” a product that is measurable. The production levels of mRNA are highly variable and depend upon the presence of outside drugs, the diet and health of the individual, the environment surrounding that individual, and the base code in the DNA.  What transcriptomics can tell us is the rate and extent of activation of a specific region of coding DNA. There is still a further complication.

Proteomics is the study of the proteins expressed in a cell, tissue, or organism. While the presence of mRNA can tell us the extent to which a region of DNA was transcribed it does not provide correlative data with protein expression. Said another way: DNA tells you what the cell is capable of, RNA tells you what’s being activated, but protein tells you what the call can actually do. Proteins are the major players in the cell. They catalyze reactions, provide structure, and can act as signaling molecules.

What does all this mean? I don’t want to go into more details about protein structure and function but I want to pull back from the details and try to hit the big picture. Drug development focuses on finding compounds that can affect biological systems. The drugs themselves are often either small molecules or protein derivatives. The better we understand the genomics, transcriptomics, and proteomics of humans the better the drugs can be.

Here’s a hypothetical situation or two:

Person A needs a drug for high blood pressure. Company X makes a small molecule antagonist (SMA) for receptor Q. The SMA will interact with Receptor Q and prevent it’s function, affecting production of the renin-angiotensin system and lowering blood pressure.

Situation 1: Person A has a mutant form of Receptor Q with an altered active site that responds appropriately to the endogenous (normal) compounds in the body but has only a 10% binding of the SMA compared to the wildtype receptor. In this case a genomic analysis would provide information about the mutation and alert the doctor. The solution would be to use a different SMA that was designed specifically for the mutant receptor. Why would we not simply increase the dose of the original SMA? You run the risk of providing a toxic dose, increase the chances of drug-drug interactions if the patient is on other medications, and it gets expensive.

Situation 2: Person A has a normal form of Receptor Q but is unresponsive to the SMA drug or any mutant-designed forms. Genomic analysis shows that the DNA sequence is normal, and mRNA analysis shows that production is at expected levels. However, there’s no protein reaching the cell surface (where many receptors are located). Proteomic analysis of the cell would reveal that a shuttling protein in the endoplasmic reticulum (for this example assume the shuttling protein is specific for this receptor, otherwise the person would be dead) is mutated and instead of sending Receptor Q to the cell surface, it sends it to the proteasome for degradation.  The solution here is less clear, but would likely mean trying a different approach to controlling hypertension through another mechanism.

The reason I brought all this up is because science is discovering more levels of complexity in the interactions of cellular machinery. A better understanding of all levels of this machinery will lead to better and safer medicine and improve the overall human condition.

Anyone interested in drug interactions and herbal supplements? I can talk about that for hours.