Friday, March 27, 2009

Sigma Xi

Here at Oakland University, this Tuesday, March 31, is our annual Sigma Xi lecture (4 pm in 201 Dodge Hall of Engineering). Each year, we invite a leading scientist to OU to give a lecture for a general audience. This year Dr. Vicki Chandler, Chief Program Director of the Gordon and Betty Moore Foundation, will give a talk about "Epigenetic Silencing Across Generations." (The term "epigenetic gene silencing" describes the switching off of a gene by a mechanism other than genetic modification. That is, a gene that would be expressed, or turned on, under normal circumstances is switched off by machinery in the cell.)

For six years, I served as the president of the Oakland University chapter of Sigma Xi, the Scientific Research Society. As readers of the
4th Edition of Intermediate Physics for Medicine and Biology become biomedical researchers, they should consider joining Sigma Xi. I joined as a graduate student at Vanderbilt University.
"Sigma Xi is an international, multidisciplinary research society whose programs and activities promote the health of the scientific enterprise and honor scientific achievement. There are nearly 60,000 Sigma Xi members in more than 100 countries around the world. Sigma Xi chapters, more than 500 in all, can be found at colleges and universities, industrial research centers and government laboratories. The Society endeavors to encourage support of original work across the spectrum of science and technology and to promote an appreciation within society at large for the role research has played in human progress."
The mission of Sigma Xi is "to enhance the health of the research enterprise, foster integrity in science and engineering, and promote the public's understanding of science for the purpose of improving the human condition." As a member of Sigma Xi, you automatically receive a subscription to American Scientist, the award-winning illustrated magazine of science and technology. I particularly enjoy Henry Petroski's monthly essay on topics in engineering, and the book reviews are outstanding. The magazine alone is worth the cost of membership. Another benefit that I look forward to each day is Science in the News, a free e-mail bulletin featuring top science and technology stories. Sigma Xi also has an annual meeting, including a student research conference. Last year, the meeting was November 20-23 in Washington, DC. The society is a strong advocate of scientific research, and is worthy of support.

Finally, you have to love the society's motto: "Companions in Zealous Research".

Friday, March 20, 2009

The West-Brown-Enquist Model for Allometric Scaling

Chapter 2 of the 4th Edition of Intermediate Physics for Medicine and Biology ends with a section on "Food Consumption, Basal Metabolic Rate, and Scaling." Here Russ Hobbie and I discuss the famous "3/4-power law" (also known as Kleiber's law), which relates the metabolic rate R (in Watts) to the body mass M (in kg) by the equation R = 4.1 M0.751 (Eq. 2.32c in our book; some browsers may not show the exponent superscripted properly). We conclude the section by writing
"A number of models have been proposed to explain a 3/4-power dependence [McMahon (1973); Peters (1983); West et al. (1999); Banavar et al. (1999)]. West et al. argue that the 3/4-power dependence is universal: they derive it from a model that supplies nutrients through a branching network that reaches all parts of the organism, minimizes the energy required for distribution, and ends in capillaries (or terminal xylem in plants) that are all the same size. Whether it is universal is still debated [Kozlowski and Konarzewski (2004)]. West and Brown (2004) review quarter-power scaling in a variety of circumstances."
When we wrote this paragraph, the origin of the 3/4th power law was still being hotly debated in the literature. Readers of Intermediate Physics for Medicine and Biology might like an update.

First, this work is highly cited. West, Brown, and Enquist's first paper in Science (A general model for the origin of allometric scaling laws in biology, Volume 276, Pages: 122-126, 1997; not cited in our book) now has over 1000 citations. Their second paper, which we list in the references at the end of Chapter 2, has nearly 400 citations. The paper by Banavar, Maritan and Rinaldo cited in Chapter 2 has over 200 citations. Clearly, these studies have had a major impact on the field.

Second, the work has generated quite a bit of discussion in the press. The December 2008 issue of The Scientist has an article by Bob Grant titled "The Powers That Might Be" about West and his colleagues and how they have coped with criticisms of their work. An interview with Geoffrey West can be found at physicsworld.com, and one with Brian Enquist at www.in-cities.com. In 2004, John Whitfield published a feature in the open access journal PLOS Biology reviewing the field ("open access" means that anyone can access the paper over the internet, without the need for a journal subscription).

Third, several recent papers in scientific journals have addressed this topic. Savage et al. have analyzed what they refer to as the WBE model in an article appearing in the open access journal PLOS Computational Biology (Volume 4, Article e1000171, September, 2008). The authors' summary states
"The rate at which an organism produces energy to live increases with body mass to the 3/4 power. Ten years ago West, Brown, and Enquist posited that this empirical relationship arises from the structure and dynamics of resource distribution networks such as the cardiovascular system. Using assumptions that capture physical and biological constraints, they defined a vascular network model that predicts a 3/4 scaling exponent. In our paper we clarify that this model generates the 3/4 exponent only in the limit of infinitely large organisms. Our calculations indicate that in the finite-size version of the model metabolic rate and body mass are not related by a pure power law, which we show is consistent with available data. We also show that this causes the model to produce scaling exponents significantly larger than the observed 3/4. We investigate how changes in certain assumptions about network structure affect the scaling exponent, leading us to identify discrepancies between available data and the predictions of the finite-size model. This suggests that the model, the data, or both, need reassessment. The challenge lies in pinpointing the physiological and evolutionary factors that constrain the shape of networks driving metabolic scaling."
In another paper, published in the December 2006 issue of Physics of Life Reviews (Volume 3, Pages 229-261), de Silva et al. write that
"One of the most pervasive laws in biology is the allometric scaling, whereby a biological variable Y is related to the mass M of the organism by a power law, Y = Y0Mb, where b is the so-called allometric exponent. The origin of these power laws is still a matter of dispute mainly because biological laws, in general, do not follow from physical ones in a simple manner. In this work, we review the interspecific allometry of metabolic rates, where recent progress in the understanding of the interplay between geometrical, physical and biological constraints has been achieved.

For many years, it was a universal belief that the basal metabolic rate (BMR) of all organisms is described by Kleiber's law (allometric exponent b = 3/4). A few years ago, a theoretical basis for this law was proposed, based on a resource distribution network common to all organisms. Nevertheless, the 3/4-law has been questioned recently. First, there is an ongoing debate as to whether the empirical value of b is 3/4 or 2/3, or even nonuniversal. Second, some mathematical and conceptual errors were found [in] these network models, weakening the proposed theoretical arguments. Another pertinent observation is that the maximal aerobically sustained metabolic rate of endotherms scales with an exponent larger than that of BMR. Here we present a critical discussion of the theoretical models proposed to explain the scaling of metabolic rates, and compare the predicted exponents with a review of the experimental literature. Our main conclusion is that although there is not a universal exponent, it should be possible to develop a unified theory for the common origin of the allometric scaling laws of metabolism."
Now, five years after we included the topic in Intermediate Physics for Medicine and Biology, the controversy continues. It makes for a wonderful example of how ideas from fundamental physics can elucidate biological laws, and a warning about how complicated and messy biology can be, limiting the application of simple models. I can't tell you how this debate will ultimately be resolved. But it provides a fascinating case study in the interaction of physics and biology.

Friday, March 13, 2009

The Discovery of Technetium

In the 4th Edition of Intermediate Physics for Medicine and Biology, Russ Hobbie and I discuss the biomedical properties of the element technetium (Tc), which plays an important role in nuclear medicine:
"The most widely used isotope is 99m-Tc. As its name suggests, it does not occur naturally on earth, since it has no stable isotopes...[It decays by emitting] a nearly monoenergetic 140-keV gamma ray. Only about 10% of the energy is in the form of nonpenetrating radiation. The isotope is produced in the hospital from the decay of its parent, 99-Mo, which is a fission product of 235-U and can be separated from about 75 other fission products. The 99-Mo decays to 99m-Tc."
Technetium has an interesting history. When Dmitri Mendeleev proposed the periodic table, he predicted that holes in his table were actually missing elements that had not yet been discovered. In The Search for the Elements, Isaac Asimov writes
"The first elements produced [by artificial transmutation] was the missing number 43 [technetium]. A claim to discovery of this element had been made in 1925 by Noddack, Tacke, and Berg, the discoverers of rhenium. They had named element number 43 'masurium' (after a district in East Prussia). But no one else was able to find 'masurium' in the same source material, so their supposed discovery had remained a question mark. It was, in fact, just a mistake. In 1937 Emilio Gino Segre of Italy, an ardent hunter for the element, identified the real number 43.

[Ernest O.] Lawrence had bombarded a sample of molybdenum (element number 42) with protons accelerated in his cyclotron. Finally he got some radioactive stuff which he sent to Segre in Italy for analysis. Segre and an assistant, C. Perrier, traced some of the radioactivity to an element which behaved like manganese. Since the missing element 43 belonged in the vacancy in the periodic table next to manganese, they were sure this was it.

It turned out that element number 43 had several isotopes. Oddly, all of them were radioactive. There were no stable isotopes of the element!...Segre named the element number 43 'technetium,' from a Greek work meaning 'artificial,' because it was the first element made by man."
Asimov tells the standard history of the discovery of technetium, but recently there has been a new twist to the story. John Armstrong of the National Institute of Standards and Technology (NIST) suggested that maybe masurium really was technetium. In an abstract to a NIST Sigma Xi colloquium in 2000 titled "The Disputed Discovery of Element 43 (Technetium)", Armstrong and P. H. M. Van Assche write
"In 1925, Noddack, Tacke and Berg reported discovery of element Z=43, which they named Masurium, based on line identification of x-ray emission spectra from chemically concentrated residues of various U-rich minerals. Their results were disputed and eventually the discovery of element 43 (Technetium) was generally credited to Perrier and Segre, based on their chemical separation of neutron-irradiated molybdenum in 1937. Using first principles x-ray emission spectral generation algorithms from the N.I.S.T. DTSA spectral processing program, we have simulated the x-ray spectra that would be expected using their likely analytical conditions (from their papers and contemporaneous reports) and the likely residue compositions suggested by Noddack et al. and Van Assche. The resulting spectra are in close agreement with that reported by Noddack et al., place limits on the possible residue compositions, and are supportive of the presence of detectable amounts of element 43 in their sample. Moreover, the calculated mass of element 43 shown in their spectrum is consistent with the amount that would be now expected from the spontaneous fission of U present in the ores they studied. The history of the original masurium/technetium controversy and the means used to reexamine the original record will be presented in this scientific detective story."
Was masurium really technitium? You will have to look at the evidence and decide for yourself. The story certainly is fascinating, and will interest readers of Intermediate Physics for Medicine and Biology.

Friday, March 6, 2009

NCRP Report No. 160

In past entries to this blog, I have reported on a growing controversy over radiation exposure from medical procedures. On December 7, 2007 I described a study by David Brenner and Eric Hall warning that the increased popularity of CT scans, particularly in children, can lead to an increased incidence of cancer. Then, just three weeks ago, I discussed the "Image Gently" website, created to raise awareness in the imaging community of the need to adjust radiation dose when imaging children.

This week the debate intensified, with three simultaneous press releases. On Wednesday, the National Council on Radiation Protection and Measurement (NCRP) issued a new study titled "Medical Radiation Exposure of the U.S. Population Greatly Increased Since the Early 1980s." This report, also known as NCRP Report Number 160, updates NCRP Report Number 93, "Ionizing Radiation Exposure of the Population of the United States", published in 1987. Readers of the 4th Edition of Intermediate Physics for Medicine and Biology may recall that Russ Hobbie and I based much of our discussion in Chapter 16 about the risk of ionizing radiation on Report No. 93. The press release announcing Report No. 160 states that
"In 2006, Americans were exposed to more than seven times as much ionizing radiation from medical procedures as was the case in the early 1980s, according to a new report on population exposure released March 3rd by the National Council on Radiation Protection and Measurements (NCRP) at its annual meeting in Bethesda, Maryland. In 2006, medical exposure constituted nearly half of the total radiation exposure of the U.S. population from all sources."
The report triggered an immediate response from the American Association of Physicists in Medicine. Their press release, titled "NCRP Report No. 160 on Increased Average Radiation Exposure of the U.S. Population Requires Perspective and Caution", begins
"Scientists at the American Association of Physicists in Medicine (AAPM) are offering additional background information to help the public avoid misinterpreting the findings contained in a report issued today by the National Council on Radiation Protection and Measurements (NCRP), a non-profit body chartered by the U.S. Congress to make recommendations on radiation protection and measurements. The report is not without scientific controversy and requires careful interpretation."
Not to be outdone, the American College of Radiology also issued its own press release Wednesday.
"A recent National Council on Radiation Protection and Measurements (NCRP) Report (NCRP Report No. 160, Ionizing Radiation Exposure of the Population of the United States) stated that the U.S. population is now exposed to seven times more radiation each year from medical imaging exams than in 1980. The American College of Radiology (ACR), Society for Pediatric Radiology (SPR), Society of Breast Imaging (SBI), and the Society of Computed Body Tomography and Magnetic Resonance (SCBT-MR) urge Americans, including elected officials and medical providers, to understand why this increase occurred, consider the Report’s information in its proper context, and support appropriate actions to help lower the radiation dose experienced each year from these exams.

'It is essential that this Report not be interpreted solely as an increase in risk to the U.S. population without also carefully considering the tremendous and undeniable benefits of medical imaging. Patients must make these risk/benefit decisions regarding their imaging care based on all the facts available and in consultation with their doctors,' said James H. Thrall, MD, FACR, chair of the ACR Board of Chancellors."
Who says medical physics isn't exciting? Seriously, this is an important topic, and deserves the careful scrutiny of anyone interested in medical physics. As always, I recommend the 4th Edition of Intermediate Physics for Medicine and Biology as a good starting point to learn the basic physics that underlies this controversy. And keep coming back to this blog for updates as the debate unfolds.