Should We Have a Molybdenum-99 Source in the United States?

In the December 14, 2007 entry to this blog, I discussed how the shutdown of a nuclear reactor at Chalk River, Ontario caused a shortage of an isotope of technetium (Tc-99m) used for medical imaging. Tc-99m is obtained from an isotope of molybdenum, Mo-99, that is produced at a handful of international facilities, including the Canadian reactor. The production and use of Tc-99m in nuclear medicine is discussed in Chapter 17 of the 4th edition of Intermediate Physics for Medicine and Biology.

The most recent (May 2008) issue of Physics Today contains an article by science writer Toni Feder that explores this topic further. Feder writes

The disruption late last year of Mo-99 production in Canada threw the nuclear medicine community into a panic. With a half-life of 66 hours, Mo-99 can’t be stockpiled. The Canadian reactor was down for maintenance, and its startup was delayed because of safety violations. Such was the upset in the nuclear medicine community that the Canadian government stepped in and ordered the reactor to start up despite some remaining safety concerns—and demoted the head of Canada’s nuclear regulatory agency.

The article also discusses plans for the production of Mo-99 in the United States. The US producers will use “low-enriched uranium” (LEU) rather than the “highly enriched uranium” (HEU) used at other facilities, including the Chalk River plant. This would have advantages for nonproliferation, and could reduce the amount of HEU available for production of weapons of mass destruction by terrorist groups. Feder continues

“Our program is to minimize civilian use of HEU,” says Parrish Staples, manager of the National Nuclear Security Administration’s program to convert reactors from HEU to LEU fuel. “The only HEU the US is currently exporting is for production of Mo-99 in foreign production facilities.” The US exports about 25 kg of HEU each year, or about half the total used for making Mo-99, he says. If the US stops exporting HEU, he adds, according to the IAEA [International Atomic Energy Agency] definition “a weapon’s worth of material would be removed [from circulation each year].”

“At some point there will be an incident somewhere in the world that will cause the US to close its borders to radioactive materials for a day, a week, two or three weeks, whatever,” says MURR [The University of Missouri-Columbia Research Reactor] director Ralph Butler. “And when you think that there are tens of thousands of patients per day [in the US] utilizing this diagnostic tool [radioactive isotopes], that’s a huge impact.” The US does not have a Mo-99 source, he adds. “There is a national need, and it’s an opportunity we [at MURR] can meet.”

A Firm Foundation For Aspiring Biophysicists

In January 1989, John Wikswo of Vanderbilt University wrote a review in Physics Today (Volume 42, Pages 75–76) about the 2nd edition of Intermediate Physics for Medicine and Biology. His review began

In our introductory physics courses as well as in our daily use of physics, we regularly encounter the early work of Galileo, Isaac Newton, Luigi Galvani, Alessandro Volta, Thomas Young, Jean Poiseuille, Julius Mayer, Hermann von Helmholtz, William Gilbert and Jacques d’Arsonval. Many of us fail to recognize that the first four were physicists who in the course of their studies of physical systems made major contributions to the life sciences, while the remainder were physicians whose fundamental contributions to physics were largely motivated by their interest in biology and medicine. In the past 40 years, the Nobel Prize in Physiology or Medicine has been awarded to a remarkable number of physicists, including Hugo Theorell, Georg von Bekesy, Francis Crick, Maurice Wilkins, Alan Hodgkin, Andrew Huxley, Haldan Hartline, Max Delbruck, Rosalyn Yalow, Allan Cormack and Geoffrey Hounsfield. There must be a multitude of reasons why each of these modern-day physicists chose a career that spanned both physics and the life sciences, but it is unlikely that any single book, with the possible exception of Erwin Schrodinger’s What is Life?, could have been the stimulus. Why are there so few books that successfully span physics, medicine and biology?

While there are excellent texts, treatises and reviews of medical and radiological physics and biophysics, none of these provides the breadth and depth required of a guidebook for a physicist or biologist desiring to explore, possibly for the first time, the realm where physics joins medicine and biology. The problem in part is that such a book should develop simultaneously both the physics and the biology without assuming extensive prior knowledge of either, and yet should explore the subject with sophistication and quantitative rigor. In 1977, I was confronting the dilemma of finding no suitable text for the very first physics course I had been assigned to teach, an introductory medical physics course for undergraduate premedical students, when a friend of mine from the Mayo Clinic told me that Russell Hobbie of the University of Minnesota was writing just the book I needed. For two years my students and I learned from typed manuscripts kindly provided by Hobbie, and my colleagues and I have been using the first edition of Intermediate Physics for Medicine and Biology ever since then. This year, we can greet our students with the second edition.

See Russ Hobbie on YouTube!

In Chapter 15 of the 4th edition of Intermediate Physics for Medicine and Biology, Russ Hobbie and I discuss the interaction of radiation with matter, a topic that is crucial for understanding the medical use of X-rays. Twenty years ago, Russ wrote a computer program called MacDose that provides a two-dimensional simulation of the photoelectric effect, Compton scattering, and pair production; the primary mechanisms of X-ray interaction. MacDose runs on any Macintosh with OS-9 or earlier, including Classic in OS-X. You can download a copy of MacDose, including a student manual and instructors guide, at our book’s website. To learn more about MacDose, see Hobbie’s article in Computers in Physics (Volume 6, Pages 355–359, 1992).

You can also download a 26 minute Quicktime movie in which Russ demonstrates MacDose and explains various concepts related to the attenuation and absorption of X-rays (you can view the movie on either a PC or a Mac). With help from my daughter Stephanie, I have uploaded this movie onto Youtube. Because of a limit on the duration of Youtube videos, Stephanie had to split the movie into three parts. Search on YouTube for “MacDose” and you should find all three. Then pop some popcorn, pour yourself a drink, find a seat, and watch Hollywood’s leading man Russ Hobbie explain how radiation interacts with matter.

 Russ Hobbie Demonstrates MacDose, Part 1

https://www.youtube.com/watch?v=eZGfHBYMuHg

 Russ Hobbie Demonstrates MacDose, Part2

https://www.youtube.com/watch?v=Rwp8eeKFycQ&t=2s

 Russ Hobbie Demonstrates MacDose, Part3
https://www.youtube.com/watch?v=hB4U7T0gH6M&t=2s

 

The Hodgkin and Huxley Model

In the 1940s and 50s, Alan Hodgkin and Andrew Huxley discovered the ionic basis for nerve conduction, work that resulted in their sharing the 1963 Nobel Prize in Physiology or Medicine. Chapter 6 in the 4th edition of Intermediate Physics for Medicine and Biology describes the Hodgkin-Huxley model in detail. Yet, no textbook can replace the experience of peering over Hodgkin's shoulder while he performs the voltage clamp experiments on a squid nerve axon that were crucial for their discoveries. Fortunately, a movie was made of these experiments, and clips from it can be found online, at a website for a neurophysiology class at Smith College. I particularly recommend the clip “Dissection and Anatomy” showing the dissection of the giant axon from a squid by J. Z. Young, and “Voltage Clamping” by P. F. Baker and Hodgkin himself.

When I teach Biological Physics at Oakland University, I like to have my students read Hodgkin and Huxley's classic paper “A Quantitative Description of Membrane Current and its Application to Conduction and Excitation in Nerve” (Journal of Physiology, Volume 117, Pages 500–544, 1952). A pdf of this article is available online. However, if you encourage your students to read it, be sure to warn them that the definition of the transmembrane potential is different than is used now, with their definition being the outside minus the inside voltage, and zero being rest. (Nowadays, researchers typically use inside minus outside, with rest corresponding to -65 mV). Writing a program to simulate the Hodgkin and Huxley model is the best way to learn about it (we have a sample of such a program in Fig. 6.38 or our textbook), but those who are not programmers might want to try this applet that allows online simulation of a nerve action potential.

Alan Hodgkin and voltage clamping.
https://www.youtube.com/embed/Wd_gKJoo25Y

 John Young dissecting a squid giant axon.
https://www.youtube.com/embed/pw6_Si5jOpo 

AAPM Celebrates Its Golden Anniversary

The quotes below are taken from the American Association of Physicists in Medicine Golden Anniversary website.

Many of the greatest inventions in modern medicine were developed by physicists who imported technologies such as X rays, nuclear magnetic resonance, ultrasound, particle accelerators and radioisotope tagging and detection techniques into the medical domain. There they became magnetic resonance imaging (MRI), computerized tomography (CT) scanning, nuclear medicine, positron emission tomography (PET) scanning, and various radiotherapy treatment methods. These contributions have revolutionized medical techniques for imaging the human body and treating disease.

Now, in 2008, the American Association of Physicists in Medicine (AAPM), the premier scientific and professional association of medical physicists, is celebrating its 50th anniversary and is calling attention to the field of medical physics achievements.

In the coming year, the AAPM will be calling attention to the many ways in which medical physics has revolutionized medicine. A few highlights include:

1. USING PARTICLE ACCELERATORS TO DEFEAT CANCER
2. BETTER DETECTION OF BREAST CANCER
3. MATTER/ANTIMATTER COLLISION IMAGING
4. ENSURING THE SAFETY OF PEOPLE WHO GET CT SCANS
5. MEDICAL PHYSICS MOMENTS IN HISTORY

This year, the AAPM journal, Medical Physics, will celebrate the 50th anniversary with a year-long celebration. Every issue published in 2008 will have an article devoted to history and reviews of special topics intended to recognize this anniversary, and will carry the AAPM anniversary logo.

The AAPM is a scientific, educational, and professional nonprofit organization whose mission is to advance the application of physics to the diagnosis and treatment of human disease. The association encourages innovative research and development, helps disseminate scientific and technical information, fosters the education and professional development of medical physicists, and promotes the highest quality medical services for patients. In 2008, AAPM will celebrate its 50th year of serving patients, physicians, and physicists.

The 4th edition of Intermediate Physics for Medicine and Biology provides an introduction to many of these important topics in medical physics.

Scholarpedia

Scholarpedia: The Bidomain Model.

Anyone who teaches college students or has teenage children knows that the first place they go to for information is Wikipedia, the free online encyclopedia that anyone can edit. I, too, find Wikipedia useful. It’s extraodinarily simple to search for information, and surprisingly accurate. But sometimes, for technical information, you may prefer a more authoritative source. Now you have it: Scholarpedia. Like Wikipedia, Scholarpedia is online, free, and simple to use. The main difference with Wikipedia is that in Scholarpedia articles are authored and maintained by experts and undergo peer review. Anyone can edit Scholarpedia, but all changes must be approved by the “curator” (often the author) of the article, who’s responsible for its content.

Scholarpedia is just getting started, so it’s incomplete. But one of the first categories added to Scholarpedia was Cardiac Dynamics. Dr. Vadim Biktashev of the Department of Mathematical Sciences at the University of Liverpool is the editor for this category, and has organized many fascinating articles related to this topic. Anyone studying Chapters 7–10 of the 4th edition of Intermediate Physics for Medicine and Biology will find these Scholarpedia articles on cardiac dynamics to be a convenient online source of additional information. I’m the author of an article on the Bidomain Model that describes the electrical properties of cardiac tissue (introduced on page 191 in our book). Other particularly good articles are Cardiac Arrhythmia by Flavio Fenton, Elizabeth Cherry and Leon Glass; Models of Cardiac Cell by Fenton and Cherry; and FitzHugh-Nagumo Model by Eugene Izhikevich and Richard FitzHugh. Another category of interest to readers of Intermediate Physics for Medicine and Biology is Models of Neurons, with an article about Neuronal Cable Theory and a planned article about the Hodgkin-Huxley Model. Also, there are excellent articles on Magnetic Resonance Imaging, Transcranial Magnetic Stimulation, and many more topics. Take advantage of this excellent source to find more in-depth information on specific topics than Russ Hobbie and I could fit into our book.

Even More on "Medical Physics: the Perfect Intermediate Level Physics Class"

In 2001, Nelson Christensen of Carleton College published an article in the European Journal of Physics (Volume 22, Pages 421–427) titled “Medical Physics: The Perfect Intermediate Level Physics Class.” (See the Jan 25, 2008 and the Oct 5, 2007 blog entries for my earlier discussions about this paper.) The primary textbook for the class was the 3rd edition of Intermediate Physics for Medicine and Biology. Below is the introduction to his paper.

Physics is changing the way medicine is practised. While a doctor will still use a stethoscope, a diagnosis now often requires devices that make use of sophisticated physics and engineering. The importance of physics in medicine may be best displayed when a physicist needs to visit their doctor: we seem to be the only people who can intimidate doctors as we are the ones who actually know how their devices work. As a consequence of the technological evolution of the discipline, medical schools are admitting more and more students who major in physics or engineering.

Almost all major engineering schools will now have a department of biomedical engineering. There are numerous opportunities in academia in medical physics and biomedical engineering. Students interested in becoming an academic physicist now have a fast-growing field to aim for, a field that is providing more and more opportunities. The industrial sector in biomedical engineering is also advancing and evolving quickly. Physicists and engineers can find numerous and lucrative opportunities with companies.

With all of these opportunities it is no wonder that undergraduates are very interested in knowing more about medical physics. Partly due to student interest, and partly due to the faculty’s desire to provide interesting physics classes, Carleton College offered an intermediate level course in medical physics. This was a course open to students who have completed the first year physics courses. We deliberately designed the medical physics course so that the curriculum would be advanced, thereby negating the possibility that this course alone would satisfy a pre-medical school requirement. At this level we then attracted physics majors and pre-medical students who had a genuine interest in studying more physics.

Medical Physcis in the News

Teachers and students using the 4th edition of Intermediate Physics for Medicine and Biology might want a simple, enjoyable way to learn about the latest breakthroughs in medical physics. I suggest viewing some of the stories and videos at the website Medical Physics in the News. This site, sponsored by the American Association of Physicists in Medicine, contains 90 second videos about recent medical physics developments. The videos are produced by Discoveries and Breakthroughs Inside Science, a syndicated science and engineering news service for local television newscasts.

For instance, a video from December 2007 titled “Baby Thinking” describes a technique using diffuse optical tomography to study brain activity in children. Diffuse optical tomography is based on the diffusion of infrared and visible light through biological tissue, a topic examined in Chapter 14 of Intermediate Physics for Medicine and Biology. The November 2007 video titled “Safer MRI Scans for Heart Patients” explains how magnetic resonance images can be obtained safely in patients with implanted pacemakers and defibrillators. Pacemakers are described in Chapter 7, and MRI is explained in Chapter 18, of our textbook.

For those teachers who spend a lecture on the technical aspects of, say, optical diffusion may want to end the class with a 90 second video describing a potential application to modern medicine. It could help make the the basic science learned from Intermediate Physics for Medicine and Biology more relevant to the students.

If You Can Solve Only One Differential Equation...

If you can solve only one differential equation, let it be

 dy/dt = k y . 

This equation states that the rate of increase of a quantity y is proportional to the present amount of y. The solution is the exponential function

y = e^kt . 

Exponential growth is extremely important in medicine and biology, and in the 4th edition of Intermediate Physics for Medicine and Biology, Russ Hobbie and I devote the entire Chapter 2 to this topic.

The exponential function is one of the most important and widely occurring functions in physics and biology. In biology, it may describe the growth of bacteria or animal populations, the decrease of the number of bacteria in response to a sterilization procedure, the growth of a tumor, or the absorption or excretion of a drug... In physics, the exponential function describes the decay of radioactive nuclei, the emission of light by atoms, the absorption of light as it passes through matter, the change in voltage or current in some electrical circuits, the variation of temperature with time as a warm object cools, and the rate of some chemical reactions.

The Essential Exponential!
For the Future of Our Planet,
by Albert Bartlett.

Albert Bartlett has written a fascinating collection of essays about the exponential function: The Essential Exponential! For the Future of Our Planet. He claims that “the greatest shortcoming of the human race is our inability to understand the exponential function.” You can see Bartlett talking about the exponential and its implications for population growth on Youtube.

e: The Story of a Number,
by Eli Maor.

The exponential function is often written using the number e = 2.718... (If you want better precision, go to Google and search for "e"). This may be the most famous number, besides π, that’s not an integer. If you would like to read about the history of e, try Eli Maor’s delightful book  e: The Story of a Number.

 Arithmetic, Population, and Energy, by Albert Bartlett.
https://www.youtube.com/embed/O133ppiVnWY

Magnetic Therapy

I’m a skeptic when it comes to “alternative medicine.” Often the claims of alternative medicine conflict with the basic laws of physics—and in the end, physics always wins. In particular, there are many dubious health claims about the biological effects of electric and magnetic fields. For instance, I don’t know of any research supporting the idea that magnets in your shoes or jewelry have health benefits, nor can I think of any plausible mechanism underlying such an effect. Are there companies that really promote such silliness? Go to Google and search for “magnetic therapy” and you’ll find that, indeed, there are.

Voodoo Science:
The Road from Foolishness to Fraud,
by Robert Park.

Bob Park is a prominent debunker of bogus alternative medicine claims. He discusses magnetic therapy in his book Voodoo Science: The Road from Foolishness to Fraud.

“Natural” remedies [such as magnetic therapy] are presumed by their proponents to be somehow both safer and more powerful than science-based medicine. Fortunately, most natural medicine is in itself relatively harmless, aside from the financial damage done by paying eighty-nine dollars for a refrigerator magnet... It can, however, become dangerous if it leads people to forego needed medical treatment. Worse, alternative medicine reinforces a sort of upside-down view of how the world works, leaving people vulnerable to predatory quacks.

Another source of useful information is the magazine Skeptical Inquirer. In particular, see the article “Magnet Therapy, A Billion-dollar Boondoggle” by Bruce Flamm (July 2006), where he claims that there exists “a worldwide epidemic of useless magnet therapy.” Also, see Stephen Barrett’s article “Magnet Therapy: A Skeptical View” published by Quackwatch, Inc., a nonprofit corporation whose purpose is to combat health-related frauds, myths, fads, fallacies, and misconduct. Barrett’s bottom line is that “there is no scientific basis to conclude that small, static magnets can relieve pain or influence the course of any disease. In fact, many of today’s products produce no significant magnetic field at or beneath the skin’s surface.”
 
How can you distinguish the legitimate from nonsense? I suspect the layman will have a hard time telling the difference between “magnetic therapy” (bogus) and “magnetic stimulation” (a well-understood technique to excite nerves in the brain). The only way I know to sort out the good from the bad is to educate yourself on the underlying physics as it applies to biology and medicine. One place to start is the 4th edition of Intermediate Physics for Medicine and Biology. Whether you consult our book or another source of information, beware of suspicious claims about the benefits of electric and magnetic fields. Bioelectricity and biomagnetism are vibrant and important fields of study (see Chapters 6–9 of our book), but there’s a lot of baloney out there too.