Friday, February 26, 2016

Top 10 Isotopes

Everyone loves “top ten” lists. So, I have prepared a list of the top ten isotopes mentioned in Intermediate Physics for Medicine and Biology. These isotopes range from light to heavy, from abundant to rare, and from mundane to exotic. I have no statistics to back up my choices; they are just my own view about which isotopes play a key role in biology and medicine. Feel free to sound off in the comments about your favorite isotope that I missed. Let’s count them down to number one.
  1. 1H (hydrogen-1). This simplest of all isotopes has a nucleus that consists of only a single proton. Almost all magnetic resonance imaging is based on imaging 1H (see Chapter 18 about MRI). Its importance arises from its large abundance and its nuclear dipole moment.
  2. 222Rn (radon-222). While radon doesn’t have a large role in nuclear medicine, it is responsible for a large fraction of our annual background radiation dose (see Chapter 16 about the medical uses of x-rays). 222Rn is created in a decay chain starting with the long-lived isotope 238U. Because radon is a noble gas, it can diffuse out of uranium-containing rocks and enter the air, where we breath it in, exposing our lungs to its alpha particle decay.
  3. 131I (iodine-131). 131I is used in the treatment of thyroid cancer. Iodine is selectively taken up by the thyroid, where it undergoes beta decay, providing a significant dose to the surrounding tissue. A tenth of its radiation arises from gamma decay, so we can use the isotope for both imaging and therapy (see Chapter 17 about nuclear medicine).
  4. 192Ir (iridium-192). This gamma emitter is often used in stents placed in blocked arteries. It is also an important source for brachytherapy (Chapter 17), when a radioactive isotope is implanted in a tumor.
  5. 129Xe (xenon-129). This isotope is used in magnetic resonance images of the lung. Although the isotope is not abundant, its polarization can be increased dramatically using a technique called hyperpolarization (Chapter 18).
  6. 10B (boron-10). This isotope of boron plays the central role in boron neutron capture therapy (Chapter 16). in which boron-containing drugs accumulate in a tumor. When irradiated by neutrons, the boron decays into an alpha particle (4He) and 7Li, which both have high energy and are highly ionizing.
  7. 60Co (cobalt-60). For many years cobalt-60 was used as a source of radiation during cancer therapy (Chapter 16). The gamma knife uses 60Co sources to produce its 1.25 MeV radiation. The isotope is used less nowadays, replaced by linear accelerators.
  8. 125I (iodine-125). Iodine is the only element with two isotopes in this list. Unlike 131I, which emits penetrating beta and gamma rays, 125I deposits much of its energy in short-range Auger electrons (see Chapter 15 on the interaction of x-rays with matter). They deliver a large, concentrated dose when 125I is used for radioimmunotherapy.
  9. 18F (florine-18). A classic positron emitter, 18F is widely used in positron emission tomography (Chapter 17). Often it is attached to the sugar molecule as 18F-fluorodeoxyglucose, which is taken up and is then trapped inside cells, providing a PET marker for high metabolic activity.
  10. 99mTc (technitium-99m). The king of all nuclear medicine isotopes, 99mTc is used in diverse imaging applications (Chapter 17). It emits a 141-keV gamma ray that is ideal for most detectors. The isotope is often bound to other molecules to produce specific radiopharmaceuticals, such as 99mTc-sestamibi or 99mTc-tetrofosmin. If you are only familiar with one isotope used in nuclear medicine, let it be 99mTc.

Friday, February 19, 2016

The Sievert Integral

In Section 17.11 of Intermediate Physics for Medicine and Biology, Russ Hobbie and I discuss Brachytherapy.
Brachytherapy (brachy means short) involves implanting directly in a tumor sources for which the radiation falls off rapidly with distance because of attenuation, short range, or 1/r2. Originally the radioactive sources (seeds) were implanted surgically, resulting in high doses to the operating room personnel. In the afterloading technique, developed in the 1960s, hollow catheters are implanted surgically and the sources inserted after the surgery. Remote afterloading, developed in the 1980s, places the sources by remote control, so that only the patient receives a radiation dose.”
Often brachytherapy is performed by implanting a source of radiation formed as a line. Below is a new homework problem for calculating the dose of radiation assuming a small line source. You will do the calculation with and without a shield surrounding the source.

Section 17.11

Problem 56 ½. Brachytherapy is often performed using a radioactive source shaped as a line of length L having a total cumulated activity à and a mean energy emitted per unit cumulated activity Δ. Assume Eq. 17.50 describes the specific absorbed fraction Φ in the surrounding tissue having an energy absorption coefficient μen and density ρ

(a) Calculate the dose D a distance h away from the center of the line source (assume h is much less than both L and 1/μen). Let x indicate the position along the source, and set x = 0 at the center, so r2 = x2 + h2. The total dose is an integral over the length of the source, which has a cumulated activity per unit length Ã/L. Evaluate this integral using the substitution x = h tanθ. In the limits of integration, ignore end effects by letting L extend to infinity. You may need the trigonometric relationships d(tanθ)/dθ = sec2θ and 1 + tan2θ = sec2θ.

(b) Repeat the calculation in part (a), except add a coaxial cylindrical shield of thickness b surrounding the line source, made of a material having an absorption coefficient μatten. The dose from a small section of the source is now attenuated by an additional factor of exp(-μattenbsecθ). Justify the factor of secθ in the exponential. Show that the dose can now be written as the result from part (a) times 2/π times a definite integral, called the Sievert integral. Derive an expression for the Sievert integral.

(c) Make a drawing that indicates the physical meaning of h, b, x, r, L, and θ. Explain why the dose is inversely proportional to L.
The Sievert integral is analyzed and tabulated in the Handbook of Mathematical Functions with Formulas, Graphs, and Mathematical Tables by Abramowitz and Stegun. It can be generalized to include end effects. The integral is named after Rolf Sievert, the Swedish medical physicist who is honored by the SI unit for equivalent dose: the sievert.

Friday, February 12, 2016

Perspectives on Working at the Physics-Biology Interface

A few weeks ago, I wrote that “I’ve always been fascinated by physicists who move into biology, and I collect stories about scientists who have made this transition successfully.” Imagine my delight when I discovered a special issue of the journal Physical Biology about Perspectives on Working at the Physics-Biology Interface. Howard Berg and Krastan Blagoev collected many stories about physicists working in biology. In their introductory editorial, they write
“Physics is analytical, heavily dependent on mathematical equations; biology is more descriptive, heavily dependent on historical facts. There is a cultural gap. In physics, a theorist who can interpret others' experimental results is revered. In biology, such a person is suspect: ideas are thought cheap, facts dear.

But cultures can change. As problems in physics have become more difficult and more expensive to solve, or have been solved and thus are less interesting, physicists have begun to explore more complex areas of endeavor, including biology. Biologists, on the other hand, have begun to appreciate the benefits of thinking more quantitatively about their data. We thought it would be of interest to hear from physicists who have negotiated this cultural gap. What did they find challenging about biology, and how did they manage to begin work in such a different field? What advice might they have for younger practitioners of the art? One of us (HCB) moved long ago from work on hydrogen masers to studies of the motile behavior of bacteria. His trajectory is given in an interview published in Current Biology [1].

Some of our contributors have been involved with biophysics since their PhD, several were trained in condensed-matter theory, and others in nuclear or high-energy particle physics. Their interests range from the structure of proteins, RNA, or natural products, to cognitive or social abilities of bacteria, to emergent properties of complex or active media, or to the behavior of immune systems or neural networks. They all have interesting points of view, some subdued, others outspoken. We hope you enjoy the mix. Our hope is that with this issue we are able to capture the situation at the beginning of the 21st Century and to follow with another issue of this kind in ten years time.”
Below I list all the papers in this special issue, along with their abstracts.

The emergence of a new kind of biology by Harold J Morowitz
'It is happily no longer axiomatic that a biophysicist is a physiologist who can fix his own amplifier. Fortunately, physicists are still drifting into biology and bringing new ideas. Please dear colleagues, do take the time to learn biochemistry.' Harold Morowitz provides a personal perspective on working at the interface between the physical and biological sciences.
Two cultures? Experiences at the physics-biology interface by John J Hopfield
'I didn't really think of this as moving into biology, but rather as exploring another venue in which to do physics.' John Hopfield provides a personal perspective on working on the border between physical and biological sciences.
A Perspective: Robert B Laughlin by Robert B Laughlin
Despite their cultural differences, physics and biology are destined to interact with each other more in the future. The reason is that modern physics is fundamentally about codification of emergent law, and life is the greatest of all emergent phenomena.
Ask not what physics can do for biology—ask what biology can do for physics by Hans Frauenfelder
Stan Ulam, the famous mathematician, said once to Hans Frauenfelder: 'Ask not what Physics can do for biology, ask what biology can do for physics'. The interaction between biologists and physicists is a two-way street. Biology reveals the secrets of complex systems, physics provides the physical tools and the theoretical concepts to understand the complexity. The perspective gives a personal view of the path to some of the physical concepts that are relevant for biology and physics (Frauenfelder et al 1999 Rev. Mod. Phys. 71 S419–S442). Schrödinger's book (Schrödinger 1944 What is Life? (Cambridge: Cambridge University Press)), loved by physicists and hated by eminent biologists (Dronamraju 1999 Genetics 153 1071–6), still shows how a great physicist looked at biology well before the first protein structure was known.
Universal relations in the self-assembly of proteins and RNA by D Thirumalai
Concepts rooted in physics are becoming increasingly important in biology as we transition to an era in which quantitative descriptions of all processes from molecular to cellular level are needed. In this perspective I discuss two unexpected findings of universal behavior, uncommon in biology, in the self-assembly of proteins and RNA. These findings, which are surprising, reveal that physics ideas applied to biological problems, ranging from folding to gene expression to cellular movement and communication between cells, might lead to discovery of universal principles operating in adoptable living systems.
Physics transforming the life sciences by José N Onuchic
Biological physics is clearly becoming one of the leading sciences of the 21st century. This field involves the cross-fertilization of ideas and methods from biology and biochemistry on the one hand and the physics of complex and far from equilibrium systems on the other. Here I want to discuss how biological physics is a new area of physics and not simply applications of known physics to biological problems. I will focus in particular on the new advances in theoretical physics that are already flourishing today. They will become central pieces in the creation of this new frontier of science.
Research at the interface of physics and biology: bridging the two fields by Kamal Shukla
I firmly believe that interaction between physics and biology is not only natural, but inevitable. Kamal Shukla provides a personal perspective on working at the interface between the physical and biological sciences.
Let's not forget plants by Athene Donald
“Many physicists see the interface with biology as an exciting place to be." Athene Donald provides a personal perspective on working at the interface between the physical and biological sciences.
My encounters with bacteria—learning about communication, cooperation and choice by Eshel Ben-Jacob
My journey into the physics of living systems began with the most fundamental organisms on Earth, bacteria, that three decades ago were perceived as solitary, primitive creatures of limited capabilities. A decade later this notion had faded away and bacteria came to be recognized as the smart beasts they are, engaging in intricate social life through a sophisticated chemical language. Acting jointly, these tiny organisms can sense the environment, process information, solve problems and make decisions so as to thrive in harsh environments. The bacterial power of cooperation manifests in their ability to develop large colonies of astonishing complexity. The number of bacteria in a colony can amount to many billions, yet they exchange 'chemical tweets' that reach each and every one of them so they all know what they're all doing, each cell being both actor and spectator in the bacterial Game of Life. I share my encounters with bacteria, what I learned about the secrets of their social life and wisdom of the crowd, and why and how, starting as a theoretical physicist, I found myself studying social intelligence of bacteria. The story ends with a bacteria guide to cyber-war on cancer.
Working together at the interface of physics and biology by Bonnie L Bassler and Ned S Wingreen
Good communication, whether it is between quorum-sensing bacteria or the different scientists studying those critters, is the key to a successful interdisciplinary collaboration, Bonnie Bassler and Ned Wingreen provide a personal perspective on working at the interface between the physical and biological sciences.
Learning physics of living systems from Dictyostelium by Herbert Levine
Unlike a new generation of scientists that are being trained directly to work on the physics of living systems, most of us more senior members of the community had to find our way from other research areas. We all have our own stories as to how we made this transition. Here, I describe how a chance encounter with the eukaryotic microorganism Dictyostelium discoideum led to a decades-long research project and taught me valuable lessons about how physics and biology can be mutually supportive disciplines.
Letting the cat out of the bag: a personal journey in Biophysics by Carlos J Bustamante
When the author arrived in Berkeley, in the mid 1970s, to study Biophysics he soon felt as if he was engaging himself in a somewhat marginal activity. Biology was then entering another of its cyclical periods of annotation that was to culminate with the human genome project. Two decades later, however, at the end of this process, it had become clear that two main tasks were acquiring a central importance in biological research: a renewed push for a quantitative, precise description of biological systems at the molecular level, and efforts towards an integrated understanding of the operation, control, and coordination of cellular processes. Today, these have become two of the most fertile research areas in Biophysics.
A theoretical physicist's journey into biology: from quarks and strings to cells and whales by Geoffrey B West
Biology will almost certainly be the predominant science of the twenty-first century but, for it to become successfully so, it will need to embrace some of the quantitative, analytic, predictive culture that has made physics so successful. This includes the search for underlying principles, systemic thinking at all scales, the development of coarse-grained models, and closer ongoing collaboration between theorists and experimentalists. This article presents a personal, slightly provocative, perspective of a theoretical physicist working in close collaboration with biologists at the interface between the physical and biological sciences.
Understanding immunology: fun at an intersection of the physical, life, and clinical sciences by Arup K Chakraborty
Understanding how the immune system works is a grand challenge in science with myriad direct implications for improving human health. The immune system protects us from infectious pathogens and cancer, and maintains a harmonious steady state with essential microbiota in our gut. Vaccination, the medical procedure that has saved more lives than any other, involves manipulating the immune system. Unfortunately, the immune system can also go awry to cause autoimmune diseases. Immune responses are the product of stochastic collective dynamic processes involving many interacting components. These processes span multiple scales of length and time. Thus, statistical mechanics has much to contribute to immunology, and the oeuvre of biological physics will be further enriched if the number of physical scientists interested in immunology continues to increase. I describe how I got interested in immunology and provide a glimpse of my experiences working on immunology using approaches from statistical mechanics and collaborating closely with immunologists.
Rejoice in the hubris: useful things biologists could do for physicists by Robert H Austin
Political correctness urges us to state how wonderful it is to work with biologists and how, just as the lion will someday lie down with the lamb, so will interdisciplinary work, where biologists and physicists are mixed together in light, airy buildings designed to force socialization, give rise to wonderful new science. But it has been said that the only drive in human nature stronger than the sex drive is the drive to censor and suppress, and so I claim that it is OK for physicists and biologists to maintain a wary distance from each other, so that neither one censors or suppresses the wild ideas of the other.
One of my favorite quotes is from Morowitz’s paper: “Like many physicists, Gamov was impatient with biochemical nomenclature and for adenine, thymine, guanine, and cytosine he substituted hearts, spades, clubs, and diamonds.” Many of the papers reinforce the need for tight collaborations with biologists, and the need to learn some biology. I agree with that view, but it was nevertheless a guilty delight to read Robert Austin’s article, in which the old physics hubris takes center stage. Read it, but don’t tell anyone that you did.

Friday, February 5, 2016

The Rest of the Story

Alan was born 102 years ago today in Banbury, England. He was descended from a long line of Quakers. Quakers are often pacifists, so Alan’s dad George didn’t fight in World War I. Instead, he took part in a relief effort in the Middle East. But war is dangerous even if you are not in the line of fire, and George died of dysentery in Baghdad when Alan was only four.

Alan’s mom was left to raise him and his two brothers alone. She encouraged Alan’s interest in science, and so did his eccentric Aunt Katie who took him bird watching. When he was 15, Alan was hired by a ornithologist to survey rookeries and heronries. He spent hours searching for rare birds in salt marshes. All this kindled his passion for learning.

Based on his strong academic record, Alan won a scholarship to study botony, zoology, and chemistry at Trinity College, part of the University of Cambridge. One of Cambridge’s distinguished zoologists gave Alan some good advice: study as much physics and mathematics as you can! So he did. He also did what all undergraduates should do: research. He was good at it; so good that he was awarded a Rockefeller Fellowship to go to New York for a year. He kept at his research, and traveled around to other parts of the United States, such as Massachusetts and Saint Louis, to learn more.

When he got back to Cambridge, Alan’s knowledge of physics allowed him to build his own equipment, enabling him to move his research in exciting directions. He and his collaborators began to get dramatic results. Just when he was on the verge of making decisive discoveries, Hitler marched into Poland and the world was at war again.

Page 2

Alan suspended his own research and dedicated his talents to defeating the Germans. The Battle of Britain was won, in part, by the development of radar. Alan worked on a special type of radar that was installed in airplanes and used by RAF fighter pilots to locate and intercept Luftwaffe bombers. Alan and a small group of scientists toiled frantically, working seven days a week. They risked their lives on test flights in planes fitted with the new radar. For six years, during what should have been a young scientist’s most productive period, Alan set aside his own interests to help the Allies win the war.

Once World War II ended, Alan returned to Cambridge. After all this time, had science passed him by? No! He took up his research where he had left off, and started making groundbreaking discoveries in electrophysiology. With his coworkers, Alan figured out how nerves send signals down their axons, first passing sodium ions through the cell membrane and then passing potassium ions.

In 1963, Alan Hodgkin received the 1963 Noble Prize for Physiology or Medicine for discovering the ionic mechanism of nerve excitation.

And now you know THE REST OF THE STORY. Good day!

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This blog post was written in the style of Paul Harvey’s wonderful “The Rest of the Story” radio program. The content is based on Hodgkin’s autobiography Chance and Design: Reminiscences of Science in Peace and War. You can read about Hodgkin's work on electrophysiology--including Hodgkin and Huxley’s famous mathematical model of the nerve action potential--in Chapter 6 of Intermediate Physics for Medicine and Biology.

Happy birthday, Alan Hodgkin!