Friday, November 20, 2020

The Virtual Museum of Medical Physics

How would you like to visit a museum dedicated solely to medical physics? Well, with COVID-19 raging, we shouldn’t visit any museums in person. But how about visiting a virtual museum? The History Committee of the American Association of Physicists in Medicine has recently opened a Virtual Museum of Medical Physics.

The Virtual Museum was launched to celebrate the 125th anniversary of the discovery of x-rays on November 8, 1895 by Wilhelm Roentgen. Existing exhibits include those about Roentgen, Fluoroscopy, Mammography, and External Beam Radiotherapy. Exhibits under construction include Computed Tomography, Ultrasonic Imaging, Magnetic Resonance Imaging, and Nuclear Medicine. Once it’s done, the Virtual Museum will be a wonderful adjunct to Intermediate Physics for Medicine and Biology. If you want to contribute to developing an exhibit, contact the Virtual Museum.

Asimov's Biographical Encyclopedia of Science & Technology, superimposed on Intermediate Physics for Medicine and Biology.
Asimov’s Biographical Encyclopedia
of Science & Technology
.
And now, the story of how Roentgen discovered x-rays, as told in Asimov’s Biographical Encyclopedia of Science & Technology.
ROENTGEN, Wilhelm Konrad 
German physicist 
Born: Lennep, Rhenish Prussia, March 27, 1845 
Died: Munich, Bavaria, February 10, 1923

...The great moment that lifted Roentgen out of mere competence and made him immortal came in the autumn of 1895 when he was head of the department of physics at the University of Wurzburg in Bavaria. He was working on cathode rays and repeating some of the experiments of Lenard and Crookes. He was particularly interested in the luminescence these rays set up in certain chemicals.

In order to observe the faint luminescence, he darkened the room and enclosed the cathode ray tube in thin black cardboard. On November 5, 1895, he set the enclosed cathode ray tube into action and a flash of light that did not come from the tube caught his eye. He looked up and quite a distance from the tube he noted that a sheet of paper coated with barium platinocyanide was glowing. It was one of the luminescent substances, but it was luminescing now even though the cathode rays, blocked off by cardboard, could not possibly be reaching it.

He turned off the tube; the coated paper darkened. He turned it on again; it glowed. He walked into the next room with the coated paper, closed the door, and pulled down the blinds. The paper continued to glow while the tube was in operation.

It seemed to Roentgen that some sort of radiation was emerging from the cathode-ray tube, a radiation that was highly penetrating and yet invisible to the eye. By experiment he found the radiation could pass through considerable thicknesses of paper and even through thin layers of metal. Since he had no idea of the nature of the radiation, he called it X rays, X being the usual mathematical symbol for the unknown. For a time, there was a tendency to call them Roentgen rays, but the inability of the non-Teutonic tongue to wrap itself about the German œ diphthong militated against that. The unit of X-ray dosage is, however, officially called the roentgen.

Friday, November 13, 2020

The SIR Model of Epidemics

In Chapter 10 of Intermediate Physics for Medicine and Biology, Russ Hobbie and I discuss models described by nonlinear differential equations. We provide several examples in the text and homework problems, but one topic we never address is epidemics.

The archetype mathematical description of an epidemic is the SIR model. A population is divided into three categories, corresponding to three dynamic variables:

    S: the number of susceptible people

    I: the number of infected people

    R: the number of recovered people.

Three differential equations govern the number of people in each category.

    dS/dt = - (β/N) I S

    dI/dt = (β/N) I Sγ I

    dR/dt = γ I

where N is the total population, and β and γ are constants. Rather than analyze these equations myself, I’ll let you do it in a new homework problem.
Section 10.8

Problem 36 ½. The SIR model describes the dynamics of an epidemic. 
(a) Add the three differential equations and determine how the total number of people (S + I + R) changes with time. Does this model include people who die from the disease? 
(b) Write the equation governing the number of infected people as dI/dt = γI (r0 – 1). Find an expression for r0. Initially, when S = N, what does r0 reduce to? This value of r0 is known as the basic reproduction number. If r0 is less than what value will the number of infected people decay, preventing an epidemic?
(c) Suppose r0 is greater than one, so the number of infected people grows and the epidemic spreads. How low must the ratio S/N become for I to begin decreasing? Once this value of S/N is reached, the population is said to have herd immunity and the epidemic decays away.
Results from a numerical simulation of the SIR model.
Results from a numerical simulation of the SIR model, using S(0) = 997, I(0) = 3, R(0) = 0, β = 0.4, and γ = 0.04. By Klaus-Dieter Keller, CC0, https://commons.wikimedia.org/w/index.php?curid=77633956

The SIR model provides insight into the COVID-19 pandemic. It’s a simple model, and many researchers have modified it to be more realistic. Yet, there is value in a toy model like SIR. It lets you to gain intuition about a dynamical system without being overwhelmed by complexity. I always encourage students to first master a toy model, and only then add additional detail.

Friday, November 6, 2020

International Day of Medical Physics

Poster for the International Day of Medical Physics.
Poster for the
International Day of
Medical Physics.

Tomorrow is the International Day of Medical Physics! This year’s theme is the “Medical Physicist as a Health Professional.”

The second half of Intermediate Physics for Medicine and Biology focuses on medical physics topics, such as ultrasound, radiation therapy, tomography, nuclear medicine, and magnetic resonance imaging. These concepts are central to the work of medical physicists in our hospitals. The COVID-19 pandemic reminds us of how important health care professionals are. They are truly essential workers.

Nine years ago the International Organization for Medical Physics established this annual celebration of medical physics. The IOMP represents tens of thousands of medical physicists worldwide. It’s mission is to advance medical physics practice by “disseminating scientific and technical information, fostering the educational and professional development of medical physicists, and promoting the highest quality medical services for patients.” Below is a message from the President of the IOMP, Madan Rehani.

A message from Madan Rehani, President of the International Organization for Medical Physics.
https://www.youtube.com/watch?v=yFlOi7k8IjA

German Cancer Research Center will host a series of live online lectures celebrating the International Day of Medical Physics

How can you celebrate this special day? Tomorrow the German Cancer Research Center will host a series of live online lectures about medical physics aimed at a general audience. They will take place 3–5 PM their time, which would be 9–11 AM my time (Eastern Standard Time in the United States). You have to register to get the zoom link, but it’s free.

November 7 was chosen for the International Day of Medical Physics because it’s the birthday of Marie Curie. Below are excerpts from the Asimov’s Biographical Encyclopedia of Science & Technology entry about Curie. Enjoy!


Asimov's Biographical Encyclopedia of Science & Technology, by Isaac Asimov.
Asimov's Biographical
Encyclopedia of
Science & Technology.

CURIE, Marie Sklodowska (kyoo-ree’) 

Polish-French chemist 

Born: Warsaw, Poland, November 7, 1867 

Died: Haute Savoie, France, July 4, 1934

Asimov begins by discussing Curie’s education.

Marie was unable to obtain any education past the high school level in repressed Poland. An older brother and sister had left for Paris in search of education and Marie worked to help meet their expenses and to save money for her own trip there, meanwhile teaching herself as best she could out of books. In 1891 her earnings had accumulated to the minimum necessary, and off she went to Paris where she entered the Sorbonne. She lived with the greatest frugality during this period (fainting with hunger in the classroom at one time), but when she graduated, it was at the top of the class….
He then describes the scientific discoveries that underlie Curie’s research
The discovery of X rays by Roentgen and of uranium radiations by A. H. Becquerel galvanized Marie Curie into activity. It was she who named the process whereby uranium gave off rays “radioactivity.” She studied the radiations given off by uranium and her reports coincided with those of Ernest Rutherford and Becquerel in showing that there were three different kinds of rays, alpha, beta, and gamma….
Later, he explains the Nobel Prize winning research Marie Curie performed with her husband Pierre.
At the physics school where the Curies worked there was an old wooden shed with a leaky roof, no floor, and very inadequate heat. The two obtained permission to work there and for four years (during which Marie Curie lost fifteen pounds) they carefully purified and repurified the tons of [uranium] ore into smaller and smaller samples of more and more intensely radioactive material… Marie’s burning determination kept the husband-and-wife team going in the face of mountainous difficulties. By 1902 they had succeeded in preparing a tenth of a gram of radium after several thousand crystallizations. Eventually, eight tons of pitchblende gave them a full gram of the [radium] salt
Asimov ends with Curie’s final years.
Her last decades were spent in the supervision of the Paris Institute of Radium. She had made no attempt to patent any part of the extraction process of radium and it remained in the glamorous forefront of the news for nearly a generation, thanks to its ability to stave off the inroads of cancer under the proper circumstances. But in the end Marie died of leukemia (a form of cancer of the leukocyte-forming cells of the body) caused by overexposure to radioactive radiation.

Marie Curie - Scientist. https://www.youtube.com/watch?v=ZEV4KJBJvEg

Friday, October 30, 2020

Fundamental Limits of Spatial Resolution in PET

In Chapter 17 of Intermediate Physics for Medicine and Biology, Russ Hobbie and I discuss positron emission tomography.

17.10 Positron Emission Tomography

If a positron emitter is used as the radionuclide, the positron comes to rest and annihilates an electron, emitting two annihilation photons back to back. In positron emission tomography (PET) these are detected in coincidence.
Anyone who has looked at PET images will be struck by their low spatial resolution. They provide valuable functional information, but little anatomical detail. Why?
The first page of “Fundamental Limits of Spatial Resolution in PET,” by William Moses, superimposed on Intermediate Physics for Medicine and Biology.
“Fundamental Limits of
Spatial Resolution in PET,”
by William Moses.

In a 2011 article in Nuclear Instruments and Methods in Physics Research A (“Fundamental Limits of Spatial Resolution in PET,” Volume 648, Supplement 1, Pages S236–S240), William Moses analyses what factors contribute to PET spatial resolution.
Abstract: The fundamental limits of spatial resolution in positron emission tomography (PET) have been understood for many years. The physical size of the detector element usually plays the dominant role in determining resolution, but the combined contributions from acollinearity, positron range, penetration into the detector ring, and decoding errors in the detector modules often combine to be of similar size. In addition, the sampling geometry and statistical noise further degrade the effective resolution. This paper quantitatively describes these effects, discusses potential methods for reducing the magnitude of these effects, and computes the ultimately achievable spatial resolution for clinical and pre-clinical PET cameras.

Detector size

The most obvious limitation of spatial resolution comes from the detector size. Usually detection occurs in a scintillator crystal that converts a gamma ray to visible light, which is detected by a photomultiplier. The width of the scintillator limits the spatial solution of the image. A typical detector size is about 4 mm.

Positron range

A positron is emitted with an energy of about a million electronvolts. It then travels through tissue until it slows enough to capture an electron and and give off two 0.511 MeV photons. The range of the positron sets a limit to the spatial resolution. Different isotopes emit positrons with different energies. One of the most widely used isotopes for functional studies is 18F, which has a range of about half a millimeter. Most other common isotopes used in PET have longer ranges.

Acollinearity

If a positron and electron are at rest when they annihilate, they emit two 0.511 MeV photons. To conserve momentum, these photons must travel in opposite directions. If, however, the positron-electron pair has some kinetic energy when they annihilate, the photons are not emitted exactly in opposite directions. Usually they deviate from 180° by up to 0.25°. This translates into about one to two millimeters of blurring in typical detector rings.

Decoding

Decoding is complicated. Many PET devices have more scintillators than photomultipliers, so the photomultipliers take turns recording from different scintillators (a process called multiplexing). The PET scanner must then decode all this information, and this decoding process is not perfect. Moses estimates that decoding introduces an uncertainty of about a third of the detector width, or around a couple millimeters in spatial resolution.

Penetration

The 0.511MeV photons can penetrate into the ring of detectors used in a PET device, causing blurring. In the illustration below, if the source (green) contains an isotope that emits two photons, then for some angles those photons (red) are detected by a single detector, but for other angles (blue) they are detected by multiple detectors. 

An illustration based on Fig. 2 of
“Fundamental Limits of Spatial Resolution in PET,”
by William Moses, showing how penetration of a
photon into different detectors causes blurring.

Sampling Error

A detector ring is more sensitive to sources at some positions compared to others (see Moses’s Fig. 3 for an explanation). This effect tends to degrade by spatial resolution by about 25%.

 

If you add all these uncertainties in quadrature, you get a spatial resolution of about 6 mm. This is worse resolution that you would have for magnetic resonance imaging or computed tomography, which is why PET images look so blurry. They are often overlaid on an MRI (see Fig. 17.25 in IPMB).

If you decided to build a PET system with the best possible spatial resolution (regardless of complexity or cost), you could eliminate all of the sources of uncertainty except positron range and acollinearity, implying a spatial resolution of about 2 mm (worse for isotopes other than 18F). PET is never going to image small-scale anatomical detail.

Friday, October 23, 2020

Qualifying Exams

First page of the 2020 Physics Qualifying Exam.
First page of the 2020 Physics
Qualifying Exam.
I have discussed the Oakland University Medical Physics PhD Qualifying Exam previously in this blog. It’s a series of three written exams over math, physics, and biology, plus an oral exam.

I’ve collected the written qualifying exams over the last ten years (2011-2020) in a single file that you’re welcome to download. These exams are broad but not deep. They cover material at a level similar to, or somewhat higher than, Intermediate Physics for Medicine and Biology. Anyone working at the intersection of physics with biology should master these topics. The exams allow you to hone your problem solving skills. If you’re a student interested in applying physics to physiology, or math to medicine, but are stuck at home and not able to attend classes because of the covid-19 pandemic, you might want to try solving the 300 problems in this collection. (Slightly less than 300, because there wasn’t a math exam in 2014 and because we sometimes repeated questions from previous years.) If you want to try some of the exams from 2010 or earlier, you can find them at https://sites.google.com/view/bradroth/home/medical-physics-graduate-program/qualifying-exams?authuser=0.

Sorry, but I don’t have written solutions for these exams. You can always email me (roth@oakland.edu) if you’re stuck.

Enjoy!

Friday, October 16, 2020

Boron Neutron Capture Therapy

In Chapter 16 of Intermediate Physics for Medicine and Biology, Russ Hobbie and I discuss boron neutron capture therapy.

Boron neutron capture therapy (BNCT) is based on a nuclear reaction which occurs when the stable isotope 10B is irradiated with neutrons, leading to the nuclear reaction (in the notation of Chap. 17)
Both the alpha particle and lithium are heavily ionizing and travel only about one cell diameter. BNCT has been tried since the 1950s; success requires boron-containing drugs that accumulate in the tumor. The field has been reviewed by Barth (2003).
The first page of Barth, RF (2003) A Critical Assessment of Boron Neutron Capture Therapy: An Overview. Journal of Neuro-Oncology, Volume 62, Pages 1–5, superimposed on Intermediate Physics for Medicine and Biology.
Barth (2003)
J Neurooncol 62:1–5.
The citation is to an article by Rolf Barth of Ohio State University.
Barth, RF (2003) A Critical Assessment of Boron Neutron Capture Therapy: An Overview. Journal of Neuro-Oncology, Volume 62, Pages 1–5.
The abstract of this seventeen-year-old review states
Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when boron-10 is irradiated with neutrons of the appropriate energy to produce high-energy alpha particles and recoiling lithium-7 nuclei. BNCT has been used clinically to treat patients with high-grade gliomas, and a much smaller number with primary and metastatic melanoma. The purpose of this special issue of the Journal of Neuro-Oncology is to provide a critical and realistic assessment of various aspects of basic and clinical BNCT research in order to better understand its present status and future potential. Topics that are covered include neutron sources, tumor-targeted boron delivery agents, brain tumor models to assess therapeutic efficacy, computational dosimetry and treatment planning, results of clinical trails in the United States, Japan and Europe, pharmacokinetic studies of sodium borocaptate and boronophenylalanine (BPA), positron emission tomography imaging of BPA for treatment planning, and finally an overview of the challenges and problems that must be faced if BNCT is to become a useful treatment modality for brain tumors. Clinical studies have demonstrated the safety of BNCT. The next challenge is an unequivocal demonstration of therapeutic efficacy in one or more of the clinical trails that either are in progress or are planned over the next few years.
I was wondering what’s happening in this field lately, so I searched the Physics World website and found a fascinating and recent article by Tami Freeman.
Boron neutron capture therapy (BNCT), a technique that deposits highly targeted radiation into tumour cells, was first investigated as a cancer treatment back in the 1950s. But the field remains small, with only 1700 to 1800 patients treated to date worldwide. This may be about to change.

“The field of BNCT seems to be progressing rapidly at the moment,” said Stuart Green, director of medical physics at University Hospital Birmingham. “The big difference compared with five or ten years ago is that the commercial interest from a variety of companies is strong now and this is driving the field…”

Speaking at the Medical Physics & Engineering Conference (MPEC), Green updated on the status of BNCT programmes worldwide, noting that clinical experience is continually increasing. The US Food and Drug Administration has now approved two boron drugs for clinical use. But by far the majority of treatments, over 1150 to date, have taken place in Japan, initially using the Kyoto University Reactor in the early 2000s, and more recently using three Sumitomo accelerator systems in Kyoto, Fukushima and Osaka.

“Very importantly, earlier this year we had the first ever medical device approval for BNCT, for treatment in Japan of recurrent head-and-neck cancer,” said Green. “This is a significant marker for the entire field....”
“For the first time, there’s a substantial and sustained effort in the commercial sector to drive this field forward,” Green concluded. “We should keep an eye on BNCT over the next few years, there’s a lot happening, and hopefully our community can play a key role.”

Why the renewed interest in this technique? First, the original clinical applications of BNCT used neutrons from a nuclear reactor. Now accelerator-based neutron sources are available that can be installed in a hospital. Second, researchers are working hard on boron-containing drugs. Currently, boronophenylalanine and sodium borocaptate are the most common drugs used clinically. Improving the delivery of these drugs, or designing entirely new drugs, could increase the usefulness of BNCT. 

We live in exciting times.

Boron Neutron Capture Therapy Animation. 

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

Friday, October 9, 2020

Generation of Unidirectionally Propagating Action Potentials Using a Monopolar Electrode Cuff

The first page from Ungar et al. (1986) “Generation of Unidirectionally Propagating Action Potentials Using a Monopolar Electrode Cuff,” Ann. Biomed. Engin., 14:437-450, superimposed on Intermediate Physics for Medicine and Biology.
Ungar et al. (1986) Ann.
Biomed. Engin.
, 14:437–450.
In Chapter 7 of Intermediate Physics for Medicine and Biology, Russ Hobbie and I discuss electrical stimulation of nerves. One of the end-of-the-chapter homework problems asks the students to
Design a stimulator that will result in one-way propagation… For an application of such [a device] during functional electrical stimulation, see Ungar et al. (1986).
The reference is
Ungar IJ, Mortimer JT, Sweeney JD (1986) “Generation of Unidirectionally Propagating Action Potentials Using a Monopolar Electrode Cuff,” Annals of Biomedical Engineering, Volume 14, Pages 437–450.
The abstract to their article states
Unidirectionally propagating action potentials, which can be used to implement transmission failure on peripheral nerve through “collision block,” have been generated electrically on cat myelinated peripheral nerve using a monopolar electrode cuff with the conductor positioned closest to the “arrest” end of the cuff. A single cathode located at least 5 mm from the arrest end resulted in unidirectional propagation with minimal current and charge injection. The range of stimulus current values that produced unidirectional propagation increased with increases in longitudinal asymmetry of cathode placement over the range of asymmetries tested (1.7:1 to 7:1). The stimulus current pulse that minimized charge injection was quasitrapezoidal in shape with a plateau pulse width of approximately 350 μsec and an exponential trailing phase having a fall time (90%–10%) of approximately 600 μsec. These parameters were found to be independent of cuff geometry. Arrest efficiency was not degraded using a cuff of sufficient internal diameter to prevent nerve compression in chronic implantation. The critical current density within the extracellular space of the electrode cuff required to produce conduction failure at the arrest end was estimated to be 0.47 ± 0.08 mA/mm2.
I’ll explain how to make a one-way stimulator using the illustration below, adapted from Ungar et al.’s Figure 1.
The design of a one-way neural stimulator.
Adapted from Fig. 1 of Ungar et al. (1986).

The nerve (blue) is threaded through a cylindrical insulating cuff (red), which resembles a short segment of a plastic drinking straw. The cathode (green) is inside the cuff; it stimulates the action potential. The anode (not shown) is far away. Current (purple curves) comes out of the cathode and enters the nerve axons, depolarizing them. Once it reaches the end of the cuff the current spreads out as it returns to the distance anode. Current there leaves the axons, hyperpolarizing them, and lowering their transmembrane potential. The locations where the axons are hyperpolarized are labeled the virtual anodes.

The key to making a one-way stimulator is to place the cathode off-center in the cuff. Most of the current leaves the cuff through the end nearest the cathode (right end), so the current density is stronger there (the purple current lines are crowded together). Only a small fraction of the current leaves the cuff through the end farther from the cathode (left end), so the virtual anode is weaker there.

Depolarization under a cathode excites an action potential, which then propagates outward in both directions (left and right). If, however, the stimulus strength is strong enough, the hyperpolarization at a virtual anode can block propagation. If the current has the correct strength, the stronger virtual anode on the right will block propagation, while the weaker virtual anode on the left won’t. In that case, an action potential will propagate to the left (the escape end of the stimulator) but will not propagate to the right (the arrest end).

Ira Ungar and his collaborators were able to test their stimulator for different cathodal current strengths. For a very weak stimulus, the cathode is below threshold and no action potential is excited. For a moderately weak stimulus, the cathode excites an action potential that then propagates to both the left and the right; both virtual anodes are too weak to block propagation. For a moderately strong stimulus, the right virtual anode is strong enough to block the action potential and you have one-way propagation. For a very strong stimulus, both ends block propagation, and no action potential leaves the stimulator.

Why construct a one-way stimulator? Suppose you have a nerve that’s constantly firing action potentials, causing unwanted muscle contraction (spasticity). You could stop the downstream propagation of those action potentials by electrically stimulating action potentials further downstream. The stimulated action potentials propagating upstream will collide with the original action potentials propagating downstream, annihilating them (colliding action potentials can’t pass through each other because they’re each followed by a region of refracotoriness). This works great unless your stimulator sends its own volley of action potentials propagating downstream to excite the muscle. To avoid this problem, you need a one-way stimulator, so you only excite action potentials propagating upstream to block those causing the trouble, but none propagating downstream.

The senior author on this article was J. Thomas Mortimer, now emeritus professor in the Neural Engineering Center at Case Western Reserve University. He earned his PhD from Case and then spent his entire career there. He has developed an online Applied Neural Control Toolkit to teach how nerves work. I heard Mortimer speak during one of the Neural Prosthesis Workshops at the National Institutes of Health; he was inspirational.

Mortimer and his team’s development of a one-way stimulator is a classic example of how physics and engineering can contribute to medicine and biology.

Friday, October 2, 2020

The Death and Life of the Great Lakes

Many readers of this blog live far from me—sometimes in countries on the other side of the world—and may not be interested in local topics germane to Michigan. Yet the Great Lakes are important to everyone; they hold 20% of the earth’s liquid freshwater. The challenges faced by the Great Lakes aren’t unique; they’re relevant to other watersheds worldwide.

For those who aren’t Michiganders, a drawing of the five Great Lakes looks like a map of Michigan

The Great Lakes
From Phizzy at Wikipedia.

Between its upper and lower peninsulas, Michigan borders four of the five lakes. I live half way between the southern tip of Lake Huron and the western edge of Lake Erie. I’ve visited all five lakes, and I’m concerned about their welfare.
The Death and Life of the Great Lakes,
by Dan Egan.
 
I recently read The Death and Life of the Great Lakes (2017), by Dan Egan. (This book was recommended to me by Congresswoman Elissa Slotkin, who’s now running for reelection in my home district). I’ve lived in Michigan for 22 years, but much of this story was new to me. In his introduction, Egan writes
Iconic disasters have a history of prompting government action. Three years after the Cuyahoga River fire of 1969, Congress passed the Clean Water Act. Two decades later, when the Exxon Valdez ran aground and dumped 10.8 million gallons of crude oil into Alaska’s Prince William Sound, images of cleanup crews using paper towels to cleanse tarred birds helped press Congress into doing something it should have done years earlier. It mandated double-hulled oil tankers.

But the disaster unfolding today on the Great Lakes didn’t ignite like a polluted river or gush like oil from a cracked hull, and so far there is no galvanizing image of this slow-motion catastrophe, though a few come to my mind. One is the bow of an overseas ship easing its way into the first navigation lock on the St. Lawrence Seaway, the Great Lakes’ “front door” to fresh waves of biological pollution. Another is a satellite photo of a green-as-paint toxic algae slick smothering as much as 2,000 square miles of Lake Erie.

Yet another is the grotesque mug of an Asian carp, a monster-sized carp imported to the United States in the 1960s and used in government experiments to gobble up excrement in Arkansas sewage lagoons. The fish, which can grow to 70 pounds and eat up to 20 percent of their weight in plankton per day, escaped into the Mississippi River basin decades ago and have been migrating north ever since. There are now mustering at the Great Lakes’ “back door”—the Chicago canal system that created a manmade connection between the previously isolated Great Lakes and the Mississippi basin, which covers about 40 percent of the continental United States. The only thing blocking the fish’s swim through downtown Chicago and into Lake Michigan is an electrical barrier in the canal—one that has a history of unexpected shutdowns.

The Chicago canal has also turned the Great Lakes’ ballast water problem [ships from the Atlantic Ocean having exotic species in their ballast water and then dumping it into the Great Lakes] into a national one, because there are dozens of invasive species poised to ride its waters out of the lakes and into the rivers and water bodies throughout the heart of the continent. Species like the spiny water flea, the threespine stickleback, the bloody red shrimp and the fishhook water flea. All organisms you probably haven’t heard of. Yet.

Few out West, after all, had ever heard of quagga mussels—until they tumbled down the Chicago canal and metastasized across the Mississippi basin and, eventually, into the arid West, likely as hitchhikers aboard recreational boats towed over the Rocky Mountains. The mussels have since unleashed havoc on hydroelectric dams, drinking water systems and irrigation networks in Utah, Nevada and California and the federal government estimates that if the mussels make their way into the Northwest’s Columbia River hydroelectric dam system they could do a half billion dollars of damage—per year.
Much of Egan’s book is about how invasive species interact with native animals. In Chapter 2 of Intermediate Physics for Medicine and Biology, Russ Hobbie and I discuss the predator-prey problem modeled by the Lotka-Volterra equations. It is a useful toy model for understanding the interplay of two species, but it doesn’t explain the workings of a large and complex ecosystem.

The Great Lakes (at least the four that border Michigan) were once isolated from the Atlantic Ocean by Niagara Falls, a barrier than even the most determined fish could not surmount. The opening of the Saint Lawrence Seaway allowed a series of nonnative animals to enter the lakes. First came the sickening sea lamprey that nearly caused the native lake trout to go extinct. Next was an explosion of alewife (a river herring). Scientists introduced coho and Chinook salmon to prey upon the alewives. In each case, the ramifications of a new species were difficult to predict. Then zebra mussels and the quagga muscles arrived, and finally the round goby. It’s a horror story, and I suspect an invasion of the Asian carp is inevitable.

Besides these exotic species, the Great Lakes (especially Lake Erie) suffer from algae blooms triggered by fertilizer runoff. Add in climate change, which is causing the water level in the lakes to fluctuate, and you have an unstable and unhealthy ecosystem. 

I’ll give Egan the last word.
If we can close these doors to future invasions [of invasive species], we may give the lakes, and the rest of the country, time to reach a new equilibrium, a balance between what is left of the natural inhabitants and all the newcomers... And if we do this, then we can focus on the major problems that still plague the lakes, which include the overapplication of farm fertilizer that is helping to trigger the massive toxic algae outbreaks, the impact a warming globe is having on the lake’s increasingly unstable water levels and the need to protect lake waters from outsiders seeking to drain them for their own profit.

Dan Egan on The Death and Life of the Great Lakes at the 2018 L.A. Times Festival of Books. https://www.youtube.com/watch?v=jtq_cN1kPkg


Friday, September 25, 2020

Comparative Anatomy is Largely the Story of the Struggle to Increase Surface in Proportion to Volume

On Being the Right Size, by J. B. S. Haldane, superimposed on Intermediate Physics for Medicine and Biology.
On Being the Right Size,
by J. B. S. Haldane.
J. B. S. Haldane’s essay “On Being the Right Size” is a classic. In the first chapter of Intermediate Physics for Medicine and Biology, Russ Hobbie and I quote it.
You can drop a mouse down a thousand-yard mine shaft; and arriving at the bottom, it gets a slight shock and walks away. A rat is killed, a man is broken, a horse splashes.
Another line from the essay is nearly as famous.
Comparative anatomy is largely the story of the struggle to increase surface in proportion to volume.
We describe the interplay between surface and volume in Chapter 2 of IPMB
Consider the relation of daily food consumption to body mass. This will introduce us to simple scaling arguments. As a first model, we might suppose that each kilogram of tissue has the same metabolic requirement, so that food consumption should be proportional to body mass [or volume]. However, there is a problem with this argument. Most of the food that we consume is converted to heat. The various mechanisms to lose heat—radiation, convection, and perspiration—are all roughly proportional to the surface area of the body rather than its mass.
If ridding our bodies of excess heat is an important issue, then we need to increase surface area without increasing volume. A similar issue arises when getting oxygen to our cells. Our circulatory and respiratory systems are elaborate strategies to increase the area over which oxygen diffuses. This is a key concept where physics and physiology overlap.

You can read Haldane's essay in its entirety here. Below I quote part of it. Enjoy!
Animals of all kinds find difficulties in size for the following reason. A typical small animal, say a microscopic worm or rotifer, has a smooth skin through which all the oxygen it requires can soak in, a straight gut with sufficient surface to absorb its food, and a single kidney. Increase its dimensions tenfold in every direction, and its weight is increased a thousand times, so that if it is to use its muscles as efficiently as its miniature counterpart, it will need a thousand times as much food and oxygen per day and will excrete a thousand times as much of waste products.
Now if its shape is unaltered its surface will be increased only a hundredfold, and ten times as much oxygen must enter per minute through each square millimetre of skin, ten times as much food through each square millimetre of intestine. When a limit is reached to their absorptive powers their surface has to be increased by some special device. For example, a part of the skin may be drawn out into tufts to make gills or pushed in to make lungs, thus increasing the oxygen-absorbing surface in proportion to the animal’s bulk. A man, for example, has a hundred square yards of lung. Similarly, the gut, instead of being smooth and straight, becomes coiled and develops a velvety surface, and other organs increase in complication. The higher animals are not larger than the lower because they are more complicated. They are more complicated because they are larger. Just the same is true of plants. The simplest plants, such as the green algae growing in stagnant water or on the bark of trees, are mere round cells. The higher plants increase their surface by putting out leaves and roots. Comparative anatomy is largely the story of the struggle to increase surface in proportion to volume. Some of the methods of increasing the surface are useful up to a point, but not capable of a very wide adaptation. For example, while vertebrates carry the oxygen from the gills or lungs all over the body in the blood, insects take air directly to every part of their body by tiny blind tubes called tracheae which open to the surface at many different points. Now, although by their breathing movements they can renew the air in the outer part of the tracheal system, the oxygen has to penetrate the finer branches by means of diffusion. Gases can diffuse easily through very small distances, not many times larger than the average length traveled by a gas molecule between collisions with other molecules. But when such vast journeys—from the point of view of a molecule—as a quarter of an inch have to be made, the process becomes slow. So the portions of an insect’s body more than a quarter of an inch from the air would always be short of oxygen. In consequence hardly any insects are much more than half an inch thick. Land crabs are built on the same general plan as insects, but are much clumsier. Yet like ourselves they carry oxygen around in their blood, and are therefore able to grow far larger than any insects. If the insects had hit on a plan for driving air through their tissues instead of letting it soak in, they might well have become as large as lobsters, though other considerations would have prevented them from becoming as large as man.

Friday, September 18, 2020

Spillover: Animal Infections and the Next Human Pandemic

Spillover: Animal Infections and the Next Human Pandemic, by David Quammen, superimposed on Intermediate Physics for Medicine and Biology.
Spillover, by David Quammen
I recently read Spillover: Animal Infections and the Next Human Pandemic, by David Quammen. This book was written eight years ago, but it helped me understand what’s happening today with the coronavirus. Quammen writes:
A person might construe this list [Ebola, HIV, bird flu, West Nile virus, SARS, and now Covid-19] as a sequence of dire but unrelated events—independent misfortunes that have happened to us, to humans, for one unfathomable reason and another. Seen that way, Machupo and the HIVs and SARS and the others are “acts of God” in the figurative (or literal) sense, grievous mishaps of a kind with earthquakes and volcanic eruptions and meteor impacts, which can be lamented and ameliorated but not avoided. That’s a passive, almost stoical way of viewing them. It’s also the wrong way.

Make no mistake, they are connected, these disease outbreaks coming one after another. And they are not simply happening to us; they represent the unintended results of the things we are doing. They reflect the convergence of two forms of crisis on our planet. The first crisis is ecological, the second medical. As the two intersect, their joint consequences appear as a pattern of weird and terrible new diseases, emerging from unexpected sources and raising deep concern, deep foreboding, among the scientists who study them. How do such diseases leap from nonhuman animals into people, and why do they seem to be leaping more frequently in recent years? To put the matter in its starkest form: Human-caused ecological pressures and disruptions are bringing animal pathogens ever more into contact with human populations, while human technology and behavior are spreading those pathogens ever more widely and quickly.
Spillover doesn’t contain much physics, but it does allude to the math describing epidemics, making it relevant to Intermediate Physics for Medicine and Biology. Chapter 3 of Spillover discusses the 1927 model of William Kermack and Anderson McKendrick. I admire Quammen for including the mathematical biology of epidemics in his book, but he seems uncomfortable talking about math, and hesitant about subjecting his readers to it. I’m glad the readers of IPMB don’t place me under the same constraint.

Amid a dense flurry of mathematical manipulations, [Kermack and McKendrick] derived a set of three differential equations describing the three classes of living individuals: the susceptible, the infected, and the recovered. During an epidemic, one class flows into another in a simple schema, SIR, with mortalities falling out of the picture because they no longer belong to the population dynamic. As susceptible individuals become exposed to the disease and infected, as infected individuals either recover (now with immunity) or disappear, the numerical size of each class changes at each moment in time. That’s why Kermack and McKendrick used differential calculus. Although I should have paid better attention to the stuff in high school [I didn’t take calculus until college!], even I can understand (and so can you) that dR/dt = γI merely means that the number of recovered individuals in the population [I would have said “the rate of increase of the number of recovered individuals…”], at a given moment, reflects the number of infected individuals times the average recovery rate.  So much for R, the “recovered” class. The equations for S (“susceptibles”) and I (“infected”) are likewise opaque [not the word I would choose] but sensible. All this became known as an SIR model. It was a handy tool for thinking about infectious outbreaks, still widely used by disease theorists.
Covid-19 is caused by a zoonotic virus: a pathogen that leaps from an animal “reservoir” to infect humans. Quammen focuses on zoonotic viruses in Spillover, but he points out that not all viruses originate in animals. For instance, polio and smallpox are viruses that infect only humans. Once we remove those viruses from the human population, they are gone forever. A zoonotic virus “hides” in some wide animal (bats are a common reservoir) until it makes the jump to humans, so they are extraordinarily difficult to eradicate. Spillover is at its best when it describes these jumps, and the scientists who study them. Moreover, Quammen’s book is an extended case study of the scientific method. Everyone should read it.

Does Quammen predict the Covid-19 pandemic? Sort of. He predicts future pandemics arising from virulent and transmissible viruses that spill over from animal reservoirs. He predicts that our growing population and technology will make such spillovers more common. He even pinpointed coronaviruses as one of the likely suspects that could cause a future plague. What scares me is that Covid-19—as disruptive as it’s been for society—is not virulent enough to be the “Next Big One.” I fear it may be only a hint of things to come.

Worried? Me too. I’ll let Quammen have the final—somewhat hopeful—word [my italics].
I don’t say these things about the ineradicability of zoonoses to render you hopeless and depressed. Nor am I trying to be scary for the sake of scariness. The purpose of this book is not to make you more worried. The purpose of this book is to make you more smart.
 
David Quammen talking about Spillover.