Friday, January 27, 2017

The Genetic Effects of Radiation

My local public library had their quarterly used book sale last weekend, and as usual I went to search for Isaac Asimov books. I collect Asimov's books in part to pay homage to the huge influence he had on me as a teenager. He was the main reason I became a scientist. No luck this time; I came back from the sale empty handed. It’s difficult for me to find Asimov books that I don’t have, because I have so many (most bought second-hand for a pittance). Nevertheless, he wrote over 500 books, and I own far fewer than that, so I always have a chance.

You would think that I would at least know about all his books, even if I don’t own a copy. Yet somehow, I was unaware of (or had forgotten about) his book The Genetic Effects of Radiation, although it is a topic closely related to Intermediate Physics for Medicine and Biology. If interested, you can download a pdf of the book free (and I think legally) here. Below I present an excerpt about natural background radiation.
Background Radiation

Ionizing radiation in low intensities is part of our natural environment. Such natural radiation is referred to as background radiation. Part of it arises from certain constituents of the soil. Atoms of the heavy metals, uranium and thorium, are constantly, though very slowly, breaking down and in the process giving off alpha rays, beta rays, and gamma rays. These elements, while not among the most common, are very widely spread; minerals containing small quantities of uranium and thorium are to be found nearly everywhere.

In addition, all the earth is bombarded with cosmic rays from outer space and with streams of high-energy particles from the sun.

Various units can be used to measure the intensity of this background radiation. The roentgen, abbreviated r, and named in honor of the discoverer of X rays, Wilhelm Roentgen, is a unit based on the number of ions produced by radiation. Rather more convenient is another unit that has come more recently into prominence. This is the rad (an abbreviation for "radiation absorbed dose") that is a measure of the amount of energy delivered to the body upon the absorption of a particular dose of ionizing radiation. One rad is very nearly equal to one roentgen.

Since background radiation is undoubtedly one of the factors in producing spontaneous mutations, it is of interest to try to determine how much radiation a man or woman will have absorbed from the time he is first conceived to the time he conceives his own children. The average length of time between generations is taken to be about 30 years, so we can best express absorption of background radiation in units of rads per 30 years.

The intensity of background radiation varies from place to place on the earth for several reasons. Cosmic rays are deflected somewhat toward the magnetic poles by the earth's magnetic field. They are also absorbed by the atmosphere to some extent. For this reason, people living in equatorial regions are less exposed to cosmic rays than those in polar regions; and those in the plains, with a greater thickness of atmosphere above them, are less exposed than those on high plateaus.

Then, too, radioactive minerals may be spread widely, but they are not spread evenly. Where they are concentrated to a greater extent than usual, background radiation is abnormally high.

Thus, an inhabitant of Harrisburg, Pennsylvania, may absorb 2.64 rads per 30 years, while one of Denver, Colorado, a mile high at the foot of the Rockies, may absorb 5.04 rads per 30 years. Greater extremes are encountered at such places as Kerala, India, where nearby soil, rich in thorium minerals, so increases the intensity of background radiation that as much as 84 rads may be absorbed in 30 years.

In addition to high-energy radiation from the outside, there are sources within the body itself. Some of the potassium and carbon atoms of our body are inevitably radioactive. As much as 0.5 rad per 30 years arises from this source.

Rads and roentgens are not completely satisfactory units in estimating the biological effects of radiation. Some types of radiation—those made up of comparatively large particles, for instance — are more effective in producing ions and bring about molecular changes with greater ease than do electromagnetic radiations delivering equal energy to the body. Thus if 1 rad of alpha particles is absorbed by the body, 10 to 20 times as much biological effect is produced as there would be in the absorption of 1 rad of X rays, gamma rays, or beta particles.

Sometimes, then, one speaks of the relative biological effectiveness (RBE) of radiation, or the roentgen equivalent, man (rem). A rad of X rays, gamma rays, or beta particles has a rem of 1, while a rad of alpha particles has a rem of 10 to 20.

If we allow for the effect of the larger particles (which are not very common under ordinary conditions) we can estimate that the gonads of the average human being receive a total dose of natural radiation of about 3 rems per 30 years. This is just about an irreducible minimum.
This is typical Asimov. Let me add a few observations.
  1. Asimov rarely wrote specifically about medical physics, although he wrote much about related topics. I think The Genetic Effects of Radiation is closer to IPMB than his other books.
  2. The Genetic Effects is over 50 years old; it is out of date. For example, it uses the archaic units of rad and rem instead of gray and sievert (100 rem = 1 Sv). Moreover, radon gas is now known to make the largest contribution to background radiation, but the word “radon” never appeared in The Genetic Effects. Yet, I was surprised how much has not changed. I think a reader of IPMB would still find much useful information in Asimov's book.
  3. The text is aimed at a general audience, rather than an expert. The book is not a replacement for, say, Radiobiology for the Radiologist, or even IPMB. Yet, for a 16-year old kid (as I was when devouring Asimov's books about science), the level is just right.
  4. The discussion is not mathematical. At times Asimov writes about mathematical results, but he rarely presents equations. Certainly Asimov’s writing has vastly fewer equations than IPMB.
  5. Asimov doesn't use a lot of figures. The Genetic Effects contains more pictures than most of his books.
  6. This excerpt illustrates the "clear, cool voice of Asimov." I admire the clarity of his writing. No one explains things better.
And now I have to return to my search for more Asimov books. I am particularly a fan of his science essay collections originally published in Fantasy and Science Fiction. I have most of them, but somehow missed the very first: Fact and Fancy (1962). Garage sale season will be here in a few months. Hope springs eternal.

Friday, January 20, 2017

Manu Prakash and the Paperfuge

Three years ago I wrote a blog post about a crazy Stanford engineer, Manu Prakash, who developed a paper origami microscope called "foldscope" costing less than a dollar. LESS THAN A DOLLAR!

Well, he’s done it again. Now his team has invented a hand-held, lightweight centrifuge called "paperfuge" costing under 20 cents. UNDER 20 CENTS!!!

I'm thinking of buying one if I can scrape up the cash. Buddy, can you spare a dime?

Excuse me if you have already heard about paperfuge on social media; its been popping up a lot on Facebook and Twitter. I hate to jump on a bandwagon, but this is so amazing I have to tell you about it.

The physics of the centrifuge is described in a series of homework problems in the first chapter of Intermediate Physics for Medicine and Biology. Please, don’t think that topics relegated to the end-of-the-chapter exercises are less important than subjects discussed in the text. Sometimes key issues such as the centrifuge lend themselves to the homework, and you learn more by actively doing the problems then by passively reading prose (even mine!).

But let me get back to Prakash. His team recently published a paper in Nature Biomedical Engineering titled Hand-Powered Ultralow-Cost Paper Centrifuge (read it online here). The abstract says:
In a global-health context, commercial centrifuges are expensive, bulky and electricity-powered, and thus constitute a critical bottleneck in the development of decentralized, battery-free point-of-care diagnostic devices. Here, we report an ultralow-cost (20 cents), lightweight (2 g), human-powered paper centrifuge (which we name ‘paperfuge’) designed on the basis of a theoretical model inspired by the fundamental mechanics of an ancient whirligig (or buzzer toy; 3,300 BC). The paperfuge achieves speeds of 125,000 r.p.m. (and equivalent centrifugal forces of 30,000 g), with theoretical limits predicting 1,000,000 r.p.m. We demonstrate that the paperfuge can separate pure plasma from whole blood in less than 1.5 min, and isolate malaria parasites in 15 min. We also show that paperfuge-like centrifugal microfluidic devices can be made of polydimethylsiloxane, plastic and 3D-printed polymeric materials. Ultracheap, power-free centrifuges should open up opportunities for point-of-care diagnostics in resource-poor settings and for applications in science education and field ecology.
I’m telling you, the paperfuge is huge. My gosh, Prakash; this whirligig may make it big. I’m a fan of can-do Manu and his breakthrough; it's a real coup.

You also might like the “News and Views” editorial that accompanies their paper. Plus, articles lauding the paperfuge are all over the internet, such as this one in PhysicsWorld and this one on the National Public Radio website.

For those of you who prefer video, check out this great clip put out by Stanford University. 

To learn more about foldscope, watch Prakash's TED talk.

Finally, here is a video about his MacArthur genius grant.


Friday, January 13, 2017

Tony Barker receives the International Brain Stimulation Award

In Chapter 8 of Intermediate Physics for Medicine and Biology, Russ Hobbie and I discuss transcranial magnetic stimulation
Since a changing magnetic field generates an induced electric field, it is possible to stimulate nerve or muscle cells without using electrodes. The advantage is that for a given induced current deep within the brain, the currents in the scalp that are induced by the magnetic field are far less than the currents that would be required for electrical stimulation. Therefore transcranial magnetic stimulation (TMS) is relatively painless….

One of the earliest investigations was reported by Barker, Jalinous and Freeston (1985). They used a solenoid in which the magnetic field changed by 2 T in 110 μs to apply a stimulus to different points on a subject’s arm and skull. The stimulus made a subject’s finger twitch after the delay required for the nerve impulse to travel to the muscle. For a region of radius a = 10 mm in material of conductivity 1 S m−1, the induced current density for the field change in Barker’s solenoid was 90 A m−2. (This is for conducting material inside the solenoid; the field falls off outside the solenoid, so the induced current is less.) This current density is large compared to current densities in nerves (Chap. 6).
Tony Barker was the lead engineer who developed the first useful magnetic stimulator. For this ground-breaking work, he recently received the International Brain Stimulation Award. An Institute of Physics and Engineering in Medicine news article states
“The pioneer of Transcranial Magnetic Stimulation of the brain has become the first recipient of a new international award.

Professor Tony Barker, a Fellow of the Institute of Physics and Engineering in Medicine, has been awarded the International Brain Stimulation Award by publisher Elsevier.

The award acknowledges outstanding contributions to the field of brain stimulation. These contributions may be in basic, translational, or clinical aspects of neuromodulation, and must have had a profound influence in shaping this field of neuroscience and medicine.

Professor Barker, who recently retired after 38 years at Sheffield Teaching Hospitals’ Department of Medical Physics and Clinical Engineering, led the small team which developed the Transcranial Magnetic Stimulation (TMS) technique in the early 1980s.

He first started his research on using time-varying magnetic fields to induce current flow in tissue in order to depolarize neurons. Prior to this effort, direct electrical stimulation, with electrodes placed on the scalp (or other body part), was the principle method used to induce neuronal depolarization. This method, however, had several flaws and the high intensity of electrical stimulation is often painful. Magnetic fields, in contract, pass through the scalp and skull unimpeded and gives much more precise results.

In 1985, Professor Barker, together with his colleagues Dr Reza Jalinous and Professor Ian Freeston, reported the first demonstration of TMS. They produced twitching in a specific area of the hand in human volunteers by applying TMS to the motor cortex in the opposite hemisphere that controls movement of that muscle. This demonstrated that TMS was capable of stimulating a precise area of the brain and without the pain of electrical stimulation. Moreover, they did this with awake-alert human volunteers.

Today, TMS has become a vital tool in neuroscience, since, depending on stimulation parameters, specific brain areas can either be excited or inhibited. The TMS technique has evolved into a critical tool in basic neuroscience investigation, in the study of brain abnormalities in disease states, and in the treatment of a host of neurological and psychiatric conditions….

Professor Barker will receive his award at the 2nd International Brain Stimulation Conference in March, which is being held in Barcelona. He will also give a plenary lecture at the conference entitled Transcranial Magnetic Stimulation - past, present and future.”
According to Google Scholar, Barker’s paper “Non-invasive magnetic stimulation of human motor cortex” in the Lancet has over 3400 citations, reflecting its impact (Oops…the citation to this article in IPMB left out the word “motor” in the title; yet another item for the errata). The figure below is from Barker’s Scholarpedia article about TMS.

The Sheffield group with the stimulator which first achieved transcranial magnetic stimulation, February 1985. From left to right: Reza Jalinous, Ian Freeston and Tony Barker

Friday, January 6, 2017


Over the Christmas break I discovered a blog written under the pen name Neuroskeptic.
“Neuroskeptic is a British neuroscientist who takes a skeptical look at his own field, and beyond. His blog offers a look at the latest developments in neuroscience, psychiatry and psychology through a critical lens.”
Neuroskeptic's interests overlap topics covered in Intermediate Physics for Medicine and Biology. For instance, often Neuroskeptic writes about functional magnetic resonance imaging, a technique Russ Hobbie and I describe in Chapter 18 of IPMB.
“The term functional magnetic resonance imaging (fMRI) usually refers to a technique developed in the 1990s that allows one to study structure and function simultaneously. The basis for fMRI is inhomogeneities in the magnetic field caused by the differences in the magnetic properties of oxygenated and deoxygenated hemoglobin. No external contrast agent is required. Oxygenated hemoglobin is less paramagnetic than deoxyhemoglobin. If we make images before and after a change in the blood flow to a small region of tissue (perhaps caused by a change in its metabolic activity), the difference between the two images is due mainly to changes in the blood oxygenation. One usually sees an increase in blood flow to a region of the brain when that region is active. This BOLD contrast in the two images provides information about the metabolic state of the tissue, and therefore about the tissue function (Ogawa et al. 1990; Kwong et al. 1992).”
Neuroskeptic’s author is obviously an expert in this method, but is suspicious about some of its claims. Often he--I will use the masculine pronoun for convenience, but I have no idea about his gender--analyzes new papers in the field. For instance, in his recent New Year’s Eve blog post he writes
“Earlier this year, neuroscience was shaken by the publication in PNAS of Cluster failure: Why fMRI inferences for spatial extent have inflated false-positive rates. In this paper, Anders Eklund, Thomas E. Nichols and Hans Knutsson reported that commonly used software for analysing fMRI data produces many false-positives. But now, Boston College neuroscientist Scott D. Slotnick has criticized Eklund et al.’s alarming conclusions in a new piece in Cognitive Neuroscience. In my view, while Slotnick makes some valid points, he falls short of debunking Eklund et al.’s worrying findings.”
Another area Neuroskeptic analyzes is functional electrical stimulation. In Chapter 7 of IPMB, Russ and I write
“stimulating electrodes…may be used for electromyographic studies; for stimulating muscles to contract called functional electrical stimulation (Peckham and Knutson 2005); for a cochlear implant to partially restore hearing (Zeng et al.2008); deep brain stimulation for Parkinson’s disease (Perlmutterand Mink 2006); for cardiac pacing (Moses andMullin 2007); and even for defibrillation (Dosdall et al.2009). The electrodes may be inserted in cells, placed in or on a muscle, or placed on the skin.”
Two recent Neuroskeptic posts (here and here) analyze a controversial method of electrical stimulation called transcranial direct current stimulation (tDCS). I share his doubts about this technique, in which week currents (about 1 mA) are applied to the scalp. In a post last August, I hinted at some of my concerns, but my suspicions continue to grow. The electric fields induced in the brain by a 1 mA current to the scalp are minuscule.

Neuroskeptic also wonders if nonionizing radiation can cause cancer, a topic covered extensively in Chapter 9 of IPMB. He writes
“Does non-ionizing radiation pose a health risk? Everyone knows that ionizing radiation, like gamma rays, can cause cancer by damaging DNA. But the scientific consensus is that there is no such risk from non-ionizing radiation such as radiowaves or Wi-Fi. Yet according to a remarkable new paper from Magda Havas, the risk is real: it’s called When theory and observation collide: Can non-ionizing radiation cause cancer?... Non-ionizing radiation such as radiowaves and microwaves consists of photons, just like visible light, but at a lower frequency. Because the energy of a photon is proportional to its frequency, very high frequency photons (like gamma rays) have enough energy to disrupt atoms…But visible light can’t do this, and still less can microwaves or radiowaves. There’s no known mechanism by which such low-energy photons could harm living tissue – except that they can heat tissue up in high doses, but the amount of heating produced by radio and wireless devices is tiny.”
Neuroskeptic is not merely a debunker. Sometimes he examines promising new methods, but always with a questioning eye. For instance, his review of a paper developing new contrast agents for MRI is fascinating.
“In a new paper called Molecular fMRI, MIT researchers Benjamin B. Bartelle, Ali Barandov, and Alan Jasanoff discuss technological advances that could provide neuroscientists with new tools for mapping the brain.

Currently, one of the leading methods of measuring brain activity is functional MRI (fMRI)…. Recent work, however, holds out the hope that a future 'molecular fMRI' could be developed to extend the power of fMRI…. Molecular fMRI would involve the use of a molecular probe, a form of 'contrast agent', which would modulate the MRI signal in response to specific conditions.”
I would be interested in knowing what Neuroskeptic (I always want to type “the Neuroskeptic” but he never uses the definite article before his name, so I won’t either) thinks about claims of using the biomagnetic field as the gradient field in MRI, as I discussed in my June 2016 blog post.

Everyone has their own gimmick, and Neuroskeptic’s is that he keeps his real identity secret. Some of you are thinking: “Oh, I wish Roth would be anonymous! We hear far too much about him and his little dog Suki and his own research in this blog.” Well, sorry. It’s too late to change now, so you are stuck hearing about Suki and me in addition to learning about physics in medicine and biology. But if you want a well-written, anonymous, and sometimes dissenting view of neuroscience, read the Neuroskeptic.