Archive for the ‘Science’ Category


Marshall & Warren: cinematic science

January 13, 2017

Portrayals of science and scientists on television and in movies are often hilariously fanciful. In the generally wonderful BBC/PBS series “Sherlock,” for example, the title character sees the chemical structures of individual molecules through an ordinary light microscope. I guess peering into a ‘scope makes for more compelling and succinct visuals than, say, running samples through an HPLC and laboriously comparing them to standards. (“It’s UNCANNY, Watson! The retention time in THIS solvent is 9.72 minutes — HIGHLY suggestive of a halogen-substituted phenol!”)

Every so often, though, you come across a real-life science story that has an undeniably cinematic arc. Such is the tale of Australian physicians Barry J. Marshall and J. Robin Warren, who won the 2005 Nobel Prize in Medicine or Physiology for discovering the bacterium Helicobacter pylori and showing that it causes most cases of gastritis and peptic ulcers.

As recounted by Marshall (2001), his work with Warren drew upon four previously disparate strands of biomedical ideas and evidence. These strands, as of the late 1970s, were as follows. (1) Spiral-shaped bacteria had occasionally been found in the stomachs of various mammals, including humans. But these bacteria were not widely suspected of causing any particular disease. (2) Gastritis –- inflammation of the stomach -– was a well-known problem generally attributed to stress, which supposedly induced secretion of excessive acid into the stomach. But some patients developed gastritis despite an impaired ability to secrete acid. (3) An enzyme called urease, which breaks urea into carbon dioxide and ammonia, had been found in the stomach; some evidence suggested that it had been produced by bacteria. But urease’s importance, if any, was unclear. (4) Formulations containing bismuth, a heavy metal, had been used to successfully treat nonspecific gastrointestinal problems. But the mechanism of action and the importance of the bismuth itself were not clear either.

In pivotal studies conducted mostly in the early 1980s, Marshall and Warren synthesized these four strands into a coherent theory, as follows. Gastritis was not caused by acid secretion problems per se but by the spiral bacterium, H. pylori, which burrows into the mucus lining the stomach and causes inflammation. While most bacteria cannot survive the low pH of the stomach, H. pylori produces and secretes urease, which helps it weather the acidic environment by producing ammonia, which serves as a buffer. Finally, bismuth can cure gastric problems by serving as an antibiotic, killing H. pylori and ending the corresponding inflammation.

This was an exciting story in and of itself, but there was more. Not only does H. pylori cause the acute condition of gastritis, it turns out to be the main culprit in the chronic conditions of stomach ulcers and stomach cancer. Antibiotics were found to cure ulcers as well as gastritis (Marshall et al., 1988), and to drastically reduce the incidence of stomach cancer.

Marshall and Warren were initially ridiculed and dismissed. One can debate the extent to which this skepticism on the part of the scientific community was appropriate, because the preliminary evidence produced by Marshall and Warren was clear, but not overwhelming. A perfect example of this is the study in which Marshall et al. (1985) fulfilled Koch’s four postulates for identifying the causative agent of an infectious disease. Meeting the postulates is strong evidence that a disease’s cause has been found (Evans, 1976), so Marshall et al.’s (1985) study could be considered strong, yet — spoiler alert! — it was conducted on only one subject, Marshall himself, who gave himself gastritis by drinking a broth of H. pylori taken from another patient. Marshall believed this necessary because he had not been able to get H. pylori to cause disease in a healthy animal (Marshall & Adams, 2008), the usual way of fulfilling Koch’s third postulate. The study was not published in an elite journal but rather The Medical Journal of Australia, whose middling reputation may have also limited awareness and acceptance of the conclusions. Moreover, the idea that bacteria could cause disease in the stomach was considered implausible by many physicians, who assumed that the stomach’s high acidity kills essentially all microbes (Weintraub, 2010).

Another major, slightly comical step forward came during Marshall and Warren’s first big clinical study, in which they checked 100 gastritis patients for the possible presence of H. pylori in their stomachs (Marshall & Warren, 1984). They had no luck with the first 34 patients, but — spoiler alert! — sample #35 came back positive after incubating over a long holiday weekend, which gave the slow-growing H. pylori extra time to reveal itself. (It was actually during Easter. How perfect is that? On the third day, the bacteria appeared again. They were alive after all! Alive, I say!) After this, all samples were incubated for four days rather than two, and most were found to contain H. pylori.

It really is a great story. Why hasn’t it been turned into a movie?


Evans, A. S. (1976). Causation and disease: the Henle-Koch postulates revisited. The Yale Journal of Biology and Medicine, 49(2), 175-195.

Marshall, B. J. (2001). One hundred years of discovery and rediscovery of Helicobacter pylori and its association with peptic ulcer disease. In H. L. T. Mobley, G. L. Mendz, & S. L. Hazell (Eds.), Helicobacter pylori: Physiology and Genetics. Washington (DC): ASM Press.

Marshall, B., & Adams, P. C. (2008). Helicobacter pylori: A Nobel pursuit? Canadian Journal of Gastroenterology, 22(11), 895.

Marshall, B. J., Armstrong, J. A., McGechie, D. B., & Glancy, R. J. (1985). Attempt to fulfil Koch’s postulates for pyloric Campylobacter. The Medical Journal of Australia, 142(8), 436-439.

Marshall, B. J., & Warren, J. R. (1984). Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. The Lancet, 323(8390), 1311-1315.

Marshall, B., Warren, J. R., Blincow, E., Phillips, M., Goodwin, C. S., Murray, R., … & Sanderson, C. (1988). Prospective double-blind trial of duodenal ulcer relapse after eradication of Campylobacter pylori. The Lancet, 332(8626), 1437-1442.

Weintraub, P. (2010). The Dr. who drank infectious broth, gave himself an ulcer, and solved a medical mystery. Discover Magazine, March 2010.


Recent videos

December 5, 2016

As long as I’m using this blog to support family causes such as my parents’ anti-fluoridation work, I should also throw in a plug for my sister’s company’s new video, which nicely showcases their customizable dresses and headbands for girls 3-7 and their dolls. Great fun for those who enjoy spontaneous, open-ended accessorizing!

Other recent videos of possible interest: my song Cranial Nerve Functions, performed by Do Peterson; my song Kidney Wonderland, performed by me at the UW Nephrology holiday party.


Fluoridated drinking water is not an elegant 21st-century solution

December 3, 2016

In a previous post, I explained why, overall, I approve of the anti-fluoridation movement. Now I want to address one specific aspect of this that is partly scientific but partly philosophical and aesthetic.

First, a bit of personal context. In the lab-research phase of my career, I spent about 7 years working on the development of new drugs for infectious diseases like malaria. To my great disappointment, my work did not contribute much to the fight against these diseases. However, as I worked in this sphere, I was dazzled by others’ advances, such as the following:

(1) A project led by Meg Phillips (UT-Southwestern) and Pradip Rathod (University of Washington) has intensively studied dihydrooroate dehydrogenase (DHODH), an enzyme thought to be a good malaria drug target. In other words, if a drug impairs this enzyme in malaria parasites (Plasmodium falciparum and related species), the parasite should die and the infected person should be cured of malaria. Over the past 15+ years, DHODH has been characterized in almost obsessive detail, enabling the design of chemicals that strongly block the Plasmodium DHODH without messing up the human DHODH or other human enzymes. A new drug based on this work, DSM265, is currently undergoing clinical trials.

Figure (taken from Phillips et al., Science Translational Medicine 7: 296ra111, 2015) showing how the drug DSM265 nestles among specific amino acids of DHODH, thus disrupting its function.

(2) Among already-approved malaria drugs, artemisinin-related compounds are the best ones we have. However, isolating artemisinin from its natural source (the plant Artemisia annua) is costly and time-consuming. A team led by Jay Keasling developed an intricate “semi-synthetic” process, involving both genetically engineered yeast and chemical engineering technology, by which artemisinins can be made cheaply in the lab from simple starting materials.

Artemisin synthesis, part 1
Artesinin synthesis, part 2
Figures (taken from Paddon et al., Nature 496: 528-532, 2013) showing how artemisin can be synthesized in a chemical engineering lab.

To me, these projects represent the pinnacle of modern biomedical science. They were exceptionally hard, but years of relentless detail-oriented work by large groups of talented scientists — not to mention generous funding from government and nonprofit groups — led to practical advances that could save uncountable lives.

When held up against such thorough, painstaking work, the strategy of fighting tooth decay by dumping fluoride into drinking water strikes me as really lame.

For the sake of this argument, I’m not taking a stand on the strength of the evidence that fluoride reduces the formation of dental caries (cavities). Let’s assume that it does. The key point here is that according to most pro-fluoridation experts, fluoride acts topically (i.e., at the surface of teeth) rather than systemically (i.e., by passing through the blood and the rest of the body).

The Fluoride Action Network argues, “If fluoride works topically, there is no need to swallow it, and therefore no need to add it to the water supply. This is especially so when considering that (1) fluoride is not a nutrient, and (2) fluoride’s risks come from ingestion.” This reasoning really speaks to me as a scientist.

As illustrated above, we live in an age of remarkable biomedical resources. With the efforts of our best scientists, we can achieve great things like cure malaria with the best precision drugs mankind has ever known. In this can-do environment, do our most sensible and sophisticated cavity-fighting efforts really involve delivering fluoride to the wrong place in the body (the gastrointestinal tract) and hoping that the right amount of it trickles to the right place (the teeth)?

Fluoridated water’s relative safety or lack thereof is, in some ways, beside the point; it’s simply not the best option that we have. As scientifically literate, non-superstitious people, if we want fluoride to act on our teeth, we should put it on our teeth (e.g., with fluoride toothpaste), then spit it out. Period.

In closing, I want to acknowledge a counterargument to which I am sympathetic. People with limited incomes are least likely to get regular professional dental care and are also least likely to be able to afford fluoride toothpaste or be aware of its value. Shouldn’t we fluoridate water to give these vulnerable people the benefits of fluoride even if they’re not brushing regularly with fluoride toothpaste?

I think it’s a reasonable question. But if I were the mayor of a fluoridated-water town, I’d redirect all fluoridation funding into programs to aggressively distribute fluoride toothpaste to all low-income people who need it. And if I were a dentist, rather than lobbying for water fluoridation, I’d focus on this more intelligent route of fluoride delivery.


I’m not an ecologist, but sometimes I play one on the Internet

December 2, 2016

This fall, I’ve been teaching introductory ecology & evolution labs for BBio 180 at UW-Bothell. It had been quite a while since I had worked directly with eco-evo material, so it was interesting to look at it with fresh eyes, sort of as my students were doing.

As the quarter progressed, I got the urge to contribute something to the excellent Dynamic Ecology blog run by bona fide ecologists, including my friend Jeremy Fox. So I pitched Jeremy a post on teaching with imperfect analogies, featuring eco-evo examples, which he liked and published.

With eco-evo analogies on my brain, I then started applying them to the realm of academic job searches, which led me to write another piece, which is posted below.

Ecology analogies for the academic job market

Dear Tenured People:

The academic job market continues to suck. Most of your students will be unable to land stable faculty jobs. Please discuss this fact, repeatedly, with your students and trainees. Explicitly acknowledging the extreme difficulty of getting a prized professorship is a vaccine against complacency and self-delusion, both in them and in you, the mentors who send them forth into the world. Since these discussions can be boring and/or dreary, you might consider enlivening them with the analogies below.


Aging Adjunct

* * * * * * *

Analogy #1: Net reproductive rate R0

I began a recent UW-BERG seminar on job searches with an odd “hook”: a worksheet on net reproductive rate, R0, defined as the average number of female offspring produced by each female parent. (Females are the focus here because males are usually not limiting to reproduction.)

From the definition of R0, it follows that, in the absence of other changes (e.g., in lifespan), the population declines if R0 is less than 1, holds steady if R0 equals 1, and grows if R0 is greater than 1.

We can then move, as the worksheet does, to the concept of the academic reproductive rate as defined by Larson et al. (2014) and Gaffarzadegan et al. (2015). The academic R0 can be considered to be the average number of PhD students graduated by a tenure-track faculty member.

Gaffarzadegan et al. have a nice graph showing that, since 1980, the number of biology PhDs has increased dramatically while the number of tenure-track faculty positions has barely changed, causing the biologist R0 to rise from 2.4 (1980-90) to 6.3 (2010-2015).

With this additional information, discussions of academic job prospects can proceed in any of several directions. At my seminar, for example, I asked attendees to use the R0 model to make predictions about the quantity and experience of applicants for teaching-centric faculty positions. We then compared the predictions to actual job search data.

For me, those data are a mixed bag. The number of applicants per position was lower than I would have guessed. However, it is sobering that even the ad-hoc temporary openings attracted many experienced candidates.

Anyway, I find the R0 analogy useful in several ways.

(A) The R0 analogy underscores that mentors’ trainees are, in some sense, their “children,” i.e., people for whom they bear some responsibility. And that professors, departments, universities, and countries should not take on more children than they can reasonably expect to support.

(B) The rise of the biologist R0 so far above 1 is a sign that our entire training system may be fundamentally unsustainable, as argued by the scientific “dream team” of Alberts et al. (2014).

(C) The focus on a single easy-to-grasp number, R0, helps us contemplate the problems underlying it, as well as possible solutions. For instance, I said “MAY be fundamentally unsustainable” above because a high R0 would be acceptable if most PhDs used their academic training as an intentional springboard to wonderful non-academic careers. However, since most biologists would prefer to stay in academia (Sauermann & Roach 2012), a high R0 is a symptom of a serious problem. Partial solutions, then, might include training fewer PhDs and/or convincing more of us to give more serious consideration to non-academic options before we put all of our eggs in one basket.

And speaking of nascent forms of life….

Analogy #2: The soil seed bank

While I liked the R0 analogy enough to feature it in my UW-BERG seminar, I almost used an alternative analogy suggested by my colleague Cynthia Chang.

The basic idea of the soil seed bank is that soil contains deposits of seeds from many different species, any of which could potentially germinate, but few of which actually do.

So what are the implications of considering newly minted PhDs as “seeds” with potential to “germinate” into full-fledged faculty members?

Well, to start with, most seeds will not ever germinate, an obvious point also illustrated by the R0 analogy. But the soil seed bank analogy can be extended to make several related points.

(A) Germination may occur after a prolonged lag, but most seeds do lose their viability over time. People may hang on as postdocs and as adjunct faculty for quite a while, but after so many years, the odds of making the transition to full-time permanent faculty are quite low. Still, the lack of a firm “expiration date” makes it hard to know when to give up.

(B) Different conditions favor different seeds. Each species of seed has its own optimal germination conditions in terms of moisture, temperature, sunlight, etc. Which seeds actually germinate at a given time depends on local conditions at that time. Similarly, within a diverse crop of youngish biology PhDs, those whose strengths match the current needs of specific departments will be most likely to lay down roots.

(C) Seeds’ success or failure depends strongly on luck. A corollary to (B) is that, as conditions change from year to year, the species that sprout will change as well. If a fire happens to sweep through a given region, fire-resistant seeds will subsequently be favored. If instead the region happens to be hit with, say, a flood, different seeds will instead win the germination sweepstakes. The job-search parallels should be clear: whether a given candidate ultimately blossoms depends not only on their personal robustness, but whether they happen to enter the job market at a time and place that happens to favor their particular strengths.

This last point is often hard for hard-luck applicants to swallow. Words to the effect of “It’s not about you, it’s just an issue of fit,” while well-intended and true, are not necessarily comforting. Having had the persistence to come this far, we figure that if we can just hang in there, we will eventually have our day in the sun.

Indeed, some of us will ultimately be great oaks or sequoias, impressive and enduring, the giants of our fields.

For now, though, we are but tiny vessels of unrealized potential and uncertain fate, weathering harsh environments, hoping against hope for a favorable wind and a soft landing.


Fluoridated drinking water: public-health triumph, or force-fed meds?

November 29, 2016

In general, I trust our government. I trust it to use my taxes wisely, protect the less fortunate among us, and enact policies based on sound research and reasoning.

If scientists from the government tell me that the scientific consensus is such-and-such, I generally believe them. Sample topics: climate change, vaccines, evolution.

Thus, when I heard that citizens’ groups were opposing the fluoridation of public drinking water, in contrast to the official position of the Centers for Disease Control and Prevention (CDC), I was initially skeptical. It sounded like a variation on the tragically misguided “vaccines are dangerous” movement.

But now that I’ve done some more reading and thinking about fluoridation, I think the anti-government fringe groups might be right!

Admittedly, a few hours of reading does not make me an expert on fluoridation. (So far, I’ve looked at the websites of the American Dental Association [ADA], CDC, Fluoride Action Network [FAN], and Rutland Fluoride Action, and followed links from these sites to other files such as the National Research Council’s 2006 report on fluoride in drinking water.) But, as someone with a Ph.D. in Physiology & Biophysics plus 14 years of postdoctoral research and teaching experience, I am qualified to comment on the issue.

It’s a challenging issue to tackle because there is a huge body of research on the biological effects of fluoride, which the two sides filter quite differently. For example, a thorough 2015 meta-analysis of the issue conducted by the independent, rigorous Cochrane Database group is touted by the FAN as showing “no valid evidence exists to prove fluoridation works,” while the ADA and CDC complain that the Cochrane analysis excluded valid studies that indicate benefits of fluoridation.

It’s hard for a neutral, semi-informed observer to know what to make of such debates.

Still, amidst the fog of disputed data and accusations of bias, the anti-fluoridation crowd does have a simple argument that I find compelling. Here it is:

1. Fluoride is a drug, not a nutrient.

2. Mass-administering a drug to entire communities, without individuals’ consent, can only be justified if we are extremely confident that the benefits-to-risks ratio is extremely high.

3. The available evidence does not warrant such extreme confidence.

Of these, claim #1 may be the most contentious. The ADA seems to disagree, as its 5 Reasons Why Fluoride in Water is Good for Communities include “It’s natural.”

“Fluoride is naturally present in groundwater and the oceans,” the ADA reassures us. Well, yes — but so is uranium-238. Should we be adding that to our water too?

The ADA continues, “[Fluoridation of water is] similar to fortifying other foods and beverages, like fortifying salt with iodine, milk with vitamin D, orange juice with calcium and bread with folic acid.”

The FAN rebuts this effectively.

It is now well established that fluoride is not an essential nutrient. This means that no human disease -– including tooth decay -– will result from a “deficiency” of fluoride. Fluoridating water supplies is therefore different than adding iodine to salt. Unlike fluoride, iodine is an essential nutrient (the body needs iodine to ensure the proper functioning of the thyroid gland). No such necessity exists for fluoride.

If fluoride is not a nutrient, then what is it? I find the FAN’s stance completely reasonable:

All water treatment chemicals, with the exception of fluoride, are added to make drinking water safe and pleasant to consume. Fluoride is the only chemical added to treat people who consume the water, rather than the water itself. Fluoridating water supplies can thus fairly be described as a form of mass medication, which is why most European countries have rejected the practice.

This classification of fluoride as a drug is consistent with official definitions from the Food and Drug Administration (FDA).

People usually are prescribed specific dosages of drugs according to their age, weight, medical history, etc. For fluoride in water, however, doses will vary wildly, not based on individuals’ “needs,” but based on how thirsty they are. It’s a bit unsettling, at the least.

Claim #2 concerns informed consent. I have some relevant professional experience, having conducted laboratory research and educational research that required approval from my university’s Institutional Review Board (IRB) as well as the consent of the research subjects themselves.

It’s a lot of tedious paperwork. In my own proposals, for example, I’ve spent many paragraphs explaining why students will not be harmed if they anonymously complete a survey, and guaranteeing that the students can nonetheless skip the survey, without being punished, if they have any objections to it. Still, I’m grateful that my institution has a serious review process that reflects its firm commitment to respecting individuals’ autonomy. This respect is a bedrock value of civilized society in general, and infringements upon it must be well-justified.

So is it OK to force-feed a drug to populations at haphazard levels related to individuals’ thirst? Sure — but only if the drug has obvious, important benefits and is extremely safe.

So — claim #3 — what does the evidence look like for benefits and risks?

Regarding benefits, the above-mentioned Cochrane study basically says that there IS evidence that fluoridated water reduces tooth decay, but that this evidence is not nearly as strong as we would like.

Regarding risks, the above-mentioned NRC report devotes over 200 pages to reviewing fluoride’s effects on the musculoskeletal, reproductive, nervous, endocrine, digestive, renal, and immune systems. For most of these systems, the NRC concluded that more research was needed, which is not particularly helpful because scientists always say that about everything (thus justifying our existence).

Still, based on data showing that high fluoride levels can compromise teeth and bones, the NRC concluded that the Maximum Level Contaminant Goal (MLCG) be altered downward from the previously established standard of 4 milligrams per liter (mg/L). More recently, the Department of Health and Human Services (HHS) has lowered its recommended level of fluoride in the water to 0.7 mg/L (down from a previous recommended range of 0.7-1.2 mg/L). These changes can be taken as an acknowledgment by experts that greater caution regarding fluoride exposure is warranted. Throw in some journal articles and government grant proposals that have made it through the peer review process, and you don’t need to be a conspiracy theorist to think that mass fluoridation has been enacted prematurely.

In a subsequent post, I will address the issue of “topical” versus “systemic” delivery of fluoride.


Crowther & Crowther (2015)

June 24, 2015

Two recently completed collaborations with my 8-year-old son:

1. Green revolution: salad spinning superseded. Bricolage 33: 110-112, 2015.

2. STEM songs: not just child’s play (display case installation, Discovery Hall, UW-Bothell)


More mandatory fun

September 25, 2014

As a follow-up to the summer’s odd teaching slides, here are some new examples fresh from this fall’s Anatomy & Physiology course (BIOL 241).

Dr. Alfred Yankovic, Adjunct Professor of Medicine

Red Rover: the nano version


Stephen, Be Heard!

September 14, 2014

The Dynamic Ecology and Phylogenomics blogs drew my attention to a new “must-read” article: On whimsy, jokes, and beauty: can scientific writing be enjoyed? by Stephen B. Heard (Ideas in Ecology and Evolution 7:64-72, 2014). The abstract is below.

While scientists are often exhorted to write better, it isn’t entirely obvious what “better” means. It’s uncontroversial that good scientific writing is clear, with the reader’s understanding as effortless as possible. Unsettled, and largely undiscussed, is the question of whether our goal of clarity precludes us from making our writing enjoyable by incorporating touches of whimsy, humanity, humour, and beauty. I offer examples of scientific writing that offers pleasure, drawing from ecology and evolution and from other natural sciences, and I argue that enjoyable writing can help recruit readers to a paper and retain them as they read. I document resistance to this idea in the scientific community, and consider the objections (well grounded and not) that may lie behind this resistance. I close by recommending that we include touches of whimsy and beauty in our own writing, and also that we work to encourage such touches in the writing of others.

To this nicely argued piece, I just want to add a few examples of indifference or hostility to my own attempts at whimsy, humor, and/or beauty.

(1) My grant proposals to the NWRCE and PNWRCE, 2010.

Striving to keep readers with me through the Conclusion section, I wrote:

We believe strongly in the importance of the central goal of this proposal, i.e., linking antibacterial compounds to Burkholderia proteins in a manner that will facilitate validation of new drug targets. This interest in compound-target links is not simply a fetish of the investigators involved in this project; within some pharmaceutical firms, knowing the target of a compound with activity against cells is considered absolutely vital for progressing compounds to leads.

A colleague discouraged me from using the word “fetish” on the grounds that “it reminds me of foot fetishes.” Perhaps she was right, but I kept it in as a tiny rebellion against unrelenting formality.

The proposals were rejected.

(2) G.J. Crowther et al., Identification of attractive drug targets in neglected-disease pathogens using an in silico approach, PLoS Neglected Tropical Diseases 4(8): e804, 2010.

This paper contained numerous lists of possible drug targets. Since one of the pathogens covered was Leishmania (the cause of leishmaniasis), the paper was known internally as the “Listmania paper” throughout 10 months of writing and revising. Meanwhile, we searched and searched for a compelling title distinct from that of our first paper on the same topic … while carefully avoiding the most interesting and evocative bit that we had come up with — i.e., the word Listmania. A coauthor killed the term by arguing, reasonably enough, that a pun about a pathogen might be insensitive to the pathogen’s victims. But a “catchier,” less cautious title might also have raised leishmania awareness more effectively.

(3) G.J. Crowther, The database: an educational resource for instructors and students, Biochemistry and Molecular Biology Education 40(1): 19-22, 2012.

The submitted manuscript included this:

The total manpower behind this website, rounded to the nearest whole number of FTE’s, is 0, so its maintenance is kept relatively simple.

Once the journal’s copy editor got ahold of it, it became:

The total manpower behind this website, rounded to the nearest whole number of Full-Time Equivalents (FTE’s), is 0, so its maintenance is kept relatively simple.

To me, this change reduced the sentence’s rhetorical punch and humor. Yet the edited version was (slightly) clearer, and I knew better than to argue for style over clarity. I reluctantly accepted the edit.

(4) G.J. Crowther et al., A mechanism-based whole-cell screening assay to identify inhibitors of protein export in Escherichia coli by the Sec pathway, Journal of Biomolecular Screening 17: 535-41, 2012.

Our submitted manuscript included the following:

While previous studies had included beta-mercaptoethanol in assay buffers, presumably to maintain cytoplasmic beta-gal in a reduced and active state, it did not appear necessary to preserve beta-gal function under our assay conditions; EC626’s response to maltose was similar with and without beta-mercaptoethanol (Fig. 3). Thus, in performing this assay, the unpleasant odor of beta-mercaptoethanol may be avoided.

A reviewer wrote, “The sentence which includes ‘the unpleasant odor of beta-mercaptoethanol’ is not appropriate.”

Here was another chance to stand up for ever-so-slightly-less-orthodox, ever-so-slightly-less-dry writing. This time I stood my ground and got my way.

“We respectfully disagree,” I responded. “It is a minor point, but the omission of beta-mercaptoethanol provided much relief to the rest of our lab, and this is worth noting.”


More juxtapositions

July 18, 2014

I have a soft spot for oddly juxtaposed teaching materials, e.g., a handout covering both lab-grown meat and the structure of the song “Hound Dog.”

Here are some strange bedfellows that appeared in animal physiology this spring and summer.


Above: two ways to convey the idea that most sodium ions (chemical symbol Na+) is outside cells rather than inside.

Above: Clostridium botulinum toxin, an inhibitor of the salt glands of marine birds … and the facial muscles of wealthy humans.

Above: In retrospect, this illustration of the importance of blood pressure regulation may have been too oblique.


The neurobiology of celebrity worship

July 8, 2014

The 5th edition of Biological Science by Scott Freeman et al. includes the following figure.
The Jennifer Aniston neuron.

Summarizing the study (R.Q. Quiroga et al., Nature 435: 1102-7, 2005) on which this figure was based, the textbook says, “Through experience, at least one of this patient’s neurons became singularly devoted to the concept of Jennifer Aniston.”

With this example, the textbook authors raise the issue of whether memories are stored in specific neurons rather than in distributed networks.

Are they are also implying that we collectively devote too many neurons to Jennifer Aniston and not enough to, say, Rita Levi-Montalcini?