Issue 07 is Coming on Monday

Featuring articles on aspirin’s murky origins, scaling proteomics, and the history of fermentation.

Issue 07 launches this Monday with a marvelously researched essay on the uncertain origins of aspirin. Author Sean Harrison spent months tracking down original translations and primary sources to unpack the history behind one of the world’s most prescribed drugs, only to discover that many commonly referenced texts are likely wrong. 

To celebrate the new issue, we are also releasing new merchandise (custom-designed shirts, hats, and posters) and hosting a biology trivia night in San Francisco on July 23! The event hosts will provide snacks and drinks, and the winning teams will get signed copies of our DNA books and free hats. Please RSVP to join.

Issue 07 also features:

1. Leech Therapy. Authors Khushi Mittal and Xander Balwit make a case for rekindling broader interest in this “alternative treatment.” Alive and well in the Balkans and beyond, hirudotherapy has been sidelined in the West due to cultural distaste and lack of investment. Falling out of fashion with the rise of the modern pharmaceutical industry, it’s ready for a comeback driven not by mania, but rather by a mechanistic understanding of the molecules and bioactive compounds responsible for its efficacy.

2. How Science Becomes Mature. Slime Mold Time Mold argues that maturity — in biology, chemistry, or anything else — requires mechanical models and the ability to talk about nuts, bolts, and the parameters that constrain how they behave. This essay makes a strong case for moving beyond impressionistic research.

3. How to Scale Proteomics. Editor Niko McCarty writes about the work of Parallel Squared Technology Institute, a non-profit research organization focused on scaling proteomics. Proteins carry out most behaviors in cells, yet the tools we have to study them are still woefully inefficient.

4. A Visual Guide to Gene Delivery. The tools for delivering gene therapies into cells have improved radically since the use of retroviruses in the early 1990s. Eryney Marrogi walks us through today’s most noteworthy gene delivery vehicles — AAVs, Lentivirus, Lipid Nanoparticles, and Herpes Simplex Virus — explaining the advantages and limitations of each.

5. A History of Fermentation. Microbiologist Rachel Dutton documents the oldest food preparation method in the world and explains why it is understudied today relative to its historical importance. Dutton discusses how microbes became the enemy of food in the era of canning and pasteurization and why we lack good datasets for understanding the microbiome, aiming to steer us towards a more fermented future. 

6. Making of the Sewers. When talking about the microbiome, we think of the gut flora, and thinking about the gut leads us to human waste. Calum Drysdale shares our enthusiasm for the topic. In a deep dive worthy of the name, Drysdale plunges us into the sewers, where we learn about wastewater epidemiology, fertilizer, and contemporary efforts to derive valuable compounds and materials from our own waste.

7. Insect Diapause. While much has been written on mammal hibernation and torpor, there are pragmatic reasons to care about similar rhythms in insects. In an essay that unites the oddities of invertebrate physiology to the need to improve pest management strategies, Ulkar Aghayeva takes us through life strategies that we seldom consider.

Stories We Want to Publish

Bottlenecks in Tree Engineering

In 1903, John Krusback, the president of a local state bank in Wisconsin, decided that he was going to grow a chair. It took eleven years to produce this naturally grown chair, later exhibited at the World Fair in San Francisco in 1915.

Krusback’s approach and other tree-shaping techniques have inspired many others to create living structures, from the “Circus Trees” to Full Grown, a contemporary furniture company in the UK that is doing what feels like the tree equivalent of growing square watermelons in molds. Today, companies like Living Carbon have advanced from grafting and molds and are using genetic engineering to produce trees that can photosynthesize more efficiently.

Still, despite this enthusiasm and the handful of successes, tree engineering remains challenging. Since we launched, we have been seeking a compelling piece explaining why. What are the bottlenecks of tree engineering, and what would overcoming them solve?

How Model Organisms Arrived in the Lab

For the last 60 years, the roundworm Caenorhabditis elegans has served as a premier laboratory model. The systematic study of its genome, development, behavior, immune system, and a full model of its connectome has indelibly influenced modern biology more than perhaps any other organism, and certainly more than any other free-living nematode. How did this happen? What led Sydney Brenner to select this organism as a model for physiological and neural development in animals?

How, for that matter, does any given model organism become a scientific staple? And conversely, how do they fall out of favor? In the 1950s, we employed beagles in radiation experiments, studying their skeletons for the effects of toxic exposure, and today, dogs are seldom used outside of veterinary research.

The stories behind such model organisms fascinate us, and we want to uncover more of them. This is especially important as we witness a move away from animal models (at least in certain contexts). What knowledge have we gained from them, and what mistakes might they have seduced us into? Before we relinquish them, which should we memorialize?

Pieces on Developmental Biology

On March 27, 1784, the poet and polymath Johann Wolfgang von Goethe wrote a letter to his friend Johann Gottfried Herder: “I have found — neither gold nor silver, but what makes me unspeakably happy — the os intermaxillare in the human!”

Goethe’s unspeakable happiness may have been overblown, as he may not have been the true discoverer, and the bone may not have been distinctly “of humans” as he postulated. However, his excitement is deserved. Where did our anatomy come from?

Our ancestors were, at one point, bony fishes. What vestiges of such vertebrates do we retain today and why? Why do we have vestigial body parts? What was the most recent organ/bone to develop? And what might devolve/evolve next (and is this even an intelligible question)?

From pieces on the discovery of HOX genes and bilateral symmetry to deep dives into how new structures emerge during evolution, we want to cover more developmental biology.

A Visual Guide to Biocatalysis

Issue 06 and 07 both include Visual Guides on Genome Editors and Gene Delivery Vehicles, respectively. We want to continue publishing Visual Guides for complex topics whose concepts would benefit from consistent and comparable illustrations. While we are open to many ideas, we would be especially excited to publish a visual guide to biocatalysis.

Enzymes are the movers and shakers of the biological world, responsible for much of the chemistry that sustains life. Humans have unknowingly harnessed the power of enzymes via microbial fermentation for longer than recorded history. However, in the past century, we have begun to uncover how these powerful biocatalysts function and how to use them for a more sustainable chemistry. We want to create a visual guide and accompanying article that could include sections like the history of biocatalysis, how enzymes work to selectively catalyze chemical reactions, the 6 primary classes of enzymes and their reactions, how enzymes work together in the cell to transform molecules, the tools and techniques that people use to work with and engineer them, and success stories where biocatalysts improved human life.

Units of Measurement

When did scientists standardize various measurements? Why is an Angstrom, equivalent to one ten-billionth of a meter, called an Angstrom? Why do the 96-well plates used in molecular biology laboratories consist of 96 wells instead of 100 or 200? Why is FLOPS a more accurate measure of computer performance than “instructions per second”? We’re open to various articles on the provenance of different measurements across scientific domains.

The Cost of Biomanufacturing

About 40 percent of all drugs on the market are biologics, derived from living cells or organisms rather than chemical synthesis. And many of the best-selling biologics — including Humira and Actemra — are antibodies, Y-shaped proteins conventionally made using Chinese hamster ovary cells grown in big steel tanks.

Many people make hand-wavey claims about how biomanufacturing is super expensive and doesn’t scale, but how much does it really cost to make, say, one gram of a medicine like Humira? We’d like to commission an essay that walks through all the steps involved in making a drug, along with the price tags.

History of Phytotrons

The world's first phytotron (a fusion of the Greek word for plant — phytos — and device — or tron) was an indoor plant research facility that could simulate "every possible climatic condition." It debuted at Caltech in 1949, during the early years of the Cold War, because the U.S. government believed that if they could control the environment, they could also control the food supply. 

Caltech's Phytotron had rooms in which temperature, gas composition, light, humidity, and more could be precisely controlled. Plants were photographed daily to document growth. Between 1945 and the 1980s, Caltech's phytotron model was copied and emulated in Australia, France, Hungary, England, and also the Soviet Union.

There are several phytotrons still in use, including at North Carolina State University. We’d like to commission a history of these remarkable facilities.

Carlsberg 1883

Several years ago, the Carlsberg brewery began selling a special European Lager called “Carlsberg 1883.” The beer was made using yeast extracted and purified from “an old beer bottle found [in] the cellars of the old Carlsberg brewery.” We’d like to commission an essay outlining the steps involved in making this beer (even though it is apparently “dull, but not undrinkable,” according to a Norwegian man who has tried it.)

What We’re Reading

1. The Magic of Code, Samuel Arbesman. A compelling argument for code as “a universal force,” in computers and biology and behind.

2. Salt: A World History, Mark Kurlansky. An astonishing chronicle of the only rock we eat.

3. Brave Genius, Sean Carroll. The remarkable story of Albert Camus and Jacques Monod, documenting their lives in Paris under Nazi occupation all the way through their Nobel Prizes. Monod was an extremely high-ranking member of the French Resistance, with ID badge #002.

4. Helmholtz, David Cahan. A magisterial biography of Hermann von Helmholtz, the 19th-century polymath and destroyer of vitalism.

5. This Is How You Lose the Time War, Amal El-Mohtar and Max Gladstone. A science fiction time travel novel, with some genetic engineering elements plot points.

6. “The Origin of the Research University,” Clara Collier

7. “The Universal Tech Tree,’ Étienne Fortier-Dubois

8. “The first non-opioid painkiller,” Michelle Ma

9. “Brain Freeze,” Aurelia Song & Charlie Dever. The story of one researcher’s involvement with and work on cryonics.

10. The Dream Machine, M. Mitchell Waldrop. A history of the modern desktop computer (in which Steve Jobs and Bill Gates are only bit players).

See you Monday,

— Niko, Xander & Ella