What I Learned in 2024

Yet another retrospective article for the holiday season.

Asimov Press, the publishing company that I run with Xander Balwit, has only been around for about a year. I really love the job because it lets me work with all kinds of writers and scientists who have compelling ideas. I get to hang out with them, help shape their ideas from “nebulous thoughts” into more crystalline prose, and then share those ideas with the world. It’s a dream job.

(P.S. Our biggest announcement ever is coming this Thursday.)

I was reflecting on some of the things I’ve learned over the last year, and decided to wrap everything together into a list (as one does during the holidays.) This is remarkably overdone and derivative, but I’ve done my best to choose interesting things that I haven’t seen covered elsewhere. Maybe you’ll get a kick out of this. Note that these are not necessarily things that happened this year; they are just things that I learned this year.

Micropipette Origins

In 1957, a 32-year-old German postdoctoral researcher named Heinrich Schnitger invented the micropipette in just three days. He did it, apparently, because he was using mouth pipettes to work with toxic molecules and hated his day-to-day work. Eppendorf, a German company, licensed his invention almost immediately and commercialized it in the 1960s. Schnitger drowned in a Bavarian mountain lake in 1964.

Schnitger was not the first person to make a micropipette, though; his was simply the first model to catch on. (“…his design had ‘all the essential features of the modern pipette,’ according to a close witness of the invention, including a spring-loaded piston, a second spring to shoot out residual liquid, and a plastic tip.”) Two Americans, James W. Brown and Robert L. Weintraub, filed a patent for an adjustable pipette with a removable tip in 1953. Their device dispensed tiny drops of liquid via the spinning of a wheel on one end, and it could be used with one hand — but modern micropipettes do not use wheels to dispense liquids! (Source)

Patents on Living Things

General Electric was performing research on engineered Pseudomonas microbes to clean up oil spills in the 1970s. They filed the first patent on a genetically modified organism, and the case ultimately went all the way to the Supreme Court, which decided the case in 1980. Before then, patent clerks rejected any applications for living organisms because of a doctrine dating back to 1889, called Ex parte Latimer, which dealt with “the patentability of a fiber extracted from needles of a pine tree.” As Rhea Purohit writes for Asimov Press:

...the U.S. Patent Office rejected [General Electric’s] application because the subject matter was a ‘natural product.’ Benton J. Hall, a lawyer-politician from Iowa and Commissioner of Patents at the time, opined that the composition of trees was ‘not a patentable invention, recognized by statute, any more than to find a new gem or jewel in the earth would entitle the discoverer to patent all gems which should be subsequently found.’

After publishing this story, Rich Pell — founder of the Center for PostNatural History — told me that Louis Pasteur was actually the first person to patent a living organism. In 1873, Pasteur petitioned for a patent called “Improvement in the Manufacture of Beer and Yeast,” outlining methods to kill bacteria by heating beer and also disclosing his Brewer’s yeast strain. (Source)

Single Cells Anticipate Seasons

The best paper I read all year is “Bacteria can anticipate the seasons: Photoperiodism in cyanobacteria,” published in Science in September. It is a masterpiece. Or, as I wrote in an article, “In just six wonderfully lucid pages, researchers from Vanderbilt University in Nashville show that cyanobacteria can ‘sense’ shortening days and change the molecular compositions of their cell membranes to prepare for cold weather.” 

I continued to explain the experiment, writing:

Cyanobacterial cells were divided into three groups. Each group grew at the same temperature — a steady 30°C. But each group was exposed to a different amount of light each day. One group was exposed to 16 hours of lightness and 8 hours of darkness each day; another to 12 hours of light and 12 hours of darkness, or ‘equinox’; and the third to 8 hours of light and 16 hours of dark.

After eight days, Jabbur dunked each group of cells into ice-cold water and measured how many lived through the ordeal. Cells exposed to less light (8 hours light, 16 hours dark) were two-to three-times more likely to survive compared to the other two groups. The effect was also linearly correlated. Cells exposed to 20 hours of darkness per day were more likely to survive the cold water compared to cells exposed to 18 hours, and so on.

I’m still blown away by the sheer simplicity and elegance of this paper. You should read it! (Source)

Plague Deaths

Nobody knows how many people died during the Black Death. This “simple” statement was something I hadn’t really considered prior to this year. But, as Saloni Dattani has written: 

Direct records of mortality are sparse and mostly relate to deaths among the nobility. Researchers have compiled information from tax and rent registers, parish records, court documents, guild records, and archaeological remains from many localities across Europe. However, even those who have carefully combed over this data have not reached a consensus about the overall death toll.

For example, in 2005, statistician George Christakos and his colleagues compiled data from over a hundred European cities. Using their data, the economists Jedwab, Johnson, and Koyama estimated in 2019 that 38.75 percent of Western Europe’s population had died on average. In contrast, the historians John Aberth (2021) and Ole Benedictow (2021) have estimated that 51–58 percent or upwards of 60 percent of Europe’s population died, respectively.

Even today, many countries do not have formal institutions to tabulate deaths. In many cases, we simply don’t know how many people die from various diseases. Dattani continues:

Since cause-of-death registries have been limited or dysfunctional in many countries in Africa and South Asia, some researchers have conducted national ‘verbal autopsies’ to fill the gap. In these studies, millions of families were interviewed about recently deceased relatives and their diseases and symptoms before death. Doctors then used their answers to estimate their cause of death.

The results suggest that we had greatly underestimated the death toll of diseases such as tuberculosis and venomous snakebites. Revised international estimates suggest that they kill over 1 million and 100,000 people, respectively, each year. (Source)

Mendel Mouse Hoax

Gregor Mendel, the Augustinian friar who founded genetics, worked with garden peas. He meticulously crossed his peas and tabulated the “phenotypes” that appeared to unravel the laws of inheritance. But nobody knows, even today, why exactly he decided to do these experiments. What was his inspiration?

In the absence of historical certainty, many writers and scholars have felt free to speculate. For example, Robin Henig, author of the book The Monk in the Garden, wrote that:

[Mendel] kept [mice] in cages in his two-room flat, where they gave off a distinctive stench of cedar chips, fur, and rodent droppings. He was trying to breed wild-type mice with albinos to see what color coats the hybrids would have. [The bishop] seemed to find it inappropriate, and perhaps titillating, for a priest who had taken vows of chastity and celibacy to be encouraging — and watching — rodent sex.

After the bishop banned mice from the monastery, Henig claims, Mendel took to garden peas instead. A similar tale has appeared in many academic and news articles (including in Asimov Press), but it’s likely apocryphal. 

Daniel J. Fairbanks, a Mendel scholar in Utah, says in his own book that there is no evidence for it. Although Mendel published work with insect pests, and even became a renowned beekeeper late in life, banning mice would have been peculiar because the monastery’s abbot regularly bred sheep and other agricultural animals.

Synthetic Biology’s Discouraging Start

The field of synthetic biology began, “officially,” in the year 2000 when two papers — published back-to-back in the journal Nature — reported the first synthetic gene circuits; assemblies of DNA that “programmed” living cells to act in desired ways. These early synthetic gene circuits (called the repressilator and toggle switch) suggested that engineers could recreate some of the complex networks within living cells and then manipulate them to carry out entirely new functions. In other words, they could “program biology.”

The repressilator was made by Michael Elowitz and Stanislas Leibler, two physicists at Princeton University. I interviewed Elowitz earlier this year, and was surprised when he told me about some of his early doubts surrounding the project:

I definitely had no idea whether it was going to work. When I asked people what they thought of the project, which I did incessantly, I got very different answers. A few well-known biologists would say, ‘No, it’ll never work that way. It just won’t work.’

And I’d ask them, ‘Why won’t it work?’ And they’d say, ‘Biology just doesn’t really work that way. You can’t predict what’s going to happen.’ Other people thought it sounded fun. So it was a mix of positive and negative feedback. It’s funny to think about that in hindsight. At the time, I was really excited about the project. I told lots of people about it, but then I’d swear them to secrecy. It was all very silly. (Source)

No More Dead Chicks

In ovo sexing is one of the most exciting technologies that I had never heard of. The gist is that we can now figure out the sex of a baby chick while it is still inside the egg; before it hatches. This enables farmers to discard chicks before they are born and, thus, before they can feel pain. That’s a huge deal because something like 6 to 7 billion one-day-old male chicks are killed each year. Egg farms kill male chicks because, well, they don’t lay eggs. So instead, they put them on a conveyer belt and drop them into a macerator that rips into their flesh. It’s absolutely brutal. You can find videos online, if so inclined.

But this is a cause area that biotechnology can make a huge impact on. And there is good news. The number of male chicks killed in European egg farms has fallen by about 20 percent in recent years. In ovo sexing is now used in about 20 percent of the European market. And this technology is — for the first time — making its way to the United States. A few weeks ago, “a US hatchery shared that it has installed the nation’s first in-ovo sexing system.” (Source)

Making Eggs Without Ovaries

In just a few years’ time, scientists may figure out how to make viable eggs (or even sperm) directly from stem cells. The technology is called in vitro oogenesis, and Metacelsus published a deep explainer on it earlier this year:

Such an approach would take cells from an adult — such as skin or blood — and reprogram them into induced pluripotent stem cells, or iPSCs. Much like embryonic stem cells, iPSCs have the ability to form any cell in the adult body; eggs included. Although generating human iPSCs is now routine, coaxing iPSCs to form eggs in a process known as in vitro oogenesis has only been successful on cells taken from mice.

If this technology pans out, it will likely cost (initially) between $150,000-$250,000 dollars, just to make the actual eggs (so not including implanting those eggs and so on). It will:

…expand the kinds of people who are able to have biological children. First, growing eggs from ovarian biopsy samples will allow women to obtain eggs even when their ovarian reserve is diminished. This could extend the age of fertility into the mid-40s. Furthermore, this technology would allow younger women to grow large numbers of eggs from tissue samples. By enabling women to freeze more eggs, they would have a better chance of having babies later. (Source)

Happy New Year,

Niko McCarty