Early versions of the Bible describe Goliath — an ancient Philistine warrior best known as the loser of a fight with the future King David — as a giant whose height in ancient terms reached four cubits and a span. But don’t take that measurement literally, new research suggests.
Archaeological findings at biblical-era sites including Goliath’s home city, a prominent Philistine settlement called Gath, indicate that those ancient measurements work out to 2.38 meters, or 7 feet, 10 inches. That’s equal to the width of walls forming a gateway into Gath that were unearthed in 2019, according to archaeologist Jeffrey Chadwick of Brigham Young University in Provo, Utah.
Rather than standing taller than any NBA player ever, Goliath was probably described metaphorically by an Old Testament writer as a warrior who matched the size and strength of Gath’s defensive barrier, Chadwick said November 19 at the virtual annual meeting of the American Schools of Oriental Research.
People known as Canaanites first occupied Gath in the early Bronze Age, roughly 4,700 to 4,500 years ago. The city was rebuilt more than a millennium later by the Philistines, known from the Old Testament as enemies of the Israelites (SN: 11/22/16). Gath reached its peak during the Iron Age around 3,000 years ago, the time of biblical references to Goliath. Scholars continue to debate whether David and Goliath were real people who met in battle around that time.
The remains of Gath are found at a site called Tell es-Safi in Israel. A team led by archaeologist Aren Maeir of Bar-Ilan University in Ramat-Gan, Israel — who Chadwick collaborated with to excavate the Gath gateway — has investigated Tell es-Safi since 1996. Other discoveries at Gath include a pottery fragment inscribed with two names possibly related to the name Goliath. Evidence of Gath’s destruction about 2,850 years ago by an invading army has also been recovered. Archaeologists have long known that in ancient Egypt a cubit corresponded to 52.5 centimeters and assumed that the same measure was used at Gath and elsewhere in and around ancient Israel. But careful evaluations of many excavated structures over the last several years have revealed that standard measures differed slightly between the two regions, Chadwick said.
Buildings at Gath and several dozen other cities from ancient Israel and nearby kingdoms of Judah and Philistia, excavated by other teams, were constructed based on three primary measurements, Chadwick has found. Those include a 54-centimeter cubit (versus the 52.5-centimeter Egyptian cubit), a 38-centimeter short cubit and a 22-centimeter span that corresponds to the distance across an adult’s outstretched hand. Dimensions of masonry at these sites display various combinations of the three measurements, Chadwick said. At a settlement called et-Tell in northern Israel, for instance, two pillars at the front of the city gate are each 2.7 meters wide, or five 54-centimeter cubits. Each of four inner pillars at the city gate measure 2.38 meters wide, or four 54-centimeter cubits and a 22-centimeter span. Excavators of et-Tell regard it as the site of a biblical city called Bethsaida.
Chadwick’s 2019 excavations found one of presumably several gateways that allowed access to Gath through the city’s defensive walls. Like the inner pillars of et-Tell’s city gate, Gath’s gate walls measured 2.38 meters wide, or four cubits and a span, the same as Goliath’s biblical stature.
“The ancient writer used a real architectural metric from that time to describe Goliath’s height, likely to indicate that he was as big and strong as his city’s walls,” Chadwick said.
Although the research raises the possibility that Goliath’s recorded size referred to the width of a city wall, Chadwick “will need to do more research to move this beyond an intriguing idea,” says archaeologist and Old Testament scholar Gary Arbino of Gateway Seminary in Mill Valley, Calif. For one thing, Arbino suggests, it needs to be established that the measure applied to Goliath, four cubits and a span, was commonly used at the time as a phrase that figuratively meant “big and strong.”
Pfizer is racing to get approval for its COVID-19 vaccine, applying for emergency use authorization from the U.S. Food and Drug Administration on November 20. But the pharmaceutical giant faces a huge challenge in distributing its vaccine, which has to be kept an ultrafrosty –70° Celsius, requiring special storage freezers and shipping containers.
It “has some unique storage requirements,” says Kurt Seetoo, the immunization program manager at the Maryland Department of Public Health in Baltimore. “We don’t normally store vaccines at that temperature, so that definitely is a challenge.”
That means that even though the vaccine developed by Pfizer and its German partner BioNTech is likely to be the first vaccine to reach the finish line in the United States, its adoption may ultimately be limited. The FDA’s committee overseeing vaccines will meet on December 10 to discuss the emergency use request. That meeting will be streamed live on the agency’s web site and YouTube, Facebook and Twitter channels.
The companies are also seeking authorization to distribute the vaccine in Australia, Canada, Europe, Japan, the United Kingdom A similar vaccine developed by Moderna and the U.S. National Institute of Allergy and Infectious Diseases also requires freezing. But it survives at a balmier –20° C, so can be kept in a standard freezer, and can even be stored at refrigerator temperatures for up to a month. Most vaccines don’t require freezing at all, but both Pfizer and Moderna’s vaccines are a new type of vaccine for which the low temperatures are necessary to keep the vaccines from breaking down and becoming useless.
Both vaccines are based on messenger RNA, or mRNA, which carries instructions for building copies of the coronavirus’ spike protein. Human cells read those instructions and produce copies of the protein, which, in turn prime the immune system to attack the coronavirus should it come calling.
So why does Pfizer’s vaccine need to be frozen at sub-Antarctica temperatures and Moderna’s does not?
Answering that question requires some speculation. The companies aren’t likely to reveal all the tricks and commercial secrets they used to make the vaccines, says Sanjay Mishra, a protein chemist and data scientist at Vanderbilt University Medical Center in Nashville.
But there are at least four things that may determine how fragile an mRNA vaccine is and how deeply it needs to be frozen to keep it fresh and effective. How the companies addressed those four challenges is likely the key to how cold the vaccines need to be, Mishra says.
The cold requirement conundrum starts with the difference in chemistry between RNA and its cousin, DNA. One reason RNA is much less stable than DNA is due to an important difference in the sugars that make up the molecules’ backbones. RNA’s spine is a sugar called ribose, while DNA’s is deoxyribose. The difference: DNA is missing an oxygen molecule. As a result, “DNA can survive for generations,” Mishra says, but RNA is much more transient. “And for biology, that’s a good thing.”
When cells have a job to do, they usually need to call proteins into service. But like most manufacturers, cells don’t have a stockpile of proteins. They have to make new batches each time. The recipe for making proteins is stored in DNA.
Rather than risk damaging DNA recipes by putting them on the molecular kitchen counter while cooking up a batch of proteins, cells instead make RNA copies of the recipe. Those copies are read by cellular machinery and used to produce proteins. Like a Mission Impossible message that self-destructs once it has been played, many RNAs are quickly degraded once read. Quickly disposing of RNA is one way to control how much of a particular protein is made. There are a host of enzymes dedicated to RNA’s destruction floating around inside cells and nearly everywhere else. Sticking RNA-based vaccines in the blast freezer prevents such enzymes from tearing apart the RNA and rendering the vaccine inert.
Another way the molecules’ stability differs lies in their architecture. DNA’s dual strands twine into a graceful double helix. But RNA goes it alone in a single strand that pairs with itself in some spots, creating fantastical shapes reminiscent of lollipops, hair pins and traffic circles. Those “secondary structures” can make some RNAs more fragile than others.
Yet another place that DNA’s and RNA’s chemical differences make things hard on RNA is the part of the molecules that spell out the instructions and ingredients of the recipe. The information-carry subunits of the molecules are known as nucleotides. DNA’s nucleotides are often represented by the letters A, T, C and G for adenine, thymine, cytosine and guanine. RNA uses the same A, C and G, but in place of thymine it has a different letter: uracil, or U.
“Uracil is a problem because it juts out,” Mishra says. Those jutting Us are like a flag waving to special immune system proteins called Toll-like receptors. Those proteins help detect RNAs from viruses, such as SARS-CoV-2, the coronavirus that causes COVID-19, and slate the invaders for destruction.
All these ways mRNA can fall apart or get waylaid by the immune system create an obstacle course for vaccine makers. The companies need to ensure that the RNA stays intact long enough to get into cells and bake up batches of spike protein. Both Moderna and Pfizer probably tinkered with the RNA’s chemistry to make a vaccine that could get the job done: Both have reported that their vaccines are about 95 percent effective at preventing illness in clinical trials (SN: 11/16/20; SN: 11/18/20).
While the details of each company’s approach aren’t known, they both probably fiddled slightly with the chemical letters of the mRNAs in order to make it easier for human cellular machinery to read the instructions. The companies also need to add additional RNA — a cap and tail — flanking the spike protein instructions to make the molecule stable and readable in human cells. That tampering may have disrupted or created secondary structures that could affect the RNA’s stability, Mishra says. The uracil problem can be dealt with by adding a modified version of the nucleotide, which Toll-like receptors overlook, sparing the RNA from an initial immune system attack so that the vaccine has a better chance of making the protein that will build immune defenses against the virus. Exactly which modified version of uracil the companies may have introduced into the vaccine could also affect RNA stability, and thus the temperature at which each vaccine needs to be stored.
Finally, by itself, an RNA molecule is beneath a cell’s notice because it’s just too small, Mishra says. So the companies coat the mRNA with an emulsion of lipids, creating little bubbles known as lipid nanoparticles. Those nanoparticles need to big enough that cells will grab them, bring them inside and break open the particle to release the RNA.
Some types of lipids stand up to heat better than others. It’s “like regular oil versus fat. You know how lard is solid at room temperature” while oil is liquid, Mishra says. For nanoparticles, “what they’re made of makes a giant difference in how stable they will be in general to [maintain] the things inside.” The lipids the companies used could make a big difference in the vaccine’s ability to stand heat.
The need for ultracold storage might ultimately limit how many people end up getting vaccinated with Pfizer’s vaccine. “We anticipate that this Pfizer vaccine is pretty much only going to be used in this early phase,” Seetoo says.
The first wave of immunizations is expected to go to health care workers and other essential employees, such as firefighters and police, and to people who are at high risk of becoming severely ill or dying of COVID-19 should they contract it such as elderly people living in nursing facilities.
Pfizer has told health officials that the vaccine can be stored in special shipping containers that are recharged with dry ice for 15 days and stay refrigerated for another five days after thawing, Seetoo says. That gives health officials 20 days to get the vaccine into people’s arms once it’s delivered. But Moderna’s vaccine and a host of others that are still in testing seem to last longer at warmer temperatures. If those vaccines are as effective as Pfizer’s, they may be more attractive candidates in the long run because they don’t need such extreme special handling.
The usually bright green plants often stand alone amid the jumbled scree that tops the Himalayan and Hengduan mountains in southwestern China — easy pickings for traditional Chinese medicine herbalists, who’ve ground the bulbs of wild Fritillaria into a popular cough-treating powder for more than 2,000 years. The demand for bulbs is intense, since about 3,500 of them are needed to produce just one kilogram of the powder, worth about $480.
But some Fritillaria are remarkably difficult to find, with living leaves and stems that are barely distinguishable from the gray or brown rocky background. Surprisingly, this plant camouflage seems to have evolved in response to people. Fritillaria delavayi from regions that experience greater harvesting pressure are more camouflaged than those from less harvested areas, researchers report November 20 in Current Biology.
The new study “is quite convincing,” says Julien Renoult, an evolutionary biologist at the French National Centre for Scientific Research in Montpellier who wasn’t involved in the study. “It’s a nice first step toward demonstrating that humans seem to be driving the very rapid evolution of camouflage in this species.” Camouflaged plants are rare, but not unheard of, says Yang Niu, a botanist at the Kunming Institute of Botany in China, who studies cryptic coloration in plants. In wide open areas with little cover, like mountaintops, blending in can help plants avoid hungry herbivores (SN: 4/29/14). But after five years of studying camouflage in Fritillaria, Niu found few bite marks on leaves, and he did not spot any animals munching on the plants. “They don’t seem to have natural enemies,” he says.
So Niu, his colleague Hang Sun and sensory ecologist Martin Stevens of the University of Exeter in England decided to see if humans might be driving the evolution of the plants’ camouflage. If so, the more heavily harvested a particular slope, the more camouflaged the plants that live there should be.
In an ideal world, to measure harvesting pressure “you’d have exact measures of exactly how many plants had been collected for hundreds of years” at multiple sites, Stevens says. “But that data is practically nonexistent.”
Luckily, at seven study sites, local herbalists had noted the total weight of bulbs harvested each year from 2014 to 2019. These records provided a measure of contemporary harvesting pressure. To estimate further back in time, the researchers assessed ease of harvesting by recording how long it took to dig up bulbs at six of those sites, plus an additional one. On some slopes, bulbs are easily dug up, but in others they can be buried under stacks of rocks. “Intuitively, areas where it’s easier to harvest should have experienced more harvesting pressure” over time, Stevens says.
Both measures revealed a striking pattern: The more harvested, or harvestable, a site, the better the color of a plant matched its background, as measured by a spectrometer. “The degree of correlation was really, really convincing for both metrics we used,” Stevens says. Human eyes also had a harder time spotting camouflaged plants in an online experiment, suggesting that the camouflage actually works.
Hiding in plain sight may present some challenges for the plant. Pollinators might have a harder time finding camouflaged plants, and the gray and brown coloration could impair photosynthetic activity. Still, despite those potential costs, these F. delavayi show just how adaptable plants can be, Steven says. “The appearance of plants is much more malleable than we might have expected.”