Louis Pasteur, the Father of Immunology

From Wikipedia

Born in France on December 27, 1822, Louis Pasteur began life as an average student but with a strong desire to learn. At first, his interests were in pastel sketching and fishing, but he aspired to attend a teachers college called École Normale Supérieure. To pay his way, he earned money by teaching math and physical science to high school children. His interests in science began when he was fascinated by

Pasteur's first pastel drawing at age 13 (Institut Pasteur)

 lectures from French chemist Jean-Baptiste Dumas at the College of Sorbonne (Paris College of Theology). These were public lectures that attracted 600-700 people at a time. Pasteur was accepted to École Normale in 1843 where he took up chemistry.

Louis Pasteur had once been thought to be a slow learner, but the truth is, he simply concentrated very carefully on everything he studied: "...he never affirmed anything of which he was not absolutely sure" (translated quote from The Life of Pasteur, by Rene Vallery-Radot). It was said that he didn't even know what it was like to skim a book because he wanted to get everything out of it. He was never satisfied with just book knowledge, though. At college, for example, they taught that phosphorus comes from extracting the mineral from bone. But he was so curious about the method they described that he bought some bones, burned and crushed them, and did the extraction himself just to have a phosphorus sample of his own!

After getting his bachelor's degree in 1845, he taught as professor of physics at the Collège de Tournon, but returned to École Normale at the urging of an old teacher. There, he got his doctoral degree in sciences in 1848 with a dissertation in chemistry and in physics. His studies focused on optical properties of chemicals, especially crystals. Pasteur was then appointed professor of chemistry at the University of Strasbourg.

Pasteur, 1848 (Institut Pasteur)

His initial interests in chemistry were about the crystal structure of two chemicals and how they responded to polarized light. But he was also dedicated to showing students the practical side of their studies. As professor of chemistry and dean of the science faculty at the University of Lille, he arranged for factory tours so students could see firsthand iron foundries and steel & metal works factories, then ask questions to the foremen. This was his attempt to instill curiosity in students. His sentiments were reflected in a quote from a university speech, "In the fields of observation, chance only favors the mind which is prepared".

But he was as honest as any scientist could be. In his own experiments, he would scribble a note in his lab reports where he found mistakes had been made. If the hypothesis itself for the work was incorrect and lead to a false result, he would write "erroneous" when the experiment failed.

In 1854, he became dean of the new faculty of sciences at the University of Lille in northern France. At that time, fermentation of beer and wine was considered a chemical process, not something caused by the metabolism of yeast. As early as 1837, Cagniard de la Tour, Theodor Schwann, and Friedrich Kützing independently proposed that yeast was a living organism that multiplied during fermentation, but most people disagreed. The thought of the day was that the chemical change of sugars to alcohol was caused instead by some "vital" or "catalytic force", even by "unstabilizing vibrations" of the chemicals. But the three researches above observed yeast cells budding under the microscope and suggested its role in the process, but they couldn't explain further.

Yeast cells with new growths (buds) forming as they grow (Wikipedia)

In 1856, the head of a beetroot alcohol manufacturer asked Pasteur for advice because some of his batches had spoiled. Pasteur noticed that the yeast cells were nicely rounded when the fermentation went well, but they were elongated when it went bad with an accumulation of acetic acid (vinegar) instead of alcohol. Even though yeast weren't yet known to cause the alcohol production, this observation gave the manufacturer something to keep an eye on, and this was the start of Pasteur's interest in fermentation.

Pasteur's drawings of yeast cells, 1862 (Yeast Research: A Historical Review)

A year later, his attention was drawn to souring of milk, too. But he observed in beer and wine tiny globules even smaller than yeast were what was responsible for failed fermention into alcohol and instead generated acids. (These were eventually explained as bacteria.) His own university colleagues didn't read his paper for 3 months, so he grew dissatisfied at Lille and accepted a director position at the École Normale.

Pasteur showed how yeast were not only alive but that they actively changed sugar into alcohol.

• He noticed that yeast cells multiplied during the fermentation process.
• When he sterilized sugar solutions and prevented yeast from entering, no alcohol was made.
• As sugar was consumed, yeast cells grew in number, and alcohol and carbon dioxide were produced.
• The alcohol and other products in fermentation bent light in a way that only living organisms can do. 

In 1862, he heated fermentation mixtures for a few moments to 50-60º C, and the problem of spoiling was solved by killing the bacteria (tiny globules) without changing the taste of the wine. People didn't believe him until he assembled a panel of wine experts to support him. Thus was born the process of pasteurization, which he patented in 1865.

 

Patent on pasteurization (Institut Pasteur)

Pasteur then attacked the notion of spontaneous generation, that is, the formation of life from organic matter and not from a previous life. Lazzaro Spallanzani (1768) boiled broth and then sealed it; no bacteria grew in it, but critics said it needed air. Franz Schulze (1836) boiled broth and introduced air that had been bubbled through strong acids and alkali; nothing grew, but people claimed the "vital force" in air had been altered with the chemical treatment. Theodor Schwann (1837) repeated the work, then passed heated air into the boiled broth instead, but even though nothing grew, naysayers claimed the "vital force" in the air had still been changed by heating.

In 1859, Pasteur challenged these claims in a letter to naturalist Felix Archimede Pouchet, who believed in spontaneous generation:

"he wrote that the question of spontaneous generation was entirely open and still awaiting proof and that all of this was unknown and warranted experimentation" (Schwartz, The life and works of Louis Pasteur, 2001)

So, he himself set up 3 swan-necked flasks as shown below. The bent neck did not allow germ-filled air to enter, but air in the top of the flask was present and sterilized (top diagram). If the same broth was exposed to air after boiling (middle diagram), the broth became contaminated with room bacteria. The bottom diagram shows that by tilting the boiled flask enough to let liquid reach a non-sterile part of the neck, contamination got in. Pasteur wrote in 1864, “Never will the doctrine of spontaneous generation recover from the mortal blow of this simple experiment. There is no known circumstance in which it can be confirmed that microscopic beings came into the world without germs, without parents similar to themselves." Despite this proof, the idea of spontaneous generation of diseases lingered into the early 1880s.

 Pasteur's experiment to debunk spontaneous generation (Bio.libretexts.org)

In 1849, the silk industry in France was decimated by a disease of the silkworms. A solution could not be found, and healthy silkworms could not be imported because the disease was worldwide. The

Healthy and sick silkworms (Frontiers in Microbiology)

French Department of Agriculture asked Pasteur to investigate even though he knew nothing about the industry nor that worms could even have diseases. From 1865 to 1870, he learned that there were two diseases, and only by selective breeding of eggs from worms that appeared healthy did he eliminate the problem and create fresh healthy stocks. But he also noticed that there were environmental factors that contributed to spreading the diseases, a point that stayed in his mind about other diseases. During his research at this time, Pasteur suffered a cerebral hemorrhage that paralyzed his left side. He was incapacitated for 3 months, during which time people had to read and write for him, but he kept pursuing the silkworm research.

Pasteur dictating a letter to his wife, about 1868 (Getty Images)

In addition to the pasteurization process, Pasteur is most widely known for his role in vaccine development. In the 1870s, scientists were still unsure about the cause of many diseases from bacteria or viruses. They couldn't understand how things so small could have such a large effect.

Around 1880, Pasteur was commissioned again by the Minister of Agriculture, this time to help resolve major problems with anthrax wiping out sheep and cattle in France. He first observed that they caught the disease only after grazing in certain fields, and that this was where sheep killed by anthrax had been buried. He tested earthworms above them and confirmed that they carried the anthrax bacteria after feeding on the sheep carcasses. As animals' mouths were cut by prickly vegetation, they became infected with earthworm excrement loaded with anthrax.

Pasteur already knew of Edward Jenner's success in vaccinating people against smallpox in 1796. But Jenner had not used smallpox virus to protect people; he used a related virus from cowpox instead. Pasteur didn't have that luxury, so he tried to weaken the anthrax bacteria chemically before reinjecting it into animals. A public demonstration in May-June, 1881 attracted 200 farmers and scientists. Half of 58 sheep, 2 goats and 10 cattle had been vaccinated, and when all were injected with anthrax bacteria, only the vaccinated ones survived, thus proving Pasteur's method worked.

Pasteur and team inoculating animals for the demonstration (History of Vaccine Development, Plotkin, 2011)

Recognizing the power of vaccines, he then searched for a disease that affected animals and humans, so he could do his testing on animals before using the final vaccine product on people. He chose rabies, which had been known for 4,000 years even though the exact cause (a virus) was not known. The disease reaches the nervous system and eventually causes death by encephalitis. 

People of Pasteur's day did not know how to culture viruses in the lab, and they are too small to see with regular microscopes. Previous research by others like Pierre-Victor Galtier suggested that injecting saliva from rabid dogs into rabbits could produce rabies, and by 1881 Galtier had demonstrated how he could protect sheep and goats against rabies virus by injecting tiny amounts of rabid saliva. That same year, Pasteur's co-researcher Émile Roux developed a model of injecting the virus directly into the brain. In 1883-1884, Paul Gibier showed that the virus lost its potency if it was dried out, so no chemical treatment was needed to weaken it.

Dogs were easier to obtain and were the main source of human infection, so Pasteur used them as test and control animals and followed all of the research of the day from 1880 to 1885. In 1884, he made his first test in dogs given weakened (dried) rabies virus from infected rabbits' spinal column. Data had shown that spinal material produced more consistent virus than saliva. The test on 50 dogs proved to be successful. 

Pasteur in his lab with dogs undergoing testing (Meisterdruke.uk)

Then, on July 6, 1865, a mother and her 9-year-old boy Joseph Meister arrived at his home after a 470-km journey. The boy had been bitten two days earlier by a rabid dog, and she sought Pasteur's help. He reluctantly instructed two doctors how to perform the 12 inoculations needed over the next ten days and worried so much that he could not work. But the boy survived, and the first human trial had been completed successfully.

Pasteur and Joseph Meister (awesome stories.com)

He later proposed building an institute specific for the administration of the vaccine, and it later grew into the prestigious Institut Pasteur which spread worldwide. He won many accolades throughout his life and died on 28 September 1895.

If you wish to see a movie about his life, starring the actor Paul Muni, go to this YouTube link.

How soaking in saunas could save our frogs

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There are over 7,700 species of frogs and toads worldwide. While new species are being discovered every year, many amphibians are in danger of extinction. Since the 1980s, a devastating disease has been found that is wiping them out at an alarming rate. What is this all about, and how can it be stopped?

From Australian Geographic, 2024

In the 1970s and 1980s, naturalists noticed a decline in the population of many amphibian species. For example, in the U.S.:

• David Bradford (University of California) saw that only 2% of the lakes in the Siera Nevada Mountains had yellow-legged frogs in 1989 compared to surveys in 1970.
• In Oregon, 80% of the Cascade Mountains frog populations that have been monitored since the mid-1970s are gone.
• The western spotted frog in Oregon was abundant until the mid 1970s, but it is now extinct west of the Cascade Mountains from at least one third of its Oregon range of habitat. Similar stories are reported from Colorado, Arizona and New Mexico.

Dead yellow-legged frogs (Rana muscosa), Sierra Nevada Mountains, CA, 2008 (AmphibiaWeb)

In other countries:

• The gastric brooding frog was discovered in 1973 north of Brisbane, Australia, and by 1981 it was thought to be extinct.
• In Costa Rica, where hundreds of golden toads used to be seen in one location in the early 1980s, fewer than a dozen were found in breeding sites less than a decade later.

Map of amphibian declines, 1980-2004 (red=caused by diseases, primarily chytrid fungus), Nature 2023

Sometimes this happens after habitats are destroyed, but often it occurs in undisturbed areas as well. Clearly, this is a worldwide phenomenon.

This decline is important for two reasons:

• Amphibians are major consumers of invertebrates, especially insects, and of other vertebrates.
• They also serve as a food source themselves for fish, birds, mammals and aquatic insects.

In addition, amphibians are good indicators of environmental stress on land and in water, because their skin can rapidly absorb toxic chemicals. Pollutants can also affect their eggs and growth rates. Natterjack toads in Britain and tiger salamanders in the Rocky Mountains, for example, have been shown to be negatively affected by acidic conditions, not just chemicals. But by 1990, the decline couldn't always be attributed to environmental factors or human intervention. And, the more serious threats to extinction seem to be caused by diseases.

Left: types of threats to amphibians, and how many species are affected

Right: extinction level (class) bases on the type of threat (Nature, 2023)

There is a fungal disease of amphibians called chytridiomycosis, chytrid for short (pronounced kit-rid). It is caused by two species of the fungus Batrachochytrium (circled in red in the left graph above). The earliest occurrences were as follows:

• Titicaca water frog, Africa, 1863
• Japanese giant salamander, 1902
• African clawed frog, 1938

But those are just instances when samples from an amphibian first showed the fungus was on it, not that the fungus killed it. In the late 1990s, chytrid was determined to be the source of Australian infections. By 2004, researchers found that chytrid fungus had been found in every continent that has amphibians, except Asia. The prevalence in Africa for so many years made them feel that Africa (especially Ghana, Kenya, South Africa, and Western Africa) was the source of the infection. 

Common midwife toad killed by chytrid (Nature, 2012)

One particular African frog was important for a special reason. The African clawed frog (Xenopus laevis) became a common lab animal for pregnancy testing in the 1930s-1940s. British zoologist Lancelot Hogben discovered in 1930 that if frogs were injected with a pituitary gland extract from an ox, frogs would ovulate in just a few hours. The extract resembles human chorionic gonadotropin (HCG), a hormone released by pregnant women, and he then noted that frogs ovulated when injected with their urine. This rapidly became a popular pregnancy test for several reasons:

• Results came after a few hours, not days with rabbit or mice testing with women's urine.
• Frogs could be used over and over, but mice and rabbits had to be sacrificed in order to examine their ovaries for signs of change (hence the expression "the rabbit died" to indicate a positive test).
• Maintaining frogs was easier than mice or rabbits, and the supply seemed unlimited from the African Rift Valley, as well as South Africa and Namibia.

Xenopus laevis undergoing ovulation in a pregnancy test (Wikipedia)

Although the Hogben frog pregnancy test has been replaced with testing that no longer involves frogs or any other animal, the Xenopus species have since become an invasive species worldwide, presumably due to their escape in distribution or release from labs into the environment. In fact, researchers now say that these problems in the world trade of that one frog species may have been the major reason why it spread around the world and began to infect other amphibians.

But let's get back to chytrid fungus and the way it affects amphibians.

The fungus produces spores with whiplike flagella on them to propel them through water. It then grows branches to allow it to attach to the skin, then form a sac where more spores can grow. The top contains a hole called a discharge pore where they are released.

Diagram of the chytrid fungal spore life cycle (Australian Government and Veterinary Research journal, 2015)

Cytrid life cycle with actual photos of the fungus (Yale E360)

Here is a photograph of frog skin showing actual discharge pores from chytrid spore sacs.

From the Australian Government pamphlet on chytridiomycosis

The first clinical signs of chytrid infection in juvenile and adult frogs may include the following symptoms:

• reddening of the underside
• abnormal spreading out of the legs
• sluggishness
• slow reflex to turn itself over when on its back
• abnormal skin shedding as white or gray material
• whitish ulcers
• spasms when handled

Reddening in different intensities (video, Zoological Society of London)

Salamander ulcers, white arrows (Veterinary Research, 2015)

Gray shedding, plus splayed leg posture (Veterinary Research, 2015)

The problem is that these are symptoms usually in the last stages of chytrid growth. Early symptoms are harder to identify: anorexia and lethargy. 

Fungus seems to be found on the skin in areas where keratin is present, mostly on the back, feet, and toes. Amphibian skin is vital to its existence, since they breathe through tiny lungs (except some salamanders), a lining inside their mouths, and their skin. The skin is a very thin layer of tissue that contains many blood vessels. While underwater, amphibians exchange 90-100% of their oxygen and carbon dioxide directly through their skin. This is useful short-term in warm months, but when they hibernate in winter, it is necessary to survive underwater. The skin also allows water to pass through.

How frogs breathe (Brown University)

As you can see from the diagram below, amphibian skin has an outer layer of epidermis (E), and directly underneath is a thick layer of capillaries (RC) to perform air and water exchange. Not shown are the vertical blood vessel branches connecting the capillary network to the arteries and veins at the bottom of the skin (LE). 

Diagram adapted from Glenn Tattersall, Brock University

RC=respiratory capillary network; E=epidermis

M=mucous gland; S and C are support tissue

SA & SV are cross-sections of arteries and veins connected vertically to the capillaries

Chytrid fungus kills amphibians by attacking the skin and producing a thickening 2-5 times thicker to 30 times thicker than normal.  The normal working of the skin is reduced, so that blood electrolytes (sodium,potassium, magnesium, and chloride) decrease, and eventually, the amphibian dies of cardiac arrest, not being smothered. 

Andean frog heavily infected with chytridiomycosis (New Scientist, 2019)

What can be done to stop or prevent chytrid from affecting so many amphibian species? First, you have to find it, and that's not always easy.

Chytrid may be present at only 5-7 spores per liter, so detecting it in water samples requires filtering large amounts and then growing the concentrated sample on agar plates. Attempts to measure its presence on fish fins or feathers (both good sources of keratin) used as bait have proven ineffective. Free-swimming spores live for only 24 hours, and then go dormant, too, so that presents a problem in detecting them. Rock scrapings as potential attachment sites are difficult to filter. Insect bodies are not made of keratin, but an investigation into whether several types of insects might be hidden sources for chytrid have failed to find any.

Removing healthy specimens before an area is affected is time-consuming and laborious, although in some cases it has been done on a small scale. Changing the environment's chemistry or temperature is also problematic, as is adding various antifungal chemicals. Some researchers have found a bacteria in frog skin that inhibits chytrid growth, as a sort of natural immune system. They proposed "bioaugmenting" amphibians that are in danger with this bacteria to strengthen their resistance to chytrid, and then releasing them into the wild. But this raises a lot of questions about whether this activity it may cause other problems to the ecosystem.

KM Taylor (University of California) has taken another approach in 2022. She grew the chytrid fungus on agar plates as usual, then washed the plates and filtered out the fungus and spores. What was left was any chemical the fungus had secreted. She then poured this into ponds of the Blue Oak Ranch Reserve and monitored the frogs there. Adding the chytrid metabolite increased the population of forg skin bacteria that would normally fight off chytrid. This is a promising sort of field "vaccination" still in testing.

Agar growth of chytrid; Barnett mixing up the "vaccine";

applying it to a pond (Natural Reserve System, University of California)

Australian researchers noted that the death rate of captive or wild frogs cut to chytrid was higher at colder temperatures. All frogs exposed to chytrid fungus in the lab at 17°C (63°F)and 23°C (73°F) died, whereas half of them at 27°C (81°F) survived. Anthony Waddle of Marquarie University (Sydney, Australia) wondered if by providing frogs with a warm place to spend time, the effect of chytrid might be prevented. So, he gave them mini-saunas.

He infected frogs with chytrid and provided them with enclosed shelters that had bricks with holes to serve as miniaure saunas. Frogs could choose between shaded and unshaded areas, with or without saunas. Waddle said, "We found frogs flocked to the sunny saunas, heated up their little bodies, and quickly fought off infection." The saunas were built with easily accessible materials: plastic greenhouse shelter, masonry bricks, plastic cable ties, and black paint. Details can be found online here.

Waddle's assembly of frog saunas (Australian Geographic)

Distribution of frog saunas in moist ground near a water source.

It is not clear yet what exactly kills the chytrid fungus. The frogs that Waddle tested were shown to rise in body temperature to 30°C (86°F), which he said "is sufficient to kill chytrid fungi". But is it the temperature itself, or does the warming somehow enhance the bacteria that produce chemicals against it? More research is needed, but for now, at least these inexpensive frog saunas can be used in areas like parks or other natural habitats that are not hard to reach.

Meteorite impacts identified as driver of moon's tenuous atmosphere

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The moon is made of green cheese. The moon has a dark side that never sees the light of the sun. There is no atmosphere on the moon. All of these are false, but that last one might come as a surprise, and it deserves closer investigation. Let's dive in and see what surrounds the Earth's moon.

Planets and their moons are formed from materials that make up their suns. Depending on their size, mass, and distance from the sun, they will end up with different exterior and interior structures, including atmospheres.

It is thought that the Earth's moon formed around the time that the Earth was still hot and molten, about 4.6 billion years ago. Something named Theia (the size of Mars) collided with Earth, and the debris that was ejected came together and formed the moon. So, the Earth's and moon's building block materials are the same. But why does Earth have such a thick atmosphere, and the moon doesn't?

Illustration of giant impact theory of moon formation (Citronade, Wikipedia)

Generally speaking, the stronger the gravitational pull, the thicker the atmosphere that a planet can hold near its surface. Over time, though, the sun's radiation blows away the lightweight elements like hydrogen and helium from the planets. Volcanic activity on the inner planets (Mercury, Venus, Earth, Mars) adds to the gases in their atmospheres. These events and more all combine to create a constantly changing mixture of gases. Here is what makes up the atmospheres of the 8 planets in our solar system.

There are very small traces of other gases in most atmospheres, too.

As of August 4, 2024, the solar system has 293 known moons around its planets: Earth (1), Mars (2), Jupiter (95), Saturn (146), Uranus (28), Neptune (16), dwarf planet Pluto (5). Only about 15 have atmospheres (Saturn's moon Titan has the densest), and most of these barely have anything at all. They are called exospheres instead. The particles in an atmosphere are packed tightly enough to bounce off each other, but in an exosphere, the density is too thin, so they are considered "collision-less". 

The outer layer of a regular atmosphere has an upper layer of exosphere as the air thins out. See the diagram below for a comparison image of that from Earth's atmosphere.

The layers of the Earth's atmosphere and altitude of various objects or phenomena (NASA):

the exosphere reaches from 400 km to 10,000 km.

If the moon is just a piece of the ancient Earth, what has been found about gases surrounding it?

As far back at the 18th century, the Croatian scientist Roger Joseph Boscovich proposed there was no atmosphere there. He published a paper in 1753 with his results based on simple observations like:

• Stars suddenly disappear behind the moon instead of fade at its edge.
• There are no apparent clouds.
• There are no apparent instances of haze or winds blowing there.

An early hint that something might be there came from photos from the NASA Surveyor 7 lander in 1968. After sunset, a "glow" appeared on the horizon, which should not be seen if there is nothing above the surface to reflect or refract light. See the various pictures below.

Moon glow on the horizon, seen by Surveyor 7, 1968 (Planetary Society)

Various Apollo missions also detected this lunar horizon glow. But by the early 1970s, it was determined to be refraction off moon dust kicked up as high as 10 km by infrared and ultraviolet rays from the sun stripping off electrons from moon dust and sending them above the surface. That's not an atmosphere. That's moon dust particles.

Three Apollo missions left behind instruments to try recording whatever thin atmosphere might be detected. Many of them gave results (argon-40, helium-4, oxygen, methane, nitrogen, carbon monoxide and carbon dioxide) that were hard to interpret because the moon lander and the instruments themselves gave off particles that interfered with the instruments. One, the Lunar Atmosphere Composition Experiment (LACE) presumably detected helium. 

LACE instrument left by Apollo 17 (NASA)

In 1985, sodium was found clinging just above the lunar surface, and then in 1989 potassium was found, too, both detected from instruments on Earth. If they were above the surface, this might explain why there is less of those two elements in lunar soil (regolith) than in Earth soil samples. They are being ripped off the lunar surface somehow.

The two signals for sodium wavelengths measured from Earth (National Astronomical Observatory of Japan)

In 1998, NASA sent the Lunar Prospector spacecraft to orbit and map the moon for 19 months. It measured elements leaving the surface, whether as gamma rays from the sun hit the surface, or as radioactive elements (radon, polonium) under the soil release neutrons upward. Since the Lunar Prospector was in orbit, there was no interference with measurements like the surface tools of Apollo. Therefore, the Lunar Prospector measurements were more reliable.

Illustration of Lunar Prospector (Lunar and Planetary Institute)

Ten years later (2009), NASA sent the Lunar Reconnaisance Orbiter (LRO) specifically to examine the thin exosphere of the moon. It confirmed helium that had been detected by Apollo 17. Some comes from breakdown of thorium-232 and uranium-238 underground and released during moonquakes, but some also accumulates as part of the solar wind plasma (made of electrons, protons, and helium nuclei called alpha particles).

Illustration of LRO (Wikipedia)

Shortly after that, the Lunar Atmosphere and Dust Environment Explorer (LADEE) spacecraft was sent by NASA in 2013. Its orbital measurements found helium-4, neon-20, and argon-40 elements in the thin exosphere.

LADEE during testing (NASA)

In its examination of the surface and exosphere, LADEE found two processes at work which send elemental particles into the exosphere: solar wind sputtering and meteorite impacts. Sputtering is the removal of atoms from lunar rock when electrons or protons from the solar wind hit. Meteorites (and micrometeorites) hit with such force that they heat up the rock (to 2,000-6,000º C) and vaporize atoms off it. Together, these are called space weathering, and the materials they release help to make up the moon's exosphere.

Adapted from Universita del Salento, Italy

Sputtering makes up <30% of released elements, while micrometeorites make up 70%. Gamma radiation also contributes a small fraction. LADEE did not learn this percentage, though; only a 2024 study by Nicole Nie in the Department of Earth, Atmospheric, and Planetary Sciences at the Massachusetts Institute of Technology determined that, over 50 years since the Apollo missions. 

Nie examined moon rock samples returned by Apollo, and with the latest technology determined the stronger effect of micrometeorites over sputtering. The moon (and Earth) is always passing through space debris from comets and asteroids, so the vaporization of impacts keeps replenishing the thin exosphere. During times when the Earth and moon are passing through such debris, the exosphere increases in thickness. Compare it to the amount of condensation on a windshield as you drive in and out of fog banks.

Even so, whether atoms are generated by vaporization or sputtering, they may sometimes be lost to space in the moon's low gravity, or they may be energized by photons from the sun and bounce back to the moon's surface.

Model from Nie's experiments, 2024 (PSD=photon-stimulated desorption)

The known elements in the moon's exosphere are argon, helium, neon, potassium, and rubidium, plus small percentages of other elements. Sodium gets resorbed back into the lunar rock. 

The exosphere reaches only about 100 km above the moon's surface, but it is so sparsely dense that it is invisible to the naked eye. It has about 80,000 atoms per cubic centimeter, which might seem like a lot. But, air at sea level on Earth contains much more: about 2 x 10¹⁹ molecules and atoms (a 2 followed by 19 zeros) per cubic centimeter.

So, solar wind and meteorite collisions contribute to what we now know as the moon's exosphere. Billions of years ago, however, when Earth's nearest body was molten, volcanic activity may have released more gases and created an actual atmosphere. But nobody was around to see it. In any case, it's a busy situation out there.

Computer simulation video of the origin of the moon. (NASA Ames Research Center)

Meet the American who wrote the moon-landing software: Margaret Hamilton, computer whiz mom

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Margaret Hamilton was born Margaret Elaine Heafield on August 17, 1936, in Paoli, Indiana. About school, she said, ...there was something about math that I just liked more than anything else. I liked deriving the answers because I didn't want to memorize. Her desire to study math, solve problems, and work on the Apollo program as an early software engineer set a standard that went formally unrecognized by the public for decades. Her software even exists in the International Space Station.

She began studying mathematics at the University of Michigan in 1955, then transferred to Earlham College in Richmond, Indiana, and got her bachelor of arts degree in math. where her mother had been a student. She earned a BA in mathematics with a minor in philosophy in 1958. There, she met her future husband, James. They married that year and had a child soon thereafter. Margaret considered going on further into graduate study in abstract mathematics at Brandeis University, but she changed her mind in 1959. Her husband went on to law school, and Margaret briefly taught math at a high school.  

Margaret Hamilton, university age (YouTube)

To support the family, in mid-1959 she started work at MIT in the meteorology department under her mentor Edward Norton Lorenz. Lorenz was responsible for chaos theory, which takes complex patterns and laws of dynamic systems to understand what appears to be randomness but is really predictable. Lorenz coined the term "butterfly effect", which suggests that a tiny change has the potential to have large long-range effects. His most important application of chaos theory was to develop simulations of weather patterns. Margaret set about to study how to write weather-predicting software. At the time, there were no courses in computer science and software engineering or even disciplines with those names, so she had to teach herself everything including software programming. She said, When I first got into it, nobody knew what it was that we were doing. It was like the Wild West.

From 1961 to 1963, she tranferred to MIT's Lincoln Laboratory, which is a U.S. Department of Defense funded research and development center. Its goals were to apply advanced technology to problems of national security. There, Margaret worked on the Semi-Automatic Ground Environment (SAGE) Project, which was a was a series of computers across the U.S. connected to local radar systems. It provided an overall picture of the airspace of the country as part of detection for the perceived threat of nuclear attack from Russia. She wrote software to help identify enemy aircraft. The vital link to national security at that time impressed upon her the importance of writing reliable software.

Hamilton and associate with prototype computer system

at Lincoln Laboratory, 1962 (Computer History Museum)

Reliability wasn't just something to concern any programmer for the sake of the software working correctly. It was a mark of personal pride or embarrassment. As Margaret put it:

When the computer crashed during the execution of your program, there was no hiding. Lights would be flashing, bells would be ringing and everyone, the developers and computer operators, would come running to find out whose program was doing something bad to the system.

Then, in 1965 she changed jobs again. Margaret became the director of the Software Engineering Division at the MIT Instrumentation laboratory (now Charles Stark Draper Laboratory). The lab's founder, a research associate at MIT, led work at the Aeronautical Instrumentation Laboratory in 1933. They developed anti-aircraft gunsights, gun-bomb gunsights, gyroscopes for for ballistic missile guidance, navigation system for the B-29 bomber, submarines, and satellites. It's Mars probe concept in 1959 led directly to ties with NASA.

But Margaret has seen an advertisement in 1964 to recruit software developers to send man to the moon. MIT had the contract to write the computer software. As she put it, 

I was attracted both by the sheer idea and the fact that it had never been done before. I was the first programmer to join and the first woman they hired. Male engineers were already working on the project, but they were hardware engineers and it wasn’t their thing. I had it as my background. I think [the lab] just figured that I could handle the unknown. (The Guardian, July 2019)

So, in 1965, Margaret's timing and experience were perfect for America's need on the young Apollo space program to send the first astronauts to the moon. She was the first programmer and the first woman to be hired. Years later, she said, 

I was hired to do what they called programming, they also call it software engineering today, but not back then. One of my first assignments was to work on algorithms having to do with lunar landmark tables. (Apollo Guidance Computer History Project, conference speech, July 27, 2001)

Working on Apollo software (YouTube)

Her role in a male-dominated world of science and engineering can be summarized in two quotes:

• When I took over, one of the bosses at the top said he had no doubt I could do the job but was worried the men working in the group might rebel. Well, they didn’t. More than anything, we were dedicated to the missions and worked side by side to solve the challenging problems and to meet the critical deadlines.
• Programming was never considered to be women’s work, at least not in any of the many projects I have been involved with. Human computers [who did calculations by hand] were mostly all women and there were women who used calculating machines ... but they weren’t programmers. They didn’t write software. When I first came to Apollo, there were no other women writing software. (The Guardian, 2019)

In fact, Margaret actually coined the job title "software engineer"; in her mind, software developers had the right to be called engineers. To understand the difference between software engineering and programming back then, you have to know what the Apollo Guidance Computer (AGC) was, and how it worked. Software languages like FORTRAN and BASIC weren't around or were barely invented (FORTRAN, 1957; BASIC, 1964). Engineers used assembly language, which directly talked to the machines they controlled, but the language was very complex. Here's the code to add 5 + 10.

The Apollo guidance computer (AGC) had only 72 kilobytes of memory. No chips. It ran using something called core rope memory. Thin wires were weaved into a tray by hand, and when current passed through them, the output represented a binary 1 or 0, to tell a device to start something or stop it or to reset it. Here is the completed AGC with its keypad:

Apollo guidance computer (Computer History Museum)

Commands were entered on the keypad mostly as number codes. The first number was the subject of a sentence, and the next number was the verb. 

AGC keypad with digital display (YouTube, "Computer for Apollo" (1965))

Inside the larger box were 4 trays of the woven wire assemblies. Each assembly, complicated as it was, contained only 12 kilobytes of read-only memory. They looked like ropes:

One tray and closeup of core rope memory (Wikipedia)

At 32, Hamilton began writing software for the AGC in summer, 1968. Keep in mind that Apollo 8 went around the moon in December that year! Apollo 8's mission was to send 3 astronauts around the moon ten times without landing. As she described it, nobody really accepted the idea that any mission would have to abort, so the software to control that wasn't very important. They considered her a beginner and gave the project to her thinking it would never be needed.

Hamilton the "beginner", later led the team (YouTube)

Before the flight, her 4-year-old daughter (who often slept on the office floor) was playing with the controls and accidentally pressed a button that crashed the computer by putting it into prelaunch mode. Margaret learned from that, but her bosses would not let her put in software to prevent the prelaunch from operating after the craft had taken off. Astronauts were considered perfect and beyond making mistakes. Months later, when Apollo 8 was in orbit around the moon and preparing to come home, Commander Lovell did make the same mistake, deleting all navigation data, and put his craft at risk of burning up on reentry. Margaret and her team spent 9 hours going through the code in an 8-inch-thick book to find the solution. After that, NASA allowed her to install the safety code she had advised earlier.

Hamiton (1969) standing next to the Apollo 11 documentation (Wikipedia)

Margaret also recognized that astronauts would be doing many things at once with the flight computer, and that it might not recognize an emergency. Despite being told there was no solution, she designed one in a day, so the computer would warn the astronauts to stop what they were doing.

A few minutes before the Apollo 11 spacecraft landed on the moon seven months later, the alarm sounded. The computer was taking in too much data, and the astronauts were unaware of just what data was unnecessary to complete the landing. Margaret's error detection and recovery mechanisms (to reboot the computer automatically) had warned them and saved the lives of astronauts Armstrong and Aldrin.

Hamilton testing controls inside the Apollo spacecraft (Wikipedia)

After Apollo ended in 1972, Hamilton worked for a time on the Space Shuttle and Skylab programs. Then, in 1976 she cofounded the company Higher Order Software, which further developed ideas about error prevention and fault tolerance. Their product USE.IT would automatically analyze other software specifications for errors, and after they were fixed, it would design the source code and documentation. This was very useful in government programs.

In 1986, she founded Hamilton Technologies, Inc. This created "products and services to modernize the planning, system engineering and software development process in order to maximize reliability, lower cost and accelerate time to market."

Official photo for NASA, 1989 (Wikipedia)

From 1986 to 2022, she earned many awards, including the Augusta Ada Lovelace Award in 1989, the NASA Exceptional Space Act Award in 2003 (very prestigious award), and the Outstanding Alumni Award from Earlham College in 2009. She also kept in touch with NASA and spoke at conferences related to guidance computer systems.

Hamilton at a 2002 conference (Caltech)

In 2016, President Obama conferred on her the Presidential Medal of Freedom.

On the fiftieth anniversary of the moon landing, Google celebrated Margaret Hamilton. A display of her face and the Apollo 11 event was created with 107,000 mirrors in the Mojave Desert to reflect moonlight over an area larger than Central Park. Watch and see.

Short interview 2017

https://www.youtube.com/watch?v=4sKY6_nBLG0