All of Neptune's clouds have mysteriously disappeared, and the sun may be to blame

Link to article

Earth has often been described as a pale blue marble in space, but the planet Neptune is much deeper blue. It's been known since the 1800s when it was separately discovered by John Couch Adams (1843) and Urbain Le Verrier (1845-46). The name "Neptune" comes from the Roman god of the sea, which coincidentally matches its deep blue color, even though that was not known at the time. Voyager 2 provided the first close-up photos in 1989, and that was when the high-altitude clouds of 80% hydrogen and 19% helium were seen. But since then, their appearance has changed considerably, and the reason for that is only now coming to light.

Picture of Neptune by Voyager 2 (NASA/JPL-Caltech)

First of all, why is Neptune blue -- essentially all blue? The trace amount of methane in the upper atmosphere absorbs red wavelengths of light from the sun and reflects back blue. 

Second, we know that on Earth, clouds form when water vapor in the air (which comes from evaporation on the surface) runs into dust particles. These collect until the vapor changes (condenses) into liquid form and eventually clouds. Evaporation from lakes, oceans, rivers, pools, and other places is driven by heat from the sun as part of the water cycle.

Cloud formation (from ClimateKids.NASA.gov)

But Neptune doesn't have liquid water. The average temperature there is -353 Fahrenheit (-214 Celsius). It's not a uniform temperature all over the planet, of course. In fact, scientists have used infrared telescopes to measure changes at the south pole during its long summer. Yes, Neptune has seasons like Earth because it is tilted nearly the same as our planet. But because it takes 165 years to revolve around the sun, each season is about 40 years long! But in the pictures below, you can see that instead of being dark red (hot), the south pole cooled down (white) during summer. The difference is 46-52 degrees F (26-29 degrees C). The reason is unknown.

Infrared images of Neptune. Note cold white on the south pole growing during summer (EarthSky.org)

So, what makes clouds on Neptune if there's no liquid water? It's the frozen methane (not the methane mixed evenly with hydrogen and helium) in the upper atmosphere that looks white and casts shadows on the blue background of the lower atmosphere. The lower atmosphere is still very cold, so it may be made of hydrogen sulfide, ammonium sulfide, ammonia, and even water ice, all under great pressure.

Neptune is known to have the most violent storms in the solar system. Winds up to 1,305 miles per hour (2,100 km per hour) have been measured. Those are 9 times faster than the fastest on Earth. But how are winds created? On Earth, the sun heats the air, land, and waters but unevenly. As the hot air from land rises, it is replaced by heavier cold air; thus, that influx of air moves, and we call that wind.

Images from scijinks.gov

But at 2.8 billion miles from the sun (compared to the 93 million miles for Earth), Neptune receives far less energy from the sun, about 1% of what Earth gets. And, there is almost no significant rocky core (and no liquid water) on Neptune compared to Earth. So how does wind form there, let alone blow so strongly? The first thing to keep in mind is that they blow only in the upper 600 miles (1,000 km) of its atmosphere.

Cross section of Neptune (Wikipedia)

There are two theories why winds are created on Neptune. One is that some process in the upper layer reduces friction. The other is that there is some unknown heating coming from the core.

The newest data from the University of California at Berkeley concerns a related phenomenon: clouds. From instruments on Earth and the Hubble space telescope, they noticed that in the 40-year summer season, there was a change in cloud patterns during an 11-year cycle. They are disappearing.

Cloud patterns dying off 2002-2023 (UC Berkeley/W.M. Keck Observatory)

That same 11-year cycle coincides with the sun's activity. It isn't a constant source of heat, light, and radiation. Every 11 years, its magnetic poles flip, so north becomes south and vice versa. That changes the amount of sunspots and solar flares. More of each occur at the maximum solar activity, and each one sends out strong magnetic radiation into the solar system. They can cause beautiful views like the aurora borealis on Earth when the radiation interacts with the planet's own magnetic field, or they can disrupt electronic communications (radio blackouts). 

Solar activity cycle (skyjinks.gov)

Out on Neptune, these bursts of energy are thought to cause more clouds. The thought nowadays is that, unlike cloud formation on Earth, somehow the energy from sunspots and flared (maybe also from UV light) interacts with the chemicals in the upper atmosphere slowly over 2 years to create enough condensation to form clouds. When the activity from the sun is low, the reaction slows or stops, and clouds disappear. 

Here's a 5-min YouTube video on Neptune's winds. Note the mention of diamond rain!

Pills from the 3D printer

Link to article

Pills come in many shapes and sizes as well as names. They deliver medicine at different rates and for different reasons, depending on the patient's age, illness, or disposition towards swallowing. With 3D printing technology, scientists are finding ways to create pills in complex shapes that will allow drugs to be released more efficiently. How and why is this being considered?

A complex pill shape proposed for study 

What are the many types of pills? Tablets are compressed powders into a disk, sphere, or oblong shape. Caplets are smaller and usually have a smooth coating. Capsules are powder, miniature pellets, or liquid contained inside a hard or soft shell. Chewable tablets are meant to be ground by the teeth and taste good. Some tablets are meant to be broken down on or under the tongue, or by dissolving in water. Some meds are small packets of powder meant to be poured into the mouth, followed by washing down with a liquid. 

Image from fotostock.com

Researchers at the Max Planck Institute for Informatics in Germany are using mathematical modelling to figure out what shape of pill would dissolve the best in the body. Since it optimizes that process and deals with the topology (shape) of pills, the design is called topology optimization.

If you think about it, the idea is very simple. The more surface area that something has to come into contact with water or body fluids, the easier it will be to dissolve. Crystalline shapes like those below give a lot of surface area to the weight of the drug.

Some designs for 3D pills (Max Planck Institut)

Researchers determine what kind of timeline the drug needs in order to be spread throughout the body, how much should be in the blood or tissues, for example, and how long it can remain active, and then they work out mathematical models of the proper shape a pill would have to be in order to dissolve, release, and maintain that amount of active ingredient.

Dr. Vahid Babaei and his colleagues from Max Planck took the mathematical data and programmed a standard 3D printer to build the desired shape. The material they use is a polymer called AquaSys 12O, which dissolves rapidly in tap water. It is sold as an amber-colored filament wrapped around a spool.

AquaSys 12O (Amazon.com)

The AquaSys 12O absorbs light when it is dissolved in water. That means scientists can measure how much of it is in the water by the amount of light that they measure with special devices. They keep the water in the beaker agitating to mix uniformly with a spinning  magnet on the bottom, while a camera records how much light is measured as the pill dissolves. Eventually, the undissolved pill fragment settles on the bottom, and the amount of light stops changing. 

Experimental setup to measure light from dissolving pill shapes (ACM Transactions on Graphics journal, 2022)

How long it takes, and what kind of time pattern is seen are both used to improve on pill shapes. The graphs below show how different shapes release the AquaSys 12O more and more until it finally levels off after some point. The pattern of that release depends on the shape of this fake pill.

Experimental data of dissolving shapes of AquaSys 12O over time 

Now, the body doesn't have a spinning magnet, and the liquids inside the stomach and intestines don't mix as vigorously as in a beaker. If the AquaSys 12O shape is left to dissolve without any turbulent water action, the shape breaks down differently, but it still provides data that researchers can use. Later, when this research reaches the lab animal stage, blood samples can be taken over time to confirm how much of the drug is in the body.

Heart-shaped AquaSys 12O dissolving in undisturbed water (ACM Transactions on Graphics journal, 2022)

All of this is just around the corner. In 2015, the first (and so far only) 3D-printed drug was approved by the US FDA. Spritam is made by Aprecia Pharmaceuticals for epilepsy. Others are undoubtedly on the way. The UK company FabRx was created in 2014 to make such specially designed pills, and it estimated this will be quite common in 5-10 years' time. As of July 2022, three other companies have gotten into the commercialization, so it looks like FabRx was not wrong.

If you're interested in learning more about new technologies to deliver medicine to the human body, here's a cool website with animated images showing 7 new potential methods.

Here are some short videos on the 3D pill printing process, too.

How to 3D print the 'wonder pill'  (6:50)

Developing 3D Printed Drugs for Personalized Medicine with FabRx (1:34)

Customising 3D printed pills as a treatment for patients (2:49)

Alexander Fleming: penicillin and so much more

Mention the name of the scientist Alexander Fleming, and many will say, "Oh, he's the guy who discovered penicillin!" That's only partly true, but it's the story or legend we have come to accept. What's the real story, and what else do we know before and after Fleming's discovery?

Sample of the fungus from Fleming's lab, donated to Douglas Macleod, St. Mary's Hospital (Science Museum London)

Born in southwestern Scotland on August 6, 1881, Alexander Fleming grew up on a farm with seven siblings. He moved to London at 13 to live with his older brother Thomas, who was an ophthalmologist. Alexander had to quit school, and he worked in a shipping company until his brother convinced him to use recently acquired inheritance money from an uncle to study medicine at St. Mary's Hospital Medical School. There, he got his bachelor's degree with distinction in 1906. He'd been a private in the London Scottish Regiment of the Territorial Army and was considered a good marksman, so the captain of the St. Mary's rifle club wanted him  to join, and to do that he introduced Fleming to Sir Almoth Wright (also a club member) to conduct research there on vaccine therapy in his newly established laboratory of the Inoculation Department. Otherwise, he'd have had to leave St. Mary's to pursue a career in surgery. Almoth developed the first British vaccine against typhoid, and other noted researchers worked there, including Augustus Desire Waller, who developed the first electrocardiogram in 1887.

The young researcher Fleming at St. Mary's

Fleming worked with Wright on several projects. Earlier, in 1905, German bacteriologist August von Wassermann had developed a diagnostic test for syphilis, which Fleming was tasked with simplifying in 1909. A year later, Paul Ehrlich, a German physician, discovered an arsenic compound that cured syphilis, and Fleming used his previously published work to develop a better method to administer this new drug.

Then, he served as a captain in the Royal Army Medical Corps in France during World War I, after which he returned to St. Mary's where he got a master's degree. It was while he worked in field hospitals during the war that he was exposed to the horrific results of battle and how poorly medicine at the time was combatting infections like gangrene, tetanus, and general septicemia. Fleming noticed how antiseptics were used even for deep wounds but to no avail, which resulted in loss of limb or life. He even published a paper on it in 1917 to show how gauze absorbed antiseptics so much that it made them useless for such injuries. But nobody paid much attention. Another paper he wrote that year showed how antiseptics kill the body's protective white blood cells more than they kill bacteria, so they are useless except on the surface of a wound. And, if there was a lot of pus in the wound, that tended to block the entry of the antiseptic anyway. Again, field doctors continued their regular practices.

Treating battle injuries in World War I

Back in London, he remained interested in how the body itself fought disease. In 1921, when he had a cold, he wondered whether mucus from his nose would have any antibacterial effect, so he applied it to one of his Petri dishes. Bacteria that had blown in randomly onto the plate grew in colored patches except 1 cm (half an inch) outside the drop of his mucus. "This is interesting", he calmly told a research assistant. Something had seeped from the mucus through the plate agar and killed the bacteria! 

He then tested other fluids like tears, saliva, sputum, serum, and more and found it in all of them. He named this material lysozyme, meaning that it causes the lysis (destruction) of bacterial cells like an enzyme. It was weak but present in many tissues, suggesting its importance in natural immunity. In the bacterial plates below, you can see the effect using tears. The left petri dish has whitish bacteria growing on the place except near a paper disk soaked in tears. The right dish shows how mixing bacteria with tears causes them to break apart and grow in a more disrupted way, less dense than without tears.

Figures from Fleming's 1922 paper on lysozyme

Fleming managed to find time to do research despite being promoted to Assistant Director in 1919. As AD, he acquired massive responsibilities for financial support over medical supplies, as well as salaries and housing of technicians, research workers, and office staff, most of whom lived at St. Mary's. He was also in charge of directing most of the research done there and coordinating commercial activities such as vaccine production and antitoxin testing in the hospital.

Enter the year 1928. Fleming was studying a common bacteria called Staphylococcus (colloquially called "Staph") because it is a very common one spread by the wind and feces and because it is therefore a common contaminant in wounds. His lab bench was very cluttered (see below), and he was running several experiments at once, whether in test tube cultures or petri dishes.

Fleming's lab bench (Wikipedia)

On September 3, 1928, at age 47, he came back to his lab after a vacation and began to examine and tidy up many of the cultures with junior researcher Merlin Pryce. On one petri dish that he'd inoculated with Staph before his break, he noticed a gray-greenish patch of mold. That plate is shown below. Notice that like the lysozyme culture with tears, there is a blank space of agar gel between the Penicillium mold and

the bacteria. Once again, this suggested something he called "mold juice" was excreted by the Penicillium species and flowed into the agar, not only stopping bacteria from growing in that zone, but obliterating what had already grown in Fleming's absence. Once again, he reacted with a curt, "That's funny". He repeated the experiment on September 28 with success.

Fleming examining a petri dish culture of Staph (steemit.com)

Where did the Penicillium mold in Fleming's petri dish come from? His lab window was sealed shut. The particular species on his plate is not a common airborne one, so two speculations have arisen. The Royal Society of Chemistry thought that it came from Fleming's messy lab and spilled coffee which would have killed other molds around, allowing this special one to breed. Another thought is more reasonable. There was a laboratory one floor below where Charles La Touche was studying molds and fungi, so it might have drifted in from there. Fleming's messiness might have actually helped in another way. It is reported that after his return from vacation, he glanced at his cultures and missed the one that was later deemed key. He put it on top of other plates in a bath of Lysol (in use since 1889) to disinfect things before throwing them away, and it was only when he and Pryce were reviewing the plates before disposal that he took notice of the reaction. This also explains why he felt the need to repeat the experiment; the one he saw was not covered in the Lysol, but he wanted to be sure it had not accidentally entered the plate.

But this is not where the story ends. Fleming didn't leap to purification and mass production of the active chemical agent he called penicillin and become world famous. In fact, he wasn't the first to notice that molds help combat bacteria. 

• Ancient physicians from Greece, Serbia, and India used molds even though they didn't know why they worked. Russian peasants did the same with soil containing mold. 
• England's Royal Botanist John Parkinson published a book Theatrum Botanicum (with a 157-word title!) in 1640 on herbalist remedies like Penicillium.

From 1850-1890, the world got used to the notion of bacteria causing illnesses, thanks to the work of Louis Pasteur and Robert Koch. Treating wounds and diseases was still not performed very consistently due to the lack of knowledge. 

• Researchers like Sir John Burdon-Sanderson (1870) and Joseph Lister (1871) had both noted that species of the Penicillium mold would inhibit growth of bacteria. Sanderson just grew mold on the top of test tubes and saw no bacteria underneath. No reason given. Lister had simply noted that urine samples did not grow bacteria if they had mold in them.
• Theodor Billroth, the German "father of abdominal surgery", noticed in 1874 that Penicillium but not bacteria grew in some test tube cultures. He supposed that the sterilizing process of the liquid media or the mold itself had somehow changed the chemical composition of the growth liquid to make it unsuitable for bacteria. 
• Physicist John Tyndall also noted Penicillium's antibacterial properties in 1875, but he ascribed them to choking the oxygen from the top of the test tube culture where they grew, not by producing any chemical.
• In 1895, Italian medical officer Vincenzo Tiberio noticed that people in his home became sick after the walls of the well were cleaned of mold (including a Penicillium species), so he thought it afforded some protection to the well water. He scraped it off and used it in culture, on animals, and eventually on humans with success, thinking the mold made some curative material. Italian medicine ignored his results as a coincidence.
• French physician Ernest Duchesne recorded the opposite effect, typhoid bacteria killing Penicillium mold in culture, but when he injected both together into guinea pigs in 1897, the animals didn't die of typhoid. So he thought the mold made something to weaken the bacteria. Unfortunately, his doctoral work was ignored by Louis Pasteur simply because Duchesne was an unknown researcher in his early 20s.
• Since then, papers around the world sporadically reported antibacterial effects of Penicillium--Sturli (1908), Lieske (1921), Twight (1923), and Gratia & Dath (1924)--but none of these  attracted great attention for medical purposes.

Gilbert Shama wrote an article in the 2017 Journal of Pharmaceutical Microbiology summarizing these and other instances which he labels it as "simultaneous discovery", something not uncommon in science. Fleming got the credit, probably because he tried to tie the lab results to potential usefulness in medical practice.

Fleming published his findings from the fateful petri dish in 1929. Although a modest sized paper (10 pages), it didn't inspire the medical community. That by itself is odd because it described the following properties of crude batches, all practical for potential mass production:

• it dissolves easily in water
• it can be filtered into a sterile solution
• it can survive moderate heating (56C/132F, or 80C/176F)
• it is most stable at body pH
• it was effective against many types of bacteria
• it was not toxic to rabbits or mice or white blood cells
• it did not irritate skin or corneas

When he read another paper on penicillin that year, he again suggested its use for treating human infections, but nobody was interested in this lab oddity. The same thing happened at a conference of renowned scientists shortly thereafter.

Being trained in surgery and doing research in bacteriology, Fleming was no chemist, so he and his assistants found it impossible to mass produce penicillin in a pure form, only as a crude extract from the bottom of flasks. A year later, he gave up.

Batch cultures of Penicillium (British Pathe)

Shortly thereafter in 1935, "sulfa drugs" were discovered. These were sulfonamides capable of curing diseases caused by Staph and streptococcus bacteria, and the race was on to produce even more. Penicillin took a back seat. And then World War II broke out.

Australian Howard Florey (pharmacologist) and German Ernst Chain (biochemist) worked at the University of Oxford at the time. Despite having little funding there, they set up a lab to study antibacterial products made by two bacteria and Penicillium based on reading Fleming's papers. They convinced the Rockefeller Foundation in the U.S. to fund them for 5 years. Like with Fleming, they had no problems in growing Penicillium. With more resources than him, Florey and Chain hired six women to mass product the mold.

Florey and Chaim's scaled up batch production (Wikipedia)

With their expertise, they solved the problem of extracting pure penicillin from the raw culture liquid. Florey was searching for a single chemical to kill all bacteria, but he settled on penicillin with its major effects. His comment on this altruistic venture show how the two of them were just ordinary scientists:

"People sometimes think that I and the others worked on penicillin because we were interested in suffering humanity. I don't think it ever crossed our minds about suffering humanity. This was an interesting scientific exercise, and because it was of some use in medicine is very gratifying, but this was not the reason that we started working on it." (Florey)

In March 1940, they tested their batches on rats, mice, rabbits, and cats. Their first human test was on a 43-year-old policeman on February 12, 1941. Britain's chemical industry then was devoted to wartime efforts, so Florey went to the U.S. to solicit help. A contact at the Department of Agriculture's Northern Regional Research Laboratory (NRRL) in Peoria, Illinois improved the growing process and purification methods. American pharmaceutical companies Merck, Squibb, and Lilly had done some penicillin research already, and Pfizer was about to. Collaborative agreements were made in 1942 between all but Lilly to help Florey, while his Oxford lab conducted clinical trials and published on 187 cases in 1943. Pfizer opened the first commercial penicillin production plant on March 1, 1944. Penicillin eventually became mass produced through concerted efforts by many players and was available without restrictions by early 1945. On D-Day, every Allied soldier carried a dose with them.

Advertisement from National World War II museum

Chain tried to convince Florey to file for a patent on penicillin production, but Florey said it should be free for all. An advisor to the Scientific Advisory Panel to the British Cabinet told Florey it would be unethical. Chain's result from speaking to the Secretary of the Medical Research Council was the same. Americans Robert D. Coghill and Andrew J. Moyer ignored the British situation and filed for a patent on penicillin production, unlike other researchers. This drove Fleming crazy, and he wrote about that:

"I found penicillin and have given it free for the benefit of humanity. Why should it become a profit-making monopoly of manufacturers in another country?"

Despite penicillin's success, Fleming's further research was showing that many bacteria can develop resistance to drugs like penicillin. He cautioned that it should be used appropriately to avoid that problem.

In 1944, Fleming, Florey, and Chaim together won the Nobel Prize in Physiology or Medicine for their combined discoveries. Fleming was also knighted in that year. He died on March 11, 1955 of a heart attack.

Receiving the Nobel Prize (1945)

The history of developing penicillin for mass production can be found at this link.

For a better brick, just add poop

Link to article

The world produces about 1.5 trillion bricks per year, mostly from China (67%) and India (13%), and the number is rising. The ovens used to bake clay into bricks use 375,000,000 tons of coal, so it would be better for the environment to find an alternate means. Most bricks use clay as the main substance,  but the annual removal of clay from the ground is enormous. Imagine 12,000 holes that are each as deep as 100-story buildings and have the area of soccer fields. That's what is being taken from the Earth to make bricks every year. A research team from Brazil has found a way to take solid human waste and combine it with clay to reduce that burden. Its reuse of the waste material serves another beneficial purpose; the material would otherwise be burned (using more fossil fuels) and buried (taking up landfill space, 100,000 tons in Brazil alone every year).

Picture from Science News Explores

Clay is made basically from 6 components, 7 if you count water:

• 50-60% silica (silicon dioxide, SiO2)
• 30% alumina (aluminum oxide, Al2O3)
• 8% iron oxide (Fe2O3)
• 5% magnesia (MgO)
• 1% lime (calcium oxide, CaO)
• 1% organic matter

Alumina makes them moldable, silica binds to alumina for strength and to prevent cracking, shrinking, and warping. Lime and iron oxide help in the binding process, and the iron adds color. Magnesia adds a yellow color and reduces shrinkage. Organic matter is inevitable and adds unwanted porosity.

Dr. Tuani Zat and colleagues from the Department of Structures and Civil Construction, Federal University of Santa Maria, Brazil have come up with a method to improve the composition by adding human waste. Not raw feces, but sludge, which is the end result of processing in a wastewater treatment plant. Sewage is filtered then shredded in a comminutor before being sent to a settling tank to separate liquid from the biosolid known as sludge. (In the diagram below, you see that in the lower left. Additional steps will aerate the liquid layer, in the top half of the diagram, to remove dissolved gases and break down organic debris.)

wastewater treatment process (Brittanica.com)

Raw sludge is further treated and then disposed by dumping into the ocean, fertilizing farms, or burying in landfills after pathogens are killed with the addition of quicklime. But Zat decided that this dried human waste might be a valuable addition to brick clay because in addition to the organic material, it contains silicon, aluminum, and calcium. Baking the mixture with clay would effectively kill any bacteria and parasites and destroy viruses.

Sludge ready for disposal (Science New Explores)

Ceramics around the world use sludge mixed with clay, too, with the amount of sludge varying from 2.5% to 20% as a wet material. The amount of organic material in sludge is what affects how well it will bind to the clay particles, and sludge from different populations of people do not have the same composition. So, Zat and her team tested various mixtures to make bricks. Another Brazilian team measured the range of particle sizes of clay and human sludge. The graph below shows that clay has many more particles less than 0.08 mm in diameter, and that is good because those can surround the larger sludge particles to hold them together when heated.

Analysis from Brazilian researchers in 2020 (Journal of Building Engineering)

That other Brazilian team tested mixtures of sludge and clay to assess how economical it would be for brick making. They also compared different baking temperatures and found that a fairly low temperature could be used. Regular bricks cost about $0.16 each to make, but when mixed with sludge, and accounting for energy savings of materials and lower heat, they were able to make comparable quality bricks for $0.025 per brick. So, Zat's team was on the right track.

A combination of 15% sludge and clay were used by Zat's team, and researchers elsewhere found similar results to make useful bricks. Some dried the sludge first, and then filtered (sieved) it and clay to a certain particle size maximum before adding water and then molding & baking.

From a Moroccan study in Cleaner Engineering and Technology, 2021

Another item in the original article describe how sludge can be used to make a cement replacement for building concrete, too.  This would afford savings in the worldwide construction industry as well.

Here is a cool YouTube video showing how bricks are made from start to finish.

5-minute YouTube video

What's Up With Mars?

People have been looking at Mars for millennia. In 1609, Galileo was the first to look at it with a telescope. Italian priest and astronomer Angelo Secchi was among the first to draw pictures of its surface in 1858. He drew what he called canale (plural canali), which just mean "channels" to him. Another Italian astronomer Giovanni Schiaparelli also made sketches of the canali and even gave names to various geographical structures that he saw in 1877. The word was misinterpreted by American Percival Lowell as "canals" when he made his own observations in 1894, and this was the first time the notion of irrigation structures by intelligent alien life was proposed.  We've come a long way since then.

Schiaparelli's map of Mars geography (Wikipedia)

Astronomers around the world had an active interest in studying Mars, but it was only in 1954 that the International Mars Committee was formed to coordinate observatories around the world in their studies. Three years later, the Soviet Union put Sputnik 1 into orbit around the Earth as the first artificial satellite, and in 1959 it landed the first manmade object Luna 2 on the Moon to measure radiation, magnetic fields, and the solar wind. It was the United States, though, that successfully sent the first exploration vehicle to Mars.

You can read about all successful and failed attempts to visit Mars by all countries at this link. The rest of this blog article will deal only with the 21 successes and what we have learned. Yes, that many! Get ready to read about Russia, the U.S., India, China, the United Arab Emirates, and the European Union.

1 - NASA's Mariner 4 (launched November 28, 1964) reached Mars on July 15, 1965 and performed a flyby to gather data and take photos. 

Images of Mars from Mariner 4

2 - Mariner 6 and 7 were the next successful flights, and both were flybys, too, in February & March of 1969. They flew over the Martian equator and south pole to examine the atmosphere and the surface features. Their pictures of the dark areas confirmed that there were no canals.

Mariner 6 (Wikipedia)

3 - NASA's Mariner 9 orbiter arrived on November 14, 1971, becoming the first spacecraft to orbit another planet. It paused for 2 months to allow a planet-wide dust storm to settle, then took photos and measurements. After almost a  year, it had monitored 85% of the surface.

Image from Mariner 9 (Wikipedia)

4 - Two weeks later, on November  27, 1971, the Soviet Union managed to get its Mars 2 orbiter, lander, and rover to the fourth planet. Sort of. The orbiter made 362 orbits and sent back data on gravity and magnetic fields plus 60 photos, but the lander with its attached lander crashed. Its twin Mars 3 arrived in December, 1971, and the orbiter lasted for 20 orbits. The landing package was the first to soft land on Mars, but the lander lost communications in less than 2 minutes, so the rover was unable to be deployed.

Mars 2 orbiter/lander/rover package (Wikipedia)

5 - The Soviet Mars 4 failed to orbit and could only fly by, sending back some pictures in February, 1974. The Mars 5 orbiter arrived also in February, 1974 and remained in orbit where it measured gamma rays and surface temperatures for 16 days out of the planned 3 months. The next two attempts were scheduled as flybys, Mars 6 and Mars 7. The Mars 6 flew by, but its lander crashed. Mars 7 took solar measurements, but its lander misfired and is now in orbit around the sun.

Mars 6  flyby/lander package (Wikipedia)

6 - The U.S. made the first actual successful landing with Viking 1 on July 20, 1976 which operated for over 6 years. Its orbiter relayed 57,000 pictures to Earth, and the lander conducted 3 experiments on soil samples to test for life. Results: inconclusive. The Viking 2 spacecraft arrived on August 7, 1976 and deployed its lander on September 3. The orbiter made close approaches to the moon Deimos and was turned off on  July 25, 1978. The lander performed elemental analyses of the soil and similar tests for life until its batteries died on April 12, 1980.

First color view from Viking 1 lander (Wikipedia)

7 - The last successful Soviet explorer was Phobos 2, which was intended to examine the moon Phobos more than Mars itself. Computer failure allowed it to make only 3 passes by the moon, but it took 37 pictures covering 80% of it. It arrived on 29 January 1989, and the attempt to put 2 landers on the moon failed when communications were lost on 27 March 1989.

8 - On 11 September 1997, the U.S. placed into orbit the Mars Global Surveyor, which lasted for 10 years in orbit. To achieve that, it was the first spacecraft to use aerobraking, where it made several passes through the atmosphere to slow it down. The MGS took many pictures (including the famous "face") and was the radio relay to Earth for future landers Spirit and Opportunity until 2006. 

Image of MGS (space.com)

9 - The Pathfinder was America's next step in Mars exploration in 1997. It was built cheaper by virtue of its landing process. A capsule descended on a parachute until a certain point, then its heat shield was ejected from below to allow for a lander/rover package to unwind on a cord. Before hitting the ground, the capsule fired retro rockets to slow it down even more. A series of balloons surrounding the lander/rover were inflated, and then its cord to the capsule was released. The lander/rover was protected inside the cushioning effect of the balloons until it stopped bouncing. After the balloons deflated, arms on the lander peeled them away, and its radio and camera unfolded. Inside, the rover Sojourner then rolled out to explore as the first rover on Mars. Watch the animation below showing this landing.

From YouTube

Sojourner contained instruments that let it analyze mechanical, geochemical, and evolutionary history of the land, and it had 3 types of cameras. It roamed about 100 m (330 ft) in total, less than 12 m (39 ft) from the Pathfinder station itself, and in its 83 days of operation, it relayed 550 photographs to Earth. The lander made over eight million measurements of the atmospheric pressure, temperature and wind speed as well as analyzed the airborne dust particles.

Sojourner rover examining a rock (Wikipedia)

10 - Four years after Pathfinder, the U.S. placed another spacecraft, Odyssey, into orbit on October 24, 2001. After aerobraking for 76 days, it was ready to work on February 19, 2002. Its thermal imagers and light sensors located bulk water ice under the surface at the equator. It is still in service feeding data for future programs, and it is expected to run until 2025.

11 - The European Space Agency placed its orbiter Mars Express around the red planet on December 20, 2003. It contained the Express orbiter and the Beagle 2 lander made it to the surface but failed to open its solar panels, so communication with it were lost. The orbiter found ice in the south pole that was 85% carbon dioxide ice and 15% water ice. It also has found various important compounds in rocks and the air. It should remain operational until 2035.

12 - NASA successfully planted two rovers, Spirit and Opportunity, on Mars in June and July, 2003. Spirit stayed active for over 6 years and covered 7.73 km (4.8 miles), both far exceeding expectations. Opportunity operated for 14 years, 138 days (57 times its designed lifespan) and covered 45 km (28 miles) before getting stuck.

Image of Spirit and Opportunity (Wikipedia)

13 - NASA's Mars Reconnaissance Orbiter (MRO) was intended to search for water on Mars. It reached orbit on March 10, 2006 and is still operational. It took over for Pathfinder as a relay station for Spirit and Opportunity. NASA also successfully placed its sixth lander, Phoenix, on Mars from May 25, 2008, to November 2, 2008. Its duties were to assess the local habitability and to research the history of water. It landed like the Viking landers, with a parachute and retro rockets, unlike Pathfinder. It was the first to land near any of the poles. In one of its experiments, it scraped the dirt, found subsurface ice, and monitored it evaporate to demonstrate its chemical composition. It was operational for 161 days (expected 90) until a sandstorm covered its solar panels.

Phoenix landing and results of subsurface ice evaporation (Wikipedia)

14 - Next, NASA executed a risky landing procedure for the Curiosity rover of the Mars Science Laboratory (MSL) on August 6, 2012. Because it was meant to collect massive amounts of data in preparation for future manned landings, Curiosity had more than ten times the mass of scientific instruments as Spirit and Opportunity, was twice as long, and was five times heaver (899 kg (1,982 lb)), so the balloon cushion was not an option. Instead, NASA developed a "sky crane".

Sky crane landing operation after parachute is ejected (spaceflightnow.com)

   

Curiosity was designed to operate for 687 days and cover an area of 5x20 km (3.1x12.4 miles). Eleven years later, it is still there providing data.

15 - India got into the space game with its Mars Orbiter Mission. It entered orbit on 24 September 2014.  Its mission concluded on September 27, 2022. Goals: atmospheric studies and mapping.

16 - MAVEN  (Mars Atmosphere and Volatile Evolution) is an ongoing U.S. orbiter project that began on September 22, 2014 and is still operational. Its goal is to  study how atmospheric gases are lost to space.

17 - The ExoMars Trace Gas Orbiter is a joint effort by the ESA and Russia.  It entered orbit on October 19, 2016 and is still operational, although its Shiaparelli lander crashed. Its goal is for a better understanding of methane (CH4) and other trace gases.

18 - America's InSight (Interior Exploration using Seismic Investigations, Geodesy and Heat Transport) lander landed on November 26, 2018, and its last contact was December 15, 2022. It was meant to study the deep interior of the planet.

Artist rendering of InSight (Wikipedia)

Two probes MarCO A and MarCO B  (Mars Cube One) launched on the same rocket as InSight but separated soon after launch to travel independently. Their purpose was to  test new miniaturized communication and navigation technologies as InSight landed. These were the first CubeSat (cube-shaped satellites) used outside Earth orbit. Each was only 10×20×30 cm. 

MarCo A and B design (Wikipedia)

19 - Hope is the name for the orbiter still in operation and put up by the United Arab Emirates on 9 February 2021. Its goal is to study daily and seasonal weather cycles, weather events in the lower atmosphere such as dust storms, and how the weather varies in different regions.

UAE Hope (Wikipedia)

20 - China joined the space race to Mars in 2021 with a complex of orbiters and landers. The Tianwen-1 ("heavenly questions") orbiter entered orbit on February 10, 2021 and is still operational. It was intended to study surface and subsurface geology, atmosphere, and presence of water. Its Tianwen-1 lander made landfall on May 14, 2021.  From the lander, the Zhurong rover (named after a Chinese mytho-historical figure associated with fire and light) was deployed on May 22, 2021 and is still operational. 

Tianwen-1 package of orbiter and lander/rover (Wikipedia)

The rover set up a remote camera on the surface, while in space In September 2020, the Tianwen-1 orbiter deployed the Tianwen-1 First Deployable Camera (TDC-1). It is a small satellite with two cameras to take photos of and test the radio connection with the orbiter.

21 - Finally, the U.S. Perseverance lander and Ingenuity helicopter rover are the most recent Mars projects to date.  They landed as a package using the sky crane technology on 18 February 2021. Ingenuity was deployed from Perseverance on 3 April 2021 and made its first flight on April 19, 2021. Since then, it has made 54 missions despite the expected five. Both instruments are still operating.

Landing sites over history (interactive map on Wikipedia)

Here is a good NASA website with many of the explorations mentioned above.

In case you're wondering how big these landers and rovers are, here's a really cool 5-minute YouTube video with background music, showing all landers (successful or otherwise), their moving parts, and their relative size to a person.

Also, see this 1898 newspaper article on Martian canals.