A story of insulin and the treatment of diabetes 

There are two main types of diabetes: type 1 and type 2. With type 1, your body stops making insulin due to an autoimmune reaction (the body attacks itself by accident) against beta cells in the pancreas. With type 2, it still makes insulin, but your body doesn't use it efficiently. So, with type 1, you need insulin injected into your body daily or you will die. You may not even know you have type 2 because of a range of severity; it begins slowly over time and affects mostly adults. Women may also contract diabetes when they are pregnant.

Pancreatic islet cells from human stem cells used to treat diabetes (sciencenews.com)

The number of people in the world with type 1 diabetes was 9 million in 2017 (WHO), with most living in high-income countries. There is no known cause. Overall, including type 2 diabetes, the number rose from 200 million in 1990 to 830 million in 2022. Over 2 million died in 2021, and other consequences of diabetes can be blindness, kidney failure, heart attacks, stroke and lower limb amputation. Clearly, controlling diabetes is very important across the globe.

The pancreas is the gland that makes insulin, which is a hormone. The pancreas is also an organ that is part of the digestive system because it makes various enzymes that break down food in the first section of the small intestine called the duodenum. Insulin is made by beta cells, which are part of a cluster of cells called the Islets of Langerhans.

Location and anatomy of the human pancreas (Wikipedia)

The body breaks down carbohydrates, fats, and proteins into smaller chemical compounds that become easier for cells to use. The small intestine absorbs most of the food breakdown products, and special cells help these nutrients cross the intestinal lining so they go into the bloodstream. From there, the blood carries them to places where they are used or stored. Carbohydrates are broken into sugars like glucose, proteins are broken into amino acids, and fats are broken into fatty acids and glycerol.

Inside the small intestine, the inner layer is made of tiny folded ridges called villi. Each of these villi has even more, smaller ridges called microvilli. From there, the epithelial cells take glucose from the intestine and pass it to capillaries or the lymph system.

Cross-section of the small intestine, closer look at the microvilli and glucose uptake

(Modified from Wikipedia)

Glucose is your body’s main source of energy. Insulin helps it to get inside cells so they can use it. Below are 2 diagrams to show this. The one on the left is a simplified one; the one on the right shows more details.

How insulin acts to bring glucose into cells (modified from news-medical.net)

• Left diagram: Insulin and glucose have separate receptors that attach to them on a cell surface. Insulin binds first and opens the glucose receptor to let it enter.
• Right diagram: (1) insulin binds to its receptor. (2) that causes the receptor to change on the inside portion. (3) The change sends biochemical signals to a glucose transporter called GLUT4 inside cells. It floats on standby until this happens and is attached to a membrane bubble called a vesicle. (4) When insulin receptors change inside the cell, a signal is sent to move the GLUT4 vesicle to the cell membrane where it fuses. Now, GLUT4 acts as a gateway to let only glucose inside the cell.

How did we learn about the pancreas and insulin?

An Egyptian document described a condition where patients produced excessive urine. Physicians of the 5th and 6th century BCE first noticed that some people had urine with a sweet taste and called the condition madhumeha ("honey urine"). Chinese doctors described a "wasting thirst" which included excessive thirst and urination. The Greeks named the condition diabetes from a word meaning "to pass or run through". Diabetes mellitus was given as the full name from the Latin word meaning "honeyed" or "sweet". But until the late 19th century, the pancreas was not thought to be involved.

In 1869, Paul Langerhans, a German medical student, discovered two different groups of cells in the pancreas: one produced fluids for digestion, and the others (named the islet cells after his name) which had an unknown function. But, in 1889, two German scientists Oskar Minkowski and Joseph von Mering removed the pancreas from a dog and observed that the dog then developed diabetic symptoms, suggesting it was an important organ for controlling blood sugar. Eugene L. Opie as a medical student at Johns Hopkins University noticed in 1900 that islet cells were damaged in people who had diabetes (probably type 1), so the islet cells were thought to produce insulin. From 1899 to 1906, many researchers investigated the different cell types in the pancreas by staining them with different chemicals. In 1906, pathologist and anatomist Lydia DeWitt tied off the pancreatic duct in cats and noticed that even though this caused damage to the pancreas and its digestive function, it didn't stop glucose metabolism (by insulin, which had not yet been isolated). Islet cells secrete it directly into the bloodstream from surrounding capillaries. These and other findings narrowed down the source for insulin.

Minkowski (left) and von Mering (right) (from the FDA "100 Years of Insulin")

Canadian physician Frederick Banting and University of Toronto researcher John Macleod were the first to extract insulin successfully in 1921 from islet cells, not whole pancreases. They worked initially on live dogs as sources, then switched to fetal calves from a slaughterhouse. Banting and Macleod's team was using the name "isletin" for the chemical they had isolated because it came from islet cells in the pancreas. But the term "insulin" was being used in Europe more commonly since 1916 when Belgian researcher Jean de Meyer, had already proposed the term “insulin”, from insula (Latin for “island,”). 

Notebook entry from Banting's lab with dog subject. Note the word "isletin" used. (Harvard Countway Library)

The work was done at Connaught Laboratories, part of the Department of Hygiene at the U of Toronto. After promising results of injecting the insulin into dogs and rabbits, the first human test subject was in 1922. 

(left) Banting's laboratory; (right) Connaught Laboratories insulin extraction equipment (University of Toronto)

But their method (patented in 1923) to produce insulin couldn't provide a large quantity. American pharmaceutical giant Eli Lilly and Company took over, and with its access to slaughterhouses, they were able to source thousands of pounds of pig and cattle pancreases as sources of insulin. Their product Iletin was the first commercially available insulin. Even though it was a mixture of pig and cattle insulin, it was still effective in humans, and the mixture's content differed depending on which animal pancreas was more available at the time.

Package of Iletin from Eli Lilly (collection.sciencemuseumgroup.org.uk)

In the 1940s-1950s, pig-derived insulin was found to have fewer allergic reactions, and by the 1970s-1980s most or all of Lilly's insulin came from pig pancreases. The next phase in insulin production came in 1975 at the birth of the recombinant DNA revolution. The Swiss company Ciba-Geigy created the first synthetic insulin, and it was from human DNA. In 1978, Genentech demonstrated how this could be made by E. coli bacteria after the gene was inserted. The first human trials took place in 1980. The next 5-6 years saw several companies learning to produce it this way.

One-minute explanation of making recombinant human insulin. (YouTube)

Currently, cellular production is the commonest method to produce recombinant insulin. E. coli and two types of yeast contribute equally to the world's supply. Three pharmaceutical companies manufacture 90-96% of it, making marketing and sales concerns problematic.

There are 5 types of insulin used by patients depending on a variety of factors. They involve how fast they take effect and how long they stay active: rapid-acting, short-acting, intermediate-acting, long-acting, and ultra-long-acting. Type 1 diabetes patients usually need injections 1-2 times a day. Type 2 patients might need only the long-acting type. To get it into the body, there are 3 basic devices: syringe, pen, or subcutaneous pump. There is even an inhaler with powdered insulin.

Insulin delivery systems

A fifth method is experimental at this time. Instead of injecting or inhaling insulin itself, the new treatment involves transplanting insulin-making cells. Here are three examples.

• CellTrans, Inc. Lantidra is a recently FDA-approved (2023) cell therapy which takes pancreatic cells from deceased donors and infuses them into type 1 diabetics. 

• ViaCyte. Another proposed cell therapy method is to put cells in a membrane capsule which is implanted in the body. These are stem cells from embryos that were stimulated to become pancreatic cells. The membrane is like Gore-Tex and allows blood vessels to grow across the walls and through the cell mass, but not to allow the body's immune system to contact the encapsulated cells.

Encapsulation system from ViaCyte (Cell Reports Medicine, 2021)

• Vertex Pharmaceuticals. A third cell therapy system involves taking healthy adult bone marrow donors' cells, isolating mesenchymal stem cells, and programming them like the embryo stem cells mentioned above, so that they transform into beta-like cells which respond to glucose in the blood. These cells naturally settle in the liver instead of the pancreas.

Schematic of removing bone marrow cells to produce cells transformed for transplantation

(BioMedical Research & Therapy, 2021)

Many factors are involved in deciding which treatment for diabetes is best.

• efficacy of the type of insulin
• ease of use (for example, a pen vs an insulin syringe)
• cost (varies by country, but when immunosuppressive drugs are needed for cell therapy, the price is very high)
• availability (sometimes where ethical or religious concerns about the source of insulin or stem cells blocks access)
• patient conditions (age, type, and extent of diabetes)
• doctors' advice 

Micro-sparks between water droplets may have started life on Earth

Link to article

How did life begin on Earth? Nobody knows with a high level of certainty. Hypotheses have been around for a long time. Basically, what is needed is the right chemicals to mix, a way to mix them, the right atmospheric conditions, and energy to boost their reactions. And time, lots of time. The most common elements needed are carbon, hydrogen, oxygen, nitrogen, sulfur, and phosphorus. This article will talk about only the energy sources researchers have speculated could help make the building blocks.

In the 1920s, Soviet biochemist Alexander Oparin and British scientist J.B.S. Haldane came up with concepts to explain how life might have started from the raw materials on the planet. Both thought that it all started in the oceans and used lightning and UV light from the sun as energy sources. Oparin described organic molecules formed in the ocean into droplets (coacervates) where chemical reactions could take place more efficiently. Haldane described the overall situation as a "hot dilute soup" (later changed by various sources into "primordial soup") and focused on the possible chemical reactions in general. 

Coacervates: micro-droplets of organic material in water (Wikipedia)

At the time, scientists had a poor understanding of the chemistry involved in geology. Most felt that since the atmosphere today has a lot of oxygen, it must have always had it. But Oparin and Haldane disregarded that idea. Some pointed to the fact that oxygen is necessary for fire, not just life. Microbiology was not as advanced as today, so they also thought that anaerobic bacteria (bacteria that cannot live in the presence of oxygen) were just defective life forms. 

Geochemistry results in the 1930s-1950s showed that extremely old mineral deposits like iron did not contain oxygen. That suggested the atmosphere lacked oxygen, and that's when origin of life hypotheses began using that idea as background for further studies.

Oparin and Haldane proposed only hypothetical notions; they conducted no experiments. Twenty years later in 1952, PhD student Stanley Miller and his mentor & Nobel laureate Harold Urey put together a lab experiment to test the Oparin-Haldane concept. Using information they thought to be accurate at the time about the ancient Earth's atmosphere, they did the following. Methane, ammonia, and hydrogen were sealed in a 5-liter glass flask to simulate the atmosphere at the time. They ran electrical sparks through it to simulate lightning that would have occurred. This was connected to a 500-milliliter flask half-filled with water that was heated to boiling to simulate the oceans (minus salt content). Water vapor flowed into the atmosphere flask. Water vapor that cooled and condensed flowed into a trap where samples could be taken. If any chemicals in the atmosphere mixed with the water vapor, they could be analyzed for changes. In just one day, trap water was pink; after a week, it was dark red and cloudy. 

Image from Wikipedia

Five amino acids were found. At the same time (1952-1953), other investigators were conducting similar experiments. One found no change, and another found a sticky resinous mixture too complex to analyze. Miller repeated his work in 1957 with a different atmosphere, based on new assumptions (like what gases might have come out of volcanoes).

• 1952 atmosphere: methane, ammonia, hydrogen, water
• 1957 atmosphere: different combinations of methane, ammonia, hydrogen (or nitrogen), water, hydrogen sulfide, carbon monoxide

Stanley Miller and his apparatus (From Astronoo.com)

He found 22-23 amino acids in his mixture, along with hydrogen cyanide (HCN) and chemicals called aldehydes and other organic materials. HCN is a very reactive molecule important in forming other organic (carbon-containing) compounds.

After Miller's death in 2007, Professor Jeffrey Bada inherited Miller's equipment and found samples from the 1952 work. Analysis showed the old mixture now had over 20 amino acids.

Bada holding a vial containing Miller's original samples (Scripps Institution of Oceanography)

Since Miller's ongoing work from the 1950s and beyond, Bada and others conducted additional experiments with different conditions, usually using electrical sparks as the energy source, but some also used just heat. Ultraviolet (UV) radiation from the sun likely had a stronger effect on an early Earth than it does now because there was no ozone layer back then to block it. It is thought to be a strong influence on creating HCN, for example.

• Joan/John Oró (1961) showed that HCN could form building blocks of nucleic acids leading to DNA & RNA. He and colleagues also in 1971, showed the high abundance of amino acids and various hydrocarbons in the Murchison meteorite in 1971. 
• Carl Sagan and Bishun N. Khare (1979) examined the tar-like residue from experiments such as Miller's (and their own where they used UV radiation). They named it tholins, and it is a mixture of many polymers that can be broken down into many types of organic molecules (sugars, amino acids, nucleic acid building blocks).
• In 2012, Sarah Horst and her colleagues treated gases found in Titan's atmosphere with UV radiation and generated tholins. They also found that these could make amino acids and nucleic acid precursors.

Carl Sagan (The Conversation)

Another hypothesis with a different energy source concerns deep-sea hydrothermal vents. These are sites of some of the oldest fossils in the world and are found everywhere.

Locations of known hydrothermal vents (yellow circles) (Martin et al., 2008; Nature Review)

The heat (60°C-405°C) from these alkaline vents comes from underground magma mixing with seawater that seeps through pores. It comes out mixed with many minerals and gases, and temperature gradients form between the vent and 2°C seawater. The heat plays a minor role in providing energy for the chemical reactions. It is the chemistry itself that is so reactive that changes happen on their own. The smoky plumes eventually spread sideways for thousands of kilometers before settling. Inside the vent chimneys, pockets can form with isolate chemical reactions and provide more concentrated conditions.

A hydrothermal vent, one of many found all over the world's seas (From Oregon State University, SciNews)

The smoky plumes eventually spread sideways for thousands of kilometers before settling. Inside the vent chimneys, pockets can form with isolate chemical reactions and provide more concentrated conditions.

Diagram of hydrothermal vent showing seawater carrying minerals (Astrobiology, 2023)

Finally, aside from lightning, UV radiation, heat, and direct chemical reactions underwater, another source of energy has been suggested to produce organic molecules. In shallow pools, a combination of UV radiation, mild underground heat, and a wet/dry cycle has been shown to produce organic molecules. Montmorillonite clay and mica are the two most common examples of surfaces where these pools might form. Both are composed of aluminum silicates but are different enough to give researchers separate ideas on forming primordial compounds. The clay swells and shrinks a littlein wet/dry cycles (such as those found in caves, where montmorillonite is commonly found), but mica does it more; any trapped organic molecules might be mixed better with that mechanical action. Clay's sodium and calcium are better for polymerizing reactions than the potassium in mica, but mica holds the compounds more tightly. Each has been shown to form the following molecules.

• Clay and mica: RNA precursors
• Clay: peptides and nucleobases
• Mica: protocells and flavin mononucleotide (a molecule that helps chemical reactions take place)

Cross-section of mica sheets showing how thin spaces and large gaps can hold molecules

in concentrated pockets for better reactions (Hansma, 2022; Biophysical Journal)

Recently, Richard Zare and his team at Stanford University have come up with another means to inject energy into the process of making organic molecules. They feel that lightning strikes may not have been frequent enough in an early Earth, and that even when they did occur, the changes in atmospheric components caused by these infrequent electrical discharges would simply be diluted in the oceans and washed away. 

We know that regular lightning interacts with nitrogen (N2) in the atmosphere to make mostly nitrates (NO₃^-) and to a lesser degree nitrites (NO₂^-) by combining it with oxygen and water. These later combine with water vapor to form nitrous acid (HNO₂) or nitric acid (HNO₃). There was less oxygen in the young Earth atmosphere, but lightning would still have made changes. 

And some have even speculated that lightning caused by volcanoes creates more HCN than from regular cloud lightning. The reason is that there is more concentrated starting material in volcano plumes where the lightning takes places. Ash within a volcanic plume creates static electricity when its particles rub together, thus generating lightning.

Volcanic lightning from Mount Shinmoedake, Japan, 2011 (Reuters)

Cloud lightning is formed when a mass of negative and positive charges build up in the top and bottom of storm clouds. These charges are formed when ice crystals (0.01-0.5 mm diameter) bump into graupel (2-5 mm diameter) and transfer an electron. Graupel is a soft hail-like ice crystal that falls through supercooled water and gets coated in a frosty layer. It is usually negative and heavier, and air currents send the positive lighter ice crystals higher into the cloud.

Graupel (left, HowStuffWorks) and its formation in a cloud (Saunders, 2008; Space Science Reviews)

As the negative charged particles increase on the bottom of a cloud, they send out an invisible "ladder" of electrons, this attracts positive ions from the ground, and a connection is made which is seen as a bolt of lightning. Similar things happen within a cloud or from cloud to cloud.

Lightning formed between the negative "ladder" and ground positive charges (NOAA.gov).

Instead of volcanic or regular cloud lightning, Zare has recently presented data in April 2025 on "microlightning" as an energy source to form organic molecules. Zare read a 2024 report from a former colleague Anubhav Kumar from the Indian Institute of Science Education and Research. Kumar and his researchers noticed that microdroplets of water emitted from steamers, humidifier, and spray bottles changed atmospheric nitrogen (N2) the way lightning did. They determined it was due to a weak electric discharge (corona discharge) at the air–water interface. 

Pure water has no electrical charge, but tiny water droplets can acquire a positive or negative charge. In 1890, German researchers Julius Elster and Hans Geitel followed up on Elster's 1879 doctoral thesis which examined electrical phenomena of finely dispersed liquids. Together, without any knowledge of electrons, they they developed a theory of the electric processes in thunderstorm clouds and measured a negative charge 500 meters above a waterfall, suggesting the misty water droplets had a charge on them.

Elster and Geitel, and their electroscope to measure precipitation electricity (History of Geo- and Space Sciences)

Zare and associates conducted 2 experiments. In the first, they built a chamber and filled it with methane, nitrogen, carbon dioxide, and ammonia, then used a nebulizer to inject water in microdroplets. Liquid samples were removed, but gaseous samples were analyzed directly in the chamber with a device called a mass spectrometer.

Zare's experimental setup to detect organic molecules formed 

from water mist and microlightning (Science Advances, 2025)

The second setup involved suspending a drop of water with sound waves, then using the same waves to split smaller drops from the main one. A photon detector measured light coming off the different sizes of drops when they collided.

Suspending a drop of water and measuring luminescence (Science Advances, 2025).

• Results from the first experiment showed the production of glycine (an amino acid), uracil (a building block of nucleic acids), urea (useful in making more amino acids), and organic molecules with cyanide components (cyanoacetylene, cyanoacetaldehyde, and cyanoacetic acid).
• In the second experiment (conducted in the dark with high-speed cameras), they saw flashes of light when large and small microdroplets of water touched each other.

Open to full screen to see blue flashes of microlightning near the center of the screen.

These results are not conclusive, but they strongly suggest that sprays of water can generate electric micro-sparks similar to lightning and transform the environment arouund them. Thunderstorms, ocean waves, raindrops hitting the ground, waterfalls, and other mechanisms generate microdroplets which can all contribute to a potential to ionize atmospheric gases. Such sources are more widespread than random lightning bolts and might produce more organic molecules in a wider area than localized lightning strikes. They likely contributed to the effects of cloud and volcanic lightning, UV radiation, and the wet-dry cycles on clay surfaces to bring about building blocks of life in a young Earth. 

What's more, these may all serve as models for what could happen on other planets as well, depending on the chemicals present and the right temperatures. And, given enough time.