Humble bacteria dominated an agricultural revolution.

In Europe, flour is the most important food raw material, but for more than 200 years, flour merchants have had a headache for a big fleshy bug. They are the larvae of the Mediterranean powder borer, two centimeters in size, quietly hiding in the warehouse where the flour is stored, devouring the flour uncontrollably. They breed desperately in warm flour warehouses and bakeries, then feather, mate quickly, leave the next generation, and then die-it takes only seven weeks to reproduce, with each female laying nearly 600 eggs.

It doesn't matter if you eat the flour and leave behind dead skins, corpses, and feces. The real trouble for flour makers is that when processing flour, their fat bodies fit into the machine along with the flour and then jam the parts, causing damage to the machine or factory shutdown-in an industrial society, affecting production is really the biggest headache.

Don't think that making flour is a small business. It was a flour factory at the beginning of the last century. Picture: The book of wheat-an economic history and practical manual of the wheat industry (1908)

Since 1879, these insects have been plaguing the whole of Europe, leaving flour merchants helpless. In 1927, Bacillus thuringiensis was finally isolated from the dead larvae of the Mediterranean powder borer, Chilo suppressalis. This success made humans really aware of the important role of Bacillus thuringiensis, and finally stopped letting the bacteria slip through their fingers as they did on previous occasions.

Gram-stained Bacillus thuringiensis under a 1000-fold optical microscope. Picture: Dr. Sahay / wiki commons

A gift that was almost missed.

The Japanese have dealt with this bacteria since the end of the 19th century. At that time, Japan's sericulture industry faced an unprecedented blow-the seemingly healthy silkworm suddenly raised its front body, stopped eating mulberry leaves, swollen its chest and spit out liquid as if an alien was about to break its chest at any time. As long as a few hours, these silkworms will suddenly fall dead paralyzed, not long after the death of the body becomes soft, rapid decay, a large amount of dark brown liquid from the body. Even the silkworms, which are very lucky not to die, develop very slowly. For a while, Japan's silk industry was overshadowed by death.

Workers prepare a cocoon farm for silkworms that are ready to spin silk at a Japanese silkworm farm at the turn of the 19th century and the 20th century. Picture: Boston Public Library

In 1901, bacteriologist Fanyin Shidu isolated a rod-shaped bacteria from the dead silkworm, which he named Bacillus sotto according to the disease. No one knows why Shi du Fanyin put the matter aside and did not continue to study, and his findings were never mentioned again.

Ten years later, Ernst Belliner, a German microbiologist, rediscovered the bacteria in the Thuringia region of the German Empire. Bellina republished the species in 1915, naming it after the site of discovery and calling it B.thuringiensis, which is still in use today.

A street view of Elfort, the largest city in the Tulingen region, in 1915. Picture: Public domain / wiki commons

However, I doubt that the people who drafted the Chinese name of this species did not realize that the adjective was actually a place name, so they made it "Bacillus thuringiensis" according to the British pronunciation of thu-run-gien.

Unfortunately, although Belliner described Bacillus thuringiensis in great detail and even pointed out that there were many protein crystals in these bacteria-these crystals were named parasporal crystals like a regular diamond, however, he actually lost the culture medium. As a result of the accident, Bacillus thuringiensis was shelved again for another 10 years.

Bacillus thuringiensis under electron microscope. The c in figure A corresponds to the crystal in the cell. Photo: Swiecicka Iet al. (2008) Appl. Environ. Microbiol.74 (4): 923930

Safe poison

With the success in 1927, human research on Bacillus thuringiensis finally entered the fast track. It was soon discovered that Bacillus thuringiensis was highly specific-Lepidoptera insects were targeted by them.

At that time, Gypsy moths were raging in the forests of the United States, and the US government naturally became the first person to eat crabs. As soon as the Europeans saw it, they were happy to use the bacteria commercially.

Bacillus thuringiensis on sheep blood Agar medium. Picture: PHIL / CDC / wiki commons

In 1938, France launched the first commercially available Bacillus thuringiensis pesticide Sporine, which is designed to deal with succulent bugs that destroy the flour industry. From today's point of view, this pesticide can be described as "crude". It only dissolves Bacillus thuringiensis into the water.

Although crude, but easy to use, the water-soluble preparation of Bacillus thuringiensis was an important pesticide until the 1950s. Compared with chemical insecticides, Bacillus thuringiensis is not only easy to degrade, but also almost absolutely safe to animals and plants except Lepidoptera insects. Until today, when it is widely used in genetically modified technology, some radical "environmental groups" have reluctantly found that when mice are fed with Bacillus thuringiensis protein in "large doses" for a "long time", there is a risk of liver damage.

In 1998, a plane was spreading Bacillus thuringiensis in a coniferous forest in Oregon to deal with insect pests. Picture: public domain

However, the disadvantage of Bt protein is that it is easy to degrade. When the sun is bigger, the active ingredients in these pesticides will become invalid as soon as the ultraviolet rays are illuminated. In the face of more lasting and cheaper chemical pesticides, with the exception of a few farmers who insist on the so-called "green organic" in the hope of getting higher product prices, other farmers have basically switched to chemical pesticides.

In 1956, Canadian insect pathologist Thomas Angus first discovered that the insecticidal ingredients of Bacillus thuringiensis were hidden in the parasporal crystals found in Bellina. These crystals are actually protein crystals, and Angus has a nice name for the proteins that make up these crystals: Bt toxin.

The name translates literally as "Bt toxin", but now it is generally called "Bt toxin protein" or "Bt protein". The structure of this protein is so ingenious that it is nontoxic, so it is a big blame to call it a toxic protein.

Under electron microscope, the crystal of Bt protein in Bacillus thuringiensis. Picture: Jim Buckman / wiki commons

Of course, although it is non-toxic, when it enters the insect, under alkaline conditions, it will be activated by special enzymes in the digestive tract of Lepidoptera insects and become toxic substances. The activated toxic substances will destroy the cellular structure of insect intestines and eventually lead to intestinal perforation and enterolysis, resulting in a painful death.

However, under acidic conditions, the Bt protein is so unstable that when mammals eat it, they are hydrolyzed to seven, seven, eight and eight in the stomach. Even if a very small amount of Bt protein is lucky enough to enter the alkaline gut, mammals lack insect-specific enzymes that convert Bt protein into toxic substances, which makes it impossible for these proteins to escape being digested or excreted.

The birth of genetic engineering weapons

In the 1980s, the study of Bacillus thuringiensis toxic protein has been very mature, people finally found that Bacillus thuringiensis is actually an organism with a large number of subspecies, and each subspecies has different characteristics, will produce different proteins, may be aimed at different organisms.

The spatial structure of Bt protein. Picture: Lucena WAet al. (2014) Toxins6 (8): 2393-2423

Because they are present in crystals (crystal), these proteins are also named Cry proteins, such as the most famous Cry1Ab secreted by Kurstark subspecies. As more and more strains are detected and more and more Cry proteins are found, the scope of killing insects is naturally wider and wider, from the earliest Lepidoptera insects to the later Coleoptera and Diptera insects, more and more agricultural pests have encountered the corresponding "weapons".

A commercial Bacillus thuringiensis tablet used to control mosquitoes. Picture: Claus Ableiter / wiki commons

Because the proteins of these two families have one thing in common: blood to the target, it is safe and harmless to almost all other organisms, which makes the concept of "safe and efficient insect-resistant crops" very attractive. In 1985, the Belgian developed the world's first transgenic insect-resistant tobacco, and three years later, American companies successfully developed the first batch of insect-resistant cotton.

In the early 1990s, China suffered an unusually serious cotton bollworm disaster: in 1992, when cotton bollworm swept in, 150000 tons of pesticides were used but to no avail. Radar was used to monitor the flight path of the insects, and traps and intercepts were caught halfway. In the end, it still had little effect. According to conservative estimates, the direct economic loss in that year was at least 6 billion yuan, and the overall economic loss reached the level of 10 billion yuan.

Under the crisis, China began to plant genetically modified cotton produced by American companies in 1995 and in North China in 1997, with almost immediate results, and cotton production gradually returned to normal. Today, almost all cotton in China's cotton fields is genetically modified insect-resistant cotton.

The cotton field is about to have a bumper harvest. Picture: Kimberly Vardeman / wiki commons

Of course, in addition to providing timely help, genetically modified insect-resistant cotton also brings an unexpected extra benefit-a reduction in cost. This characteristic was already shown when insect-resistant cotton was first introduced into China. The pesticide cost of insect-resistant cotton is much less than that of non-transgenic cotton, reducing the number of applications, reducing labor consumption, and increasing production at the same time-generally speaking, technological progress has given human beings great convenience and economic benefits.

Ascending double spiral ladder

However, an awkward reality is that in nature, with a spear, there will inevitably be a shield. Just like antibiotics encounter resistance.

According to strict planting standards, when planting GM crops, it is necessary to plant a certain number of non-GM, non-insect-resistant "shelters". They will inevitably be eaten by a variety of pests, but their existence can effectively reduce the pressure on species selection and prevent the premature emergence of drug resistance.

The role of insect shelters is to allow more non-resistant insects to survive. Picture: syngenta-us.com

However, in many underdeveloped areas of the world and areas where agricultural land is scarce, "witty" farmers intentionally or unintentionally choose to ignore this rule. It seems that their land has produced higher returns, but, uh, more and more agricultural pests have developed resistance early under extreme selection, killing farmers and seed companies unprepared.

Of course, captivity is not a human character, and it was soon discovered that the weapons provided by Bacillus thuringiensis were not limited to the Cry tribe. Scientists have found another protein in the Israeli subspecies of Bacillus thuringiensis. Unlike the Cry protein, it is distributed in the cytoplasm (Cytoplasm) rather than in the crystal, so it is called the Cyt protein.

Cyt protein is very special, although it can bind to insect intestinal cell membrane like Cry, making a mess of insect field, but it is not related to Cry family proteins, and the specific mechanism of action is different.

Comparison of resistance of transgenic peanut leaves (left) and common peanut leaves to pests. Picture: Herb Pilcher, USDA ARS / wiki commons

Cyt proteins work by binding to phosphatidylethanolamine on the insect cell membrane, requiring no enzyme and simply rudely dissolving their cells directly. When it comes to toxin, Cyt is actually more appropriate. Their selectivity is achieved through another way-the proportion of phosphatidylethanolamine on the cell membrane of Diptera insects is more than half, so it is easy to be riddled with holes directly by Cyt, while in Lepidoptera insects that Cyt cannot kill, and in the cell membranes of our vertebrates, phosphatidylcholine is dominant-so although Cyt can occasionally bind to our cell membranes, it is still safe for us.

With two sets of antibiotics, we seem to have a way to do something about resistant pests. Just like in the hospital, encounter a kind of resistant bacteria, as long as you change the medicine, you can reshuffle the cards. Of course, Cyt still has its shortcomings, facing the helplessness of Lepidoptera pests, it will directly affect its scope of use.

An experimental field of genetically modified corn in Ohio, USA. Picture: Lindsay Eyink / wiki commons

In addition, there will be a corresponding complex process to reduce the production of resistant pests through two different resistant crops, and there is no way to stop "smart" farmers and "smart" seed companies from abusing them in series, leading to the birth of a number of Cry-resistant and Cyt-resistant "super pests".

Now, seed companies also seem to have encountered bottlenecks in the search for new Cry,Cyt, and GM crops don't seem to have much to do in the face of possible "super pests".

We sometimes feel that we have conquered nature, but we still have a long way to go in wrestling with nature.

This is the 148th article in the fourth year of the species calendar, from the author of the species calendar @ C.CristataX.

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Bacillus subtilis (Bacillus subtilis)