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Greatest Biotechnology Inventions

General

Top 25 Biotechnology Inventions – agricultural and medical

1) Domestication of 8 Neolithic founder crops

occurred in Mesopotamia from 10,500 BCE -7000 BCE: emmer wheat, einkorn wheat, barley, lentil, pea, chickpea, bitter vetch, flax. (flax, 3 cereals, 4 pulses). Collection and consumption of wild grains occurred for 100,000 years prior to agriculture. Crops are the greatest of biotechnology inventions.

These 8 crops formed the basis for agriculture

particularly of Mesopotamia, Egypt, India, Middle East, North Africa, and Europe.

World population was about 4 million persons in 10,000 BCE.

World population grew 60x to 250 million by the Roman empire (1 AD). From the Roman empire to now, population has grown another 30x to 7.5 billion. Domestication of rice in China occurred later in 9000 BCE.  Earlier harvesting of wild cereals and grain grinding technology dates to 21,000 BCE Israel at the Ohalo site of hunter-gatherer-fisher site on the Sea of Galilee.

Land requirements for agriculture are a fraction (<1%) that for hunter-gatherer societies.

The “first agricultural revolution” or Neolithic revolution transformed societal structure from a nomadic hunter-gatherer to an agricultural settled society.

The first civilization in Sumer Mesopotamia occurred around 4500 BCE, 5000 years after the Neolithic agricultural revolution.

World population increased 50% from 4-6 million from 10,000 BCE-4500 BCE.

Clearly, agriculture did not directly lead to civilization. 5000 years passed from the agricultural revolution before the first true cities appeared. Food production produced some excesses but with dramatically decreased food variety affecting nutrition. Since 1940, crop yields have increased 300% worldwide.

Plant agriculture ranks as the #4 Greatest Invention of All Time.

2) Domestication of livestock

based on DNA analysis: aurochs (now extinct ancient cattle), boar (pigs), sheep, and goats began around 11,000 BCE. Archaeological evidence dates: dog domestication (13,000-20,000 BCE), sheep domestication (9000 BCE in Middle East), goats (8500 BCE in Middle East), pigs (8300 BCE in Middle East), cow (8,300 BCE in Middle East), cat (7,500 BCE in Middle East), humped cow (6000 BCE in South Asia), Llama (4000 BCE in South America), horse (3500 BCE in central Asia), chicken 2000 BCE east Asia/Middle East), turkey (0 AD in North America), duck (1000 AD in east Asia/Middle East).

Livestock allowed the transition from hunter-gatherer society to a pastoral society and accelerated the transition to a settled agricultural society.

Pastoralism dramatically decreased necessary land requirements compared to hunter-gatherer societies but has greater land requirements than for strict agricultural societies. The Mongols of the 1300s were the last dominant pastoralist culture.

Modern pastoral societies tend to be monotheistic, patriarchal, land sharing, and semi-nomadic.

Milk, meat, hides, wool, sinew, and bones changed human existence. Domestication also brought a very significant disease reservoir with these animals to human existence. Livestock domestication ranks as the #5 Greatest invention of All Time.

3) Plow/Domestication of Oxen.

Scratch Plow (ard). Nearly as important an invention as the wheel/axle, the scratch plow first appeared in Czechoslovakia in 3500 BCE or Mesopotamia in 4000 BCE (Pryor, Fredric L. “The Invention of the Plow” Comparative Studies in Society and History, Vol 27, No 4 October 1985). Egyptians saw use a metal tipped scratch plow by 3500 BCE. Superseded only by data storage inventions of writing, printing, and computing the scratch plow is supremely important in ancient history. The scratch plow was at the heart of the big bang of 3500 BCE. Domestication of grains became widespread around 9500 BCE. However, 5500 years passed before civilizations began around 3500 BCE.

Why did the dawn of agriculture and crops not produce the rise of civilizations until 5500 years later?

Before the ard, scratch plow, farmers used stone hoes and wooden seed drills to plant, till, and grow their crops. Domestication of oxen occurred around 4000 BCE in the Middle East. The co-invention of the plow with the domestication of oxen is very similar to the co-invention of the wheel/axle with the domestication of the horse. With the oxen as a driving mechanism, beast of burden, the extremely physical nature of plowing could be done without excessive human labor.

Turning soil with the plow and oxen was a huge advance for crops in comparison to hand tools of hoes and seed drills.

Estimates of world population between 8000 BCE and 4000 BCE showed an increase from 4-7 million over 6 thousand years (before the invention of the plow) based on the US census bureau estimates at Census.gov “Historical Estimates of World Population”. Between 4000 BCE and 3000 BCE, world population doubled again from 7 million to 14 million.

The repeated doubling of the world population over one thousand years was likely related to the plow and the expansion of agriculture.

The world population doubled again between 3000-2000 BCE to 27 million. The world population doubled again between 2000-1000 BCE to 50 million. The expansion of agriculture with an effective plow again seems a likely explanation for this dramatic, steady rise in world population. The invention of the plow combined with the domestication of oxen at 4000 BCE that produced the population increase beginning in 4000 BCE. The plow ranks as the #10 Greatest Invention of All Time.

4) Vaccination

Around 1000 AD, the Chinese used inoculation with smallpox to prevent smallpox infection. Very significant risk of smallpox infection occurred with inoculation of the live virus. In 1796, Edward Jenner used cowpox vaccination to prevent smallpox. Jenner’s vaccination did not risk smallpox, only cowpox. Eradication of smallpox officially occurred in 1980.

The worldwide eradication of smallpox is one of humanity’s greatest achievements.

The pioneering research of Louis Pasteur on rabies occurred in the later 1800s. The Salk polio vaccine originated in 1955. Eradication of 2 of 3 strains of polio occurs (type 2 in 2015 & type 3 in 2019). The first vaccine to prevent (cervical) cancer, the HPV vaccine, began use in 2006.

Thomas Jefferson, “Medicine has never before produced any single improvement of such utility (as vaccination)”

Vaccines exist for: smallpox, cholera, rabies, tetanus, typhoid fever, bubonic plague, tuberculosis, diphtheria, scarlet fever, tetanus, pertussis, yellow fever, typhus, influenza, encephalitis (tick borne), polio, anthrax, Japanese encephalitis, anthrax, measles, mumps, rubella, pneumonia, meningitis, hepatitis B, chicken pox, haemophilus influenza B, Q fever, hepatitis A, Lyme disease, rotavirus.

Since 1750, world life expectancy has more than doubled (age 35-72) and infant/child mortality is less than 1/8. Much of these life gains is attributable to vaccinations.

Estimates on the number of lives saved with vaccinations range up to 1-2 billion.

Vaccines rank as the #18 Greatest Invention of All Time.

Leading Causes of Death in 1850: tuberculosis, dysentery (bloody diarrhea), cholera (explosive watery diarrhea), malaria, typhoid fever (salmonella), pneumonia, diphtheria, scarlet fever, meningitis, whooping cough ** ALL 10 MOST COMMON CAUSES OF DEATH IN 1850 ARE INFECTIONS. 3/10 dysentery, cholera, and typhoid fever resulted from contaminated water. Vaccines exist for 8/10 most common causes of death from 1850.

Leading Causes of Death in 2020: heart disease, cancer, accidents, lung disease (COPD), stroke, Alzheimer’s dementia, diabetes, influenza/pneumonia, kidney disease, suicide ** ONLY 1/10 MOST COMMON CAUSES OF DEATH IS INFECTION. Vaccines for pneumonia and influenza are only partially effective.

5) Antibiotics/antimalarials/antivirals

In 0 AD, artemisinin herb treatment of malaria began in China. In 1632, Spanish missionaries began use of quinine from bark in the treatment of malaria. By 1880, identification of malaria plasmodium falciform occurs,

In 1900, German physician Paul Erlich theorizes the existence of a “magic bullet” which kills bacteria without injuring the host.

Erlich’s lab discovers the first antibacterial medicine Salvarsan (arsphenamine) for the treatment of syphilis in 1907. By 1918, synthesis of quinine for the treatment of malaria occurs. In 1928 Alexander Fleming discovers penicillin. In 1935, first sulfonamide antibiotic, Prontosil. By 1942, benzyl penicillin released. In 1944, streptomycin is the first aminogyloside antibiotic. By 1946, chloroquine appears. In 1952, erythromycin released. Also in 1952, isoniazid released for treatment of tuberculosis. In 1955, tetracycline released. By 1972, artemisinin isolated for the treatment of tuberculosis. By 1990, AZT protease inhibitors (AIDS/HIV) invented. 1940-1962 was the Golden Era of Antibiotics when all major antibiotic classes appeared. Estimates that antibiotics saved over one billion lives. Antibiotics rank as the #19 Greatest Invention of All Time.

Penicillin is the single most important drug in history.

(Peter Hog, 2016).

Penicillin has saved over 80-200 million lives since its introduction.

6) Hollow needle/hypodermic syringe

Arguably the greatest medical device of all time.

(Steven Levy, MDDI Qmed, 2014).

hollow needle/hypodermic syringe greatest biotechnology inventions

Estimates of the number of lives saved due to the hollow needle and transparent syringe range from 2-3 billion.

In the 800s, Arabic surgeon Ammar ibn’Ali al-Mawsili used a small glass tube and suction to remove cataracts. Pre-Columbian Native Americans used hollow bird bones and small animal bladders of liquids to give injections. In 1656, Christopher Wren used a goose quill and an animal bladder to give a dog opium injection intravenously. In the 1660s experiments with human injections by J.D. Major of Kiel and J. S. Elsholtz of Berlin. Injections then fell out of favor for 2 centuries, perhaps related to complications or ineffectiveness of the injections.

Francis Rynd of Ireland invents the hollow metal needle in 1844.

Scottish Alexander Wood invented the translucent hypodermic all glass syringe in 1851.

Glass syringes allow visible measurement of liquid to be injected. The first injected medicine was morphine. At that same time in 1853, Charles Pravaz of Lyon, France simultaneously with Wood developed a non-transparent silver metal syringe which did not allow visual measurement of liquid volumes. In 1897, Maxwelll W. Becton and Fairleigh S. Dickinson started a company, Becton,Dickinson and Co (BD). At first, they imported from H. Wulfing Luer of Paris all glass syringes. But by 1906, the company began manufacturing the syringes in the US. Then in 1925 Dickinson patents the Yale Luer-Lok syringe mechanism. Later, in 1949, invention of disposable glass syringes costing 5 cents each occurred.

Australian Charles Rothauser invented the clear plastic disposable syringe in 1955 called Monojet.

Even so, sterilizing reusable glass syringes remained common. In 1961, the Plastipak plastic disposable syringe by Becton, Dickinson and Co (BD) ultimately would replace glass syringes with a design almost unchanged in the last 60 years. Uses of needle/syringe: administration of vaccinations, administration of drugs (parenteral) which cannot be taken by mouth, IV fluid administration, IV blood transfusions, aspiration of body cavities for fluid diagnosis, blood draws for diagnostic testing, musculoskeletal injections, placement of catheter guide wires. 6% of the world’s population has a phobia of needles.

7) Woven fiber cloth

Studies on human body lice suggest clothing dates at least to 170,000 BCE

Dyed flax fibers date back to 36,000 BCE Georgia (Dzudzuana Cave)

Weaving dates at least to 27,000 BCE from clay imprints in Czechoslovakia (Dolni Vestonice).

String from plant fibers dates to 17,000 BCE Israel (Ohalo II )

Woven vegetable fibers date to 8000 BCE Peru.

Sheep bred for longer hair (wooly sheep) begins in Iran around 6000 BCE. Then woven wool rugs begin to appear at that time.

Later, artifacts of textile arts: net gauges, needles, and weaving sticks date to 5000 BCE.

At first, flax was initially the preferred fiber for weaving in Egypt dating to 5000 BCE

Spinning with weaving date to 3400 BCE Egypt.

Silk from insect casings in China date to 3200 BCE.

Wool cloth from domestic sheep specifically bred for long hair originated in 3000 BCE.

Then wool replaced flax in Egypt by 2000 BCE.

The first wool shears date to the Iron Age. Hand plucking of wool occurred prior to this time.

Later, wool, linen, and leather were the clothes of the Roman empire.

Then, modern textiles include: wool, silk, linen, hemp. straw, cotton, flax, rayon, polyester, acrylic, nylon, and spandex.

8) Nitrogen fixation fertilizer – Haber-Bosch process

Mesopotamians, Egyptians, Romans, and ancient Germans all recorded using manure and minerals to improve plant growth.

Manure and compost are organic fertilizers, Use of manure as fertilizer dates back at least to 6000 BCE. Also the benefits of crop rotation between legumes and cereals appeared in the fertile crescent as early as 6000 BCE. Compost use as fertilizer likely dates back as long as manure. Non-compost materials like peat, bark, sawdust improve water absorption but do not provide nutrients to plants.

Manure use as fertilizer leads to hygiene problems and water contamination risks.

The big 3 primary nutrients are nitrogen(N), phosphorus (P), and potassium (K). These inorganic fertilizers receive an NPK numerical value. Nitrogen is the most important and potassium the least important of the 3.

Use of nitrogen fertilizers has gone up almost 2000% since 1961.

Nitrogen is also the most absorbed nutrient by plants. Also, nitrogen is necessary for DNA, RNA, and amino acid production. Nitrogen works best in the middle stages of plant growth before reproduction. Green leafy plants need the most nitrogen. Phosphorus works throughout the plant life cycle, especially for flowering and reproduction. Use of phosphorus fertilizers have gone up 500% since 1961. Potassium aids photosynthesis, helps roots, and improved drought resistance.

Secondary plant nutrients are: calcium, magnesium, and sulfur.

90% of fertilizers see application as solids.

Nitrogen fixation can be natural with bacteria in the soil or with symbiotic bacteria in root nodules of legumes such as soybeans, peanuts, alfalfa, clover, beans, peas, chick peas, lentils.

Nitrogen fixation (since 1910) can also be synthetic.

In 1910, Germans Fritz Haber, Carl Bosch developed a synthetic nitrogen fixation process which converts nitrogen to ammonia using heat, pressure, and iron oxide catalyst. Haber received the Nobel prize for this work in the chemical process in 1918. Bosch received the Nobel prize in 1931 primarily related to the industrial scaling up on nitrogen fixation. In addition, Germans used nitrates to create explosives in WW I. However, the main use of Haber-Bosch process is fertilizer production. Prior to the Haber-Bosch process, the main sources of inorganic nitrates was saltpeter mining and guano from tropical islands. Manure and compost were the primary fertilizers. Since 1948, US agricultural production has increased 200%. Since 1910, estimates of world population without the Haber-Bosch process are around 50% less people. That is, rather than 7.5 billion people currently, estimates of world population are around 3.7 billion without the Haber-Bosch process.

Put another way, 50% of the current world population depends on the Haber-Bosch process to maintain agricultural productivity.

Meat production has doubled since 1950 related to increased production of corn and soybeans since that time. The Haber-Bosch process has led to 3.7 billion more people alive today related to increased agricultural productivity in the last century. 40% of crop yield increase in the last century is attributable to nitrogen applications made possible with the Haber-Bosch process.

9) Pasteurization

Heating of wine for preservation dates at least to 1117 AD in China. In 1768, Italian Lazzaro Spallanzani found heating meat broth to boiling then sealing the broth prevented early spoilage. Later, in 1795, French chef Nicolas Appert used heat in the canning process for food preservation. In 1864, Louis Pasteur of France discovered that heat short of boiling (50-70 C) for 30 minutes dramatically decreased spoilage in wine, beer, and 20 years later, milk. Pasteurization decreases spoilage by inactivating enzymes and killing yeast and bacteria. Pasteurization does not sterilize foods since spores are not inactivated.

Improperly handled (spoiled) milk produces 3x more food borne illnesses than any other food item.

Above all, pasteurization dramatically decreases food borne illnesses and improves shelf life of foods. Disadvantages of pasteurization: decrease of some vitamins, kills helpful (probiotic) bacteria, increases in certain allergies, tooth decay issues, infant colic, vitamin D deficiency, osteoporosis.

Commonly pasteurized food items: eggs, beer, canned food, dairy products including milk, low alcohol beverages, juices, wine, nuts, syrups, water, and vinegar. Much more recent technologies include: high-pressure processing (HPP), pulsed electric field pasteurization (PEF), and microwave volumetric heating (MVH).

10) Tissue transplants

The first successful blood transfusion occurred by James Blundell in 1818 in the UK. In 1869, first skin transplant occurred.

In 1900, Karl Landsteiner of Austria identified the A, B, and O blood types

which when matched, dramatically improved blood tranfusion safety. In 1906 the first corneal transplant occurred,

First kidney transplant (from a twin) occurred in 1954.

Jean Daussset in 1958 discovered the first HLA for which he later received the Nobel Prize in 1980.

In 1958, the HLA (human leukocyte antigen) discovery allowed tissue matching, dramatically improving transplantation safety.

First cadaver organ transplants occurred in 1962-1963. Then, the first sibling kidney transplant occurred in 1960. Next, the first successful heart transplant occurred in 1967. Then the first successful liver transplant took place in 1967.

The first heart lung bypass machine originated in 1967. Next, the first bone marrow transplant occurred in 1968. Then the discovery of cyclosporine anti-rejection properties occurred in 1976. The first heart lung transplant took place in 1981. Later, the first intestine transplant transpired in 1987. Then the fIrst successful hand transplant took place in 1997 in France. Finally, the first full face transplant was in 2010 in Spain. Blood transfusion is the most common tissue transplant. Cornea and musculoskeletal tissues transplant most frequently of solid tissues. Kidney is the most transplanted organ.

11) Soap/detergent

Soap is simply a salt of a fatty acid. Soaps and detergents are amphiphilic, that is, they have a fat soluble part of the molecule (fatty acid or hydrocarbon) and a water soluble part of the molecule (salt or sulfate). Soaps come from natural ingredients such as fats and oils.

By 2800, BCE Babylonians invented soap,

described as fats boiled with ashes. Soap use was not for bathing but in the cleaning of cotton and wool for textiles at that time. By 1500 BCE Egyptians uses vegetable and animal oils with alkaline salts to treat skin conditions. Then by 600 BCE, the Phoenicians made soap from goat’s tallow and alkaline salts. The name soap originated from the Roman legend of Mount Sapo when rain mixed animal fat with ashes to form soap. While soap making occurred with olive oil in Italy, France, and Spain, soap saw use in Mesopotamia, Egypt, ancient Greece, and Rome.

Bathing was fashionable in ancient Rome.

After the fall of Rome in 476 AD, bathing declined in most of Europe. Bathing again became fashionable in the 1600s in Europe but primarily with the wealthy because of heavy taxing of soap . Later, in 1791, French chemist Nicholas Leblanc patented a process for making soda ash from common salt. Then Earnest Solvay’s discoveries decreased the cost of soap manufacturing. So by 1850, soap making was widespread, fast growing, and inexpensive. Later still, by the mid-1800s, milder soap for personal used separated from harsher laundry soap, and dish soap.

In 1900, German scientists invented detergents.

Detergents are entirely synthetic.

Detergents work better than soap in hard water and will form far less soap scum.

During WW I and WW II the fats and oils used in soap manufacturing faced shortages. In the 1930s US companies developed household detergents. Substitute detergents have since replaced most types of soap, even bar soap is usually a synthetic detergent. In 1953, detergents out sold soaps. Since 1960, enzymes and special stain removing agents see use in detergents. Liquid hand soaps appeared after 1970. Then, disposable wipes appear in 2000.

Most bar soaps, dish soaps, and liquid soap are actually synthetic detergents.

12) Medical Imaging and x-ray technology.

X-rays are high energy photons that occur when electricity comes in contact with a hot cathode in a vacuum. X-rays emit from electrons and have slightly longer wavelength than gamma rays. In contrast, gamma rays emit from the atomic nucleus and are of a slightly shorter wavelength than x-rays. X-rays are medically important due to different rates of absorption by the elemental composition of tissues. The higher the atomic number of the element, the greater the absorption of x-rays. Heavier atoms (higher atomic number) such as calcium and phosphorus of bone absorb more x-rays while gaseous space absorbs far less x-ray energy. Water is intermediate in x-ray absorption. Mutagenic properties of x-rays result in significant cancer risks.

Production, naming, and detection of x-rays by German Wilhelm Roentgen in 1895.

By 1896, medical applications of x-rays began to appear. In 1896, Thomas Alva Edison invents the Vitascope (later called fluorscope) for live x-ray viewing for surgeries. Edison stops research in 1903 when his employee Clarence Madison Dally suffered bilateral arm amputations due to cancer from radiation. Dally was the first known death from x-ray exposure. Wilhelm Roentgen wins the Nobel prize 1901 for his x-ray work. In 1914, Marie Curie creates radiological train cars for x-ray imaging of wounded war victims to assess field injuries before surgery.

In 1971, invention of the CT scan occurs.

Later the Nobel prize in 1979 goes to British Godfrey Hounsfield and Allan McLeod Cormack for the CT scan.

By 1974, Michael Phelps invents the PET scan in the US.

Next in 2014, University of Canturbury began work on the first COLOR X-ray scanner.

13) New World domesticated crops/Second Agricultural Revolution

North America crops include: wild rice, tobacco, maple syrup, strawberry, blueberry, pumpkin, sunflower. Central America and Mexico crops include: cocoa, avocado, papaya, corn (maize), peppers, squash, cashew, pecan, cotton, tobacco, chilie. South America crops include: peanut, rubber, pineapple, green beans, lima beans, potato, sweet potato, tomato. Above all, the “Magic eight New World ingredients ” by food historian Lois Ellen Frank include: potatoes, tomatoes, corn, beans, chilies, squash, cacao, and vanilla.

Corn is the most grown grain crop in the world.

Perhaps surprisingly, one bushel of corn converts to: 8 pounds of beef, or 16 pounds of pork, or 22 pounds of chicken. Because 40% of grown corn converts to ethanol (biofuels) and 36% of grown corn is fed to livestock. that leaves 25% for human diets. Corn yields have increased in the US 5x since 1940 (2 tonnes/hectare – 10 tones/hectare in 2015). Corn production is 2x rice in the world. In 1998, corn bypassed wheat as the most commonly grown crop in the world. Corn (widespread), tomatoes (Italy), and potatoes (Ireland, Russia) had a huge impact on European agriculture.

The Second Agricultural Revolution comprised several events: 1) new crops from the discovery of the New World such as corn, potatoes, tomatoes, beans, and peppers 2) end of feudalism with land redistribution 3) switch to high yield crops such as wheat and barley and away from low yield crops such as rye 4) new techniques such as selective plant breeding, livestock breeding, use of fertilizer, crop rotation, and increased mechanization and improved transportation. Inventions of the second agricultural revolution include: Jethro Tull’s seed drill, sickle, moldboard plow, fertilizers, threshing machines, horse drawn reapers, harvesting machines. and later, combine harvesters. Farms moved away from communal, subsistence agriculture to more private, commercial agriculture. People moved out of agricultural areas to cities. Urbanization contributed to the industrial revolution.

In the world today, wheat, rice, and corn comprise 60% of the world’s calories. 55% of world’s total crop calories go to people’s diets (27% in US), 36% to livestock, 9% to biofuels. Yet, 30,000 known edible plant species exist.

14) Pain/anesthesia. Opium domestication

In 4000 BCE, Sumerians use opium poppy for pain relief. Then in 3400 BCE, aspirin use began from willow bark in Egypt. Acupuncture by  2500 BCE in China begins. Then by 1600 BCE, acupuncture is widespread in China. Later in 2250 BCE, Babylonians use henbane herb (Hyoscyamus niger) for toothache relief. Then around 400 BCE, Assyrians and Egyptians used carotid compression to induce unconsciousness for minor surgery, circumcision and cataract surgery.

By 400 BCE, Hippocrates describes opium anesthesia.

Later, in 160 AD, Chinese Hua Tuo created an herbal mixture called Mafeisan mixed with wine for general anesthesia. Beginning from 800s, herbal soaked sponges with opium, mandrake, henbane, and hemlock see use. In the late 1200s, Theodoric of Lucca used opium and mandrake soaked sponges for anesthesia. Then in 1540, from ethanol and sulfuric acid creates diethyl ether. Further, Japanese Hanoka Seishu tries to duplicate Hua Tuo’s methods with use of 7 Chinese herbals producing unconsciousness for 6-24 hours. Morphine isolated 1805 by German Fierich Serturner,

Until the 1840s, alcohol and opium were the common limits of anesthesia.

Then in 1846, ether as anesthesia originated with William TG Morton dentist.

Later, in 1847, childbirth with chloroform sees use for the first time. In 1853, French Charles Pravaz and British Alexander Wood invent the hypodermic syringe. Combined with the hollow needle invented by Irish Francis Rynd (1845) allows parenteral medicine administration. In 1898, German August Bier administers the first spinal anesthesia using cocaine. Then in 1902, French Jean-Anthanase Sicard and Fernand Cathelin invent epidural anesthesia. In 1942, first use of muscle relaxant curare occurs.

By 1950, all the elements of modern anesthesia are present

including the anesthesia machine for controlled inhalational anesthesia. Later, Paul Janssen invents fentanyl, 100X more potent than morphine in 1960. In 1964, first use of ketamine for anesthesia.

15) MRI

In 1882, Nikola Tesla describes the rotating magnetic field.

Later, beginning in 1956, the Tesla unit measures the strength of a magnetic field. Higher Tesla magnetic fields from MRI scanners produce better quality images.

Then, in 1937, US Isidor I. Rabi of Columbia University developed the quantum phenomenon of nuclear magnetic resonance and measured the magnetic moment for a nucleus for which he received the Nobel Prize in 1944. In 1952, Felix Bloch and Edward Mills Purcell define the basic science of nuclear magnetic resonance.

Nuclear magnetic resonance originates from the hydrogen atoms of water in tissue. Different amounts of water in different tissues produce different electromagnetic signals in a magnetic field. The signals require interpretation by a computer to create images.

Detection of harmless radio waves created in a strong magnetic field is the basis for MRI.

Then in 1969, the concept of MRI scanner develops. Also by 1972, MRI as a cancer detector in living organisms develops with Raymond Damadian of the US. Damadian identifies the differences in cancer MRI signals compared to normal tissues in T1 and T2 weighted sequences. In 1972, Ramadan files patents for MRI technology. However, Damadian’s methods for imaging were severely flawed. In 1972, 2-D imaging method for MRI originated with Lauterbur. Then, Lauterbur creates living mouse 2-D images in 1974. British Peter Mansfield developed a much faster imaging method which made real time MRI of living specimens possible. His echo-planar method of using a magnetic field gradient is critical for improving speed of the MRI The first human MRI produced in 1977 taking 5 hours by Raymond Damadian.

Later in 2003, Paul Lauterbur and Peter Mansfield share the Nobel Prize for the MRI.

Stronger magnetic fields carry the hope for better quality, higher resolution MRI scans in the future.

16) Ultrasound/echocardiography

Ultrasound is sound waves with a frequency above the level of human hearing. In 1794, Italian Lazzaro Spalllanzani studied bats echo location, concluding that bats use sound rather than sight for navigation.

In 1877, brothers Pierre and Jacques Currie discover piezoelectricity and the piezoelectric effect in France. Piezoelectric effect is useful for the creation of transducers to generate and detect ultrasound.

Later in 1914, Reginald Aubrey Fessenden from Canada invents the first SONAR (sound navigation and ranging) system developed to detect icebergs.

Then by 1915, the first sonographic (SONAR) device created by Paul Langevin to detect objects in the ocean bottom. Later in 1917, SONAR detects submarines for the first time.

In 1948 George D. Ludwig uses A-mode of ultrasound to detect gallstones.

1953. Inge Edler and C. Hellmuth Hertz perform the first successful echocardiogram.

By 1958, U/S use in OB/GYN begins with Ian Donald.

In 1966, Don Baker, Dennis Watkins, and John Reid use Doppler ultrasound technology to study heart blood flow.

Later, in 1986 3-Dimensional ultrasound technology for fetus study.

Advantages of ultrasound: painless, low cost imaging, ideal for soft tissue assessment, fast, able to use in ER or at bedside, visualizes moving tissues, Doppler capabilities, no ionizing radiation (safe), ok for use with metal objects such as needles (unlike MRI).

Disadvantages of ultrasound: very operator dependent, patient dependent (obesity impairs quality of images)

Uses of ultrasound technology:

live fetus study, heart assessment (echocardiogram with Doppler), abdominal organ assessment (kidneys, liver, gall bladder, spleen, pancreas), bone density determination, breast cancer detection, ultrasound guided biopsy, ultrasound guided catheterization, foreign body localization, ophthalmic (eye) ultrasound, genital/prostate ultrasound, transvaginal, ultrasound, transrectal ultrasound, transesophageal ultrasound, acoustic microscopy, physical therapy treatment of injured or inflamed tissues, breaking up of stony or calcified lesions in tissues, ultrasound impaction treatment (UIT) which enhances the mechanical and physical properties of a metal, improving mixing and accelerating chemical reactions (ultrasonification), ultrasonic cleaning, ultrasonic disintegration of organic materials, ultrasonic humidification, ultrasonic welding of plastics. sonic weapons, and underwater wireless communications.

17) Minimally invasive/Catheter Surgery

In 3000 BCE, Egyptians catherize bladder with metal pipes.

Galen of Pergamon reports using a needle shaped instrument to remove a cataract affected lens around 150 AD.

Then by 1711, first heart catheter surgery in a horse by Claude Bernard using brass pipes, a glass tube, and a goose trachea.

Later in 1752, Benjamin Franklin invents flexible urinary catheter.

Later in the 1700s, coude tipped catheters for urinary retention begin use.

In 1844, Charles Goodyear invented vulcanization of rubber which allowed the making of flexible rubber urinary catheters widely available with mass production.

By 1929 first human cardiac cathertization by Werner Forssmann in Germany. In 1935, Frederic E. B. Foley invents the first latex balloon urinary catheter The foley catheter remains the standard urinary catheter today. In 1958, first coronary angiogram performed by Mason Sones. Thomas J. Fogarty performs first balloon catheter surgery for blood clot removal in 1961.

In 1964, translumenal angioplasty developed by Charles T. Dotter.

Then in 1964, Dotter invented peripheral artery balloon angioplasty catheter. Dotter is famous as the father of interventional radiology.

Later in 1974, first balloon angioplasty performed by Andreas Gruentzig. By 1977, first PTCA percutaneous translumenal coronary angioplasty performed in Zurich, Switzerland by German Andreas Gruentzig. By 1982, steerable over wire balloon systems appear. Swedish Ingemar Henry Lundquist invented the over-the-wire balloon catheter in the early 1980s. The first angioplasty stents (bare metal stenting) appear in the mid1980s. First implantable cardioverter-defibrillator (ICD) implant in 1985. First catheter pacemaker 1962-1963 (first pacemaker surgery done open 1926 Mark Hill, Edgar Booth). In 1986, coronary arthrectomy and coronary wall stents appear. In 1990, the Rotoablator for providing rotational atherectomy sees use. Intravascular ultrasound appears in 1990. In 1997, one million angioplasties performed worldwide making

angioplasty is one of the most common surgical procedures in the world

The first coronary angioplasty with a drug eluting stent occurred in 1999 by Stertzer and Luis de la Fuente in Buenos Aires, Argentina. In 2003, the first marketed drug eluting stent, Cypher by Johnson and Johnson appears. In 2004, several studies confirm vastly superior results with drug eluting stents.

18) Green Revolution

The first agricultural revolution (Neolithic revolution) occurred in 10,000 BCE with the 8 Neolithic founding crops of Mesopotamia.

Then, the second agricultural revolution occurred with the industrial revolution and light mechanization beginning in the 1600s in Europe. The end of feudalism, the rise of capitalism, and reorganization of farmland defined the period. Features of the second agricultural revolution include: improved crop rotation (Norfolk 4 field rotation system), improved crop and livestock breeding, increased use of fertilizer, use of the Rotterdam moldboard plow from 1650, increased use of horses, mechanization of agriculture (Jethro Tull’s seed drill from 1700) and mechanization of transportation. Improved access to markets with the rise of capitalism.

In 1793, Eli Whitney invents the cotton gin. The cotton gin helped to mechanize agriculture.

Eli Whitney’s ideas of interchangeable parts with machines highly influenced American invention.

“Green revolution” 1940s-present. The third agricultural revolution.

Increased use of fertilizers, pesticides, hybrids, and heavy mechanization.

Self-propelled mechanized reaper/harvester combines appeared in 1938.

Then, peak tractor sales were in 1950.

Later, in 1954, corn head attachments available for combines.

Third agricultural revolution (Green Revolution) from 1940 to present.

Green Revolution is high yield hybrids, pesticides, herbicides, fertilizers, expansion of irrigation, and heavy mechanization. Norman Boraug, PhD (U of MN) “father of the Green Revolution”. Credited for saving 1 billion from starvation in Mexico, India, and Pakistan. Crop yields have increased 400% since 1940 in US, wheat yields have increased 300% since 1940 in Europe.

source: census.gov, United States Census Bureau, 2018.

Nutrition determines infant and child mortality more than any other single factor.

Malnourished children are more prone to disease, particularly infections.

Since 1940, corn yields have increased 400% in the US. Wheat yields since 1940 have increased 300% in Europe.

19) Psychotropic medications

In 1949, lithium used to treat psychosis. By the 1960s, lithium becomes the treatment of choice for bipolar disorder.

In 1951, thorazine (chlorpromazine) becomes the treatment of choice for psychosis and schizophrenia.

Thorazine is considered one of the top 10 drugs in history (#7).

In 1957, Tofanil (imipramine) becomes the first mood elevating drug (anti-depressant).

Haldol (haloperidol) invented by Paul Janssen in Belgium in 1958 for schizophrenia.

By 1959, Parnate beomes the first MAO inhibitor antidepressant.

In 1960 Librium then in 1963 Valium invented by Leo Sternbach of Hoffmann-La Roche of New Jersey for the treatment of anxiety, seizures, and alcohol withdrawal.

By 1961, Elavil (amitriptyline) becomes an extremely successful tricyclic antidepressant.

In 1977, Zoloft (sertraline) appeared as an extremely successful antidepressant with a variety of other indications.

Further by 1983, Depakote (divalproex sodium) began use for manic depression.

In 1988, FDA approves Prozac (fluoxetine) which becomes a blockbuster selective serotonin reuptake inhibitor (SSRI). The most widely prescribed medications for depression are SSRI drugs.

In 1993. Effexor and Paxil appear for depression.

Then in 2007, Abilify (aripiprozole) became FDA approved with use primarily as a second adjuctive antidepressant.

In 2008, Seroquel (quetiapine) is a second generation antipsychotic for schizophrenia and bipolar disorder.

20) Fermentation

Fermentation is the preservation of food with microorganisms,

bacteria or yeast often in the absence of oxygen. Alcohol beverage production or lactic acid dairy products are common. Fermentation occurs naturally in the digestive tracts of all animals including humans. Fermentation may improve the nutritional value of some foods by production of vitamins by the bacteria or yeast.
Cheese is first made in 8000 BCE with the domestication of sheep and goats. Ruminant stomachs contain rennet, an enzyme to make cheese. Storage of milk in animal stomachs likely led to cheese production.

In 7000 BCE, Sumerians of Mesopotamia make beer.

Further in 7000 BCE, China fermented beverage of fruit, honey, and rice.

Wine making begins in Georgia in 6000 BCE.

Then in 4000 BCE, Egyptians used yeast to make leavened bread and wine.

Pickling develops in Indus river valley civilization around 2400 BCE.

In 2000 BCE Mexico, fermentation of beverages occurs.

Further, in 2000 BCE, widespread fermentation of milk products existed.

1750 BCE in Sumer, Mesopotamia, barley ferments into beer.

In 1500 BCE meat preservation with sausages in Babylon.

In 220 BCE, Chinese use fermented (moldy) soybean curds as antibiotic

to treat infections. Fermented tea sees use for infections.

Later, in 1276, the whiskey distillery originates in Ireland.

In 1500, fermentation of yoghurt and sauerkraut begins.

By 1854, Loius Pasteur determines yeast causes fermentation.

In 1907, German Eduard Buchner receives Nobel Prize for determining enzymes in yeast cells not the yeast cells themselves cause fermentation.

In 1927, Arthur Harden and Hans Euler-Chelpin define the exact enzymes of fermentation and win the Nobel Prize of 1929.

By 1940, fermentation produces antibiotics.

Then in the 1970s, probiotic foods become common.

Fermented foods: beer, wine, leavened bread, buttermilk, cheese, cocoa (chocolate),

cod liver oil (traditional), kefir (fermented milk), ketchup, kimchi, miso (fermented soya bean), pickles. salami, sour cream, soy sauce, tabasco sauce, vinegar, Worcestershire sauce, yogurt, sauerkraut, and pickled fish (herring). Fermentation allowed long term storage of food. Fermentation produced important traditions which have continued to the present day with surprisingly few major alterations.

21) Genetic Engineering

In 1859, Charles Darwin writes on the Origin of Species describing natural selection and selective breeding. In 1865, Gregor Mendel defined the basic laws of inheritance becoming the father of genetics. Rediscovery of Gregor Mendel’s work is in 1900. Wilhelm Johannsen coins the word “gene” in 1909. Dominant or recessive genes inherit as units. In 1940, plant gene mutations occurred with radiation exposure. George Beadle and Edward Tatum propose one gene, one enzyme hypothesis in 1941.

In 1944, discovery occurs proving that DNA not proteins determine inheritance.

In 1953, James Watson and Francis Crick with the aid of Rosalind Franklin’s x-ray diffraction data determine the double helix structure of DNA. Watson and Crick receive the Nobel Prize in 1962.

In 1958, Arthur Kornberg is the first person to synthesized DNA in vitro. Using nucleotides and DNA polymerase enzymes, Kornberg’s synthesis earned him the Nobel Prize.

Then in 1962, the identification of the genetic marker from jellyfish GFB green fluorescent protein occurs, again winning the Nobel Prize.

Deciphering of the genetic code of 4 nucleotides occurs in 1966.

4 letters determine 20 kinds of amino acids.

In 1967, DNA ligation enzymes isolated. In 1968, DNA restriction enzymes isolated which cut alien sequences of DNA.

By 1971,Paul Berg spliced the DNA from 2 different species to create the first approximation of recombinant DNA. Paul Berg wins Nobel Prize in 1980. Stanley Cohen and Herbert Boyer create recombinant DNA (rDNA) which can replicated on its own in 1972.

In 1975, George Kohler and Cesar Milstein create monoclonal antibodies by merging myeloma cancer cells with B cells. Also in 1975, Frederick Sanger develops a rapid method of DNA sequencing still used today.

In 1978, first in vitro fertilization (test tube baby) Louise Brown is born.

By 1981, first trans genetic animal created when rabbit gene transferred into a mouse by Thomas Wagner. In 1982, human insulin produced by Genentech. In 1983, polymerase chain reaction (PCR) discovered.

By 1986, first recombinant vaccine made for hepatitis B using yeast cells by Pablo D.T. Valenzuela. Recombinant vaccines are later produced for human papilloma virus, whooping cough, pneumococcal pneumonia, meningitis, Hib and shingles.

In 1993, CRISPR principles invented by Jennifer Doudna and Emmanuelle Charpentier. They received the 2020 Nobel Prize.

In 1988, first GMA corn created with Baccillus thuringiensis antipest gene. Then by the 1990s, GMO squash, soybeans, cotton, papayas, potatoes and canola appear.

By 1994, GMO tomato (Flavr Savr) comes to market and fails.

Later, in 1996, cloning first occurred with Dolly the sheep.

By 1999, sequencing of the first human gene occurs.

In 2001, first gene targeted drug therapy occurs.

In 2003, Glo-Fish invented as the first genetically altered pet. Also in 2003, Sequencing the human genome finishes. In 2006, HPV vaccine is the first anti-cancer vaccine preventing infection by human papilloma virus. In 2006, stem cell research begins with Shinya Yamanaka from UCSF.

By 2010, first entirely synthetic life form Mycoplasma mycoides created by Craig Ventor.

In 2015, GMO salmon come to market. Human embryo CRISPR gene editing occurred in China in 2015. In 2018, first human trials of CRISPR to treat thalassemia begin.

22) Sanitation systems/chlorination

Diarrhea and diseases of bad water include: typhoid fever (Salmonella typhi), cholera (Vibrio cholerae), giardiasis (giardia parasite), dysentery or shigellosis (Shigella dysenteriae), Escherichia coli, hepatitis A, Salmonella, Legionella. Also, diarrhea causes 4% of world wide deaths. Further, diarrhea was the primary symptom of typhoid fever, cholera, and dysentery, 3 /10 most common causes of death in 1850. Now with appropriate water treatment systems, none of the top 10 causes of death now are related to contaminated water.

Water chlorination and water sanitation systems have saved an estimated 175 million lives.

98% of water treatment systems in the US use chlorine. However, the first chlorination of water supply was in Germany in 1894. Chlorine kills bacteria and viruses but not on all protozoan cysts. Despite the health benefits, chlorination produces small amounts of trihalomethanes which is a known carcinogen as a by product.

Home drinking water systems typically employ a sediment filter, an activated carbon filter, a reverse osmosis filter, ultraviolet light exposure to sterilize the filtered water (optional).

23) Eyeglasses

The invention of spectacles or eyeglasses dates to 1285 with Salvino D’Armate in northern Italy (Pisa).

6/10 (64%) of persons in the developed world use eyeglasses of some type to aid vision.

We know that 75% of adults need corrective lenses.

11% of corrective lens wearers use primarily contact lenses. Commonly used eyeglass types include: myopia lenses, presbyopia lenses, bifocals, even trifocals, safety glasses, sun glasses, and contact lenses. Occasional use of specialized glasses such as 3-D glasses occurs. 10 million Americans have had Lasik corrective eye surgery or about 700,000/year or about 1/25 Americans.

24) Aquaculture

Above all, over 70% of the world’s surface is water. While aquaculture is a recent phenomenon, 97% of domesticated seafood species have occurred since the 20th century. However, ancient Egyptians farmed fish 2000 BCE.

Aquaculture production has grown steadily (8%/year since 1970)

while wild caught fish has remained steady or declined (-3%) since 1990. In 2014, more farmed seafood than caught wild seafood supplies the world. That is, more captured than farmed seafood exists. Farming of shrimp, salmon, tilapia, catfish, mollusks, crabs, lobster, carp, and seaweed dominates wild caught varieties. Farming occurs with 580 different species in the world’s waters. Farmed fish production occurs in tanks, ponds, and ocean enclosures. China is the largest producer of farmed seafood (61% of world supply).

While all of Asia produces 91% of world farmed seafood,

Washington, Mississippi, and Alabama produce 40% of US aquaculture. China and Thailand grow about 75% of world’s farmed shrimp. Wild fish stocks are down 70% due to overfishing. Farmed fish are the most efficient protein. Tilapia are particularly good for food production as they are herbivores and do not require being fed fish products and can be raised in large tanks with controlled conditions.

Above all, one kg of fish food leads to almost one kg of fish (1:1)

whereas chickens are 4:1 and pigs 8:1. Fish produce food efficiently for two reasons: 1) Cold blooded animals have a slower metabolism than warm blooded animals. 2) Fish do not need heavy skeletons to support their weight in water. Shellfish are the most efficient food producers, are immobile and easily contained, and clean the water with their filtering activities. Clams and oysters do not need to be fed. Aquaculture will grow by 50% in the next 15 years. USA imports 95% of our seafood.

25) Randomized controlled trials (RCT)

Randomized clinical trials are the gold standard for scientific study of medical treatments. RCT allow comparison of treatment methods in a way that is unbiased. The first randomized controlled clinical trial was in 1747 by James Lind, in the UK for the evaluation of treatment of scurvy. However the first published randomized controlled clinical trial occurred 2 centuries later in 1948 by Austin Bradford Hill with streptomycin treatment of pulmonary tuberculosis. Since 1747, USA life expectancy has more than doubled (age 35-80). Since 1747, infant and child mortality is less than 1/8. RCT produced much of the gains in survival due to accurate determination of the best treatment available for any given medical condition.

As of 2004, more than 150,000 RCT have been documented.

While comparing 2 treatments scientifically with controlled randomized double blinded studies, the

placebo effect is an important factor to take into account with trial planning.