Polymerase Chain Reaction (PCR)

Polymerase Chain Reaction (PCR) turns a tiny bit of DNA into a much larger amount which can subsequently be sequenced.

In 1983, Mullis figured out a way to multiply the tiniest piece of DNA by orders of magnitude, making millions of copies. This is how the smallest bit of DNA, from bacteria, viruses, historical artifacts, or even crime scenes, can be multiplied and analyzed. Mullis won the Nobel Prize in Chemistry in 1993.

PCR and DNA profiling go together like Sherlock Holmes and Watson. Created by Alec Jeffreys, profiling identifies people or animals and their relationship to one another. Mullis shared the 1993 Nobel Prize in Chemistry.

PCR is the impetus for the science fiction book and movie Jurrasic Park. In that book, minuscule amounts of dinosaur DNA create living dinosaurs. Many wrongfully convicted innocent people are free due to PCR/DNA. Furthermore, the technique helped identify countless violent criminals.

Mullis is an eccentric, moving between serious scientific work and unusual ventures. He owns a business selling jewelry containing artificially grown DNA from famous people (ex: Elvis). He also started businesses to help the immune system identify and auto-mutate cells to enable, for example, a universal flu vaccine. Despite his scientific background, he’s both a climate-change denier and also denies the well-proven link between HIV and AIDS.

Cetus paid Mullis a $10,000 bonus for his work and sold the patent to Roche for $300 million. Predictably, much patent litigation ensued which, for the most part, Roche/Cetus won.

Statins

Statins dramatically lower blood cholesterol, and the likelihood of heart attacks. Akira Endo discovered statins.

Akira Endo & His Molds

Endo is a Japanese researcher with a lifelong fascination related to fungi. Recalling that Fleming accidentally discovered penicillin, he theorized that fungi might hold other miracle drugs.

Endo noted that Americans are much heavier than Japanese people while studying in New York. Specifically, he noted elderly overweight people suffering from heart attacks. In contrast, Japanese people are slimmer. However, they are more likely to suffer a genetic abnormality resulting in excessive cholesterol levels leading to heart attacks. Children with this genetic problem suffered heart attacks as young as five years old. Therefore, high cholesterol was a serious health problem in both the US and Japan.

Back in Japan, Endo worked with thousands of molds searching for one that lowered cholesterol. In 1972, working at Sankyo, he came across a mold that worked which he and his team called compactin. Originally, the mold was found on a bag of old rice.

Concurrently, Michael Brown and Joseph Goldstein published a 1973 paper showing the receptor for cholesterol is regulated by genetics and other substances. In essence, they proved in a paper what Endo was seeing in the lab. Brown and Goldstein won the Nobel Prize.

Commercialization of Statins

Development of compactin continued. The compound demonstrated enormous promise in humans. However, dogs administered far higher doses of compactin — about 200x the correct dose — developed lymphoma cancer. Subsequently, Sankyo ceased work on compactin but licensed the drug and research to Merck.

Merck slightly changed the compactin molecule (Endo argues it is the same molecule) and renamed it lovastatin. The Japanese studies worked in the US and, by avoiding the extreme dosages, there were no side effects. The FDA approved lovastatin in September 1987. Since then, there have been several new statins developed. Statins are widely prescribed around the world and have dramatically decreased cholesterol and the resulting risk of a heart attack.

Computed Tomography (CT or CAT scan)

Computed Tomography (CT or CAT scans for short) are 3-dimensional x-rays.

Self-taught innovator Hounsfield, while on a camping trip, wondered if he could x-ray the contents of a box in 3D by moving the x-ray machine. That worked. Eventually, he implemented it in his own machine and used that to image a cow brain. Subsequently, he tried a human brain: his own.

His 3D x-ray machine, known later as a CT scanner, was small. At the urging of colleagues, he built a full-body model.

In the 1960’s, Allan Cormack worked through mathematical formulas for CT scanning. Markedly, Hounsfield never saw Cormack’s research (few people did: it was not well known).

In 1979, Hounsfield and Cormack shared the Nobel Prize for the innovation of the CT scanner.

CT scans were developed after the earliest MRI machines. However, MRI took so long to perfect that CT scans was commercialized first.

Hounsfield was never interested in material goods and did not worry about money.

“Don’t worry too much if you don’t pass exams, so long as you feel you have understood the subject. It’s amazing what you can get by the ability to reason things out by conventional methods, getting down to the basics of what is happening.”

Godfrey Hounsfield

Charge-Coupled Device (CCD)

1969

William Boyle
George Smith

“We are the ones who started this profusion of little cameras all over the world.”

William Boyle

Charged Coupled Devices (CCD’s) are a special type of chip that reacts to light. They are inexpensive and especially useful in imagining, enabling digital photography and video.

William Boyle and George Smith worked for Bell Labs. Their research on “Charge Bubble Devices” advanced slowly. Eventually, they were told in a week they’d be reassigned to the more promising memory division.

In 1969, faced with losing their funding and lab, the two brainstormed. In one hour, they outlined the idea which became the CCD, the sensor driving all early digital video and photography. Forty years later their one-hour invention won them the 2009 Nobel Prize.

The device itself is made up of “charge bubbles” — a series of metal-oxide semiconducting capacitors (MOS). Light changes the photons to electrons that are then flushed to a capacitor. Boyd and Smith figured out how to quickly measure each row of MOS light to create still and moving pictures.

MOS, like most imaging, only captures black and white. However, by filtering for red, green, and blue then combining them electronically, the technology produces color images. Cameras typically then combined and enhance the images into smaller and more manageable files, typically a JPEG.

Boyle and Smith’s CCD soon became ubiquitous, famously used to capture and send images from the moon back to earth where other equipment would have been too heavy and bulky.

Other Bell Labs researchers are critical, arguing that Boyle and Smith stumbled upon CCD’s accidentally and did not think up or use the technology for imaging. “They wouldn’t know an imaging device if it stared them in the face,” said Eugene Gordon who, along with Michael Tompsett, applied CCD’s to imaging.

“I can clearly remember the day that George and I developed the concept for the CCD,” answers Boyle. “It’s pretty firm in my mind. I’ve documentation that disproves most of what they’re saying, and the rest of what they’re saying is not at all logical.”. Smith simply called them “liars.”

CCD chips made for early video equipment and digital cameras. However, CMOS chips eventually overtook CCD chips for most imaging solutions. The advantage of CMOS is it reads directly from the chip, rather than reading line by line, making it faster and ultimately less expensive.

Fiber Optic Cable

Fiber optic cable is extremely thin cable that uses light, rather than electricity, to send information.

Background

In 1854, John Tyndall demonstrated that light bends through water. In 1880, Bell showed an analog voice signal propelled by light. He called it a Photophone. However, the process was subject to interference and abandoned.

Additionally, Europeans demonstrated that home lighting could be transmitted via light. Progress on the light over glass technology continued to evolve.

Eventually, in 1958, The US Army Signal Corps in New Jersey tasked Sam DiVita to find an alternate transmission material besides copper. Accordingly, DiVita turned by Second Lieutenant Richard Sturzebecher who had a degree in glass technology. Sturzebecher theorized that glass made using SiO2 would be flexible and carry light. No sooner did he try a sample under a microscope than it carried so light so well it gave him a splitting headache.

US Military Researches Light

Afterward, the army then put out a private research bid to develop information-carrying glass fiber cables. Corning won the bid to invent early fiber optic cable due to their work purifying SiO2. Accordingly, the army awarded them funding from 1963 to 1985 for fiber optic research.

Charles Kao

Early fiber optic cable failed to carry light past a few kilometers. Eventually, in 1964, Kao realized the problem was due to imperfections in the silicon fiber. Subsequently, he invented a fiber-optic cable far less prone to drop light, the modern fiber optic cable.

Kao worked with ITT and others to commercialize his technology and seems to have done well for himself financially besides academically. Thereafter, he won the 2009 Nobel Prize in physics, a knighthood, and countless honorary degrees and professorships.

Integrated Circuits (Microchips)

In early electronic computers, each circuit involved a vacuum tube. They were large, relatively slow, and consumed a lot of power.

Shockley, Brattain, and Bardeen created the semiconductor. Their circuits eliminated the need for vacuum tubes.

Kilby and Noyce discovered that semiconducting material held burned-in semiconductor circuits. Their printed circuits worked like the much larger metal counterparts. Furthermore, many circuits could be printed and tied together with a single piece of silicon.

These collections of circuits integrated on one chip are what we today refer to as microchips. You are reading this thanks to Kilby and Noyce’s invention.

Kilby worked for Texas Instruments. Noyce was one of the Traitorous Eight, the group who left the abusive, managerially incompetent Shockley. He was working at Fairchild Semiconductor, the firm funded by Doriot student Arthur Rock.

Kilby and Noyce never worked together but, at the same time, addressed the same problem. Kilby, tasked with shrinking the size of a semiconductor, thought of creating it from semiconducting material. He used geranium. Noyce realized that silicon worked better and that multiple circuits could be etched on one silicon wafer.

Their Integrated Circuit won the Nobel Prize in 2000 and went on to change the world. Noyce passed away in 1990 so only Kilby was eligible for the prize. Neither claimed sole credit nor disparaged the other.

Consequently, Kilby, a prolific innovator, was rewarded as an employee and led a comfortable life. Meanwhile, Noyce left Fairchild, co-founded Intel, and died a billionaire.

DNA Sequencing

DNA sequencing creates a map of DNA. The process reads DNA like a computer reads a hard drive. Eventually, the technology will allow scientists to understand and manipulate life functions.

In 1955, Sanger discovered how to sequence DNA, which would later win him the Nobel Prize. He is one of four people in the world to win the Nobel Prize twice.

In 1977, the first full DNA sequence was performed. Allan Maxam and Walter Gilbert created a chemical-based method that allowed purified samples of DNA to be sequenced without further cloning.

Progress proceeded rapidly. By 1987, Sanger sequencing machines could generate about 1,000 base pairs per day. By 2001, automated genomic sequencing centers generated up to 10 million base pairs per day. In 2005, new instruments were released that allowed the inexpensive sequencing of entire genomes. These were called “next-generation sequencing,” illustrating the difference of the STEM crowd from their more creative classmates. This period is referred to as the “democratization” of sequencing due to the low-cost and potentially high-impact sequencers.

Next-generation sequencers were highly parallel, with many base pairs being sequenced at the same time. They worked at a tiny scale, typically on a chip. The sequencers were fast, low-cost, and read a small amount of DNA rather than a large part of the strand.

The Human Genome Project, sequencing an entire person, started in 1990 and completed in 2003; it cost about $1 billion. Today, sequencing an entire genome takes about an hour and costs about $100.

DNA sequencing is seen as the key to future medicine. For example, scientists can eventually sequence a person, a virus, and devise a specific medicine that kills a specific virus in a specific person. The method is already in primitive use in the field of oncology, where customized immune “t-cells” are tuned to kill cancer cells. When it works, patients report being able to literally see cancer tumors melt away after being injected. While the medical technology promises to eventually be a Star-Trek like system — take a scan and give a shot that cures anything — it is still in its infancy.

Nuclear Power

One of the great physicists, Fermi won the Nobel Prize in 1938, at the age of 37. No sooner did he receive his prize than he fled from his home in fascist Italy to New York City, taking US citizenship.

Eventually, Fermi and the other nuclear scientists had convinced President Roosevelt that the Nazis could and would produce a nuclear bomb, which led the US government to grant them virtually unlimited funding.

On Dec. 2, 1942, Fermi’s reactor ー under the squash court at the University of Chicago ー went critical to become the first self-sustaining nuclear reaction.

Fermi would eventually work on the Manhattan Project, to develop nuclear weapons and the Atomic Energy Commission.

Like many early nuclear scientists, Fermi died of cancer at the young age of 53.

Eventually, in 1951, Walter Zinn connected a Fermi reactor to the rest of the equipment needed to generate electricity. This created the first working nuclear power plant.

Electron Microscope

Electron microscopes enable scientists to see extremely small particles.

In the 1920s, scientists discovered that electrons in a vacuum behave much like light except they can be manipulated with electric and magnetic fields. Since electrons curve around particles, these electron microscopes are vastly more powerful than traditional light-based microscopes.

Ruska invented the electron microscope at Siemens, as an employee. Eventually, he eventually left to serve as director of the Fritz Haber Institute then as a professor at the Technical University of Berlin. Although the microscope worked it did not produce especially useful images.

Eventually, Max Knoll invented the first Transmission Electron Microscope, refining Ruska’s invention. Knoll’s microscope produced vivid images. Later enhancements included the Scanning Tunneling Microscope.

Ruska won the Nobel Prize for physics in 1986.

Antibiotics

“I did not invent penicillin. Nature did that. I only discovered it by accident.”

Sir Dr. Alexander Fleming

Few medical discoveries impacted life expectancy and quality of life more than antibiotics. Before their discovery, simple wounds were often fatal. For example, during the US Civil War, most soldiers eventually died from infection, not from their wounds.

No sooner did he return to his lab on Sept. 3, 1928, than Dr. Alexander Fleming, a bacterial researcher, noticed that bacterial growth was oddly inhibited in one of his petri dishes. At first, he called the agent inhibiting the growth, Penicillium, “mould juice” but later changed the name to Penicillin.

Subsequently, many other scientists worked over time refining his innovation into a usable drug, with work rapidly progressing during the onset of WWII. Florey and Chain worked on the core drug and Heatley figure out how to manufacture it in bulk. Fleming, Chain, and Florey shared the Nobel Prize.

Following in the footsteps of other great scientists, Fleming donated his patent rights to the US and UK governments, ensuring penicillin could be widely produced at low cost.

King George VI knighted Fleming in 1944. Although he lived well as a respected academic researcher most financial compensation flowed to others.