Viagra (Sildenafil)

It’s hard to write seriously about Viagra. No sooner did the drug help erectile dysfunction than it opened the opportunity for countless puns. Additionally, the name of co-inventor Albert Wood worsens the situation. However, in hindsight, Viagra cured a serious problem.

Background

Wood and Viagra co-inventor Peter Dunn were working on a blood pressure medicine. Early tests were disappointing. Viagra didn’t meaningfully control blood pressure but it was impossible to ignore a side effect that popped up. Subsequently, men reluctantly reported erections.

While we try to maintain a serious composure in these entries it is impossible to imagine study participants reporting Viagra’s side effects without at least a smirk. Notwithstanding, they overcame the embarrassment and rose to the occasion.

Before Viagra, there was no cure for erectile dysfunction. Nobody thought the problem was serious. Thanks in part to the AIDS epidemic sex again became taboo, something necessary only to make babies. Puritans defined sexual gratification as a dirty primal instinct reserved solely for men.

Thanks to sexist portrayals of women as Victorian matriarchs uninterested in sex, people positioned Viagra solely as a drug for men. There is no acknowledgment that, except for gay men, it is useless without a woman.

Yes, men with erectile dysfunction wanted erections. And their sexual partners wanted the same. And nothing is wrong with that. Erectile dysfunction affected the well being of countless men and women.

Pfizer’s Multi-Billion Dollar Mistake

Bell and his team alleged were working on a high-blood-pressure drug that proved ineffective but had an unintended side effect, causing erections in men. Pfizer pivoted to testing the usefulness of their drug and found it effective to treat erectile dysfunction. Viagra became a blockbuster.

Dunn and Wood are the first registered patent holders for Viagra, in UK patent WOWO9849166A1. “I can’t say anything, you’ll have to talk to the press office,” said Wood when asked who invented Viagra.

Furthermore, a Pfizer spokesperson, answering questions about whether Dunn and Wood were adequately rewarded, answered with uncharacteristic honesty. “Life might seem cruel, but they are paid to work for the company and the company owns their innovations. Literally, hundreds of people at Pfizer have been involved in developing the drug. You can’t really point to two individuals and say they spawned Viagra.”

Protease Inhibitors

History

They first called it gay men’s cancer. Then announced it affected intravenous drug users. People became skeptical when they added Haitians as a risk factor. Being gay, a drug user, or black was a death sentence? My openly gay high school English teacher became sick and quickly died in the middle of a semester.

Eventually, the monster disease that ended the sexual revolution started by the birth control pill gained a name, Acquired Immunodeficiency Syndrome, or AIDS. Making it especially scary, the disease slept undetected for years until it woke up to quickly kill the next victim.

Nothing was subtle about death from AIDS. They became emaciated and developed all manner of exotic cancers. The vast majority died but some, for reasons not understood to this day, resisted the disease for a long time.

Eventually, doctors traced AIDS to the HIV virus. Good to know but it didn’t stop public panic. In the blink of an eye, the worst permanent sexually transmitted disease went from herpes, an embarrassing annoyance, to a killer.

A Killer, Unleashed

Basketball legend Magic Johnson contracted HIV: people refused to play with him. Science fiction legend Isaac Asimov caught the virus from a blood transfusion and, like countless others, it killed him. Tennis legend Arthur Ashe died of AIDS. Movie star Rock Hudson, the wretched red baiter Roy Cohn, 50s housewife heartthrob Liberace, and countless other died. The disease didn’t discriminate between rich or poor, liberal or conservative. The only difference wealth and power made was whether sufferers died in top-tier hospitals or public wards.

A New Hope

Two protease inhibitors, a class of antiretroviral drug, came about in late 1995-1996. They existed as seldom used anti-virus drugs but Ho experimented, using combinations with AIDS patients. The results were immediate.

By 1995, the death rate from AIDS increased approximately 20 percent per year in the US alone. AIDS was not a sexually transmitted disease, said the experts. By then nobody believed them.

Within two years, after Ho’s use of antiretrovirals, AIDS deaths dropped by over half, from 41,699 annual deaths to 16,685. Due to protease inhibitors, people infected with HIV have a lifespan compatible to people who are virus-free. More recently, low dose protease inhibitors are used as a prophylactic and prevent contracting HIV.

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.

Synthetic Drugs via Genetic Manipulation (Biotech)

Synthetic hormones via genetic manipulation allow for new and improved drugs. For example, insulin that remains stable at room temperature, growth hormones grown in a vat instead of harvested from cadavers, and countless others.

Background

Herbert Boyer was a scientist working on synthesizing DNA, one of many.

Robert Swanson was a venture capitalist. He left Citi, where he ran a $100M venture capital fund, to struck out on his own. The then two-person firm of Kleiner, Perkins gave him a desk but not a job.

Swanson convinced Boyer to start a company to create synthetic hormones.

The first one they worked on was growth hormone somatostatin. Development took a long time, landing Swanson in the hospital with a nervous breakdown. However, they achieved creating the synthetic hormone Aug. 15, 1977.

Kleiner, Perkins, & Genentech

Subsequently, they went on to create synthetic insulin, rather than animal-derived insulin. Racing against others they achieved that, too, licensing it to Eli Lily who branded it Humulin. In Oct. 1985, Genentech released human growth hormone.

While starting Genentech, Swanson survived for six months on unemployment. Eventually, after Boyer and others gained some traction, Kleiner & Perkins invested $100,000 and the company. Kleiner, Perkins eventually invested another $100,000 that subsequently returned 800x their investment.

Besides funding issues, Boyer faced ridicule from the scientific for commercializing his work. Additionally, he was subject to patent challenges from thought partners later.

There was widespread public hysteria about creating biohazards. Luddites argued that manipulating human DNA would inadvertently unleash a zombie apocalypse. As of 2019, the only sign of a zombie apocalypse is people walking while staring at smartphones, a phenomenon not tied to synthetic hormones.

Micro-Electro-Mechanical Systems (MEMS)

MEMS are literally microscopic-machines. The best-known MEMS are the accelerometers that have become ubiquitous in smartphones, allowing precise tracking of movement on the X, Y, and Z-axis. Significantly, MEMS are the reason your phone can sense movement. Additionally, other MEMS devices include miniature microphones, projectors, cameras, and countless others.

MEMS were first proposed in 1959 via a paper by physicist Richard Feynman, “There’s Plenty of Room at the Bottom.” He theorized about the growth in micro and nanotechnology.

In 1964, Harvey Nathanson of Westinghouse introduced the first working MEMS device, a tiny transistor. Subsequently, during the 1960s and 1970s work continued, with machines etched into silicon working as pressure sensors. Eventually, these evolved into MEMS-based blood pressure monitoring devices.

In 1979 HP released a MEMS controlled inkjet nozzle to create the inkjet printer.

The first crude MEMS accelerometer dates to 1982. Airbags were important because they must fire when needed, never fire when not needed, and react almost instantly.

By 1993 Analog Devices produced the first real 3D MEMS accelerometer. At $5 it cost far less and functioned far better than other solutions. Countless airbag deployments relied on this inexpensive yet accurate accelerometer. Eventually, Nintendo adopted it for use to track motion in the Wii gaming system.

MEMS technology continues to develop with scientists working on microscopic insulin pumps, glucometers, DNA arrays, and other lab-on-a-chip applications.

Magnetic Resonance Imaging (MRI)

MRI allows physicians to see and diagnose soft tissue without surgery.

Background

MRI is one of these cases where everybody argues somebody else invented it for patent priority. However, courts and historians find that physician Raymond Damadian was first to make an MRI that scans people (prior MRI’s would scan small pieces of organic material).

Damadian went on to form Fonar Corp. They failed to sell working MRI machines but made a lot of money via patent litigation. Eventually, Fonar won a $128.7 million patent infringement case against GE.

Nobel Fiasco

Despite a strong record, and agreement by most historians, the 2003 Nobel Prize for Medicine, for the MRI, went to Lauterbur and Mansfield.

Damadian argues, persuasively, their “innovation” is the application of his work. They renamed his machine but focused it primarily on the imaging, with a different name. Damadian named his machine Nuclear Magnetic Resonance Spectroscopy (NMR). Scientists believe the word “nuclear” would scare patients so renamed it Magnetic Resonance Imaging (MRI). Radiologists thought the word “imaging” to be important, but the machine is the same.

Lauterbur couldn’t stand Damadian and announced he would reject a Nobel Prize if asked to share it with him. Despite a surly personality, Lauterbur did figure out how to aim the MRI to different places and also how to transform the cellular resonance (the “R”) into the images we associate with MRI’s today. Lauterbur also claims to have created the idea of a whole-body scanner but scientists widely believe that Damadian announced the idea first. Damadian’s full-body MRI scanner is a Smithsonian exhibit as the first MRI machine.

Mansfield acted much more collegial, congratulating Damadian on his first scan and giving him credit (Mansfield created the second scan).

Damadian Invented MRI

Damadian first started experimenting with MRI in 1971 but it wasn’t until Jul. 3, 1977, that he ran the first successful scan. The images were much cruder by then more abundant CT scanners. What people didn’t realize is how much more an MRI would eventually see.

The National Cancer Institute had withdrawn its support of Damadian, quoting an NCI spokesman, Larry Blaser: “We don’t look on nuclear magnetic resonance as a promising area of diagnosis.” (Evans)

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

Controlled Drug Delivery

Controlled drug delivery is a simpler and more convenient way to slowly release drugs than taking low-dose pills or injections at frequent intervals. Additionally, it also lowers the risk of incorrect dosage.

Zaffaroni invented controlled (slow) release drugs, mimicking the way the body releases hormones. Eventually, he created many pharma companies that went on to sell various slow-release drugs.

Zaffaroni improved his slow drug delivery by inventing the transdermal patch, founding a company ALZA for that innovation alone. Significantly, in 2001, ALZA sold to Johnson & Johnson for $10 billion.

Other Zaffaroni controlled drug delivery use cases include drugs to treat glaucoma, non-insulin dependent diabetes, chronic pain, nausea and motion sickness, and nicotine addiction. A skin patch, that looks like adhesive tape, delivers the drugs.

In-Vitro Fertilization

In-Vitro Fertilization (IVF) allows eggs to be fertilized outside the womb. In a controlled environment, fertilization is more likely to be successful.

In 1936, In-Vitro Fertilization (IVF) was first performed on rabbits by Dr. Gregory Pincus of Harvard University. He announced his invention and mentioned it might someday work on humans.

Rather than celebrate the breakthrough, the world was less than ecstatic, envisioning a Frankenstein. Eventually, a public outcry cost him tenure at Harvard and consigned him to become a private researcher where he invented the birth control pill.

Pincus co-invented the birth control pill with John Rock and his lab partner was JC Chang. It’s no coincidence that Chang went on to be the first to perfect an IVF rabbit, essentially copying Pincus’ work minus the hysteria. Rock was the first to extract a human egg, focused on the same type of work Pincus originally targeted.

Despite the breakthrough in human fertility — in-vitro fertilization and birth control pills — none of the men won a Nobel Prize.

Eventually, Patrick Steptoe and Robert Edwards completed IVF for humans. If they credited Pincus, Rock, or Chang at all they did so quietly.

To their credit, they refused to patent the process. Like the inventors of insulin and antibiotics, they did the opposite, publishing and teaching doctors how to achieve in-vitro fertilization. Their goal was reducing infertility and millions of babies have been born due to IVF. It’s also possible that since Pincus perfected the technique long before, it was ineligible for patent protection.

None of the men died either well-off or destitute. However, none achieved significant financial gain directly from IVF which, as of 2018, costs about $18,000 per attempt in the US.

Edwards was awarded the 2010 Nobel Prize for medicine for his work on IVF. Neither Edwards nor the Nobel committee mention Pincus, Rock, and Chang. They join a list of scientists who made groundbreaking breakthroughs where others gained the recognition. For example, Jonas Salk saved countless lives with his invention of the polio vaccine and was similarly snubbed by the Novel committee.

There are those who suggest antisemitism more than scientific merit played a large role since both Pincus and Salk were both Jewish.