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When you think of world-saving heroes, obvious answers come to mind: Superman, Captain America, Randy Quaid’s character from Independence Day, the usual.  But there are real life people who have thousands, millions, and in one case a billion lives in the real world, even within living memory, and you’ve probably never heard their names.  

Some heroes are work hard at it, but for others it comes naturally.  Take the case of James Harrison. In 1951, a 14-year-old Harrison awoke from a major chest surgery in an Australian hospital.  Doctors had removed one of his lungs in a procedure that had taken several hours and would keep him hospitalized for three months.  But Harrison was alive, thanks in large part to 13 units, almost two gallons, of transfused blood he had received. Harrison vowed that he would become a blood donor to help others, though he did have to wait four years before he was old enough.  After turning 18, Harrison made good on his word, donating whole blood regularly with the Australian Red Cross Blood Service.

 

Around the same time, doctors in Australia were struggling to figure out why thousands of births in the country were resulting in miscarriages, stillbirths, or brain defects in the babies.  “In Australia, up until about 1967, there were literally thousands of babies dying each year, doctors didn’t know why, and it was awful,” Jemma Falkenmire, of the Australian Red Cross Blood Service.  The babies, it turned out, were suffering from hemolytic disease of the newborn, or HDN. The condition most often arises when a woman with an Rh-negative blood type becomes pregnant with a baby who has Rh-positive blood, and the incompatibility causes the mother’s body to reject the fetus’s red blood cells.

 

Doctors theorized that it might be possible to prevent HDN by injecting the pregnant woman with a treatment made from donated plasma with a rare antibody, if they could find it.  Researchers scoured blood banks to see whose blood might contain this antibody, and found a donor in New South Wales: James Harrison. By then, Harrison had been donating whole blood regularly for more than a decade. He has said he didn’t think twice when scientists reached out to him to ask if he would participate in what would become known as the Anti-D Program.  Needless to say, he agreed. Before long, researchers had developed an injection, called Anti-D, using plasma from Harrison’s donated blood. The first dose was given to a pregnant woman at Royal Prince Alfred Hospital in 1967, according to Robyn Barlow, the Rh program coordinator who found Harrison.

 

Every two weeks for over for sixty years, James Harrison made the trek to the Red Cross to donate blood.  His plasma has been used to make millions of Anti-D injections. Because about 17 percent of pregnant women in Australia require the Anti-D injections, the blood service estimates Harrison has saved 2.4 million babies from death or life-stunting disabilities in the country.  Scientists still aren’t sure why Harrison’s body naturally produces the rare antibody, though, but think it is related to the blood transfusions he received as a teenager. Through the decades, Harrison has brushed off excessive praise, seeing nothing particularly remarkable in what he did.  Countless others did think Harrison is remarkable, though. He picked up the nickname the “Man With the Golden Arm,” along with accolades large and small, from the Medal of the Order of Australia in 1999 to the Guinness Book of World Records in 2003.

 

Harrison made his final trip to the blood donation center. At age 81, he was already past the age limit allowed for donors, and the blood service had decided Harrison should stop donating to protect his health.  In total, Harrison donated 1,173 units of blood. That puts my 30 donations over the last 20 years to shame. How long has it been since you donated? It only takes 15 minutes and there’s cookies. Don’t be bothered if they have Hydrox and not Oreos.  Hydrox are actually the original and Oreo is the knock-off, even though Oreo won when the two brands finally ended up in court. Besides, Hydrox are kosher. What did all that have to do with James Harrison? Not much; it’s just how my brain works, like a coked-up squirrel running a maze.  The struggle is real.

 

From needles for drawing blood, we move to needles for injecting vaccines.  As someone who did not die as a child from a wholly-preventable disease, I think vaccines are the bee’s knees.  And most of the vaccines that have kept us alive for the past two generations were created by one man, who didn’t even want credit for it.  Virologist Maurice Hilleman dedicated his life to creating vaccines to eradicate childhood illnesses. By the time of his death in 2005 at the age of 85, he had developed more than 40 vaccines including Measles Mumps and Rubella (MMR), chickenpox, meningitis, pneumonia, hepatitis A and hepatitis B.

 

The fragility of life was with Maurice Hilleman from the day he was born in 1919, when both his twin sister and mother died.  This was the same year the Spanish flu killed around five percent of the world’s popular. Hilleman grew up tending chickens on his father’s farm, which would prove surprisingly relevant in later years, before earning a full scholarship to Montana State University.  Majoring in chemistry and microbiology, he graduated first in his class, then on to graduate school, earning his doctorate in microbiology from the University of Chicago in 1944.

 

When Hilleman started his first job at the pharmaceutical company E. R. Squibb & Sons in 1944, American soldiers deployed in Japan had been contracting Japanese encephalitis-B from infected mosquitoes.  As chief of the Department of Respiratory Diseases at Army Medical Center (known today as Walter Reed Army Institute of Research), Hilleman studied pandemics. He was able to recognize patterns in the type and severity of pandemics, to the point where he predicted with stunning accuracy when they would hit.  When Hilleman and a colleague saw signs of an impending flu pandemic spreading through Hong Kong in 1957, they were determined to stop it. Racing against the clock, the men oversaw the production of 40 million vaccines that were quickly distributed in the U.S. About 69,000 Americans died from the flu, but experts say the toll would have been far worse without the vaccines.  Hilleman received the Distinguished Service Award for his work.

 

If you find stories of underreported pandemics interesting, Google American Samoa and Spanish Flu.  That island was one of the only places not to see a single influenza death, because the governor took the reports he was hearing seriously and blocked all incoming ships from making port.  Tangent-bonus fact: the 1918 flu pandemic was called the Spanish flu not because it came from Spain, but because Spain reported on it freely in the news, whereas the opposing sides of WWI both kept the severity of the outbreak to themselves so the enemy wouldn’t know how badly they’d been hit.

 

Hilleman moved to the Merck pharmaceutical company and continued his laser-focus attention on the prevention of other diseases. Some of them hit particularly close to home. When his daughter Jeryl Lynn came down with the mumps in 1967, he swabbed her throat and collected the virus specimens to take back to his lab. His other daughter, one-year-old Kirsten, was among the first to take the experimental vaccine. “There was a baby being protected by a virus from her sister, and this has been unique in the history of medicine, I think,” Hilleman remembered in an interview.  The strain that Hilleman collected from his daughter that night has reduced the incidence of mumps to fewer than 1,000 cases a year, from 186,000. For perspective that’s going from the capacity of Rose Bowl Stadium twice-over to half the capacity of my suburban high school. How did the chickens mentioned earlier contribute? Fertilized chicken eggs were used to incubate vaccines. They’re a cheap source of protein *and life-saving medicine.

 

In 1963, the Food and Drug Administration granted the first license for a vaccine against measles.  Under pressure from public health officials to stop a disease then killing more than 500 American children every year, Dr. Hilleman and Dr. Joseph Stokes, a pediatrician, devised a way to minimize the side effects by giving a gamma globulin shot in one arm and the measles vaccine in the other.  Dr. Hilleman then went on to refine the vaccine over the next four years, eventually producing the much safer “Moraten” strain that is still in use today. Rather than put his name on it, Hilleman named it “Moraten,” short for “more attenuated enders.” “Attenuated” means weakened and much of the early work on the virus had been done in the laboratory of John F. Enders at Boston Children’s Hospital.  

 

Another crucial event in the development of M.M.R. happened that spring of 1963: An epidemic of rubella began in Europe and quickly swept around the globe.  In this country alone, about 11,000 newborns died and an additional 20,000 suffered birth defects, including deafness, heart disease and cataracts, according to the CDC.  Dr. Hilleman was already testing his own vaccine, but agreed to work with a vaccine being developed by federal regulators, which he later described as “toxic, toxic, toxic.”  By 1969, he had cleaned it up enough to obtain F.D.A. approval and prevent another rubella epidemic. Finally, in 1971, he put his vaccines for measles, mumps and rubella together to make M.M.R., replacing a series of six shots with just two.

 

Did I say “finally”?  In 1975, Hilleman joined Merck & Co (yes, they’re ‘big pharma’ but we’re talking about Hilleman right now).  In 1978, having found a better rubella vaccine than his own, Dr. Hilleman asked its developer if he could use it in the M.M.R.  The developer, Dr. Stanley Plotkin, of the Wistar Institute in Philadelphia, was momentarily speechless. It was an expensive choice for Merck, and might have been a painful one for anyone other than Dr. Hilleman.  “It’s not that he didn’t have an ego. He certainly did,” Dr. Plotkin recalled in a recent interview. “But he valued excellence above that. Once he decided that this strain was better, he did what he had to do,” even if it meant sacrificing his own work.

 

It’s impossible to know how many lives Maurice Hilleman’s worked has saved.  By one estimate, it’s eight million….per year. Though he was forced to retire at age 65, he continued to work for the greater good, such as serving as an advisor to the World Health Organization (WHO).  He was not awarded a Nobel Prize, but in 1988, President Ronald Regan awarded him the National Medal of Science. He died of cancer in 2011. Rather than a retirement full of accolade, Hilleman got hate mail and death threats, thanks to the discredited ““study”” linking the MMR vaccine to autism published by (let’s call a spade a spade) utter con artist Andrew Wakefield.  I may only be one tiny podcaster, but Dr. Maurice Hilleman, you have my gratitude. And if you are of the anti-vax camp and somehow listen to my show, rest assured that I hold firmly to the belief that everyone is entitled to their own opinion. They are not, however, entitled to their own facts.

 

When it comes to deadly animals, sharks, cobras, and anything native to Australia all collectively pale in comparison to the kill count of the mosquito, courtesy of its tiny passenger, malaria.  In 2008, the mosquito-borne parasites that cause the illness, Plasmodia, infected 247 million people and caused almost one million deaths. The ailment strikes children particularly hard, especially those in sub-Saharan Africa.  It affects more than 100 countries, from Asia, Latin America, the Middle East, to parts of Europe, thanks in no small part to traveling humans. Symptoms include fever, headache, and vomiting; malaria can quickly become life-threatening by disrupting the blood supply to vital organs.

 

The single greatest arrow in our quiver in the fight against malaria was discovered by a doctor looking not only to the future, but also to the wisdom of the past.  The drug is called artemisinin and is in use today because of work in 1970s by Chinese scientist Youyou Tu and her team, who spotted references to a fever-easing plant in ancient Chinese medical texts and sought to extract the active ingredient to combat malaria.  Because of their work, malaria death rates have decreased 47% worldwide and infection rates among children have dropped 46%.

 

Tu was born in Zhejiang, China in 1930.  A tuberculosis infection interrupted her high-school education, but inspired her to go into medical research.  In 1955, Youyou Tu graduated from Beijing Medical University School of Pharmacy and continued her research on Chinese herbal medicine in the China Academy of Chinese Medical Sciences. Tu studied at the Department of Pharmaceutical Sciences and later trained for two and a half years in traditional Chinese medicine.

 

Youyou’s entire life changed in 1969.  She had been working as a pharmacology teacher and research scientist at Beijing’s Academy of Traditional Chinese Medicine – a unique institute of historians, chemists, scientists, and doctors dedicated to bringing traditional Chinese practices up to scientific standards, when she suddenly found herself appointed head of a newly formed research group of chemists and pharmacologists at the institute for a top-secret military program called Project 523.  Established by Chairman Mao himself, Project 523’s main goal was to find ways of preventing and curing malaria. For two years, the project had focused on developing western-style antimalarial drugs, but synthetic compounds they tested bore no fruit. Project 523 turned to traditional Chinese medicine and herbal remedies for answers. This was actually a surprising turn of events. One of the main objectives of Mao’s Cultural Revolution was to preserve communist ideology by purging China of traditional literature and art.  Intellectuals and scholars were now considered to be the lowest caste of Chinese society and scientific research was only sanctioned if its purpose was practical.

 

Tu had been specifically chosen, she was informed, because of her unique combination of skills. She had a degree in western pharmacology, yet she knew how to differentiate thousands of traditional herbs.  Youyou felt deeply honored, especially since she was young and a woman appointed to this post. She knew the road ahead would be difficult. Strains of malaria were resistant to every available drug and scientists worldwide had already screened over 240,000 compounds without a shred of success.  Also not making things any easier for Tu Plus was the facts that she was a single parent. Her husband had been “sent down to the countryside” on a mandatory exchange program for “re-education.”

 

Tu and her team traveled from village to village to talk to traditional medicine practitioners.  Since most of their skills had been handed down orally, the team recorded the remedies and treatments they learned in notebooks.  They also combed the library for every medical text they could lay their hands on. In the end, they collected over 2,000 recipes for herbal, animal, and mineral prescriptions, choosing from these 640 with the best hope of a potential cure.  Back in Beijing, her team began distilling the most viable prescriptions into 380 herbal extracts they could test on malaria-infected mice. One of their biggest challenges was overcoming the primitive conditions of their own lab. They were forced to use household pots and pans as equipment, their facilities were poorly ventilated, and exposure to harsh organic solvents caused them all health issues.  

 

By 1971, the team was fairly certain it should focus solely on the herb quinghao, or sweet wormwood.  Its first mention as a medicinal herb dated back 2,000 years to a silk scroll from the Han Dynasty called Prescriptions for 52 Kinds of Diseases.  But quinghao cropped up frequently as an ingredient in remedies for intermittent fevers, a symptom of malaria, in multiple medical texts throughout the centuries.  But there were many unanswered questions: Which species of quinghao? From what region of China? When should the plant be harvested? And which part should they use? Other research groups in Project 523 joined the quest.  Through a painstaking process of elimination, Artemisia annua L was found to be the *only variety of quinghao containing antimalarial properties. However, no extract of it had produced a consistent, positive effect on malaria-infected mice.

 

Frustrated, Tu turned once again to ancient texts for clues.  She reread a medical manuscript from the East Jin Dynasty, written in 340 that advised: “A handful of quinghao immersed in two liters of water, wring out the juice, and drink it all.”   It was so simple! Ge Hong steeped his quinghao in cold water, but they had been boiling theirs. The heat had no doubt damaged the herb’s active ingredients. Her team immediately modified its extraction methods and sure enough, on October 4, 1971, they finally found an extraction – Sample No. 191 – that proved to be 100% effective in curing malaria- infected mice. They began testing infected monkeys, and it again proved effective. In early 1972, they called their new drug Artemisinin.  The next step was, of course, to begin testing humans. To speed things along, Tu and her team volunteered to use themselves as test cases, confident that 2,000 years of Chinese medicine couldn’t be wrong. By August of 1972, Tu was able to perform clinical trials of Artemisinin on 30 malaria patients.

 

It would take another five years of intensive chemical analysis before Artemisinin’s molecular structure could be isolated. In 1981, Tu presented the drug at a World Health Organization meeting on malaria in Beijing and in 1986, the Chinese Ministry of Health finally granted Artemisinin status as an officially approved drug.  It had taken 15 long years for Mao’s secret Project 523 to produce a cure, but it was one that would ultimately save millions of lives. From the 1990s, artemisinin gradually took on a frontline role, replacing previous generations of medicines that had lost their effectiveness as malaria parasites became resistant to them.

The drug acted fast initially to attack the parasite, but was used in conjunction with longer-lasting medicines to destroy those parasites that continued to hold out, said Teresa

 

Artemisinin has greatly increased the odds of survival for people hit with the most stubborn strains of the disease.  The chances of dying from malaria have halved from one in five a decade ago to nearly one in 10 today in severe cases where people were hospitalised.

World Health Organisation statistics show that malaria deaths fell from about two million per year in the early 2000s to an estimated 584,000 in 2013. Photo: US Centres for Disease Control and Prevention.  World Health Organisation statistics show that malaria deaths fell from about two million per year in the early 2000s to an estimated 584,000 in 2013.

 

The malaria parasite has a tremendous ability to mutate, causing it to build resistance to treatments when they are prescribed or used incorrectly.  There have been two examples in history of malaria drugs losing their effect, at a cost of millions of lives. From the 1950s to 1970s, chloroquine-resistant parasites spread from Asia to Africa.  Chloroquine was then replaced by sulphadoxine-pyrimethamine (SP), which itself lost its parasite-killing powers and was followed by artemisinin. There are reports from Myanmar and Africa that even the aremisinin isn’t working as well as it once had, but doctors with the WHO are testing increased doses and combination therapies.

 

There were some controversy attached to the decision to award Tu the Nobel prize in Physiology or Medicine in 2015 as hundreds of scientists were involved with Project 253, but it was Tu who brought in the sweet wormwood plant and created a method for extracting the active ingredient, as well as conducting the first human trials.  Throughout Tu’s career, she has continued to use the strategy of building on the knowledge of the past to create solutions for the future. She is a research scientist, pharmacologist, educator – and now Nobel Laureate – but she considers herself, first and foremost, a lifelong student.

 

A medical crisis need not be germ-based to spread dangerously.  Around 1960, tens of thousands of babies were born with improperly developed limbs, and, in some cases, malfunctioning eyes, ears, or other organs.  It was a tragedy like never seen before, catastrophically striking families in more than 40 countries, from Germany, Japan, England, but not the United States.

 

The cause of these birth defects was a new sedative called thalidomide, which had been approved in these countries to treat pregnant women for morning sickness.  It seemed like a godsend, especially for woman with hyperemisis gravidarum, which is like morning sickness gone nuclear and can be a serious problem. The studies done on this drug before it was approved were limited in scope and did not reveal its devastating side effects. It was quickly taken off the market, but for the many babies who were hurt or even prematurely died, the damage was done.

 

So why was thalidomide not approved in the U.S.?  It was largely because of one woman — a new drug reviewer named  Frances Oldham Kelsey. Born in 1914 in British Columbia, Kelsey earned both her bachelor of science and master of science degrees from McGill University, Montreal.  In the mid-1930s, Kelsey wrote to Eugene Geiling, a researcher at the University of Chicago, asking to work in his lab and study for a doctorate. Dr. Geiling replied with an offer of a scholarship, addressing the letter to “Mr. Oldham.”  In her autobiography, she remembered Dr. Geiling as a “very conservative and old-fashioned” man who “did not hold too much with women as scientists.” His assumption that Frances Oldham was male might have played a role in her scholarship and subsequent education.  Quick tip: female Frances is spelled with an E like “her” and male Francis is spelled with an I like “his.” There you, now you’ll never mix it up.

 

In 1938, Kelsey earned her Ph.D. from the University of Chicago, and went on to teach there from 1938 to 1950.  Dr. Frances Oldham married Dr. Fremont Ellis Kelsey, a fellow faculty member at University of Chicago, in 1943. Their two daughters were born while she earned her medical degree at the University of Chicago Medical School.  Kelsey then worked as an editorial associate at the American Medical Association, pharmacology professor, and a general practitioner, before moving to Washington, D.C., to begin her long and distinguished career at the Food and Drug Administration, where she became chief of the Division of New Drugs, director of the Division of Scientific Investigations, and deputy for Scientific and Medical Affairs, Office of Compliance.

 

Kelsey was assigned by the FDA to review applications from pharmaceutical companies for drug approval.  It was a job she was well-suited to, have already proven herself to be masterful detective. While she was earning her PhD in Pharmacology, Kelsey helped pinpoint a toxic ingredient in another drug called Elixir Sulfanilamide.  The Elixir was marketed as something of a cure-all for anything from gonorrhea to a sore throat, which should always raise an eyebrow. The drug was very bitter, so its makers added a sweet-tasting solvent to make it more palatable. The sweetener, Kelsey discovered, was antifreeze.  The drug had already killed more than 100 people by the time the FDA was able to take it off the market. Bonus fact: While it is imperative to keep antifreeze away from children and pets, it’s a wives tale that cats will drink it because of its sweet taste. Cats can’t taste sweet at all.  Why would they lick it up off the garage floor then? Maybe just to run up a vet bill. Like the internet says, cats are assholes. Trust me to know; I have seven right now, six of which are inside. It’s like living in a furry, angry koi pond.

 

When the paperwork for thalidomide, sold under the brand name Kevadon, hit Kelsey’s desk in the fall of 1960, she was expect to approve it, since it was already popular in Europe.  Her critical eye, however, quickly spotted holes in the data “proving” that thalidomide was safe and effective, and she rejected the application. The results in their application were more testimonials than quantifiable science and the developers had failed, or refused, to do a placental barrier test, which shows whether a drug taken by a pregnant woman reaches the fetus.  A chemist working under Kelsey who spoke German also pointed out a higher-than-acceptable number of translation errors in the English copy of the application. In something of a baptism by fire, the thalidomide application was the first she handled in her new position. And there was push-back, you’d better believe, as the drug company lodged complaints against Kelsey with her superiors.  Nevertheless, for the next fourteen months, she wouldn’t budge. In November 1961, Dr. Kelsey’s careful vigilance was vindicated. Kevadon was taken off the market in its native West Germany and in other countries soon after.

 

In the aftermath of thalidomide’s European release, thousands of children in Europe were born with partial limbs, blindness, deafness, and/or cognitive impairment, that is to say those who did not die in utero, which is thought to be as much as four times as many.  Thalidomide’s effects on fetal development are so dramatic and predictable that doctors can actually pinpoint during which week of pregnancy the mother began to take it by which body system was affected. There’s a fascinating documentary on Netflix about the legal struggles of the families afterwards called called “Attacking the Devil: Harold Evans and the last Nazi war crime.”  Kelsey’s refusal to budge prevented the same from happening in the US. That’s not to say there was zero ‘children of thalidomide’ in the states, thanks to drug reps giving out samples without FDA approval, but it was only about 1% the number of cases seen abroad.

 

On August 7, 1962, President John F. Kennedy awarded Frances Kelsey the highest honor given to a civilian in the United States, the President’s Award for Distinguished Federal Civilian Service. She was the second woman to ever receive the award. Kennedy acknowledged “Her exceptional judgment in evaluating a new drug for safety for human use has prevented a major tragedy of birth deformities in the United States. Through high ability and steadfast confidence in her professional decision she has made an outstanding contribution to the protection of the health of the American people.”

 

Kelsey helped shape and enforce amendments to FDA drug regulation laws to institutionalize protection of the patient in drug investigations. These regulations required that drugs be shown to be both safe and effective, that informed consent be obtained from patients when used in clinical trials, and that adverse reactions be reported to the FDA.  In 2000, Kelsey was inducted into the National Women’s Hall of Fame, and in 2001, at the age of 87, she became a Virtual Mentor for the American Medical Association.

 

And that’s where we run out of ideas, at least for today, but I can almost guarantee you that this is the first installment of a series.  There were at least ten names on my list when I started, but I was only about to cover four, so I chose ones within a theme. I didn’t even get to Sadiman, the man who saved his entire village in Indonesia from drought, flood, and starvation by single-handedly replanting a forest.  Absolute legend. Would you like to hear more stories like these? Share this episode on your social media and say “give us more unsung heroes!” Thanks for spending part of your day with me.

 

 

Sources:

https://www.washingtonpost.com/news/to-your-health/wp/2018/05/12/for-six-decades-the-man-with-the-golden-arm-donated-blood-and-saved-2-4-million-babies/

https://www.ericksonliving.com/tribune/articles/2018/06/legacy-dr-maurice-hilleman

https://www.smithsonianmag.com/smithsonian-institution/you-should-thank-maurice-hilleman-helping-you-live-past-age-10-180965369/

https://hillemanfilm.com/dr-hilleman

https://www.nytimes.com/2013/05/07/health/maurice-hilleman-mmr-vaccines-forgotten-hero.html

https://www.scmp.com/news/china/society/article/1864597/drug-chinas-nobel-prize-winner-tu-youyou-worked-has-saved

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966551/

https://blog.eftours.com/ef/news/nobel-journeys-tu-youyou

https://futurism.com/meet-the-woman-who-saved-millions-of-lives-and-stopped-an-epidemic

https://cfmedicine.nlm.nih.gov/physicians/biography_182.html

http://advocatesaz.org/2018/03/14/whats-in-a-name-frances-oldham-kelsey-and-the-power-of-skepticism/