section 3 4-6 – THE WONDERS WE CREATED AND THE POTHOLES WE DUG

Chapter 4 penicillin, TB, Syphilis and smallpox

Penicillin became available during the Second World War. It was discovered in the 1920s by Alexander Fleming, a Professor of Bacteriology at the University of London who was a medical officer in World War I. “Not known for fastidious laboratory organization,” he once had a cold, dropped mucous into a petri dish full of bacteria, placed the dish amidst the clutter at his desk,²⁶” and left it there forgotten, for two weeks. When he came back he noticed that his bugs were gone. He investigated and discovered lysozyme, the enzyme in tears and saliva that was responsible. He wrote up his finding, his account was published, and people in the field learned who he was.

On another occasion he noted that fluid coming from a penicillium mold killed the bacteria growing in the Petri dishes. He called the juice penicillin after the mold that produced it. Collecting a small amount, he wrote an article that was published in a medical journal and largely forgotten.

A decade later a group of Brits led by Howard Florey (a pathology professor) and Norman Heatley got interested in Fleming’s fluid. They got hold of the Penicillium mold and extracted enough to treat a few lab animals. In May of 1940 “they infected eight mice with a fatal dose of streptococcus. Four of the creatures were then injected with penicillin. Hours later “the untreated mice were dead and the penicillin-treated mice were still alive…. Penicillin’s spectacular possibilities were obvious.” More needed to be done, but Britain was at war and Florey’s research could not proceed. That’s why he and Heatley brought some of the mould to the U.S. They convinced scientists at the agricultural research lab in Peoria Illinois to help them search for a Penicillium mold that would produce more than a trickle of the magic juice. One of the labs mycologists, Kenneth Raper, found the super mold growing on a cantaloupe in a nearby store. It was “50 times more potent than anything previously tested, and it became the primogenitor for almost all of the world’s penicillin.” The group then looked for companies that could generate large amounts of the antibiotic and Pfizer stepped up big time. Their engineers knew had learned how to ferment gluconic acid in deep tanks and Pfizer purchased an old ice plant in Brooklyn that contained fourteen 7,500-gallon tanks. Then they converted the building into a highly productive penicillin factory.⁶⁵ After the war the company manufactured a second antibiotic, streptomycin, and later a third antibiotic, Terramycin.

In the decades before I entered the profession, students spent a lot of time learning about two of mankind’s chronic transmissible diseases: Syphilis and Tuberculosis. Scientists still aren’t sure if Syphilis arrived in the New World in the body of one of Columbus’ sailors or whether the bacilli was acquired from inhabitants of the Americas and, along with maize and potatoes, was brought to Europe. Some are still periodically examining the remains of ancient humans and looking for evidence.

In my days as a doctor syphilis was called the great imitator. If someone got sick and syphilis was the possible cause of the problem we were taught to always rule it out.

By the 1950s a blood test for its presence, the VDRL was drawn every time a person entered a hospital or obtained a marriage license. The test was invented before the World War I in a US public health service “venereal disease research lab”, hence its name. The test detects the antibody a person started making when they were infected by syphilis. Once penicillin, became available we could cure the disease and its incidence in the U.S. dropped. But it didn’t go away and “Syphilis still occasionally presents with non-typical features in a person who has another sexually transmitted disease, HIV.

The bacillus that causes the other chronic infection that has tormented mankind for thousands of years, tuberculosis, was identified in 1882 by the German physician, Robert Koch. Many seemed to cure their disease by spending a year in a sanatorium, breathing clean air and leading a healthy life. In the 1950s doctors were able to successfully treat most TB infections with a combination of antibiotics: streptomycin, discovered in 1943, INH in 1952, and Rifampin in 1963. Between 1954 and 1985 the number of infected people in the U.S. dropped from 80,000 to 20,000, and experts predicted that within a few decades TB would disappear. They were wrong. Poverty, HIV, and bacterial resistance reversed the trend, and the incidence of T.B. started to rise.

One of 4 people alive today, at some point in their lives was infected by the cough of a person with tuberculosis. 90 percent didn’t get sick. They mounted a cell mediated immune response and their body encased and imprisoned the bug, but didn’t kill it. It sometimes escapes. 10 million people currently have an active infection and a million and a half die each year.¹⁹

When I started medical school (1958), tuition was $600 a semester. By 2019 my school was charging $65,000 per year. With housing, food, and travel a student’s “estimated annual expenses were over $87,000.” They don’t say why they are selectively lowering tuition, but in 2019 the school plans to decrease fees by an average of $20,000 per student per year.⁷

The planet wide eradication of smallpox wasn’t the result of a new drug. It was the consequence of the expansive use of the century old vaccine that prevented people from developing the infection. A viral disease that plagued the human race for at least 10 centuries, Smallpox caused high fevers, severe headaches, vomiting, exhaustion, and a papular rash. It killed as many as three in 10 of those who were afflicted, and the people who survived were sometimes permanently scarred. George Washington got the disease when at age19 he was visiting Barbados. He was sick for a month and the disease left him with lifelong facial pock-marks.⁹

In1853 and 1867 the British Parliament made vaccination with modified cowpox compulsory. Much as cats and tigers are members of the same species, the viruses that cause cowpox and small pox are members of the same family. Each can cause pustular lesions. People who develop cowpox sometimes run a fever and are sick for a week. When a person recovers (or is vaccinated) their body is protected from the oft lethal disease.

Widespread vaccination in the U.S. contained the illness in the early 19^th century. Then people in the U.S. stopped vaccinating. There were outbreaks, and states attempted to enforce existing vaccination laws or pass new ones. The disease disappeared from North America in 1952 and from Europe in 1953. As recently as 1967 (according to the CDC) 10 to 15 million people in Africa, Asia, Indonesia, and Brazil were contracting Smallpox each year. That year 2 million died, many were scarred for life, and the World Health Organization started a program of worldwide vaccinations. They hoped to eliminate the terrible disease and seem to have succeeded. The bug’s last known “natural” victim was infected in 1977.⁵

Chapter 5 – narcotics, syphilis, TB, Vaccines

In 1935 a German physician and chemist discovered the first antibiotic, sulfa. (See chapter on FDA) Chloral hydrate, the first synthetic hypnotic was introduced in 1869, and in 1860 Albert Niemann, a German chemistry student “extracted cocaine from coca leaves and found and wrote that “when applied to the tongue it left a peculiar numbness.”

In the 1930s German chemists almost accidentally discovered the first synthetic pain relieving and addicting drug, meperidine—Demerol. In the subsequent century chemists developed a number of additional synthetic narcotics. One was created in 1953 by a group of European chemists led by Paul Janssen of Belgium. They added carbons, benzene and other chemicals to the part of meperidine that causes sedation and analgesia and in 1960 came up with fentanyl. The drug is 100 to 200 times more potent than morphine. I used it on patients when I performed colonoscopies. Doctors like it. Owned by Johnson and Johnson, it has recently been the cause of a number of over dose deaths.

In June 1971 President Nixon declared the U.S. war on drugs. Over the subsequent decades the Federal Drug Enforcement Agency grew to a force of over 10,000. In 2016 about 200,000 Americans were incarcerated for Drug offenses. And In 2018, over 67,000 people in the U.S. died from a narcotic overdose.

In my days as a doctor syphilis was called the great imitator. If someone got sick and syphilis was the possible cause of the problem we were taught to always rule it out.

Mid Century

In 1962, aside from antibiotics doctors had (in retrospect) relatively few medications to work with. We had aspirin, barbiturates, and a number of treatments that were largely the derivatives of plants, minerals and animals. (Colchicine, for example, was extracted from Colchicum autumnal…the meadow saffron and was used to treat gout and a few other maladies.) We worked with glass syringes and hypodermic needles made of steel. After they were utilized, the needles were washed, sharpened, sterilized and reused. When I was an intern (in 1963) we treated people who were stricken by a myocardial infarctions with “quiet and rest.” One fateful night I entered a room—the door was closed– to do an admission history and physical on a man who was having a heart attack. The patient was in trouble. He was confused, pale, sweating–dripping wet and barely had a blood pressure. He was in cardio-genic shock. I started an IV and infused the available drugs. Nothing helped and he died. Nowadays heart attack victims who don’t instantly die are rushed by ambulance to a nearby hospital where a cardiologist and team are waiting to catheterize their coronary arteries and to unblock and “stent” the occluded vessel. (Some of the improvements in care are not due to better drugs.)

By the 1950s physicians had digitalis, quinidine, nitrates for diseases of the heart. Excess fluid accumulation could be flushed by an injection of a mercury based diuretic; there was a new promising diuretic called chlorothiazide.

By my first year in med school, doctors could slow the coagulation of blood – and prevent and treat venous blood clots–with the anticoagulant Warfarin–Coumadin. Produced by certain fungi dicoumarol initially got people’s attention when it caused the death of a number of cows in the 1920s. The animals had eaten moldy sweet clover, it kept their blood from clotting normally, and they bled to death. Researchers spent decades trying to extract the responsible chemical and “in the dimness of dawn on June 28, 1939, after working all night, Harold Campbell at the University of Wisconsin (finally) saw crystalline dicoumarol on a microscope slide.” A few years later, led by the son of a Lutheran minister, Wisconsin researchers synthesized the chemical’s long acting derivative, called it Coumadin, and marketed it as an effective rat poison. On further thought the decided to use it as a medication for people.¹²

VACCINES

Maurice Hilleman, the scientist who ultimately created 40 vaccines, was born on a hot summer Montana day on a farm near the banks of the Yellowstone and Tongue River. His mother had eclampsia and died when he was 2 days old, but before she died she gave her baby to the childless couple down the road. Maurice claims he was put to work as soon as he was able to tell a weed from a seed. “Everyone in Montana had to earn their keep. “.On the farm they sold what they grew, and he picked berries, and watered the animals. As a teenager he worked at J.P. Penny’s in the nearby town and “helped cowpokes pick out chenille bathrobes for their girlfriends.” Deciding he didn’t want to go to the local college because he “didn’t want to be strapped down by the church dogma,” Maurice won a scholarship to Montana State University. Graduating first in his class, he was admitted to the PhD program in microbiology at the University of Chicago. “Despite receiving a scholarship, money was always in short supply. Hilleman lived in a squalid apartment and survived on a single meal each day. At 6 feet 1 inch tall, he weighed less than 140 pounds.¹⁴”

The Chicago University system, as he described it, was one where professors didn’t want to be bothered unless “you discover something. “While in school he determined that the bug that infected three million Americans a year and scarred the fallopian tubes of many women was not a virus. It was a bacterium, a Chlamydia that grew in cells and it could be killed with antibiotics. After he graduated his professors wanted him to stay in academia “I was not allowed to look for a job in industry; but I came from a farm. I wanted to do something—to make something³⁸.”

In 1944 as a new employee of Squibb he developed a vaccine for Japanese Encephalitis Virus. It normally can be found in pigs in parts of South East Asia and it is transmitted by mosquitoes. Usually mild, the infection sometimes causes fever, seizures, and serious long term movement problems. In 1944 World War Two was raging, the U.S. was getting ready to fight the Japanese, and the army wanted a vaccine that would protect soldiers. Hilleman offered to make the vaccine for $3 a dose and he won the contract. Squibb gave him a horse barn and an engineer. An old farm boy, he bulldozed out the manure, painted the floor, and went to work. From U. of Chicago days Hilleman knew the virus would grow in the brain of a mouse so he did some testing. As he later explained to fellow “vaccinologist” Burt Dorman, making a vaccine is like getting the old tractor working. You fiddle with it. If that doesn’t work you fiddle with it some more. Once Hilleman figured out how to make the vaccine he assembled a crew of 30 women. They injected the virus into the skulls of mice and waited for it to grow. After a few days they killed the rodents with ether and “harvested 30,000 brains a day.” The organs were homogenized with a blender, washed, centrifuged, and washed again and again. The process was repeated until the solution contained pure viruses. The life forms were then inactivated with formaldehyde. Three months later Squibb had enough vaccine to immunize 200,000 troops.³⁸

After the Second World War the U.S. military and the World Health Organization were on the lookout for the next influenza pandemic. In 1957 Hilleman was working at Walter Reed military hospital when he read about a flu outbreak in Hong Kong that infected ten percent of the population–250,000 people. He contacted an army physician in Japan who got an infected navy serviceman to gargle and spit into a cup. A month later Hilleman put the spit into a fertilized egg and a flu virus grew. He then checked the serum of hundreds of people and found that no one had antibodies to that strain of flu. Most of the humans alive had never been exposed to the virus. The only people who had antibodies were a few 70 and 80 year olds who had survived the flu epidemic of 1889-90.

Hilleman figured that a virus would arrive in the fall and it would be devastating. No one alive had ever experienced anything like it. He “sent out a press release and warned the world” but no one seemed to believe him. “Joe Bell” a prominent U.S. Public Health service epidemiologist, known for his attention to detail commented “what pandemic? What Influenza?” “How,” Hilleman wondered, “could people live in this world and be so stupid.” Eventually Hilleman went to a restaurant where the head of the U.S. influenza commission was eating. He interrupted the man’s meal, showed him the information, and told him that ignoring his findings was “a big mistake.” The commissioner checked the data and agreed; it was a pandemic virus.

Hilleman contacted 6 companies that produced flu vaccine. He cut the red tape, side stepped a few rules, and told chicken growers to NOT kill roosters. As a farmer he knew roosters were usually killed late in the hatching season and companies would need a lot of fertilized eggs. By late fall 40 million doses of vaccine were available and many people were immunized. The disease arrived in the U.S. that September in the body of a girl who attended a church conference in Grinnell Iowa and in the lungs of Boy Scouts from Hawaii who attended a jamboree at Valley Forge Pennsylvania. The 1957 flu killed 70,000 Americans and 4 million worldwide, but thousands of lives were saved.

In the 1950s Hilleman moved to the Merck Company and started a revolution of sorts. Over the years his group turned out products that prevented a staggering 40 animal and human diseases.

His vaccine for Hepatitis B was made using killed virus. To convince the public it was safe he asked Merck mid level executives to be the first to be injected. No one volunteered the first time so he brought the execs back and explained that “No” was not an option. Fearing the vaccine might have been contaminated with HIV some of the injected execs later admitted they took the shot but were “scared to death.”

When he later learned the vaccine production was being accelerated Hilleman met with the people making it. He had killed the viruses with formaldehyde, pepsin and urea. The process was effective but it was slow. When he heard the company was making it faster Hilleman assumed steps were being skipped. No one knew if it affected the vaccine’s safety. He gathered the production crew and told them someone was “changing the fucking process so he can get more yield and earn a bonus. Meatheads are everywhere.³⁸”

In 2005, 3 years before he died Hilleman famously told his colleagues that “the most apt description of me was as a man who appeared to be a bastard, but if you looked deeper inside you still saw a bastard.”

The vaccines for measles mumps and chicken pox became available in the late 60s and early 70s. In 1957, the year before I graduated from med school, the people I interviewed all remembered their childhood illnesses, staying home for a week, fevers, rash, and a swollen jaw.⁸

In the 1950s Jonas Salk and Albert Sabin developed immunizations for polio. The studious son of immigrants, young Jonas Salk was “a perfectionist” and a good student. He went to medical school, became a research bacteriologist, and, instead of joining the army, assisted Thomas Francis, the man who developed a flu vaccine for the army. The son of a steel worker, Francis—they called him Tommy, was 41 when the U.S. entered the war. The nation remembered how the flu had killed more soldiers than the enemy during the prior conflict and the government didn’t want a repeat. Salk was military age but discovering a vaccine for flu was more important than another soldier with a gun.

In 1947, at age 33 Salk was given a laboratory at the University of Pittsburg and was funded by the March of Dimes. The official charity that supported the development of a vaccine was created and promoted by Franklin Roosevelt. He was the U.S. president during the depression of the 1930s and led the country during most of the Second World War years. Unable to walk without help after he developed paralytic polio at age 39, he had a disability that was public knowledge. The virus was feared. 1952 there was an outbreak of Polio in the United States and over 57,000 infections and 3145 deaths.

Salk’s vaccine used live virus that was chemically inactivated and injected. In the early ‘50s it was given as part of a placebo controlled trial to 2 million school children. In 1955 the study proved it was safe and effective, Salk became an instant icon, and his life changed. His celebrity status troubled his medical colleagues and affected his marriage of 28 years. He ended up divorcing his first wife and he married Francoise Gilot, a woman who had once been the “longtime lover of Pablo Picasso.” He founded a research institute in San Diego, was interviewed, and in a book was psychologically picked apart. His interviewer wrote that the man “movie stars came to visit and babies were named after” was “conceited but vulnerable–mild-mannered, but often arrogant and combative.³⁹”

The other developer of a polio vaccine was born in Poland and was15 when he and his parents came to the United States. Albert Bruce Sabin eventually went to medical school and graduated in 1931. While studying Polio at the Children’s Hospital Research Foundation in Cincinnati, Ohio, he discovered that polio viruses lived in the small intestines before they attacked nerves. During the Second World War Sabin developed a number of vaccines for the army. When the war ended he returned to Ohio and he isolated a polio mutant that grew in the intestines and prevented infections with the wild virus. The U.S. at the time was committed to Salk and wouldn’t allow Sabin to test, produce, or administer his creation.

In 1955 the Russians founded a Polio Research Institute in Moscow, and in 1956 its head virologist Mikhail Chumakov visited Salk in Pittsburgh and Sabin in Cincinnati. Sabin spoke a little Russian, Chumakov a little English, and they became friends. The following year Sabin spent a month giving lectures in Russia, meeting with researchers, and promoting his vaccine. When he returned home the Salk vaccine was being widely used and an American researcher advised Sabin to toss his vaccine “in the sewer.” In 1958 Chumakov tested a vaccine made with Sabin’s seed virus on 20,000 Russian children. It was safe, easy to administer, and effective. Chumakov got permission from the public health chief of the Politburo and distributed the oral vaccine to more than 15 million Soviets and later to 23 million children in East Germany, Czechoslovakia, Hungary, Romania, and Bulgaria. An expert sent by the WHO agreed the vaccine seemed to be working but “definitive results would take time.”

Sabin refused to patent the Oral vaccine, and it is currently widely used in the poorer countries of the world.

On April 26, 1955 half of the 760,000 doses of Salk vaccine made by Cutter in Berkeley California, were recalled when the nation learned the vaccine was making some kids sick and was causing paralysis and a few deaths.

Thousands of kids developed a stiff neck and fever, 51 were permanently paralyzed, and 5 died. The formaldehyde in the vats had failed to inactivate the virus completely and the vaccine was pulled from the market. In 1961 the Sabin vaccine became available in the U.S. and was widely used. 26 years later the Salk, injectable vaccine was reintroduced. This time it was safe. Since 2000 the Salk product has been the only vaccine used in the U.S. and Europe. In the rest of the world “more than 10 billion doses of oral vaccine were given to 3 billion kids during the last 20 years. The World Health Organization thinks they have prevented 13 million cases of polio, but it’s also caused a few problems. Mutatants of the oral vaccine occasionally occur in a person’s intestine, and they have caused 760 cases of polio and can cause paralysis.⁴⁰”

During the last half of the 20^th century states started requiring kids who attended public schools to be immunized. Most families complied; the rest were usually shielded by “herd” immunity. If all or most kids in a community are protected, those who have not been immunized are unlikely to be exposed to the disease. The shots sometimes caused fever and joint aches, and one in a million kids developed encephalitis, a serious brain inflammation. The complications led to law suits and Pharma wanted to stop producing vaccines. In response, Congress passed the 1986 National Childhood Vaccine Injury Act, and the government started compensating the families of people who were harmed.

In 2020 a novel, sometimes lethal Coronavirus kicked off a terrible epidemic.

Chapter 6 HIV

One morning in the 1980s I attended a conference at the medical center, and heard about a tumor, Kaposi’s sarcoma, a cancer of old Italian men. It was affecting members of the gay community. Pneumocystis, a microbe that had lived harmlessly in most lungs for a millennium, was causing pneumonia in young men. Similar infections had previously attacked the lungs of kidney transplant recipients whose immune system was suppressed. Some had trouble swallowing and white dots of yeast covered their esophagus. Previously healthy young men and women developed a bizarre assortment of diseases. Many were quite ill, occupied many of our hospital beds, and were receiving multiple medications. For almost a decade everyone who contracted HIV eventually died.

In 1983 scientists in France and in the U.S. at almost the same time isolated the responsible virus. The microbe was colonizing, taking over, and ultimately destroying T lymphocytes, a vital constituent of the system that keeps a lid on many of the organisms that live in the body. As the virus destroys more and more of our defenders, the immune system loses its ability to control the indigenous microbes.

We soon learned of cases of the disease in 33 countries. Actor Rock Hudson died with AIDS and the Hollywood community rallied. Our blood supply was tainted. Ryan White, a kid with hemophilia had the condition and was not allowed to attend classes. A journalist who worked for the San Francisco Chronicle published a book called: “And the Band Played On.” The Gay community was particularly afflicted and decimated, and the book told of their struggle and “governmental indifference and political infighting”. Condoms were encouraged and needle exchange programs were initiated. Gay bath houses were attacked by the police in many cities. Laws were passed that forbade physicians from testing people for HIV without permission.

After the HIV virus wiped out most of a person’s T lymphocytes, their immune system was unable to control the bugs that normally inhabit a body and their disease had morphed into the full blown acquired immunodeficiency syndrome—AIDS.

The HIV virus, we later learned, is not highly contagious. You could shake hands or hug someone who had the virus growing in their body. Two principles of medicine, however, were turned on their head: In otherwise healthy people, infectious illnesses were usually caused by a single microscopic organism. When it was eradicated the person could stop taking antibiotics. In people with AIDS antibiotics often suppressed but failed to eliminate the creatures responsible for a disease. These individuals commonly required lifelong low doses of antibiotics to prevent a recurrence.

Also, when we identified the organism causing an infection (like Pneumocystis) we weren’t out of the woods. The creature had attacked the body because the immune system reached a low point. Additional problems were brewing.

Within a few years medical detectives in the Cameroon found chimp feces that contained Simian Immune Virus (SIV) with DNA that was identical to the DNA of the most common type of Human Immune Virus (HIV). The source of the epidemic was a chimpanzee infected with the simian immune virus.

In the early 20^th century chimps were wild game– “bush meat” in parts of Africa. When wounded, the animals struggled. Presumably on one occasion a human was injured by a chimp he was killing. Blood containing the Simian Virus entered the hunter’s body and the virus survived and thrived. Later the pathogen was sexually passed to one person after another. Sometime in the early decades of the century an infected individual moved to Leopoldville, (now Kinshasa). In 1920 the town was the capitol of the Belgian Congo and was full of migrants. Scientists figure that by the time the colony became an independent country (1960) an estimated 1,000 to 2,000 people were living with HIV. A physician of the day probably encountered many sick souls who had developed diarrhea, fever and wasting. There’s no reason to believe that anyone at the time suspected their symptoms were the result of a new virus.

As the Congo, now a new country, was getting started, UN aid workers and volunteers from Haiti were flown in to provide medical care and assistance. One of them presumably caught HIV, eventually went home, and the virus spread quietly in Haiti for a few years. Then unknowing carriers visited the U.S. and Europe and passed it on.¹

After they identified the cause of the disease, scientists learned how the RNA virus methodically infects a cell and, use a special enzyme it brought with it, (reverse transcriptase), to make a DNA version of itself. The DNA then integrates–becomes part of the host chromosome–becomes a gene.

BRIEF GENETIC TUTORIAL (again–sorry)
Our alphabet has 26 letters and we use them to make words.
The DNA of living organisms uses 4 letter alphabet. They “letters” are molecules called nucleotides.
Genes are strands of nucleotides. They tell a cell what to do and make and they occupy up to 3 percent of a body’s DNA. We aren’t sure what the other 97 percent of the DNA is there for.
Every cell in a person’s body has 3 billion pairs of DNA nucleotides.
They exist in groups called chromosomes. Each cell has 23 pairs of chromosomes.
The nucleus of every cell in the body contains all 20,000 genes. Some are turned on and some aren’t.
To summarize: The HIV virus knows how to create a DNA version of itself. That DNA becomes a gene and it commands the cell to make more HIV viruses.

R., a gay 35 year old carpenter, was renting an apartment I owned in the SF Bay area. I came by one afternoon and heard coughing from the house. R. let me in and told me he didn’t feel well and was having trouble breathing. His condition worried me and I suggested he visit a hospital. He went and the doctors made a diagnosis of Pneumocystis Pneumonia. He had AIDS. Treatment was started but he got worse and needed to be intubated. A tube was inserted through his mouth, passed his vocal cord, and into the main breathing tube. A respirator kept him alive for a week. It took a few weeks before R. recovered and was able to leave the hospital, but he knew AIDS was a death sentence. After he came home he moved out of the apartment, bought a house, fixed it up for his family and invited my wife and me over for Sunday afternoon Tea. He told us that he had long wanted have a home of his own before he died. He looked good, seemed relaxed, and was proud of what he had recently accomplished. We never saw him again.

The counter attack against HIV started when scientists at Burroughs-Wellcome synthesized compounds that might hinder the activity of the reverse transcriptase enzyme. In 1985 they sent eleven promising compounds to researchers at the National Cancer Institute, and people at the NCI identified a chemical that worked in the test tube. The drug, AZT, was given to people with HIV, and their lives were prolonged.

25 months later the FDA approved the drug, and it was marketed by GlaxoSmithKline. The company sold 225 million dollars worth in 1989.

In the late 1980s and in the 1990s manufacturers started cranking out (and selling) anti HIV drugs. Some of the agents targeted protease, an enzyme that plays a role in the production of more viruses. The first Protease inhibitors became available in 1996.

Drugs that work against the enzyme that turns HIV RNA into DNA, (like turning a photograph into a negative) were created by Emory university professors. They discovered 2 important drugs (emtricitabine and lamivudine.) “Everyone was intrigued but skeptical about our work—no one realized the importance of what we had found,” Schinazi (the physician who developed the drug) said. He “pushed Emory University to file patent applications.” They did and less than ten years later the University was paid $540 million…a lot of money but considerably less than big Pharma often pays to control a significant medication. .

Two of the drugs that most effectively prevent and suppress the HIV virus were created in Prague Czechoslovakia by Anotonin Holy. An intuitive researcher, Holy had been sneaking promising chemical creations through the iron curtain to a colleague in Belgium named Erik De Clercq for 20 years. At the time a number of rules and regulations restricted trade between the Communist countries and the West. But Czechs were able to export the hops that Belgians used to make beer and they could import powdered Belgian milk. Somehow the chemicals got through. In 1981 De Clercq visited Prague. Holy took his friend to dinner and stuffed his coat with vials of newly developed compounds.

In the mid 1980’s the Bristol Myers head of virology was John Martin. A respected researcher, he had developed the cytomegalovirus fighting drug, guancyclovir when he was in his 20s and was working for Searle. Pharmaceutical leaders were starting to pay attention to HIV and researchers were developing compounds. At one point Martin heard about a promising new group of antivirals that were discovered by a researcher in Czechoslovakia. Called “acyclic nucleotide phosphonates” they were just chemicals in a test tube. No one knew if they were safe or effective. But for some reason De Clercq in Belgium thought they were special. So Martin visited Prague and met Holy. As the two strolled through the city’s narrow streets and cobblestone alleys they got to know and like one another. Holy wasn’t a complainer. His lab facilities were limited but he managed to do his work and he had no desire to leave the country of his birth. When Martin returned to the U.S., a CIA officer tried to convince Martin to turn Holy into an “asset” and Martin declined.

In July 1989 Gorbachev allowed the nation’s of the Soviet Bloc to break away from Russia. The iron curtain fell, and commerce and travel between the East and the West became relatively easy. About that time Bristol Myers merged with Squibb and the company’s leadership and goals changed. The following year Michael Riordan the long suffering, optimistic CEO of Gilead, a failing startup, convinced Martin to jump ship and become one of his company’s new leaders. Martin (perhaps a little uncertain about his role in the new mega company) agreed and brought two of his best researchers with him. At the time a number of pharmaceutical manufacturers were trying to fabricate drugs that suppressed the HIV virus, but Gilead was not one of them. The chemicals Holy had created had been tested in Belgium and they effectively neutralized the HIV virus. But they needed tweeking before they would be ready for human consumption. Bristol Myers had planned to license and modify them. Gilead wasn’t a player.

Then in mid 1991, with the head of Squibb calling the shots, the newly formed mega company decided they weren’t interested in Holy’s chemicals. They didn’t want to take the risks and make the investment necessary to perhaps develop another HIV medication. Realizing Squibb’s error, Martin phoned Holy and convinced him to sign a licensing agreement with Gilead. In July 1991 Holy, Martin, and De Clercq met in a restaurant near the Eiffel Tower and signed a deal on a napkin. Holy’s nucleotide became the basis of several of the most potent medications that are currently used to prevent and treat HIV, and Gilead was finally an important player.

In 1995, influenced in part by well healed pharmaceutical companies, the World Trade Organization was formed. It required members “to honor 20 year patents on drugs”. Poor countries were given until 2005 to comply with the mandate. (Half the big drug makers are headquartered outside the U.S.).

In 1996 a three drug regimen was shown to successfully suppress the HIV virus. The disease could be controlled in advanced nations. But the companies that owned each drug’s patent charged what they thought they could get away with. The medications were too pricy for most people in the developing world.

As Nobel Prize winner Joseph Stiglitz explained: Patents are created for each nation’s needs. They give the inventor a monopoly for a number of years. When they are appropriately designed they promote innovation and societal well being. When they are not appropriately designed people die and innovation is suppressed.

Most nations allow people and companies to patent unique, non obvious inventions. When it came to medications, India had a different approach. The country gained its independence from England in 1947. In 1966 Nehru’s daughter, Indira Gandhi became prime minister. At some point she met with the head of the Indian drug maker—Cipla. He convinced her to allow inventors to patent the process –the way they manufactured a drug. But the drug itself could NOT be patented in India. That was the law in India before the country joined the WTO—the World Trade Organization. After India joined they changed their patent law. Drugs could now be patented.

In September 2000 Yusuf Hamied, the CEO of Cipla, was invited to the European Commission in Brussels for high level talks with health ministers and heads of large pharmaceutical companies. The meeting was supposed to discuss access to medicines, especially those that suppressed AIDS, in the developing world. At the large gathering, after the leaders of various companies made their remarks, Hamied spoke. Saying he represented the developing world and an opportunity, he offered to provide the three anti retroviral drugs that suppressed HIV at a cost of $800 a year; and/or to set up factories in other nations; and to provide needed medicines to pregnant women so they would not infect their unborn child. Founded in 1935 by Hamied’s father, Cipla is a major pharmaceutical company. His proposal was serious and significant. But his offer was ignored.

In the early 2000’s, according to Denis Broun M.D. of Unitaid, the powers- -that–be believed “Treatment for AIDS was something for the rich. It was unthinkable for Africans.” Yusuf Hamied felt the whole of Africa was being taken for a ride.¹

A year after the Brussels meeting James Love, an AIDS activist called Hamied and asked how cheaply he could produce the three drugs that suppressed the virus. The key to pricing in medicine (according to Hamied) is the cost of the active pharmaceutical ingredients. If you can get them cheaply, the end product is cheap. Hamied told Love that Cipla would pay the cost of manufacturing a generic regimen. He would only charge for the material. Nevirapine would cost 65 cents a day. 3TC, lamivudine, 35 cents. And there would be no charge for d4T, Stavudine. The materials were too cheap. In other words the three drug regimen would cost $350 a year.

Donald McNeill of the New York Times felt the offer “was a watershed event.” He put the price of generics on the front page of the NY times, and papers around the world spread the news.

Shortly thereafter Peter Mugyenyi, a Uganda physician and director of the continent’s largest research and treatment center, decided to take matters into his own hands. “I knew where drugs were, and as a doctor it was my job to save my patients lives.” He contacted Cipla in India, and in defiance of patent laws ordered the drugs.

When the medications arrived at the airport they were impounded and the doctor was arrested. He refused to leave the airport without his medications. Eventually the authorities relented. Other nations acted. To many it seemed like the blockade for inexpensive drugs in Africa was broken.

In 2002 Kofi Annan, the diplomat from Ghana who was the Secretary-General of the United Nations, proposed a Global Fund to buy the drugs. The U.S. insisted that the fund could only buy branded medications or they would pull out.

Poor countries couldn’t and wouldn’t comply with the WHO directive. HIV was a killing their people. 143 countries favored relaxation of patent protection.

“In 2003 South Africa’s competition commission ruled that Glaxo Smith Kline and another company had violated the country’s anti competitive act. Glaxo was charging excessively high prices and was refusing to license their patents to generic manufacturers in return for reasonable royalties. The company eventually agreed to allow three generic manufacturers to make and sell three of its AIDS drugs,³ and the company took a 5% fee.

Prior to 2003, the U.S hung tough. Then the Irish singer Bono got together with one of the day’s more influential Republican senators, Jesse Helms, and attitudes changed. When they met the Senator was 80 and walked with a four-pronged cane. He was a rightwing evangelical Christian who had exploited racial prejudices in his election campaigns and had called homosexuals “weak, morally sick wretches”.

Bono, by contrast, had publically supported Greenpeace, Amnesty International, and had joined Jubilee 2000, a 40 country movement that advocated cancelling third world debt for the millennium. At one point the Jubilee campaign asked Bono to get the Baptist Nigerian President to write a letter to Baptist churches across southern US states. He was supposed to explain the Biblical principles behind debt cancellation.

The Baptist leaders listened, and Bono suddenly had access to a lot of strongly Christian Republicans. That’s why he was able to meet and speak with Jesse Helms. Helms had been very tough on the concept of foreign HIV drug assistance. “He’s a religious man”, Bono said, “so I told him that 2103 verses of scripture pertain to the poor, and Jesus speaks of judgment only once – It’s not about being gay or sexual morality, but about poverty. I quoted that verse of Matthew chapter 25: ‘I was naked and you clothed me.’ He was in tears. And later publicly acknowledged that he was ashamed…”

After the meeting vice president “Dick Cheney walked into the Oval office, and told President Bush that, ‘Jesse Helms wants us to listen to Bono’s idea.” That led to negotiations and Bush’s 2003 plan.

That January in his State of the Union message President Bush announced his policy towards HIV had changed. His words: “Today on the continent of Africa nearly 30 million people have the AIDS virus, and across that continent only 50,000 are receiving the medicine they need. Many hospitals tell people: “you have AIDS. Go home and die.” In an age of miraculous medicines no person should have to hear those words.”– “Anti retroviral drugs can extend life for many years. And the cost of those drugs has dropped from $12,000 a year to under $300 a year. Seldom has history offered a greater opportunity to do so much for so many. “

Bush would ask congress to spend $15 billion dollars over 5 years to combat the disease. Since its creation in 2003, the “President’s Emergency Plan for AIDS Relief (PEPFAR)” received more than $70 billion in congressional funds …$6.56 billion in fiscal 2017. The Trump budget plans to cut the amount the government contributes in 2019 by a billion dollars.

The under $300 number caught the drug industry by surprise, and they fought back. Within days the administration changed its approach. Rather than generic anti retro-virals the U.S. government money would be used to buy high priced branded drugs, and fewer lives would be saved.

As Bill Clinton later put it, “If you ran the numbers there was no way the money was enough to save the number who had to be saved in a hurry… it would never be enough unless they bought generics.”

Many of the drug manufacturers are headquartered outside the U.S. One hundred and twenty three nations (probably goaded by large corporations) signed an intellectual property rights agreement.-TRIPS, that “came into effect” in January 1995. It allows members “to promote access to medicines for all.”

Clinton decided to ignore the politics of the situation and do the right thing. At the time India was a member of the World Trade Organization but patents issued before 2005 were still valid.⁹

In late November 2006 Bill Clinton announced an agreement between his foundation, two Indian drug makers: Cipla and Ranbaxy; Aspen Pharmacare, of South Africa, and Matrix Laboratories of Dubai. The companies agreed to make pills for children that combined three HIV drugs and cost $60 a year. Two million children in Africa had been infected by their mother and only 10 percent were receiving drugs. Without treatment 80% would be dead by age 5.

The companies also apparently agreed that “The cost of anti-retroviral drugs (in general) was going to drop to $140 a year, and pills would cost 36 to 38 cents a day.” The cost of making the medicines would be paid for by a $35 million grant from an international drug-buying consortium and $15 million from the Clinton Foundation. The funds guaranteed the volume of drugs purchased would be “high enough to justify the lower prices.” “The large quantity orders for generics was critical to bringing prices for anti retroviral treatment in Africa below $100 per person per year.”

“After that the difference between branded and generic anti-retro-virals, and the scale of human tragedy in Africa made it impossible for donor funds to spend vast sums of money on expensive drugs. The global fund and Pepfar eventually committed themselves to buying generics, and the number of people treated exploded.”¹

In 2017, per the U.N., 19.5 million people, more than half those infected, were being treated, but 2 million additional people had acquired the disease. Over 25 million HIV carriers lived in Sub Sahara Africa. That year worldwide 75% of people who carried the virus knew they were infected.⁴

The UN thinks they can end the epidemic if 90% of those infected know they are infected. Then 90% of those infected would need to take anti retroviral drugs that effectively lower the measurable blood level of HIV 90 percent of the time. Seven countries have achieved the 90/90/90 goal.

In 2019 the U.S. is still pretty far from getting HIV under control. One in six men who has sex with other men will eventually acquire HIV. Half are Latino or black. In 2015 there were about 6500 AIDS-related deaths in the U.S.

The CDC (Center for Disease Control) thinks that 1.1 million people are currently infected and 40,000 inhabitants will acquire HIV each year. 83-88% of those infected have been diagnosed, and 85% of the people regularly take medicine that controls the virus; only half take enough pills in the right dose.

People with “decent” health insurance are commonly required to pay two thirds of the cost.⁵ The estimated average annual cost of HIV drugs is about $20,000 ($360,000 lifetime.) In the appropriate age and income situations Medicare and Medicaid supply the meds. The non-profit Ryan White Foundation helps when people can’t afford the drugs. And there are federal programs for some populations.

Pharmaceutical companies have managed to keep the price of drug combinations relatively high by combining one or two relatively cheap anti-retro-virals with an expensive newer drug that is still patented. Some contend that people are more likely to take one pill that contains several drugs than they are to take a few capsules.

Most new infections can be prevented with a daily pill that contains two of the more effective anti-viral drugs, but it is not always covered by insurance.⁸

Anthony Fauci of the NIH is quoted as saying: “if we had a vaccine this effective-wow”. He was talking about a drug containing polymer that is implanted in a person’s body and slowly elutes significant quantities of a medication that suppresses HIV.

We haven’t learned how to eliminate the HIV virus from a body. The HIV DNA has become one of the genes of too many T cells. But genetic engineering is new and developing. Que sera.