On 5th October, three scientists were awarded the Nobel Prize in Physiology or Medicine for the discovery of the hepatitis C virus. The discovery led to a curative treatment for the widespread, fatal virus, which infects somewhere between 71 million and 170 million people worldwide. This chronic disease is often silent for many years, but eventually it may cause cirrhosis, skin problems, blood disorders, and weight loss. In its most severe stages, hepatitis C can lead to liver damage, liver cancer, and liver failure. While a hepatitis C diagnosis today is not necessarily a death sentence, the virus has left a centuries-long trail of destruction. Tracing the history of this virus reveals some of the most disconcerting of human behaviors, and a lesson in ways in which poverty and oppression shape global health.
Ancient Egypt is a case in point, a country where hepatitis C rose to epidemic proportions due to poverty and its accompanying perilous living conditions and poor sanitation. That story begins on the banks of the Nile River, which, starting at least 5,000 years ago, was home to a centuries-long infestation of snails that was nearly impossible to eradicate.
The snails played host to a parasitic worm called Schistosoma, which caused an illness known as Bilharzia (after Theodore Bilharz, the German doctor who discovered it in 1851), snail fever, or simply schistosomiasis. The parasite found an easy home among the Nomadic people who settled in the fertile Nile valley 5,000 years ago. The Nile River was the center of their lives. When they walked barefoot, the worms found their feet. When they bathed, the worms landed on their skin.
Inside a human host, the worm burrows in, loses its tail, enters the circulatory system and finds its way to the liver or bladder, where it matures into adulthood. Males and females mate and when their human host urinates or defecates — which ancient Egyptians often did right in the Nile — the flatworm eggs are laid and the cycle begins anew.
The impoverished lifestyle along the Nile delta allowed snail fever to flourish. Two mummies from the Twentieth Dynasty of ancient Egypt (1250–1000 BC) were diagnosed with schistosomiasis by an archaeologist in 1910. Poor Egyptians fleeing the countryside to escape corvée — unpaid labor forced upon them by the ruling class during the 18th and 19th centuries — gravitated toward the Nile deltas where they could farm their own meager fields, further increasing the demand for river water.
People can survive for years with Schistosoma worms living inside them but eventually there will be problems, including liver disease, as the parasite eats away at the digestive system of its host, causing the liver to become inflamed, and the urine to become laced with blood. It was the sight of men peeing blood that led Napoleon’s aides to remark on the “menstruating males of Egypt” during his campaign in the region in the final years of the 18th century. By the 19th century, peeing blood was so common among Egyptian men that it was considered a normal part of growing up for boys, even a sign of fertility. Efforts to eradicate the snails — including hygiene solutions like toilets and chemical sprays — failed.
But in the 1950s, scientists believed they landed on a solution: An injectable medication called tartar emetic became available and targeted the worm directly inside its human host. Egypt’s Ministry of Health dispatched dozens of health workers to rural areas along the Nile armed with needles and tartar emetic. The problem was what they didn’t know: that a virus called hepatitis C had also arrived on the shores of the Nile. Exactly how and when this virus entered the country isn’t widely known, but it was not surprising that the virus would be living among the Egyptian population; by the mid 1900s, the pathogen had already made its way around the world, largely inside needles used to move substances in and out of veins.
The health workers didn’t realize that the needles used to provide the tartar emetic needed to be sterilized or changed after each use. They didn’t know that the minuscule virus that causes hepatitis C could be passed through the blood and transported on the tip of a hollow needle used to inject medication.
The Ministry of Health’s good intention simply traded one liver-sickening illness for another. From the 1950s through the early 1980s, tartar emetic killed the parasite and the needles carried hepatitis C from village to village, farmer to farmer. Although a minority of cases occur through sexual transmission or from mother to baby during birth, the virus is most commonly transmitted through the blood via needles. Egypt was left with the highest incidence of hepatitis C in the world, the direct result of this public health measure.
Where there is abuse and poverty, there is hepatitis C
If you were to make a map showing how hepatitis C traveled around the world, the effort to treat schistosomiasis along the Nile would be just one path. Yet every route bears a similar hallmark: Poverty and oppression seem to create ideal scenarios for the virus to spread.
According to research following the genetics of the virus back in time — and the creation of ancestral viral trees, similar to the trees that trace the evolution of plants and animals — slave ships traveling from West Africa to Europe also carried hepatitis C. By comparing the genetic sequences of viral strains in different regions of the world and turning back the clock on those sequences, researchers can see when they would last have been similar, like spotting close childhood friends who eventually went their separate ways.
Genetic sequences from Benin, the site of several European slave-trade ports, match sequences found in Suriname, the former Dutch colony on the northern coast of South America. The viral genome found among a cluster of people in Hispaniola matches the genome found in several other Caribbean and South American locations, indicating that the virus was introduced to these regions at the same time. Using these sequences, researchers have discovered that the introduction of the virus to these regions coincides with the peak of the transatlantic slave trade. Hepatitis C left Africa with the people stolen from its shores, and, as the human cargo was sold into the ultimate captivity, the virus was set free to colonize population after population. And when slavery was abolished, the virus attached itself to poverty, traveling, for example, to Indonesia with Chinese laborers willing to work for the paltriest wages.
A third hepatitis
Much more recently, the primary route for hepatitis C transmission was blood transfusions. Indeed, it was that pathway that led to its identification. First, a medical doctor from New York University named Saul Krugman figured out that the liver-attacking pathogen that entered the body orally was a different virus from the one that entered the body through the blood. He found this out by intentionally giving the virus to children at the Willowbrook State School, a residential facility for mentally disabled children in Staten Island, New York. Hepatitis rates there were already presumed to be at 100%, so Krugman reasoned that giving them the virus on purpose was fair and would actually improve their care. He injected the children with hepatitis and charted the course of their illness. He also made milkshakes with feces from infected residents and fed them to newly admitted children. The project, which lasted from 1958 to 1964, ended abruptly when his methods came to light. The school was shuttered in a little over 20 years later.
The gruesome experiment left researchers with the knowledge that hepatitis A, which enters the body orally, was different from hepatitis B, which enters the body through the blood. The next step was to find a way to get hepatitis B out of the blood supply so that transfusion recipients would not contract the virus, which meant finding the virus itself. Two researchers at the NIH — one was Harvey Alter, a recipient of the 2020 Nobel Prize — were searching random blood samples from around the world for any antigens, proteins that sit on the surfaces of foreign invaders like bacteria and viruses. They did this by pitting each sample against blood from hemophiliacs; because the latter receive so many transfusions, their blood often contains a plethora of antibodies, proteins manufactured in response to an antigen. When an antigen meets its antibody, a milky white line appears at the boundary. So if that line appeared between a sample from the researchers’ collection and blood from a hemophiliac, the researchers would know that the sample contained some kind of pathogen.
One day in 1965, that milky white line appeared between blood from an Australian Aboriginal person and blood from a hemophiliac. That was strange. Yes, the hemophiliac’s blood would have many antibodies. But the idea that any blood that person had received had been exposed to a pathogen present in the blood from remote Australia was a stretch. But when the scientists searched their vast collection for the antigen, they found it in 10% of blood samples from people with Down syndrome. Among people with Down syndrome living in large care facilities, the rate rose to 30%.
The mystery was solved when they realized that blood from a boy with Down syndrome that did not have the antigen at first was found to have it upon retesting; the difference was that he had developed hepatitis in between. And one of their research assistants tested positive for the antigen after she developed hepatitis. The final proof came when a researcher from Japan showed that the Australia antigen could be transmitted by blood transfusion. They’d found hepatitis B.
But when people continued to contract hepatitis from blood transfusions, scientists figured out that some third element could also cause the feared liver disease. They called it non-A, non-B hepatitis at first, having no idea what that third cause might be. It would take years to find what we now know as hepatitis C.
Hepatitis C research is underfunded
Once the blood supply was made safe from the virus, transfusion-caused cases of hepatitis C plummeted.
Yet despite so many changes and medical advances that could have eradicated hepatitis C, the virus continues to thrive. An estimated 2.4 million people have hepatitis C; one estimate puts the number at 5 million. In Western countries, nearly all cases stem from drug use. Between 2006 and 2012, for example, cases among young adults in Kentucky, Tennessee, West Virginia, and Virginia — the heart of the U.S. opioid epidemic — spiked 364%. Addiction has taken the role once held by slavery and well-intentioned ignorance. Again, where there is abuse and poverty, there is hepatitis C.
The modern transition of hepatitis C from a disease transmitted unknowingly to innocent hemophiliacs and open-heart surgery patients receiving blood transfusions to one transmitted through dirty needles filled with heroin kept the infection largely out of the limelight. The annual U.S. research budget for hepatitis C is about a fifth that of breast cancer, which is diagnosed in just under 300,000 women in the U.S. each year. Because people with the virus tend to be poor, advocacy efforts have small coffers. There are no widespread marches or walks or runs for hepatitis C. Because hepatitis C is so tightly tied to injection drug use, the disease, which is four times more prevalent worldwide than HIV, garners little compassion. Calls for testing often don’t reach those who need to hear it; an estimated 75% of people living with the virus don’t know they have it.
In part, the shunning of hepatitis C may be connected to the fact that the most effective means for preventing it are typically the same measures for reducing harm from injection drug use: syringe exchanges, substance abuse treatment, and community outreach, which can be politically controversial. Prison testing and treatment programs could also go a long way toward reducing the prevalence of the disease because so many people infected with the virus are incarcerated each year, but that opportunity is rarely seized. Federal guidelines in the late 1990s stated that people with the virus should not be treated until they had gone six months without using illegal drugs. In the early 2000s, an update to that recommendation stated that drug users should receive treatment on a case-by-case basis, just like anyone else. This change has made some difference, but not a lot. That addiction itself is now recognized as a disease has done little to alter the virus’s reputation. No politician ever built a platform on funding hepatitis C research.
Attention increased with the advent of a groundbreaking curative treatment, made possible through the discovery made by the three scientists just awarded the Nobel Prize on Monday. But that attention has not been entirely positive; the treatment can be prohibitively expensive for the typical hepatitis C patient. A full course of the drugs, which takes about 12 weeks, can cost up to $100,000. An eight-week course of Harvoni, one of the breakthrough drugs, costs $63,000. Private insurers have nothing to gain by covering the cost of these very expensive drugs, raising concerns about whether they will continue to do so. In response to the outrage over the price tag, drugmaker Gilead released generic versions of their hepatitis C cures, but they still cost up to $24,000 for the full treatment. The annual mortality rate has been declining since 2013, but only minimally each year considering a cure has been available since the end of 2014. The cycle continues.
For centuries, hepatitis C virus has served as a reflection of societal ills. Medical progress made against the disease will do little to stop it while humanitarian progress is stalled. As long as there is a terrain of abuse to be mapped, the virus will be there to serve as cartographer.
Written by: Jessica Wapner
Jessica Wapner is a freelance science journalist from New York with bylines in Wired, the New York Times, Popular Science and many other major publications.
Source: Elemental
