Infection Challenge: Infecting Volunteers To Get A COVID-19 Vaccine Sooner

Some researchers advocate shortening the procedure for clinical trials to develop a vaccine by infecting healthy volunteers with the live virus. This 'challenge infection' method raises an ethical dilemma.

Testing a vaccine in Germany
Testing a vaccine in Germany
Nathaniel Herzberg

PARIS — It's a moral dilemma fit for philosophy books and it's being contemplated around the globe. Should we deliberately risk the health of a few to potentially save thousands of others? More specifically, should we speed up the development of a vaccine against Covid-19 by infecting healthy people?

These volunteers could potentially develop a disease that has already killed more than 500,000 worldwide, yet advocates of this method have no qualms. The title of an article published by pediatrician Stanley Plotkin (University of Pennsylvania) and bioethicist Arthur Caplan (New York University) on May 22 in the journal Vaccines makes their stances clear: "Extraordinary diseases require extraordinary solutions." According to the paper, "Developing and distributing an efficacious vaccine as quickly as possible is a moral imperative for the world" and will require rethinking "the usual path of development"— meaning some steps in the current vaccine-validating process need to be skipped.

Conversely, William Haseltine, president of the think tank Access Health International and former professor at Harvard Medical School, argued in Project Syndicate that testing the efficacy of potential Covid-19 vaccines by injecting the live virus into humans is "unnecessary, uninformative and unethical."

Both arguments grasp the unconventional nature of the situation. Purposefully infecting participants with COVID shortens the venerated procedure governing clinical vaccine trials, which takes place in three phases. The first, carried out on a small number of humans, verifies the absence of side effects. The second phase, often conducted on a few hundred or thousands of people, continues this research process and above all verifies that the vaccine does indeed lead to the development of antibodies. But will they be able to protect against the real virus? This is the role of the third phase, the longest and most complex.

In this stage, tens of thousands of volunteers are enrolled: half receive the drug to be tested, the other half a placebo. Then they are sent home to live in normal conditions, taking the usual precautions against infection. Six to eighteen months later, researchers monitor both groups. If all goes well, the vaccinated people will have been better protected. But it takes time for the results to be statistically valid— and for the virus to circulate.

There is no shortage of volunteers.

As early as March 31st, three U.S. doctors in The Journal of Infectious Diseases suggested replacing this last phase with a controlled infection. The idea is to deliberately infect a few hundred people, half of whom have been vaccinated, and to study the results.

"Obviously, challenging volunteers with this live virus risks inducing severe disease and possibly even death," wrote Nir Eyal, Marc Lipsitch and Peter Smith. "However, we argue that such studies, by accelerating vaccine evaluation, could reduce the global burden of coronavirus-related mortality and morbidity."

"Developing and distributing an efficacious vaccine as quickly as possible is a moral imperative for the world" — Photo: Chaiwat Subprasom/SOPA Images/ZUMA

This method, known as a "challenge infection", is not new, strictly speaking. In 1796, Edward Jenner discovered vaccination by inoculating his farm boy's son with smallpox, who he believed was protected from the disease thanks to having contracted with another, benign, cow-borne infection: the vaccinia. But, of course, ethical standards have changed. Is the world in a place where we should disregard the fundamental principle of medicine: Do not willfully harm a patient? Yes, if volunteers "autonomously authorize the risks to themselves, and their net risk could be acceptable if participants comprise healthy young adults," as Eyal, Lipsitch and Smith wrote.

There is no shortage of volunteers. The organization 1 Day Sooner, which promotes the use of this method against the new coronavirus, has already gathered the commitment of more than 30,000 people from 140 countries. Its website links to studies showing that the risk of dying from Covid-19 in young and healthy subjects does not exceed 1 in 3,000, identical to the risk of kidney donors. What's more, challenge infections have been used over the last decades to fight against influenza, cholera, malaria and dengue fever. These arguments have convinced 35 members of the U.S. House of Representatives: On April 20, they wrote to the Food and Drug Administration (FDA) asking to authorize this method, which is, according to them the best solution against the "enormous human cost of the Covid-19 epidemic."

The FDA hasn't responded. The World Health Organization (WHO), on the other hand, issued a report on May 6 providing "key criteria for the ethical acceptability of Covid-19 human challenge studies," particularly in the selection of volunteers: young, healthy subjects, already exposed in their daily lives to the virus, but not part of an essential profession. This is a strict framework but not an outright refusal for participation. Opponents disagree. "We want to infect people with a virus that we still know very little about," says Haseltine. "We're constantly discovering new pathologies that are induced, even in young people."

Joanne Langley, a pediatrician and infectious disease specialist at Dalhousie University in Canada, says: "As a researcher, I would refuse to lead a challenge infection that would expose participants to a deadly disease for which we have no treatment."

A major practical point is that if the challenge infection is, as its proponents suggest, conducted on young volunteers with no co-morbidities, what information will it provide about protecting those truly at risk? This especially concerns the elderly, whose immune systems develop far fewer antibodies.

It's not just Americans; The British, who have used this procedure throughout the 20th century, may consider a human challenge study. The Chinese are also rumored to be preparing for one. In France, there's no question about taking the plunge. "It's not in the plan," says Virginie Pirard, head of the ethics unit at the Pasteur Institute. This stance is informed by careful thinking. The institute is taking part in another challenge, however, which is due to start in September in the U.S. It targets shigellosis, a fatal diarrheal disease in children, but with moderate symptoms in adults, who are the only subjects in the trial and are sensitive to antibiotics. Three years of review and advice preceded the green light. "The situation with SARS-Cov2 is very different," says Pirard. "Without curative treatment and knowledge of all the factors that can cause severe cases, the risk of developing severe infections, even in young people, is too great, even in a very controlled environment."

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The True Horrors Behind 7 Haunted Locations Around The World

With Halloween arriving, we have dug up the would-be ghosts of documented evil and bloodshed from the past.

Inside Poveglia Island's abandoned asylum

Laure Gautherin and Carl-Johan Karlsson

When Hallows Eve was first introduced as a Celtic festival some 2,000 years ago, bonfires and costumes were seen as a legitimate way to ward off ghosts and evil spirits. Today of course, with science and logic being real ghostbusters, spine-chilling tales of haunted forests, abandoned asylums and deserted graveyards have rather become a way to add some mystery and suspense to our lives.

And yet there are still spooky places around the world that have something more than legend attached to them. From Spain to Uzbekistan and Australia, these locations prove that haunting lore is sometimes rooted in very real, and often terrible events.

Shahr-e Gholghola, City of Screams - Afghanistan

photo of  ruins of Shahr-e Gholghola,

The ruins of Shahr-e Gholghola, the City of Screams, in Afghanistan

Dai He/Xinhua via ZUMA Wire

According to locals, ghosts from this ancient royal citadel located in the Valley of Bamyan, 150 miles northwest of Kabul, have been screaming for 800 years. You can hear them from miles away, at twilight, when they relive their massacre.

In the spring 1221, the fortress built by Buddhist Ghorids in the 6th century became the theater of the final battle between Jalal ad-Din Mingburnu, last ruler of the Khwarezmian Empire, and the Mongol Horde led by Genghis Khan. It is said that Khan's beloved grandson, Mutakhan, had been killed on his mission to sack Bamyan. To avenge him, the Mongol leader went himself and ordered to kill every living creature in the city, children included.

The ruins today bear the name of Shahr-e Gholghola, meaning City of Screams or City of Sorrows. The archeological site, rich in Afghan history, is open to the public and though its remaining walls stay quiet during the day, locals say that the night brings the echoes of fear and agony. Others claim the place comes back to life eight centuries ago, and one can hear the bustle of the city and people calling each other.

Gettysburg, Civil War battlefield - U.S.

photo of rocks and trees in Gettysburg

View of the battlefields from Little Round Top, Gettysburg, PA, USA


Even ghosts non-believers agree there is something eerie about Gettysbury. The city in the state of Pennsylvania is now one of the most popular destinations in the U.S. for spirits and paranormal activities sight-seeing; and many visitors report they witness exactly what they came for: sounds of drums and gunshots, spooky encounters and camera malfunctions in one specific spot… just to name a few!

The Battle of Gettysburg, for which President Abraham Lincoln wrote his best known public address, is considered a turning point in the Civil War that led to the Union's victory. It lasted three days, from July 1st to July 3rd, 1863, but it accounts for the worst casualties of the entire conflict, with 23,000 on the Union side (3,100 men killed) and 28,000 for the Confederates (including 3,900 deaths). Thousands of soldiers were buried on the battlefield in mass graves - without proper rites, legend says - before being relocated to the National Military Park Cemetery for the Unionists.

Since then, legend has it, their restless souls wander, unaware the war has ended. You can find them everywhere, on the battlefield or in the town's preserved Inns and hotels turned into field hospitals back then.

Belchite, Civil War massacre - Spain

photo of sunset of old Belchite

Old Belchite, Spain

Belchite Town Council

Shy lost souls wandering and briefly appearing in front of visitors, unexplainable forces attracting some to specific places of the town, recorded noises of planes, gunshots and bombs, like forever echoes of a drama which left an open wound in Spanish history…

That wound, still unhealed, is the Spanish Civil War; and at its height in 1937, Belchite village, located in the Zaragoza Province in the northeast of Spain, represented a strategic objective of the Republican forces to take over the nearby capital city of Zaragoza.

Instead of being a simple step in their operation, it became the field of an intense battle opposing the loyalist army and that of General Francisco Franco's. Between August 24 and September 6, more than 5,000 people were killed, including half of Belchite's population. The town was left in rubble. As a way to illustrate the Republicans' violence, Franco decided to leave the old town in ruins and build a new Belchite nearby. All the survivors were relocated there, but they had to wait 15 years for it to be complete.

If nothing particular happens in new Belchite, home to around 1,500 residents, the remains of old Belchite offer their share of chilling ghost stories. Some visitors say they felt a presence, someone watching them, sudden change of temperatures and strange sounds. The ruins of the old village have been used as a film set for Terry Gilliam's The Adventures of Baron Munchausen - with the crew reporting the apparition of two women dressed in period costumes - and Guillermo del Toro's Pan's Labyrinth. And in October 1986, members of the television program "Cuarta Dimensión" (the 4th dimension) spent a night in Belchite and came back with some spooky recordings of war sounds.

Gur Emir, a conquerer’s mausoleum - Uzbekistan

photo of Gur Emir (Tomb of Timur) i

Gur Emir (Tomb of Timur) in Samarkand, Uzbekistan

Chris Bradley/Design Pics via ZUMA Wire

The news echoed through the streets and bazaars of Samarkand: "The Russian expedition will open the tomb of Tamerlane the Great. It will be our curse!" It was June 1941, and a small team of Soviet researchers began excavations in the Gur-Emir mausoleum in southeastern Uzbekistan.

The aim was to prove that the remains in the tomb did in fact belong to Tamerlane — the infamous 14th-century conqueror and first ruler of the Timurid dynasty who some historians say massacred 1% of the world's population in 1360.

Still, on June 20, despite protests from local residents and Muslim clergy, Tamerlame's tomb was cracked open — marked with the inscription: "When I Rise From the Dead, The World Shall Tremble."

Only two days later, Nazi Germany invaded the Soviet Union, with the people of Samarkand linking it to the disturbing of Tamerlane's peace. Amid local protests, the excavation was immediately wrapped up and the remains of the Turkish/Mongol conqueror were sent to Moscow. The turning point in the war came with the victory in the Battle of Stalingrad — only a month after a superstitious Stalin ordered the return of Tamerlane's remains to Samarkand where the former emperor was re-buried with full honors.

Gamla Stan, a royal massacre - Sweden

a photo of The red house of Gamla Stan, Stockholm, Sweden

The red house of Gamla Stan, Stockholm, Sweden


After Danish King Kristian II successfully invaded Sweden and was anointed King in November 1520, the new ruler called Swedish leaders to join for festivities at the royal palace in Stockholm. At dusk, after three days of wine, beer and spectacles, Danish soldiers carrying lanterns and torches entered the great hall and imprisoned the gathered nobles who were considered potential opponents of the Danish king. In the days that followed, 92 people were swiftly sentenced to death, and either hanged or beheaded on Stortorget, the main square in Gamla Stan (Old Town).

Until this day, the Stockholm Bloodbath is considered one of the most brutal events in Scandinavian history, and some people have reported visions of blood flowing across the cobblestoned square in early November. A little over a century later, a red house on the square was rebuilt as a monument for the executed — fitted with 92 white stones for each slain man. Legend has it that should one of the stones be removed, the ghost of the represented will rise from the dead and haunt the streets of Stockholm for all eternity.

Port Arthur, gruesome prison - Australia

a photo of ort Arthur Prison Settlement, Tasmania, Australia

Port Arthur Prison Settlement, Tasmania, Australia

Flickr/Eli Duke

During its 47-year history as a penal settlement, Port Arthur in southern Tasmania earned a reputation as one of the most notorious prisons in the British Empire. The institution — known for a brutal slavery system and punishment of the most hardened criminals sent from the motherland— claimed the lives of more than 1,000 inmates until its closure in 1877.

Since then, documented stories have spanned the paranormal gamut: poltergeist prisoners terrorizing visitors, weeping children roaming the port and tourists running into a weeping 'lady in blue' (apparently the spirit of a woman who died in childbirth). The museum even has an 'incidence form' ready for anyone wanting to report an otherworldly event.

Poveglia Island, plague victims - Italy

a photo of Poveglia Island, Italy

Poveglia Island, Italy

Mirco Toniolo/ROPI via ZUMA Press

Located off the coast of Venice and Lido, Poveglia sadly reunites all the classical elements of a horror movie: plagues, mass burial ground and mental institute (from the 1920's).

During the bubonic plague and other subsequent pandemics, the island served as a quarantine station for the sick and anyone showing any signs of what could be Black Death contamination. Some 160,000 victims are thought to have died there and the seven acres of land became a mass burial ground so full that it is said that human ash makes up more than 50% of Poveglia's soil.

In 1922 a retirement home for the elderly — used as a clandestine mental institution— opened on the island and with it a fair amount of rumors involving torture of patients. The hospital and consequently the whole island was closed in 1968, leaving all the dead trapped off-land.

Poveglia's terrifying past earned it the nickname of 'Island of Ghosts'. Despite being strictly off-limits to visitors, the site has been attracting paranormal activity hunters looking for the apparition of lost and angry souls. The island would be so evil that some locals say that when an evil person dies, he wakes up in Poveglia, another kind of hell.

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