On the 17th of this month, the UK government approved the world’s first novel coronavirus control trial (known as the New Coronavirus Challenge Study), which plans to infect up to 90 volunteers in a rigorous laboratory setting to gain important information about the virus.
Novelty as the research may sound, the concept behind it has a long history, dating back to the late 18th century.
However, the challenge of novel coronavirus is still being debated: is it necessary?
What unique insights does it offer?
Writing | Luo Dinghao
Nearly 90 healthy adults in the UK are about to embark on a journey.
Instead of a normal journey, they will be in London’s Royal Free Hospital, where they will face a novel coronavirus (SARS-CoV-2) and each will be rewarded with around £4,500 (£4,500).
The process is straightforward: The 90 warriors will take on the Novel Coronavirus challenge, putting their health at risk and offering scientists a shortcut to research.
At this very moment, the number of novel coronavirus infections worldwide continues to rise. The total number of infections has so far exceeded 100 million, including more than 27.8 million in the United States.
Vaccination, on the other hand, is not far behind, with more than 180 million people worldwide having received at least one dose of the new crown vaccine as of December 18.
At the same time, many variants of the novel coronavirus are rapidly emerging, thanks to its own characteristics and large infection base.
Last December alone, the world witnessed two high-impact variants (B.1.1.7 in the UK and B.1.351 in South Africa), and many new and potentially influential strains have emerged during the recent winter outbreak.
All this means that the vaccines developed by scientists need to be replaced quickly, which will require more clinical trials.
The UK government approved the world’s first trial of the new crown challenge on 17 January.
In the first phase, up to 90 volunteers will be exposed to the virus in the P3 virus laboratory to determine the minimum dose of the virus that can infect humans.
The aim of this phase is to provide the basis for future research into vaccine and drug challenges.
Once the minimum dose of infection is known, scientists can conduct further tests to confirm the effectiveness of potential vaccines and drugs.
But many people and scholars remain skeptical of the study.
Further discussion of this controversial human trial requires an understanding of the historical and ethical implications behind it.
To infect humans
The “Challenge Study”, to be conducted in the UK, may sound novel, even daunting, but the concepts behind it are old and have made great contributions to human society many times over.
Studies like the Challenge study, collectively known as controlled human infection, or CHI, are designed to expose healthy, low-risk human subjects to the virus in a tightly controlled environment.
Together with candidate vaccines or drugs, CHI tests can provide a great deal of information about the disease itself and treatment options in a short period of time.
The history of the CHI test dates back to the late 1700s, when Britain was plagued by the variola virus.
In the early days of the smallpox epidemic, the most commonly used prevention and control method is “human pox vaccination” : smallpox patients on the pustules broken, and then with a knife will flow out of the pus swab under the skin of the seed.
Since smallpox usually only wreak havoc through the lungs, the virus inoculated under the skin does not actually cause serious damage. Most patients will become immune to smallpox after experiencing mild symptoms.
But it was also important to note that deaths still occurred because the inoculation was still with the real smallpox virus.
ON MAY 14th 1796 Edward Jenner, the “father of vaccines”, carried out his world-famous “vaccination experiment” in Berkeley, a small town in south-west England.
The experiment was inspired by the folklore that a person who had been infected with cowpox could not get smallpox again.
Ms. Jenner inoculated 8-year-old James Phipps under the skin with pus from a cowpox puss belonging to a milkmaid, Sarah Nelmes.
Over the next few days, Phipps experienced a brief, low-grade fever.
Over time, Jenner gave Phipps multiple subcutaneous injections of the smallpox virus, but Phipps showed no signs of illness, and Jenner concluded that Phipps’s vaccinia had successfully protected him against smallpox.
To verify the vaccine’s effectiveness, Jenner gave the same vaccine to 23 other subjects.
The results showed that vaccination did provide immunity against smallpox.
Jenner said this method as “vaccination” (vaccination), etymology is Latin for “vacca”, meaning “cow”.
After Jenner’s “vaccination test,” similar CHI tests followed.
In the 1950s and 1960s, for example, scientists conducted the infamous hepatitis virus research at Willowbrook State School in the United States, exposing School students to the virus without proper consent.
This study successfully revealed the existence of two different hepatitis viruses, A and B, but because of the ethical conflict it caused, researchers had to find a way to standardize the CHI test.
In recent decades, with the development of medical ethics research, CHI tests have gradually become more standardized, and the control and supervision have become more perfect.
In 2018, published in the journal lancet infectious diseases, a reiew from Leiden University (Universiteit Leiden), the University of Tubingen in Germany (Universitt Tubingen) and the University of Liverpool in England (Liverpool University) of five scientists are summarized in the last few decades CHI test, and found that the recent CHI tests have passed strict scientific supervision, most subjects are given explicitly agreed to test,
The number of serious adverse events (SAE) was extremely low.
For example, in several influenza and malaria CHI trials conducted from 1990 to 2014, involving a total of about 6,000 subjects, there were only four cases of SAE.
This shows not only that the treatments or vaccination regimens offered by the CHI trials are effective on their own, but also that the subjects enrolled in these studies were carefully screened out of applicants who might have been harmed by the trials.
Some pathogens infect only humans, making animal models time-consuming, laborious and pointless.
In some CHI trials, with the help of volunteer subjects, scientists have successfully created human models of human pathogens, such as human rhinoviruses, providing critical information for their treatment and prevention.
Roestenberg et al.
The Lancet Infect.
All of this evidence suggests that CHI tests are not only increasingly regulated, but also offer unique insights that animal models cannot.
Challenge the new champions
But even amid this optimism, the novel coronavirusCHI trial is proving difficult.
First of all, different from influenza virus and rhinovirus, novel coronavirus is spread in human only for more than 1 year, we have not yet had a clear understanding of its physiological effects, do not know whether the virus can cause long-term, still lasting sequelae after recovery.
Second, some scholars have suggested that CHI testing may no longer provide important insights at a time when the recent mass vaccination campaign has begun to pay off, and the number of new diagnoses in Israel, the United Kingdom, the United States and many European countries is declining.
But the pros argue that there is plenty of evidence that novel coronavirus does little to affect young, healthy adults, and that many people get better quickly after experiencing mild symptoms.
And unlike earlier CHI trials, the New Crown Challenge provides volunteers with a detailed description of the experiment and is only included if the subjects give their consent.
In addition, the recent emergence of novel coronavirus variants has spurred demand for new vaccines that can prevent the infection of mutant strains, and some researchers believe that CHI trials can quickly confirm the effectiveness of these new vaccines, replacing conventional phase III clinical trials.
Nir Eyal, director of the Center for Population Bioethics at Rutgers University, said the new crest trial would require only a few hundred volunteers, making it much faster than a phase III trial with tens of thousands of people.
This means that challenge tests can quickly verify the effectiveness of vaccines and treatments, or dramatically reduce the impact of a mutant strain.
Even so, many scholars are skeptical about the New Crown Challenge experiment.
Matthew Memoli, an immunologist atthe Institute of Allergy and Infectious Diseases in the United States, said that only a good understanding of Novel coronavirus could properly assess the risk of a challenge trial;
There is not enough information to support plans for a challenge trial.
Other researchers noted that even one death could make it harder to approve future CHI trials for other diseases, even though the risk of death in healthy subjects was extremely low if the challenge trial was carried out rushly.
As a result, some people believe that the audit and supervision authorities need to think twice before carrying out the new crown challenge trial.
In the world’s first trial of the new crown challenge, approved by the UK government, researchers will try to reduce the discomfort of their subjects.
Once the subjects became infected, they were given treatment drugs such as Remdesivir and Regn-CoV2, which quickly alleviated symptoms and kept the subjects healthy.
The goal of this stage is to determine the minimum dose of virus required for infection.
After that, scientists will conduct further tests to confirm the effectiveness of potential vaccines and drugs.
It’s important to note that this is a preliminary study, using a strain called Novel Coronavirus that was popular in Europe last summer, not a recent variant.
But the success of this preliminary study could pave the way for new crown challenges to be tested against mutant strains.
As Christopher Chiu, the leader of the preliminary study, put it, the researchers are also “considering which new crown variant to test next.”
However, this pilot study alone could provide us with the question “What is the lowest dose of virus necessary to cause infection?”
“How exactly does the immune system behave in the early stages of infection?”
“And” What’s the difference between symptomatic and asymptomatic patients?”
And so on.
In fact, Edward Jenner’s title as the “father of vaccines” has long been controversial.
John Fewster realized in 1768 that vaccinia infection made people immune to the smallpox virus, and for more than a decade researchers from Britain and continental Europe investigated the possibility of using vaccinia as a smallpox vaccine.
This article describes it in detail.
[Note 2] Knowledge of hepatitis viruses has improved greatly since then, and five major hepatitis viruses (hepatitis A, hepatitis B, hepatitis C, hepatitis D and hepatitis E viruses) have been classified.
[Note 3] This is controversial. Most of the scholars who support the CHI trial are conservative and support that the CHI trial should be viewed as a supplement to, rather than a complete replacement for, phase III trials.