While scientists strive to improve human health and well-being, gain-of-function research could cause more harm than good.
By Yuhong Dong M.D., Ph.D.
We’re not afraid of the tigers in the zoo because we trust they cannot attack. But what if someone opens the cage?
Many viruses are highly lethal in nature but cannot infect humans. Fear arises when these viruses break the species barrier.
This can happen naturally or through risky research practices, particularly gain-of-function (GOF) research.
What Is GOF?
Just as all substances have functions, specific genes enable viruses to spread rapidly or cause severe diseases. GOF research involves introducing new functioning genes into a virus, enhancing its ability to infect hosts or increasing its virulence.
There are at least three main types of new functions a virus can gain:
Gain-of-function research on viruses often results in the viruses gaining new functions such as the ability to infect humans, enhanced transmissibility, or increased virulence. (Illustration by The Epoch Times, Shutterstock)
- Expanded Host Range GOF research can enable viruses to infect new species that they previously could not. This includes crossing the species barrier to infect humans, which poses significant risks for zoonotic outbreaks and potential pandemics. A 2015 Nature Medicine article provides a pertinent example. A bat-derived SARS-like coronavirus, initially noninfectious to humans, became capable of human infection after GOF studies at China’s Wuhan Institute of Virology (WIV).
- Enhanced Transmission GOF research can result in viruses gaining the ability to spread more efficiently between hosts. This includes changes that allow a virus to be transmitted through new routes or, more effectively, through existing ones. In 2012, GOF research at the University of Wisconsin-Madison significantly transformed the H5N1 bird flu virus. Initially non-airborne, the virus acquired the ability to transmit through the air, demonstrating the profound impact of GOF studies on viral capabilities.
- Increased Virulence Viruses can gain mutations that make them more virulent, meaning they can cause more severe diseases in infected hosts. This can involve an enhanced ability to evade the host’s immune system or increased replication rates within the host. A 2022 preprint paper shows researchers at Boston University created a lethal version of the Omicron variant.
GOF can also be used to generate positive traits in germs. For example, by adding a human insulin gene, a germ gains the new function of producing insulin.
GOF Research of Concern
Because viral genes are relatively easy to edit, GOF studies frequently involve viruses. However, some of these studies carry significant risks and can lead to dire consequences.
The U.S. National Science Advisory Board for Biosecurity (NSABB) defines GOF research of concern as “research that can be reasonably anticipated to generate a pathogen with pandemic potential,” characterized by two attributes:
- Highly transmissible, with the potential to spread widely and uncontrollably among human populations
- Highly virulent and likely to cause significant morbidity and/or loss of human life
If accidentally released from a lab into the general population, such pathogens could cause uncontrollable hazards. Additionally, the military application of GOF falls within the scope of bioweapon threats.
Methods of GOF research generally include genetic editing, which involves directly modifying a virus’ genes, and reassortment, which involves combining genetic material from different viral strains to create new variants.
In reality, the scope of GOF research can be much broader. Due to viral genes’ highly variable and adaptable nature, even routine culturing of viruses in cells or animals can lead to unexpected genetic alterations.
Double-Edged Sword
Scientists often conduct GOF research to understand the viruses and develop drugs or vaccines.
While these reasons may sound scientifically justified, the main debate centers on the risks versus the assumed benefits. GOF research can theoretically aid in studying viral mechanisms and provide insights for developing drugs or vaccines. However, the associated risks are significant, particularly the potential to generate dangerous pathogens.
A decade ago, two published studies on bird flu viruses were conducted by a U.S. lab and a Dutch lab, sparking significant discussion.
Both studies were designed to better understand how the viruses’ genes could be modified to make them more transmissible in mammals. The goal was to help people better prepare for a potential future pandemic.
Unexpectedly, after both groups of researchers separately edited the genes of a deadly H5N1 bird flu virus, they produced new strains capable of easily spreading via air droplets between mammals.
The edited virus could spread more easily among mammals and became easier to transmit to humans.
“Why would scientists deliberately create a form of the H5N1 avian influenza virus that is probably highly transmissible in humans?” This critical question was raised in a 2012 Nature article.
Subsequently, in October 2014, U.S. authorities announced a “pause” on funding for 18 GOF studies involving influenza, MERS, or SARS viruses.
The pause was short-lived. In 2018, the U.S. National Institute of Allergy and Infectious Diseases and the Dutch Healthcare Authority approved funding for further GOF research, sparking another wave of objections. Harvard University epidemiologist Marc Lipsitch expressed concerns in a Science article, stating that scientists are being asked to “trust a completely opaque process where the outcome is to permit the continuation of dangerous experiments.”
Finally, after yielding to public pressure, investigators for the two research studies declined to renew the grants originally submitted for their GOF research. Consequently, such bird flu GOF studies were officially halted in the United States in 2020.
In the United States and most European countries, where scientists can express their opposing opinions, the development of GOF experiments faces multiple regulatory hurdles and ethical reviews.
However, in countries without these safeguards, the pursuit of GOF research could proceed unchecked, potentially putting the world at significant risk.
Workers are seen next to a cage with mice inside the BSL-4 laboratory in Wuhan, capital of China’s Hubei province, on Feb. 23, 2017. (Johannes Eisele/AFP via Getty Images)
China’s Bird Flu GOF Research
Risky GOF studies on bird flu viruses in China have been underway since the 2010s.
In a study published in Science in May 2013, a group of scientists at Harbin Veterinary Research Institute in Harbin, China, conducted GOF research by combining the highly lethal but not easily transmissible H5N1 avian influenza virus, with the highly contagious H1N1 swine flu strain, which infected millions of people in 2009.
The resulting hybrid viruses were then tested for their ability to infect mammals, revealing the potential risks associated with such genetic manipulation of pathogens. This research underscored the dual-use nature of gain-of-function studies, highlighting both their potential to inform pandemic preparedness and the significant biosafety and biosecurity concerns they raise.
As a result, the researchers created a new, more virulent virus. An H5N1 hybrid strain, which integrated genes responsible for transmissibility from the H1N1 virus, acquired the capability to easily spread among guinea pigs through respiratory droplets.
In 2021, a collaborative project involving researchers from the United States, the United Kingdom, and China sought to enhance surveillance and vaccine development. While not explicitly labeled as a GOF study, these experiments conducted in a Chinese laboratory involved genetic modifications typical of GOF research.
The experiments used a routine viral laboratory research approach known as “serial passage,” which involves growing the virus from one cell or animal model to another. Viral mutations with greater transmissibility or pathogenicity can often be selected during this process. The animal models were also carefully chosen to reproduce the virus for specific research purposes. We’ve explained this in detail in a previous article.
Nonetheless, the most widely known GOF studies conducted in China involve research on coronaviruses.
Breaking the Barrier
Bats are known carriers or natural reservoirs of many viruses. Bat-hosting coronaviruses typically only infect bats or wild animals, not humans. However, this situation has changed with the advent of GOF research.
In 2015, a team of Chinese scientists conducted GOF studies on a bat coronavirus at the WIV, which is affiliated with the Chinese Academy of Sciences and under the administration and control of the Chinese Communist Party (CCP).
In this study, the researchers took the gene for spike protein—the spike-shaped structure on the surface of a virus—from a bat SARS-like virus and inserted it into the backbone of a SARS virus, the virus that caused the first pandemic of this century.
The newly created SARS-like virus, coded as SCH-014-MA15, could infect human airway cells and achieve a transmission similar to the SARS virus. It also gained the ability to infect mammals like mice and successfully cause lung diseases.
WIV created a chimeric virus that was originally not infectious to humans but has gained a new ability to infect human cells. (Illustrated by The Epoch Times, Shutterstock)
The WIV has also conducted other GOF research on bat SARS-like viruses with effective results.
According to a leaked 2014 NIH report, WIV researchers experimented on a natural bat coronavirus capable of binding with human ACE2 receptors, significantly increasing its potency. They used this bat virus to engineer three new chimeric coronaviruses.
The results showed that in the lungs of mice, these newly created coronaviruses produced far more virus particles—up to 10,000 times higher than the original virus.
Between Day 2 and Day 4 post-infection, three viruses resulting from the GOF research at the WIV exhibited approximately a 10,000 times higher viral load in the lung tissues of humanized mice with a transgenic hACE2 gene than the normal virus. The graph illustrates the significant difference in viral load among the three viruses, depicted using cubes. (Illustrated by The Epoch Times)
Additionally, the body weight of the infected mice dropped rapidly, particularly with one new viral strain, SHC014, suggesting that the engineered virus caused severe disease. Body weight is commonly used as a marker of health status in mice.
Meanwhile, another new virus, WIV-16, did not cause a drop in body weight, possibly indicating an asymptomatic infection.
Viruses resulting from GOF research at the WIV caused a notable decline in the body weight of humanized mice carrying a human hACE2 transgenic gene. (Illustrated by The Epoch Times)
Loose Oversight
In contemporary China, under the totalitarian CCP regime, public oversight is limited, and Chinese citizens are often prohibited from voicing concerns about these risky biomedical experiments.
Many labs in China study dangerous pathogens, but the lack of transparency in public safety makes it difficult to assess how these labs are managed.
While benign viruses exist, most viruses close to humans are dangerous. When scientists handle risky viruses in their laboratories, misconduct or accidental leaks of these dangerous pathogens can occur, posing significant safety risks to researchers and nearby populations.
To protect human safety, biosafety regulations are established to manage these labs. There are four biosafety levels (BSLs), with BSL-3 and BSL-4 labs handling the most dangerous viruses.
According to a 2021 investigative report published in the Journal of Law and the Biosciences, China had 48 BSL-3 labs and its first BSL-4 lab at the WIV. China still plans to increase the number of BSL-4 labs to five to seven by 2025.
While Chinese labs often have sufficient technical capacity, they face a major challenge due to relatively loose biosecurity regulations. Several documented lab leak incidents from BSL-3 and BSL-4 labs in China have occurred.
In 2004, a World Health Organization spokesman in Beijing, Bob Dietz, reported that the SARS virus escaped twice from the Chinese Institute of Virology in Beijing, which is affiliated with the Chinese Center for Disease Control and Prevention.
In July and August 2019, a government-operated vaccine facility in Lanzhou experienced a leak, causing the spread of Brucella bacteria via aerosol to nearby communities and individuals.
Brucella is easily aerosolized and can cause brucellosis, a common livestock disease that can lead to chronic illness or death in humans.
Following the leak, in September 2020, the Lanzhou government health commission confirmed that at least 3,245 people were infected. According to Global Times, a Chinese regime-owned news organization, by December 2020, the number of confirmed cases had risen to 10,528.
The WIV was constructed in 2003, around the same time as the SARS outbreak in China. Ongoing projects at the WIV include research on the following viruses:
- SARS
- COVID-19
- Ebola: a virus that causes severe bleeding and organ failure and can lead to death
- West African Lassa: a rat-originated virus that can spread to humans and cause death
- Crimean-Congo hemorrhagic fever: a deadly tick-borne virus that affects livestock and can jump to humans
Secret activities at the WIV reportedly include extensive GOF research for military purposes. The military application of GOF research, also called dual-use research, is a significant concern.
A 2023 UK Biolabs report evaluated the statutory oversight of dual-use research. China scored zero out of 10 in the rating for conducting GOF studies for military purposes. A lower score indicates inferior safety regulation.
BSL-4 laboratory on the campus of the Wuhan Institute of Virology in Wuhan, China. (Hector Retamal/AFP via Getty Images)
‘Wooden Barrel Theory’
The risky nature of GOF research is unlikely to convince rational people or policymakers to support it in the name of drug or vaccine development. GOF is not the only method or the most efficient way to protect people and prevent future pandemics.
There is abundant scientific evidence supporting low-cost and accessible ways to enhance immunity in preparation for a pandemic caused by a virus or germ. These methods include taking vitamin D and other supplements, maintaining a balanced diet, engaging in regular exercise, practicing meditation, and sustaining a healthy mental state.
Following these practices can strengthen natural immunity, helping people to better defend themselves against pathogens. For example, those with robust and balanced immunity are less likely to be affected by a cold virus and can recover quickly if they do get infected.
On the other hand, those with weakened or unbalanced immunity may be more prone to developing pneumonia and might even require emergency medical care.
Moreover, there are less risky ways to develop drugs and vaccines.
To enhance public safety, the NSABB released draft guidelines in January 2023, introducing stricter oversight of GOF research in the United States.
In a recent U.S. congressional hearing held on June 18, 2024, regarding the origin of SARS-CoV-2, there was significant debate over the definition of concrete data supporting a lab-related origin. However, there was some consensus on several key points:
- The United States should not fund any GOF research.
- The United States should not provide financial support to labs that do not adhere to international biosafety standards.
- Whether from a wet market or the Wuhan lab, China is to blame. Complete transparency and accountability from those working in the WIV are essential.
In addition to the United States, regulatory authorities in other major countries, including the European Food Safety Authority (EFSA) and the Public Health Agency of Canada, have also raised concerns about GOF studies.
In 2022, a joint review paper by researchers from Japan and the UK reevaluated the need for research involving pathogens with pandemic potential. They concluded that “the risks of such research are clearer than before, whereas its benefits seem less apparent.”
However, such dangerous research is still ongoing in China. This includes creating new SARS-like viruses, using SARS-related viruses to study interspecies transmission, and isolating more ACE2-dependent viruses from bats.
The ongoing research conducted by Chinese labs poses a significant risk of producing more dangerous viruses or pathogens and potentially releasing them into the environment.
In current China under the totalitarian CCP regime, BSL-3 and BSL-4 labs studying dangerous pathogens lack adequate public safety oversight, posing significant threats to global safety. China holds the lowest bar in the world “barrel” in terms of viral GOF research. (Illustrated by The Epoch Times)
This is similar to the “wooden barrel theory,” which illustrates that a barrel’s capacity is not determined by the longest wooden bars but rather by the shortest. In other words, its capacity is determined by its weakest component.
In the context of global safety, it is crucial to uphold strict standards in highly regulated countries and address deficiencies in those with the lowest standards of medical ethics and minimal regulation. Highly risky GOF research under a totalitarian regime raises the stakes for a potential global disaster.
Views expressed in this article are the opinions of the author and do not necessarily reflect the views of The Epoch Times. Epoch Health welcomes professional discussion and friendly debate. To submit an opinion piece, please follow these guidelines and submit through our form here.
