Prominent virologist defends the Chinese Hybrid H5N1-H1N1 research, calls it ‘good science’
There was much written concerning the research published earlier this month in Science, where researchers from China’s Harbin Veterinary Research Institute reported creating an avian H5N1 (highly pathogenic) and pandemic 2009 H1N1 (easily transmissible) hybrid, that according to them, achieved airborne spread between guinea pigs.
Included in the media reports were criticisms from some in the research, virology and public health community.
The reactions on the research were mixed, much like the “controversial” research done earlier by Fouchier and Kawaoka.
One expert in the field noted on his blog recently that the research was “good science”.
I had the opportunity to ask a few questions today from the writer of the above blog post and Professor of Microbiology & Immunology in the College of Physicians and Surgeons of Columbia University, Vincent Racaniello Ph.D. concerning his thoughts on the newest research from China.
Herriman: How does the Chinese study advance the study of influenza virology? Of predicting pandemics? What exactly did we get out of it in your view?
Dr. Racaniello: The Chinese study, in which reassortants of H1N1 x H5N1 were tested, advances our understanding of influenza virology because it shows that 1) All possible reassortants between the two strains are viable and replicate efficiently in embryonated chicken eggs; this means that the segments of the two viruses are compatible; 2) some of the reassortants acquired the ability to transmit via aerosol among guinea pigs. The H5N1 virus does not transmit by aerosol among guinea pigs; exchanging the RNA encoding the H5N1 PA, NS, NA, or M proteins conferred transmissibility to H5N1 virus. This is fundamentally important because now studies can proceed to determine exactly how these viral proteins influence transmission. Once the mechanisms are determined, we can then ask whether they are also important for human to human transmission of human strains – in other words, are the mechanisms revealed by this guinea pig experiment applicable to other species? I do not view the work as helping to predict pandemics – this is often cited as the purpose of this work but I don’t think this is the correct way to portray it. We have little knowledge of what enables some viruses to transmit among hosts while others do not. If we could understand a species-specific mechanism – whether it be guinea pigs or ferrets – this can lead to studies to understand the underlying mechanisms.
I think the best opportunity to study human-to-human transmission might come from the current H7N9 viruses infecting humans in China. At the moment these viruses do not have the ability to transmit among humans; if the strain should evolve to acquire this property, then we will know the exact mutations needed for human to human transmission. This would be unprecedented, as we do not have such ‘paired’ viruses for any influenza of humans. We could then understand the underlying mechanism and see if they are also important for aerosol transmission in other mammalian species.
Herriman: Do you have biosecurity concerns with research such as this study, or the Fouchier or Wisconsin study for that matter?
Dr. Racaniello: I do not have biosecurity concerns with the current Chinese study or the Fouchier and Kawaoka studies. Here is my logic. Based on my experience in virology, and reading of the literature, I do not believe that animal models are predictors of what viruses do in humans. An example: pharmaceutical companies routinely test drugs and vaccines in two animal models; but in the end, they always do a clinical trial. If animals were predictive, this would not be needed. Often drugs and vaccines don’t work the same in people as they do in animals. By this view, the viruses that transmit in guinea pigs/ferrets will not transmit in humans. If, on the other hand, you feel that animal models *do* predict what viruses do in humans, then we can still rest assured, because the viruses in all three studies transmit by aerosol but they are not lethal – they just cause influenza. We already have influenza viruses that do that, so there is no biosecurity concern. The potential risks are far outweighed by the benefits of the research.
Herriman: On your blog you state:”I firmly believe that laboratory-constructed viruses do not have what it takes to be a human pathogen: only viral evolution in nature can produce the right combination of RNA segments and mutations. I also believe that scientists are quite responsible when it comes to safe handling of pathogens.”
Interesting statement…Can you elaborate on that?
Dr. Racaniello: New influenza viruses arise in animals, as the viruses reassort and undergo extensive mutation. The viruses that can ‘jump’ to humans are selected from a vast pool of reassortants and mutants, a pool different from the one we create in the laboratory. Nature is a wonderful agent of bioterror, because from the huge pool of viral variants nearly any virus can be selected for a particular trait. The fact that more animal viruses do not infect humans shows that many of the mutations that would enable spread to humans are simply not compatible with viral replication – they carry a fitness cost. In the laboratory, an H5N1 virus is made with a single RNA segment from H1N1 virus. This may be able to transmit among guinea pigs, but it does not have any of the other mutations that would be present in nature – and it has not gone through the strong selection forces in nature. That humans believe they can produce virulent viruses for bioterrorism is a severe case of hubris – to think that we can even come close to the diversity and selection that occurs in nature is laughable.
What scares many scientists is the fear of virulent viruses killing millions of people. Fear clouds their vision and makes them forget their virology basics.
As for safe handling of pathogens – we have a very good record of keeping dangerous strains safe in laboratories; considered the number of experiments that have been done the safety record is excellent. I’ve been inside a BSL-4 facility (http://www.virology.ws/threading-the-neidl/) and I can tell you it is the safest place on Earth to work with dangerous pathogens. Those who criticize scientists’ ability to do dangerous work in a secure manner simply don’t know how well these facilities operate.
Herriman: Why do you believe as many scientists that did came out in opposition of the Chinese study?
Dr. Racaniello: I can’t answer for the few scientists who criticized the Chinese study. I assume they did not read the paper and cannot appreciate its contribution to our understanding of virology. I also think there is a misconception that these studies might be useful for predicting pandemics; as I said above that is not the main value of the work and pandemic control should not be used to justify them. But I think the public best understands pandemic control, not mechanisms of aerosol transmission, and perhaps that is why that explanation is used.
These gain-of-function experiments (gaining transmission) are almost always accompanied by a loss-of-function: in this case, loss of virulence. Anything a scientist does to a virus in the lab is likely to cause reduced virulence, because the scientist does not know how to tinker with the virus without causing a loss of fitness. We simply do not know how to duplicate the evolution that goes on in nature. Anyone who thinks we can is mistaken.
I’ve been mutating poliovirus for 30 years (I was the first virologist to be able to do such manipulations with an animal virus) and I can tell you that no virus I have made has ever been close to the virulence of wild type strains. This is one reason why I speak out so strongly against the safety of this work on influenza virus. I will be the first to admit that there is always a first time – but given what we have seen so far, the likelihood seems remote. Hence, the benefits of the work far outweigh the risks.
Thank you Dr. Racaniello for your thoughts and expertise on the topic.
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