I’m a professor of pharmacology. I teach in 3rd medicine, and until 2013 he taught laboratory practices with albino mice of BALB/c inbred strains. Students injected drugs under my supervision with a syringe into a living being for the first time in their lives. They did so intraperitoneally, which is safe in these rodents and is considered pharmacokinetic equivalent to the intravenous line in humans.
Not now. Future doctors practice with dolls and then with you, kind reader, or with me, or whoever ends up being your first patient, who will also become the first living being to which they will inject a drug. This is true after RD 53/2013. And Spanish society has assumed it, I think, without debate and in a way that is not entirely conscious.
In any event, it should be checked, asking society for «informed consent» in application, in a broad sense, of the principle of autonomy. The one «that obliges to respect the freedom of decision of any patient on any intervention».
That we can be given a drug without acquiring «previous experience» is the result of the debatable application to mice of the principle of non-malfience (not doing evil to that animal), which, in this case, may involve not applying the principle of charity (doing good to a human being).
Animal models for developing human vaccines
But this is sinful minutes compared to other conflicts that provoke these norms based on moral animalism. My purpose is to report on how these standards affect the development of vaccines, where a key point is their previous experimentation, in the preclinical phase, in suitable animal models.
Suitable involves two things.
The first is that it is an immunogenicity model, with high response of neutralizing antibodies (Ac), extrapolable to humans. In a mouse there can be a high production of antibodies after administration of the experimental vaccine, and then in humans that response is very low, which is a considerable waste of time and resources.
The second condition is especially relevant: this model should allow to rule out the risk of immunopathology. A vaccine may not cause serious adverse effects in mice, while in humans it causes aggravated disease, or a pathological immune response.
With Covid-19 disease, models based on mice and other species that are not already «infective models» that are susceptible to infection by some route of inoculation (intranasal, endotracheal, intramuscular or intravenous) seem adequate. Except, perhaps, in the case of the transgenic mouse with humanized ACE2 receptors (receptors that the virus uses to infect human cells), or in ferrets and monkeys Macacus rhesus. But are these the best models for extrapolable immunogenicity and absence of immunopathy?
The answer, exclusively scientific and non-ideological, is no. The right animal model is NHP (non-human primates), primates with the greatest genetic proximity to humans. That is, the great apes: chimpanzees, gorillas and bonobos. The greater the genetic proximity, the more extrapolable the results in immunogenicity and immunopathy will be.
Is this evidence being applied to the investigation? In principle, at least in the West (Europe and the US), it does not apply. In essence because these models with great apes are incompatible with LPG (Good Laboratory Practice).
In Spain the answer is bluntly not. Because RD 53/2013 prohibits all experimentation, including vaccines for emerging viruses, in large apes (only allows it in Macacus rhesus). This DR is logically the result of a directive of the European Union, 2010/63/EU. But that, while in Spain it was applied in its maximalist version, other countries included the prudent «unless the urgency for the arrival of emerging viruses required it» (referring to experiment on other apes other than macaques).
Promising vaccines for COVID-19 with chimpanzee adenovirus
With the Covid-19 vaccine, something interesting has happened in relation to all this.
The design that, in my opinion, has the most chance of giving rise to the first viable vaccine is the antigen-based one on the virus’s «viral surface spicul) (spike S) protein, which binds to the ACE2 receptor in target cells, vectorized with attenuated attenuated catarrales adenovirus type 5.
The Chinese are the ones who have gone the furst in this line, but in the clinical phase in hUmanos have found that there was pre-existing immunity in 50% of volunteers. That is, half of patients are immune to that cold adenovirus, which decreases the effectiveness of the vaccine.
However, at Oxford University researchers Andrew Pollard and Sara Gilbert have used the same design but with chimpanzee adenovirus, and will immediately begin the clinical phase with 510 volunteers. Pending the results, this would be the most promising vaccine. But, as there are restrictions on the use of great apes in experimentation in the UK, and they cannot be kept in captivity and manipulated, I do not know how this vaccine has developed with chimpanzee adenovirus. What is clear is that in Spain the Royal Decree we were talking about earlier would prevent them from obtaining them from these apes.
Transparency on the use of animals in scientific experimentation
That’s the way it is, and they’re likely to stay the same when the next emerging viruses arrive, perhaps more lethal than this one. Solution? Until recently it has been not to talk about the issue so as not to create conflicts. Fortunately, the attitude is changing. On September 20, just before the start of the pandemic, the «Transparency Agreement on the Use of Animals in Scientific Experimentation in Spain» promoted by the Confederation of Scientific Societies of Spain was presented at the CSIC with the aim of «speaking clearly about when, how and why animals are used in research».
Interestingly, the United Kingdom, which was the country where animalism originated and which has suffered the most violent actions of these groups, is a pioneer in publicly claiming the use of experimental animals, as Wendy Jarret, promoter of the British agreement on transparency in animal experimentation, has explained. According to Jarret, British public opinion has changed in just two years, increasing acceptance of animal use in scientific research. In addition, the violent acts of animalist groups have virtually disappeared. I think this is the way: to explain and inform, to treat citizens as adults. And let them decide.
Maybe I can never give mice to my students anymore, and they’ll only use computer simulations and silicone mockups. But at least because your future patients have given their consent, after being informed.
Luis Martín Arias, Senior Lecturer in Pharmacology, University of Valladolid
This article was originally published in The Conversation. Read the original.