The legislative decree recently approved by the Council of Ministers for the implementation of EU 2010/63 directive is full of holes. The European dictate that it has been quite “mistreated” by the Italian Parliament Commissions – which he had the misfortune to encounter – in particular for two “memorable” cheap shots. Poor figure apart, many are asking now if the Italian law is ready to be thrown away yet, perhaps by appealing to the European Court of Justice. Whatever the ending, however, the new law makes the practice of animal experimentation in Italy more uncertain, as the plausibility of international investments in Italian labs.

We asked Gaetano Di Chiara – neuropharmacologist of the University of Cagliari and vice-president of Gruppo 2003 – to comment the critical points of this new law.

The new law allows testing on alive animals. Biomedical research continuity seems therefore guaranteed. 
The legislative decree for the implementation of EU 2010/63 directive, just published, allows the use of non-human vertebrates and cephalopods (yes, octopuses and squids), but forbids, Art.5, comma 2, studies in vivo for substances of abuse and xenotransplants.  

Is it so important to experiment substances of abuse on animals?
Matarese et al., in their commentary of Trends in Molecular Medicine (18, 439, 2012), which is significantly entitled "In vivo veritas, in vitro artiphicia" explain why in vitro studies must be validated in vivo.
In regard to substances of abuse, there is not even the dichotomy between in vitro and in vivo, since these studies are based on behavioural paradigms where the animal voluntarily self-administer the substance or carries out complex cognitive tasks. There are no models, in vitro or in silico, that can exactly reproduce the mechanisms used by human or animal brains: if they existed, we would have a thoroughly understanding of the brain. But there is no need to be neuroscientists to realize that we are still far, far away from this goal.

Studying substances of abuse if fundamental for the comprehension of the neurobiological mechanisms which are at the base of natural gratification; on the other side, the study of abuse properties of centrally-acting drugs is necessary for developing new treatments for drug addiction, for verifying the abuse potential of new recreational drugs (that continuously appear on the market) and of centrally-acting drugs developed for the treatment of psychiatric conditions, for which it is necessary to exclude the capability of inducing addiction. Therefore, researches on substances of abuse pertain exactly to the legitimate use of animal experimentation as attested by the decree. This is the most paradoxical aspect of the ban of in vivo studies for substances of abuse: the contradiction, without any explanation, of the Art.1 comma 3a, 3b of the same decree that allows the use of animal (vertebrates and cephalopods) for in vivo studies in basic and biomedical translational research.

In truth, the law forbids this experimentations, but a temporary regulation (article 42) allows the suspension of the ban until December 2016. Therefore it will be possible to conduct these experimentations up to that date, won’t it be?
The irrationality and the contradictory nature of this decree are so macroscopic that they had to be noted by the legislators, in this case the various Parliament Commissions, first at the Senate then at the Chamber of Deputies, which the implementation of the EU directive has being passing through.
However, this long procedure did not manage to cancel the ban on substances of abuse, which proceeded “unharmed” by the delegation to the government process and then the Council of Ministers. Therefore, in order to kill this legislative monster, they created a new one, similar in size: the temporary regulation, included in the Article 42, the last one, clearly added in extremis. This regulation states that bans on substances of abuse and xenotransplants are suspended until December 31, 2016 and that, after that date, their realization will be subject to the Zooprophylactic Institutes of Lombardy and Emilia-Romagna Regions, which will consider if alternative methods to in vivo studies are available. If by June 2016 these Institutes will assess that no alternative methods exist, the ban might be cancelled.

Then…
Then everything should continue as before, but always with the uncertainty that something may change according to the “animalist” majority in the Parliament. Conditional is a must, because the same article does not say what might happen and it is easy to foresee, based on previous similar cases where medicine and politics have been merging (the case Stamina is a clear example), that anything might happen.
In the best hypothesis, the most obvious since studies on substances of abuse are largely of behavioural ones, it will be declared that there are no alternative methods to in vivo studies and the ban will be suspended for another 3 or 4 years and so on. It is clear that even in this case, however, the destiny of an entire research sector will be affected, since none is ready to fund or do research on such a short-term and with such an uncertain future. In certain cases, for extremely innovative researches, three years are the necessary time for just developing the methodology.

Xenotransplants seems quite exotic. Are we experimenting those as well?
Of course. Despite their name, they are not unusual at all. This term, in fact, does not refer to transplants of animal organs into humans only (usual practice for cardiac valves), but also to the realization and use of in vivo animal models for the development of anti-cancer drugs.

Why do you think they attacked just the substances of abuse and xenotransplants?
The animalist lobby wanted to hold back in vivo research and they succeeded in the two areas where ignorance and mystification could grip best. In the case of substances of abuse they played the card of drug-addiction being more a social problem than a healthcare or medical one, stating that pharmacological therapies are not effective, which is completely false and intellectually dishonest.

But these bans – though cancelled by the suspension – were somehow present in EU directive too?
The EU directive not only has no trace of ban for the use of animal for research on substances of abuse, but does not contain any prohibition in general. The legislation, in fact, does not forbid the use of animals for experimentation, but establishes a series of rules that researches must follow in order to reduce animals’ suffering to a minimum.
The ban on substances of abuse, like the one on xenotransplants, makes the Italian law dissimilar, because it is more restrictive than the UE directive, and therefore breaches the Article 2 of the directive itself. This article establishes that, in matter of animal testing, the Member States cannot adopt more restrictive rules than those stated by the same directive, unless these rules had already been in operation by 2010. The last laws on animal experimentation in Italy are dated 1988 and 1992, but there is no trace of the bans now present in the new decree. The Article 2 has been clearly included by the EU directive in order to protect research and avoid that the implementation of the legislation could offer the excuse to introduce more restrictive national rules.

The Italian law could then be not legitimate? 
Of course. We know for sure that scientific societies and patient associations are appealing to the European Court for the cancellation of the ban.

Are there any other questionable points in the decree for the implementation of the EU legislation?
We could list all the slip-and-fall accidents of this law, from the administrative complications to the obstacles for the so-called transgenic animals, to the non-repeatability of chronic experiments and so on.
But I think this is the time to fight against these absurd and illegitimate bans, appealing to the European Court of Justice by using the Paragraph 2 of the EU directive.