As more countries legalize marijuana for medicinal purposes, researchers try to better understand its health effects. Miriam Melis, a pharmacologist at Università di Cagliari, in Sardinia, investigates how using marijuana during pregnancy affects brain development in the offspring. To do so, she studies the offspring of mice given low doses of the drug’s psychoactive ingredient during pregnancy. But, if a ban on the use of animals in studies of addiction becomes effective, Melis might have to stop her research as early as next year.
The provision is part of a bill that the Italian government approved in 2014 to implement a European directive from 2010 which aimed at standardizing the use of animals in research across the European Union. The Italian law imposes tighter restrictions than the directive, in particular on studies of drug abuse and xenotransplantation — the animal-to-human transfer of organs, which scientists hope could ease the shortage of organ donors. Since the law was approved, the Italian government has postponed the bans, initially until 2017 and then until 2021. Last December, it further deferred the bans to 1 January 2022 in a decree, which must now be approved by the Parliament and made law by early March.
The legislative limbo is having a “devastating” impact on the country’s ability to innovate and attract research money, says Roberto Caminiti, a physiologist at Università di Roma La Sapienza. It could be also very costly. The European Directive does not allow countries to impose stricter rules than those in the directive itself, unless they were already in place before it. In 2016, the European Commission has started a legal action against Italy that might lead to a fine of millions of euros per month.
“The fine would be bad,” says biologist, Giuliano Grignaschi, head of the Animal Care Unit at Università di Milano and director of a group that advocates animal research. “But it’s even worse that researchers in Italy won’t be able to do what they could do in any other country.”
Animal research has been the centre of furious political debate in Italy. The 2014 legislation sought a compromise between the concerns of animal-rights campaigners and the needs of researchers, says Beatrice Lorenzin, a member of Parliament with the Democratic Party, who in 2014 co-proposed the bill when she was Health Minister. At the time, she says, activists and Parliament members argued that animal studies on drug abuse and xenotransplantation could be phased out and replaced with alternative options. Some found it immoral to use animals to study ‘bad habits’ (but scientific evidence shows that addiction to alcohol or drugs is a brain disorder). Others questioned the benefits of xenotransplantations for patients.
But the alternative to animal experiments isn’t available yet, Lorenzin adds, so much so that the Italian government had to repeatedly postpone the bans. Meanwhile, Parliament has continued to push back a permanent solution. “In the Senate, there are very deep-rooted positions on the subject that have not yet allowed the elimination of those bans,” says Elena Cattaneo, a stem-cell scientist at Università di Milano.
In March 2020, Italy’s National Bioethics Committee (CNB), a governmental advisory panel of biomedical and legal experts, recommended the bans be cancelled. But there too, divisions emerged. Six of the 26 members voted against the motion, noting that animal models fail to account for the complexity of addiction in humans and raising ethical concerns on xenotransplantations. CNB member and bioethicist Luisa Battaglia from Università di Genova sees xenotransplantation as a “serious” case of animal exploitation, and says donor shortage should be rather solved by increasing human donations. Keeping the bans is important to boost research into alternative methods to animal testing, says Salvatore Amato, a professor in philosophy of law at Università di Catania, another CNB member who opposed the March motion. “Researchers will not seek new ways if there are no obstacles to the old ones.”
Lack of alternatives
In this climate of uncertainty, scientists have had trouble getting research funding, which is usually awarded for at least three to five years, and some have been excluded from international collaborations. “Over the past seven years, our lab has applied for fewer grants than it used to, because the duration of some grants exceeded the supposed implementation of the ban,” says Nicola Simola, a pharmacologist at Università di Cagliari.
The damage would be even greater if the bans become effective next year, says Roberto Ciccocioppo, a pharmacologist at Università di Camerino. “Either researchers close their labs or they move to another country” he says. He says banning addiction studies would also hamper safety studies of new medicines that target the brain to treat pain, mood disorders, seizures and neurodegenerative diseases. Such studies evaluate whether a medicine can cause addiction, and typically assess how rodents behave after receiving several doses of the medicine compared to a substance of abuse. As for alternative methods, Simola says that a handful of nerve cells in a dish can’t reproduce the interactions between the brain and other organs, and even the most advanced computer models can’t mimic a complex living organism. A recent report by health minister, Roberto Speranza, supports this idea.
Others worry that the ban on xenotransplantation studies would end the development of potentially life-saving procedures. Currently there are more patients who need a kidney or liver transplant than donors. Pig organs could in principle be compatible with humans, but there are several obstacles to overcome, such as the risk of transmitting infections or triggering an immune reaction. Current experiments involve transplanting organs from pigs to animals that are closer to humans, such as monkeys. Grignaschi says it is impossible to replace such animal studies. “It is like testing a pacemaker: sooner or later, it will have to be implanted in a living organism,” he says.
Lorenzin and other members of the Parliament have proposed to postpone the bans until at least 2024 before approving the government's decree. Marco Bella, a member of Parliament with the Five Stars Movement and a chemist at Università di Roma La Sapienza, says the best solution would be to amend the law and scrap the bans altogether.
The Ministry for Health has not responded to requests for comment from Nature Italy. A spokesperson for the Minister of University and Research Gaetano Manfredi said in an email that “the position […] is to adopt the European directive without changes.”