Venom To Cure Disease, On The Frontier Of Modern Snake Medicine

A European program has been researching how the pharmaceutical industry could use the peptides found in venomous creatures for new therapeutic medicines.

A biologist shows a drop of venom that comes from the fangs of a ''Yarara'' snake in Buenos Aires, Argentina.
A biologist shows a drop of venom that comes from the fangs of a ''Yarara'' snake in Buenos Aires, Argentina.
Vahé Ter Minassian

PARIS â€" Nicolas Gilles points to a dozen metal boxes in a refrigerator, all filled with preserved samples of animal toxins, mini proteins that are among the most dangerous substances found in Mother Nature â€" secretions made to paralyze, suffocate or kill. The refrigerator contains more than 4,000 from 201 venomous species: snakes, spiders and cone snails, among them.

This researcher at the Atomic Energy and Alternative Energies Commission outside Paris coordinates a European project called Venomics, which has been studying therapeutic uses of animal venom. Launched four years ago, the project ended a few weeks ago with a closing conference designed for the media at the French National Museum of Natural History in Paris. It was an opportunity for participants from all over Europe to make assessments about their activities and talk about leads for the future.

The idea of creating drugs made from animal substances that are designed to attack prey or protect against an enemy isn't new. "To produce their neurotoxic, cardiotoxic or hemotoxic effects, venoms affect specific cells of living organisms through peptides," Gilles explains. Some of these mini proteins are capable of fixing themselves to the sensory neurons and ion channels of cells, to change their functions or block their production.

And that's precisely how the pharmaceutical industry could use these proteins: to produce new, more precise treatments with fewer side effects and to treat pains or illnesses such as diabetes, cancer or cardiovascular diseases.

Of course, because of the high production costs, the complexity of the manufacturing processes and the immune problems that they pose, peptide drugs are still rare on the market. In 2010, there were barely 60, and only five of them came from animals. But Gilles says that using biotechnologies "could change the situation." Especially when it seems worthwhile. Extracted from the saliva of a Mexican lizard called the Gila monster, Byetta is prescribed to treat type 2 diabetes and is among the pharmaceutical industry's best sellers, with sales of more than $1 billion.

Biologist pressing the head of a ""Yarara"" snake to extract its venom in Buenos Aires, Argentina â€" Photo : EMartin Zabala/Xinhua/ZUMA

The objective of Venomics was to advance the research on these animal toxins, and to sequence the peptides contained in the venoms of 201 different types of animals, then produce them individually. The aim was to build a library of samples that a pharmaceutical manufacturer could test.

Raw material

But first the researchers had to obtain the raw material for their studies: venoms and venom glands from a wide variety of animals, some of them exotic and not exactly docile. "Two expeditions in French Guiana, another in Mayotte and a final one in French Polynesia were dedicated to the gathering of insects, myriapoda, cone snails and terebridae mollusks," says Gilles' colleague Frédéric Ducancel, who personally dove in the Polynesian Makemo atoll, a lagoon surrounded by coral reefs, to collect samples. "The rest â€" snakes, scorpions, spiders, lizards, bees, centipedes, ants, sea anemones, stonefish and rays â€" were supplied by amateur breeders, and by Alphabiotoxine, a specialized company based in Belgium."

The team then began analyzing the material using highly complex techniques. From this 25,000-peptide bank, 4,000 were then synthesized through chemical methods, or even, says Renaud Vincentelli from the University of Aix-Marseille, "by using refolded expression processes that consisted of producing them through bacteria."

Finally, even though this wasn't the primary objective of Venomics, biologists managed to establish that about 30 of these mini-proteins resembled cellular sensors and could likely interest the pharmaceutical industry.

"We could imagine setting up a new European project dedicated to the scientific exploit of this data in order to understand, for instance, why individuals within the same species of cone snails present different venoms according to their level of development or the region they're in," Gilles explains. "It could also aim to enlarge the toxin bank in order to make it attractive to the pharmaceutical industry market."

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How Thailand's Lèse-Majesté Law Is Used To Stifle All Protest

Once meant to protect the royal family, the century-old law has become a tool for the military-led government in Bangkok to stamp out all dissent. A new report outlines the abuses.

Pro-Democracy protest at The Criminal Court in Bangkok, Thailand

Laura Valentina Cortés Sierra

"We need to reform the institution of the monarchy in Thailand. It is the root of the problem." Those words, from Thai student activist Juthatip Sirikan, are a clear expression of the growing youth-led movement that is challenging the legitimacy of the government and demanding deep political changes in the Southeast Asian nation. Yet those very same words could also send Sirikan to jail.

Thailand's Criminal Code 'Lèse-Majesté' Article 112 imposes jail terms for defaming, insulting, or threatening the monarchy, with sentences of three to 15 years. This law has been present in Thai politics since 1908, though applied sparingly, only when direct verbal or written attacks against members of the royal family.

But after the May 2014 military coup d'état, Thailand experienced the first wave of lèse-majesté arrests, prosecutions, and detentions of at least 127 individuals arrested in a much wider interpretation of the law.

The recent report 'Second Wave: The Return of Lèse-Majesté in Thailand', documents how the Thai government has "used and abused Article 112 of the Criminal Code to target pro-democracy activists and protesters in relation to their online political expression and participation in peaceful pro-democracy demonstrations."

Criticism of any 'royal project'

The investigation shows 124 individuals, including at least eight minors, have been charged with lèse-majesté between November 2020 and August 2021. Nineteen of them served jail time. The new wave of charges is cited as a response to the rising pro-democracy protests across Thailand over the past year.

Juthatip Sirikan explains that the law is now being applied in such a broad way that people are not allowed to question government budgets and expenditure if they have any relationship with the royal family, which stifles criticism of the most basic government decision-making since there are an estimated 5,000 ongoing "royal" projects. "Article 112 of lèse-majesté could be the key (factor) in Thailand's political problems" the young activist argues.

In 2020 the Move Forward opposition party questioned royal spending paid by government departments, including nearly 3 billion baht (89,874,174 USD) from the Defense Ministry and Thai police for royal security, and 7 billion baht budgeted for royal development projects, as well as 38 planes and helicopters for the monarchy. Previously, on June 16, 2018, it was revealed that Thailand's Crown Property Bureau transferred its entire portfolio to the new King Maha Vajiralongkorn.

photo of graffiti of 112 crossed out on sidewalk

Protestors In Bangkok Call For Political Prisoner Release

Peerapon Boonyakiat/SOPA Images via ZUMA Wire

Freedom of speech at stake

"Article 112 shuts down all freedom of speech in this country", says Sirikan. "Even the political parties fear to touch the subject, so it blocks most things. This country cannot move anywhere if we still have this law."

The student activist herself was charged with lèse-majesté in September 2020, after simply citing a list of public documents that refer to royal family expenditure. Sirikan comes from a family that has faced the consequences of decades of political repression. Her grandfather, Tiang Sirikhan was a journalist and politician who openly protested against Thailand's involvement in World War II. He was accused of being a Communist and abducted in 1952. According to Sirikhan's family, he was killed by the state.

The new report was conducted by The International Federation for Human Rights (FIDH), Thai Lawyer for Human Rights (TLHR), and Internet Law Reform Dialogue (iLaw). It accuses Thai authorities of an increasingly broad interpretation of Article 112, to the point of "absurdity," including charges against people for criticizing the government's COVID-19 vaccine management, wearing crop tops, insulting the previous monarch, or quoting a United Nations statement about Article 112.

Juthatip Sirikan speaks in front of democracy monument.

Shift to social media

While in the past the Article was only used against people who spoke about the royals, it's now being used as an alibi for more general political repression — which has also spurred more open campaigning to abolish it. Sirikan recounts recent cases of police charging people for spreading paint near the picture of the king during a protest, or even just for having a picture of the king as phone wallpaper.

The more than a century-old law is now largely playing out online, where much of today's protest takes place in Thailand. Sirikan says people are willing to go further on social media to expose information such as how the king intervenes in politics and the monarchy's accumulation of wealth, information the mainstream media rarely reports on them.

Not surprisingly, however, social media is heavily monitored and the military is involved in Intelligence operations and cyber attacks against human rights defenders and critics of any kind. In October 2020, Twitter took down 926 accounts, linked to the army and the government, which promoted themselves and attacked political opposition, and this June, Google removed two Maps with pictures, names, and addresses, of more than 400 people who were accused of insulting the Thai monarchy. "They are trying to control the internet as well," Sirikan says. "They are trying to censor every content that they find a threat".

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