Science

Could ‘alcosynth’ provide all the joy of booze – without the dangers?


‘This is what my brain looks like,” says David Nutt, showing me an intense abstract painting by a friend of his that is sitting on the windowsill in his office. Nutt’s base at Hammersmith hospital has a cosy, lived-in feel – a stark contrast to the gleaming white laboratory he oversees as director of the neuropsychopharmacology unit at Imperial College London. Lab coats hang on a hook by the door, an ancient kettle sits in the corner and next to the painting is an unruly collection of objects that offer clues to his research interests: brain-shaped awards, an atomic model of Nutt’s invention for detecting inflammation in the brain of Alzheimer’s and Parkinson’s patients, a poster for the 1967 film LSD Flesh of Devil and two carved wooden mushrooms – the final items hinting at his role at Imperial’s psychedelic research group.

All that is missing is something to do with the demon drink, to reflect Nutt’s ambitious plan to bring a safe synthetic alcohol substitute called Alcarelle to the masses. Nutt has long been developing a holy grail of molecules – also referred to as “alcosynth” – that will provide the relaxing and socially lubricating qualities of alcohol, but without the hangovers, health issues and the risk of getting paralytic. It sounds too good to be true, and when I discuss the notion with two alcohol industry experts, they independently draw parallels with plans to colonise Mars.

Yet Alcarelle finding its way into bars and shops is starting to look like a possibility. Seed funding was raised in November 2018, allowing Nutt and his business partner, David Orren, to attempt to raise £20m from investors to bring Alcarelle to market. “The industry knows alcohol is a toxic substance,” says Nutt. “If it were discovered today, it would be illegal as a foodstuff. The safe limit of alcohol, if you apply food standards criteria, would be one glass of wine a year.”

As a psychiatrist, he says, “most of my professional life I’ve been treating people for whom alcohol is a problem, and a lot of my professional research relates to that”. A decade ago, Nutt was sacked from his position as a government drugs adviser after questioning the skewed moral standards by which we judge drug and alcohol use (he memorably said that horse riding was more dangerous than taking ecstasy). Shortly after this, he presented data in the Lancet showing that booze is more harmful to society than heroin or crack. Yet Nutt is no prohibitionist. He enjoys a “very small” single malt before bed, and even co-owns a bar, the irony of which causes him to erupt into one of his frequent and endearing guffaws. “My daughter and I own a wine bar in Ealing,” he says, after he has recovered his composure. “I’m not against alcohol. I like it, but it would be nice to have an alternative.” One day, he hopes to add Alcarelle to the menu at his bar.

Nutt with his business partner David Orren … trying to bring Alcarelle to market.



Nutt with his business partner David Orren … trying to bring Alcarelle to market. Photograph: Alicia Canter/The Guardian

The long road to Alcarelle began in 1983 when Nutt was a PhD student and discovered an alcohol antidote. Yes, a drug that actually reverses drunkenness. “I was studying the effects of alcohol on the Gaba system,” he says. Put very simply, alcohol’s primary brain effect is stimulating the Gaba receptor. When they are stimulated Gaba receptors calm the brain, by firing off fewer neurons. His study was, says Nutt, the first proof of this. Nutt gave rats alcohol, administered a chemical that blocks Gaba receptors and the rats sobered up.

The antidote was too dangerous to be of any clinical use because if you accidentally took it when sober, it would cause seizures (like severe alcohol withdrawal does). Besides, as he says, “what’s the point of stopping someone being intoxicated when the alcohol is destroying their liver and their brains?” Crucially, however, Nutt now knew that stimulating Gaba was the route to tipsy bliss – if only we could do so harmlessly.

Twenty years later, while working on a government report on the future of brain science, addiction and drugs, it dawned on Nutt that scientific understanding had reached a point at which this could, in theory, be achieved. “I wrote a little thought piece in the Journal of Psychopharmacology,” he recalls. “People said it was ‘too challenging, too crazy’. It was 2005, and the concept of disruptive technology didn’t exist. They said: ‘It’s clever but you’ll never do it,’ but I kept talking about it because it was clever and we can do it.”

What Nutt now knows is that there are 15 different Gaba receptor subtypes in multiple brain regions, “and alcohol is very promiscuous. It will bind to them all.” Without giving away his trade secrets, he says he has found which Gaba and other receptors can be stimulated to induce tipsiness without adverse effects. “We know where in the brain alcohol has its ‘good’ effects and ‘bad’ effects, and what particular receptors mediate that – Gaba, glutamate and other ones, such as serotonin and dopamine. The effects of alcohol are complicated but … you can target the parts of the brain you want to target.”

Handily, you can modify the way in which a molecule binds to a receptor to produce different effects. You can design a peak effect into it, so no matter how much Alcarelle you consume, you won’t get hammered. This is well-established science; in fact Nutt says a number of medicines, such as the smoking cessation drug varenicline (marketed as Champix), use a similar shut-off effect. You can create other effects, too, while still avoiding inebriation, so you could choose between a party drink or a business-lunch beverage.

Coming up with the concept was the easy bit, says Nutt. Finding the right molecule was more challenging, “but the real challenge is taking that molecule to a drink. The regulatory side is much harder than the science.” Because Alcarelle has not undergone safety testing yet, only Nutt, Orren and a few others at the lab have tried it, mixed with fruit juice because it doesn’t taste nice by itself. “We’re allowed to try it whenever we want,” says Nutt. “We tested a lot of possible compounds, to try to find which are most likely to work. It would be dishonest to spend millions of pounds on something when you haven’t a clue if it does what you want.”

Nutt, Orren (a business adviser and former tech entrepreneur) and their team have come up with a five-year plan. Alcarelle will probably be regulated as a food additive or an ingredient, so food regulations rather than clinical trials apply. To get approval, they need to create a drink product complete with its own bottle, and they are working with food scientists on that. This process usually takes about three years, but, because of Alcarelle’s unique functional qualities, they expect it to take longer.

“There will obviously be testing to check the molecule is safe,” says Nutt. “And we need to show that it’s different from alcohol. We will demonstrate that it doesn’t produce toxicity like alcohol does.” For example, when our liver metabolises alcohol, it produces the carcinogen acetaldehyde, and consistently drinking too much can increase the risk of mouth, throat and breast cancers as well as strokes, heart disease and liver, brain and nervous-system damage. “And of course we don’t want hangovers. We have to show it doesn’t have the bad effects of alcohol,” says Nutt.

Ultimately, the aim isn’t for Alcarelle to become a drinks company, but to supply companies in the drinks industry with the active ingredient, so that they can make and market their own products. You would expect that the alcohol industry would view Alcarelle as its nemesis, but Orren says that industry players “are approaching us as potential investing collaborators”. This doesn’t surprise Jonny Forsyth, a global drinks analyst at Mintel. “The industry is increasingly investing in alcohol alternatives,” he says. “We have seen a lot of investment in cannabis … They’re looking at nonalcoholic gins and soft drinks because they know people are drinking less [alcohol], and this is a trend that is going to carry on. If the science is right, and if it’s easy to mask the taste, I think it’s got a great chance.”

Gerard Hastings of the Institute for Social Marketing at the University of Stirling has advised the House of Commons health select committee during its investigations into the alcohol, tobacco and pharmaceutical industries. He believes that the alcohol industry would embrace Alcarelle just as Coca-Cola has embraced the zero-calorie sweetener stevia, and the tobacco industry has invested in vaping, “to own the solution as well as the problem … If they can continue to sell products to the health-conscious and the less health-conscious, then they will do so.” Similarly, lab-grown meat (meat cells cultured without the need to rear and kill animals) has seen heavy investment by global meat suppliers.

Forsyth sees the fact that you can never get drunk on Alcarelle as an enticing marketing angle for younger consumers, who, he says, are driving the downward trend in alcohol sales. For them, he says, “it’s much cooler to be healthy, but it’s also about control. They don’t want to end up on Instagram looking drunk; their manager might see that. Something that would automatically control their drinking would be very appealing.”

One potential stumbling block may be that Alcarelle isn’t natural. “Natural things aren’t always healthy,” says Forsyth, “but in the mind of the consumer, ‘natural’ and ‘healthy’ are pretty much the same concept. One of the reasons cannabis is doing so well is because it’s a plant.” However, he sees the joys of alcohol without the hangover as “a pretty powerful reason to partake of it even if it’s not natural”. One way to address the problem would be to flavour the drink with natural botanicals, but Nutt and Orren are keen to go further. “We have a project to see if we can find these molecules in nature,” says Orren.

Alcohol, meanwhile, is natural and has been with us for ever. It is seen as God-given – after all, Jesus turned water into wine – and is so deeply woven into the fabric of our society that, at least for older generations, on some occasions there can be no substitute. Alcarelle isn’t aiming to replicate fine wines or Nutt’s single malt. “We think, once we’re approved and on the market,” says Orren, “we are going to see an amazing and wonderful explosion of creativity. The drinks industry employs really creative people.” He notes the celebrity-chef status of mixologists, “because people are really interested in the formation of tastes and flavours”.

Of course, tipsiness is perhaps the greatest flavour enhancer. “There’s a very important interaction between taste, flavour, smell and the effect,” says Nutt. “People say: ‘I just love the taste of my 1984 Chateau Latour,’ and I say to them: ‘The truth is you wouldn’t if you had never got drunk on it. If you gave that to your child, they would spit it out. You acquire the love of the taste. What gives you the love of the taste is the effect of the alcohol and, of course, the knowledge that it’s really expensive.’” But whatever flavour/effect ratio drives our alcohol appreciation, we have chosen, he says, “to ignore the harms of alcohol because we enjoy it. What I’m trying to do is provide something to enjoy that is much less harmful. That’s the ambition.”



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