Can brain tweaking make us perfect humans?

New research suggests that neural engineering could extinguish some of our basest tendencies. David Cox talks to the specialists

Ohio State University professor Krystof Bankiewicz never imagined that he’d find himself working with alcoholic monkeys. Yet, through his research into the progressive neurodegenerative disease, the expert in Parkinson’s disease began to realise that – through these monkeys – he might have a unique window into the brain pathways of addiction and ways of reshaping them for the better.

“I strongly believe that we have to view all brain disorders, such as addictions, through the lens of different wiring,” he says. “The brain is incredible at organising connections, but certain individuals are more predisposed to being wired in certain ways.”

Both Parkinson’s and addictions are intrinsically linked to a substance called dopamine, often known as the pleasure chemical. Activities such as sex, drinking, taking illicit drugs, winning £10 on a slot machine or watching pornography all flood the brain with surges of dopamine, creating a desire to repeat the experience.

Some people are particularly susceptible to swiftly becoming dependent on these dopamine surges, which can subsequently develop into an addiction. When these behaviours turn into chronic habits, the brain starts to produce less and less dopamine each time, which is why addicts often explain that their drinking or drug use does not actually provide them with any pleasure.

Parkinson’s, a disease which gradually kills off dopamineproducing cells in the brain, is very different, but many of the latest therapeutic approaches utilise ingenious ideas for replacing the lost dopamine. One particular therapy being studied involves delivering the gene for a protein called glial-derived neurotrophic factor (GDNF) into the brain, which then encourages dopamine production.

Professor Bankiewicz began to wonder whether delivering GDNF to brain areas associated with addiction and reward through gene therapy, could help reset the dysfunctional pathways seen in alcoholics back to normal. To prove it, he took macaque monkeys, who share the same human weakness for alcohol, and plied them with a monkey-friendly solution which was similar in strength to beer. Four alcoholic macaques were then given the GDNF therapy, with swift results.

“It was responsible for a complete cessation of alcohol interest in these animals,” says Professor Bankiewicz. “They were also no longer interested in sugary drinks or even eating excessively, while the monkeys who didn’t receive the therapy kept drinking more and more.”

The study, which was published in the journal Nature Medicine earlier this week, has created the hope that it could one day represent a solution to alcohol use disorder, which remains a major social problem around the world. Alcohol misuse remains the biggest risk factor for death, disability and ill health among those aged between 15 and 49 in the UK and was associated with 20,970 deaths among all age groups in 2021.

Professor Bankiewicz suggests it could also be used as a solution to other severe addictions, for example opioid addiction. “Alcohol addiction is a huge social issue as 90 per cent of sufferers currently relapse and some of them are incredibly severe cases,” he says. “I think this is perhaps where gene therapy could be justified.”

Re-engineering the brain to try to alter human behaviour has begun to emerge as a new frontier in medicine, particularly given the limitations of traditional psychotherapies as addiction treatments. While cognitive behavioural therapy is currently considered the gold standard for the treatment of alcohol use disorder, more than 60 per cent of patients relapse within the first year.

One of the reasons for this is that, while destabilising life events such as trauma can contribute to the onset of addictions, research has increasingly shown that they also have a genetic origin. Various genes active in the brain can create innate urges which are difficult to resist, once vulnerable people are exposed to vices such as gambling, nicotine or other addictive substances. “Our genes influence our dispositions, which influence our natural tendencies, which make some people more likely to experience problems,” says Danielle Dick, a psychiatry professor at Rutgers University in New Jersey and author of the book The Child Code.

A recent study co-authored by Professor Dick, using data from around 1.5 million people, found that those with gene variants linked to impulsivity tended to be more likely to participate in smoking and substancetaking in adolescence and adulthood before later developing related conditions such as obesity and lung cancer.

Research has increasingly shown that mutations in certain genes can increase our propensity to overeat or make us more likely to become addicted to sugar and ultra-processed foods. One such gene is the melanocortin 4 receptor (MC4R) which forms part of the brain circuitry that senses how much fat we’re carrying. Around 0.3 per cent of the

UK population carry mutations in MC4R which cause their brains to subconsciously conclude that they’re carrying less fat than they really are, driving them to overeat. By the age of 18, people with these mutations have been estimated to be already 18kg heavier than those without.

The highly successful semaglutidebased obesity drugs, such as Ozempic and Wegovy, attempt to counteract the effects of such mutations by injecting a synthetic version of the hormone GLP-1, which acts on the brain to create a feeling of fullness.

But there may be other ways of targeting the brain to suppress excessive appetite, or similar cravings. Scientists at King’s College London and the University of Tübingen in

Germany are currently investigating whether applying low-level electrical stimulation to a brain region involved in response inhibition, can help treat a binge-eating disorder, a form of food addiction where sufferers feel continually compelled to eat to excess.

There are many different types of non-invasive brain stimulation, a field which is rapidly emerging as a newer, relatively safe way of trying to influence brain networks, without the side effects which typically come with pharmacological drugs. One form, known as transcranial magnetic stimulation (TMS), is now being touted as a potentially novel way of helping people to cease smoking.

In a new study published in the journal Nature Communications, neuroscientist Professor Barbara Sahakian and colleagues at the University of Cambridge took brain scans of 800 people at three timepoints – 14, 19 and 24 – and analysed the impact of smoking. The scans revealed that over time, smoking appears to shrink a region of the frontal lobe, known as the left ventromedial prefrontal cortex which is involved in willpower and feelings of pleasure. Professor Sahakian’s idea is that TMS may help to give chronic smokers better control over their addiction, making it feel easier for them to quit.

“In smoking, this area of the brain gets reduced, so then behaviour becomes disinhibited and that may be why smoking cigarettes can often lead on to marijuana and alcohol use,” says Professor Sahakian. The hope might be that this reduction can be mitigated by transcranial stimulation, and thereby you could re-establish inhibitory control.”

One of the biggest aims for TMS is to try and tackle one of the world’s deadliest substance addictions – cocaine use disorder. Cocaine addiction is particularly powerful with one in five people who experiment with the drug, becoming dependent on it at some point in their life. Psychological treatments for the addiction are limited in their effectiveness and US research ranked it as one of the leading killers among all illicit drugs between 2010 and 2016.

The idea of TMS is to try and adjust the brain’s reward, motivation and decision-making circuits in a way which reduces the overwhelming cravings which leave many addicts helpless. So far studies have been small and delivered modest results, which has led other researchers to pursue more radical solutions. At the Mayo Clinic in Rochester, Minnesota, a groundbreaking clinical trial is currently underway, which represents one of the first times that a gene therapy has been studied for addiction in humans.

Unlike Professor Bankiewicz’s proposed gene therapy for alcohol use disorder, this treatment does not impact dopamine. Instead, it delivers an enzyme that protects the brain by inactivating cocaine 1,400 times faster than normal.

“The chemical reaction is extremely rapid and so when an individual consumes the drug, the brain receives a significantly smaller quantity because it is metabolised so quickly,” says W Michael Hooten, a Mayo Clinic anaesthesiologist who is leading the trial. “So it blunts the reward of the cocaine.”

At the same time, the therapy also lowers the levels of a hormone called ghrelin which drives cocaine cravings, thus making brain receptors involved in controlling impulses more sensitive again. When the therapy was previously studied in mice, they were found to swiftly display no further desire for the drug.

This all represents ways in which we can increasingly adjust the chemicals, hormones and even networks in the brain which influence our behaviour, perhaps for the better. Criminologists around the world have even begun researching how forms of non-invasive brain stimulation could be used in the rehabilitation of violent offenders in years to come.

Last year a paper published in the journal Current Psychology by researchers at the University of Messina, Italy, revealed growing evidence to suggest that applying low-level electrical activity to areas of the prefrontal cortex, which is involved in social skills, could help limit aggression and impulsivity and promote empathy.

While this research is still at a very early stage, the scientists suggested that it could help with the reintegration of criminals into society, particularly those diagnosed with antisocial personality disorders.

But at the same time, there are some serious ethical questions which relate to this brave new world of brain modulation. If impulsive individuals know that their behaviour could simply be cured or tamed whenever they want by undergoing therapy, could it make them even more impulsive? Prof Bankiewicz admits that this is one of the many unknowns.

“If I were to look at the crystal ball here – I believe that these therapies will drive a permanent change in those who have incurable addictions,” he says. “But would that predispose them to be more reckless, knowing that there is something available? It’s a good question, and I don’t know the answer. Perhaps in some people, maybe not in others.”

There is also the element of risk, particularly when it comes to gene therapy. The field has long been dogged by safety concerns, for example fears that it may induce cancer in the longer term, which have not entirely gone away. Prof Bankiewicz says that applying such a therapy comes down to weighing up the risks and benefits, and such therapies should only be considered for individuals with very severe addictions, for whom all other approaches have failed.

Prof Sahakian says that there are also the ethical issues involved when administering a therapy which changes someone’s behaviour and personality, perhaps permanently.

“I think there’s a number of ways that we’ll be changing the brain in future, and we have to think about who’s responsible for managing those changes when they’re made,” she says. “There’s now a discipline called neuroethics and it relates to all these questions – is it safe? Is it ethical? Are we changing even the personhood of the person because there’s questions about how these therapies might alter your perception of yourself.”

But at the same time, these therapies could have profound benefits for many of the most vulnerable individuals in society.

“People really do suffer from addiction,” says Professor Bankiewicz. “They just cannot control it. It’s a huge social issue. So I think if something like this could help bring those people back to work, to their families, and everything else that they’re missing now, it may be worth it.”

‘Dopamine therapy was responsible for a complete cessation of alcohol interest’