This breath test can detect liver disease earlier
A company in England has made a test that picks out the compounds from breath that reveal if people have liver disease.
Every year, around two million people worldwide die of liver disease. While some people inherit the disease, it’s most commonly caused by hepatitis, obesity and alcoholism. These underlying conditions kill liver cells, causing scar tissue to form until eventually the liver cannot function properly. Since 1979, deaths due to liver disease have increased by 400 percent.
The sooner the disease is detected, the more effective treatment can be. But once symptoms appear, the liver is already damaged. Around 50 percent of cases are diagnosed only after the disease has reached the final stages, when treatment is largely ineffective.
To address this problem, Owlstone Medical, a biotech company in England, has developed a breath test that can detect liver disease earlier than conventional approaches. Human breath contains volatile organic compounds (VOCs) that change in the first stages of liver disease. Owlstone’s breath test can reliably collect, store and detect VOCs, while picking out the specific compounds that reveal liver disease.
“There’s a need to screen more broadly for people with early-stage liver disease,” says Owlstone’s CEO Billy Boyle. “Equally important is having a test that's non-invasive, cost effective and can be deployed in a primary care setting.”
The standard tool for detection is a biopsy. It is invasive and expensive, making it impractical to use for people who aren't yet symptomatic. Meanwhile, blood tests are less invasive, but they can be inaccurate and can’t discriminate between different stages of the disease.
In the past, breath tests have not been widely used because of the difficulties of reliably collecting and storing breath. But Owlstone’s technology could help change that.
The team is testing patients in the early stages of advanced liver disease, or cirrhosis, to identify and detect these biomarkers. In an initial study, Owlstone’s breathalyzer was able to pick out patients who had early cirrhosis with 83 percent sensitivity.
Boyle’s work is personally motivated. His wife died of colorectal cancer after she was diagnosed with a progressed form of the disease. “That was a big impetus for me to see if this technology could work in early detection,” he says. “As a company, Owlstone is interested in early detection across a range of diseases because we think that's a way to save lives and a way to save costs.”
How it works
In the past, breath tests have not been widely used because of the difficulties of reliably collecting and storing breath. But Owlstone’s technology could help change that.
Study participants breathe into a mouthpiece attached to a breath sampler developed by Owlstone. It has cartridges are designed and optimized to collect gases. The sampler specifically targets VOCs, extracting them from atmospheric gases in breath, to ensure that even low levels of these compounds are captured.
The sampler can store compounds stably before they are assessed through a method called mass spectrometry, in which compounds are converted into charged atoms, before electromagnetic fields filter and identify even the tiniest amounts of charged atoms according to their weight and charge.
The top four compounds in our breath
In an initial study, Owlstone captured VOCs in breath to see which ones could help them tell the difference between people with and without liver disease. They tested the breath of 46 patients with liver disease - most of them in the earlier stages of cirrhosis - and 42 healthy people. Using this data, they were able to create a diagnostic model. Individually, compounds like 2-Pentanone and limonene performed well as markers for liver disease. Owlstone achieved even better performance by examining the levels of the top four compounds together, distinguishing between liver disease cases and controls with 95 percent accuracy.
“It was a good proof of principle since it looks like there are breath biomarkers that can discriminate between diseases,” Boyle says. “That was a bit of a stepping stone for us to say, taking those identified, let’s try and dose with specific concentrations of probes. It's part of building the evidence and steering the clinical trials to get to liver disease sensitivity.”
Sabine Szunerits, a professor of chemistry in Institute of Electronics at the University of Lille, sees the potential of Owlstone’s technology.
“Breath analysis is showing real promise as a clinical diagnostic tool,” says Szunerits, who has no ties with the company. “Owlstone Medical’s technology is extremely effective in collecting small volatile organic biomarkers in the breath. In combination with pattern recognition it can give an answer on liver disease severity. I see it as a very promising way to give patients novel chances to be cured.”
Improving the breath sampling process
Challenges remain. With more than one thousand VOCs found in the breath, it can be difficult to identify markers for liver disease that are consistent across many patients.
Julian Gardner is a professor of electrical engineering at Warwick University who researches electronic sensing devices. “Everyone’s breath has different levels of VOCs and different ones according to gender, diet, age etc,” Gardner says. “It is indeed very challenging to selectively detect the biomarkers in the breath for liver disease.”
So Owlstone is putting chemicals in the body that they know interact differently with patients with liver disease, and then using the breath sampler to measure these specific VOCs. The chemicals they administer are called Exogenous Volatile Organic Compound) probes, or EVOCs.
Most recently, they used limonene as an EVOC probe, testing 29 patients with early cirrhosis and 29 controls. They gave the limonene to subjects at specific doses to measure how its concentrations change in breath. The aim was to try and see what was happening in their livers.
“They are proposing to use drugs to enhance the signal as they are concerned about the sensitivity and selectivity of their method,” Gardner says. “The approach of EVOC probes is probably necessary as you can then eliminate the person-to-person variation that will be considerable in the soup of VOCs in our breath.”
Through these probes, Owlstone could identify patients with liver disease with 83 percent sensitivity. By targeting what they knew was a disease mechanism, they were able to amplify the signal. The company is starting a larger clinical trial, and the plan is to eventually use a panel of EVOC probes to make sure they can see diverging VOCs more clearly.
“I think the approach of using probes to amplify the VOC signal will ultimately increase the specificity of any VOC breath tests, and improve their practical usability,” says Roger Yazbek, who leads the South Australian Breath Analysis Research (SABAR) laboratory in Flinders University. “Whilst the findings are interesting, it still is only a small cohort of patients in one location.”
The future of breath diagnosis
Owlstone wants to partner with pharmaceutical companies looking to learn if their drugs have an effect on liver disease. They’ve also developed a microchip, a miniaturized version of mass spectrometry instruments, that can be used with the breathalyzer. It is less sensitive but will enable faster detection.
Boyle says the company's mission is for their tests to save 100,000 lives. "There are lots of risks and lots of challenges. I think there's an opportunity to really establish breath as a new diagnostic class.”
The limits of digital privacy are becoming clearer in the post-Dobbs era, as a wide range of data sources can reveal online and offline activities, including whether a woman seeks an abortion.
Since the recent reversal of Roe v. Wade — the landmark decision establishing a constitutional right to abortion — the vulnerabilities of reproductive health data and various other information stored on digital devices or shared through the Web have risen to the forefront.
Menstrual period tracking apps are an example of how technologies that collect information from users could be weaponized against abortions seekers. The apps, which help tens of millions of users in the U.S. predict when they’re ovulating, may provide evidence that leads to criminal prosecution in states with abortion bans, says Anton T. Dahbura, executive director of the Johns Hopkins University Information Security Institute. In states where abortion is outlawed, “it’s probably best to not use a period tracker,” he says.
Following the Dobbs v. Jackson ruling in late June that overturned Roe, even women who suffered a miscarriage could be suspected of having an abortion in some cases. While using these apps in anonymous mode may appear more secure, “data is notoriously difficult to perfectly anonymize,” Dahbura says. “Whether the data are stored on the user’s device or in the cloud, there are ways to connect that data to the user.”
Completely concealing one’s tracks in cyberspace poses enormous challenges. Digital forensics can take advantage of technology such as GPS apps, security cameras, license plate trackers, credit card transactions and bank records to reconstruct a person’s activities,” Dahbura says. “Abortion service providers are also in a world of risk for similar reasons.”
Practicing “good cyber hygiene” is essential. That’s particularly true in states where private citizens may be rewarded for reporting on women they suspect of having an abortion, such as Texas, which passed a so-called bounty hunter law last fall. To help guard against hacking, Dahbura suggests using strong passwords and two-factor authentication when possible while remaining on alert for phishing scams on email or texts.
Another option for safeguarding privacy is to avoid such apps entirely, but that choice will depend on an individual’s analysis of the risks and benefits, says Leah Fowler, research assistant professor at the University of Houston Law Center, Health Law & Policy Institute.
“These apps are popular because people find them helpful and convenient, so I hesitate to tell anyone to get rid of something they like without more concrete evidence of its nefarious uses,” she says. “I also hate the idea that asking anyone capable of becoming pregnant to opt out of all or part of the digital economy could ever be a viable solution. That’s an enormous policy failure. We have to do better than that.”
The potential universe of abortion-relevant data can include information from a variety of fitness and other biometric trackers, text and social media chat records, call details, purchase histories and medical insurance records.
Instead, Fowler recommends that concerned consumers read the terms of service and privacy policies of the apps they’re using. If some of the terms are unclear, she suggests emailing customer service with questions until the answers are satisfactory. It’s also wise for consumers to research products that meet their specific needs and find out whether other women have raised concerns about specific apps. Users interested in more privacy may want to switch to an app that stores data locally, meaning the data stays on your device, or does not use third-party tracking, so the app-maker is the only company with access to it, she says.
Period tracking apps can be useful for those on fertility journeys, making it easier to store information digitally than on paper charts. But users may want to factor in whether they live in a state with an anti-abortion stance and run the risk of legal issues due to a potential data breach, says Carmel Shachar, executive director of the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School.
Consumers’ risks extend beyond period tracking apps in the post-Roe v. Wade era. “Anything that creates digital breadcrumbs to your reproductive choices and conduct could raise concerns — for example, googling ‘abortion providers near me’ or texting your best friend that you are pregnant but do not want to be,” Shachar says. Women also could incriminate themselves by bringing their phones, which may record geolocation data, to the clinic with them.
The potential universe of abortion-relevant data can include information from a variety of fitness and other biometric trackers, text and social media chat records, call details, purchase histories and medical insurance records, says Rebecca Wexler, faculty co-director of the Berkeley Center for Law & Technology. “These data sources can reveal a pregnant person’s decision to seek or obtain an abortion, as well as reveal a healthcare provider’s provision of abortion services and anyone else’s provision of abortion assistance,” she says.
In some situations, people or companies could inadvertently expose themselves to risk after posting on social media with offers of places for abortion seekers to stay after traveling from states with bans. They could be liable for aiding and abetting abortion. At this point, it’s unclear whether states that ban abortion will try to prosecute residents who seek abortions in other states without bans.
Another possibility is that a woman seeking an abortion will be prosecuted based not only on her phone’s data, but also on the data that law enforcement finds on someone else’s device or a shared computer. As a result, “people in one household may find themselves at odds with each other,” says K Royal, faculty fellow at the Center for Law, Science, and Innovation at Arizona State University’s Sandra Day O'Connor College of Law. “This is a very delicate situation.”
Individuals and corporate executives should research their options before leaving a digital footprint. “Guard your privacy carefully, whether you are seeking help or you are seeking to help someone,” Royal says. While she has come across recommendations from other experts who suggest carrying a second phone that is harder to link a person’s identity for certain online activities, “it’s not practical on a general basis.”
The privacy of this health data isn’t fully protected by the law because period trackers, texting services and other apps are not healthcare providers — and as a result, there’s no prohibition on sharing the information with a third party under the Health Insurance Portability and Accountability Act of 1996, says Florencia Marotta-Wurgler, a professor who specializes in online consumer contracts and data privacy at the NYU School of Law.
“So, as long as there is valid consent, then it’s fair game unless you say that it violates the reasonable expectations of consumers,” she says. “But this is pretty unchartered territory at the moment.”
As states implement laws granting anyone the power to report suspected or known pregnancies to law enforcement, anti-choice activists are purchasing reproductive health data from companies that make period apps, says Rebecca Herold, chief executive officer of Privacy & Security Brainiacs in Des Moines, Iowa, and a member of the Emerging Trends Working Group at ISACA, an association focused on information technology governance. They could also buy data on search histories and make it available in places like Texas for “bounty hunters” to find out which women have searched for information about abortions.
Some groups are creating their own apps described as providing general medical information on subjects such as pregnancy health. But they are “ultimately intended to ‘catch’ women” — to identify those who are probably pregnant and dissuade them from having an abortion, to launch harassment campaigns against them, or to report them to law enforcement, anti-choice groups and others in states where such prenatal medical care procedures are now restricted or prohibited, Herold says.
In addition to privacy concerns, the reversal of Roe v. Wade raises censorship issues. Facebook and Instagram have started to remove or flag content, particularly as it relates to providing the abortion pill, says Michael Kleinman, director of the Silicon Valley Initiative at Amnesty International USA, a global organization that promotes human rights.
Facebook and Instagram have rules that forbid private citizens from buying, selling or giving away pharmaceuticals, including the abortion pill, according to a social media post by a communications director for Meta, which owns both platforms. In the same post, though, the Meta official noted that the company’s enforcement of this rule has been “incorrect” in some cases.
“It’s terrifying to think that arbitrary decisions by these platforms can dramatically limit the ability of people to access critical reproductive rights information,” Kleinman says. However, he adds, “as it currently stands, the platforms make unilateral decisions about what reproductive rights information they allow and what information they take down.”
Should We Use Technologies to Enhance Morality?
Should we welcome biomedical technologies that could enhance our ability to tell right from wrong and improve behaviors that are considered immoral such as dishonesty, prejudice and antisocial aggression?
Our moral ‘hardware’ evolved over 100,000 years ago while humans were still scratching the savannah. The perils we encountered back then were radically different from those that confront us now. To survive and flourish in the face of complex future challenges our archaic operating systems might need an upgrade – in non-traditional ways.
Morality refers to standards of right and wrong when it comes to our beliefs, behaviors, and intentions. Broadly, moral enhancement is the use of biomedical technology to improve moral functioning. This could include augmenting empathy, altruism, or moral reasoning, or curbing antisocial traits like outgroup bias and aggression.
The claims related to moral enhancement are grand and polarizing: it’s been both tendered as a solution to humanity’s existential crises and bluntly dismissed as an armchair hypothesis. So, does the concept have any purchase? The answer leans heavily on our definition and expectations.
One issue is that the debate is often carved up in dichotomies – is moral enhancement feasible or unfeasible? Permissible or impermissible? Fact or fiction? On it goes. While these gesture at imperatives, trading in absolutes blurs the realities at hand. A sensible approach must resist extremes and recognize that moral disrupters are already here.
We know that existing interventions, whether they occur unknowingly or on purpose, have the power to modify moral dispositions in ways both good and bad. For instance, neurotoxins can promote antisocial behavior. The ‘lead-crime hypothesis’ links childhood lead-exposure to impulsivity, antisocial aggression, and various other problems. Mercury has been associated with cognitive deficits, which might impair moral reasoning and judgement. It’s well documented that alcohol makes people more prone to violence.
So, what about positive drivers? Here’s where it gets more tangled.
Medicine has long treated psychiatric disorders with drugs like sedatives and antipsychotics. However, there’s short mention of morality in the Diagnostic and Statistical Manual of Mental Disorders (DSM) despite the moral merits of pharmacotherapy – these effects are implicit and indirect. Such cases are regarded as treatments rather than enhancements.
It would be dangerously myopic to assume that moral augmentation is somehow beyond reach.
Conventionally, an enhancement must go beyond what is ‘normal,’ species-typical, or medically necessary – this is known as the ‘treatment-enhancement distinction.’ But boundaries of health and disease are fluid, so whether we call a procedure ‘moral enhancement’ or ‘medical treatment’ is liable to change with shifts in social values, expert opinions, and clinical practices.
Human enhancements are already used for a range of purported benefits: caffeine, smart drugs, and other supplements to boost cognitive performance; cosmetic procedures for aesthetic reasons; and steroids and stimulants for physical advantage. More boldly, cyborgs like Moon Ribas and Neil Harbisson are pushing transpecies boundaries with new kinds of sensory perception. It would be dangerously myopic to assume that moral augmentation is somehow beyond reach.
How might it work?
One possibility for shaping moral temperaments is with neurostimulation devices. These use electrodes to deliver a low-intensity current that alters the electromagnetic activity of specific neural regions. For instance, transcranial Direct Current Stimulation (tDCS) can target parts of the brain involved in self-awareness, moral judgement, and emotional decision-making. It’s been shown to increase empathy and valued-based learning, and decrease aggression and risk-taking behavior. Many countries already use tDCS to treat pain and depression, but evidence for enhancement effects on healthy subjects is mixed.
Another suggestion is targeting neuromodulators like serotonin and dopamine. Serotonin is linked to prosocial attributes like trust, fairness, and cooperation, but low activity is thought to motivate desires for revenge and harming others. It’s not as simple as indiscriminately boosting brain chemicals though. While serotonin is amenable to SSRIs, precise levels are difficult to measure and track, and there’s no scientific consensus on the “optimum” amount or on whether such a value even exists. Fluctuations due to lifestyle factors such as diet, stress, and exercise add further complexity. Currently, more research is needed on the significance of neuromodulators and their network dynamics across the moral landscape.
There are a range of other prospects. The ‘love drugs’ oxytocin and MDMA mediate pair bonding, cooperation, and social attachment, although some studies suggest that people with high levels of oxytocin are more aggressive toward outsiders. Lithium is a mood stabilizer that has been shown to reduce aggression in prison populations; beta-blockers like propranolol and the supplement omega-3 have similar effects. Increasingly, brain-computer interfaces augur a world of brave possibilities. Such appeals are not without limitations, but they indicate some ways that external tools can positively nudge our moral sentiments.
Who needs morally enhancing?
A common worry is that enhancement technologies could be weaponized for social control by authoritarian regimes, or used like the oppressive eugenics of the early 20th century. Fortunately, the realities are far more mundane and such dystopian visions are fantastical. So, what are some actual possibilities?
Some researchers suggest that neurotechnologies could help to reactivate brain regions of those suffering from moral pathologies, including healthy people with psychopathic traits (like a lack of empathy). Another proposal is using such technology on young people with conduct problems to prevent serious disorders in adulthood.
Most of us aren’t always as ethical as we would like – given the option of ‘priming’ yourself to act in consistent accord with your higher values, would you take it?
A question is whether these kinds of interventions should be compulsory for dangerous criminals. On the other hand, a voluntary treatment for inmates wouldn’t be so different from existing incentive schemes. For instance, some U.S. jurisdictions already offer drug treatment programs in exchange for early release or instead of prison time. Then there’s the difficult question of how we should treat non-criminal but potentially harmful ‘successful’ psychopaths.
Others argue that if virtues have a genetic component, there is no technological reason why present practices of embryo screening for genetic diseases couldn’t also be used for selecting socially beneficial traits.
Perhaps the most immediate scenario is a kind of voluntary moral therapy, which would use biomedicine to facilitate ideal brain-states to augment traditional psychotherapy. Most of us aren’t always as ethical as we would like – given the option of ‘priming’ yourself to act in consistent accord with your higher values, would you take it? Approaches like neurofeedback and psychedelic-assisted therapy could prove helpful.
What are the challenges?
A general challenge is that of setting. Morality is context dependent; what’s good in one environment may be bad in another and vice versa, so we don’t want to throw out the baby with the bathwater. Of course, common sense tells us that some tendencies are more socially desirable than others: fairness, altruism, and openness are clearly preferred over aggression, dishonesty, and prejudice.
One argument is that remoulding ‘brute impulses’ via biology would not count as moral enhancement. This view claims that for an action to truly count as moral it must involve cognition – reasoning, deliberation, judgement – as a necessary part of moral behavior. Critics argue that we should be concerned more with ends rather than means, so ultimately it’s outcomes that matter most.
Another worry is that modifying one biological aspect will have adverse knock-on effects for other valuable traits. Certainly, we must be careful about the network impacts of any intervention. But all stimuli have distributed effects on the body, so it’s really a matter of weighing up the cost/benefit trade-offs as in any standard medical decision.
Is it ethical?
Our values form a big part of who we are – some bioethicists argue that altering morality would pose a threat to character and personal identity. Another claim is that moral enhancement would compromise autonomy by limiting a person’s range of choices and curbing their ‘freedom to fall.’ Any intervention must consider the potential impacts on selfhood and personal liberty, in addition to the wider social implications.
This includes the importance of social and genetic diversity, which is closely tied to considerations of fairness, equality, and opportunity. The history of psychiatry is rife with examples of systematic oppression, like ‘drapetomania’ – the spurious mental illness that was thought to cause African slaves’ desire to flee captivity. Advocates for using moral enhancement technologies to help kids with conduct problems should be mindful that they disproportionately come from low-income communities. We must ensure that any habilitative practice doesn’t perpetuate harmful prejudices by unfairly targeting marginalized people.
Human capacities are the result of environmental influences, and external conditions still coax our biology in unknown ways. Status quo bias for ‘letting nature take its course’ may actually be worse long term – failing to utilize technology for human development may do more harm than good.
Then, there are concerns that morally-enhanced persons would be vulnerable to predation by those who deliberately avoid moral therapies. This relates to what’s been dubbed the ‘bootstrapping problem’: would-be moral enhancement candidates are the types of individuals that benefit from not being morally enhanced. Imagine if every senator was asked to undergo an honesty-boosting procedure prior to entering public office – would they go willingly? Then again, perhaps a technological truth-serum wouldn’t be such a bad requisite for those in positions of stern social consequence.
Advocates argue that biomedical moral betterment would simply offer another means of pursuing the same goals as fixed social mechanisms like religion, education, and community, and non-invasive therapies like cognitive-behavior therapy and meditation. It’s even possible that technological efforts would be more effective. After all, human capacities are the result of environmental influences, and external conditions still coax our biology in unknown ways. Status quo bias for ‘letting nature take its course’ may actually be worse long term – failing to utilize technology for human development may do more harm than good. If we can safely improve ourselves in direct and deliberate ways then there’s no morally significant difference whether this happens via conventional methods or new technology.
Future prospects
Where speculation about human enhancement has led to hype and technophilia, many bioethicists urge restraint. We can be grounded in current science while anticipating feasible medium-term prospects. It’s unlikely moral enhancement heralds any metamorphic post-human utopia (or dystopia), but that doesn’t mean dismissing its transformative potential. In one sense, we should be wary of transhumanist fervour about the salvatory promise of new technology. By the same token we must resist technofear and alarmist efforts to balk social and scientific progress. Emerging methods will continue to shape morality in subtle and not-so-subtle ways – the critical steps are spotting and scaffolding these with robust ethical discussion, public engagement, and reasonable policy options. Steering a bright and judicious course requires that we pilot the possibilities of morally-disruptive technologies.