A New Stem Cell Therapy Provides Hope to Patients with Blood Cancer
Stacey Khoury felt more fatigued and out of breath than she was used to from just walking up the steps to her job in retail jewelry sales in Nashville, Tennessee. By the time she got home, she was more exhausted than usual, too.
"I just thought I was working too hard and needed more exercise," recalls the native Nashvillian about those days in December 2010. "All of the usual excuses you make when you're not feeling 100%."
As a professional gemologist, being hospitalized during peak holiday sales season wasn't particularly convenient. There was no way around it though when her primary care physician advised Khoury to see a blood disorder oncologist because of her disturbing blood count numbers. As part of a routine medical exam, a complete blood count screens for a variety of diseases and conditions that affect blood cells, such as anemia, infection, inflammation, bleeding disorders and cancer.
"If approved, it will allow more patients to potentially receive a transplant than would have gotten one before."
While she was in the hospital, a bone marrow biopsy revealed that Khoury had acute myeloid leukemia, or AML, a high-risk blood cancer. After Khoury completed an intense first round of chemotherapy, her oncologist recommended a bone marrow transplant. The potentially curative treatment for blood-cancer patients requires them to first receive a high dose of chemotherapy. Next, an infusion of stem cells from a healthy donor's bone marrow helps form new blood cells to fight off the cancer long-term.
Each year, approximately 8,000 patients in the U.S. with AML and other blood cancers receive a bone marrow transplant from a donor, according to the Center for International Blood and Marrow Transplant Research. But Khoury wasn't so lucky. She ended up being among the estimated 40% of patients eligible for bone marrow transplants who don't receive one, usually because there's no matched donor available.
Khoury's oncologist told her about another option. She could enter a clinical trial for an investigational cell therapy called omidubicel, which is being developed by Israeli biotech company Gamida Cell. The company's cell therapy, which is still experimental, could up a new avenue of treatment for cancer patients who can't get a bone marrow transplant.
Omidubicel consists of stem cells from cord blood that have been expanded using Gamida's technology to ensure there are enough cells for a therapeutic dose. The company's technology allows the immature cord blood cells to multiply quickly in the lab. Like a bone marrow transplant, the goal of the therapy is to make sure the donor cells make their way to the bone marrow and begin producing healthy new cells — a process called engraftment.
"If approved, it will allow more patients to potentially receive a transplant than would have gotten one before, so there's something very novel and exciting about that," says Ronit Simantov, Gamida Cell's chief medical officer.
Khoury and her husband Rick packed up their car and headed to the closest trial site, the Duke University School of Medicine, roughly 500 miles away. There they met with Mitchell Horowitz, a stem cell transplant specialist at Duke and principal investigator for Gamida's omidubicel study in the U.S.
He told Khoury she was a perfect candidate for the trial, and she enrolled immediately. "When you have one of two decisions, and it's either do this or you're probably not going to be around, it was a pretty easy decision to make, and I am truly thankful for that," she says.
Khoury's treatment started at the end of March 2011, and she was home by July 4 that year. She say the therapy "worked the way the doctors wanted it to work." Khoury's blood counts were rising quicker than the people who had bone marrow matches, and she was discharged from Duke earlier than other patients were.
By expanding the number of cord blood cells — which are typically too few to treat an adult — omidubicel allows doctors to use cord blood for patients who require a transplant but don't have a donor match for bone marrow.
Patients receiving omidubicel first get a blood test to determine their human leukocyte antigen, or HLA, type. This protein is found on most cells in the body and is an important regulator of the immune system. HLA typing is used to match patients to bone marrow and cord blood donors, but cord blood doesn't require as close of a match.
Like bone marrow transplants, one potential complication of omidubicel is graft-versus-host disease, when the donated bone marrow or stem cells register the recipient's body as foreign and attack the body. Depending on the severity of the response, according to the Mayo Clinic, treatment includes medication to suppress the immune system, such as steroids. In clinical trials, the occurrence of graft-versus-host disease with omidubicel was comparable with traditional bone marrow transplants.
"Transplant doctors are working on improving that," Simantov says. "A number of new therapies that specifically address graft-versus-host disease will be making some headway in the coming months and years."
Gamida released the results of the Phase 3 study in February and continues to follow Khoury and the other study patients for their long-term outcomes. The large randomized trial evaluated the safety and efficacy of omidubicel compared to standard umbilical cord blood transplants in patients with blood cancer who didn't have a suitable bone marrow donor. Around 120 patients aged 12 to 65 across the U.S., Europe and Asia were included in the trial. The study found that omidubicel resulted in faster recovery, fewer bacterial and viral infections and fewer days in the hospital.
The company plans to seek FDA approval this year. Simantov anticipates the therapy will receive FDA approval by 2022.
"Opening up cord blood transplants is very important, especially for people of diverse ethnic backgrounds," says oncologist Gary Schiller, principal investigator at the David Geffen School of Medicine at UCLA for Gamida Cell's mid- and late-stage trials. "This expansion technology makes a big difference because it makes cord blood an available option for those who do not have another donor source."
As for Khoury, who proudly celebrated the anniversary of her first transplant in April—she remains cancer free and continues to work full-time as a gemologist. When she has a little free time, she enjoys gardening, sewing, or maybe traveling to national parks like Yellowstone or the Grand Canyon with her husband Rick.
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.
Podcast: The Friday Five - your health research roundup
The Friday Five is a new series in which Leaps.org covers five breakthroughs in research over the previous week that you may have missed.
The Friday Five is a new podcast series in which Leaps.org covers five breakthroughs in research over the previous week that you may have missed. There are plenty of controversies and ethical issues in science – and we get into many of them in our online magazine – but there’s also plenty to be excited about, and this news roundup is focused on inspiring scientific work to give you some momentum headed into the weekend.
Covered in this week's Friday Five:
- Puffer fish chemical for treating chronic pain
- Sleep study on the health benefits of waking up multiples times per night
- Best exercise regimens for reducing the risk of mortality aka living longer
- AI breakthrough in mapping protein structures with DeepMind
- Ultrasound stickers to see inside your body