Compassion Fatigue: an institutional issue
Michael McCabe
‘Most young doctors enter medicine with quite a profound desire to help other people. Somehow, across the first decade or so of training and work, that diminishes.
We call it compassion fatigue – the idea that doctors have a finite reservoir of caring that drains away over time, leaving some of them a cynical, couldn’t-give-a-damn husk of inhumanity.’
Nathan Consedine (North & South, September 2015, p.60)
The Greek word for compassion ‘splagchnizomai’ literally means ‘to be moved’ in ‘one’s bowels.’ Emotions were viewed as ‘residing’ in the bowels – literally ‘in the guts.’ Thus, a person without compassion was essentially unmoved by the plight of another and could be described as being ‘hard’, ‘heartless’, or ‘harsh’ with ‘no reach’ inside them.
Compassion fatigue is not limited to the healthcare professions. It is part and parcel of any professional role that involves advocacy for or care of others – it is potentially the Achilles’ Heel of all professions. Professional life is marked by the complex interplay between personal well-being, workload, role expectations, rapidly changing social and cultural norms, and by systemic issues, such as the strengths and particular shortcomings of the institutions in which the professions reside. Frequently the professional is caught in the crossfire of one or more of these dynamics with the result that his or her energy and passion for the profession and its goals dissipates. That feeling, described by many today, ‘of getting through the night’, is most notably marked by a reduced ‘reach’ of compassion, and, frequently, by cynicism.
Given its multi-dimensional nature and causation, compassion fatigue requires addressing on several levels – at a personal level, and at a communal or institutional level.
At a personal level compassion can only be sustained if the professional ‘tends to the soul.’ Being an advocate and caring for others drains the advocate and empties the caregiver. Whatever a person’s faith dimension or motivation, such roles demand ‘Sabbath’ time – times of refreshment and re-creation, times of rest and review in which we ‘listen again’ to our souls and nurture them in healthy and life-giving ways.
While bread-winners may well recognise this need for rest and recreation, such a ‘Sabbath’ break is not always possible given financial pressures on families and individuals and the demands of the profession. That is why the culture of the particular institution, be it healthcare, medicine, law, or religious faith, also requires refreshment and renewal if it is not to exacerbate or even be complicit in compassion fatigue amongst its personnel.
However, institutions themselves can demonstrate compassion fatigue, evident above all in the ways in which they respond to those who are most vulnerable, including the demands placed on personnel, the language used, and the prevailing attitudes and mind-sets of those vested with power. Nowhere is this insight being illustrated more profoundly than in the leadership and vision of Pope Francis.
In the recent Synod on the Family, Pope Francis gave a clear illustration of the need for the Church to return to the ‘compassionate reach’ of the gospel. In doing so he challenges those who would tie mercy and compassion to obedience to the law. For example, in his closing homily, commenting on the story of the healing of Bartimaeus, the blind beggar, he said,
“This can be a danger for us: in the face of constant problems, it is better to move on, instead of letting ourselves be bothered. In this way, just like the disciples, we are with Jesus but we do not think like him. We are in his group, but our hearts are not open. We lose wonder, gratitude and enthusiasm, and risk becoming habitually unmoved by grace. We are able to speak about him and work for him, but we live far from his heart, which is reaching out to those who are wounded. This is the temptation: a ‘spirituality of illusion’: we walk through the deserts of humanity without seeing what is really there…a faith that does not know how to root itself in the life of people remains arid and, rather than oases, creates other deserts.”
At the conclusion of the Synod Pope Francis then offered a number of antidotes to compassion fatigue, at both a personal and institutional level, including
- Attempting to see the ‘issues having to do with the family’ in the ‘light of the Gospel’ without ‘falling into a facile repetition of what was obvious or has already been said.’
- ‘Seeing difficulties and uncertainties which challenge and threaten the family in ‘the light of the Faith, carefully studying them and confronting them fearlessly, without burying our heads in the sand.’
- Portraying, once again, the vitality and vision of the Catholic Church, ‘which is not afraid to stir dulled consciences or to soil her hands with lively and frank discussions about the family.’
While Pope Francis was speaking specifically about the family, his wisdom and courage gives fresh heart to all caregivers and advocates of compassion and mercy and reminds us not to neglect the ways in which ‘compassion fatigue’ may permeate the very institutions within which we practice our respective professions.
Rev Dr Michael McCabe is the founding director of The Nathaniel Centre and Parish Priest of Our Lady of Kapiti Parish, Te Whaea o Kāpiti.
Carrying the Weight of Ourselves: Compassion and the Divine Art of Kindness
Bernard Leuthart
I am riding to plague again.
Sometimes under a sooty wash
From the grate in the burnt-out gable
I see the needy in a small pow-wow.
What do I say if they wheel out their dead?
I'm cauterised, a black stump of home.
Seamus Heaney
Not so long ago, I had 86 year-old Alf in to cut a lesion from his shoulder. Alf is my idea of gracious old age - deep respect and real joy burning in his blue eyes as he spends everyday in service of someone else.
Things seemed to go very well with the procedure and Alf fell asleep while I worked. As I finished up, trimming and tucking my edges, Alf woke and made a strange declaration. He had been dreaming, he said, of an incident at the end of the War when he was assigned at age twenty-one as a sniper in Gibraltar. Guarding the harbour, he had been ordered to fire on a sailor whose craft had breached a strategic position. He had hesitated, and his sergeant had pressed him to take the shot.
"I killed him, I'm sure," said Alf. "A boy my age - I saw him fall dead into the sea."
Then graceful, radiant Alf broke into floods of tears.
"I am sorry to cry, " he said, "but I have been dreaming of the pain of that mother whose boy I shot and what she carried, and if anything was able to repair it?"
We shared a thought about the weight of life to be carried in struggling to be good and happy. He smiled his eyes again and left.
I have been troubled often in recalling Alf's story and what I think it tells us about carrying the weight of ourselves and working at happiness, holiness and kindness; the daily balancing act of bringing - dragging - the raw stuff of our humanity towards divinity. How that takes a daily act of faith; of fidelity to living compassionately.
The salient wisdom flowing out of Alf's story and the unspoken, transcendent experience that his life has become in redeeming his own narrative offer a potent reminder that if we are to manage the lumbering weight of ourselves, if we are to find our feet despite the numbness, enmity, dissatisfaction, brokenness, separation and fatigue in our complicated lives - let alone in the lives of those for whom we care - then we must embed compassion in our dailyness and ordinariness, down amongst our very matter. To know deep satisfaction in ourselves demands that we develop a contented, unconditional focus on the well-being of others; a disposition for kindness from a warm, alive, open heart.
Suzanne Aubert, who recently updatedis about to update her status to 'Venerable', nailed the attitude when she enjoined her sisters to; "Be easy of access. Receive others amiably. Have a heart ready to devote itself." But how to have such a heart so disposed amongst the clamour and shambles of ourselves fronting up at home and at work?
First, begin in contemplation. Compassion begins in practising being still and being present. Experiencing real presence requires a kenotic self-emptying - a preparedness to sit within the tension between disturbance and joy and practise forgetting ourselves; letting go and letting God. Being present, meditating and mindfully attending to breathing - shifting and sifting the weight of our very human selves - allows us to be buffeted about by the divine.
The effort required is a detachment from our own weight - our faults, our inability to reconcile and forgive, our old hates: in short, it is a letting go of our resistance to grace. The foul weight of resentment, numbness, and self-hate closes us to the possibilities of compassion (first, to ourselves). When we are unbound and more able to forget and forgive ourselves, God knows what compassion and abundance might flow into our divisions and our engagements.
Teresa of Calcutta wryly observed:
"People are unreasonable, illogical and self-centred: forgive them anyway.
If you are kind, people may accuse you of ulterior motives: be kind anyway."
Her words highlight for me the unease between carrying the cross-bar of ourselves and embracing the extraordinary lightness of being that opening abundantly to others can bring.
On a similar note, a good friend of my mother's told her at her dying:
"I've always believed that people are sacraments: - Be an outward sign."
Fidelity to living compassionately - as blue-eyed, deeply-loving and serving Alf has illustrated - offers us a means to open to the abundance and possibility that might break in and deeply disturb our tired humanity to show us divinity. The Dalai Lama, quintessential example of living graciously and warmly in the liminal space between disturbance and joy, reminds us that kindness is everything. We are invited, quite simply, to be an outward sign of this material.
Dr Bernard Leuthart is Clinical Director at Waiwhetu Medical Group in Lower Hutt.
Getting Tired of Me Getting Tired of You?
James Lyons
Donor fatigue is not an uncommon expression. The number of requests for donations coming through the mailbox and other media has been increasing to the point where deciding where and what to give has become very complex.
There are so many needs, one person told me, that I know my little contribution is never going to make a difference. Now I don’t give anything!
Others feel quite exhausted by the constant flow of requests. Some get bewildered. Some get angry. Tiredness means no energy. No energy means no motivation; good intentions do not translate to action.
Compassion Fatigue is similar but less visible. It affects in particular those in the caring professions. As a priest, I have been asked to reflect on this phenomenon from a pastoral perspective.
In the day-to-day pastoral ministry a priest or lay pastoral leader is confronted with a variety of human needs:
- A parent calls very worried about the teenage child who wants nothing to do with the Church.
- A family seeks help with the payment of school Attendance Dues.
- A knock at the door presents a need for assistance with food, perhaps housing or for an ear to listen to a sad tale of abandonment or embezzlement.
- A grandparent worries over grandchildren who haven’t been baptised.
- Parishioners in hospital or hospice need to be visited, their families comforted.
- A death in the parish requires other commitments to be set aside.
- Couples preparing for marriage need to be given time and attention.
The list is endless!
There have been times when, as a priest, I have caught myself racing through an appointment because of my familiarity with the issue. I forget that, for the person involved, this is their first experience of death or loss or setback, etc., while I have dealt with it several times.
It is easy to anticipate their questions and not to be totally alert and present to their unique situation. This can give the impression that I don’t care or do not take seriously their particular concern.
When one problem or emergency follows another, when you know there are several emails or phone messages awaiting your attention, the temptation to dismiss people as quickly as possible is hard to resist. Or else you carry on, but you feel so very tired, and you know you are not focussing as well as you could, or should.
Compassion fatigue, in the pastoral sense, is not so much exhaustion of motivation but more a loss or absence of the ability to concentrate and to fully engage. It is very much a case of “the spirit is willing but the flesh is weak”!
One factor that might allow this kind of fatigue to be less detected in the clergy, is that pastoral ministry quite often deals in the realm of the spirit and that’s harder to see. A doctor who, through inattention may misdiagnose or prescribe the wrong medicine, will be quickly called to account. But a priest who doesn’t really listen in the confessional or offers some outdated theological advice, or gives out some over-worn cliché response, is not going to be so readily caught out.
This sort of behaviour may not be so much the result of compassion fatigue but rather a laziness, perhaps even arrogance, that is irresponsible. Pastoral workers owe it to themselves as much as to those in their care, to stay relevant through study and reflection. Not to do so is to risk becoming a disappointment to themselves; that, in turn, can lead to depression and total shutdown.
While doctors and other professionals usually see people on an “appointment only” basis, priests are more “open season” to callers. A phone call or door knock can come at any time of day or night and there is an assumption on the part of the people that the priest will answer. No matter he may have just returned from a parish meeting or funeral preparation, the caller has a need that cannot be postponed.
Despite real efforts to hide weariness or annoyance at the interruption, the caller will often pick this up, going away with an “he doesn’t really care” impression.
Personally, the worst time is just before Mass: Someone wants you to remember a special intention at Mass; another tells you of the death of a relative overseas; a car has been parked with its lights on – can you please make an announcement; there’s a cake stall after Mass but we forgot to put it in the newsletter – will you tell everyone; today is a special day for Mr & Mrs… - can you give them a blessing; it’s my birthday, will you say a prayer for me…
Loving and caring as such requests show themselves to be, their timing is challenging. It is in these moments that compassion fatigue hits me between the eyes.
James Lyons is a priest serving in pastoral ministry for the Archdiocese of Wellington
Sustaining Compassion
Anna Holmes
Compassion means suffering with. It is about bearing witness to suffering. Bearing witness is not just being a bystander but entering into the world of the sufferer. Mirror neurones in human brains reflect this suffering. Medical students are encouraged to practice empathy. This is an act of spiritual connection, of compassion, that recognises our common humanity.
As a medical student in the early 1960s I was taught how to deal with suffering by observing the way in which my teachers dealt with it. We did not have formal teaching on ethics and relationships but we saw our teachers kneeling by bedsides, treating patients with gentleness and courtesy, as one human being to another. I accompanied a GP on visits, first in a poor neighbourhood where he took the prescription to the patient because, he said, “They will not go and collect it”’. Next we went to a patient recovering from a heart attack. The GP told me “He was just sitting in the hospital and I knew he would be better looking at his view of the Braid Hills. So I said I would look after him and he was sent home.”
Last month I read two articles on burnout in doctors, suggesting that many doctors in NZ and the US suffered from ‘compassion fatigue’. The NZ article suggests four key factors: fatigue, difficult patients, external distractions and clinical complexity. It was most common in younger GPs. It also suggests that turn offs for doctors are patients who are aggressive, smelly or dislikeable and compassion is lacking for such patients. The US article also suggested bullying by senior staff and not being supported were factors in compassion fatigue.
When I interviewed 22 NZ GPs for a thesis on spirituality, 16 of them said they had been burnt out. They were unable to respond compassionately to the needs of their patients, family and self. It was nearly always as a result of simultaneous personal and work problems and a lack of support. A number had also been bullied.
The advent of scientific medicine has changed expectations for doctors and patients. It has shifted the focus of medicine from caring to curing. The technological and therapeutic triumphs make students think that most things can be cured. They expect a medical world that is predictable and controllable. In fact it is nothing of the kind. An ageing population means that they are going to have to deal with many patients with chronic or terminal diseases. These are not curable but require care and compassion.
The innate compassion of many of the students is impressive. They spend five weeks working in a rest home and write an essay about their experience. These often show an extraordinary growth in understanding, from ignorance of the elderly to understanding them as treasures, even when they are demented or disabled. Students wonder at the rich and interesting lives of the ‘elderlies’ depicted in photographs on the walls of their rooms.
So how can compassion be enabled for doctors and patients?
Work conditions are important – recognising the limits each person has for work and providing mentoring and support. Having experienced working 80 hours a week as a house surgeon I do not think this is just about exhaustion. It is about having a community of work where all staff care for each other.
Dealing well with difficult staff is also important. I still relish the story of a contemporary of mine who when asked by a grumpy surgeon whether he thought he was God replied ‘No sir, just his house surgeon.’ The Royal Australasian College of Surgeons recently published a report about bullying in hospitals that found half the trainees had experienced it.
Doctors who continue to enjoy their work ensure that they have balance in their lives with body, mind, spirit and human connections all attended to. They have creative activities outside medicine that feed their spirit – painting, writing, gardening, climbing mountains, cooking and many others.
Junior doctors spend many hours working on computers to obtain and transmit clinical information about their patients. But they also need enough time to spend with patients and in reflection. I do wonder whether working shifts in medicine is as satisfying as caring for a patient from admission to discharge.
While spirituality is acknowledged as being important in health and healing, there is very little attention paid to it in medical school or hospitals. Scientific thinkers tend to reject concepts that cannot be explained by science. I believe that this may be partly responsible for the increase in burnout. If medical work connects doctors deeply to self, other, the natural world and the transcendent, it enables healing and growth. If cure is the main focus it fails to satisfy. Memorable patients for the doctors I interviewed were often those who died well under their good care. One of my memorable patients was dirty, smelly and unable to talk but he had a beautiful, toothless smile.
Anna Holmes MB ChB PhD is a Clinical Senior Lecturer in the Department of General Practice, Otago Medical School.
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References:
Time Magazine, Vol.180, No 9-10 September 7-14, 2015, p 44-50.
North and South, September 2015, p. 59-64.
Editorial: Compassion Fatigue
In a recent article in North & South Magazine[i], Donna Chisholm discusses the issue of compassion fatigue amongst doctors and some of the implications of this for patients. It is claimed that around 50 percent of doctors report compassion fatigue, and that there is an exodus of a quarter of young doctors from the country within three years of graduation, many of whom report stress and burnout.
Compassion fatigue has been described in terms of the draining away of what is seen as a finite reservoir of caring. However, recent research from Auckland University’s department of psychological medicine indicates that the ‘leaky reservoir’ model may not be adequate. Its survey of nearly 600 doctors indicates that, in fact, younger doctors report more obstacles to compassion. This work suggests that there are four key factors that need to be looked at and over which a doctor has little control: burnout/fatigue, difficult patients, external distractions and clinical complexity.
Chisholm highlights ‘difficult patients’ as one of the more interesting outcomes of the research. While ‘burnout’ tops the list of influences, “a patient’s attitude and demeanour are almost as important. That means if your doctor actually likes you as a person, you’ll probably get more compassionate care.” (p.61). One of the study authors suggests that “doctors are normal people. If they are confronted with a person who is unpleasant, demanding, non-compliant, ungrateful, malodorous … they won’t like them and they won’t care for them.” (p.61). The report’s author posits that there is an evolutionary aspect to this – it is inefficient to keep caring for people who don’t deserve it. He believes it is basic human functioning to ask ‘Do I like you?’ and that the answer to that question is the first decision that is made; in his opinion “no amount of professional training will ever get us past that fact. Ever.” (p.62).
A more hopeful analysis is offered by an Auckland City Hospital emergency department physician who suggests that while emergency departments are places where patient behaviour is likely to be at its worst, this is no reason for doctors to leave their compassion at the door. He has become considered by his colleagues the person best able to deal with the difficult cases - the angry drunks, the drugged and the homeless regulars who just turn up for a feed – and says: “I’ve learnt to like the people you wouldn’t normally like.” (p.62). Changing the way he thinks about patients has been the key to changing the way he acts, and while fatigue and burnout are factors in compassion failure, he believes that ‘healthy thinking’ can reduce it.
This approach is supported by other research undertaken with doctors that found that those who didn’t feel stressed had one main trait in common, that of being connected to their purpose, or a ‘higher calling’: “The doctors who are absolutely thriving all sound like they’re on a mission.” (p.62). One 60-year-old GP finds he now feels more compassion for his patients than he did 25 years ago. While he has over time become better at the ‘mechanical’ aspects, diagnosis and treatment, he also tries to listen to his patients, to understand what’s happening through ‘their eyes’. A fourth year student suggested that a lot of young doctors do not really listen to patients, “they’re filling out a check box in their head of things they feel they need to ask. I think that detracts from the fact that there’s a patient who’s an individual in front of you. Maybe they have information that’s not on your checklist.” (p.63).
A former primary-care nurse who trains health workers in how to better communicate with patients believes the ‘difficult patient’ problem is exaggerated and that ‘difficult patients’ are created by the way they are spoken to. At the same time, she does not believe every nurse and doctor can be taught to be compassionate and empathetic, and that around a third who attend her workshops “will never get it.”
The factors involved in compassion fatigue include a mix of environmental factors such as workload, the complexity of some illnesses, the behaviour of patients, as well as the evolutionary and personal factors that cause doctors to respond in certain ways to their patients. None of these is easily changed. However, finding ways of preventing compassion fatigue is important, for the doctors themselves but also because empathy and compassion are associated with better patient out-comes, and failure of compassion with poor decisions.
Of course, compassion fatigue is not restricted to the health professions; it also affects teachers, politicians, social workers, chaplains/pastors, prison workers, youth workers, counsellors and parents. With that in mind we have asked seven different practitioners from a variety of caring professions to offer their reactions to, and insights on, the North & South article.
We believe there is something of substantial personal value for every reader in the richness of the authors’ reflections offered in this issue.
Sue Buckley is a researcher for The Nathaniel Centre and Dr John Kleinsman is the director of The Nathaniel Centre.
[i] ‘Cold Comfort’ by Donna Chisholm. North & South, Issue 59, September 2015. Pp. 59-64.
Guest Editorial: All lives matter … all means ALL
Wendi Wicks
On Tuesday 25 July, at the Kanagawa Kyodokai at Tsukui Yamayuri En, west of Tokyo, 19 disabled people were stabbed to death as they slept. The killer was a former employee at the residential/rehabilitation facility for disabled people. He moved rapidly through the building – in 50 minutes he killed 10 men and 9 women and injured 24 others. He then drove himself to the police station to hand himself in. He said it was better “that disabled people disappear”.
This was not the first time he had made explicit his belief that disabled people should be eliminated. In February he attempted to hand deliver a letter to the speaker of the Japanese parliament.
In it he outlined in stark terms his belief that disabled people should be killed:
“I believe there is still no answer about the way of life for individuals with multiple disabiIities. The disabled can only create misery. I think now is the time to carry out a revolution and to make the inevitable but tough decision for the sake of all mankind … I envision a world where people with multiple disabilities can be euthanased with an agreement from the guardian.”
He claimed he could wipe out a total of 470 disabled individuals and offered a “plot”, to be put before the prime minister, whereby he would kill 260 people, be arrested but only imprisoned for 2 years and then receive plastic surgery and a new identity. All of this would be “for the sake of Japan and world peace”, and would be suitably remunerated by the government.
So how did this tragedy play out in the media? Given the prolonged outpourings of grief and solidarity with those killed when it came to similar multiple killings in Paris, Nice, Orlando and Kabul, one might expect something similar. There one saw wall-to-wall coverage, Twitter storms and trending hashtags; altered profile images to indicate solidarity. There were repeated updates, headlining news bulletins on radio and TV – some talkback hosts made wise sayings, other TV hosts left the soothsaying to their guests. Many attended memorial events or vigils.
But in the case of Tsukui Yamayuri En, Japan’s worst mass killing since World War 2, the response was a roaring silence. Hashtags, memorials, public outrage, panels of soothsayers just didn’t happen for the general public, or in international settings. We disabled people know because we looked.
In contrast, disabled people worldwide reacted with a storm of comment, horror and action. New Zealand disabled people led off with a vigil – most attenders were disabled people and there was no media attention. Protests, memorial services and marches of solidarity followed worldwide. Many excellent blogs with sound analysis were written. But only disabled people mourned in public.
A particularly challenging part of our public mourning and memory was when we found that the men and women killed at Kanagawa Kyodokai would not be named, because, it was said, their relatives were too ashamed to acknowledge having a disabled family member: in effect erasing disabled people from the public record and perpetuating our invisibility. It is an obscenity, felt strongly by us and still stinging. All the disabled people who have learned of this lack of names recoil in either body or spirit.
Sadly, what happened in Japan is symptomatic of the everyday invisibility of disability we experience. Society sees disabled people as not really needing human rights, because we aren’t fully human. It seems that our names or identities don’t matter. We are pegged as ‘takers’ of society’s precious resources. As reflected in court judgements, it is understandable if disabled people are abused because caring can be difficult and stressful. And if this is understandable, well it may be OK to euthanase them.
The message here, (as in Hitler’s Germany where over half a million disabled people were gassed, starved, neglected, or sent to the death camps), is the opposite of “all lives matter”. To the general public, and in the media, our lives don’t seem to matter, and the realities of how we live are seen to be a good reason for our deaths. There is an invisibility of the humanity of disability.
So Tsukui Yamayuri En is not our first and nor is it an unusual encounter with such attitudes and their consequences. It is most troubling that we encounter similar attitudes as common currency: when disability is seen in negative un-affirming terms; where people believe ‘better dead than disabled’, notably if one needs assistance with bathing, toileting, or getting in and out of bed (loosing dignity in such processes); when we are seen to suffer, have unendurable pain, feel hopeless and a burden. In these ways disabled lives are daily discounted.
While these inimical attitudes exist about disabled people, we will remain at risk of the extermination the Japanese knifeman advocated for – whether in New Zealand or elsewhere.
In this context, any attempt to put up assisted suicide legislation with so-called eligibility criteria will also have deadly consequences. As various select committee reports make clear (Scotland, UK, Victoria, Bulgaria), legal safeguards and criteria cannot make such legislation sufficiently robust. Disabled people deserve much better - it is our world too.
Wendi Wicks is a celebrant, writer and strong advocate for disability rights. She convenes “Not Dead Yet Aotearoa”.
People Who Use Wheelchairs Don’t Actually Want to Kill Themselves
David Bekhour challenges the underlying and unquestioned assumption in the film ‘Me Before You’, that someone with a spinal injury and using a wheelchair will unquestionably find life too difficult and want to end it all. “People in wheelchairs don’t actually want to kill themselves”, but films such as this perpetuate the antiquated and dangerous idea that the lives of disabled people “are somehow less worth living”.
Available online at: http://medium.com/@OptimisticGrin/people-who-use-wheelchairs-dont-actually-want-to-kill-themselves-d76493596eb6#.z276ob8mt
Stem cell research
Celina Capistrano
In 2004, a Nathaniel Report article outlined ethical issues surrounding the use of human stems cells in research and medicine. The following is an update on that article, providing a description of the different types of stem cells and the ethical issues associated with these. It also reports on the recent discovery of a new gene-editing technique, CRISPR/Cas9, and some of the ethical issues that are involved with its use.
Human Stem Cells
Human stem cells, characterised by their ability to develop into a range of different cell types, were first discovered in the mid-20th century and isolated in embryos in 1998. They may be found in embryos or derived from non-embryonic sources.
Human embryonic stem cells (hESC) can be derived in two ways: (i) using early stage embryos (blastocysts) created from eggs fertilised with sperm in vitro, embryonic stem cells (ESCs) can be isolated from the inner cell mass of the blastocyst and exposed to factors that allow these ESCs to continue growing; (ii) by a process called Stem Cell Nuclear Transfer (SCNT) where genetic material from an adult cell (e.g. skin or connective tissue) is injected into an egg that has had its genetic material removed (enucleated egg). The egg is then stimulated to develop until it reaches the blastocyst stage, thus becoming a ‘cloned’ embryo, at which point the inner cell mass is removed and grown in a petri dish (in vitro). One of the key scientific advantages of producing pluripotent cells (cells that can give rise to all cell types)by SCNT is that it enables a patient’s own cells to be used, thus avoiding the problems of immunological rejection that occur when using stem cells originating from another person. Both of these procedures, however, involve the destruction of the embryo and consequently give rise to significant moral and ethical issues concerning the value of, and respect for human life. Additionally, with SCNT there is the extremely controversial issue of creating human clones. There have been research developments resulting in isolation of ESCs without destruction of the embryo thus bypassing concerns regarding embryo destruction. However, the further healthy development of such embryos remains uncertain.
Induced Pluripotent Stem Cells
Largely as a result of the ethical issues related to human cloning and embryo destruction, but also because of various research controversies, progress on human stem cell research from about 2001was somewhat stalled. However, in 2006, Japanese Scientists Dr Takahashi and Dr Yamanaka1 (Nobel prize winners in 2012) discovered how to re-programme ‘somatic’ cells (‘non-embryonic’ or ‘adult’ cells) to reverse their state back into pluripotent form through the re-expression of key embryonic genes (suppressed in the somatic state), thereby enabling these already differentiated adult cells to behave as embryonic stem cells2. These new cell forms, Induced Pluripotent Stem Cells (iPSCs), appeared to the have same essential characteristics as embryonic stem cells. With the ethical barriers to the development of stem cells now removed, these new methods have sped up the discoveries regarding stem cell research to a “near-exponential rate”3.
Since the Takahashi and Yamanaka discovery, developments in iPSC methods have provided the best opportunity to avoid the ethical objections associated with destroying human embryos as well as the problems of immunological rejection.
iPSC in therapy
With this new ability to differentiate pluripotent cells into any cell through iPSC technology, researchers are now developing new model systems to investigate the biology of early mammalian and human development as well as new approaches for regenerative medicine. These systems offer improvements in the ability to study disease at a patient specific level and to increase the potential for more efficient methods for drug discovery and screening for genetic disorders. Specific strategies to tackle a range of diseases and disorders including Parkinson’s disease, spinal cord injuries, heart disease, inflammatory diseases, joint injuries, and Age Related Macular degeneration are also being developed, and there is the potential to use iPSC in transplantation medicine.
There are still some significant safety issues that need to be overcome. For example, one of the early ways of creating iPSCs was by transfecting or inserting the desired genetic material into the adult cells through use of a virus to shuttle the transcription genes. The procedure, however, could have the potential for the virus to be integrated into the cell’s DNA and cause undesired mutations.
Though iPSC’s are the most ethical way to experiment with pluripotent stem cells, other ethical issues are likely to arise depending on where the research is heading. For example, scientists have now succeeded in creating human primordial germ cells (sperm and egg precursor cells). Some scientists will continue to advocate for the use of embryonic stem cells in research that aims to better understand embryonic development, and to find ways to treat infertility and improve in vitro fertilisation (IVF). The shift away from embryonic research due to the new technology may even lessen the rigidity of regulations in terms of these studies, which may be a problem in the future.
CRISP/Cas9
CRISPR-Cas9 is a molecular tool that is being used in laboratories to edit genes. It was noticed that in some bacteria the DNA sequence in cells was repeated many times, interspersed with unique sequences between the repeats, and this configuration was called ‘clustered regularly interspaced short palindromic repeats’ or CRISPR. It was later found that these unique sequences matched the DNA sequences of invading viruses, and that the bacteria made RNA copies of these unique sequences. This RNA would link up with an enzyme named Cas (CRISPR Associated Protein, a nuclease that can cut DNA) and guide the CRISPR/Cas complex to a matching DNA sequence, enabling the Cas enzyme to cut and disable the invading gene.
This discovery became a genome engineering tool when it was found that this technique could be used to cut not only viral DNA but any DNA sequence by altering the guide RNA to match a targeted gene sequence. Scientists can synthesise RNA sequences to match the DNA sequence they wish to target and use CRISPR/Cas9 to repair or inhibit the gene. There are a number of Cas enzymes but Cas9 is the best known.
In 2015, researchers in China used CRISPR technology to edit the genes of human embryos in their research into a cure for the blood disease, beta-thalassaemia4, and again in 2016 in an attempt to introduce a mutation that would make people immune to HIV. UK researchers were recently successful in obtaining permission from the Human Fertilization and Embryology Authority to edit human embryos using CRISPR/Cas9 genome editing technology5. Their research was aimed at developing a better understanding of successful human embryo development and the causes of miscarriage and infertility.
With CRISPR/Cas9 genome editing technology it is possible to cut out and replace defective genes, which also means that primordial germline cells can be altered. The removal of ‘defective’ traits and the possibility of creating enhanced human beings would usher in a new era of eugenics thinking and practice. A number of scientists, including Jennifer Doudna, one of the scientists who discovered the CRISPR/Cas9 technique, have noted that there are significant ethical issues associated with the development of germline editing, and that CRISPR should not be used on reproductive DNA, or germline cells, while allowing laboratory research to continue6. They are concerned that, unless there is education and discussion amongst both scientists and the public about the risks and benefits of scientific developments such as CRISPR, then (i) there a greater likelihood of unethical use of such technologies and (ii) research into the therapeutic use of genetic changes that cannot be inherited, will be put at risk.
The potential for a ‘new eugenics’ is a concern with CRISPR/Cas9 technology, and as described above, the destruction of embryos is a key ethical issue associated with stem cell research. However, there are other ethical issues associated with stem cell research and germline modification. These include the commodification of human reproductive materials; the potential for exploitation of donors (e.g. women donating eggs for the derivation of hESC lines); the possibility for human reproductive cloning; and, finally, uncertainties relating to the creation and use of human–animal hybrids and chimeras for research7.
Endnotes
1.Takahashi, K., and Yamanaka, S. (2006). “Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.” Cell 126, 663–676. DOI:http://dx.doi.org/10.1016/j.cell.2006.07.024
2. Brunt K.R, Weisel R.D, Ren-Ke L. (2012) "Stem Cells and regenerative medicine- future perspectives" Can. J. Physiol. Pharmacol., 90(3), pp.327-335. doi: 10.1139/y2012-007
3. Ibid.
4. Cyranoski, D., and Reardon, S. (2015). “Chinese scientists genetically modify human embryos.” Nature News, 22 April 2015. doi:10.1038/nature.2015.17378 (Original Article of the Research from China, Liang, P., Xu, Y., Zhang, X. et al. (2015) Protein Cell, 6: 363. doi:10.1007/s13238-015-0153-5)
5. Callaway, E. (2016) UK scientists gain licence to edit genes in human embryos. Nature News, 530(1),18.doi:10.1038/nature.2016.19270
6. Doudna, J. (2015). “Genome-editing revolution: My whirlwind year with CRISPR.” Nature, 528(1), 469–471. doi:10.1038/528469a and Doudna, J. (2015). “Perspective: Embryo editing needs scrutiny.” Nature, 528 (S6). doi:10.1038/528S6a
7. Caulfield T, Kamenova K, Ogbogu U., Zarzeczny A, Baltz J, Benjaminy S, Cassar PA, Clark M., Isasi R., Knoppers B., Knowles L., Korbutt G., Lavery JV, Lomax GP, Master Z, McDonald M, Preto N, Toews M (2015) "Research ethics and stem cells" EMBO reports, 2015, Vol.16(1), pp.2-6 doi:10.15252/embr.201439819
Celina Capistrano graduated with a Bachelor in Biomedical Sciences (BBmedSc) specialising in Molecular Pathology and Genetics in 2015. She is currently undertaking a practicum with the Malaghan Institute of Medical Research as part of her Masters in Clinical Immunology course with Victoria University, Wellington.