Placebo - an underrated treatment?

If you thought the placebo effect was all in the mind, think again.

A placebo is traditionally defined as a harmless pill, medicine, or procedure prescribed more for the psychological benefit to the patient than for any physiological effect or in research, a substance that has no therapeutic effect, used as a control in testing new drugs.

For most of us, the potency of sugar pills is synonymous with the power of positive thinking; it works because you believe you’re taking a real drug. But new research continues to rattle this assumption and peel away further layers to the inner workings and potential therapeutic applications of the ‘powerful placebo’.

Most recently, researchers at Harvard Medical School’s Osher Research Center and Beth Israel Deaconess Medical Center (BIDMC) found that placebos work even when administered without 'deception'.

It is broadly understood that to prescribe a placebo openly as an actual treatment would risk undermining the effect. But data on placebos are so compelling that Harvard associate professor of medicine Ted Kaptchuk teamed up with colleagues at BIDMC to explore whether or not the power of placebos can be harnessed honestly and respectfully.

To do this, 80 patients suffering from irritable bowel syndrome (IBS) were divided into two groups: one group, the controls, received no treatment, while the other group received a regimen of placebos – honestly described as 'like sugar pills' – which they were instructed to take twice daily.

“Not only did we make it absolutely clear that these pills had no active ingredient and were made from inert substances, but we actually had ‘placebo’ printed on the bottle,” says Prof Kaptchuk. “We told the patients that they didn't have to even believe in the placebo effect. Just take the pills.”

For a three-week period, the patients were monitored. By the end of the trial, nearly twice as many patients treated with the placebo reported adequate symptom relief as compared to the control group (59% versus 35%).

Also, on other outcome measures, patients taking the placebo doubled their rates of improvement to a degree roughly equivalent to the effects of the most powerful IBS medications.

This particular aspect of their discovery has been mirrored in other studies and is proving quietly disconcerting for pharmaceutical companies who pour billions into developing lucrative new drugs only to find that, on occasion, the placebo group in their clinical trials fared just as well or even better than the active arm.

For a range of ailments, from pain and nausea to depression and Parkinson’s disease, placebos – whether sugar pills, saline injections, or sham surgery – have often produced results that rival those of standard therapies.

But, of course, there are limits to even the strongest placebo effect. No simulation could set a broken arm or clear a blocked artery. It can ease the discomfort of chemotherapy, but it won’t stop the growth of tumours.

For the most part, placebos appear to affect symptoms rather than underlying diseases, although sometimes, as in the case of depression or irritable bowel syndrome, there’s no meaningful distinction between the two.

For more than a decade, scientists have made tremendous strides in demonstrating the biological truth of the placebo effect. Numerous studies have shown that these inert pills can trigger verifiable changes in the body. The enduring search now is to uncover the precise mechanisms that elicit placebo-related effects, and to understand how these can be reliably harnessed.

Advances in image processing are aiding investigators in this quest. A study, published in Science in 2009, utilised functional magnetic resonance imaging (MRI) to scan the spinal cords of 15 healthy volunteers, homing in on an area called the dorsal horn, which transmits pain signals coming up through the spinal cord into the pain-related areas in the brain.

During the scan, the volunteers received laser 'pinpricks' to their hands. The volunteers were told that a pain-relief cream had been applied to one of their hands and a 'control' placebo cream to the other. But unknown to the volunteers, an identical 'inactive' control cream was administered to both hands.

When people believed that they had received the active cream, they reported feeling 25% less pain and showed significantly reduced activity in the spinal cord pathway that processes pain.

Previously, it has been shown that placebo causes the release of natural opioids in areas of the brain involved in pain control. 

“We’ve shown that psychological factors can influence pain at the earliest stage of the central nervous system, in a similar way to drugs like morphine,” said Falk Eippert, of the University Medical Centre Hamburg-Eppendorf, who led the study.

A world authority in this field, Fabrizio Benedetti, professor of clinical and applied physiology at the University of Turin Medical School, has devoted more than 15 years to mapping many of the neurobiological mechanisms of the placebo effect, uncovering a broad range of the body’s self-healing responses.

He says that placebo-activated opioids, for example, not only relieve pain, they also modulate heart rate and respiration. The neurotransmitter dopamine, when triggered by placebo treatment, helps improve motor function in Parkinson's patients. Mechanisms like these can elevate mood, sharpen cognitive ability, alleviate digestive disorders, relieve insomnia, and limit the secretion of stress-related hormones like insulin and cortisol.

Impressed by such findings, some researchers and clinicians hope to import them somehow from bench to bedside – adding placebo, in a structured way, to the doctor’s medical repertoire. But any attempt to harness the placebo effect immediately runs into problems. To present a dummy pill as real medicine would be, by most standards, to lie.

And yet, research has shown that many doctors incorporate the placebo into their therapeutic arsenal. For example, a 2004 study in the British Medical Journal found that 60% of doctors in Israel used placebos in their medical practice, most commonly to ‘fend off’ requests for unjustified medications or to calm a patient.

So if the medical profession see little harm in prescribing placebos, should they should be more widely available to the general public? After all, they are the ideal medicine: placebos typically have no side effects, are essentially free, and have clinical research to back up their beneficial effects.

Actually, a variety of placebo cures are available on the internet. One of the most popular is Obecalp, natural cherry-flavoured chewable tablets for children. Launched in 2008, Obecalp claims to be the first standardised, branded and pharmaceutical grade placebo on the market. Its name is ‘placebo’ spelled backwards.

The idea is a seductive one – to harness the placebo effect to comfort children who are a little unwell, without risking side-effects. They are designed for when 'children need a little more than a kiss to make it go away'.

However, Obecalp has received mixed reactions from the medical profession. One issue is that the pills will be used without medical supervision, creating a small risk that parents may delay bringing children with a serious illness to their GP because symptoms are masked for a while by the placebo effect.

Dr Clare Gerada, vice-chair of the Royal College of General Practitioners, described the pill as 'medicalising love'. Douglas Kamerow, associate editor of the British Medical Journal, highlighted a more serious threat. He pointed out in his editorial that by giving children a tablet for every ailment, parents may encourage them to think that popping a pill is the be-all and end-all of health.

“Sure, there are kids who end up wanting a colourful plaster for every ache and injury, but I have never seen an adult addicted to plasters. I have seen many adults who want a pill for every ill.”

But perhaps the real source of the placebo’s effect is the medical care that goes along with it, that the practice of medicine and the trappings of medical care is providing tangible healing influences.

For example, a study published in the British Medical Journal in 2008 described experiments conducted on patients with irritable bowel syndrome. Two groups underwent sham acupuncture, while a third remained on a waiting list. The patients receiving the sham treatment were divided into two subgroups – the first was treated in a friendly, empathetic way and the second group had their care delivered in a businesslike fashion.

None of the three groups had received ‘real’ treatment, yet investigators reported sharply different results.

After three weeks, 28% of patients on the waiting list reported 'adequate relief,' compared with 44% in the group treated impersonally, and fully 62% in the group with caring doctors. This last figure is comparable to rates of improvement from a drug now commonly taken for the illness, without the drug’s potentially severe side-effects.

The lead investigator was Harvard Medical School’s Prof Ted Kaptchuk. In this research, and his 2010 IBS study mentioned earlier, he emphasised that, rather than mere positive thinking contributing to the placebo effect, there may be significant benefit to the actual performance of the medical treatment ritual.

If this is true, then the takeaway message is not necessarily that doctors should be prescribing more fake pills but that as much thought should go into the medication selected as to the context in which it’s given.

Prof Anne Harrington

The definition of placebo effect has now broadened beyond dosing with inert pills to include questions about whether healing is still in part an ‘art’, and issues such as how the relationship between doctors and patients affects treatment outcomes.

At its best, that doctor-patient ritual activates positive expectations, triggers associations with past healing experiences, and eases distress in ways that can alleviate suffering.

Prof Anne Harrington, professor of the history of science at Harvard University and author of the book The Placebo Effect: An Interdisciplinary Exploration, suggests that a better way to think about the placebo effect would be as “the sum total of effects”.

Part of that experience might be going into a waiting room where the patient sees lots of certificates on the wall, and where a confident doctor walks in with a white coat that designates him as a professional expert. “All of these things produce the placebo effect,” she says.

Perhaps the secret of the placebo is rooted in the patient-doctor relationship. It may be about how people respond to symbols and about the intangible parts of medicine, such as the inherent capacity of human beings for self-healing.

Journey to the other side

The indomitable spirit of Dr Kate Granger

I am surprised how often our conversation is lifted by her laughter. The spontaneous cheerful bursts are unexpected. Dr Kate Granger is terminally ill with a rare and highly aggressive type of sarcoma, yet somehow she is at ease with the prospect of her impending mortality. It is a bleak reality she has had only months to absorb but her adjustment is extraordinarily pragmatic. It’s quite inspiring.

Kate was diagnosed, out of the blue, with Desmoplastic Small Round Cell Tumour (DSRCT) in 2011. She was 29 years old, happily married, with a hectic career she loved as a third year Elderly Medicine Registrar working at Pinderfields General Hospital in Yorkshire.

She describes her cancer journey as horrendous and convoluted. On the advice of an Irishman - one of her bosses, Dr Frank Phelan, a Consultant Physician at Pinderfields - Kate wrote her story down, initially for therapeutic benefit and to fill the countless insomniac nights in hospital. But her personal diary has evolved into a poignant book, The Other Side, which has sold well over 3,000 copies since it’s publication in February 2012 and raised £20,000 for the Yorkshire Cancer Centre.

The Other Side is an emotive, uncompromisingly honest and often harrowing account of a doctor's struggle as a patient coming to terms with a devastating diagnosis, her difficult journey with an incurable disease, and her ultimate decision on New Year’s Day to cease treatment in order to retain some quality of life for the time she has left.

Kate’s book is targeted at health professionals, offering them a rare insight into a patient’s plight through the eyes of a fellow medic.

“I’m a doctor and I love being a doctor but, having experienced the other side of the healthcare system as a patient, I think some of us could learn about how to be good doctors by remembering to be good human beings. I know this experience has made me a better doctor,” says Kate.

“I want doctors to stop and think about what it is really like to be a patient. How our behaviours can have such a massive impact, whether positive or negative, on the people we care for. Little tiny things like when someone holds your hand, or sits beside you, or is really kind to you, or if someone is dismissive of you.

“I hope that, by reading the book, healthcare professionals will have a better understanding and empathy for their patients, and from the reviews I have been receiving I think I may have achieved this,” she says happily, speaking from her home in Wakefield.

At a vineyard the day before Kate was admitted to hospital

Kate was on summer holidays in California with her husband Chris in July 2011 when she started to feel unwell. Within days the niggling right-sided backache turned into a searing pain and she was hospitalised.

An ultrasound identified bilateral hydronephrposis and her creatinine was 485. A subsequent CT revealed several soft tissue masses in her abdomen and pelvis. Kate’s fear was realised: ‘Oh my God, it really is cancer.’

She was in renal failure and in constant pain. Ureteric stents were successfully inserted on both sides by a dashing young surgeon, who Kate sensed was more than a little smug about the whole situation: ‘It feels as though he is giving himself a virtual pat on the back for being such a great surgeon.’ 

She realised of course that this was a temporary solution to her problems and that months of investigation and treatment were to follow.

Back in the UK, she was admitted for a pelvic ultrasound but the following morning she noticed that MRI is written next to her name on the ward white board. She knew that it is a completely appropriate investigation but was fuming that no one had bothered to discuss this with her, not simply out of professional courtesy but because she is absolutely petrified of confined spaces.

She concealed her claustrophobia, not wanting to be a nuisance, but when the MRI technicians finally returned to the scanning room to fetch her, she was a total wreck. The paper sheet was stuck to her with sweat and she dared not open her eyes despite their reassurances that it was over.

At the time, Kate wondered how older people cope with MRI scans, especially if they have some cognitive impairment, and she silently vowed to only ever request really clinically essential scans if she ever returned to work.

The third day of admission brought her an unfortunate example of doctor’s communication skills at their worst under the most painful of circumstances. That morning, a junior doctor who had obviously ‘pulled the short straw’ entered her room and without much preamble blurted out: ‘your MRI shows evidence of spread’.

“I was so devastated,” Kate recalls, speaking so softly her words are almost inaudible. “A gynaecology SHO came to see me and he basically told me out of the blue that I have metastatic disease. There was no groundwork prepared, no exploring baseline knowledge and concerns; there was no warning shot. I wasn’t even given the option of having someone with me. I’m sitting there in a bed, in pain, alone, questioning my own mortality and being told that I have metastatic cancer. I was 29 years old and it hit me like a steam train. Then he left me alone in the room and I never saw him again. That could have been handled so much better.”

Kate also expressed disappointment that her consultant didn’t visit her until the following day. “I still think that the concept of professional courtesy should exist. I’m not saying that as a doctor you should get special treatment, but if you can’t even get special treatment and you’re in the profession, it makes you wonder about the average patient.”

The severe pain Kate experienced in the Sates returned and she feared that her stents were failing. Her creatinine level increased and she was transferred to a specialist cancer centre where she was amazed at the difference in the quality of both medical and nursing care.

Kate, ill in hospital

Kate was scheduled for an urgent nephrostomy. “Being a doctor and having experience of things before they happen to you can be really difficult. I’d seen an elderly man have a nephrostomy when I was a student and it was horrendous; the poor man had been screaming. And there I was on my way to having my nephrostomy done and all I was thinking about was him. This is going to happen to me, I thought. Sometimes ignorance is bliss,” she laughs.

Later that day, a ‘lovely consultant’ dropped by to see her. In the book, she remarked on his ‘very gentle personality’ and that he broke all the infection control rules by sitting on the edge of her bed for a chat.

“I’m not sure anybody has actually ever proven sitting on a patient’s bed is such a horrendous thing to do and I certainly used to do it all the time. Sometimes being closer to your patient to comfort them when they need you is more important than microbiology,” Kate observed.

Within days it became apparent that the nephrostomy had failed and she was scheduled for a return trip to the Interventional Radiology Room – or ‘torture chamber’ as she called it - to have another inserted. Afterwards, Kate wrote about the determined efforts of a nurse, who was distressed seeing Kate in constant pain, to make her comfortable before her shift ended. She inserted a subcutaneous cannula and proceeded to give Kate alfentanil every half hour until she was relaxed and pain free.

“It takes five injections. I cannot believe her effort and dedication, but I am so thankful that for the first time in what seems like forever I can now actually close my eyes and sleep peacefully.”

The respite was short lived, however, as Kate soon has need for the third time in five days to revisit the ‘torture chamber’ for reinsertion of the troublesome nephrostomy and to remove her infected stents. Fortunately, the new nephrostomy was a success and her renal function normalised.

Her doctors had thought Kate was suffering from ovarian cancer but a series of tests confirmed that her cancer fit into the ‘small round blue cell tumours’ – a rare, diverse set of cancers including various sarcomas and lymphomas that usually affect children and teenagers.

Kate jokes that she felt strangely disappointed that despite having a very rare tumour it did not have a cooler name. “Let’s face it not much imagination has gone into ‘small round blue cell tumour’!” she laughs.

She remembers fondly how a Teenage and Young Adult (TYA) consultant, who dropped by to discuss her diagnosis and treatment plan, pulled up a chair, sat at her bedside and explained everything at the right level with amazingly adept communication skills. On the subject of palliative chemotherapy, Kate became emotional and he instinctively reached out to hold her hand.

“This touch is extremely comforting as inside the distress and turmoil of having to decide between spending months of what life I have left undergoing chemotherapy with all its side effects and simply walking away from the hospital to die properly sets in,” she wrote.

Kate was started on ‘baby doses’ of chemotherapy but this changed once a definitive diagnosis was established – Kate had Desmoplastic Small Round Cell Tumour (DSRCT). “This news hit me hard and I was not ready to hear it,” she admits. “All that I had read about DSRCT was that it was an extremely aggressive tumour with poor response to chemotherapy and dismal survival rates.”

The consultant gently questioned if she wanted to go ahead with more chemotherapy given the fact that it was very much a palliative situation now with no hope of cure. She decided to give ‘proper chemotherapy’ a try, more for Chris and her family than for herself.

Each of her five cycles of chemotherapy was accompanied by severe side effects, including neutropaenic sepsis. But just as she was verging on abandoning treatment, test results revealed significant reduction in the size of the pelvic masses and improvement in the bone disease. This gave her the strength to persist.

A friend’s husband - an interventional radiology consultant – suggested getting metal ureteral stents inserted as a means of losing the nephrostomies permanently and Kate took this up with her doctors.

“Lots of people have asked me if I think in some respects it was easier for me being a doctor because I know what I want and I can advocate for myself. Well, this was definitely an example where that was the case.

“After ten weeks with bilateral nephrostomies, the metal ureteral stents changed my life but I had to fight quite hard with my doctors to convince them that this would work for me. They were reserved about the idea and not very receptive initially but I nagged and nagged and eventually I got them in. If I’d been a regular patient I might not even have known about this option and I might not have been able to fight my corner quite as much,” she tells Scope.

Kate’s fifth cycle of chemotherapy ended on Christmas Eve but soon after she developed more complications and once again she found her self in hospital with an excruciating abdominal pain. She had been weighing up the burden of treatment versus the benefits for a number of cycles but that New Year’s day as she lay in her hospital bed, she decided to stop treatment.

Chris and Kate renewing their wedding vows

“I don’t know how long I have left, I don’t want to know, but I’m determined to be positive. I’ve started back at work part time and I have my bucket list. Chris and I renewed our wedding vows in April and we’ve gone to Paris and London and Spain. I’m just doing lots of really nice things and sort of dragging everyone along with me on this positivity trip,” Kate chuckles to herself.

Of late, life for Kate has taken an exciting and unexpected turn. When The Other Side was self-published in February, the initial modest run of 100 copies sold out in three days. Another, larger print was ordered. But then her book was plugged on the enormously popular ‘Medical Registrar’ Facebook page and ever since Kate has been caught up in a blitz of media interviews and invitations to address medical colleagues at workshops and meetings.

She has been inundated with overwhelming support from medics and patients alike, for her remarkable courage as much as her book. Kate decided to write a sequel, The Bright Side, which is her story about living with a terminal diagnosis, the struggle to maintain positivity, and how her experiences as a patient have changed her practice as a doctor. The Bright Side was launched on Sunday 16, September.

With so much to live for, Kate is returning to hospital for more chemotherapy – albeit a lower dose on an outpatient basis.

“Despite me thinking I am all sorted and can get on with living until I die, I don’t think I’m as ready to died as I thought I was,” she confides. “I can only do my best to keep smiling and keep positive. I’m not ready to give up yet.”

The Other Side and The Bright Side can be purchased online at http://theothersidestory.co.uk/ and is also available to download for the Kindle / iPad from amazon.com

Keep up to date with Kate’s news on her Facebook page:

https://www.facebook.com/theothersidestory

The surgeon-major and the Coachford poisoning case

After the untimely death of his first wife, the hasty remarriage of Dr Philip Cross to his pretty young governess raised eyebrows in 19th-century Cork. The subsequent exhumation of the late Mrs Cross revealed evidence of poisoning that led to the death sentence for the doctor, writes Eimear Vize 

Famed Victorian hangman James Berry executed more than 130 criminals, but the figure that returned to haunt his dreams most often was Dr Philip Henry Eustace Cross. The Cork doctor, who had slowly murdered his wife so he could wed the pretty young governess, was one of the bravest men he ever executed, he said.

“When you read of a man walking firmly to the scaffold, it is nonsense. Some walk, some are carried. Of all the men I hanged Dr Cross was the only one who walked firmly,” Berry recalled.

“He told his attendances that he did not fear death, for he had met it face to face more than once on the battlefield. He died unmoved, without a word,” the hangman wrote in his 1892 autobiography, My Experiences as an Executioner.

However stoical a figure Dr Cross cut as he strode to the noose, he was nevertheless a murderer. He was tried and found guilty of poisoning his wife by slow, excruciating degrees, and has the dubious celebrity of being the last person executed in Cork County Gaol.

It was a deliberate, cruel and cowardly act of betrayal. The mother of his six children was the only obstacle between him and his 20-year-old lover, Miss Effie Skinner – a former governess at their home, Shandy Hall, in Dripsey, County Cork. And Dr Cross, a highly regarded retired British army doctor 63 years of age, plotted his wife’s demise and watched for weeks, under the guise of her carer, as she was gradually poisoned by arsenic. He was the only person with her when she died. He would later tell a friend, “she died screaming.” The case was described by the prosecuting counsel at Dr Cross’s trial as “the most cruel and bloodthirsty of the century”.

Victorian court reporter William Roughead recounted the scandalous case in his book, The Murderer’s Companion. The chapter on Dr Cross is aptly titled ‘The Shadow on Shandy Hall – What love cost an old man’. In it Roughead expresses surprise at how this “qualified slayer bungled this homicide”. The incompetence of a skilled practitioner such as Dr Cross really passes belief, he said. “The inexpertness of the expert is inexplicable.”

But then Philip Cross was often described as “very reckless” and, as a lad preparing for his profession, many stories were told of his pranks at the paternal abode, Shandy Hall. A sketch of the house shows an unpretentious dwelling of two storeys, standing amid trees in the garden, the front railings of which bordered the road to Coachford.

As Surgeon-Major Cross, he was for many years attached to the 53rd regiment, and served in the Crimea, Canada and other foreign stations. He does not appear to have been popular in the army, although it is recorded that his courage was indomitable, and that with fearless bravery he repeatedly saved the lives of others at the peril of his own.

In 1869, at the age of 45, Dr Cross wooed and won, despite the opposition of her parents, a well-born and attractive young English lady, Miss Mary Laura Marriott, who was 18 years his junior. The couple married in London on August 17 at St James’s Church, Piccadilly, and after a term of service overseas, the doctor retired and they began their life partnership at Shandy Hall some two miles from Cork.

Shandy Hall, Dripsey

When Mrs Cross’s father died in the 1870s, Dr Cross succeeded to her fortune of £5,000, which allowed him to comfortably occupy his time as a gentleman farmer. He was also an avid hunter. This led to trouble with the neighbouring farmers and the doctor suffered the current local penalty of popular disapproval: boycotting. But he was not a man to take things lying down, as Roughead recalled: “attacked with stones by roughs at a coursing meeting, he made such a good use of his riding whip – without which he seldom appeared in public – that his assailants were soon glad to beat a retreat.” Some may not have liked him but, in general, Dr Cross was highly regarded as an intelligent and well-bred gentleman who could claim friendships in the grandest social circles.

Life for the doctor and his wife was relatively uneventful, punctuated every year or so with the birth of another of their six children. That was, until the arrival of the bewitching young governess, Miss Effie Skinner. Dr Cross had never been a ladies’ man, and often expressed his aversion to what he termed ‘chattering females’. So for a time, everything went on smoothly in the doctor’s house. But it was the calm that preceded the storm.

Dr Leonard Parry observed in his 1928 book, Some Famous Medical Trials, which details the ‘Coachford Poisoning Case’, that Dr Cross had gradually become aware of Miss Skinner’s “many favourable points”. It was the summer of 1886, shortly after she had started work at Shandy Hall.

Dr Parry wrote: “He recognised her beauty, her good nature, her capability in the management of the home and the children, her cheerfulness and good temper; all these completely overwhelmed him, and an ardent desire for possession took hold of him. His infatuation became noticeable to his wife, who spoke to him on the subject, but, needless to say, unavailingly. One day he startled the governess, who had never given him the slightest encouragement, by suddenly seizing her in his arms and passionately kissing her on the lips.”

Miss Skinner fled from him but apparently never mentioned the incident to Mrs Cross. “And from this fact the doctor drew quite erroneous conclusions,” said Dr Parry.

But Mrs Cross could not fail to perceive the change in her husband’s behaviour and challenged him on the subject. He resented her interference and denied that his interest in the girl was other than paternal. For three months the wife’s suspicions continued to grow stronger, until finally she insisted that the governess should be dismissed, which, despite the doctor’s vigorous protests, was done. The subject remained a sore one and the domestic atmosphere was thundery.

According to Dr Perry, Dr Cross convinced Miss Skinner that she had to leave the house due to the “ridiculous and unreasonable jealousy” of his wife. The governess believed him. She went to live in Dublin and a correspondence began between them. Dr Cross paid frequent visits to the capital, and it was not long before they were staying nights together in a Dublin hotel under assumed names. “But this did not satisfy Dr Cross. He wanted Miss Skinner for his real wife. His dislike for his lawful partner grew intense but he was anxious to maintain his good name and position, and he determined to devise some means of getting rid of her without arousing any suspicion or scandal. The method he adopted was so silly and clumsy that it is difficult to imagine that an educated and clever man could have been so foolish. Detection was inevitable,” remarked Dr Perry.

The court case, as reported in the British Medical Journal of December 24, 1887, heard that Dr Cross had bought a pound of arsenic in 1886 “for sheep dipping”. It was from this supply, it is believed, that he began to dispense tiny quantities into his wife’s food. One of the prosecution’s witnesses, Miss Jefferson, an old school friend of Mrs Cross, visited her frequently at Shandy Hall. An avid diarist, her detailed accounts of Mrs Cross’s dramatically diminishing health proved invaluable in the case against her murdering husband.

In her diary she had recorded the whole story of Mrs Cross’s illness, with all the symptoms of slow poisoning by arsenic. “While Miss Jefferson was there Mrs Cross had an attack of ‘spasms of the heart’, with vomiting, cramps and diarrhoea,” the court was told. “This began on May 10 and it continued until her death. Her eyes were inflamed and irritated. Dr Cross was the only person to attend his wife. He said she was suffering from some form of bilious fever, and he hinted at typhoid.”

To save appearance, Dr Cross called in a medical cousin, who obligingly concurred with the doctor’s diagnosis: a bilious attack. To others, Dr Cross represented her case as heart disease.

Early in the morning of Thursday, June 2, Mrs Cross died in agony with only her husband present. One of the maids was awakened by her mistress’s “terrible cries”. Dr Cross remained alone with the dead body throughout the night. In the morning he announced to the maids, with callous levity, his loss: “Get up girls: the Missus is gone since past one last night.” He gave no explanation of the four minutes of screaming in the night.

Dr Cross certified the death typhoid fever and buried his wife with “indecent haste” at 6am on Saturday, June 4. He gave her a paltry five-guinea funeral, and in attendance by her graveside was a publican, the driver of the hearse and the devious widower Dr Cross.

Less than a fortnight later he married Miss Skinner. Perhaps he would have gotten away with murder were it not for the suspicious speed with which he replaced his recently deceased wife.

He was reunited with his lover in London less than a week after the funeral – the court heard that a hotel bill for two people was found on Dr Cross covering dates from June 10-13 – and they were married on June 17 at St James’s Church, Piccadilly, the very church in which his first marriage was celebrated. After a short and somewhat superfluous honeymoon, Dr Cross brought his blushing bride home to Shandy Hall, and installed her as the new mistress. Their homecoming proved to be the last straw.

“Suspicions being aroused, the body of the late Mrs Cross was exhumed on July 23, and a post-mortem examination having been held, arsenic was found, and the prisoner was arrested,” the BMJ court reporter stated.

William Roughead said the trial of Dr Cross for the alleged murder of his wife by poison began before Mr Justice Murphy, presiding judge at the Munster winter assizes, on Wednesday, December 14, 1887. “Immense interest was taken in the proceedings; admission to the court was by ticket, and for such there were several thousand applications,” he said. “Throughout the four days’ hearing every available inch of space was occupied, a great number of ‘ladies’, so called, having secured seats.”

The BMJ account of the court proceedings identified Dr Charles Yelverton Pearson, professor of materia medica in Queen’s College, Cork, as the man who made the post-mortem examination. In his evidence, Dr Pearson confirmed that there was no sign of putrefaction in the intestines and that the heart and lungs were healthy. There was no sign of typhoid fever.

However, he found white particles in the gullet, which were arsenic. In the liver he found 1.28 grams of arsenic. He also found arsenic in the spleen and kidneys. The quantity of arsenic present was quite sufficient to cause death, he noted. He also found traces of strychnine. It appeared that the unfortunate lady had been slowly and regularly poisoned with arsenic, and the finishing stroke given with strychnine – which doubtless caused the characteristic screams heard at midnight by the maid. In these circumstances, Dr Cross, protesting his innocence, was found guilty and sentenced to death.

The final resting place of Mary Laura Cross, aged 46

Once the verdict of guilty had been returned, the prisoner addressed the court, which he did for half an hour. “He protested his absolute innocence. The arsenic he purchased had all been used for the dipping of his sheep. None had been found in the house,” said the BMJ report. “He was 63 years of age. Did they think that, having regard to his age and to his poor children, he was likely to do such a thing! He never did it. Why should he? He had stood to lose £40 a year by her death, and other money that was likely to come from her brother.”

He produced two prescriptions from a doctor to show that arsenic and strychnine had been prescribed for his wife, and he said his wife had talked to Miss Skinner about the effects of arsenic on the complexion. Finally, he claimed that he had married Miss Skinner because he had “done her a wrong” and because he wanted her to look after his children. Judge Murphy sentenced him to be hanged on January 10, 1888.

By the time it came for his execution Dr Cross’ hair had turned white. The hangman was James Berry. The execution was not one of Berry’s most successful ones because of a problem regarding the proud criminal involved.

For most of his life Dr Cross had been a well-born gentleman, and his friends in the area of Cork were from the aristocracy and upper classes. In fact the governor of the prison did not attend the execution because of his feelings about Cross (he sent a deputy instead).

Berry found that these friends were at the execution to give the condemned man some emotional support. Dr Cross, grateful for their attendance, wanted to stand at attention with respect to them, facing as he died. Berry, however, traditionally faced his subjects at executions towards the wall. But each time Berry turned Dr Cross to the wall, the doctor would turn around again.

For all the notice that the man he was going to kill took of him, Berry might not have been there.

Finally, an official ordered Berry to stop this silliness and allow the doctor to die facing his friends, reminding him that Dr Cross was a respected soldier. Berry did as he was told, and Dr Cross died without a word.

The reluctant hangman

James Berry

James Berry was Britain’s hangman during the latter half of Queen Victoria’s reign. A man of strange contradictions – capable of cold, callous detachment but so affected by his job that he was often unable to speak before an execution – Berry was the last hangman able to write freely about his work.

Berry was an ex-policeman who took a genuine interest in his ‘victims’ – even creating his own ‘black museum’. Aiming to be both efficient and merciful he worked to a table of drops of his own creation. Unfortunately, this did not prevent a few horrific incidents. The most notable was the execution of Robert Goodale who was decapitated by the force of the drop. In contrast, in the famous case of John Lee – “the man they couldn’t hang” – Berry was unable to open the gallows trap. After three attempts – during which the gallows trap worked perfectly when Lee was removed – Lee was reprieved.

During his eight years as hangman, Berry executed over 130 men and women – and even claimed to have hanged Jack the Ripper. He enjoyed publicity and toured the country talking of his experiences and showing lantern slides of grim prison scenes and executions. Yet in later life this contradictory character suffered from depression and became almost suicidal.

He was haunted by nightmares of the people he’d killed and eventually became a preacher and ardent campaigner against capital punishment