Healing through faith: meeting a chaplain coupled with biblical readings could produce lymphocyte changes that correlate with brain activity (HEALING study)

Study design

The following randomized, parallel, open-labeled, controlled clinical trial study design was used:

For the graphic overview of the study design presented above, see Figure 1.

Figure 1. Healing Study design.

“1.” and “2.”: blood samples.

A total of 351 patients were screened for eligibility, 60 were randomized. Data from three patients were excluded from further analysis, because their medical condition required acute usage of oral NSAID/metamizole sodium. We analyzed results for a total of 20 patients in the bedside group (with an enrollment rate of up to two patients per week - Healing I), 18 patients in the chapel group (with an enrollment rate of three to five patients per week - Healing II), and 19 patients in the control group; we analyzed data from 57 patients in total. Of these, 22 patients were subjected to fMRI. We reported one technical failure to analyze fMRI data from one patient (the first patient in the chapel group), although the event was non-recurring. No other exclusion or loss of data occurred after randomization.

Measurements in the chapel (n = 18) occurred in five independent groups (minimum of three, maximum of five patients in each group). In three of the five groups (for 11 patients), we gave patients the option to receive communion: Catholic Eucharist, or Reformed Lord’s Supper. Of the 11 patients, five opted to receive Catholic Eucharist (four patients) or the Reformed Lord’s Supper (one patient).

The complete date range for participant recruitment was from 10 September 2015 to 2 January 2017; the nature of the interventions did not require follow up after 2 January 2017. There were no changes in trial outcome or methods after the trial commenced. The trial was stopped once the number of planned enrollments was met. We identified no harm or unintended effects on patients during or after the study.

For an overview of the enrollments, see HEALING study’s CONSORT Flow Diagram (cf. Figure 1 in the Extended data).

The complete protocol was approved by the Hungarian Medical Research Council’s Committee for Research Ethics (Appr.: 7245-1/2014/EKU (55./2014), authorization number: SOR/074/00130-4/2014), and our institutions’ Internal Ethical Boards (IG/02013-003/2015; 270/2015). Written informed consent was obtained from all participants. The research was conducted according to the principles expressed in the Declaration of Helsinki.

Enrollment

Inclusion criteria were: adult age (>18 years), being hospitalized, the ability for verbal communication, alertness, orientation, no sign of psychosis in their medical history, and willingness to participate in the study after written, informed consent. The hospital’s Infectious Diseases and Nephrology Wards were involved in the recruitment process. We proposed the enrollment for all patients satisfying the above criteria, except in case of any exclusion criteria. Mobility was also an inclusion criterium for the events taking place at the chapel and the fMRI measurements. Due to the chaplain’s limited time availability, not all eligible patients were able to participate in the study. The decision was based on the patient’s degree of need and willingness, as assessed by, and at the discretion of, the chaplain, using a quick stratification scoring system specifically designed to address the practical needs of this study (see Appendix 1, Extended data). Exclusion criteria were the inability to communicate verbally, psychotic state (as reported by the physician responsible for the patient), altered mental state, unwillingness to participate, active and treated malignant disease, steroid, oral non-steroidal anti-inflammatory drugs (NSAIDs) or metamizole- sodium use, since these could have influenced the measured immunological parameters.

Random assignment was based on the chaplain’s availability on the day of the measurement, rather than chance allocation of all the patients willing to be visited, so that the results of the control group were not biased by disappointments or frustrations caused by the cancellation/postponement of an anticipated visit. Thus, the atmosphere in the control group reflected the genuine psychological environment of a common day at the hospital, undisturbed by out-of-the ordinary events. The randomized control group consisted of patients who knew the goal of the measurement but were explicitly asked to help with their participating in the control group, i.e., they knew they were controls and that they weren’t going to meet the chaplain (by request, the encounter could be scheduled for a later occasion).

Enrollment was arranged by the investigator. In order to minimize allocation bias, a covariate-adaptive, blocked, stratified randomization method was used: block size was fixed to 19 (±1) enrollments for each group, with a 1:1 allocation ratio. For the control group we enrolled patients whose diagnoses and number of days in the hospital was similar to the intervention groups, in order to ensure a good balance of participant characteristics, as the intervention groups were saturated.

Personal encounter with the chaplain with listening to the biblical passage, and psycho-immunological measurements

The same passage was read in both groups (Isaiah 40, 27-31 – see Figure 2). Among the five groups in the chapel, communion was offered to three groups: Eucharist for Catholics, and Lord’s Supper for members of the Reformed church. We asked the patients and the chaplain to complete a questionnaire designed for the study (HEALING questionnaire, preliminary pilot testing, see Appendix 2, Extended data). In the groups at the chapel, we used the validated PSS-14 score.³² We took blood samples 30 minutes prior to, and 60 minutes after the encounter; due to some anticipated differences in the length of the visits, which were about 30 minutes each, it was the time interval between the two samples that was fixed to 120 minutes. We supplemented the lab measurements with microscopic examination of the blood smears^33-35 (see Figures 4, 5, and 6), and measurements of IFNγ- (Healing I), or immunoglobulin M-, A-, G-, and C3- levels (enzyme linked immunosorbent assays), as well as some blood clotting factors (partial thromboplastin time [PTT] and international normalized ratio [INR]) (Healing II).

Figure 2. Read aloud to all patients in the bedside or chapel groups, and during subsequent fMRI-s.

Isaiah 40:27-31. New King James Version (NKJV).

Patients heard readings by the chaplain and in their native language, Hungarian, in the study.

Figure 3. Control text read to all patients in the bedside or chapel groups during fMRI-s.

“Innate (non specific) immune system” (extract). From: Szalka A, Timár L. Infektológia [Infectology]. Budapest: Medicina; 2005.

Patients heard the text read by the chaplain in their native language, Hungarian, in the study.

Figure 4. Activated lymphocytes – microscopic examination of blood smear in the Healing Study.

Figure 5. Large granuled lymphocyte (LGL) - microscopic examination of blood smear in the Healing study.

Figure 6. Small condensed lymphocyte - microscopic examination of blood smear in the Healing study.

For an overview of the measured psychological factors and immunological parameters, and the corresponding abbreviations, see Table 1.

In the case of nominal values, non-parametric, associative-tests (i.e., Kolmogorov-Smirnoff) were used; in the case of immunological parameters, a normality testing followed by a parametric, paired-samples t-test was used. For all parameters measured in the study, we performed a network-analysis using two different methods: a Bayesian analyzer developed at UTE Budapest,³⁶ and R package IsingFit [R code used: IsingFit (data, family = ‘binomial’, AND = TRUE, gamma = 0.1, plot = TRUE, progressbar = TRUE, lowerbound.lambda = NA, vsize = 10)],³⁷ followed by a correlation analysis. The usually used p value of 0.05 was divided by the number of comparisons analyzed (Bonferroni correction).

Repeated biblical readings from audiotape and fMRI measurements

Later, an fMRI examination was carried out, which was contingent upon availability of the fMRI and the capability of the patients to be mobilized. After providing written informed consent, the patients enrolled in the fMRI examination were comforted to prevent any possible anxiety related to the measuring environment (narrowness and loudness often posing a challenge for patients), given instructions on the process, then laid down into the fMRI equipment, where they could hear the reading of the study on audiotape. Patients could stop the exam at any time by pressing a button.

To examine the regions of the brain that could be impacted by the current measurement, we performed fMRI measurements using a “block-design” technique in three functional states:

The MRI examinations were performed using a 1.5T Siemens Magnetom Avanto MR scanner (Syngo software versionVB17/A, Siemens Medical Solutions, Erlangen, Germany); for the timing of the stimulation and synchronization of data collection, Nordic Aktiva v1.1. equipment (Nordic Neurolab, Bergen, Norway) was used. For all patients enrolled, a structural 3D T1-weighted axial MP-RAGE recording (TE = 4.73 ms, TR = 1540 ms, TI = 800 ms, flip angle = 15°, slice-thickness 0.8 mm, 0.9 × 0.9 × 0.9 mm voxel-size) and a 3 sec. repetition time, 145 components’ blood oxygenation level dependent (BOLD) recording sequence (T2* gradient echo, TR = 3000ms, TE = 42 ms, flip angle = 90°, interleaved 4 mm axial slice thickness, 3.6 × 3.6-pixel size) was performed. During the fMRI measurements, the stimulation always started with a 15-second-long block of silence, followed by seven sections of activation blocks for 60 seconds each. The latter constituted of a 30-second-long active, and a 30-second-long control section or silence. During the measurements, the “block design” type stimulation was performed in a “c → as → ac → as → ac → as → ac → as” sequence order for all patients.

In the first phase of processing the fMRI image database, we assigned the T1-weighted structural images’ transformation into the MNI152 atlas-space using the FSL 5.0 and ANTS 1.9 programs^38,39; using the segmentation algorithm of the FreeSurfer 5.0 software package⁴⁰ in native space, we created the so-called brain-T1 pictures, only containing the images originating from the surface of the brain. With the help of the brain-T1 pictures, we transformed the motion-corrected fMRI picture sequences into the T1-picture corresponding to the person in question, and then with the defined atlas-space transformation we transformed it into the MNI152 atlas-space.^38,39 Finally, on all fMRI image sequences, after eliminating the first four recordings containing the T1-effect, we applied an 8 mm isotropic Gaussian filtering. We used the SPM12 software⁴¹ to perform the statistical analysis on the created fMRI picture database at individual and population level. During the processing of the individual fMRI image sequences, using the a-c, a-s and s-c contrasts, we generated the statistical image databases (contrasting pictures) showing the differences between the effects of the various stimuli, which we used in the population-level analysis to statistically characterize the effect of the stimuli. Finally, we examined the differences in BOLD-answers linked to the active and control audio-stimuli, and their correlation with concrete clinical data corresponding to each patient. In the SPM analysis, in the comparison of the statistical differences between a-c, c-a, a-s, s-a, c-s and s-c activities, we sorted out the activation clusters containing a minimum of 100 voxels, with a Student-t = 3,58 threshold corresponding to the non-corrected p < 0.001 value from the SPM {T} pictures. We then used the MNI152 spatial coordinates of the cluster maximum, the maximal t-value, the corresponding FWE-corrected probability (peak-level inference), the size of the cluster and the FWE-corrected probability of the occurrence of the cluster (cluster-level inference) to characterize them.⁴¹

Part 1: Psycho-immunological changes measured after the experience of the meeting

To the question of whether they believe in God, the majority of patients (Healing I: 65%, Healing II: 77.8%) answered positively. Only 25%-38.9% of the patients responded that they actively practiced their faith. A total of 35% and 44.4% of the patients reported cathartic, or a very positive experience at the end of the measurement (maximal rating of 5/5 at Question “AI” in the HEALING “after” questionnaire, i.e., the patient’s overall satisfaction with the visit, as reported on a single item rating scale). 60% and 66.7% reported the visits to be deeply emotional (rating of minimum 4/5 at Question “AVI” in the HEALING “after” questionnaire, i.e., the patient’s assessment on the emotional depth of the encounter, as reported on a single item rating scale).

Although changes in immunological parameters appeared to show tendentious deviations in both groups (bedside and chapel, see Figures 7 and 8), after Bonferroni correction, these changes were not statistically significant. Of note for further research, it was the personal, one-to-one meetings, and not the group sessions that showed an albeit unsignificant, but considerable, small effect size in lymphocyte changes, consistently across the measurements: effect size for dLy-abs was d = 0.23 in the bedside (Healing I), but d = 0.09 in the chapel (Healing II) group; effect size for dLy-% it was d = 0.28 with p = 0.08 by means of laboratory-, and d = 0.31 with p=0.053 by microscopic examination of blood smears, at the bedside (see p values of immune changes in Tables 2, 3, 4, Extended data). While all possible correlations were checked between the psychological and immunological parameters measured, no significant correlation emerged (see visualization of all correlations, Figures 5, and a highlight on stronger psycho-immunological correlations, Figure 6 in the Extended data).

Figure 7. Changes in lymphocyte counts in Healing I (bedside) and Healing II (chapel) study.

Columns show the number of patients. 1 – dark brown: lymphocyte count (Ly-abs) and percentage (Ly %) decreased; 2 - blue: Ly-abs and Ly % did not change in the same direction; 3 – light brown: Ly-abs and Ly % increased. Taking the control group as baseline condition (center), blue arrows indicate two possibilities to elicit change: either intervention at the bedside (arrow to the left) or intervention in the chapel (arrow to the right). Yellow arrows indicating possible trends.

Figure 8. Columns show the number of patients with lymphocyte count decrease, no change and increase, respectively; in case a meeting took place, numbers above the columns indicate the average of subjective scores (from 1 to 5) by which the artists (SHoRT) or the chaplain (HEALING) evaluated the encounter.

Part 2: Results of the fMRI measurement

We obtained evaluable functional Magnetic Resonance Images (fMRIs) from a total of 21 patients in the second part of the study.

The comparison of the “active biblical reading (a)” block with the “reference silence (c)” block showed significant (p < 0.001) activation in the right- and left BA 22 (Wernicke) and right- and left BA41 (Primary Auditory) areas solely. The comparison of the “scientific control (s)” block with the “reference silence (c)” block showed significant (p < 0.001) activation in the same areas solely. The comparison of the “active biblical reading (a)” block with the “scientific control (s)” block during fMRI did not show any demarcated brain area that would have a significantly different activity among all patients (see Figures 2-4, Extended data).

After that, we performed several subgroup analyses to explore the correlations between the psychological factors or the immunological parameters, and the changes in fMRI activities between the “active biblical reading (a)” and the “scientific control (s)” blocks. We created the subgroups of patients according to the extent of the change that was measured in the psychological factors (chaplain’s overall satisfaction with the visit – “PI” – and patient’s overall satisfaction with the visit and on the emotional depth of the encounter – “AI”, “AVI” - as reported on the single item rating scales corresponding to the questions of the HEALING “after” questionnaire), or the immunological parameters (changes in the lymphocyte count [dLy-abs], percentage of lymphocytes [dLy%], and lymphocyte/neutrophil ratio [dLy/Neut], values as measured automated laboratory, changes in the percentage of large granulated lymphocytes [dLGL%] as measured with microscopic examination of blood smears). The subgroups contained approximatively similar (half-half) number of patients.

It was solely among the dLy-abs subgroups that there showed to be a tendency in regards to the change in fMRI activity. We found a weak difference between activity in the area of leftBA39 between the subgroup of patients who showed an increase in lymphocyte counts, versus the subgroup of patients who showed no relevant increase in lymphocyte counts (p = 0.393). No other psychologic or immunologic pair of subgroups showed any difference in regards of their change in fMRI activity.

After that, we aimed to correlate the dLy parameters with the areas showing change in the fMRI activity (still for the changes in fMRI activities between the “active biblical reading (a)” and the “scientific control (s)” blocks only). An invert linear correlation emerged (p = 0.019 with dLy%, p = 0.003 with dLy-abs) between the change in activity of the left BA39 area and the change in lymphocyte counts (see Figures 9 and 10; p = 0.003, r = -0.9584). Finally, we performed the correlation analysis between the change in fMRI activity between the “active biblical reading (a)” - “scientific control (s)” periods, and the dNeut, dLy/Neut, AI, AVI, and PI factors or parameters, but we found no significant correlation.

Figure 9. dLy-abs vs. a-s fMRI at leftBA39.

Change in lymphocyte count (“dLy”) versus difference between activation during the active biblical reading “a” and the scientific control “s” block (“response”) during fMRI at the leftBA39.

Figure 10. dLy vs. fMRI at leftBA39.

Change in lymphocyte count (“dLy”) versus difference between activation during the active biblical reading “a” and the scientific control “s” block (“response”) during fMRI at the leftBA39 (p = 0.003, r = -0.9584).

Accounting for both the correlation analyses and the subgroup analyses, altogether we examined only 12 factors or parameters, and therefore the level of significance was 0.05/12 = 0.00417. The correlation between the left BA39 area and change in lymphocyte count remained significant after the Bonferroni correction.

Limitations

Our study has several limitations.

First, the small sample size does not allow to extrapolate far-reaching conclusions; however, it is noteworthy that the sample size reaches or exceeds that of previous basic psycho-neuro-immunological^13–17 and is standard in basic fMRI studies.^27–29

Second, patients were being treated for various illnesses while immersed in a clinical environment. However, the exact goal of the study was to know whether patterns marked enough to overwrite the heterogenicity of diagnoses could be elicited by the meetings. The diversity of the patients’ psychological and somatic conditions was managed by the encounter-centered study design, and the time interval between both data collections was relatively small (two hours, as to follow the beforementioned literature’s ranges for time intervals^13,16,18), as compared to the length of the patient’s stay in the hospital (ranging from several days, up to weeks). The difference between the control and the intervention groups did not affect the main, significant result found with fMRI examinations, since that part of the study was performed within an auto-control setting, i.e., only the patients previously visited by the chaplain were brought to the fMRI, and their results were not compared to those of the non-visited group, but it was their own registrations during the scientific reading and their own reference states of silence that served as control.

Finally, the limitations of all studies on spirituality are related to general concerns over their reproducibility. The study design of the current measurement addressed this issue by putting a strong emphasis on assuring that the encounters remain as authentical as possible for the intervention groups (large room left for the chaplain’s spontaneity), and by reproducing the genuine atmosphere of a usual day in the hospital for the control group (open randomization based on the chaplain’s availability instead of chance allocation causing disappointments).

The term “spiritual experience” refers to a very broad range of collective and personal experiences, and its neural aspects (“neural correlates of spirituality”) seem to heavily depend on the study design that is used to record them (cf. “Mystical experience in the lab”⁴²). As Andersen et al. state, “while studying powerful mystical experiences in believers in a controlled environment would enable researchers to identify, isolate and analyze central aspects of the phenomenon, we need an experimental setting with the power to actually elicit spontaneous mystical experiences”. In line with this, the demarcability of the spiritual experiences’ neural imprint appears to depend on whether the nature of the experience itself is on the less (for ex., the recitation of Buddhist scriptures, by monks²⁷) or the more (for ex., the recalling of the most intense mystical experience one ever had in her religious life, by nuns⁴³) subjective side of the spectrum. While an abundance of relevant literature elaborates on what happens with the “self” during meditation,⁴⁴ mindfulness,⁴⁵ or praying,²⁸ the current study intentionally investigated a different area of the spiritual experience, by conceptualizing the spiritual experience in terms of meeting with a significant other. Our standpoint was that the spiritual experience is fundamentally not, or not just a different state of mind, but the opportunity to transcend one’s “self” through meeting a significant other person. Although additional, secondary effects of meditation or praying cannot be excluded when a patient is visited by a chaplain (at times, patients are occasionally given the opportunity to pray or to meditate on a biblical passage), this study was not so much focused on the effects of these adjunct elements, but on the even involuntary effects of an interactive, direct meeting with a person of faith.

From this followed the main methodological challenge of this study, which was that genuine meetings with chaplains in hospitals always contain a spontaneous (“inspired”) element. Right from their initiation, such authentic meetings are always based on the chaplain’s intuition, and this spontaneous element has a major effect on the whole meeting - and hence on any psycho-neuro-immunological imprint, would there be any. The large room left for the chaplain’s inspiration reflects the original setting of the biblical times in which the “Word of God” was firstly said, when such meetings happened as a spontaneous act of the participants - i.e., this is also how Jesus met people. Had we taken this spontaneous element out, we would have suffocated the very phenomenon of which we were trying to estimate the potential psycho-neuro-immunological imprint. The question raised was whether meetings with a chaplain can elicit immunological changes in patients, if these meetings are left as authentical, as spontaneous as they originally are. This methodological decision to leave the spontaneous element in, did not affect the reproducibility of the study - to the contrary, by proposing the possibility of the meeting for every patient available on a ward on the day of the measurement, by establishing a rough order for the visits (“HEAL Score”) to help manage the time available, but by always leaving to the chaplain the final choice for the patient she intends to visit, and only asking the chaplain to include the same biblical passage in every spontaneous meeting: these are the ways this study proposes to be reproducible.

Taking Salopek’s “slow journalism” concept as a model [he makes a 21,000-mile-long journey (33.780 km) by foot, to retrace the pathways of our ancestors, the first humans who migrated from Africa and journeyed around the Earth - he posits that one must devote time to inter-personal connections in order to fully comprehend the human phenomenon - “Out of Eden Walk,”⁴⁶], we consciously stood for the concept of “slow science” for a slow pace of methodology. It was the consciously slow pace of enrollment, together with the ecumenical atmosphere of the study, that served to reinforce the authenticity of the encounters. For example, in the case of two patients, both were challenging to transport – we took them with their entire beds in the elevator to the hospital chapel, located one floor beneath the Infectious Disease Ward - somehow evoking the biblical scene of the four men who brought their paralytic friend down the roof, lowering him with cords, to let him reach Jesus through the crowd (Mk 2,4).

Psycho-immunological viewpoint

Contrary to the authors’ expectations, also grounded on preliminary scientific reviews relating faith with psychoneuroimmunology,⁴⁷ no significant psychoimmunological result emerged. The authors assume that one possible reason behind this resides in that the study could have been underpowered as relative to the small size of the changes. The other reason could be that the majority of the patients, although truly grateful for being visited, were not that motivated to meet a chaplain so as to live it as a transformative experience. If we turn our attention from mass healings to the personal healing accounts in the New Testament – the healing of a man with leprosy (Mt 8, 2-4), the healing of a sick woman with bleeding (Lk 8,43-48), the healing of the blind (Mk 10, 46-52), the healed seem to share at least a few of the following traits: their conditions were critical, often compounded by remorse and loneliness; the sick themselves, or a close relative strongly wanted their healing; and Jesus appears almost like an ultimate, last hope, last chance for them (“What do you want me to do for you?” (Mk 10,51) “Your faith saved you” (Mk 5,34), “If I can do something? Everything is possible for the one who believes” (Mk 9,23); see also Grün et Robben⁴⁸); and as a consequence, they lived their encounter with Jesus as a transformative experience. Conversely, the psychological effect was mostly not that dramatic for the patients enrolled in this study. Indeed, in spite of the thorough enrollment process, only 40% of the patients in the bedside group, and 5.5% of patients in the chapel group were given an H4 Score, showing that even among the “chosen,” the prescreened group of patients whom were evaluated with the HEAL Score, it is only this tiny fraction of patients that the chaplain was absolutely sure they needed her visit. The PSS-14 scores reveal that their average level of stress in the month preceding the measurement was not outstandingly high (the PSS-14 had a mean value of 27/56), and their responses to the Healing Questionnaire showed that the psychological or physical wounds incurred through their daily lives were not perceived to be that deep either (see Tables 2, 3, and 4, Extended data). The only psychological factor that showed an - albeit weak - correlation with any immunological parameter, was the blaming of oneself (answer “BI2_b”, i.e. “It is my fault that I became sick. I blame myself …” to the question on whether the patient feels responsible for his chronic illness (es)) – yet this was one of the rarest answers among the patients (10% to 22% of the patients, in the bedside (Healing I) and chapel (Healing II) group respectively). In other words, by the time the visit arrived, most of the patients were not so wounded in their personal lives so as to experience the visit as a life-altering event. Patients were open to the visit but their feelings of being exhausted and their need for help mostly concerned their current situation of being hospitalized.

Although the measured immune changes were too small to be clearly distinguishable from other clinical effects, it is noteworthy that the results from the adult’s hospital bed show a striking similarity with those of the “ShoRT study”, where the children from whom blood samples were drawn in a non-painful way through branules, were visited by Smiling Hospital artists [SHoRT²¹]. It was once again the more successful visits that generated more marked changes in lymphocyte counts. However, the growing inconsistency in lymphocyte changes as patients got closer to the chapel, and especially the results of the group receiving communion (without exception in this subgroup, we measured decrease in lymphocyte counts, which is usually considered as sign of stress in the psycho-neuro-immunology literature; see Figure 7), could refer to the sense of fascination and admiration mixed with tones of fear, as reflected by the psychological or religious term tremendum (see Rudolf Otto’s terminology of the “numinous” and “mysterium tremendum et fascinans” to describe the experience of the holy⁴⁹). While the primary purpose of the intervention was to elicit positive emotions, the authors found that the same biblical reading could cause a wide range of thoughts and feelings, and different facets of the same emotional pattern could be amplified; this included fear of God, a recurrent motive of biblical encounters between God and man. For instance, in the Book of Exodus, God says to Moses: “I will make all my goodness pass before thee … Thou canst not see my face: for there shall no man see me, and live.” (Exodus 33, 19-20, KJV). More measurements are needed to map the main emotional themes at play during meetings with a chaplain and to clarify the statistical significance of these observations.

Neurological viewpoint

First and foremost, it is worth noting that the most easily implementable technically, entailing the least possibility of error in the laboratory measurement, and automated lymphocyte count showed significant correlation with the fMRI results. This part of the study was not affected by the any unintended bias in the randomization process, since the fMRI part of the study was performed within an auto-control setting, for visited patients only. Yet, as Lieberman and Cunningham pointed out, whenever fMRI is used as a principal tool in a research setting, the number of measurements performed during each examination are so high that from a statistical point of view, even the use of the most conservative p values cannot rule out the possibility of type I errors, rendering the results of every fMRI study only meaningful following comparison with previous, and verification by subsequent studies, in case these also support the interpretations proposed.⁵⁰ The current paper discusses a plausible interpretation of the findings while further research is needed to confirm the results.

Given that we could not rule out potential effects of magnetic resonance on immunological parameters from the fMRI examination, we intentionally separated fMRI measurements from immunological measurements. We laid out the “block-design” setting we used based on a meta-analysis of 48 studies,⁵¹ and works by Leff et al.,⁵² and Beaucousin et al.,⁵³ who described different activation patterns on the fMRI of patients exposed to readings featuring different emotional content.

The fact that the comparison of the “a”-“c” and “s”-“c” periods resulted in a significant change in fMRI activity of the Primer Auditory Areas, whereas no such difference was detected when comparing “a” and “s”, proves that the measurement was physiologically trustworthy: the patients heard the biblical readings, and control text likewise.

Since the study design intentionally left a large space for spontaneity and subjectivity, it is not surprising, in the hindsight, that no distinct brain area emerged when comparing the “a” and “s” periods. As stated above, the spontaneous meetings with a person of faith are on the most subjective, the most colorful and hence the less generalizable part of the spiritual experiences’ spectrum. We would have probably found general differences in brain areas between hearing a religious recitation and a neutral/scientific recitation among all participants, if the intervention group was composed of participants highly trained in meditation, for ex. Buddhist monks. The participants of the HEALING study were ordinary people with various religious background, that probably resulted in more subjective differences in the way they perceived a sacred text.

There were no general differences that could be unanimously detected among all the patients between the active prayer block and the control block, so hearing a religious recitation did not affect the brain differently than a neutral/scientific recitation, unanimously for all the patients enrolled – but the main finding of the study is that a significant correlation emerged between lymphocytes and brain activity of the active minus scientific control block. This finding totally echoed previous psycho-immunological findings mentioned in the Introduction, especially results by Bennett et al.¹⁶ who found no general immunological changes following the presentation of a humorous videotape for healthy volunteers, but measured a significant correlation with change in immune parameters when they found a way to somehow quantify how the video was subjectively perceived by the patients. Their research group used Humor Response Rating Scales, to which the fMRI recordings correspond to in our study, representing different tools for the same end: to measure individual differences in the way the interventions are perceived.

It is remarkable that contrary to our expectations, although the immune parameters’ database was by many scales scarcer than the whole brain activities’ enormous database, we did not get several and obviously false positive results. The lack of general demarkable areas of activation when comparing the “a” and “s” periods reduced the chance of getting type I errors related to dense activation patterns. Just a single correlation emerged, suggesting it was reasonable not to account this result as for just a spurious effect. The sole fixed, generalizable element of the visits were the biblical readings, and consistent with this, the sole brain area that correlated with any of the measured immune parameters was involved in the understanding of these readings, as detailed below.

The biblical passage is an ancient, more than two and a half thousand years’ old text with plain words, and simple language structure, and is thought to have originally been intended to offer comfort. In contrast, the control text contained many difficult words for the layman, had long and difficult to follow sentences, and contained several words with potentially fear-inducing connotations. Thus, the result of the correlation analysis suggests the change in lymphocyte counts is related to the subjectively perceived content of the biblical reading as opposed to control text by the patients. The fact that the changes in lymphocyte counts were not significant, despite some widening in the confidence intervals, signaled that these changes were subject to limitations by the circumstances and by the disease; however, the correlation of these changes with the fMRI-s indicated that even when biblical readings did not appear to have a physiological effect, they could have an ordering, arranging effect, along some specific guiding principle, on a key parameter like the lymphocyte counts. In other words, although the lymphocyte changes’ effect size was too small to produce significant changes under the limited sample size of this study, the amplitude of their change appeared to vary along the evolution of a single parameter: the activation of the left angular gyrus.

According to neurosynth.org, previous scientific publications related to the region in the 2 mm area of the -52, -56, 26 cluster, have linked this area to the tactile and manual reconstruction of shape recognition, the learning of words, emotional speech, and the encoding of belief systems in neural pathways, and their linking with ethical decision making.^54–60 It must be highlighted that the only brain area that showed a correlation with any of the immune parameters measured in this study - the left BA39, gyrus angularis - was contralaterally the same that is activated during meditation on/recitation of Buddhist scriptures.²⁷ Although the depth of understanding could only mean cognitive understanding, due to the core nature of the phenomenon observed and the study design, it can also refer to broader spiritual experiences – which, in turn, contain cognitive and emotional components alike and are not, or only partially, subject to conscious influence.

Conclusions and clinical relevance

The results of this measurement suggest there exists a brain area the activity of which changes together with the lymphocyte counts during a meeting with a chaplain coupled with biblical readings in hospitals (for an excursus on theological perspectives, see below). Provided they accept that the visits cannot be forced, nor the success of the meetings fully anticipated, the physicians inviting a chaplain to meet their patients could consider these visits as an additional factor that could exert an influence on the patients’ lymphocyte counts, and hence alter their recovery from the disease - depending on the depth the chaplain’s core message is understood.

Excursus: theological perspectives

The authors would like to warn against interpreting the results of the study solely in terms of healing being accelerated by intimate religious experience. It is the religious sensibilities raised by the topic this measurement touched, and to avoid any potential distortions in the interpretation of the results presented above, that we feel obliged to include the theological viewpoint in the discussion of the results. The results obtained could raise root-questions: why have we not measured more immunological changes, if the “Word of God” is believed to heal? And, if lymphocyte counts are correlated with an area of the brain involved in understanding words, does that mean that those who try to understand the biblical passage better, will have more healing lymphocytes? These are theological questions also. Thus, the spiritual, religious nature of the phenomenon observed obliges the integration of the theological viewpoint in the careful interpretation of the results.

For centuries in the European tradition, theology – originally in close association with other areas of the basic scholar fields “septem artes liberales” (seven liberal arts) - has been the delegated branch of academic studies as far as any aspect of the Bible was involved. More recently, modern research methodology has been embraced, especially by the reformed theologians of 20-21^th centuries’ academic Christian theology, rendering it a branch of science only differing from other specialties by the principal focus of its observations being the “Word of God” instead of the natural world.³¹ This legitimizes the examination of how findings relate to the relevant theological literature in the discourse of a study involving religion, especially in the case of a study which used a biblical passage at its core.

When one is examining the effect of the Word of God on man, trying to correlate it with any human parameter, dialectical theologians immediately emphasize the inherent asymmetry in the relationship between God and man. As Tillich submitted, we cannot control God with our will: “The experience of Spiritual presence does something that the human soul in itself cannot”⁶¹ Thus, the theologian points out that the immunological and neurological changes described in the measurement did not happened to the patient’s efforts, but without their knowing it. The content itself of the biblical message does not hold the promise of immediate physical healing. According to the Bible, Jesus’ healings give the impression that those had a signal value. Jesus did not heal everybody (cf. the account of the healing at Lake Bethesda, Jn 5, 1-9), and in a critical moment he himself accepted his own death. There are instances when Jesus’ Gospel has been theorized to give strength not just to overcome the disease, but to endure it. Nevertheless, correlation also exists in theology. Tillich wrote: “The answers emerging from the event of revelation are comprehensible only if they are in correlation with the questions of our whole existence, the existential question.”⁶¹ Tillich used the method of correlation mainly in respect of the dialogue between the Christian message and the contemporary society (culture). The present paper describes how the method of correlation can also be used in the dialogue between natural sciences, social sciences and theology. Indeed, in Christian religion, the encounter between God and man can take place within a human relation, or also during a biblical reading, i.e., listening to the “Word of God”.³¹ In this context, the meeting with the chaplain could trigger the recollection of some genuine, primordial experience of meeting with the transcendent, a phenomenon that could be the expression of ancient, maybe even pre-Christian patterns buried in our collective subconscious, and bringing up ancient, genuine, instinctive reactions, according to Jung’s concept on the working mechanism of “archetypes”, i.e., of inherited inner patterns buried in the collective subconscious.⁶² The simultaneous change of the nervous and immune systems that was recorded in the present study during repeatedly listening to the Bible, confirms the possibility that in addition of the psychological effects, general biological patterns could also be activated during the meeting of God and man. In line with this concept, beyond the personal healing stories, the Bible’s synoptic contain numerous accounts of mass healings – i.e., Mt 4,24.8,16.12,15.14,14.15,30.19,2.21,14; Mk 6,56; Lk 4,40.9,11 – giving the impression that the meeting with Jesus also brought about general healing effects in people.

The contradiction presented above – namely, that the Word of God would be healing, whilst the main message of the Word sometimes does not bear healing, but cross – is solved if we put the question and the results of our study in the context of modern theologians’ evolutionary theory, which states that religiousness and life of faith also have developmental aspects, therefore can be understood as having an evolutionary dimension, with a direction of growth, at times including the notion of suffering through the process (see Whitehead⁶³ and “process theology”), and thus cannot be considered as opposed to the natural sciences’ concept of evolution.

According to Pannenberg, “at the end of the 19^th century in the first half of the 20^th, sadly, Christian churches and theologians could not recognize that the teaching of evolution gives an unprecedented possibility for theology in regards of the possibility of its relationship with modern science. The fight against Darwinism was one of the mistakes resulting in the most serious consequences during the history of the relation of theology with sciences.”⁶⁴ The findings of the current study can be a small contribution to support this position, and put a novel lighting on the fact that, despite the lack of significant and noticeable biological effects, some form of religious belief could so indefatigably spread over and survive in the whole human species up until that day. If indeed, depending on the depth of spiritual understanding, the religious experience could influence the lymphocyte count, then it could contribute to prevent or recover from the diseases, hence provide an evolutionary advantage in the sense the natural sciences use this term. On the other hand, from the theologian’s perspective, the goal of evolution is not the survival and accommodation in the narrow sense of the word. Teilhard de Chardin wrote: “as early as in St. Paul and St. John we read that to create, to fulfill and to purify the world is, for God, to unify it by uniting it organically with himself”, and God is “from this point of vantage in the heart of matter, assuming the control and leadership of what we now call evolution.”⁶⁵ He states that “through human socialization, whose specific effect is to involute upon itself the whole bundle of reflexive scales and fibers of the earth, it is the very axis of the cosmic vortex of interiorization which is pursuing its course.”⁶⁵ Pannenberg often alluded to Gods’ appearance in world history, in the person of Jesus, as an event that can be considered the portent, the anticipation of the future.⁶⁶ In this sense, healings are of signal value because they hint a precursory picture of a harmonious God-man relationship, including all its psychical and physical aspects – as Pannenberg wrote: if, “(like Teilhard de Chardin), we can consider life’s evolution as the process of the creation of life forms of increasing complexity and at the same time becoming increasingly introspective, then we can also state, that in the succession of different forms of life by the creatures, is expressed the increase in the shareholding of the divine Spirit, of life’s Spirit.” ^64,65

Faith is an evolutionary advantage, in the theological sense because the goal of evolution is the increase in the shareholding of the divine Spirit.⁶⁵ This is the end towards which the result of our measurement converges.

Underlying data

Figshare: Healing Study Beres et al. - Part 1: Psychological and Immunological Changes after meeting a Chaplain coupled with Biblical Readings among Hospitalized Patients, https://doi.org/10.6084/m9.figshare.16750384.v1.⁶⁷

Figshare: Healing Study Beres et al. - Part 2: fMRI Changes after meeting a Chaplain coupled with Biblical Readings and Recalling the Visits with Audiotapes among Hospitalized Patients, https://doi.org/10.6084/m9.figshare.16751851.v1.⁶⁸

Extended data

Figshare: HEALING Study Beres et al. - F1000Research - extended data, https://doi.org/10.6084/m9.figshare.17029715.v3.⁶⁹

Reporting guidelines

Figshare: CONSORT checklist for “Healing through faith: meeting a chaplain coupled with biblical readings could produce lymphocyte changes that correlate with brain activity (HEALING study)”, https://doi.org/10.6084/m9.figshare.17029715.v3.⁶⁹

Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).