References on Using Human Beings Instead of Non-human Primates
The following are just a few references that involve people for studies that are being conducted on non-human primates, sometimes concurrently in the same report of a study and sometimes demonstrating substantive differences between the species. These provide evidence to argue against the need for non-human primates when the researchers are getting the same information from ethical studies involving people. They are listed by descending date of publication.
To date, projections from DPPC to M1 grasp zone have been identified in monkeys and have been postulated to exist in humans based on clinical and transcranial magnetic studies. This work uses diffusion-MRI tractography in two samples of right- (n = 50) and left-handed (n = 25) subjects randomly selected from the Human Connectome Project. … Together, these results support the existence of a direct sensory-parietal-motor loop suited for fast manual control and more generally, for any task requiring rapid integration of distal sensorimotor signals.
Peripersonal space (PPS) is a multisensory representation of the space near body parts facilitating interactions with the close environment. Studies on non-human and human primates agree in showing that PPS is a body part-centered representation that guides actions. Because of these characteristics, growing confusion surrounds peripersonal and arm-reaching space (ARS), that is the space one's arm can reach. Despite neuroanatomical evidence favoring their distinction, no study has contrasted directly their respective extent and behavioral features. Here, in five experiments (N = 140) we found that PPS differs from ARS, as evidenced both by participants' spatial and temporal performance and by its modeling. We mapped PPS and ARS using both their respective gold standard tasks and a novel multisensory facilitation paradigm.
Here, we performed a cross-species transcriptomic comparison of human and rhesus placenta and determined that while the majority of human placental marker genes (HPGs) were similarly expressed, 952 differentially expressed genes (DEGs) were identified between the two species. … Overall, our findings help elucidate the molecular translatability between human and rhesus placenta and reveal notable expression differences in several HPGs and genes implicated in pregnancy complications that should be considered when using the rhesus animal model to study normal and pathological human placentation.
This study confirmed that there are large differences in hydrolase activities between humans and marmosets…The data obtained in this study may be useful for considering whether marmosets are appropriate for examining the pharmacokinetics and efficacies of new chemical entities in preclinical studies.
The overall predictivity of the RAF [relative activity factors] approach is consistent with that of the relative expression factor (REF) approach. As the established model can predict Kp,uu,brain and Kp,uu,CSF using only in vitro and physicochemical data, this model would help avoid ethical issues related to animal use and improve CNS drug discovery workflow.
We here applied repetitive pneumatic stimulation of digit 1 (D1; thumb) and digit 5 (D5; little finger) on both hands to investigate finger/hand representation maps in the complete S1, but also in cytoarchitectonic Areas 1, 2, 3a, and 3b separately, in 21 healthy volunteers using 3T fMRI.
Furthermore, we stratified a cohort of 49 patients with autism and 72 healthy controls of 1112 subjects using functional connectivity patterns, and identified dysconnectivity profiles similar to those in monkeys.
Mice were also used to get tissue. Not sure if this is something that would have to be done every time or if it was just to set things up this time.
Staphylococcal enterotoxin type B (SEB) is associated with food poisoning. Current methods for the detection of biologically active SEB rely upon its ability to cause emesis when administered to live kittens or monkeys. This technique suffers from poor reproducibility and low sensitivity and is ethically disfavored over concerns for the welfare of laboratory animals. The data presented here show the first successful implementation of an alternative method to live animal testing that utilizes SEB super-antigenic activity to induce cytokine production for specific novel cell-based assays for quantifiable detection of active SEB.
Spontaneous and movement-related GPi field potentials were recorded from DBS leads in 5 externalized PD patients on and off dopaminergic medication, as well as from 3 rhesus monkeys before and after the induction of parkinsonism with the neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine.
These results provide the first large-scale description of population-average brain skews and their inter-individual variations, their replicable associations with handedness, and insights into biological and other factors which associate with human brain asymmetry.
The functional definition of the two hand-knob sectors, within a large cohort of patients, show they potentially play different roles in motor control suggesting that the human hand-knob is an anatomo-functional heterogeneous region organized along a motor-cognitive gradient.
Serum from various human donor cohorts was obtained with Ethics committee approval and informed consent obtained from BioIVT (Hicksville, NY) normal healthy adults (n = 6), adults with =1 sexual partner (n = 30), pediatric donors (age 1–5 days; n = 10), HPV+ serum from cervical cancer patients at CIN2/3 staging (Proteogenex Inglewood, CA; n = 3)…
The results revealed significant species differences regarding qualitative and quantitative aspects of microsomal metabolism. None of the tested animal species fully matched human microsomal metabolism of the three A1AR ligands. … Surprisingly, rhesus macaques appear unsuitable due to large differences in metabolic activity towards the test compounds. [emphasis added]
Specifically, black letters on a white background (high contrast between figure and ground) are judged to be taller than gray letters and gray pseudoletters on a white background (low contrast between figure and ground) for adult humans. In the current study, we assessed whether this effect would extend to nonverbal stimuli (shapes) such that high-contrast shapes would lead to greater size estimates relative to low-contrast shapes for human children and rhesus monkeys in a two-choice discrimination task.
The dorsal hippocampal commissure (DHC) is a white matter tract that provides interhemispheric connections between temporal lobe brain regions. Despite the importance of these regions for learning and memory, there is scant evidence of a role for the DHC in successful memory performance. We used diffusion-weighted magnetic resonance imaging (DW-MRI) and white matter tractography to reconstruct the DHC in both humans (in vivo) and nonhuman primates (ex vivo). … These findings highlight a potential role for the DHC in recognition memory, and our tract reconstruction approach has the potential to generate further novel insights into the role of this previously understudied white matter tract in both health and disease.
2020-03-04: Barrett, Rachel L.C.; Dawson, Matthew; Dyrby, Tim B.; Krug, Kristine; Ptito, Maurice; D'Arceuil, Helen; Croxson, Paula L.; Johnson, Philippa J.; Howells, Henrietta; Forkel, Stephanie J.; Dell'Acqua, Flavio and Catani, Marco. "Differences in Frontal Network Anatomy Across Primate Species" The Journal of Neuroscience 40(10):2094-2107.
Twenty-six children (ages 5-12 years, 17 females) and 28 adults (ages 22-28 years, 14 females) participated in our study. … MRI data were collected using a 3 T GE scanner in the Center for Cognitive and Neurobiological Imaging at Stanford University.
We collected three-dimensional trunk kinematic data during bipedal walking in six humans and five Japanese macaques. The human subjects walked on a treadmill, and the animal subjects walked on a 5-m runway.
Donor human eyes (n = 3) were obtained within 24 h postmortem and all donated material was free of any known retinal pathology and contained no obvious ocular trauma or undiagnosed retinal injury at the time of tissue isolation.
Six healthy male subjects were each administered a single oral dose of 60 mg [14C]-deflazacort. Plasma and urine were collected and deflazacort metabolites in plasma were quantified by high performance liquid chromatography radio-profiling followed by liquid chromatography-mass spectrometry characterization.
While we could match several marmoset and human resting-state networks based on their functional fingerprints, we also found a few striking differences, for example, strong functional connectivity of the default mode network with the superior colliculus in marmosets that was much weaker in humans. Together, these findings demonstrate that many of the core cortico-subcortical networks in humans are also present in marmosets, but that small, potentially functionally relevant differences exist.
A clinical study in overweight human participants demonstrated that a single dose of BFKB8488A caused transient body weight reduction, sustained improvement in cardiometabolic parameters, and a trend toward reduction in preference for sweet taste and carbohydrate intake.
These results suggest that the functional roles of UDP-glucuronosyltransferase (UGT) enzymes expressed in the liver and intestines in the metabolism of BPA extensively differ among humans, monkeys, dogs, rats, and mice.
…we used high spatial resolution 7T fMRI to study the response to thermonoxious skin stimulation. We observed the predicted response of BA3a in the depth of the central sulcus in five human volunteers. … Ablation of this region has been shown to reduce pain sensibility and might offer an effective means of ameliorating some pathological pain conditions.
Here, we examined nonadjacent dependency processing in common marmosets, chimpanzees, and humans using "artificial grammars": strings of arbitrary acoustic stimuli composed of adjacent (nonhumans) or nonadjacent (all species) dependencies.
Forty neonates (15 female, 25 male; mean gestational age at birth = 38.99 weeks, gestational age range at scan = 37-44 weeks) were obtained from the initial release of the Developing Human Connectome Project (dHCP, http://www.developingconnectome.org) . … Forty adults (15 female, 25 male; age range 22-36 years) were obtained from the Human Connectome Project (HCP), WU-Minn HCP 1200 Subjects Data Release (https://www.humanconnectome.org/study/hcp-young-adult) .
The IM [potential immunogenicity] of inotersen in humans was evaluated in a pivotal phase 2/3 clinical study in patients with hereditary TTR [hereditary transthyretin] amyloid polyneuropathy (hATTR-PN).
The HIV-ART-vedolizumab-ATI (HAVARTI) trial is a single-arm, dose-ranging pilot trial in healthy HIV-positive adult volunteers receiving ART. Twelve consenting persons will be enrolled in sequential groups of 4 to each serial dosing vedolizumab regimen (300 mg, 150 mg, 75 mg). The primary outcomes are: (1) to assess the safety and tolerability of seven serial infusions of vedolizumab at each of three doses; (2) to identify the immunovirological measures, including pVL and T-cell kinetics, that characterise HIV/ART cases before, during, after vedolizumab treatment and ATI; and (3) to seek SVR of pVL after ATI. Secondary outcomes will include immune reconstitution and pVL suppression as well as immune reconstitution and long-term safety following re-initiation of ART in the absence of SVR.
We studied patients with medial or lateral thalamic lesions (likely involving either the MD [medio-dorsal] or the ventrolateral (VL) nuclei). Patients performed a double-step task testing motor updating, a trans-saccadic localization task testing visual updating, and a localization task during fixation testing a general role of motor signals for visual space in the absence of eye movements.
The goal of the present experiments was to determine whether electrophysiologic response properties of the ON and OFF visual pathways observed in animal experimental models can be observed in humans.
…two key properties of ON versus OFF pathways found in single-unit recordings are recapitulated at the population level of activity that can be observed with scalp electrodes, allowing differential assessment of ON and OFF pathway activity in human.
Here we present results from a novel behavioral task in which both monkeys (Macaca mulatta) and humans localized visual and auditory stimuli and reported their perceived sources through saccadic eye movements.
We describe the remarkable case of a medically healthy right-handed 15-year-old boy who developed an ischemic infarct of the banks of the right parieto-occipital sulcus (POs). … We describe the neuroanatomy and neurophysiology of the dorsal visual stream and correlate the localization of this type of infarct in our patient with the known functional neuroanatomy. Although lesional studies in Macaque monkeys and functional MRI studies in humans have documented the clinical-functional correlations of POs lesions and perceived motion deficits, our case is one of the very first human cases in the literature that pinpoints the Zeitraffer phenomenon to a specific and strategic circumscribed ischemic stroke in the region of the POs.
We studied the impact or early cerebellar damage on long-term functional recovery in three groups of 15 posterior fossa survivors, comparable with respect to their tumour characteristics (type, size and location) but operated at different ages…
Here we attempted to induce plastic changes in the LLSR [long-latency stretch reflex] by pairing noninvasive stimuli that are known to activate reticulospinal pathways, at timings predicted to cause spike timing-dependent plasticity in the brainstem. In healthy human subjects, reflex responses in flexor muscles were recorded following extension perturbations at the elbow.
These data suggest that human IgE binds with different characteristics to human and cynomolgus monkey IgE effector cells. This is likely to affect the potency of IgE effector functions in these two species, and so has relevance for the selection of biologically-relevant model systems when designing pre-clinical toxicology and functional studies.
Human safety and tolerability and pharmacokinetics
In order to establish the tolerability of TPA023B, fasted, healthy young (18–45-year-old) male volunteers were given single doses of drug (ranging from 0.05 to 3?mg administered as dry-filled capsules) and then monitored clinically according to standard procedures. Blood samples were obtained at various times (1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120 and 144?h) after dosing for subsequent analyses of plasma drug concentrations.