Evaluating the ability of a locally focused culling program in removing chronic wasting disease infected free-ranging white-tailed deer in Illinois, USA, 2003-2020.

In northern Illinois, chronic wasting disease (CWD) was first identified in free-ranging white-tailed deer (Odocoileus virginianus; hereafter referred to as "deer") in 2002. To reduce CWD transmission rates in Illinois, wildlife biologists have conducted locally focussed culling of deer since 2003 in areas where CWD has been detected. We used retrospective spatial, temporal and space-time scan statistical models to identify areas and periods where culling removed higher than expected numbers of CWD-positive deer. We included 490 Public Land Survey "sections" (∼2.59 km2 ) from 15 northern Illinois counties in which at least one deer tested positive for CWD between 2003 and 2020. A negative binomial regression model compared the proportion of CWD positive cases removed from sections with at least one CWD case detected in the previous years, "local area 1 (L1)," to the proportion of CWD cases in adjacent sections-L2, L3, and L4-designated by their increasing distance from L1. Of the 14,661 deer removed and tested via culling, 325 (2.22 %) were CWD-positive. A single temporal CWD cluster occurred in 2020. Three spatial clusters were identified, with a primary cluster located at the border of Boone and Winnebago counties. Four space-time clusters were identified with a primary cluster in the northern portion of the study area from 2003 to 2005 that overlapped with the spatial cluster. The proportion of CWD cases removed from L1 (3.92, 95% CI, 2.56-6.01) and L2 (2.32, 95% CI, 1.50-3.59) were significantly higher compared to L3. Focussing culling efforts on accessible properties closest to L1 areas results in more CWD-infected deer being removed, which highlights the value of collaborations among landowners, hunters, and wildlife management agencies to control CWD. Continuous evaluation and updating of the culling and surveillance programs are essential to mitigate the health burden of CWD on deer populations in Illinois.

Spatial analysis of chronic wasting disease in free-ranging white-tailed deer (Odocoileus virginianus) in Illinois, 2008-2019.

Understanding the geographic distribution and clustering of chronic wasting disease (CWD) among free-ranging white-tailed deer (Odocoileus virginianus) populations can inform disease management practices. We used a retrospective analysis of surveillance data to evaluate CWD's spatial and temporal dynamics within 16 CWD-infected northern Illinois counties. Of 42,541 deer samples collected and tested for CWD from recreational hunter harvest between 2008 and 2019, we recorded 359 (0.84%) CWD-positive samples. We observed variability in CWD cases over time and space. By county, the median CWD-positive proportion was 0.84%, varying from a minimum of 0.14% in McHenry County to a maximum of 6.28% in Boone County. Across years, there were differences among CWD-positive proportions with a median of 0.90%, ranging from a minimum of 0.27% in 2012 to a maximum of 1.60% in 2019. We used a retrospective discrete Poisson scan statistic model to evaluate the space-time clustering of CWD-positive deer. We identified a statistically significant (p < .001) primary cluster C1 (area = 23.59 km2 ; RR = 10.48), occurring from 2010 to 2015 in the north-central part of the study area, and a secondary cluster C2, occurring from 2014 to 2019 (area = 9.27 km2 ; RR = 3.88) in the north-west of the study area. Detected CWD-positive space-time clusters suggest that the risk of CWD is not random. Space-time clusters of CWD can be used to evaluate the effectiveness of the Illinois CWD management programme. The area surrounding the older C1 cluster has undergone longer and more intense CWD management compared with C2. Currently, the older C1 cluster is no longer as high risk compared with the newer cluster C2, suggesting that management efforts in C2 should be increased. However, all CWD clusters should be targeted with surveillance, prevention and management programmes, including reducing deer densities to limit further spread of CWD.

Association of chronic wasting disease susceptibility with prion protein variation in white-tailed deer (Odocoileus virginianus).

Chronic wasting disease (CWD) is caused by prions, infectious proteinaceous particles, PrPCWD. We sequenced the PRNP gene of 2,899 white-tailed deer (WTD) from Illinois and southern Wisconsin, finding 38 haplotypes. Haplotypes A, B, D, E, G and 9 others encoded Q95G96S100N103A123Q226, designated 'PrP variant A.' Haplotype C and 4 other haplotypes encoded PrP 'variant C' (Q95S96S100N103A123Q226). Haplotype F and two other haplotypes encoded PrP 'variant F' (H95G96S100N103A123Q226). The association of CWD with encoded PrP variants was examined in 2,537 tested WTD from counties with CWD. Relative to PrP variant A, CWD susceptibility was lower in deer with PrP variant C (OR = 0.26, p < 0.001), and even lower in deer with PrP variant F (OR = 0.10, p < 0.0001). Susceptibility to CWD was highest in deer with both chromosomes encoding PrP variant A, lower with one copy encoding PrP variant A (OR = 0.25, p < 0.0001) and lowest in deer without PrP variant A (OR = 0.07, p < 0.0001). There appeared to be incomplete dominance for haplotypes encoding PrP variant C in reducing CWD susceptibility. Deer with both chromosomes encoding PrP variant F (FF) or one encoding PrP variant C and the other F (CF) were all CWD negative. Our results suggest that an increased population frequency of PrP variants C or F and a reduced frequency of PrP variant A may reduce the risk of CWD infection. Understanding the population and geographic distribution of PRNP polymorphisms may be a useful tool in CWD management.

Differential gene expression in chronic wasting disease-positive white-tailed deer (Odocoileus virginianus).

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) that affects cervid species throughout North America. We evaluated gene expression in white-tailed deer collected by Illinois Department of Natural Resource wildlife managers during annual population reduction (e.g., sharpshooting) and disease monitoring efforts throughout the CWD-endemic area of northcentral Illinois. We conducted comparative transcriptomic analysis of liver and retropharyngeal lymph node tissue samples between CWD-positive (n = 5) and CWD-not detected (n = 5) deer. A total of 74,479 transcripts were assembled, and 51,661 (69.36%) transcripts were found to have matched proteins in NCBI-NR and UniProt. Our analysis of functional categories showed 40,308 transcripts were assigned to at least one Gene Ontology term and 37,853 transcripts were involved in at least one pathway. We identified a total of 59 differentially expressed genes (DEGs) in CWD-positive deer, of which 36 and 23 were associated with liver and retropharyngeal lymph node tissues, respectively. Functions of DEGs lend support to previous relationships between misfolded PrP and cellular membranes (e.g., STXBP5), and internal cellular components. We identified several genes that suggest a link between CWD and retroviruses and identified the gene ADIPOQ that acts as a tumor necrosis factor (TNF) antagonist. This gene may lead to reduced production of TNF and impact disease progression and clinical symptoms associated with CWD (i.e., wasting syndrome). Use of candidate genes identified in this study suggests the activation of endogenous processes in CWD-positive deer, which in turn may enable earlier detection of the disease.

Inter-serotype reassortment among epizootic haemorrhagic disease viruses in the United States.

First described in 1955 in New Jersey, epizootic haemorrhagic disease (EHD) causes a severe clinical disease in wild and domestic ruminants worldwide. Epizootic haemorrhagic disease outbreaks occur in deer populations each year from summer to late autumn. The etiological agent is EHD virus (EHDV) which is a double-stranded segmented icosahedral RNA virus. EHD virus utilizes point mutations and reassortment strategies to maintain viral fitness during infection. In 2018, EHDV serotype 2 was predominantly detected in deer in Illinois. Whole genome sequencing was conducted for two 2018 EHDV2 isolates (IL41747 and IL42218) and the sequence analyses indicated that IL42218 was a reassortant between different serotypes whereas IL41747 was a genetically stable strain. Our data suggest that multiple strains contribute to outbreaks each year.

Machine learning identified an Alzheimer's disease-related FDG-PET pattern which is also expressed in Lewy body dementia and Parkinson's disease dementia.

Utilizing the publicly available neuroimaging database enabled by Alzheimer's disease Neuroimaging Initiative (ADNI; http://adni.loni.usc.edu/ ), we have compared the performance of automated classification algorithms that differentiate AD vs. normal subjects using Positron Emission Tomography (PET) with fluorodeoxyglucose (FDG). General linear model, scaled subprofile modeling and support vector machines were examined. Among the tested classification methods, support vector machine with Iterative Single Data Algorithm produced the best performance, i.e., sensitivity (0.84) × specificity (0.95), by 10-fold cross-validation. We have applied the same classification algorithm to four different datasets from ADNI, Health Science Centre (Winnipeg, Canada), Dong-A University Hospital (Busan, S. Korea) and Asan Medical Centre (Seoul, S. Korea). Our data analyses confirmed that the support vector machine with Iterative Single Data Algorithm showed the best performance in prediction of future development of AD from the prodromal stage (mild cognitive impairment), and that it was also sensitive to other types of dementia such as Parkinson's Disease Dementia and Dementia with Lewy Bodies, and that perfusion imaging using single photon emission computed tomography may achieve a similar accuracy to that of FDG-PET.

Reproductive characteristics of female white-tailed deer (Odocoileus virginianus) in the Midwestern USA.

Knowledge of reproductive characteristics of wild populations is necessary to inform responsible management decisions that promote herd health. As management, goals, and free-ranging populations change over time and landscapes, updated knowledge of reproductive characteristics are needed to inform responsible management practices. We estimated reproductive characteristics of female white-tailed deer in Illinois, including pregnancy rate, litter size, fetal growth and fetal sex ratio. We found maternal age to have an important influence on several reproductive factors. Approximately 66% of tested females (n = 3884) were pregnant and pregnancy rates increased with increasing maternal age, from 20.5% in fawns to 85.8% in adult deer. Litter size ranged from 1 to 5 fetuses per pregnant female. The average litter size was 1.9 ± 0.54 fetuses per pregnant female and also increased with age, from 1.2 in fawns to 2.0 in adults, respectively. Breeding season peaked in November with the mean estimated conception dates of fetuses varying with maternal age. Fawns conceived fetuses later in the breeding season (December 2) compared to yearlings and adults (November 11 and 8, respectively). We measured the body mass index (BMI) of all fetuses and found that litter size and female age influence fetal size. We found no bias in fetal sex ratio (average 1.0:1.0, male:female) but we observed a sex bias in fetal size (mean BMI male = 0.71, female 0.67) across all maternal age classes. A comparison of the current study and previous reports indicate that variation in maternal age within a population is an important driver of reproductive metrics, likely because maternal age and body size or condition are related. Furthermore, variation in resource availability will influence reproductive rates, especially among fawn females.

Lewy Bodies, Vascular Risk Factors, and Subcortical Arteriosclerotic Leukoencephalopathy, but not Alzheimer Pathology, are Associated with Development of Psychosis in Alzheimer's Disease.

BACKGROUND: The neuropathological correlates of psychosis in Alzheimer's disease (AD) is unclear, with some studies reporting a correlation between psychosis and increased AD pathology while others have found no association. OBJECTIVE: To determine the demographic, clinical, and neuropathological features associated with psychotic symptoms in clinically attributed and neuropathologically proven AD. METHOD: We separately reviewed two overlapping groups of clinically diagnosed (cAD) AD patients with neuropathology data and neuropathologically definite (npAD) cases (regardless of clinical diagnosis) from the NACC database, and explored the relationships between psychosis and clinical variables, neuropathologic correlates, and vascular risk factors. Delusions and hallucinations, defined according to the NPI-Q, were analyzed separately. RESULTS: 1,073 subjects in the database fulfilled our criteria (890 cAD and 728 npAD patients). 34% of cAD and 37% of npAD had psychotic symptoms during their illness. Hallucinations were associated with greater cognitive and functional impairments on the MMSE and CDR, while delusional patients showed less impairment on CDR, consistent across cAD and npAD groups. Burden of AD pathology appears to relate to presence of psychotic symptoms in the clinical AD group, but this result is not confirmed in the neuropathologically confirmed group suggesting the findings in the clinical group were due to misdiagnosis of AD. Lewy body pathology, subcortical arteriosclerotic leukoencephalopathy, and vascular risk factors, including a history of hypertension and diabetes, were associated with the development of psychosis. METHOD: Vascular and Lewy body pathologies and vascular risk factors are important modifiers of the risk of psychosis in AD.

Prion protein gene sequence and chronic wasting disease susceptibility in white-tailed deer (Odocoileus virginianus).

The sequence of the prion protein gene (PRNP) affects susceptibility to spongiform encephalopathies, or prion diseases in many species. In white-tailed deer, both coding and non-coding single nucleotide polymorphisms have been identified in this gene that correlate to chronic wasting disease (CWD) susceptibility. Previous studies examined individual nucleotide or amino acid mutations; here we examine all nucleotide polymorphisms and their combined effects on CWD. A 626 bp region of PRNP was examined from 703 free-ranging white-tailed deer. Deer were sampled between 2002 and 2010 by hunter harvest or government culling in Illinois and Wisconsin. Fourteen variable nucleotide positions were identified (4 new and 10 previously reported). We identified 68 diplotypes comprised of 24 predicted haplotypes, with the most common diplotype occurring in 123 individuals. Diplotypes that were found exclusively among positive or negative animals were rare, each occurring in less than 1% of the deer studied. Only one haplotype (C, odds ratio 0.240) and 2 diplotypes (AC and BC, odds ratios of 0.161 and 0.108 respectively) has significant associations with CWD resistance. Each contains mutations (one synonymous nucleotide 555C/T and one nonsynonymous nucleotide 286G/A) at positions reported to be significantly associated with reduced CWD susceptibility. Results suggest that deer populations with higher frequencies of haplotype C or diplotypes AC and BC might have a reduced risk for CWD infection--while populations with lower frequencies may have higher risk for infection. Understanding the genetic basis of CWD has improved our ability to assess herd susceptibility and direct management efforts within CWD infected areas.

Detection of chronic wasting disease in the lymph nodes of free-ranging cervids by real-time quaking-induced conversion.

Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of deer, elk, and moose, is the only prion disease affecting free-ranging animals. Since the disease was first identified in northern Colorado and southern Wyoming in 1967, new epidemic foci of the disease have been identified in 20 additional states, as well as two Canadian provinces and the Republic of South Korea. Identification of CWD-affected animals currently requires postmortem analysis of brain or lymphoid tissues using immunohistochemistry (IHC) or an enzyme-linked immunosorbent assay (ELISA), with no practical way to evaluate potential strain types or to investigate the epidemiology of existing or novel foci of disease. Using a standardized real-time (RT)-quaking-induced conversion (QuIC) assay, a seeded amplification assay employing recombinant prion protein as a conversion substrate and thioflavin T (ThT) as an amyloid-binding fluorophore, we analyzed, in a blinded manner, 1,243 retropharyngeal lymph node samples from white-tailed deer, mule deer, and moose, collected in the field from areas with current or historic CWD endemicity. RT-QuIC results were then compared with those obtained by conventional IHC and ELISA, and amplification metrics using ThT and thioflavin S were examined in relation to the clinical history of the sampled deer. The results indicate that RT-QuIC is useful for both identifying CWD-infected animals and facilitating epidemiological studies in areas in which CWD is endemic or not endemic.

Posterior cortical atrophy: an investigation of scan paths generated during face matching tasks.

When viewing a face, healthy individuals focus more on the area containing the eyes and upper nose in order to retrieve important featural and configural information. In contrast, individuals with face blindness (prosopagnosia) tend to direct fixations toward individual facial features-particularly the mouth. Presented here is an examination of face perception deficits in individuals with Posterior Cortical Atrophy (PCA). PCA is a rare progressive neurodegenerative disorder that is characterized by atrophy in occipito-parietal and occipito-temporal cortices. PCA primarily affects higher visual processing, while memory, reasoning, and insight remain relatively intact. A common symptom of PCA is a decreased effective field of vision caused by the inability to "see the whole picture." Individuals with PCA and healthy control participants completed a same/different discrimination task in which images of faces were presented as cue-target pairs. Eye-tracking equipment and a novel computer-based perceptual task-the Viewing Window paradigm-were used to investigate scan patterns when faces were presented in open view or through a restricted-view, respectively. In contrast to previous prosopagnosia research, individuals with PCA each produced unique scan paths that focused on non-diagnostically useful locations. This focus on non-diagnostically useful locations was also present when using a restricted viewing aperture, suggesting that individuals with PCA have difficulty processing the face at either the featural or configural level. In fact, it appears that the decreased effective field of view in PCA patients is so severe that it results in an extreme dependence on local processing, such that a feature-based approach is not even possible.

Posterior cortical atrophy: visuomotor deficits in reaching and grasping.

Posterior Cortical Atrophy (PCA) is a rare clinical syndrome characterized by the predominance of higher-order visual disturbances such as optic ataxia, a characteristic of Balint's syndrome. Deficits result from progressive neurodegeneration of occipito-temporal and occipito-parietal cortices. The current study sought to explore the visuomotor functioning of four individuals with PCA by testing their ability to reach out and grasp real objects under various viewing conditions. Experiment 1 had participants reach out and grasp simple, rectangular blocks under visually- and memory-guided conditions. Experiment 2 explored participants' abilities to accurately reach for objects located in their visual periphery. This investigation revealed that PCA patients demonstrate many of the same deficits that have been previously reported in other individuals with optic ataxia, such as "magnetic misreaching"-a pathological reaching bias toward the point of visual fixation when grasping peripheral targets. Unlike many other individuals with optic ataxia, however, the patients in the current study also show symptoms indicative of damage to the more perceptual stream of visual processing, including abolished grip scaling during memory-guided grasping and deficits in face and object identification. These investigations are the first to perform a quantitative analysis of the visuomotor deficits exhibited by patients with PCA. Critically, this study helps characterize common symptoms of PCA, a vital first step for generating effective diagnostic criteria and therapeutic strategies for this understudied neurodegenerative disorder.

Evaluation of a wild white-tailed deer population management program for controlling chronic wasting disease in Illinois, 2003-2008.

We evaluated population management programs for controlling chronic wasting disease (CWD) in wild white-tailed deer in Illinois between November 2002 and March 2008. The intervention consisted of measures of deer removal from three deer population control programs: Illinois Department of Natural Resources culling, deer population control permits and nuisance deer removal permits. We included in the analysis a total of 14,650 white-tailed deer CWD test results. These data also included location and demographic data collected from both deer harvested in the interventions as well as deer from hunter harvests and deer vehicle collisions. We quantified intervention pressures as the number of years of intervention, the total number of deer removed and the average number of deer removed per year. We accounted for temporal and spatial variations of intervention by using mixed logistic regression to model the association between intervention pressures and CWD prevalence change. The results showed that deer population management intervention as practiced in Illinois during the study period was negatively associated with CWD prevalence and the strength of association varied depending on age of deer and the measure of intervention pressure. The population management programs showed a more consistent association with reduced CWD prevalence in fawn and yearling white-tailed deer than in adult deer. Our results also suggested that frequent and continuing intervention events with at least moderate intensity of culling were needed to reduce CWD prevalence. A longer study period, however, is needed to make a more definite conclusion about the effectiveness of similar population management programs for controlling CWD in wild white-tailed deer.

The walk is never random: subtle landscape effects shape gene flow in a continuous white-tailed deer population in the Midwestern United States.

One of the pervasive challenges in landscape genetics is detecting gene flow patterns within continuous populations of highly mobile wildlife. Understanding population genetic structure within a continuous population can give insights into social structure, movement across the landscape and contact between populations, which influence ecological interactions, reproductive dynamics or pathogen transmission. We investigated the genetic structure of a large population of deer spanning the area of Wisconsin and Illinois, USA, affected by chronic wasting disease. We combined multiscale investigation, landscape genetic techniques and spatial statistical modelling to address the complex questions of landscape factors influencing population structure. We sampled over 2000 deer and used spatial autocorrelation and a spatial principal components analysis to describe the population genetic structure. We evaluated landscape effects on this pattern using a spatial autoregressive model within a model selection framework to test alternative hypotheses about gene flow. We found high levels of genetic connectivity, with gradients of variation across the large continuous population of white-tailed deer. At the fine scale, spatial clustering of related animals was correlated with the amount and arrangement of forested habitat. At the broader scale, impediments to dispersal were important to shaping genetic connectivity within the population. We found significant barrier effects of individual state and interstate highways and rivers. Our results offer an important understanding of deer biology and movement that will help inform the management of this species in an area where overabundance and disease spread are primary concerns.

The effect of primary care management on lipids testing and LDL-C control of elderly patients with comorbidities.

PURPOSE: This article presents results of a randomized clinical trial evaluating the effectiveness of the Medicare Coordinated Care Demonstration, Illinois site, on selected clinical outcomes over 36 months. PRIMARY PRACTICE SETTINGS: Interdisciplinary teams, located at primary care practices, provided case and disease management services to 999 patients. RESULTS: Intervention group patients had higher lipids-testing rates during the first 2 years than control group patients. Once tested, more than 80% of patients in both groups were retested in subsequent years. There were no differences in the percentage of intervention group patients who were in low-density lipoprotein cholesterol (LDL-C) control at program entry and at the end of 36 months as compared with control group patients (maintained control). However, a higher percentage of intervention group patients who were not in the LDL-C control at baseline were in control after 36 months as compared with control group patients (achieved control). IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: This study suggests that physician-nurse case management team care has the potential to augment the effectiveness of primary care by increasing adherence to testing protocols among elderly patients with multiple chronic illnesses, but this effect diminishes over time as guidelines are adopted into general practice. It suggests that LDL-C therapeutic control can be improved through increased lipids testing and the use of lipid-lowering medications. The results also indicate that care management strategies targeting more intensive patients versus less intensive patients are cost-effective strategies that can be expanded beyond lipids testing and control to other clinical health status measures.

Prion sequence polymorphisms and chronic wasting disease resistance in Illinois white-tailed deer (Odocoileus virginianus).

Nucleic acid sequences of the prion gene (PRNP) were examined and genotypes compiled for 76 white-tailed deer from northern Illinois, which previously tested positive for chronic wasting disease (CWD), and 120 negative animals selected to control for geographic location and age. Nine nucleotide polymorphisms, seven silent and two coding, were found in the sampled population. All observed polymorphisms except two of very low frequency were observed in both negative and positive animals, although five polymorphic loci had significantly different distributions of alleles between infected and non-infected individuals. Nucleotide base changes 60C/T, 285A/C, 286G/A and 555C/T were observed with higher than expected frequencies in CWD negative animals suggesting disease resistance, while 153C/T was observed more than expected in positive animals, suggesting susceptibility. The two coding polymorphisms, 285A/C (Q95H) and 286G/A (G96S), have been described in white-tailed deer populations sampled in Colorado and Wisconsin. Frequency distributions of coding polymorphisms in Wisconsin and Illinois deer populations were different, an unexpected result considering the sampled areas are less than 150 km apart. The total number of polymorphisms per animal, silent or coding, was negatively correlated to disease status. The potential importance of silent polymorphisms (60C/T, 153C/T, 555C/T), either individually or cumulatively, in CWD disease status has not been previously reported.

Evaluation of a primary care nurse case management intervention for chronically ill community dwelling older people.

AIM: The purpose of this study was to test the effectiveness of a collaborative primary care nurse case management intervention emphasising collaboration between physicians, nurses and patients, risk identification, comprehensive assessment, collaborative planning, health monitoring, patient education and transitional care on healthcare utilisation and cost for community dwelling chronically ill older persons. BACKGROUND: Primary care teams comprised of nurses and primary care physicians have been suggested as a model for providing quality care to the chronically ill, but this type of intervention has not been systematically evaluated. DESIGN: A non-randomised, 36 month comparison of two geographically distinct primary care populations was conducted. METHODS: Six hundred and seventy-seven persons aged 65 and older were determined to be at high-risk for mortality, functional decline, or increased health service use. The treatment group (n = 400) received the intervention and the comparison group (n = 277) received usual care. Health plan claims files provided data on number of hospitalisations and bed days, emergency department (ED) visits, physician visits and total cost of care. RESULTS: After adjustment for baseline variables, there were no significant differences between the treatment and comparison group in the percentage of patients hospitalised or ED visits. However, among those hospitalised in the treatment group, the likelihood of being re-hospitalised was significantly reduced by 34% (p = 0·032). After adjusting for the cost of the intervention, although not statistically significant, the reduced hospital use resulted in cost savings of $106 per patient per month in the treatment group. CONCLUSIONS: The results indicate that a collaborative primary care nurse case management intervention has the potential to be an effective alternative to current primary care delivery system practice. RELEVANCE TO CLINICAL PRACTICE: The study suggests that a chronic care intervention emphasising collaboration between physicians, nurses and patients, may be more effective when implemented in integrated provider networks.

Responding to the challenge of novel technology: an industrial hygiene and safety program for antibody production in maize.

The production of pharmaceutical proteins in plants, particularly in maize (corn), offers solutions to the limited production capacity and flexibility of current cell culture technologies. Implementation of this technology presents unique challenges to industrial hygiene, safety, and occupational medicine, including the handling of pharmaceuticals in the context of agricultural production and the processing of grain for extraction. Protein-related challenges include: (1) widely varying potential for hazard depending upon the activity of the protein and nature and location of the target molecule; (2) limited data related to industrial routes of exposure; and (3) the inability to obtain relevant animal data because of high species-specificity. These challenges necessitate the development of novel approaches to industrial hygiene and safety. Realizing that much remains to be learned, our approach uses conservative assumptions to assure protection of employee health.