Consent and Internet-Enabled Human Genomics

This month, PLoS Genetics is publishing an article from the company 23andMe reporting the first genome-wide association studies (GWAS) on multiple traits ascertained by self-reported information provided through the Internet from over 10,000 participants who pay the company for providing whole genome genotypes. The paper passed through scientific review by a panel of three experts relatively quickly and is sure to attract the attention of anyone with freckles, curly hair, or an aversion to asparagus. Novel associations are described for four intrinsically interesting traits (out of 22 considered), while known associations with hair and eye color are replicated in a dynamic data-gathering context. Additionally, intriguing observations on the interaction between genetic self-knowledge and self-report of phenotypes are described. The implications of the successful application of this Internet-enabled approach to GWAS research were considered to be more than sufficient to warrant publication in the journal

Comparison of the effects of salmeterol/fluticasone propionate with fluticasone propionate on airway physiology in adults with mild persistent asthma

<p>Abstract</p> <p>Background</p> <p>This study compared the effect of inhaled fluticasone propionate (FP) with the combination of salmeterol/fluticasone propionate (SFC) on lung function parameters in patients with mild asthma.</p> <p>Methods</p> <p>Adult patients with mild persistent asthma (≥ 80% predicted FEV₁) receiving 200–500 μg of BDP or equivalent were randomised to receive either FP 100 μg or SFC 50/100 μg twice daily from a Diskus^®inhaler for four weeks. The primary outcome was the change from baseline in airway resistance (sRaw) at 12 hrs post dose measured by whole body plethysmography. Impulse oscillometry and spirometry were also performed.</p> <p>Results</p> <p>A comparison of the geometric mean sRaw at 12 hrs post dose in the SFC group to the FP group gave a ratio of 0.76 (0.66 – 0.89, p < 0.001) at week 2 and 0.81 (0.71 – 0.94, p = 0.006) at week 4. Similarly, significant results in favour of SFC for oscillometry measurements of resistance and reactance were observed. FEV₁was also significantly superior at week 2 in the SFC group (mean difference 0.16L, 95% CI; 0.03 – 0.28, p = 0.015), but not at week 4 (mean difference 0.17L, 95% CI -0.01 – 0.34, p = 0.060).</p> <p>Conclusion</p> <p>SFC is superior to FP in reducing airway resistance in mild asthmatics with near normal FEV₁values. This study provides evidence that changes in pulmonary function in patients with mild asthma are detected more sensitively by plethysmography compared to spirometry</p> <p>Trial registration number</p> <p>NCT00370591.</p

Relationship between peripheral airway function and patient-reported outcomes in COPD: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Health status, dyspnea and psychological status are important clinical outcomes in chronic obstructive pulmonary disease (COPD). However, forced expiratory volume in one second (FEV₁) measured by spirometry, the standard measurement of airflow limitation, has only a weak relationship with these outcomes in COPD. Recently, in addition to spirometry, impulse oscillometry (IOS) measuring lung resistance (R) and reactance (X) is increasingly being used to assess pulmonary functional impairment.</p> <p>Methods</p> <p>We aimed to identify relationships between IOS measurements and patient-reported outcomes in 65 outpatients with stable COPD. We performed pulmonary function testing, IOS, high-resolution computed tomography (CT), and assessment of health status using the St. George's Respiratory Questionnaire (SGRQ), dyspnea using the Medical Research Council (MRC) scale and psychological status using the Hospital Anxiety and Depression Scale (HADS). We then investigated the relationships between these parameters. For the IOS measurements, we used lung resistance at 5 and 20 Hz (R5 and R20, respectively) and reactance at 5 Hz (X5). Because R5 and R20 are regarded as reflecting total and proximal airway resistance, respectively, the fall in resistance from R5 to R20 (R5-R20) was used as a surrogate for the resistance of peripheral airways. X5 was also considered to represent peripheral airway abnormalities.</p> <p>Results</p> <p>R5-R20 and X5 were significantly correlated with the SGRQ and the MRC. These correlation coefficients were greater than when using other objective measurements of pulmonary function, R20 on the IOS and CT instead of R5-R20 and X5. Multiple regression analyses showed that R5-R20 or X5 most significantly accounted for the SGRQ and MRC scores.</p> <p>Conclusions</p> <p>IOS measurements, especially indices of peripheral airway function, are significantly correlated with health status and dyspnea in patients with COPD. Therefore, in addition to its simplicity and non-invasiveness, IOS may be a useful clinical tool not only for detecting pulmonary functional impairment, but also to some extent at least estimating the patient's quality of daily life and well-being.</p

CRISPR in context : towards a socially responsible debate on embryo editing

Following the birth in 2018 of two babies from embryos altered using CRISPR-Cas9, human germline gene editing (GGE) moved from abstract concern to reality. He Jiankui, the scientist responsible, has been roundly condemned by most scientific, legal and ethical commentators. However, opinions remain divided on whether GGE could be acceptably used in the future, and how, or if it should be prohibited entirely. The many reviews, summits, positions statements and high-level meetings that have accompanied the emergence of CRISPR technology acknowledge this, calling for greater public engagement to help reach a consensus on how to proceed. These calls are laudable but far from unproblematic. Consensus is not only hugely challenging to reach, but difficult to measure and to know when it might be achieved. Engagement is clearly desirable, but engagement strategies need to avoid the limitations of previous encounters between publics and biotechnology. Here we set CRISPR in the context of the biotechnology and fertility industries to illustrate the lessons to be learned. In particular we demonstrate the importance of avoiding a ‘deficit mode’ in which resistance is attributed to a lack of public understanding of science, addressing the separation of technical safety criteria from ethical and social matters, and ensuring the scope of the debate includes the political-economic context in which science is conducted and new products and services are brought to market. Through this history, we draw on Mary Douglas’ classic anthropological notion of ‘matter out of place’ to explain why biotechnologies evoke feelings of unease and anxiety, and recommend this as a model for rehabilitating lay apprehension about novel biological technologies as legitimate matters of concern in future engagement exercises about GGE