The transition of new biotechnologies into clinical trials is a critical step in approving a new drug or therapy in health care. Ethically recruiting appropriate volunteers for these clinical trials can be a challenging task for both the pharmaceutical companies and the US Food and Drug Administration. In this paper we analyze the Jewish halachic perspectives of volunteering for clinical trials by focusing on an innovative technology in reproductive medicine, mitochondrial replacement therapy. The halachic perspective encourages individuals to volunteer for such clinical trials under the ethical principles of beneficence and social responsibility, when animal studies have shown that health risks are minimal.
This brief introduction is followed by a published version of my Nobel Laureate lecture, re-published herein with the kind permission of the Nobel Foundation. Much has happened since my original research, for which that prize was awarded. Hence, I am pleased to offer a few thoughts about the future of my research and its possible impact on humankind.
Although the original work on nuclear transfer and reprogramming was done over half a century ago, advances continue to be made. In particular the Takahashi and Yamanaka induced pluripotent stem cells (iPS) procedure has opened up the field of cell replacement to a great extent. Now, more recently, further advances make this whole field come closer to actual usefulness for humans. Recently, in the UK, the government approved the use of mitochondrial replacement therapy to avoid the problems associated with genetically defective mitochondria in certain women. Although the House of Commons (members of Parliament) and the House of Lords had to debate and discuss whether to allow this kind of human therapy, I was very pleased to find that both bodies approved this procedure. This means that a patient can choose to make use of the procedure; it does not in any way force an individual to have a procedure that they are not comfortable with. In my view, this is a great advance in respect to giving patients a choice about the treatment they receive. I am told that the UK is the first country in the world to approve mitochondrial replacement therapy.
Now that the Clustered Regularly Interspaced Short Palindromic Repeat (CRISPr) technology is being widely used and works well, one can foresee that there will be those who wish to use this technology to make genetic changes to humans. For example, if a human has a gene that makes it susceptible to infection or any other disorder, the removal of that gene might give such a person immunity from that disease. If this gene deletion is done within the germ line, the genetic change will be inherited. However, one can imagine that various people will strongly object and say that this technology should not be allowed. I would very much hope that various regulatory bodies, governments, etc. will allow the choice to remain with the individual. I can see no argument for such bodies to make a law that removes any choice whatsoever by an individual.
Background: Following the announcement of actress Angelina Jolie’s prophylactic bilateral mastectomies and subsequent prophylactic oophorectomy, there has been a dramatic increase in interest in BRCA testing and prophylactic surgery.
Objective: To review current medical literature on the benefits of prophylactic mastectomy and oophorectomy among BRCA-positive women and its permissibility under Jewish law.
Results: Recent literature suggests that in BRCA-positive women who undergo prophylactic oophorectomy the risk of dying of breast cancer is reduced by 90%, the risk of dying of ovarian cancer is reduced by 95%, and the risk of dying of any cause is reduced by 77%. The risk of breast cancer is further reduced by prophylactic mastectomy. Prophylactic oophorectomy and prophylactic mastectomy pose several challenges within Jewish law that call into question the permissibility of surgery, including mutilation of a healthy organ, termination of fertility, self-wounding, and castration. A growing number of Jewish legal scholars have found grounds to permit prophylactic surgery among BRCA carriers, with some even obligating prophylactic mastectomy and oophorectomy.
Conclusion: Current data suggest a significant reduction in mortality from prophylactic mastectomy and oophorectomy in BRCA carriers. While mutilation of healthy organs is intrinsically forbidden in Jewish law, the ability to preserve human life may contravene and even mandate prophylactic surgery.
Bladder cancer is a common disease with a stable incidence for the past few decades despite advancements in molecular and genetic determinants of cancer development and progression. Cystoscopy remains the standard for detection and surveillance of bladder cancer, but it is an invasive and potentially costly procedure. With the knowledge of molecular alterations associated with bladder cancer numerous urine-based tumor markers have become commercially available. These urine markers have been evaluated in all clinical scenarios for the detection of bladder cancer including screening, hematuria, atypical cytology evaluation, and surveillance, but given the relative lack of impactful trials they are not routinely utilized. The efforts to develop markers with increased sensitivity to replace cystoscopy for the detection of bladder cancer have thus far been unsuccessful as well. This review addresses role of urine markers for screening, detection, and surveillance of bladder cancer.
Historically speaking, in many societies a select few carried the burden of preserving and transferring knowledge. While modern society has broadened the scope of education, this is not enough in the medical sciences. We must ensure that all those who pursue a career in medicine become life-long learners who will grow and contribute well beyond their years in medical school. In considering how to attain this goal, we were intrigued by the similarities between generations-old wisdom of teaching and learning methods in Jewish culture and modern educational principles. Both aim to nurture a culture of learners. Our objective was to parallel the methodologies, pedagogic directives, and demands made of students in the Jewish tradition, to the principles used in medical education today. We surveyed the traditional Jewish culture of teaching and learning. We compared it to modern medical teaching methods and looked to see what lessons might be gleaned. In the traditional Jewish community, life is focused on education, and producing “learners” is the ideal. This culture of learning was developed over the generations and many educational methods are similar to modern ones. Some of the pedagogic principles developed successfully in Jewish society should be considered for adaptation in medical education. Further comparative research could help to expand the ways in which we teach medicine.
Objective: Urology practice has undergone several changes in recent years mainly related to novel technologies introduced. We aimed to get the residents’ perspective on the current residency program in Israel and propose changes in it.
Methods: A web-based survey was distributed among urology residents.
Results: 61 residents completed the survey out of 95 to whom it was sent (64% compliance). A total of 30% replied that the 9 months of mandatory general surgery rotation contributed to their training, 48% replied it should be shortened/canceled, and 43% replied that the Step A exam (a mandatory written certifying exam) in general surgery was relevant to their training. A total of 37% thought that surgical exposure during the residency was adequate, and 28% considered their training “hands-on.” Most non-junior residents (post-graduate year 3 and beyond) reported being able to perform simple procedures such as circumcision and transurethral resections but not complex procedures such as radical and laparoscopic procedures. A total of 41% of non-junior residents practice at a urology clinic. A total of 62% of residents from centers with no robotics replied its absence harmed their training, and 85% replied they would benefit from a robotics rotation. A total of 61% of residents from centers with robotics replied its presence harmed their training, and 72% replied they would benefit from an open surgery rotation. A total of 82% of the residents participated in post-graduate courses, and 81% replied they would engage in a clinical fellowship.
Conclusion: Given the survey results we propose some changes to be considered in the residency program. These include changes in the general surgery rotation and exam, better surgical training, possible exchange rotations to expose residents to robotic and open surgery (depending on the availability of robotics in their center), greater out-patient urology clinic exposure, and possible changes in the basic science period.
George London was one of the most compelling vocal artists of the early twentieth century. At the age of 47, the great bass-baritone retired from singing. It has been suggested that the premature ending of his operatic career was due to unilateral vocal cord palsy (UVCP). When London retired, the common belief was that this UVCP was caused by viral hepatitis, although there is no evidence to support such an etiology. London’s medical records eliminate the possible etiology of a neck neoplasm, and the long period of time between a heart attack he experienced and his diagnosis of UVCP makes a cardiovascular etiology an unlikely causative factor. London’s relatively young age, the diagnosis of laryngitis prior to his UVCP, and the course of his disease indicate that the underlying cause of the termination of his singing career was post-viral neuropathy. This paper describes the clinical evidence related to London’s vocal cord function and explores the possible causes for his UVCP, which apparently led to his early retirement.
Urological malignancies are a major source of morbidity and mortality in men over 40. Screening for those malignancies has a potential benefit of reducing both. However, even after more than two decades of screening for prostate cancer, the implications of most resulting information are still a matter of debate. Controversy extends over several aspects of prostate cancer screening programs, including age of onset, defining populations at risk, most appropriate intervals, as well as the optimal methods to be used for screening. The medical community is still divided regarding the effectiveness of prostate cancer-related death prevention and its benefits-to-harms ratio, reflecting an inconsistency regarding screening recommendations. Similarly, benefits of screening for urothelial and kidney tumors are yet lacking high- level evidence, although recent evidence supports screening of populations at risk. Clearly, the current era of evolving molecular and genetic biomarkers harbors the potential to change screening practice. In this paper, we review current guidelines as well as giving an update on new developments which might influence screening strategies in common urological malignancies.
Objective: The impact factor has emerged as the most popular index of scientific journals’ resonance. In this study we aimed to examine the impact factor trends of journals published by scientific bodies in the United States of America (USA) and Europe (EU).
Methods: We randomly chose 11 categories of Journal of Citation Reports and created three research classes: clinical medicine, laboratory medicine, and basic science. The impact factor values for the years 1999–2015 were abstracted, and the impact factor of US and EU journals was studied through the years.
Results: A total of 265 journals were included in the final analysis. The impact factor of US journals was higher than that of EU journals throughout the study period. In addition, for both US and EU journals the median impact factor increased throughout the study period. The rate of annual change in the impact factor throughout the study period was lower for US than EU journals (1.85% versus 3.55%, P=0.019). A higher median annual increase was seen in the impact factor during the period 1999–2008 compared to the period 2009–2015 for both US (P<0.001) and EU (P=0.001) journals. In fact, during the second period the US median impact factor value did not show significant changes (P=0.31), while the EU median impact factor continued to increase (P<0.001).
Conclusion: The impact factor of EU journals increased at a significantly higher rate than and approached that of the US journals during the last 16 years.
Dominant negative mutations in STAT3, a critical signaling molecule and transcription factor in multiple organ systems, lead to a rare monogenic disease called the STAT3 loss-of-function, autosomal dominant hyper-IgE syndrome (STAT3LOF AD-HIES). The original name for this syndrome, Job’s syndrome, was derived from the observation that patients had a propensity to develop skin boils, reminiscent of the affliction cast upon the biblical Job. Many fascinating observations have been made regarding the pathogenesis of the disease and the role STAT3 plays in human health and disease. Additionally, quite a few phenotypic descriptions from the Book of Job are similar to those seen in patients with STAT3LOF AD-HIES, beyond just the boils. This complex multisystem genetic disorder is a challenge clinically and scientifically, but it also brings into question how we approach genetic syndromes beyond just the technical aspects of research and treatment.
