Since genetic engineers assembled their first tool kits in the 1970s heart-broken parents and medical researchers have longed to use such technologies to fix faulty genes. The first clinical attempts at such "gene therapy" began in the 1990s. The gene therapists have soldiered on, and in the past few years they have found themselves helped by the most impressive piece of kit yet - a system called CRISPR-Cas9. Some years ago, biologists discovered an odd feature in the genomes of some bacteria that they described as "clustered, regularly interspaced short palindromic repeats" - CRISPR for short. Because it is so simple and easy to use, CRISPR has generated huge excitement in the worlds of molecular biology, medical research, commercial biotechnology - and gene therapy. To date gene therapies have been designed to fix everyday sorts of cells, such as those of the blood, or the retina, or the pancreas. CRISPR makes it possible to think about aiming at the special cells that make sperm and eggs, or the genome of a fertilised embryo awaiting implantation in the womb. One of CRISPR's great attractions is that it can be used to introduce, or remove, a number of different genes at a time. A number of eminent molecular biologists have called for scientists to avoid any attempts at human germ-line modification, even if they are in countries where regulation might allow it, before there has been a much fuller discussion of the implications.
Recent empirical and theoretical literature sheds light on the disappointing experience with implementation of primary health care programs in developing countries. This article focuses on the evidence showing two weak links in the chain between government spending for services to improve health and actual improvements in health status. First, institutional capacity is a vital ingredient in providing effective services. When this capacity is inadequate, health spending, even on the right services, may lead to little actual provision of services. Second, the net effect of government health services depends on the severity of market failures-the more severe the market failures, the greater the potential for government services to have an impact. Evidence suggests that market failures are the least severe for relatively inexpensive curative services, which often absorb the bulk of primary health care budgets. A companion paper, available from the authors (see p. 219), offers a perspective on how government funds can best be used to improve health and well-being in developing countries. It gives an alternative view of appropriate public health policy, one that focuses on mitigating the characteristic market failures of the sector and tailoring public health activities to the government's ability to deliver various services.
The aim of this paper is to present a method which allows to select, more accurately than it is currently done, embryos, at the desired stage of development, which will lead to births, although perhaps with some slight differences in precision, that are deemed to be important. Thus we show that embryos, pronuclei and oocytes consist at least of two types: those suitable for procreation and those not suitable and both types can be recognised easily by an automatic procedure at whatever stage is desired. From their digitilised images before transfer, specific characteristics are formulated automatically and through a particular pattern recognition algorithm the specimen is recognised as belonging to one of two groups with a high precision. The algorithm works in two stages: in the first, the images and their outcomes are used to train the algorithm and in a second stage, on the basis of the rule learnt in training, embryos, pronuclei or oocytes are classified. As multiple transfers and pregnancies occur the training must be carried out with an imprecise ‘teacher’ through a suitable algorithm which can handle this.
Many clinics that offer in vitro fertilization (IVF) have begun to market the following options to couples: (1) an a la carte program where the couple pays $7,500 per attempt regardless of the outcome; or (2) a moneybackguarantee program where the couple pays a $15,000 fee that covers up to three attempts, however, if after three cycles there is no livebirth delivery, then the full $15,000 is refunded. We assess the a la carte versus the moneybackguarantee programs, and find the surprising result that the moneybackguarantee program appears (for the patients) to be "too good to be true." That is, the moneyback guarantee yields a substantial negative expected profit per couple for the clinics. More importantly from the patients' perspective, the moneyback guarantee is the better option for all couples with less than 0.5 success probability per cycle. Virtually all traditional IVF patients have had percycle success probabilities below 0.5. A detailed analysis of the key variablesi.e., success rate per attempt, heterogeneity of couples' rates of success, individual couples' "learning" on successive attempts, and cost to the clinic per attemptshows that these moneyback guarantees are unprofitable for the clinics. Since presumably clinics are not in business to lose money, the standard analysis must be missing something major. We suggest that the marketing of moneyback guarantees is inducing couples who would previously have usedsuccessfullyother less invasive procedures with fewer side effects and less risk of multiple births to decide to proceed directly to IVF, and that this scenario makes the moneyback guarantees profitable for the clinics. The implications of earlier use of IVF are then considered from an overall public policy point of view. Just as mothers everywhere tell their children, "When something looks too good to be true, then it is too good to be true!"