MRC National Institute for Medical Research, London

The media often predict epidemics of cholera but they rarely happen; Haiti at the present time is different.

We were a little surprised that nobody mentioned the origins of Cholera’s fearsome reputation in 19th century European pandemics. These were characterised by massive loss of life from a disease that spread so rapidly that victims could die within three hours of the first symptoms. The causal organism is still just as dangerous but public health authorities everywhere know it can be controlled by effective sanitation and ensuring drinking water is safe. The media unfailingly predict cholera epidemics after a natural disaster because of fears that these safeguards might breakdown, although until the Haiti outbreak there were few 20th century examples.

An outbreak of cholera always involves water contaminated with human faeces (or from marine algae from the Bay of Bengal). Whether this happens after an earthquake depends on the breakdown of infra-structure. We felt that very few essays really captured this. Epidemics can gather momentum because the organism becomes more virulent as it passes through humans. Severely over-crowded and unsanitary refugee camps are the obvious danger spots but even the poorest countries manage to avoid this with help from the WHO. So why did a Cholera epidemic develop in Haiti after the January 2010 earthquake? It had not been seen in Haiti for a hundred years but a serious epidemic broke-out in the following October. As entrants were writing these essays it became known that the source was Nepalese medical workers (established by genetic characterisation of the cholera strain).

The human genome contains extraordinary amounts of information that might affect our fate. Is it worth knowing and can we use it to our advantage?

This topic was the subject of the three winning entries. Authors of essays on this topic needed to evaluate the usefulness of genetic screening, the perceived dangers of disclosing genetic information and the prospects for improving human life. The three winners were aware that the topic is often branded as “controversial” but they found examples of successful and uncontroversial genetic screening (phenylketonuria and congenital hypothyroidism) that can be treated so that people live an almost normal life.

Strategies to avoid inheritance of genetic disease are the major source of controversy. Couples who know they are carriers of a specific genetic disorder would want to be sure their children did not develop the disease - which are often severe leading to a premature death. The finalists wrote well about the value of pre-implantation diagnosis for allowing selection of embryos that are free of a genetic disease. The authors mentioned that this was controversial but did not quite convey that some of the controversy comes from people who use spurious arguments about eugenics to discredit the practice. After all, avoiding the birth of a small number of children with life-threatening diseases is utterly different to the practices favoured by eugenicists. Communities known to have a high incidence of particular diseases often have programmes to help people find the best way to avoid a pregnancy that might produce a child with a serious genetic disease. The winner mentioned the Dor Yeshorin programme in New York, in which members of this community take the test for Tay-Sachs disease (carriers are very common in Ashkenazi Jewish communities) and a 'match-maker' tells couples if there is any reason to believe that a child is likely to be homozygous for the disease.

All three winners recognised that genome sequencing could reveal all sorts of uncomfortable facts. One finalist mentioned the disturbing possibility of an individual discovering they were a carrier of a dominant neurodegenerative disorder such as Huntington’s disease with no known Information on 'celebrity genomes' would have made for an entertaining essay. Ozzy Osbourne wondered if a gene might be found that explained how he got into his 7th decade in spite of abusing his body so badly!

In many cultures consanguineous marriages are taboo.

Most essays on this topic did not explain the scientific argument why first cousins should avoid having children. The danger is that the couple have a significantly higher risk of having children that are homozygous for a genetic disease that can be serious and incurable. The precise level of risk of inheriting a genetic disease in different communities is not always easy to quantify, but it is clearly greater in some societies. In some parts of the Islamic world today more than 50% or marriages are with cousins. Reports from British towns with a large Muslim population suggest that up to 10% of births may be impaired by genetic disease arising from the high prevalence of cousin/cousin marriages. A few entries showed considerable knowledge of this and wrote well about it.

Cousin-cousin marriages were probably the rule in the ancient world, possibly as a device to keep inheritances in the family and the custom has continued in some regions. For reasons that are not understood, the early Christians eventually banned the practice but Protestants became more relaxed about it, after the Reformation. Several entrants were aware that 30 American states introduced laws in the late 19th century that prohibited marriages between first cousins, as a strategy to reduce the risk of births of physically and mentally handicapped children.

Some people think IVF is an audacious and immoral gamble; are there moral or practical hazards?

The heart of this topic is a dilemma; does the value of the procedure outweigh the moral or practical hazards. Two finalists were in no doubt that women who want a baby would be for it even though it is only successful in 1 in 3 cases. They recognised that IVF is an arduous undertaking but dwelling on the adverse effects to the mother unbalanced the essay at the expense of the risk to the child of problems arising from IVF (the higher incidence of birth defects, such as cerebral palsy associated with multiple births).

In general essays did not review the problems that IVF solved. For example women without ovaries or who are post-menopausal can now have a child, and women who need chemotherapy can store eggs for fertilisation and implantation later. Entrants generally recognised the Vatican’s objections to IVF with sensitivity and accuracy but were not clear that non-Catholics have no moral obligation to follow Catholic precepts. Essay writers might have explained the ethical argument for the procedure put forward by the science community - which is that the fertilised egg doesn’t acquire personhood until it is clearly distinct from the placenta and has acquired the character of an embryo. The same argument is used to justify the use of 'spare embryos' for stem cell research within 14 days of fertilisation. One entrant recognised that IVF provides a route to avoid genetic disease (by selection of appropriate embryos) that would be of enormous value to women who know they are at risk of passing on a genetic disease.

Is the answer ingenious switches that control mRNA synthesis?

Perhaps we gave away too much with this title; clearly the answer is selective transcription. Examples are all-important; the finalist who wrote on this topic recognised myosin and actin were important to muscle cells but this isn’t as good an example as globin (made only in reticulocytes and no other cell) or insulin (made in the endocrine pancreas). Many variants of muscle proteins are present in most cells, engaged in specialist activities like transporting vesicles. No one wrote about in situ hybridisation, a technique that shows unequivocally specific mRNA molecules associated with particular cells. The best essay on this topic described very effectively how RNA polymerase manages to make mRNA selectively by transcribing specific sequences of the genome from 'entry points' that are the promoters of genes. Additional protein factors are needed (transcription factors) to co-operate with RNA polymerase to initiate transcription selectively. The importance of methylation as a means of silencing genes is a complicated story that could not be told in any detail here but our finalist evidently appreciated its importance. The best essay on this topic would have been much stronger if it had showed why differential transcription matters: the answer is that an egg needs a programme to create specific cell types in the right place at the right time. Our finalist knew the importance of hox genes in setting up a pattern in the developing embryo that is a necessary prelude to histological differentiation of specific tissues. A little more detail and focus would have made this essay very incisive.