About Sumaya Anwar

Sumaya Anwar is a student of biological sciences at UCL, with a special interest in genetics. Having previous experience as a broadcast journalist, producer and researcher, she now actively works as a presenter and writer. An outgoing, sociable person, she is always interested in finding out others opinions in the pursuit of seeing an issue from every angle. This is reflected in her writing, with a versatile style that would suit a multitude of different topics. Holding a strong belief that a combination of ambition and hard work make anything possible, Sumaya perseveres to make science assessable as well as understandable to everyone.

Beauty and The Business

Janet Ginnings

The beckoning of the beauty industry’s buffed fingernails awaits 2013’s budding entrepreneurs. However, despite hitting an astounding valuation of £15 billion in this United Kingdom this year, one must not be blindly lulled by the siren’s song, as with all sector of business, the ugly prospect of failure remains. As Aldous Huxley once said ‘Experience is not happens to a man; it is what man does with what happens to him’, businesswoman Janet Ginnings personifies this quote, having not only made the most out of the opportunities given to her but also being quick to make opportunities when none could be seen over the horizon. From working as a beautician, to founding her own incredibly successful Mayfair salon in 1996, she is one whose wise words should be considered for anybody brave enough to test the turbulent tides of beauty business.

EXPECT A TOUGH START…
On average 80% of businesses will fail to launch, so remember if you fail to prepare, prepare to fail. Janet says ‘During the initial phase of setting up a business start up capital costs are incurred and at the very same time the client base is being developed’. A business plan is compulsory, cash flow must be watched like a hawk and especially with beauty effort needs to be maintained towards building a relationship with potential clients, to keep them coming back time and time again. Janet Ginnings hair and beauty salon has seen the likes of Elle McPherson and Sadie Frost pass its doors; furthermore the salon does not limit its client base, with male grooming treatments ranging from facials to body ‘tertucking’.

PASSION AND KNOWLEDGE SHOULD INFLUENCE YOUR BUSINESS FIELD OF CHOICE
‘I’m passionate about my business…my aim is to provide an inspirational way of looking into skin and hair regime’. We all know that business is about unique concepts or a fresh way of approaching grounded methods. Janet has drawn from her heritage, from her life experiences, ‘I was brought up to look after my skin and hair by my mother and grandmother. This has always been my passion…being brought up at a farm, my mother used herbs and spices for body scrub and mask. Lots of theses spices have been used from the kitchen e.g chickpea flower was used for face wash, cracked wheat goat’s milk was used as scrub’. This has impacted her Indian Kitchen, which carries out treatments using Mother Nature’s very own produce.

DO NOT FEAR THE COMPETITION, BEAT THEM!
If one thing is guaranteed when it comes to running a business, it is that there will be plenty of others trying to take your place. ‘One has to be on top of one’s business. There is always someone better than you around the corner. This must not scare you but make you aware and be prepared for competition. This is just part of life.’

Ambition and drive are the spices of life, always believe you can succeed and make it happen by working smart not just hard.

Alzheimer’s: Darkening Corners of Once Bright Minds

November 26th 1901 saw the German psychiatrist and neuropathologist, Alois Alzheimer, historically cement his observations of the first woman to ever be diagnosed with the condition, Auguste Deter, 51 years old.  ‘She sits on the bed with a helpless expression… she looked as if she didn’t understand the question… she seems trying to remember… her spontaneous speech is full of paraphrasic derailments and perseverations’.

Over a century later, the disease’s namesake holds strong.

Alois Alzheimer

Dr Alois Alzheimer

With an estimated 650,000 people in the UK suffering from dementia, set to rise to 1 million by 2021, an ageing population and consideration of how the disease causes once bright minds, to see glints of memories passed consumed into oblivion; the recent rise in research funding towards this field, could not have come sooner.

Alzheimer’s disease is the most common cause of dementia, with a range of effects, from the characteristic loss of memory to the disintegration of reasoning skills. The root causes remain obscure, however it seems evident that the brain experiences atrophy – a process whereby the brain itself wastes away in accordance with the degeneration of neurons. Spreading over time, this degeneration will affect many areas, such as the hippocampus whose function is linked to memory, and grey matter, involved in the processing of thoughts. On November 4th, 1904, Alois Alzheimer spoke of this ‘unusual disease of the cerebral cortex’. In reference to the post-mortem pathological examination of 55 year old Auguste Deter, he revealed that ‘in the centre of an otherwise almost normal (neuron) cell there stands out one or several fibrils due to their characteristic thickness and peculiar impregnability’; in fact studies have gone on to show an abnormal amount of amyloid plaques and tau tangles in the brains of affected patients. The unusual ‘thickness’ and ‘impregnability’ Alois described is therefore likely to be a reflection of the protein and fibres building up in the brain, this correlates with a lower efficiency of the transmission of messages, and the eventual destruction of these cells.

‘All in all we have to face a peculiar disease process which has been verified recently in large numbers.’

Alzheimers womanWhile promises of a brave new world, in which disease has been annihilated, never rests far from the consciousness of numerous scientists, the people need to know how to actively impact their own health. While they battle through obstacles in pursuit for the final solution, remember that all knowledge is power and the following aims to outline risk factors; the A.l.z.h.e.i.m.e.r.s of Alzheimer’s disease:

Age – is the greatest risk factor for developing Alzheimer’s disease. After reaching 65 the risk doubles every 5 years and nearly half the people over 85 have Alzheimer’s. It is apparent that increasing age means increasingly increasing disease susceptibility and understanding the exact reasons for this could not only be of paramount importance to curing Alzheimer’s, but also numerous other age-onset diseases.

Lifestyle – it goes without saying that the decisions we make in everyday life, have a significant impact on our long term health. Stoptober has arrived, so why not take the opportunity to kick those butts out for good – see https://stoptober.smokefree.nhs.uk/ for further information. Controlling high blood pressure/ blood glucose if you have diabetes, reducing cholesterol level, maintaining a healthy weight with regular exercise and a healthy balanced diet – all of these will work towards lowering your risk for this destructive disease. Whilst the market continues to floods with ‘miracle drugs’ claiming a number of arguably beneficial effects, remember to always consult with a practitioner.

Z..umba! – This fun dancercise may be a good way to begin increasing your exercise intake, especially if the thought of a room, full of daunting equipment sends a chill down your spine.

Heart Disease – a number of lifestyle factors and conditions associated with vascular disease and stroke can raise the risk of developing Alzheimer’s disease, these include: high blood pressure, high cholesterol, obesity, diabetes and smoking.

Early detection – In addition to the above suggestions, make sure you take full advantage of regular health checks as you get older. In England, Wales and N.Ireland, only 44% of people with dementia are thought to have received a formal diagnosis.

Inheritance – Genetic factors are known to play a role in the development of some forms of Alzheimer’s disease, as it can be seen to run in the family – one form is a single gene disorder. Three genes have been identified (the strongest being apolipoprotein e4 (APOE e4), it is important to note that they only account for less than 5% of cases and most genetic mechanisms for the disease in families if largely unknown. In additions the early a person experiences symptoms, the stronger the genetic influence on it’s development e.g. symptoms appearing in the 40’s or 50’s. However, having a family member suffer from the disease, does not necessarily put others at risk for various reasons – namely, they may have not had the defective gene/s passed on. If you are concerned about inheritance, consult your doctor who may be able to refer you for genetics counselling and advice.

Mild cognitive impairment – People who suffer from MCI encounter symptoms of cognitive decline and memory difficulties. These symptoms are not strong enough for a dementia diagnosis, however they are more severe than would be expected for their given age – this increases the risk of developing dementia later in life, however delaying or even preventing the progression all together is still possible.

Education – Studies have shown that a chronic engagement in mentally stimulating activities may be associated with a lower risk of developing Alzheimer’s disesase – including higher levels of formal education, activities such as playing a musical instrument and maintaining a stimulating occupation. In this way, the brain may be developing more connections between neurons.

Relax – Studies have also shown an association between socially stimulating activities and a reduced risk of developing the conditions. Enjoying an active life, packed with personal hobbies and interests may also act in the favour of prevention or slower progression.

Sex – Alzheimer’s disease has a higher prevalence in women (67%) than men (44%).

Is Ageing A Disease?

ageingWith mice being genetically engineered to live 26% longer than average, age-incidence of a broad spectrum of age-related disease being reduced in the lab and dietary restriction significantly increasing lifespan across species, research seeking treatment for ageing is in action. Telomere modification, free radical level reduction and human growth hormone replacement, all dawn as promising avenues, which may not only decelerate, but may one day reverse the changes associated with ageing. Whilst, current knowledge of the biology of ageing remains too incomplete to assess whether interventions, such as the above, will one day extend average and maximum lifespan, one must the core question: Is ageing even a disease?

Diseases should be cured, it is accepted that this includes age-related diseases. From cancer to neurodegenerative diseases, age is the major risk factor for the majority of these serious illnesses. Treating each individual disease, has a relatively small effect on life expectancy, compared to tackling the process of ageing itself was treated. The definition of disease is historically ambiguous and sensitive to cultural perspectives, homosexuality used to be thought of as a mental illness and late-onset Alzheimer’s disease was only defined as a pathology in 1977. Disease is regarded clinically as the state in which the limits of the normal have been transgressed, health is considered in terms of the absence of disease and expected level of function, at a given gender and age. As ageing is universal, it would seem it is natural, but this does not alter the reality that ageing is a deterioration of normal function. If chronological devices exist, all bodies that exist can be said to age relative to the measurements provided by this, in this way physicians are interested in a set of biological changes over time, such as a higher frequency of cells with chromosomal aberrations in the elderly to decreased melanin formation and white hairs (Hayflick 1974), these changes are universal and inevitable. However, universality and inevitability do not disproof ageing as a disease, rather a special type of disease which everyone inevitably endures.

As one ages, a number of pathologies are gained, to include loss of homeostasis and molecular damage accumulation, which result in the same outcome as severe disease states – death. The perspective of modern biogerontology concludes there is little to distinguish ageing from  a disease state, yet there is a reluctance to view ageing itself as a disease. These unremarkable natural processes in the aged, are confidently viewed as disease where they occur in the young, for example consider the premature ageing disease, progeria. Weismann (1891) argued that ageing and debilitation must be seen as the organism’s new mutational and adaptive responses to fluctuating environments, so ageing benefits the population by removing the superannuated and allowing evolutionary change to take place, which implies ageing to be a very natural part of life. Paradoxically, the evolutionary theory of ageing (ageing being a consequence of a reduction in the force of selection against mutations with deleterious effects later in life, leads to accumulation within population alleles with deleterious effects) potentially illustrates ageing as a lethal genetic disease, with no purpose in terms of fitness. It has been put forward, that evolutionary selection rarely act on entire species or population, rather on individuals and their phenotypic traits which may confer an advantage in certain environments, increasing the likelihood of passing on genes. In this way it is more likely that ageing can be seen as a lethal genetic disease, rather than an evolutionary process under selection. So should ageing be redefined? It seems appropriate, furthermore, a clinical redefinition of ageing as a disease state may lead to added benefits, such as proper safety and efficiency testing of anti-ageing treatments.

Obvious personal, social, economic and environmental problems spring to mind when considering life extension, although a similar change occurred since ancient times (e.g. compare Ancient Assyrians Hebrews and Romans to Syrians, israelis greeks and italians today there has been an increase from 35 to 75 years) and human nature has been able to cope, granted this is no proof that it will be able to do it again given a much greater scale of change. Nevertheless, this does not hold as a compelling argument against the research; with a clever enough government, policies can be put in place when the time comes.

Image reproduced from scmnewused.blogspot.com

Are You A Man or A Mouse?

How the Mus musculus is furthering our understanding of human inherited diseases

In 1907 Cuenot mated two yellow mice giving an unexpected, unmendelian 2:1 offspring ratio.
5 years later Castle and Little repeated the experiment, determining that 1 in every fourth offspring had died during embryonic development.
Nearly a century ago, mice where already paving the way to crucial discoveries, such as that of lethal genes, imagine what they have taught us to this day.

Are you a man or a mouse?

The film set of a laboratory is never truly complete without several cages of our rodent acquaintances, the Mus musculus. However, it may come as a shock to know that these creatures are lifting the lid on a number of human inherited diseases such as Marfan’s Syndrome, which affects 1 in 4,000 people and Huntington’s disease affecting 1 in 15,000. The concept of man and mouse being essentially constructed by nearly identical genetic instructions seems ludicrous; nevertheless scientifically unravelling our genetic code has brought up numerous startling findings.

The human genome consists of approximately 20,000-25,000 genes, hereditary units of coded information determining specific characteristics displayed by living organisms and unnervingly more than 3,700 are known to have 100,000 germline mutations associated with human inherited diseases. Research is crucial to understand these diseases, though the use of human subjects springs up an endless list of complications, from timescale needed to gather results and observations to unethical risk to life. As a result, scientists use a whole host of creatures to further our understanding of human genetics from the roundworm Caenorhabditis elegans, to the humble fly, Drosophila melongaster. The questions ‘What exactly do I have in common with these creatures?’ and ‘Surely the research could never be directly applicable to humans?’ may come to mind and are more than fair to ask. The correct term for these creatures is model organisms; organisms such as the Mus musculus with their mammalian origin and 99% genes in common with human beings. In addition, the Haldane report has fully sequences the mouse genome, another advantage to having a much smaller genome than ours. On a practical level, mice are easy to care for, quick to breed and provide results within a feasible timescale. The key is that mice can be afflicted with the same diseases as humans; therefore duplicating a gene such as exon 3 on the cftr allele swiftly creates a mouse model for cystic fibrosis. Experimentation further allows us to understand the nature of the disease, as 40% of the mice died within 7 days due to intestinal obstruction.

The importance of maternal diet during pregnancy is relatively well acknowledged, however a study using mice coat colours, may have mothers-to-be everywhere thinking twice about what they consume. Mutation of the agouti gene by unmethylation led to mice with yellow coat colour, it was discovered that these mice where more likely to be obese as well as prone to diabetes and cancer. Mice with brown coats have methylated agouti genes and these where found to be of healthy weight and at a lower risk of disease. Pregnant yellow mice with a methyl-rich diet birthed brown coat colour mice, indicating that nutrition does genetically affect a foetus during pregnancy also highlighting that human disease such as obesity can be inherited as a result of maternal diet during pregnancy. In another study researchers drew a similar conclusion that nutrition influences gene expression during embryonic development, which was passed down through generations because of epigenetic inheritance; intracisternal A-particle (repeated transposable elements e.g. there are one thousand copied in the mouse genome) (IAP) reterotransposon was inserted in front of the agouti gene to produce patchy mouse coat colour down the female germ line but not the male germ line.

Most recently gene targeting in embryonic stem cells produces mice with alterations to specific endogenous genes, knock-out mice are providing great insight into human inherited disorders as individual genes can be targeted and more advanced techniques are being developed. With over 300 new inherited disease genes being found every year, and one hundred year’s on since their first (if accidental) use, the role of mus musculus in broadening our knowledge of human inherited disorders is unarguably spectacular. So next time a mouse scuttles into the kitchen, perhaps it would be more fitting for it to find a piece of cheese on a plate rather than a mouse trap.

Live Young and Prosper: The Dauer Way

The global average life expectancy during the early twentieth century was 31 years; today it stands at 67.2 years. The “Big Three”: food, health and hygiene are being hailed as miracle life longevity factors; however improving overall quality of life is far more complex than simply extending it. Without actually slowing down the pace at which we age, all this proposes is potentially a greater number of years spent with age related diseases, such as Alzheimer’s. But how much do we truly understand about aging?

35 genes believed to determine lifespan have been unveiled by research at the Louisiana State University Health Centre, coding for a wide range of cellular functions they indicate aging is multifactorial. At least four physiological processes are thought to play a role in aging including metabolic control, resistance to stress, gene deregulation and gene stability. Scientists will persevere in unravelling the mystery of aging and the complexity of the process means it may be one of the hardest nuts we will ever try to crack. The very nature of aging makes it difficult to gather substantial data; long term experimentation on human beings is unfeasible due to the crippling time constraints. Nevertheless, when there is a will there is a way and this is where model organisms step in.

Caenorhabditis elegans

The nematode, Caenorhabditis elegans makes an excellent aging model organism; living 2-3 weeks, the hermaphrodites among them are able to produce around 300 genetically identical offspring, providing the advantage of allele homozygosis and its small 97 megabase genome is fully sequenced. Most importantly, the Caenorhabditis elegans shares 35% similar genes with us, that are used as candidate human longevity genes and the development stages of each somatic cell are known from zygote to adult worm. Going through the complex developmental processes of embryogenesis, morphogenesis and growth, in four stages (L1, L2, L3 and L4) there is plenty to suggest that what we learn from the Caenorhabditis elegans may be directly applicable to us. When placed in harsh conditions, the L1 and L2 larvae become dauer larvae with delayed development and dark intestines produced by storage of fat. When the harsh conditions subside they re-enter the developmental process, carrying on as normal. This may seem insignificant, however these dauer larvae live 10 times the average lifespan of a normal nematode, in human terms that means reaching the age of about 700!

A study carried out by Golden JW and Riddle DL identified pheromone, food and temperature as dauer-inducing factors. The pheromone is a measure of population density, causing dauer formation at L2 and inhibiting recovery based on pheromone dose. Lack of food causes caloric restriction, a method which has also proven to extend lifespan in rodents. The enhancement of the dauer larvae formation needs exposure to high temperature at L1 stage. Two sensory mutants defective in thermotaxis have altered sensitivity to the pheromone but the pheromone response remains temperature dependent. The ways in which the dauer respond to inducing factors was found to be age dependent, with the older larvae having a greater tendency to recover. The dauer larvae seem to able to control the pace at which that metaphorical clock ticks, no doubt the day we learn to apply this in humans will be pivotal to the very nature of science.

To date the oldest age a human being has got to is 122 years, while average lifespan has certainly increased, maximum lifespan is yet to be understood and manipulated. As technology develops, our knowledge will continue to grow and maybe soon birthday cards will go up to 700 years or more.

Images reproduced from raindeocampo.wordpress.com and web.expasy.org

Breaking Down Bayesian

Science is the river of life.
And as each droplet of knowledge is added to the flow, it advances slightly, modifying what was previously known.

The 1740’s saw Thomas Bayes, an English reverend, conduct a thought experiment that would impress any modern day psychic. With no more than an assistant, two balls and a table, designed so that a ball thrown at random had an equal chance of landing anywhere on the table, Bayes was to predict where the ball had been thrown without even looking.

Thomas Bayes

Brushing all spirits aside, he began to formulate a theorem which would go on to become paramount in genetic risk assessment and association studies. Bayes relied on gaining new information so that he could narrow down the area in which the ball was likely to be, this was done using a second ball and being told whether it had landed to the left or the right of the original ball. Throw after throw saw the area become smaller and smaller, leading Bayes to discover that: Initial Belief + New Data -> Improved Belief

Nevertheless, the element of guess work did not sit well with our eighteenth century academics, resulting in Bayes never publishing his work. It wasn’t until after his death that Richard Price providentially stumbled upon the discovery whilst going through his friends notes. Price re-edited and shared the findings in ‘the Essay towards Solving a Problem in the Doctrine of Chances’.

With the world bearing a number of exceptional minds, it seems almost inevitable that a theory will be independently rediscovered and Bayesian’s statistical methods are no exception. In 1774, an outstanding mathematician by the name of Pierre Simon Laplace published the mechanism, before awareness of Bayes work. It was only a matter of time before Laplace was enlightened with the initial discovery; this only encouraged him further to develop the theorem, using a huge database – birth records.

Laplace noted that slightly less males than females were being born and having set out a system of inductive reasoning based on probability, he found this to be a recurring trend whilst analysing records from Paris, Naples, St. Petersbury, London, rural France, Egypterica. He went on to state that the trend was ‘a general law for the human race’ and made the Bayes theorem into the mathematical equation that we are familiar with today:

P(C|E) = P(E|C) Pprior(C)
Æ©P(E|C`) Pprior(C`)

Calculating the probability of a particular hypothesis, such as the chances of giving birth to a child who is either a carrier or affected by a certain genetic disorder uses Bayes humble equation, as additional information about the pedigree or genetic testing have been shown to vastly improve the results of genetic risk assessment. Single–SNP tests in genome wide association studies demonstrate Bayesian methods advantageous nature when it comes to assessment of association between genetic variant or other phenotypes.

Centuries have passed since Bayes first etched down the roots of probability, a once laughed at belief stands today as a solid concept, guiding us towards more informed future.

Image reproduced from en.wikipedia.org

The Formation Of Man

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The New Year never fails to rein in an eclectic range of resolutions, from the life changing to the downright dumbfounding; nevertheless these feats are attempted in the hope o development. Whether wishful thinking or willpower is permeating 2013’s endeavors, commendable personal development has already been achieved and all before the initial breathe – embryonic development. Details have historically been disputed over what goes into making a Homo sapien; from Aristotle proposing fathers dominantly contributed to their offspring’s characters being disproved be Harvey’s Exercitationes de Generatione Animalum stating it was in fact the egg from which the being came. Even the concept that the whole human form had always existed in a miniature form and grew throughout life was believed by preformationism. With the sequencing of the human genome, increased understanding of its molecular basis, the field of epigenetics as well as developmental biology, processes and theories have been cleared up; both males and females contribute to the characters of their offspring.

Embryonic development retains a certain level of compelling mystery and the beauty of its complexity validates analysis:

Cleavage follows fertilisation, in which the cells divide, increasing in mass with little growth; resulting in overall size not increasing. These cells are totipotent, able to become any cell type within the body, making these stem cells incredibly significant. As time progresses, the cells the cells fate slowly become more and more committed to a particular fate. Embryonic stem cells have the ability to revolutionise both understanding of processes as well as new medication and gene therapies, on the other hand the use of growing human embryonic stem cells strictly for experimental purposes are controversial, leading to great ethical dispute.

After this the vital stage of gastrulation takes place; cell movement establishes three fundamental layers of cells: the ectoderm giving rise to parts such as the skin and nervous system, the mesoderm giving rise to parts such as muscle and bone, and the endoderm giving rise to parts such as the gut, lungs and pancreas.

Simultaneously, a number of other processes take place, for example: axis are determined such as back to front and head to toe, the nervous system is established in neurulation and segmentation is also established; while very vivid in insects, humans to have segmentation in terms of the like of arms and legs made during limb formation.

Overall a single cell has increased fifty trillion fold; so whether finding the cakes to tempting to cut out, losing a battle to procrastination or concluding that the freezing January temperatures are far too grueling a concept to attend that gym session, take comfort in our prenatal conquest.

Embryonic tissue development in animals

Embryonic tissue development in animals

Image reproduced from php.med.unsw.edu.au and bio1151.nicerweb.com

Personalised Genome: The Good, the Bad and the Ugly

As new age technology, such as high-throughput sequencing and nanopores, slashes both costs and time needed for genomic analysis, the age where commercialisation of individual one thousand pound gemones dawns. With its inevitable manifestation around the corner, it has never been more pressing to assess impacts, both social and clinical, so that we can truly be prepared for the changes in how the genetic world interacts with everyday life.

epigenetics

As 10,000 new germline mutations are identified annually, and 300 new inherited disease genes highlighted, personalised genomic sequencing could be used to locate, monitor and understand further disease-associated mutations, though this will only be possible if the data is in fact made public. Inheritance of disease will be better understood, which is a very exciting prospect for potential parents, as current prenatal tests only identify a fraction of potential defects. Currently personalised genome sequencing is used for prenatal and preimplantation genetic testing of conditions such as Turner’s syndrome and muscular dystrophy; however these tests are currently available only to high risk children. With the potential commercialisation of sequencing, testing may be readily available to everyone, undeniably changing the way in which these tests are implemented and as with most change, the line between it being positive and negative lies thin.

‘All creatures would agree that it was better to be healthy than sick… well fitted than ill fitted for their part in life; in short that it was better to be a good rather than a bad specimen of their kind’ – Galton

Global screening of embryos for disorders could lead to self directed human evolution, in other words, eugenics. The risk of profitable ‘designer babies’ could lead personal genomics to encounter ethical scrutiny, therefore a balance will have to be struck:

‘Given the power and the authority granted to parents to seek to improve or better their children… at least (by) some forms of genetic selection or alteration (it) seems equally ethically defensible if they are undertaken freely and do not disempower or disadvantage their children’ – Galton

Certain countries have banned inappropriate preimplantation diagnosis, such as that for sex selection in the UK.

After heart disease, cancer and stroke, adverse drug reaction is the fourth most common cause of death for americans, the fast growing field of pharmacogenetics will find genomic profiles vital in the production of personalised medication. Not only would personalised medication reduce deaths from undesirable reaction, but these tailor made gems would benefit both diagnosis as well as treatment efficiency. While focusing on disease, it must be said that it’s susceptibility is complex, often involving multiple genes, with a partial influence of environmental exposure to certain substances, such as carcinogens. Shedding light on perhaps a limitation of sequencing is the reality that it is not likely to have a great deal of predictive power; a study analysing over 53,000 pairs of monozygotic twins for the incidence of 24 diseases, ranging from autoimmune to obesity associated diseases and cancer, implied 2% of women undergoing whole genome sequencing would have mutations linked to ovarian cancer detected; at least a one in ten chance of developing ovarian cancer. However, the remaining 98% having found no mutations would still be at a 1.4% risk, that of the general public; it would be fair to say that the day when sequences produces infallible figures is a while away.

Unfortunately sequencing may also reveal to patients more than they were prepared to know, diagnosing age-onset, incurable diseases such as Alzheimer’s disease. And once the diagnosis has been confirmed, who else has the right to know? New guidelines issued by the UK GMC allow disclosure of patient information, given the diagnosis of a genetically heritable disease to family members if it is ‘justified in the public interest’. Genetic availability dawns a problematic issue as the UK lacks a counterpart to the USA Genetic Information Nondiscrimination Act.

There also remains the risk of people missing out on potentially life-saving intervention; as genomic sequencing enable quick, cost-efficient diagnosis and family history has long been collected as a means of assessing risk, individuals may not get tested in the fear of employment and insurance discrimination. Although comfort can be taken in the fact that the US Department of Energy and the National Institute of Health devotes 3-5% of their annual Human Genome Project budget towards studying the ethical, legal and social issues surrounding genetic availability, illustrating how research into the issue is currently active.

Sequencing potentials are astounding; from revolutionising diagnosis of disease to screening embryos for chromosomal abnormalities. Personal genomic sequencing allows useful deviations from the reference genome to be analysed. In turn, these incentivise an increase in the sophistication of modern technology. The ethical issues of pharmacogenetics, eugenics and social discrimination dawn as a result of personal genomic sequencing; although there is evidence that research is going towards investigating problematic issues, with rules and regulations already in place. As time progresses, so will our knowledge, all that remains is the hope that we are prepared for the double helix’s dormant revelations.

Image reproduced from pharmaceuticalshealthcare.blogspot.com

Mitochondrial Disease, Down on Your Knees!

IVFA new approach to in vitro fertilisation, which aims to combat inherited mitochondrial disease has received UK government backing. With draft regulations currently in production, the procedure utilising DNA from three individuals could be in use by 2015.

Maintained exclusively down the maternal lineage, these diseases stem from defects within mitochondrial DNA (mtDNA); found within cellular structures known as mitochondria – dubbed the cells ‘powerhouses’, they function to provide the body with more than 90% of it’s energy. With 1 in every 6,500 newborns being born with mitochondrial defects, 10 couples are set to benefit annually from three person IVF. Developed in the seventies, in vitro fertilisation is the creation of an embryo outside of the womb. For couples considered to be ‘at a higher risk’ of genetic disease, techniques such as preimplantation embryonic screening, aid the segregation of healthy embryos from those with chromosomal abnormalities, to maximise the potential success of the IVF cycle; couples tend to find the reality of IVF, an emotionally, physically and financially draining series of repetitions. With 70% of embryos lost to genetic defects, it seems the support for three person IVF couldn’t have come sooner, yet, fears have arisen that any leniency towards genetic modification of a human being may begin to
culminate in the nonsensical abuse of the science, that is, down the ‘slippery slope’ to eugenics.

Dr David King, Human Genetics Alert, warns of the ‘slippery slope whilst talking on the bbc – ‘The biggest concern is once we cross this crucial ethical line, which says that we shouldn’t create babies that have been genetically altered then it becomes very difficult… we will eventually get to this future that everyone want to avoid of designer babies.’

Pioneered at Newcastle University, three person IVF effectively does what is says on the tin; the mother’s defective mitochondrial DNA is replaced with the healthy DNA of a female donor via egg or embryonic modification. 20,000-30,000 genes from the mother and father, 37 mitochondrial genes from the donor; ~ 0.1% genetic alteration to the child’s germ line sees future generations set to inherit the donor DNA.

The progressive inherited neurometabolic Leigh’s disease which holds a prognosis of rarely more than 5 years for infants, is one of a number of disease which may be tackled by three person IVF – in this light tar-ing the procedure as unethical hardly seems fair. It could be argued that denying people the toolkit from which to build a potential healthy future, redirected away from generations of genetic abnormalities is inexcusable, especially when stringent rules and regulations are being created, as well as monitored, by the HFEA (Human Fertilisation and Embryology Authority).

Prof Dame Sally Davies, chief medical officer for England – ‘Scientists have developed ground-breaking new procedures which could stop these disease being passed on, bringing hope to many families seeking to prevent their future children inheriting them… It’s only right that we look to introduce this life-saving treatment as soon as we can.’

We truly are in the enviable position of watching this story unfold before our very eyes. Despite inevitably bringing with it a number of social, ethical and clinical implications, for families with mitochondrial disease this may the *‘excellent news’ they have been waiting for.

*Prof Doug Turnbull, the director of the Wellcome Trust Centre for Mitochondrial Research at Newcastle university.

Image reproduced from newhopefertilityblog.com

Casts Away!

Image credit: webmd.com

Image credit: webmd.com

New drug may reverse the effects of osteoporosis, but caution is warranted.

A new drug, recently featured in a top medical journal, could be that ‘magic bullet’ needed for the three million UK osteoporosis sufferers. Studies have highlighted a number of benefits, including increased bone formation and bone mineral density, whilst decreasing the bone decay rate.

Osteoporosis sees a general loss of bone particularly in postmenopausal women. This occurs everywhere, but the skull and jaw. Weakened and fracture-prone bones make falling a terrifying prospect. Persistent, unpleasant side effects to current drugs, mean effective therapies are still being sought after.

 A research team, led by Dr Michael McClung, founding member of the Oregon Osteoporosis Center, spent one year evaluating the safety and efficacy of the drug.

”Most osteoporosis drugs work by stopping the progression of bone loss, but they don’t have the capability of rebuilding the skeleton,” McClung said. ”This really is a new day in the consideration of how we treat osteoporosis, with the capability of truly stimulating bone production and rebuilding the skeleton, not simply keeping it from getting worse”. 

 McClung’s team found bone mineral density to increase by 11.3% at the lower spine, large increases of bone mineral density at the hip, as well as decreased bone resorption. Importantly, no significant side effects were observed.

 The drug, which is administered simply via injection, or orally, is designed to exploit a pre-existing bone forming process in the body. A protein, called Sclerostin, interrupts this process so bone is not formed.

 The body naturally needs to control bone formation, very precisely as bone overgrowth could have all kinds of bad consequences.

The drug works by getting rid of Sclerostin, so that bone can be formed once again, in addition to the many other benefits mentioned.

 The current standard treatment for osteoporosis is Teriparatide, a hormone based therapy. It has proved a safe and effective method since 2002. However, the need for daily injection and high cost mean it is not ideal.

 Romosozumab, the sclerostin based therapy, lasts much longer in the body, potentially meaning it can be administered as scarcely as every three months.

 Nevertheless, the novel drugs greatest feature may also be its worst. Sclerostin based therapy persists in the circulation, lasting for weeks or even months; once it has entered the body it cannot be taken out.

Currently in Phase Two human clinical trials, it may be a while before Romosozumab is readily available through the NHS. The initial promising findings must now be coupled with a cautious progression.

Castration of the Nation

Will there be a next generation?

Chlamydia infections are known to have an impact on female reproductive organs, but with new research now indicating an infection can cause male infertility it seems there is no place those unseen beasts will not venture to stop us multiplying.

With 89 million new cases being reported a year globally, it is no surprise that Chlamydia is one of the most ubiquitous sexually transmitted infections caused by the pathogenic bacterium Chlamydia trachomatis. The infections are fast proving to be both deadly, as worldwide the magnitude of morbidity is enormous and difficult to diagnose with most victims not experiencing any symptoms whatsoever.

While the list of complications which can arise from Chlamydia trachomatis infection seems to be an endless one, it is pelvic inflammatory disease which threatens fertility so the fact that numbers have shot up over the past twenty years is horrifically ominous. Approximately 20 % of women with Chlamydia lower genital tract infection will develop pelvic inflammatory disease, of which 3% will be rendered infertile and 2% getting adverse pregnancy outcomes. Essentially Chlamydia trachomatis is an obligate intracellular bacterium, upon breaking an entry into the body; its cells lynch onto to fallopian tube cells’ microvillus and multiply before lyses. ‘Confocal microscopy’ has now confirmed that the bacterium disrupted the homeostasis of epithelial tissue in fallopian tubes by activating panacrine wnt signalling in turn this not only damages infected epithelial cells but also uninfected cells beyond. With pelvic inflammation disease numbers escalating a secondary epidemic of tubular factor infertility as well as ectopic pregnancy has followed. Another study showed that the presence of antichlamydial antibodies and tubular factor infertility were closely correlated in females. IVF treatment was less effective as well as early pregnancy loss more likely when these antibodies were present. Given an infected female is pregnant, Chlamydia trachomatis can then be transmitted from mother to child during birth, leading on to yet more complications such as pneumonia.

Light is just starting to be shed on the link between Chlamydia and male infertility, however as the British Fertility Society have pointed out not enough research has been done and recent cuts to funding make the situation look even more dire. Generally, it is known that if left untreated nongonoccal urethiritis, caused by Chlamydia trachomatis, causes testicular swelling among other serious acute complications, making infertility all too possible. There is evidence that Chlamydia trachomatis could be a factor in sperm pathology, as a study examining 627 sperm samples found that those which were infected were of 14.4% lower volume, 6.4 % lower concentration and 9.3% lower velocity. Another study showed that infected sperm had three times the normal level of DNA fragmentation. However it was concluded that antibiotic treatment for Chlamydia infection can significantly improve male fertility.

An entire infertile generation may seem like an incomprehensible concept, however as antibiotic resistance remains rife; the day may come when we can no longer keep up with the unseen world’s evolution.

Nobel Women

Inventas vitam juvat exclouisse per artes - “And they who bettered life on earth by their newly found mastery”

Taken from Vergilius Aeneid, these are the words which adorn the medal of one of science’s most prestigious awards, the Nobel Prize in Physiology or Medicine.

The 27th November 1895 saw Alfred Nobel, inventor of the dynamite, give the majority of his fortune towards an international award known as the Nobel Prize; consisting of a personal diploma, cash reward and medal. Actively involved in medical research, it was appropriate that Physiology and Medicine would become amongst the five possible Nobel prizes. But how does one go about being globally acknowledged and celebrated for their work? In none other than Mr Nobel’s words himself, they must ‘have made the most important discovery within the domain of physiology or medicine’.

The unenviable task to distinguish which discovery has most greatly impacted mankind falls to the 50 Nobel Committee elected-voting professors making up the Nobel Assembly, at the Karolinska Institutet in Sweden. The Nobel Assembly have a choice of candidates suggested by invited nominators, the candidates selected are then assessed by specifically appointed expert advisors who aid the Nobel Assembly and all these filters set in place to make the best possible decision for that given year. The winner is then ordained a ‘Nobel Laureate’; it’s origin hailing from ancient Greece where circular laurel wreaths, composed of leaves and branches, crowned athletic victors, as well as symbolising honour during poetic gatherings.

Science has long been a largely male dominated field, nevertheless over the past 22 years the number of women making the top 1% of academic scores has risen from 8% to 25%. Women are undoubtedly starting to show the statistics, suggesting males vastly outnumber the females in this field, the door. As a female scientist myself, it’s a promising indication that science will continue to progress into a gender balanced field and with the 200th Nobel Laureate likely to be announced this year, it is fitting to look back at the incredible discoveries women have made in the domain of physiology or medicine.

GERTY CORI

Gerty Cori becomes the first female Nobel Laureate in Physiology or medicine in 1947 for the ‘discovery of the course of catalytic conversion of glycogen’. Amongst the team was her husband, Carl Cori giving the achievement a joyous family element.

ROSALYN YALOW

The 1977 Nobel Prize in Physiology or Medicine was shared between Rosalyn Yalow, Andrew V. Schally and Roger Guillemin ‘for the development of radioimmunoassay of peptide hormones’.

BARBARA McCLINTOCK

Barbara McClintock was acknowledged ‘for her discovery of mobile genetic elements’, moreover she stands as the only female in history to obtain an unshared prize! This truly makes 1983 an inspirational year for female scientists everywhere.

RITA LEVI-MONTALCINI

The 1986 Nobel Prize in Physiology or Medicine waste shared between Rita Levi-Montalcini and Stanley Cohen ‘for their discoveries of growth factors’. This discovery was key to furthering our understanding of nervous system development, as the growth factors released by nerve cells where involved in stimulating and regulating the process.

GERTRUDE B. ELION

The 1988 Nobel Prize in Physiology and Medicine was shared between Gertrude B. Elion, Sir James W. Black and George H. Hitchings ‘for their discoveries of important principles for drug treatment’.

CHRISTIANE NUSSLEIN-VOLTARD

The 1995 Nobel Prize in Physiology and Medicine was shared between Christiane Nüsslein-Volhard, Edward B. Lewis and Eric F. Wieschaus ‘for their discoveries concerning the genetic control of early embryonic development’.

LINDA B. BUCK

The 2004 Nobel Prize in Physiology or Medicine was shared between Linda B. Buck and Richard Axel ‘for their discoveries of odorant receptors and the organisation of the olfactory system’.

FRANCOISE BARRE-SINOUSSI

The 2008 Nobel Prize in Physiology or medicine was shared between Françoise Barré-Sinoussi, Luc Montagnier and Harald zur Hausen ‘for their discovery of the human immunodeficiency virus’.

CAROL W. GREIDER and ELIZABETH H. BLACKBURN

2009 saw two women winning the Nobel Prize in Physiology and Medicine, shared with Jack W. Szostak ‘for the discovery of how chromosomes are protected by telomeres’.

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Revolution Through Competition: Unravelling the Archon Genomics X Prize with Dr Eugene Schuster

We truly are living in the age of technology, but not as we know it. Machines will no longer be developed through scientific knowledge; scientific knowledge will be developed through machines.

Dr Eugene Schuster
Functional Genomics of Aging
Genetics, Evolution and Environment
University College London

 

 

 

Science Writer Sumaya Anwar interviews Dr Eugene Schuster to find out more about the Archon Genomics X prize. The $10 million prize competition, which awaits a team capable of sequencing 100 genomes, at a cost of $1000 per genome, in 30 days or less with no more than 1 error in 1,000,000 bases!

It seems surprising to see head-to-head competition in the scientific world, is this something you have come across often or is the vision of scientists working fully together and sharing their findings more realistic?

There is a growing movement in the scientific community for this type of competition – another example is https://www.innocentive.com and shows that the crowdsourcing movement has entered into the scientific community. I think the impact of these types of competitions will be limited and focused to very particular research areas and will not greatly expand as a funding source for academic research. This is because research is very expensive to conduct and you need funding from the beginning. Only an extremely well funded lab or company could undertake such a project and most likely would already have funding in place to do this type of research – so winning the X prize would only be a bonus. However, I think it is much more likely that crowdfunding – when someone proposes to build or do something and ask the public for funds to accomplish the task – will become a bigger part of scientific funding in the future.

The 100 genomes to be sequenced have been donated from centenarians; as a researcher within the aging field how would this genomic database benefit you?

Although, my group studies ageing in a tiny worm called Caenorhabditis elegans, we are interested in identifying evolutionarily conserved mechanisms that can affect lifespans. We would clearly benefit by this research because when human genes are discovered that might help humans to live past 100 we can immediately test if the equivalent genes in worms also affect lifespan. For example, we study a gene called daf-16 in worms and almost 20 years ago the scientist Cynthia Kenyon discovered that this gene plays an important role in extending the lifespan of worms. In the past few years the equivalent gene in humans (called FOXO3A) has been implicated in helping humans to live past 100. We believe that by understanding the role of this gene in worms we can start to understand what it does in humans.

Which standard of the competition do you think is going to be most difficult to meet: 98% completeness of the sequences, the time restriction of 30 days or less, the cost restriction of $1,000 per genome or achieving complete haplotype phasing of the chromosomes?

Complete haplotype phasing will be the most difficult to achieve. It is very difficult to predict inheritance without sequencing the parents or related individuals. To do this probably requires the ability to sequence very long stretches of single strands of DNA with very little error – which is probably beyond current methods.

The process of aging is no doubt complex; research tends to be conducted on model organisms, would the development of genomic sequencing technology mean the end of model organism use?

No because having genomic information does not mean the end of experiments. Large sequencing studies in human will only provide weak evidence that a gene may be involved in a disease or the prevention of a disease. Experiments will have to be done to show a definitive link between the disease and the gene and it is much easier to test these links in model organisms. In worms, you can do an aging experiment in a few weeks. If I started a study in humans, it is likely that the study would out live me.

Steve Jobs had his genome sequenced for $100,000; $1,000 seems much more commercially viable for the general public. What does the current price stand at?

To get a high quality genome with very few errors it would cost about $10,000 today. Once the price gets near $1000 (approximately the cost of an MRI scan) then it can become reasonable for insurance companies or the NHS to sequence a genome if there is good reason to suspect that there is a genetic basis for a disease or symptom. However, this does not include the cost of making sense of that genome and including analysis and interpretation costs may significantly add to the price.

Which technologies are currently at the forefront in terms of cost-efficient sequencing and how do they achieve this?

Two companies that have recently announced low cost genome sequencing are Ion Torrent and Oxford Nanopore Technologies. Both companies will use a semiconductor based technology – Ion Torrent bases the technology on detecting ion charges during the sequencing process and Oxford Nanopore detects changes to the electrical current as a strand of DNA is passed through a nanopore. The major cost savings of these technologies is that they do not rely on optics (i.e. expensive lasers and scanners) nor on labelled samples (older technology typically relies on costly fluorescent labels to detect sequence).

This competition was first proposed in October 2006, what date would you estimate the commercialisation of the $1000 genome?

I would estimate that it will take 2 years before the first commercial $1000 genome (including the cost of interpretation) is available.

Ebola: the race against time

As the death toll rises to more than 5,000, the World Health Organisation have declared the Ebola outbreak in Western Africa a ‘Public Health Emergency of International Concern’.

First described in 1976, the virus is thought to have originated from the fruit bat, its natural host. Subsequent close contact to bodily fluids of infected animals, including the chimpanzee and forest antelope, has led to human transmission via broken skin or mucous membranes. Certain cultural practises, notably burial ceremonies involving washing the deceased contributes to its rapid spread.

Disrupting blood flow by forming blood clots, the virus attacks nearly every organ and tissue in the body and is also known as Ebola Hemorrhagic fever. Following a two to twenty one day incubation period, onset of fever fatigue, muscle pain, headache and sore throat followed by vomiting and symptoms of impaired kidney and liver function are indicative of infection. Whilst the exact mechanism of disease is unclear, it can be inferred that the immune is severely affected and cause of death ranges from massive blood loss, renal failure or shock.

Individuals undergo blood tests at treatment centres to confirm a diagnosis. All arrivals receive supportive care, including rehydration and antimalarial treatment to improve chances of survival, however the fatality rate still stands at around 50%.

The experimental drug Zmapp works by attacking proteins on the surface of the virus and is the latest combination of three antibodies investigated by researchers. The scientific journal Nature published the only clinical trial data on 18 rehsus monkeys, which had a 100% survival rate. No human data on the drug is available and whilst two US aid workers and one Britain have recovered after taking Zmapp, a Liberian doctor and Spanish priest died despite treatment. It is unclear whether Zmapp boosts any chance of recovery.

With no licensed treatment or vaccine the fast track effort towards a safe and efficient cure is of utmost importance, the world is observing this race against time.