Contents
List of contributors
Diversity: editorÊs introduction
BODY
2
A cure for HIV? MILAD JEILANI
9
The cure for diabetes ALEX KOFFMAN
13
Designer babies MILO FABIAN
16
Embryonic stem cells DILEN PATEL
IDEA
22
Science and the riddle of consciousness FRANCIS AZNARAN
25
The riddle of consciousness BARNABY CULLEN
28
Colour experience: the example of Mary ALI NEDEN
31
The explanatory gap: physical facts and the facts of consciousness HARRY GOODHEW
34
Consciousness and the brain MAX NUGENT
37
Collective worship in schools TOMMY CURRAN JONES
41
Is bribery ever justifiable? DILLON HARINDIRAN
MONEY
47
If micro-finance wonÊt save them, what will? ARNAV KAPUR
52
The future of the NHS RUPERT WOOD
56
Income inequality in developing countries TAYLER YU
62
Should teachersÊ pay depend on their pupilsÊ examination results? DILLON HARINDIRAN
NUMBER
67
BachÊs use of alterations to Ritornello and Fortspinnung in the Allegro of Brandenburg Concerto No. 5 ED EDWARDS
71
Job promotion competitions JOSH ROBINSON
76
A clockwork universe? MARCO IOVINO
PAST
84 Why did Britain not follow FranceÊs revolutionary path in the late 18th and early 19th century? WILLIAM BEDDOWS
88
The British as Âabsent-mindedÊ imperialists OLIVER DANIEL
92
The collapse of the western Roman Empire NED TIDMARSH
97
The Venerable Bede and Imperial Rome SEB WAKELY
SOCIETY
101
A critique of democracy CHARLES APTHORP
104
Democracy and Liberalism WILL COOK
108
Liberty and modern society WILL SPENCE
112
China in Africa: friend or foe? WILL THOMAS
117
Intellectual property rights DARSHAN CHOHAN
WORD
ChaucerÊs The MillerÊs Tale and Postmodernism HENRY PAGE
122
GoetheÊs Die Leiden des jungen Werther and PropertiusÊ Monobiblos NIK NICHEPEROVICH
125
131
LorcaÊs death and writing in the Spanish Civil War GEORGE STANBURY
134
The Homeric hero ANDREW JONES
To ÂBe Again? Musings on KrappÊs Last Tape and A Kind of Alaska JOSEPH SPENCE
138
140
Sappho and Virgil PATRICK KING
Contributors
CHARLES APTHORP is taking a gap year but plans to apply to read History and Politics at Oxford next year.
FRANCIS AZNARAN is leaving to read Mathematics at Warwick.
WILLIAM BEDDOWS plans to apply to read History at Oxford next year.
DARSHAN CHOHAN is going to St. CatherineÊs College, Cambridge to read Law.
WILL COOK is off to Oriel College, Oxford to read PPE.
BARNABY CULLEN is in the Remove, and is a keen historian.
TOMMY CURRAN JONES is in the sixth-form, and is interested in humanities and social sciences.
OLIVER DANIEL is in the sixth-form, and is a keen geographer and historian.
ED EDWARDS is off to Gonville and Caius College, Cambridge to read Music.
MILO FABIAN is going to College, Oxford to read Biological Sciences.
HARRY GOODHEW is in the Remove and is mainly drawn to scientific investigation.
DILLON HARINDIRAN is taking a gap year, but will apply to read Economics and Management at Oxford.
MARCO IOVINO has decided to attend university in the USA. Next year he will be at Pomona College in California.
MILAD JEILANI will next year be studying Medicine at College, Oxford.
ANDREW JONES is going to The QueenÊs College, Oxford to study Classics.
ARNAV KAPUR will next year be studying Law at St. CatherineÊs College, Cambridge.
PATRICK KING is off to Magdalen College, Oxford to study Classics.
ALEX KOFFMAN will next year be studying Medicine at College, Oxford.
MAX LESLIE is going to Edinburgh to read Economics.
ROBERT LOOPUIT is in the sixth-form, and is interested in the law and history.
ALI NEDEN will next year be studying Classics at Durham.
NIK NICHEPEROVICH is in the sixth-form and is a keen classicist.
MAX NUGENT is in the Remove, and is a keen linguist.
DILEN PATEL is going to Imperial College to read Medicine.
JOSH ROBINSON is off to Warwick to read Mathematics.
JOSEPH SPENCE is the Master of the College.
WILL SPENCE is going to College, Cambridge to read HSPS.
GEORGE STANBURY is in the sixth-form and, while an enthusiastic linguist, is also interested in Psychology.
WILL THOMAS is in the sixth-form and is a keen geographer.
NED TIDMARSH is going to St. PeterÊs College, Oxford to read History.
SEB WAKELY teaches Classics at the College, and is known for his sunny disposition.
RUPERT WOOD is in the sixth-form and is an economist.
TAYLER YU is going to study History and Economics at College, Oxford.
Diversity: editorÊs introduction
Neil Croally
A school should be many things. Semantron attempts to embody that prescription. There are essays here from students and from staff, on subjects from literature to Physics, History to Medicine, Economics to Mathematics. Many of the essays, though not all, are based on the Extended Essay produced by students in their last summer holiday at the school. These too – in their subject matter, of course, but also in their formatting and referencing – are various. I have not attempted to impose the sort of order most publishers would require.
Why not?
These essays are not the work of Semantron . More important, it is good to see how minds develop. I hope that the contributors to this issue will, at some point, look back at their work published here and say ÂOh! ThatÊs what and how I was thinking then.Ê Five of the essays in the section Idea were written to compete for prizes in the Erasmus Competition. Ali NedenÊs essay won third prize. Dillon HarindiranÊs essay on teacherÊs pay won the Staton Prize, which is awarded by RegentÊs Park College, Oxford.
PART ONE
BODY
1
A cure for HIV?
Milad Jeilani
The Human Immunodeficiency Virus (HIV) has plagued the human race for over three decades, and has risen to become one of the deadliest diseases in human history, claiming a staggering 1.6 to 1.9 million lives each year. 1 For years the Âcure for HIVÊ has been on the lips of the most prominent scientists, yet to this day it manages to elude us. But we havenÊt given up hope yet. After all, it took 105 years after the discovery of the typhoid bacterium to develop a vaccine for typhoid. But the time lag is getting shorter. It only took 16 years from the discovery of the hepatitis B virus to the development of a vaccine. 2 Still, there is renewed hope after recent success concerning the now famous ÂBoston patientsÊ: two HIV-positive patients that received bone-marrow transplants, leaving them apparently cured of HIV. HIV is a lentivirus, and like all viruses of this type, it attacks the immune system. The name ÂlentivirusÊ literally means Âslow virusÊ because they take such a long time to produce any adverse effects in the body: it can take up to 15 years for the first signs of HIV infection to appear. 3 In fact, it is so well hidden that the only thing that gives it away is the presence of antibodies against HIV in the blood. However, this does not mean that all is well in this dormancy. There are two types of cells of the immune system that are infected by HIV: CD4 lymphocytes – the regulatory cells of the immune system, and macrophages – these ingest foreign proteins and flag them for the immune system. During the silent phase, some 100 million virus particles are destroyed daily, while simultaneously about 2 billion CD4 1 [Student BMJ, The worldÊs deadliest virus , 2013] 2 [Aidsmap, Why is it so hard to make a vaccine against HIV? , 2013] 3 [AIDS.gov, Stages of HIV, 2009] The virus
lymphocytes (5% of the total population) are destroyed by the virus each day and need to be replaced. 4 Such is the extent of the viral onslaught that after a number of years the replenishment of the CD4 lymphocytes fails to keep up with the virus, resulting in a profound depression of immune function. Furthermore, once this immune function has been compromised, the individual is left to the mercy of opportunistic infections. These are bacterial, viral, fungal or protozoan infections that usually do not cause disease in a healthy host, but which take advantage of weakened immune systems, and can cause devastating illnesses. 5 The Centres for Disease Control (CDC) have developed a list of more than 20 opportunistic infections that are considered as AIDS-defining infections. These include PCP (a rare form of pneumonia), KaposiÊs sarcoma (a tumour), Tuberculosis and Wasting Syndrome. 6 Without treatment, people who are diagnosed with AIDS typically survive about 3 years. Once someone has a dangerous opportunistic infection, life expectancy falls to about 1 year. 7 Another problem with treating HIV is that itÊs a retrovirus. After infecting a body cell, a retrovirus turns its own RNA genome into DNA and then integrates this DNA into the host cellÊs DNA. 8 The virus then lies dormant within the cell indefinitely – for as long as the cell is alive. In this state, the virus is known as a latent virus. It is invisible to the immune system and anti-retroviral drugs (ARVs), because these only kill viruses that are actively replicating. The latent virus can 4 [Schoub, AIDS and HIV in perspective , 1999] 5 [AIDSMEDS, Opportunistic Infections (OIs) , 2011] 6 [AIDS.gov, Opportunistic Infections , 2009] 7 [AIDS.gov, Stages of HIV , 2009] 8 [Global Health Forum, Why we canÊt (yet) cure HIV , 2009]
2
also reactivate itself, and begin replicating once more. This is why an infected individual cannot stop taking ARVs, since some of the latent viruses will inevitably reactivate. This latent ÂreservoirÊ, along with the extensive damage to the immune system is the major barrier to the eradication of HIV. 9 At the moment, the best treatment available is highly active anti-retroviral therapy (HAART), which consists of a combination of at least three ARVs. There are six classes of ARVs. 10 Each of the first five classes are a different enzyme inhibitor, which block the action of certain enzymes used by the virus to infect a host cell, e.g. they stop conversion of RNA into DNA, or the manufacture of proteins required to maintain cell structure. 11 CCR5 antagonists are the final and most important class. These act to dampen the sensitivity of the CCR5 receptor – a protein on the surface of white blood cells. 12 Although it seems illogical to attack your white blood cells – the very cells fighting off the virus, studies have shown that the CCR5 protein is used by the virus to enter and infect host cells. 13 Thus, by shutting off the CCR5 protein, these antagonists reduce the ability of the virus to infect cells. In fact, people who have a mutation called the ÂCCR5- ∆ 32 mutationÊ do not have any CCR5 proteins on their white blood cells, and so have natural immunity to HIV. 14 Clearly, HAART is a sophisticated programme of treatment for HIV sufferers. And in high-income regions such as North America, Western Europe and Australia, HAARTÊs impact has been dramatic. Opportunistic infections are now uncommon, and average life expectancy is at an all time high at 63 years, which is only 13 years below 9 [PLOS Pathogens, Rapid Quantification of the Latent Reservoir for HIV-1⁄ , 2013] 10 [Patient.co.uk, Antiretroviral Agents , 2012] 11 [Aidsmap, Integrase Inhibitors , 2013] 12 [Wikipedia, CCR5 , 2013] 13 [Wikipedia, Receptor Antagonist, 2013] 14 [FoundCare, What is HIV antiretroviral treatment?, 2013] HAART
that of the general population in these regions. 15 However, HAART is not without disadvantages. In regions most affected by HIV, sufferers are unable to afford the costly HAART cocktails, and partial treatment often proves to be a poor alternative. 16 HAART medications also receive criticism due to their schedules. Often confusing and easy to forget, such regimens may be risky since missing a time-tabled ingestion can have serious consequences on efficacy. Also, as with any potent, lifelong therapy, side effects are common, including bone problems, liver damage, diarrhoea, nausea and more. 17 One of the first major breakthroughs in combating HIV came off the back of years of painstaking research and a large helping of luck. Timothy Ray Brown, the ÂBerlin patientÊ, was diagnosed with HIV in 1995 and with leukaemia (a cancer of the blood) in 2006. Brown had already undergone chemotherapy, but needed a bone marrow transplant. His doctor, Gero Hutter, suggested they seek a donor with the CCR5- ∆ 32 mutation, which gives the carrier natural immunity to HIV. 18 Hutter theorized that a transplant from such a donor could make the recipient resistant to HIV also. No one apparently had tried this, and his idea received mixed reaction from other doctors. But within weeks, tests showed promise that Brown was cured – the virus in his blood had dropped to undetectable levels, and the cancer had disappeared. However, researchers in California recently found traces of HIV in his tissues, leading to speculation that the virus had returned. 19 Mr Brown and his doctors dismissed the The Berlin patient 15 [NHS, What is the life expectancy for someone with HIV? , 2013] 16 [HIV Positive Voices, Highly Active Antiretroviral Therapies (HAART) For Treating HIV , 2013] 17 [Live Strong, The Side Effects of HAART , 2010] 18 [Huffington Post, Timothy Ray Brown, ÂBerlin PatientÊ, And His Doctor Are Convinced⁄ , 2012] 19 [Daily Mail, First man believed cured of AIDS says the disease is gone forever⁄ , 2012]
3
findings, saying whatever traces of HIV remained were dead.
The Boston patients
This summer, two anonymous HIV sufferers, known as the ÂBoston patientsÊ, are said to have been cured. The key to their ÂcureÊ is the bone marrow transplants they underwent three and five years ago respectively. Normally, doctors wouldnÊt recommend such a drastic procedure for HIV alone – the treatment carries a 20% risk of death – but both patients had life-threatening lymphomas (a type of blood cancer), complications of their HIV. The bone marrow transplants successfully treated both the cancer and the HIV infection. For years after their transplants, the Boston patients remained on ARVs. But for three and five months now (at the time of writing: half-way through August 2013), they have been off their medications, and the virus remains at bay. 25 Nevertheless, doctors will need to follow the men closely for at least a year, because the virus may be hiding out in latent reservoirs. 26 If the men stay healthy, they will be the third and fourth patients ever to be cured of HIV, after Timothy Ray Brown and the baby in Mississippi. 27 The Boston patients are the most promising development yet on our way to finding the cure for HIV. Researchers and doctors are excited about the news, especially since the Boston patientsÊ treatment differed from that of Brown in one key way – Brown was given stem cells that were predisposed to resist HIV infection due to CCR5- ∆ 32, while the stem cells that the Bostonians received had no such resistance. Their doctors believe that the transplanted cells must therefore have been protected from infection by the antiretroviral drugs taken during cancer treatment. 28 The finding is very important for people with HIV who also need blood-cell transplants, but the treatment is unlikely to 25 [New Scientist, Double good news from HIV front line , 2013] 26 [Nature, Stem-cell transplants may purge HIV , 2013] 27 [Nature, InfantÊs vanquished HIV leaves doctors puzzled , 2013] 28 [Bloomberg, Stem Cell Transplants Clear HIV in Two Patients in Study , 2013]
So, have we found the cure for HIV? Well, the CCR5- ∆ 32 mutation is present only in people of European descent, and then only in 4-16% of these people. 20 Furthermore, donors have to be of the same blood group as the patient. In fact, Hutter repeated the procedure in 2008 with 12 other people who had both HIV and cancer, but some were too sick to undergo treatment, and others couldnÊt find matching donors or ran into other roadblocks. 21 Scientists hope to investigate other avenues for a more reliable remedy. Separately, the International Maternal Paediatric Adolescent AIDS Clinical Trials (IMPAACT) Group is trying to replicate the Berlin patientÊs cure by giving CCR5- ∆ 32- mutated blood from umbilical cords to children with HIV. 22 The trials mark a change for the field: so far, most research worldwide has focused on adults. In 2012, the National Institute of Allergy and Infectious Diseases (NIAID) spent US$18 million on HIV cure research in adults, and just $45,000 on children. Yet 3.3 million children worldwide have HIV. 23 Children have been an afterthought in the fight against HIV, but the immune system of the child might be more easily manipulated to allow a cure. This was highlighted in March 2013, when it was announced that a baby in Mississippi who received treatment for HIV within 31 hours of birth stopped medication at 18 months without the virus rebounding. 24 Paediatric treatment
20 [Wikipedia, CCR5 receptor , 2013] 21 [Huffington Post, Timothy Ray Brown, ÂBerlin PatientÊ, And His Doctor Are Convinced⁄ , 2012] 22 [Nature, InfantÊs vanquished HIV leaves doctors puzzled , 2013] 23 [Nature, Bid to cure HIV ramps up , 2013] 24 [abcNews, Mississippi Baby Born With HIV ÂFunctionally CuredÊ, Doctors Say , 2013]
4
be used more generally because the risks from transplants are high.
programmes (injecting drug users can exchange used needles for new ones, in order to discourage sharing and re-use); and sexual abstinence. The pharmaceutical side of prevention includes: condoms; vaccines which would protect uninfected individuals from contracting HIV (although no effective vaccine has yet been produced); and finally circumcision (removal of the foreskin from the human penis). A 2009 study done on sexually active men in Africa found that circumcision reduces the infection rate of HIV among heterosexual men by 38–66% over a period of 24 months. 31 The WHO recommends considering circumcision as part of a comprehensive HIV programme in areas with high endemic rates of HIV, such as sub- Saharan Africa, where studies have concluded it is cost-effective against HIV. The apparent success with the Boston patients has caused a surge in optimism that a cure could be imminent. Nevertheless, 30 yearsÊ experience of struggle against HIV means we must accept that a viable cure for most HIV patients may still be a long way off. With an estimated thirty-three million people 32 currently living with HIV, for the foreseeable future it seems we cannot give up on a multi-faceted approach, combining education, diagnosis, treatment and prevention. 31 [Wikipedia, Circumcision , 2013] 32 [World Health Organization, Fast Facts on HIV , 2013]
Perhaps the Berlin and Boston cases should not be viewed too optimistically. Their ÂcuresÊ have come at a high price – intensive chemotherapy and life-long immuno- suppressants and still a significantly lower life expectancy. Alternatively, if we simply improved our HIV testing strategies and detected HIV earlier, we could keep patients healthy and improve their chances. One in four of those in the UK who are living with HIV are not aware they are infected. 29 In developing countries in particular, the problem of treating HIV is compounded by the prejudice and abuse often directed at sufferers. The consequences are wide- ranging, including being shunned by family and community, poor treatment in healthcare and psychological damage, leading to negative attitudes towards HIV testing and treatment. Also, despite reductions in the price of drugs, treatment reminds expensive to buy and to administer. Some activists are worried that the focus on treatment is detracting from prevention. 30 HIV prevention encompasses social as well as pharmaceutical strategies: requiring people to change their behaviour in order to gain protection from HIV. The social side includes sex education; needle exchange 29 [Lipkin, Professor W. I., 21 st Century Challenges , (Lecture). 2011] 30 [de Waal, AIDS and Power: why there is no political crisis – yet , 2006] HIV prevention
5
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Aidsmap. (2013). Why is it so hard to make a vaccine against HIV? [Accessed on 30 July 2013]. http://www.aidsmap.com/Why-is-it-so-hard-to-make-a-vaccine-against-HIV/page/1271042/
AIDSMEDS. (2011). Opportunistic Infections (OIs) . [Accessed on 02 August 2013]. http://www.aidsmeds.com/articles/OIs_4898.shtml
AIDS.gov. (2013). Opportunistic Infections . [Accessed on 02 August 2013]. http://aids.gov/hiv-aids-basics/staying-healthy-with-hiv-aids/potential-related-health- problems/opportunistic-infections/
AIDS.gov. (2013). Stages of HIV . [Accessed on 25 July 2013]. http://aids.gov/hiv-aids-basics/just-diagnosed-with-hiv-aids/hiv-in-your-body/stages-of-hiv/
Avert. (2013). The Origin of HIV and AIDS . [Accessed on 20 July 2013]. http://www.avert.org/origin-aids-hiv.htm
Bennet, S. (2013). Stem Cell Transplants Clear HIV in Two Patients in Study . [Accessed on 16 August 2013]. http://www.bloomberg.com/news/2013-07-03/stem-cell-transplants-clear-hiv-in-two-patients-in- study.html Bongaarts, J.; Pelletier, F.; Gerland, P. (2009). Global Trends in AIDS Mortality . [Accessed on 05 August 2013]. http://www.popcouncil.org/pdfs/wp/pgy/016.pdf Castellano, A. (2013). Mississippi Baby Born With HIV ÂFunctionally CuredÊ, Doctors Say . [Accessed on 16 August 2013]. http://abcnews.go.com/Health/mississippi-baby-born-hiv-functionally-cured- doctors/story?id=18645410 Coghlan, A. (2013). Double good news from HIV front line . [Accessed on 18 July 2013]. http://www.newscientist.com/article/mg21929244.800-double-good-news-from-hiv-front- line.html#.UiEYQdJJOAg Daily Mail. (2012). First man believed cured of AIDS says the disease is gone forever... despite researchers finding traces of the virus remaining in his body . [Accessed on 12 August 2013]. http://www.dailymail.co.uk/news/article-2178481/Timothy-Ray-Brown-says-cured-AIDS-despite- finding-virus- body.html
De Waal, A. (2006). AIDS and power: why there is no political crisis – yet . London: Zed Books Ltd.
FoundCare. (2013). What is HIV antiretroviral treatment? [Accessed on 08 August 2013]. http://www.foundcare.org/HIV-Antiretroviral-Treatment
Hayden, E. C. (2013). Bid to cure HIV ramps up . [Accessed on 10 August 2013]. http://www.nature.com/news/bid-to-cure-hiv-ramps-up-1.13268
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Hayden, E. C. (2013). InfantÊs vanquished HIV leaves doctors puzzled . [Accessed on 15 August 2013]. http://www.nature.com/news/infant-s-vanquished-hiv-leaves-doctors-puzzled-1.12531
Hayden, E. C. (2013). Stem-cell transplants may purge HIV . [Accessed on 15 August 2013]. http://www.nature.com/news/stem-cell-transplants-may-purge-hiv-1.13297
HIV Positive Voices. (2013). Highly Active Antiretroviral Therapies (HAART) For Treating HIV . [Accessed on 09 August 2013]. http://www.hivpositivevoices.org/highly-active-antiretroviral-therapies-haart-hiv/ Laird, G. M.; Eisele, E. E.; Alireza Rabi, S. (2013). Rapid Quantification of the Latent Reservoir for HIV-1 Using a Viral Outgrowth Assay . [Accessed on 04 August 2013]. http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003398 Lipkin, Professor W. I. M.D. PhD. (2011). 21 st -Century Challenges. [Lecture]. [Accessed on 24 August 2013]. http://www.21stcenturychallenges.org/focus/professor-w-ian-lipkin/
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World Health Organization. (2013). Fast facts on HIV . [Accessed on 20 August 2013]. http://www.who.int/hiv/data/fast_facts/en/
8
The cure for Diabetes
Alex Koffman
Diabetes mellitus, or simply diabetes, is a group of diseases which impair the bodyÊs natural ability to control the concentration of glucose in the blood. There are two main types, Type 1 develops in children and young adults and accounts for about 10% of all cases of diabetes. Type 2 develops in later life and accounts for 90% of cases of diabetes. In the United Kingdom, there are 2.9million diagnosed cases of diabetes with 400 new cases being diagnosed every day. 1 Diabetes UK predicts this number will rise to 5 million by 2025. 2 Presently there is no definitive cure for diabetes; however most people with diabetes lead relatively normal lives as a result of insulin therapy, a special diet and careful monitoring of their blood sugar which must be continued for the rest of their life. If diabetes can be controlled successfully using this method then why should we invest time and money coming up with a cure? The simple fact is that not every diabetes sufferer controls their blood glucose levels well. If a diabeticÊs blood glucose is left to rise uncontrollably, as a result of them refusing to take insulin, they become severely hyperglycaemic. If left untreated, the blood becomes acidotic, is more acidic than normal, and the patient will experience nausea, dehydration and blurry vision before progressing into a diabetic coma and eventually death. Although in most cases this can be treated effectively, death does occur in 1% of patients due to the rapid onset of the symptoms. 3 1 http://www.diabetes.org.uk/About_us/What-we- say/Statistics/Diabetes-in-the-UK-2012/; http://www.nhs.uk/Conditions/Diabetes/Pages/Diabetes.aspx. 2 http://www.diabetes.org.uk/Documents/Reports/Diabetes_in _the_UK_2010.pdf. 3 Joint British Diabetes Societies Inpatent Care Group (March 2010). ÂThe Management of Diabetic Ketoacidosis in AdultsÊ.
There are many more adverse effects of poor blood glucose control. High blood glucose can affect the heart, causing a much higher risk of developing Coronary Heart Disease. It can also affect blood vessels; this not only increases the risk of a stroke by between 2 to 4 times but can also cause poor circulation to the leg and foot which can result in necrosis and gangrene, meaning the affected area has to be amputated. 4 In fact, poorly controlled diabetes accounts of 60% of amputations not related to injuries. High glucose levels as a result of diabetes can also cause kidney failure; in fact 44% of kidney failures are caused by diabetes complications. Despite insulin therapy being available, over 1 in 10 adult deaths in the UK can be attributed directly to diabetes. 5 In addition to the effect that diabetes can have on peopleÊs health, the cost of diabetes in the UK is huge. £14billion a year, equivalent to £25,000 per minute, is spent on treating diabetes and its complications by the NHS in England and Wales alone. This means that 10% of the NHSÊs budget is spent on a single disease. There are also extensive social costs of diabetes. It is estimated that the cost of absenteeism and early retirement caused by diabetes is a further £15.3billion a year. 6 This makes the total annual cost of diabetes close to £30billion, almost double the cost of treating all forms of cancer. 7 Although effective treatment is available, it is expensive and some people are unable to treat themselves properly. The most suitable solution to both of these problems is to 4 http://diabetes.webmd.com/risks-complications- uncontrolled-diabetes. 5 http://www.diabetes.org.uk/Documents/Reports/Silent_assass in_press_report.pdf.
6 http://www.diabetes.co.uk/cost-of-diabetes.html. 7 http://www.bbc.co.uk/news/health-20222759.
9
develop a cure which is effective in a large majority of cases. The cure must allow the patient to control their blood sugar naturally, giving them insulin independence. It is also very important that the cure be able to prevent the serious side effects of diabetes. In order to investigate how diabetes could be cured it is critical that we know how important body functions, that diabetes affects, work. Much of the carbohydrates you eat are broken down in the small intestine into the sugar β -glucose which is then transferred into the blood stream where is absorbed in body tissues and respired. The body regulates blood glucose levels with two hormones, glucagon and insulin. Insulin causes liver cells to absorb glucose from the blood and convert it into a molecule called glycogen which is stored in the liver and skeletal muscles. Glucagon works in the opposite way, causing the liver to convert glycogen into glucose which is released into the blood stream. The group of diseases that affect insulin production and therefore prevent natural, effective blood glucose control are called diabetes. The two types of diabetes affect the body in completely different ways but cause the exact same problem. Type 1 is the most severe form of diabetes. It is an autoimmune disease, meaning that the body launches an immune response against some of its own cells. In the case of type 1 diabetes the cells being attacked are those responsible for the regulation and production of insulin, known as islet cells, located in the pancreas. As these cells have been destroyed, the body is unable to regulate the concentration of glucose in the blood. 8 Perhaps the simplest solution for type 1 diabetes would be to do a whole-organ pancreas transplant. In theory this would replace the islet cells and all surrounding tissue which has been destroyed by the immune system in type 1 diabetes sufferers. This treatment is currently used in a very small percentage of cases, only about 1,300
per year worldwide. After a year, 83% of patients are no longer dependant of insulin therapy and regain their ability to regulate their blood glucose. However, there are a tiny number of pancreases available for transplantation compared to the number of people with type 1 diabetes meaning that the treatment is unsuitable for widespread use. A greater disadvantage to this treatment relates to the drugs used after the surgery. In order for the transplanted pancreas to be accepted by the patientÊs body, immunosuppressant drugs (drugs which inhibit the immune system) must be taken throughout the rest of the patientÊs life. This makes the patient more susceptible to other infectious diseases, which may be more dangerous to the patientÊs health than the original diabetes. As a result, very few hospitals offer this treatment on its own unless the diabetes is life threatening. However, many hospitals will offer a pancreas transplant to patients if they also have to undergo a kidney transplant as the regime of immunosuppressant drugs after the operation is the same for both. In conclusion, pancreas transplantation is an effective cure for type 1 diabetes however it poses a risk to the patientÊs health and as a result, relatively few people are eligible for it. 9 Another experimental treatment currently being tested is Âislet cell transplantationÊ. This treatment involves removing islet cells from a deceased donor and transplanting them into the patientÊs liver. Firstly, the donorÊs pancreas is placed in a purified collagenase solution which allows islet cells to be extracted after the pancreas has been digested. These pure islet cells are then infused into the patientÊs liver through a catheter in the hepatic portal vein. As with a whole-organ pancreas transplant, an immunosuppressant drug regime must be followed for life. Islet cell transplantation is still at trial stage and only a select few hospitals are authorized to carry out the procedure. Presently the success rate for the procedure is low. Only 58% of patients in
9 http://stemcells.nih.gov/info/scireport/pages/chapter7.aspx.
8 http://en.wikipedia.org/wiki/Diabetes_mellitus_type_1.
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one study were insulin-independent after one year. 10
cell transplantation cannot be an effective widespread cure for type 2 diabetes.
The current ineffectiveness of this treatment may be due to the effects of the immunosuppressant drugs used to prevent the islet cells from being rejected. Calcineurin inhibitors and Sirolimus (both commonly used to prevent rejection of organ transplants) can impair islet cell function and also decrease the bodyÊs sensitivity to insulin, causing diabetes-like symptoms. 11 This is rather ironic as the drugs needed to prevent the body from rejecting the islet cells can also cause the transplanted islet cells to fail. A second adverse effect of immunosuppressant drugs, particularly calcineurin inhibitors, is that they are nephrotoxic (poisonous to the kidneys). Most patients are able to tolerate the drugs reasonably well and as a result their kidney function will slowly improve after the initial toxicity. However some patients, particularly those with pre-existing kidney problems, may experience complete renal failure as a direct result of the immunosuppressant drugs, which results in the patient needing a kidney transplant to survive. In addition to these problems, islet cell transplants currently require 2 donor pancreases for every treatment. In conclusion, Islet cell transplantation is a relatively successful method for treating type 1 diabetes. However, it poses similar risks to whole pancreas transplants, with the addition risk of the islet cells failing. However the reduced immunosuppressant drug regime used in islet cell transplantation poses a lower risk of infections than a whole pancreas transplant over the long term. Therefore, islet cell transplantation is a very promising cure for type 1 diabetes, especially as new stem cell research may make it possible to artificially produce islet cells of the patientÊs exact tissue type. Despite this, without further development in immunosuppressant drugs or methods to make more donor pancreases available, islet 10 http://www.transplantation-proceedings.org/article/S0041- 1345(04)01555-6/abstract . 11 http://care.diabetesjournals.org/content/26/12/3288.
Type 2 diabetes is the most prevalent form of diabetes and develops in adults. It is a disease which causes tissues to become insulin resistant. This means the tissues will not respond to the normal amounts of insulin produce by the pancreas. Type 2 diabetes is also characterized by relative insulin deficiency. 12 One of the main factors believed to cause type 2 diabetes is a personÊs weight. Studies have shown that obesity is associated with 60-80% of cases of type 2 diabetes in Caucasian adults. It is believed that carrying excess fat causes the body to store some of these lipids in inappropriate places such as the heart, the liver and blood vessels. When this occurs, the probability of developing insulin resistance increases dramatically. Although this link has been proven, the science and reasoning behind it is uncertain. If we were able to prevent fat from accumulating in inappropriate parts of the body then we could potentially stop type 2 diabetes developing as a result of obesity and to some extent reverse pre-existing diabetes which was originally caused by excess weight. Scientists in Sweden have identified a protein called VEGF-B which is involved in the storage of fat in the body. It was thought that perhaps inhibiting this protein, using the monoclonal antibody 2H10, would prevent obesity from being a major causal factor for type 2 diabetes. Studies to prove this effect were then carried out using normal mice. These mice were made obese using a high fat diet and then allowed to develop type 2 diabetes. Once treated with 2H10, the miceÊs diabetes was reverse to various extents, allowing glucose levels to be controlled without insulin therapy. In addition, mice which were in the process of developing diabetes as a result of their obesity were also treated with 2H10, which stopped the natural onset of diabetes. This 12 http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 #cite_note-Pathologic_Basis_of_Disease-2.
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study shows that to some extent, type 2 diabetes can be cured. Despite this early success, more rigorous testing will be needed before a human trial of this treatment can take place, however its prospects of success in humans are good. 13 The symptoms of diabetes express themselves because blood glucose levels are not kept under control. In the case of type 2 diabetes this is because tissues become insulin resistant, and no longer respond to the normal amounts of insulin produced by the islet cells. As a result blood glucose levels increase, as body tissues are less able to absorb glucose. If we were able to increase the amount of insulin the body produced, counteracting insulin resistance, we may be able to reduce, or potentially wipe out, the symptoms of diabetes. Researchers in the Harvard Stem Cell Institute may have discovered a way to do just that by discovering a human hormone, called betatrophin, which causes the body to produce pancreatic beta cells are 30 times the normal rate. The advantage of these replicated beta cells is that they respond to the bodyÊs natural method for regulating insulin. This reduces the risk of the new cells over producing insulin, which would cause severe hypoglycaemia. Essentially,
these new cells stimulate insulin resistant tissues to absorb glucose by producing greater quantities of insulin. Work has been done with mice and has been seen to completely eradicate diabetes. However, it is not a complete cure. Researchers believe that betatrophin may have to be taken monthly or even weekly if it is to be effective. It is estimated that clinical trials on humans may occur between three and five years from now. 14 In conclusion, diabetes is a costly and harmful disease which is set to become more prevalent in the years to come, despite treatment methods being available. Work has been started on researching a cure even though very little is known about the complex biological processes that cause diabetes to manifest itself. Some of these cures are promising and have seen great success in early stages of testing. Unfortunately each treatment has its own disadvantages that make it unlikely to be the universal cure for diabetes that we need. Taking into consideration the huge developments made in medicine and science over the past few decades, I believe that a cure for diabetes will ultimately be discovered.
14 http://news.harvard.edu/gazette/story/2013/04/potential- diabetes-breakthrough/.
13 http://www.medicalnewstoday.com/articles/250792.php.
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Designer babies
Milo Fabian
The issue of embryonic screening has been a matter over which there has been a large amount of fevered debate. People, as with the indomitable rise of genetically modified (GM) crops, are scared of what can be interpreted as the ÂGod complexÊ of geneticists. People are frightened that this element of selection will lead to a genetically stratified dystopian society, based on an individualÊs genetic traits. In this essay, I will endeavour to test the validity of that belief by exploring the possibility of advanced embryonic selection and, by means of ethical examination, studying whether or not the very act of embryonic and genetic selection poses a risk to society as a whole. Embryonic screening can be carried out during the process of in vitro fertilization (IVF). The genomes of embryos created by IVF can be sequenced in part or entirely in order to determine whether they contain detectable genetic abnormalities. This is done to provide the parents with a greater probability of a successful implantation and pregnancy, reducing the likelihood of a miscarriage and of the child having a postnatal genetic disorder. It is believed that a significant proportion of the failed attempts to implant and other failures in IVF are due to aneuploidy, an embryo having the incorrect number of chromosomes in its genetic code. Therefore, techniques are sought which aim to assess the chromosomal number before implantation into the motherÊs uterus. One such technique is a pioneering new method, involving extracting the DNA of embryos that are only about 3 days old, then using a technique called next-generation sequencing (NGS) to break up their The science
genomes into sections, and determining chromosomal abnormalities from the data collected. NGS involves using DNA helicase to ÂunzipÊ, or separate, the strands of the DNA double-helix structure from one another, and the passing of individual nucleotides across the structure of the DNA in the presence of DNA polymerase. When the correct complimentary base pair (i.e. A, T, C, or G) attaches to the DNA single strand, it releases a few H + ions, reducing the pH of the system. The base pair that has attached can be determined from how much the pH drops and therefore the complimentary base pair must be present on the original strand of DNA from the embryoÊs genome. This technique is held to be the fastest, most cost-effective method of sequencing embryonic genomes, which still maintains a high level of accuracy. The need for the sequencing to be fast – ideally under 24 hours – is owing to the fact that the embryos have a very high rate of mitotic division. This means that, while the DNA of the embryo is being examined on Day 3 after fertilization, the embryo is still developing rapidly, and by the fifth day an embryo must be implanted if there is to be a reasonable chance of success at embedding the embryo in the uterine wall. After the fifth day, you run the risk of the embryo becoming too developed or the uterus becoming too hostile for successful implantation. Genetic selection at the moment is limited to gender and potentially eye and hair colour, but with a large degree of error. These genotypic quantities can only be chosen in the embryo if they are contained within the genetic codes of the biological parents of the embryos. Therefore, any selection will serve only to combine the best features of the childÊs parents. This is the
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basis upon which many scientists base their conclusion that the very concept of ÂdesigningÊ your own baby is a farce, as features that are not present in the progenitorÊs genome cannot be passed on to the baby. Therefore, to conclude this section, I believe that from an entirely scientific perspective the prospect of a Âdesigner babyÊ, in the sense that it is meant, is impossible. The most choice that would be possible with the current method is to arrange the most preferable traits of the parents. There are many ethical reasons that say that such selection should not be carried out and indeed that the fact that the research is being conducted at all is a contravention of nature and calls into question the true value of life. 6-8 embryos are produced per IVF cycle, and many are discarded because of genetic defects, or even because of their gender. Do people not deserve life if they are the ÂwrongÊ gender? It is the conviction of many that life begins at conception, and if this is to be believed, then IVF would be unendingly destroying the future lives of millions of people. However, once the genes that code for certain aspects of a person have been identified, geneticists will become able to manipulate those genes in order to genetically modify embryos. This is the true door to the concept of a Âdesigner babyÊ, one that can be sculpted and shaped in any way the parent deems ideal. This is the most frightening realm into which only our imaginations can delve but it will be very real before we know it. The ethics
In the not too distant future, it will be possible to select for phenotypic characteristics, like the colour of a childÊs eyes and hair, athletic ability, etc. A parent having the ability to choose things so woefully unimportant as cosmetic appearance gives the parent a sense of disappointment over the fact that they did not select for a certain trait. That strikes me as a horrible world in which to live. Can a parent truly love a child when they are so obsessed with their exterior and not instead accepting of a son or daughter in their entire? Can it not be seen that a personÊs most valuable assets are not superficial but are the intangible clouds of their personality? These true qualities will never be predicted by genetic selection as a personÊs true self is formed after birth. Therefore, I believe that genetic selection should only be considered in so far as it is genetic screening, of defects and disorders in order to reduce the suffering of parents, especially mothers, going through the hardship and emotional turmoil of IVF. From a conservative viewpoint, the idea of a child that is specifically selected for by its parents is plainly abhorrent, and the idea should be fought. But I believe that the science does not support the idea of being able to ascribe your child with particular characteristics. Therefore, I conclude that the world a fear of the rise of genetically superior Âdesigner babiesÊ is irrational because it will not be possible until there has been a massive expansion in our ability to manipulate the human genome.
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Bibliography
http://www.youtube.com/watch?v=8M1KDjNgkeo . Â Dr. Dagan Wells discusses using the NGS Ion PGM™ Systemfor preimplantation genetic testing Ê, 2013.
Jones, Mary and Jones, Geoff. Â Human Biology for A2Ê . Cambridge: Cambridge University Press, 2005. http://www.bio-itworld.com/2013/2/22/ivf-clinic-deploys-ion-torrent-sequencing-embryo-screening.html. Â IVF Clinic Deploys Ion Torrent Sequencing in Embryo ScreeningÊ , 2013.
ÂGattacaÊ, Dir. Andrew Niccol, Columbia Pictures, 1997.
http://en.wikipedia.org/wiki/In_vitro_fertilization#Discarding_unwanted_embryos. ÂIn vitro fertilizationÊ, 2013.
http://bioethics.georgetown.edu/pcbe/reports/reproductionandresponsibility/chapter3.html. Â Screening and Selection for Genetic TraitsÊ , 2004.
http://www.newscientist.com/article/mg21929253.900-first-baby-born-after-full-genetic-screening-of- embryos.html?full=true#.UicS5dIe3rA. Â First baby born after full genetic screening of embryosÊ, 2013.
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Embryonic stem cells
Dilen Patel
ParkinsonÊs, AlzheimerÊs, diabetes, heart disease and cancer are a few of the many diseases that are currently untreatable and only their symptoms can be managed. Stem cells have the potential to treat many of these diseases, and also be used to regenerate organs reducing the need for transplants. Stem cells are cells located all around the body, and are undifferentiated. This means that they can divide and multiply into many different cells types in the body 1 . Furthermore, as is the case in many tissues, they act like an internal repair system, indefinitely multiplying to replace other cells. This is because when each stem cell divides, it either becomes another stem cell or has the potential to become another type of cell which is more specialised, such as liver cells and red blood cells. At present, three types of stem cells have been discovered and researched; embryonic stem cells, adult stem cells and umbilical stem cells. Research has proven that embryonic stem cells have the most potential as they can differentiate into any of the numerous different cell types, and are therefore said to be ÂpluripotentÊ. Whereas the other types of stem cells cannot differentiate as easily because they are found in specific organs or in the bone marrow and so are restricted to only the cells that function there. 2 Found in the inner cell mass of a blastocyst (3 to 5 day embryo), embryonic stem cells are removed and can be used in potentially any area of the body where specialization into tissues and cells is required. Once placed into the body, the embryonic stem cells can replace the damaged tissue which isnÊt carrying out the function required. Thus the impact of embryonic stem cells on 1 Stem Cells Basics: Introduction (2009) 2 What Are Stem Cells and What Are They Used For? (2010)
present and future medicine could be immense, as they could theoretically treat diseases which donÊt currently have a treatment. For example, in people suffering from type 1 diabetes, the cells that usually produce insulin are damaged by the immune system itself. However new research indicates that it may be possible to control the differentiation of human embryonic stem cells in a cell culture to develop cells that produce insulin. These cells could then be used in transplantation therapy to treat people with diabetes. 3 Embryonic stem cells have great potential to be used in transplantation therapy, as they can replace, generate and protect cells. For example, when treating spinal cord injuries, transplantation of stem cells repairs the damage by replacing the nerve cells that have died, generate new supporting cells that will reform the myelin sheath and stimulate the re-growth of damaged axons, and protecting the cells at the site of the injury by releasing substances such as growth factors and removing toxins. Advances in stem cell therapy are already taking place, for instance doctors at Moorfields Eye Hospital, London, carried out the worldÊs first human trial using embryonic stem cells to treat patients with StargardtÊs macular dystrophy. By taking healthy immature cells from a human embryo and developing them into cells found in the retina, doctors injected these cells into the diseased eye. After the surgery, structural evidence showed that the cells had attached to the eyeÊs membrane, and continued to survive throughout the study (16 weeks). The procedure was deemed 3 What Are the Potential Uses of Human Stem Cells and the Obstacles That Must Be Overcome before These Potential Will Be Realized? (2009)
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