Wednesday, June 17, 2009

Tay-Sachs disease: Origin and Prevention

Tay-Sachs is an autosomal recessive disease most commonly found in Jews of Ashkenazi descent. Approximately 1 in 30 Ashkenazi Jews in America are carriers for the disease compared to 1 in 300 for the total population.Tay-Sachs is caused by a single mutation in the gene coding for the enzyme beta-hexosaminidase A, resulting in the accumulation of excess ganglioside GM2 in nerve cells of the brain. In the first year of a child’s life they may experience symptoms such as; blindness, deafness, dysphasia, muscular atrophy and paralysis.The child will slowly deteriorate and will most likely die by the age of 4. Another, rarer form emerges later in life and may result in an unsteady gait and neurological deterioration. The characteristic sign of the disease which was noticed by Tay himself is the appearance of ‘cherry-red’ spots in the eyes.


There are several theories to explain the prevalence of Tay-Sachs in Ashkenazi Jews; one of the more popular theories is the founder effect. In this hypothesis, it is believed there was originally a low incidence of the mutated allele in the Ashkenazi population.Then by a presently unknown cause a large number of people in the population without the allele died. Therefore there was now a higher proportion of people with the defective gene. Once the population re-grew to its original size there was a higher number of people with Tay-Sachs than before. However the founder effect requires certain criteria in order to take place.Firstly, the sudden population decrease must be followed by little or no migration or interbreeding with other societies. Also, being a carrier of the Tay-Sachs allele must not affect a persons chance to reproduce.

A second theory known as heterozygous advantage, is where there is a selective advantage for carriers of the allele. The most widely held theory is that the allele for Tay-Sachs gives the carrier a resistance against Tuberculosis, so those with the alleles have a higher chance of surviving an outbreak of TB. As a result of this resistance the prevalence of the lethal allele increases after every TB outbreak in the Ashkenazi population.

A third theory is genetic drift, which describes random events that cause some alleles to become more prevalent than others, irrespective of environmental or sexual selection . (You may find it interesting to know that Darwin was unaware of genetic drift and therefore evolutionary biologists are no longer known as Darwinists). For example, if by chance carriers in a given generation were to breed more than non-carriers, you‘d expect the prevalence of Tay-Sachs to increase in the next generation.

The final theory is that parents that have a child displaying the Tay-Sachs phenotype may have more children than normal to ensure that they have at least some children that reach a reasonable life expectancy. This means that there may be higher prevalence of the allele in future generations.

There are reasons (which I am about to explain) why most of the theories I have described may not be viable:
Ashkenazi jews have a higher gene frequency of 22 listed genetic disorders, therefore if the founder effect were to be a prevailing theory, early Ashkenazi ancestors must have been carrying several defective genes, this is an unlikely event making the founder effect an untenable theory.
Another problematic theory is heterozygous advantage, in a study by B Spyropoulos et al. data was found that has shown grandparents of Tay-Sachs carriers die from proportionally the same causes as those grandparents of non-carriers. This suggests there is no advantage of being a carrier regarding resistance against any cause of disease, including TB. Also , in another study (Shaw and Smith,1969) it is said that if theTay-Sachs allele offered resistance to TB it would take 300 generations to reach the current frequency of the detrimental allele in the Ashkenazim, who have been a separate group for only 70 generations. In addition one would expect that if TB gave significant resistance, other ethnic groups under comparable conditions would also have a higher prevalence of Tay-Sachs. Similarly, it is doubtful that the genetic drift theory acts alone, because it is unlikely that random chance could produce such a large prevalence of Tay-Sachs in so few generations of Ashkenazi jews compared to the rest of world . A good example of its large prevalence (mentioned earlier), is the united states of America, where the prevalence of Tay -Sachs is 10 times higher is the Ashkenazim than the total population. However, this theory could contribute to other theories and increase their effect.
Finally, with respect to the final theory I described tt is impossible to prove/disprove carrier parents had more children, although it is a seemingly viable hypothesis.
Many theories exist explaining the disease’s prevalence but it is difficult to prove/disprove them. Further research needs to be done but is likely there will never be definite conclusion.


Currently, very few methods exists for the prevention of Tay-Sachs. One of the most popular methods for prevention, whilst still having the opportunity to have children, is genetic testing. By receiving information that evaluates the probability of having affected children, parents can make an informed decision as to whether having children is the right decision or not.Pre-natal testing is also available for pregnant women, it allows pregnant women to get tested to see if they are carrying an affected fetus. This gives the pregnant women and her partner the option to have an abortion because they know it is affected.Of course, there are othzer options including abstinence, contraception and chemical castration. Perhaps in the future gene therapy may be a legitimate mode of Tay-Sachs prevention.Research is currently being done by researchers (from 6 prestigious academic institutions) of the Tay-Sachs Gene Therapy Consortium to test whether vectors can be used to transport therapeutic genes into a few diseased cells in the brain. The aim of the therapy is to produce a compensatory amount of Hex B enzyme to be distributed about the entire brain. In practice it should ideally restore the brains ability to function properly.


Why do human females experience the menopause?

Oxford Concise Medical Dictionary defines menopause as the time in a woman’s life when the ovaries cease to produce an egg cell every four weeks, menstruation ceases and the woman is no longer able to bear children.
In UK, the average age for a woman to reach menopause is 52 years. The question is why do human females experience the menopause? In my research, I have come across two main popular lines of thought. So what are they?
The first idea is the theory of programmed senescence where reproductive cessation is an inevitable outcome of aging. This is linked together with the idea that genetic traits for reproductive cessation have always been present in the population but because in the past, women did not live as long as they do now, menopause was not as evident then as it is now. Doubts about this line of thought arise from the fact that menopause occurs so much more earlier in life compared to other physiological declines such as senility. Furthermore, if this was all there was to explain the menopause, then would this not mean that the same consequences would apply to the male population? This leads to the second main idea proposed which is known as “evolutionary adaptation”.
This idea suggests that menopause occurs in order to increase the chances of the survival of the mother, her offspring and her grandchildren. To explain further, the risk of death of the mother during childbirth increases with the maternal age. Therefore the menopause could be potentially viewed as a safeguard for the mother and her offspring. The mother will not be exposed to the increased chances of death during childbirth in her older years and the children are less likely to perish from lack of maternal protection and care. This also means that the post-menopausal woman will be available to help her daughters to look after her grandchildren and further promote the chances of their survival. A study supporting this theory is that of African hunter-gatherers. It suggests that post-menopausal women are able to provide food and because of this, their daughters are able to breast feed for a shorter time and have more babies during their fertile years. However this idea could be viewed from another perspective, where the fact that the post-menopausal woman is available to look after her grandchildren is a side effect of her menopause and not a cause of it.
A further idea to this theory of evolutionary adaptation is, in the case where there was no grandmother to help the daughter, menopause ensures that a woman cannot have so many children, that the abundant number prevents her from providing adequate care to some of her other children and so putting them at risk and decreasing their chances of survival. An argument that has arisen from this line of thought is that if the menopause is used as a way to ensure that a woman should not be overwhelmed by having too many children to look after, then would it not have been more plausible for a woman’s body to be sensitive to her levels of stress and thus have prevented further pregnancies at that particular time?
In my opinion, the theory of senescence, evolutionary adaptation and also the role of the post-menopausal woman all offer partial plausible explanations as to why human females experience the menopause. I do feel, however, that none of them could individually be used as a complete explanation to this question and probably the answer would involve a combination of all three ideas. While agreeing on the most part with all the three ideas, I am inclined to feel that the role of the post menopausal woman is slightly weak, as that role could just have easily been taken on by the father of the children.
Oxford Concise Medical Dictionary (7th Edition)
Natural History (Craig Parker)
Evolution of Human Menopause (Shaneley DP and Kirkwood TB)
National Institute of Aging
Hawks K, The Grandmother Effect. Nature 2004

Has human evolution stopped?

The human family, the Hominidae separated from the apes around 5 to 7 million years ago and the modern human species, the Homo sapiens appeared in East Africa around 200,000 years ago. However, it is difficult to know whether we have evolved a great extent since then. We must consider the fact that evolution acts on many different levels; through natural selection, sexual and kin selection etc. Natural selection is mediated by the environment and is primarily for improved survival in the prevailing conditions of the time. Sexual selection however is exerted by other members of the population so that they can mate with individuals who they believe to have preferential traits while kin selection is a process sometimes directed by individuals towards their relatives, a kind of altruism which allows reproductive success of their relatives. These, especially natural and sexual selection are external forces ultimately dictating the speed of evolution by increasing or reducing allele frequencies on the basis of their reproductive benefit. However, they may be impeded by genetic drift which sees to alter gene frequencies on the basis of random distribution of parental genes in the offspring which introduces an element of chance. The effects of genetic drift are more pronounced in large populations due to the increase in the possible combinations of genes. Because evolution is a trade off between natural selection and genetic drift, one dominates over the other depending on how strong selection pressures on a particular locus are to cause gene frequency shifts.
One reason that has emerged to suggest that human evolution is stopping or slowing down is based on the huge increase of our population on the evolutionary scale and in recent times. Figures from February 2009 suggest that the world population has now reached 6.7 billion and for example, for a British child, there is a 99% chance that it will reach its reproductive age compared to 500 years ago when this was only 50%. Large populations have a higher stability than smaller ones as newly arising mutations will be swamped by the already established genes. Therefore, mutation rates of genes can be high but retention in the population will be more difficult. Another point is that although the acquisition of point mutations are fairly constant, DNA has repair mechanisms to allow retainment of its original condition.
Steve Jones, a geneticist at UCL, has argued that natural selection is no longer important for humans. Since it works by ensuring the survival on those who are more reproductively successful, through medical intervention, we have altered this so that nearly anyone in the population can have a child. He therefore believes that human evolution has indeed stopped. However, saying that natural selection is no longer significant among humans is not necessarily correct.
Since the transition from hunter-gatherer behaviours to more agricultural (and technological) ways, we have developed characteristics specific to this. For example, once people began rearing cattle, gaining milk derived nutrition spanning life, instead of it being halted at the infant stage, became advantageous which gave rise to lactose tolerance. Due to this, presently, the gene for lactose digestion appears in 80% of Europeans. However, for Steven Pinker, author of ‘How The Mind Works,’ the emergence of culture meant a move towards ‘non-genetic means to adapt’ for example through behavioural changes.
One of the greatest triumphs of our species was to develop consciousness. Consciousness is something very difficult to define however. When faced with a stimulus, we can retrieve information from past experience to relate to the present situation and make a conditioned response. However, other animals can also do this. We on the other hand can also register the event as being pleasant or not i.e.have an emotional response to it to trigger goal states. In this I mean we can then decide ourselves which course to take after this. Therefore, objects can become things of desire and increasing our experience of them may lead to an enhanced potential for survival and reproduction in the environment. This step in our reaction introduces the state of being self aware due to the level of control consciousness has allowed us to have. Self awareness is also a prerequisite for the understanding of others and manipulation of the environment, which is what we have achieved and also, the formation of culture. 50,000 years ago tribe formation because of this and new hunting techniques with the invention of tools because of increased intelligence allowed the number of tribes in an area to proliferate and in doing so increase opportunities for social interactions.
Humans have also developed left-right asymmetry of the brain which apes do not show. The importance of this is that besides the opposing sides of the body being controlled by the opposite hemisphere, the two hemispheres also differ in their functioning. For example often the left is the dominant which specialises (on average) in logical and sequential/mathematical reasoning. The right is related to more artistic abilities such as shape and colour recognition (e.g. faces) i.e understanding patterns. The development of these features has given a new course for selection pressures to act on. However, not just on single genes as intelligence and increased congition etc. are caused by interactions of a variety of genes. Selection pressures however can seek to form an optimal combination of genes. Therefore, many would argue that in fact human evolution is accelerating by cultural development through these means and creating behavioural change. Increase in urbanisation and technology through our ingenuity has meant as Ian Tattersall put in ‘Becoming Human: Evolution and Human Uniqueness’ that ‘we are being besieged by social stimuli’ so this is what we are adapting to.
In our evolutionary history, it has been found that instead of gradual allele frequency shifts (phyletic gradualism) causing change, there were periods of species stability interrupted by speciation, extinction and replacement –punctuated equilibrium, which was put forward by Niles Eldredge and Stephen Jay Gould in 1972. They found that a new species can be created from a pre-existing one when the selection pressures are large and the species is able to adapt, speciation occurred as a short-term process compared to in phyletic gradualism. Therefore, there is little evolutionary change during most of their history but when evolution occurs, it is rapid and short-term. If the pre-existing population is divided due to a physical barrier, caused by anything such as a seaway, the population begins to diverge and because smaller gene pools are less stable, speciation occurs even faster. Therefore, there is little evolutionary change during most of their history but when evolution occurs, it is rapid. However, in ‘evolutionarily recent’ times, we have found means to overcome physical barriers such as seaways and terrestrial barriers such as mountains etc. and therefore, we are becoming more uniform in our species with the human population being constantly mixed . It has therefore been put forward that we are tending towards a ‘uniformly brown-skinned population.’However, Robert Moyzis at the University of California at Irvine believes that due to the accumulation of various SNPs (single nucleotide polymorphisms, single base changes) in certain populations, we are diverging because of the differences between races.
Therefore, there are many theories as to what will happen in our evolutionary future. Many focus on cultural changes due to behavioural development and others on morphological change. However, it is very unlikely that human evolution has stopped. This would mean that the mechanisms for evolution no longer apply to us which separates us from the rest of the animal kingdom and seems to single us out as being special when in fact we arose the same humble way that other creatures have. We cannot say that we are improving either as this would commit evolutionary fallacy that each stage if evolution works to improve us. Evolution seems to act on many levels and it is difficult to predict what direction it is heading as it is essentially blind. Therefore we also may not be able to rely on our past evolutionary history as a means to put light on the future.
Becoming Human: Evolution and Human Uniqueness, Ian Tattersall, Oxford University Press, 2000
How The Mind Works, Steven Pinker, Penguin, 1998
Human Evolution; an Illustrated Introduction, Roger Lewin, Blackwell Publishing, 2005
Cells, Embryos and Evolution, John Gerhart and Maarc Kirschner, 1997

Comparison of the sexuality of Humans, Common Chimpanzees and Bonobos

When first considering this title, it may seem a bit perverse to be delving into the details of human, chimpanzee and Bonobo sexuality. However, when considering Darwin and the theory of evolution, it is integral to discover the mating habits and social norms of all species, especially ones that are so closely related to our own, in order to further our understanding of human evolution. Homo sapiens, the Common Chimpanzee and Bonobos, otherwise known as pygmy chimpanzees, all share a common ancestor. Between these species, there are many noted areas of similarity and disparity within behaviour and physical appearance. One area that has been of particular interest to many researchers is that of social sexual behaviour. Well known
Homo sapiens are usually set apart from other mammals due to our ability to conduct ‘higher thought’ processes. Nevertheless, social sexual behaviour is also a major characteristic that separates humans from most other species. Sexual behaviour of humans is fairly distinct because they are not sexually active solely for reproductive purposes. In the human community, sexual intercourse also plays an important role socially, by creating strong bonds between individuals by increasing physical intimacy, it is the foundations of many social hierarchies and there is also a hedonistic factor as enjoyment of the activity is a large driving force behind copulation. Evidence to support this in humans, is the creation of contraceptive techniques. Humans not only have sexual intercourse when procreation is not intended, but they go one step further and take measures to ensure that reproduction is actually prevented. This is a behaviour that is almost certainly unique to the human species, even if sex as a social role is not. Bonobos are another species that uses sexual intercourse in a social context, with the same benefits as humans, such as stronger bonding and social hierarchies. It also has been seen to maintain a more peaceful environment amongst their community as aggression amongst the males can be vented through sexual acts. Atypically for species in the mammal genre, the female Bonobos are hierarchically more dominant.5 It has been theorised that this is due to the bonds that are formed between females. Wrangham, a leading primatologist, hypothesises that this grouping of females is a counter strategy to the male reproductive strategies as groups of females are greater at attracting groups of males.1 On the other hand, the Common Chimpanzee do not hold the same principles of social sexual behaviour and society tends have a more aggressive atomosphere. The Common chimpanzees have a patriarchal society where the males are dominant and, as with most animals, sexual intercourse is purely for reproduction and advancement of the species.
The Bonobos and the common chimpanzees, are part of the same genus and have many similarities mainly physically and biologically, an example being the female swelling cycle. Impending ovulation the sexual skin surrounding the perineum of the female primate, swells and reddens, and is usually shows a conspicuous maximum tumescence around the presumed time of ovulation.4 Studies have shown that in both species this swelling has a direct affect on the sexual arousal of the males. This has the obvious evolutionary advantage of attracting males sexually, when the female is most fertile. The results of the studies, show that the Bonobos seem to have a longer span of maximum tumescence compared to the common chimpanzees, although this could be a discrepancy of only 1-3 days. With this in mind, another point of comparison that could be addressed is that of the cycles of arousal between the species. In humans, sexual arousal for females is not limited by the time of ovulation as it is with most other mammals, there are only periods of heightened sensitivity. This supports the idea of a more socially orientated sexual behaviour as sexual intercourse can be initiated at any point. Bonobos are similar to humans in this instance, although they have a more obvious display of when they are at maximum tumescence. Unlike the common chimpanzees, instead of a few days out of her cycle, the female bonobo is almost continuously sexually active and attractive.
The position of sexual intercourse is one of the more shocking similarities between Bonobos and Humans. In contrast to most other primates, the Bonobos mate in what was long considered to be a uniquely human fashion. Their sexual activities vary in position and sexual contacts, including face to face copulation. The common chimpanzees have a more typical mating ritual which is generally associated with mammals, with the male approaching from behind the female. Female bonobos also partake in a sexual activity known as genito-genital rubbing, where the two females rub together their gential swelling laterally together. It is thought that this female-female interaction helps reinforce the strong bonds between the females and contributes to the female dominance.2 Females amongst the common chimpanzees are not so well attached and so such activities do not take place in this species’ communities. Male bonobos have also been seen to participate in homosexual activities. Examples are where one male briefly rubs his scrotum against the buttocks of another. Another example is the phenonmenon of ‘penis fencing’ whereby two males hang face to face from a tree while rubbing their erect penises together.2 It is unsure what benefits such acts of homosexuality can have, seeing as there is no reproductive advantage, however one explanation available is that it is a way of resolving disputes amongst individuals of the group as an act of peacemaking. There has also been some evidence of masturbation by both female and male bonobos, an action that is almost unheard of outside of a human context. This fact serves to further prove the idea that the bonobos enjoy a highly sexually based society.
Finally the most significant difference between humans and the two species of chimpanzee is the tendancy to only have one sexual partner at a time. This is not a behaviour that it found amongst the primates as each female and male have multiple partners.6 In the wild this has its advantages as it lowers the occurance of infanticide by males as there is no way of being sure which male the offspring belongs to. Also, unlike most species in the animal kingdom, the time when a person reaches physical maturity is not directly correlated to when a person first takes part in sexual intercourse.
In conclusion, Humans, The common Chimpanzee and Bonobos, despite being derived from a common ancestry have very some very different social behaviours concerning sexuality. Out of the three species Bonobos and Humans arguably have the more similar behaviours as their community as a whole largely revolves around a sexual concept. Sexuality moulds the way Bonobos interact with eachother as it does within human society. Even the way the act is carried out greatly resembles that of humans. The only major difference is that humans usually maintain a single partner throughout life, and tends to only reproduce with that partner, whereas the primates have multiple partners. Also as soon as the primate reaches physical maturity, they are then expose to sexual activities, whereas this is not necessarily the case in homo sapiens.

1 WRANGHAM, R.W. 1980. An ecological model of female-bonded primate groups. Behavior 75: 262–300
2 Bonobo Sex and Society Scientific American March 1995. FRANS B. M. DE WAAL
3Comparison of behavioral sequence of copulation between chimpanzees and bonobos Received: 30 August 2004 / Accepted: 22 January 2005 / Published online: 16 September 2005 by Chie Hashimoto and Takeshi Furuichi
4Perineal Swelling, Intermenstrual Cycle, and Female Sexual Behavior in Bonobos (Pan paniscus) American Journal of Primatology 68:333–347 (2006) by T. Paoli et al
Female Reproductive Strategies as Social Organizers DIANA PRASCHNIK-BUCHMANa Hunter College of CUNY, New York 10021, USA
5The Other “Closest Living Relative” How Bonobos (Pan paniscus) Challenge Traditional Assumptions about Females, Dominance, Intra- and Intersexual Interactions, and Hominid Evolution by AMY R. PARISH AND FRANS B. M. DE WAAL- ANNALS NEW YORK ACADEMY OF SCIENCES

The illness of Charles Darwin: a retrospective diagnosis.

The topic of this blog is the much debated illness of Charles Darwin. Firstly, an effective clinical history of his illness will be attempted, describing and classifying the symptoms. Then, possible explanations for his collection of symptoms will be addressed; including previous attempts to explain his illness.

Before 1837, Charles Darwin had, considering the poor level of medical knowledge and sanitation during the period he lived in, quite good health. He suffered from scarlet fever when he was nine and developed a mouth infection at college prior to his travels aboard the Beagle, both fairly inconspicuous illnesses for the time. Furthermore, during his five year round the world trip, he was taken seriously ill on only one occasion, which he attributed to food poisoning. It is surprising, when the extreme conditions he would have endured aboard the Beagle are taken into account that he did not suffer from illness more often during the five year voyage. There are those who claim that Darwin suffered from symptoms prior to his voyage on the Beagle and that there is evidence for a genetic disorder. However there is a far greater consensus that Darwin only began to experience the symptoms of his disorder after his return.

This good health contrasts sharply with Darwin’s health after 1837. It was at this time in his life, (when he was aged just 28) when he started to suffer from the collection of symptoms that would plague him until he died in 1882 (aged: 73.) They began with fatigue, malaise, stomach cramps and headaches, but worsened throughout his life: including worsening neurological symptoms like tinnitus, dizziness, sensitivity to temperature, further headaches, muscle spasms and tremors; as well as worsening gastrointestinal symptoms such as vomiting and colic. Furthermore, he developed cardiovascular and respiratory symptoms such as palpitations and shortness of breath. He also went on to develop dermatological symptoms such as blisters and ulcers. All of this was also accompanied by bouts of anxiety and depression.

In terms of the character and pattern of these symptoms, whilst it is true to say that the symptoms were most severe towards the end of Darwin’s life, it is not true to say they followed a progressive pattern of disease. It appears that Darwin’s symptoms took on a remitting/ relapsing character; where he had periods of relative health followed by months of illness so severe that he was bedridden and unable to work. Furthermore, stress appeared to exacerbate his condition. Indeed it is said his period of worst health was 1847-1851. This was a period of great stress. Both his father and “favourite” daughter (Annie) died; Annie aged just 10 at this time. In addition, within this period, his closest friend and scientific confidant, Joseph Hooker, left on an expedition to the Himalayas for three and half years. This was devastating news for Darwin who was relying on Hooker for fine tuning his book. Another noted exacerbating factor was preservative chemicals, Darwin’s health would tend to deteriorate when performing experiments (with chemicals). The one apparent alleviating factor was Dr. James Gully’s water cure establishment in Malvern. Darwin was persuaded to attend by his wife Emma, and stayed for four months instead of the proposed three weeks. The treatment was mainly homeopathic and probably had no effect, but another component of the ‘cure’ was a ban on alcohol, rich foods (including dairy) and tobacco as well as compulsory walks. This would have likely improved Darwin’s health.
Some have tried to explain Darwin’s illness as stemming from psychological problems, the eminent psychologist John Bowlby suggested that it was somatisation (psychological problems and emotional trauma being expressed as physical symptoms) caused by a suppressed grief for the loss of his mother. However, the extent to which Darwin suffered from the symptoms and his relative detachment to his mother, suggests that this is no the case. Another psychological explanation for Darwin’s illness was that it was mainly caused by stress that accompanied the guilt and internal conflict he felt towards his own work towards: ‘On the Origin of Species,’ as he was fully aware of its religious implications as well as how many of his colleagues and friends would react. There is support for this in the timing of the onset of his symptoms around the same time as he began work on his book. However, the severity of the symptoms he experienced surely cannot be accounted for by such a theory.

One possible suggestion for Darwin’s illness, which is based on the effect of the Malvern water treatment, is that he was lactose intolerant, as the improvement seen would have been caused by the dairy free diet at the establishment at Malvern. Furthermore, in this disease patients have chronic gastrointestinal symptoms if lactose is not removed from the diet, which chronically can cause malabsorption in the gastro-intestinal tract potentially causing neurological symptoms due to ion imbalance within the blood. However, even if we make a significant assumption in that the cardio-respiratory symptoms are caused by a separate environmental heart disease, it cannot explain the more severe of his neurological symptoms, his dermatological symptoms or indeed his fatigue.

Another, potential explanation also focuses on gastrointestinal disease. Some have blamed Crohn’s disease; the main strength of this argument is that it fully explains the gastrointestinal symptoms as well as explaining the relapsing/ remitting pattern of his disease. Furthermore, stress is known to have a role in the onset of an acute episode in Crohn’s sufferers, as is the case with Darwin’s symptoms. In terms of the dermatological symptoms Crohn’s can typically cause apthous ulcers of the mouth and other skin disorders. However, this explanation also falls down in effectively explaining the cardio-respiratory symptoms as well as the neurological symptoms. Unless as with above they are attributed to stress or other incidental disease.

A further, much popular hypothesis (endorsed by Sir Peter Medawar), is that he contracted a parasite that caused chronic Chaga’s disease after being bitten by the Triatoma Infestans bug. This disease may have gastrointestinal manifestations as well causing heart problems and the neurological symptoms could be explained as being secondary to the other symptoms or indeed a response to chronic disease. However, the dermatological symptoms described are less easily attributed to Chaga’s, although they could potentially be linked to the immune response that is believed to cause most tissue damage in Chaga’s. There is further evidence against Chaga’s, in that usually, chronic exposure to the bug’s faeces is needed to cause an infection. A factor not present in Darwin’s case.

Perhaps the most important factor to draw from these attempts to diagnose Darwin is that the more popular explanations are all linked to the immune system, and produce their effects at least in part by an inappropriate immune response. This has lead some to believe that Darwin suffered from multiple allergies, Fabienne Smith the foremost among them. This is supported by the fact that much of Darwin’s family had some sort of allergy and the death of his daughter Annie appears to be a total immune collapse. In addition the stress and chemicals that exacerbated his symptoms are typical in an allergic condition.

In conclusion, whilst there are many compelling arguments for different causes of Darwin’s symptoms, and a significant volume of information on his symptoms, and eventually there may be a popular consensus as to his illness; it will never be possible to make a definitive diagnosis.

Campbell AK, Matthews SB. Darwin's illness revealed. Postgrad Med J. 2005 Apr;81(954):248-51.
The Rough Guide to Evolution by Mark Pallen
Darwin: A Life in Science by John Gribbin and Michael White
Kumar and Clark Clinical Medicine by Kumar and Clark

Charles and Emma- Benefits and Hazards of First Cousin Marriages

At first glance this title seems to have a rather tenuous link to Charles Darwin unless you were aware that Charles Darwin married his first cousin Emma Wedgewood and was plagued with fears throughout his life that he had left his children with a ‘genetic time-bomb’. Emma and Charles shared a common grandfather Josiah Wedgewood and were born of brother and sister; Josiah Wedgewood II and Susannah Wedgewood respectively. They went on to have ten children but three died in childbirth, Mary Eleanor less than four weeks from birth, Annie (known as Darwin’s favourite child) at 10 years and Charles Waring at 6 months (1). Currently it is generally legal for first cousins to marry in most western societies, with only the USA notably banning the practice, 31 states make this practise illegal (2). Over recent times, the tradition of marrying first cousins, a practice favoured by the elite in early centuries in an attempt to not dilute the blood line and limit the claimants to family money, is becoming less common with increased transport and communication ensuring a larger population of prospective mates (3). However it is still believed 80% of marriages historically have been first cousin marriages, and are still prevalent in some societies; 3 out of 4 marriages in Bradford’s Pakistani community are inter-cousin unions(4).
It seems when debating views on first cousin marriages the scientific hazards and benefits need to be considered along with the ethical and social consequences. Darwin’s Origin of Species (5) explains evolution as the variation, non constancy of species giving them advantageous characteristics allowing them and in turn their offspring to survive, inheriting these characteristics, this principle is natural selection. The result of natural selection is gradual change due to the accumulation of heritable advantageous traits. The principle of descent with modification offers an explanation for some specie becoming extinct whilst others continue, it also explains Darwin’s tree of life; all living organisms come from common ancestors. Many theories of benefits of first cousin marriages relate to the belief that by doing so they are following the principles of evolution. The belief in common ancestors leads to belief in a continuum of animals and humans and the ultimate question, what separates humans from our ancestors, chimps; chimps mate within a community (6) therefore it is highly likely they mate with first-cousins indiscriminately, so at what point does it become our decision to actively choose a mate due to social and legal rules as opposed to the one nature causes us to be attracted to? At what point do the ‘rules’ for us choosing an appropriate mate become different to those of a chimp?
In addition sexual selection (5) is the struggle within the same sex of the same specie to ensure they mate with the partner with the most desired characteristics giving their offspring maximum chance of survival to propagate their specie with characteristics to exploit the resources available. Therefore if an individual has attracted the individual of the opposite sex who could allow them to give their offspring that desired characteristic, why should they be handicapped compared to others in their specie of the same sex as a result of a family relationship with the desired partner? If people are of the same family they may share positive characteristics, thus children born of them may have these positive attributes further exaggerated, should positive eugenics be discouraged?
Furthermore due to evidence from mitochondrial DNA it has been suggested that all humans outside of Africa developed from one branch of the ‘tree’ which left Africa in the ‘African exodus’ 60,000 years ago (5). Therefore it could be argued that as everyone is related anyway and we share more genetic similarities than one sub-specie of chimps there is little point stopping the marriage of first cousins when most marriages are between related people anyway.
From the social aspect, couples will have a stronger network to support their relationship if they are related, they are likely to share the same values and common memories, meaning the relationship is likely to be more successful, therefore more likely to conceive children and continue the specie.
The most common concern related to first cousin marriage is the genetic implications to the offspring. Studies have shown there is an increased risk of congenital malformation caused by homozygosity for autosomal recessive alleles. When estimating the probability a child of first cousins will have an autosomal recessive disease, it is assumed the grandparents each have a recessive mutation, the probability of the child inheriting the grandfather’s mutation is 1 in 64, similarly they have a 1 in 64 chance of getting their grandmother’s, giving a probability the child will be homozygotic for one of the grandparent’s mutations of 1 in 32, which when added to the risk of major congenital mutation in the general public (1 in 40) they have a 1 in 20 risk of developing a congenital abnormality.(7)
A further theory is that nature itself discourages a too close familial relationship between parents, in a study performed at Liverpool University (8) two sets of male mice were used each identical apart from their major urinary proteins, mice born of related parents have less varied proteins than those of unrelated parents. In the experiment the female mice consistently chose mice with more complex proteins suggesting they could detect the consanguinity, it is thought women may also have this ability.
Once again social opinion influences the practise, in western society it may be viewed unfavourably and people may become ostracised from society ‘We have to stop this tradition of first cousin marriages’ Keighley MP Ann Cryer (4).
However before finally weighing up the hazards and benefits of first cousin marriages it must be considered the way in which the scientific evidence of hazards is reached. Often the cultures considered are those which are either isolated, so first-cousin marriages are a higher occurrence than in some societies or in cultures where it is actively encouraged, which could lead to biased results as the children considered would not be just one off children of first cousin marriages, but an accumulation of several first cousin marriages over many generations in history.
Additionally social and economical factors may have an effect, as cultures where consanguinity is in higher occurrence may also be poorer to begin with, so the mother’s possible malnourishment could be a confounding factor (3).
Also the fertility of the children is often used to consider the success (9) of the offspring and therefore the marriage of the parents, but although a child does not go on to have children themselves, they may have success in other areas such as intelligence. For example, Darwin’s’ children; where William was a banker, Henrietta edited and published her mother’s letters and Leonard taught at the school of military engineering yet none of the three had children (10). Also one should bear in mind that it is known that there are increased genetic problems in children of older mothers (1) but this is not illegal or particularly socially unacceptable.
It may also have been noticed that many of the theories offered as benefits to first-cousin marriages are not benefits just justification to why it is acceptable and not a hazard, just a component of natural selection.
In conclusion, in my opinion first cousin marriages within our society should be neither actively encouraged or discouraged as to allow evolution and natural selection, social and legal implications should not intervene with the biological attraction people feel to their mate. If the practise is encouraged it will occur more regularly than nature intends, so the hazards will accumulate. However, if it is discouraged, natural selection is not occurring and people cannot necessarily mate with those with the most desirable characteristics. My concluding opinion is only relevant in our society where the occurrence is so small as not to be deemed a serious hazard, in smaller more isolated communities it may occur at a higher incidence, thus the hazards are likely to outweigh the benefits. Finally it is important to remember that evolution rejects determinism. We cannot predict evolution as some situations just happen; people may choose not to have children, so we cannot try to manipulate nature as we are unaware of the final consequences.

(1) (last accessed 16th June 2009)
(2)Brandon Keim- ‘Cousin Marriage OK by Science’- Wired Science December 23rd 2008
(3) Diane B. Paul, Hamish G. Spencer.‘It’s Ok, We’re Not Cousins by Blood’. The Cousin Marriage Controversy in Historical Perspective.
(4) Rowlatt J. The Risks of cousin marriage. BBC Newsnight.
(5)‘The Rough Guide to Evolution’ Mark Pallen, 2009
Page 50- The origin of Species: a one page summary
Page 204- Out of Africa
(6) (last accessed 16th June 2009)
(7) Turnpenny P. Ellard S. Emery’s Elements of Medical Genetics 13th edition.
(8)Brandon Keim- Women, Trust Your Nose: Inbred Men May smell bad- Wired Science April 17th 2008
(9) C.D. Darlington. Cousin Marriage and the evolution of the breeding system in man.
(10) (last accessed 17th June 2009)

The Pleistocene diet: a recipe for diet and health?

To answer this question I shall begin by giving a brief description of what is meant by “The Pleistocene diet”. Starting with what or should I say when the Pleistocene epoch was in our history. The Pleistocene era is the earlier of the two epochs of the Quaternary Period, from about 2 million to 10,000 years ago, and was characterized by the formation of widespread glaciers in the Northern Hemisphere and by the appearance of humans. Mammals included both small forms, such as sabre-toothed tigers and horses and giant ones, such as mammoths and mastodons. Almost all the giant mammals, including woolly mammoths, giant wolves, giant ground sloths, and massive wombats disappeared at the end of the Pleistocene and the start of the Holocene.

The Pleistocene diet refers to a diet which is similar to that of the humans at that time, without the invention of food preparation or cooking. It’s principle is that it is based around foods that were readily available, “on the table” during our evolution, foods such as meat, fish, fowl, and the roots and fruits of many plants. As whilst food stuffs such as grains, beans and potatoes are useful sources of energy, our bodies are not adapted to utilising them as a food source, as when eaten raw they contain many harmful toxins, so rendering them inedible to our evolutionary predecessors. The Pleistocene diet considers such foods as Neolithic, as they were only edible after the discovery of cooking around 10,000 years ago, and so their ingestion is not “coded for in our genes”. (1)

Furthermore the diet is based around the idea that as much as individual genetics and experiences influence your nutritional requirements, millions of years of evolution have also shaped our need for specific nutrients, that our dietary changes have outpaced our ability to genetically adapt to them, as according to Eaton. "That the vast majority of our genes are ancient in origin means that nearly all of our biochemistry and physiology are fine-tuned to conditions of life that existed before 10,000 years ago.(2)

In comparison with our evolutionary diet, today’s diet fails to meet sufficient biochemical and molecular requirements of homosapians. Evolutionary diet consisted of prehistoric man consuming around 50% of his calories from carbohydrate, mainly from fruits and roots, in comparison with modern times, where carbohydrate often takes the form of sugar and sweeteners and is devoid of essential vitamins and fatty acids.(2) The best available estimates suggest that our ancestors obtained about 35% of their dietary energy from fats, 35% from carbohydrates and 30% from protein. Saturated fats contributed approximately 7.5% total energy and harmful trans-fatty acids contributed negligible amounts. Polyunsaturated fat intake was high, with substantial cholesterol consumption. Carbohydrate came from uncultivated fruits and vegetables, approximately 50% energy intake as compared with the present level of 16% energy intake for Americans. High fruit and vegetable intake and minimal grain and dairy consumption made ancestral diets base-yielding, unlike today's acid-producing pattern. . Fibre consumption was high and Vitamin, mineral and (probably) phytochemical intake was typically 1.5 to eight times that of today except for that of Na, generally <1000 mg/d, i.e. much less than that of K.(3)

The Pleistocene diet was said to include a much greater quantity and variety of fruits and vegetables as well as dietary fibre, which aids in gastro-intestinal health. This is often a criticism of modern western diets, where the quantity and variation of fruit and vegetable intake is much lower and often insufficient to the Palaeolithic, with fewer than 9% having the recommended 5 portions per day.

A further advantage of this diet can be seen to be that it contained a greater ratio of omega 3 to omega 6 fatty acids and also a greater proportion of potassium with a lower Sodium intake, due to a diet containing less processed food.(2)

The diet advocates a high intake of:
Meat, chicken and fish
Vegetables (especially root vegetables, but definitely not including potatoes or sweet potatoes)
Nuts, e.g. walnuts, brazil nuts, macadamia, almond. Do not eat peanuts (a bean) or cashews (a family of their own)
Berries- strawberries, blueberries, raspberries etc.

Whilst in taking none of the following
· Grains- including bread,
· Pasta,
· Noodles
· Beans- including string beans, kidney beans, lentils
· Potatoes
· Dairy products

· Sugar

· Salt

So is this type of diet nutritionally viable and compliant with today’s recommended food intake?
The food standards agency advocates a healthy diet to be one that contains a variety of foods including plenty of fruit and vegetables, plenty of starchy foods such as wholegrain bread, pasta and rice, some protein-rich foods such as meat, fish, eggs and lentils and some dairy foods. It should also be low in fat (especially saturated fat), salt and sugar.(4)

The Pleistocene diet does seem to meet much of this criteria, in the form of the high content of fruits, vegetables, and protein, and low salt, and sugar intake. However it does not include any dairy products which are said to be included in modern diets.
So in theory the diet does seem suitably nutritious and provides the basis fo a healthy lifestyle, but what effects does it have when applied to modern people?
One study which looked at the short-term effects of such a diet on 14 healthy volunteers concluded that the intervention in their diets did produce some positive effects, namely reduced fat composition, and increased intake of anti-oxidants. The total energy intake was also reduced by 36% and with this the subjects mean weight decreased by 2.3kg, and their BMI also decreased by 0.8, indicating positive effects. However there was also a reduced calcium intake which in the long term could be problematic and further studies must be carried out before a definitive conclusion can be made. (5)

However one problem concerning the Pleistocene diet is its effect on teeth, and that whilst our DNA had not evolved or changed massively from that era to now, the structure and make up of our jaws and teeth have changed sufficiently to make consuming a diet of purely raw, and so often tough food, slightly problematic and predispose the partaker to dental problems.(6)

Over time humans have evolved to have smaller teeth, with a thinner enamel coating which renders them less effective at cutting into, tearing and peeling tougher food stuffs. The reason for these changes in dental structure are rooted not in the lifestyle of the earlier humans in the sense of changing from gathering to producing food, but from changes in food-preparation techniques and non-dietary usage of the teeth.(7)

Casting that issue aside for the meantime though, there are other benefits that this diet provides which can be particularly pertinent for those which long standing chronic condition. Studies have shown that a “prehistoric” diet can be of benefit to those suffering with diabetes and ischaemic heart disease by improving glucose tolerance.(8)

Another positive aspect of this diet is the reduced salt intake, as salt has been linked in with high blood pressure and so a reduction in salt intake from following such a diet can reduce the risk of hypertension.(9)

As well as this foods such as snacks, particularly in the form of energy drinks, which are much more energy dense then many of the foods available to Pleistocene man have been accredited to one of the main nutritional problems of modern society in obesity, as people are often partaking in such snacks and not compensating for them in their diet, leading to a positive energy balance, and from evolution, humans have a weak defence against over eating and so problems arise. So as a Palaeolithic diet is without these items it could also be seen as a healthier option.(10). Also humans are evolutionarily adapted to a calorie restricted diet and to survive in a state of under nutrition, 10, where due to conditions such as increased soil aridity and cooler temperatures, led to a reduction in potential food sources for Pleistocene man, and so they would change or alter the way in which they metabolised their food.(11)

It can be seen that a Pleistocene diet does vary from most modern diets, both in its type and proportion of food consumed. Results have shown that this can be a healthier lifestyle, as the high intake of animal-based foods would not have necessarily elicited unfavourable blood lipid levels due to the hypolipidemic effects of high dietary protein (19-35% energy) and the relatively low level of dietary carbohydrate (22-40% energy). Although fat intake (28-58% energy) would have been similar to or higher than that found in Western diets, it is the case that the proportion and types of fat ingested would have been vastly different with relatively high levels of MUFA and PUFA and a lower omega-6/omega-3 fatty acid ratio, would have served to inhibit the development of CVD.(12)

Therefore the Pleistocene diet, in my opinion is useful as a reference point and provides important clues to the "baseline" levels and ratios of nutrients needed for health. Suggesting that we should be eating a lot of plant foods and modest amounts of game meat, with a reduced intake of salt and refined foods, and despite it perhaps not being practical to follow it to its entirety, with an increased understanding of it, it can aid us to lead healthier and more natural lives, optimizing our surroundings and what our bodies are able to deal with.

(1) Dr. Ben Balzer. Introduction to the Paleolithic diet. Available at:
(2) Challem J. Paleolithic Nutrition:Your Future Is In Your Dietary Past.
(3) Eaton SB. The ancestral human diet: what was it and should it be a paradigm for contemporary nutrition? Proc Nutr Soc. 2006;1(65):1-6.
(4) Healthy diet. Available at:
(5) Osterdahl M, Kocturk T, Koochek A, Wändell PE. Effects of a short-term intervention with a paleolithic diet in healthy volunteers. Eur J Clin Nutr. 2008;62(5):682-5.
(6) Lucas PW, Constantino PJ, Wood BA. Inferences regarding the diet of extinct hominins: structural and functional trends in dental and mandibular morphology within the hominin clade. J Anat. 2008;4(212):486-500.
(7) Eshed V, Gopher A, Hershkovitz I. Tooth wear and dental pathology at the advent of agriculture: new evidence from the Levant. Am J Phys Anthropol 2006;2(130):145-59.
(8) Lindeberg S, Jönsson T, Granfeldt Y, Borgstrand E, Soffman J, Sjöström K, Ahrén B. A Palaeolithic diet improves glucose tolerance more than a Mediterranean-like diet in individuals with ischaemic heart disease. Diabetologia 2007;9(50):1795-807.
(9) Elliott P, Walker LL, Little MP, Blair-West JR, Shade RE, Lee DR, et al. Change in salt intake affects blood pressure of chimpanzees: implications for human populations. Circulation 2007;14(116):1563-8.
(10) de Graaf C. Effects of snacks on energy intake: an evolutionary perspective. Appetite 2006;1(47):18-23.
(11) Amen-Ra N. Humans are evolutionarily adapted to caloric restriction resulting from ecologically dictated dietary deprivation imposed during the Plio-Pleistocene period. Med Hypotheses. 2006;5(66):978-84.
(12) Cordain L, Eaton SB, Miller JB, Mann N, Hill K. The paradoxical nature of hunter-gatherer diets: meat-based, yet non-atherogenic. Eur J Clin Nutr. 2002;56:42-52.