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Can a neuroscientist read your mind?

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Are the contents of your mind really 'confidential' or will your thoughts one day be accessible to others?

Media reports into recent research have claimed that neuroscientists are now effectively able to perform ‘mind reading’. Such reporting inevitable raises ethical questions about what applications such research might eventually be put to, and, judging by some of the comments that the on-line versions of these articles have provoked, have alarmed some people regarding the eventual path that such research might take. But how accurate is the claim that neuroscientific techniques can read minds?

Early this year an article in the Guardian  ( http://www.guardian.co.uk/science/2012/jan/31/mind-reading-program-brain-words ) reported that:

‘Scientists have picked up fragments of people’s thoughts by decoding the brain activity caused by words that they hear.’

Reporting on the same experiment the Daily Mail ( http://www.dailymail.co.uk/sciencetech/article-2095214/As-scientists-discover-translate-brainwaves-words–Could-machine-read-innermost-thoughts.html ) claimed:

 ’It’s a staggering development that could have tremendous implications….judges could use mind-reading machines to find out if murder suspects are telling the truth….mind reading devices might be used to eavesdrop covertly on the most private thoughts and dreams.’

The experiment in question, conducted by Dr Brian Pasley and colleagues (1) involved the recruitment of patients who were to undergo brain surgery. The researchers placed electrodes upon the auditory areas of the brain during the period when the patients’ skulls were open and their cerebral cortex exposed. They then played the patients a sequence of different words and recorded the electrical activity generated by the auditory cortex in response to this speech. Using complex modeling procedures they were able to reconstruct the spoken words solely from the neural signals recorded by the electrodes. Furthermore they were able to successfully apply this model to the electrical responses generated by a separate set of words that had not been used in creation of the model (e.g. which were in effect ‘novel’ to the model) suggesting that the model could theoretically be applied to reconstruct any speech heard by the patient.

While these results are undoubtedly impressive, has the media coverage of them been accurate? In terms of the Guardian’s report, their claim that this represents a decoding of ‘fragments of thoughts’ seems to depend on a rather broad definition of the term ‘thoughts’. What the research did was to reconstruct auditory stimuli that the auditory cortex was in the process of analysing. What has been achieved therefore is the decoding, at a detailed level, of the perceptual process, NOT the reading of internally generated thoughts. This is a significant step away from ‘decoding thoughts’ as the  process being decoded is entirely dependent on the presentation of an external stimulus. This doesn’t therefore represent ‘mind reading’ because the same result could theoretically be achieved without reference to the brain, e.g. by taking measurements from the relevant sensory organ or by just observing the sensory stimulus itself (2). Even if the research did represent mind reading, there seems little justification for the Daily Mail’s claim that the research could lead to ‘covert eavesdropping’. It should be obvious that the methodology required not only the opening up of the participant’s skull, but also the co-operation of the participant in allowing data to be taken for the construction of the model. Furthermore what is not mentioned by either article is that the reconstructed words were not actually intelligible to a human listener, but had to be ‘recognised’ via a speech recognition algorithm (an example of the reconstructed speech can be heard here:  http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001251#s5).

Actual Mind Reading?

While the results of Dr Pasley’s study required the participant’s brains to be exposed, other neuroimaging methods are not so intrusive, and could therefore be considered closer to the covert mind-reading reported by the Mail. Magnetic Resonance Imaging (MRI) allows brain activity to be measured in a non-invasive way, so that no surgery of any kind is required (although lying down in a scanner which costs millions of pounds and is the size of a small boat, is still required, making it far from ‘covert’!). MRI studies have produced some equivalent results to that of Pasley’s study, but using visual stimuli; with images (3) and short movies (4) having been reconstructed purely from data obtained from MRI scans. Of course such results don’t represent mind reading any more than Dr Pasley’s study, since they reflect a reconstruction of external sensory information. However other MRI studies have produced results that have allowed scientists to predict processes occurring within a participant’s brain that are not directly tied to the characteristic of external stimuli. A couple of studies by Yukiyasu Kamitani and Frank Tong (5,6) have shown that models can be created that allow an observer to identify to which stimulus a participant is (covertly) attending to. In effect these studies, and others like them, use the output from the perceptual processing mechanisms of the brain to identify how ‘top-down’ influences (such as expectation and attention) are driving perception. Strictly speaking they represent mindreading as although the mental processes in question are still involved in analysing external stimuli, it is not necessarily possible to garner the information provided by the MRI data in any other way (short of asking the person themselves). This is because the ‘top-down influences’ in question arise internally from the brain, rather than being a function of the external stimulus. Neuroimaging has enabled the concept of mind reading to be taken further however, into the realms of decoding mental events that don’t rely on any external stimulation at all. Recent studies have found that it is possible to decode what broad categories of objects someone is imagining, in the absence of any coincident external stimulation (7) although the performance level of the model is reasonably modest (~ 50%). Similarly, it also appears that the results of basic decision making processes can be identified from brain activity, with decisions relating to which button to press and when to press it (8) and whether a participant in lying (9) being decipherable using models constructed in a similar way to those already described. Interestingly the neural information that allows these decisions to be decoded occurs many seconds BEFORE the decision has actually been made, highlighting how conscious actions are likely driven by brain processes that are outside conscious awareness, rather than being the result of conscious ‘free will’. Most recently such work has been extended to more complex scenarios, with MRI data being used to predict at what point in solving an algebraic problem a child is at, and whether they are performing the calculation correctly (10).

The possibility of covert mind reading?

Clearly the aforementioned examples reflect mind reading, but do they represent the top of a ‘slippery slope’ that will lead to technology that will allow the sort of covert eavesdropping envisioned by the Daily Mail? The first impediment to such technology is the process of neuroimaging itself. MRI scanners are far from being portable enough to allow forced or covert application of brain scanning. Furthermore MRI scanning involves the production of a large magnetic field and the firing of electromagnetic pulses towards the object being imaged, both functions that would be totally impractical outside a controlled, isolated environment. Other neuroimaging methods, such as EEG, function by recording the electrical remnants of brain activity from outside the skull, and are therefore cheaper and more portable than MRI. However they lack the spatial resolution that would be required for any sophisticated mind reading application, and in any case they are extremely sensitive to external noise, again making them unsuitable for use outside of controlled environments.

Even if we assume that future technological advances would allow systems to be developed that would enable covert collection brain activity data, would such technology enable your innermost thoughts to be deciphered? There are a number of reasons to doubt that this would be possible. Current mind reading models are only able to distinguish between very broad categories of thoughts, or between very coarse categories of decisions (e.g. lie/truth, attending to one or other stimulus). To be able to read the specific details of an individual’s thoughts you would need models that distinguished between the literally billions of different things that someone could be thinking about, and the multitude of different decisions that they could make. To even create such models would involve the co-operation of individuals in a data collection process that would take an incalculable length of time. Even if such data were collected, and the subsequent required level of computation to create accurate models were possible, the ability to generalize such models to the brain activity of other individuals would rely on an assumption that every person’s brain being identical in terms of where different individual thoughts and memories are stored. This seems extremely unlikely, and is in fact counter to what we know about individual differences in brain anatomy and function. Thus while it is possible to aggregate data across participant to produce mind-reading for coarse decisions, it would be impossible to replicate such a method to distinguish between more subtle categories of thought. Even in situations where co-operation of the participant is attained, and only a coarse distinction between different psychological states is required, such mind reading techniques are problematic. Taking the example of the mooted ‘MRI Lie detector’ such a system will always be somewhat unreliable because, just like the current physiological lie detectors, they could be easily deceived if the participant can train themselves to act as if the truth is a lie (or vice versa). This is because the brain activity which is associated with lying most likely relates to the emotional and cognitive processes involved in creating a false story, rather than to lying per se. It follows that simply engaging in these same emotional and cognitive processes while telling the truth should produce neural activity which mimics that produced by a lie. If even the decoding of simple decisions can be subverted easily, it would seem impossible that attempts at more subtle discriminations of different thoughts would not be subject to even greater uncertainty. Finally it is important to note that all the forms of mind reading reviewed here are the result of probabilistic calculations. The parts of the brain that are deemed active at a certain point in time are the result of statistical computations as to whether a small signal is reflective of task-related neural activity or noise. Likewise the classification of such activity as belonging to one category of thought/decision over another is also based off probabilistic inference. There is no certainty in such a process; in fact it is fraught with uncertainty.

To conclude it seems very unlikely that neuroimaging methods will ever be able to perform the sort of mind reading predicted by scare stories in the press. In some cases such methods may not even represent a particular improvement on the sort of mind reading applications that already exist. What the mind reading research discussed in this article does allow is a greater understanding of how the brain works, which in turn provides insight into how the brain achieves the myriad feats it performs so frequently with apparent ease. The most fruitful practical application of such knowledge is likely to be in the treatment of patients with brain damage. For example the limited mind reading functions possible from existing neuroimaging methods may allow technology to be developed that would allow patients who suffer from brain damage to the extent that they cannot communicate using their peripheral nervous system, some primitive form of communication through their brain activity. In contrast your private thought and memories are likely to remain safe from the prying eyes of neuroscientists!

Image (top right) courtesy of Idea Go:  http://www.freedigitalphotos.net/images/view_photog.php?photogid=809

References

(1) Pasley BN, David SV, Mesgarani N, Flinker A, Shamma SA, et al. (2012) Reconstructing Speech from Human Auditory Cortex. PLoS Biol 10(1): e1001251. doi:10.1371/journal.pbio.1001251 http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001251

(2) Tong, F. & Pratte, M.S. (2012) Decoding Patterns of Human Brain Activity. Annual Review of Psychology, 63: 483-509.  http://www.ncbi.nlm.nih.gov/pubmed/21943172

(3)  Miyawaki, Y. Uchida, H. et al (2008) Visual Image Reconstruction from Human Brain Activity using a Combination of Multi-scale Local Image Decoders.. Neuron 60, 915–929, http://iopscience.iop.org/1742-6596/197/1/012021

(4)  Nishimoto, S., Vu, A.T., et al (2011) Reconstructing Visual Experiences from Brain Activity Evoked by Natural Movies. Current Biology 21, 1641–1646 http://www.sciencedirect.com/science/article/pii/S0960982211009377

(5) Kamitani Y, Tong F. 2005. Decoding the visual and subjective contents of the human brain. Nat. Neurosci. 8:679–85  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1808230/

(6) Kamitani Y, Tong F. 2006. Decoding seen and attended motion directions from activity in the human visual cortex. Curr. Biol. 16:1096–102 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1635016/

(7) Reddy, L., Tsuchiya, N. & Serre, T. (2010). Reading the mind’s eye: Decoding category information during mental imagery. Neuroimage. 50(2) 818-825  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2823980/

(8) Soon CS, Brass M, Heinze HJ, Haynes JD. 2008. Unconscious determinants of free decisions in the human brain. Nat. Neurosci. 11:543–45  http://www.nature.com/neuro/journal/v11/n5/full/nn.2112.html

(9) Davatzikos C, Ruparel K, Fan Y, Shen DG, Acharyya M, et al. 2005. Classifying spatial patterns of brain activity with machine learning methods: application to lie detection. NeuroImage 28:663–68  http://www.sciencedirect.com/science/article/pii/S1053811905005914

(10) Anderson, J.R. (2012) Tracking Problem Solving by Multivariate Pattern Analysis and Hidden Markov Model algorithms. Neuropsychologia, 50(4) 487-498. http://www.sciencedirect.com/science/article/pii/S0028393211003605

 

The dangers of self-report

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A common methodology in behavioural science is to use self-report questionnaires to gather data. Data from these questionnaire can be used to identify relationships between scores on the variable(s) that the questionnaire is assumed to measure and either performance on behavioural tasks, physiological measures taken during an experiment, or even scores obtained from other questionnaires (some studies just report on the correlations between batches of self-report measures!). Self-report measures are popular for a number of reasons. Firstly they represent a ‘cheap’ way (in terms of both time and cost) of obtaining data. Secondly they can be easily implemented to large samples, especially with the advent of on-line questionnaire distribution sites such as Survey Monkey. Finally they can be used to measure constructs that would be difficult to obtain with behavioural or physiological measures (for example facets of personality such as introversion). This issue of self-report methodology is important because studies that use this method are regularly reported in the media (see http://www.bbc.co.uk/news/health-17209448 for a recent example) and therefore have a significant impact on how the general public perceive scientific research. I therefore think it is important to discuss potential problems with self-report measures.

Most (but certainly not all) questionnaires that are used in behavioural research undergo  testing for reliability, to check that they produce consistent results when applied to the same population over time. More importantly they are normally also tested for validity, to check that the questionnaire measures what it claims to measure. Such tests are done following the logic that the questionnaire should be able to discriminate participants in a similar way to relevant non-self report measures. For example scores on a questionnaire measuring depression should be able to discriminate between depressed patients and controls, while scores on a questionnaire measuring diet should be able to predict the ‘Body Fat Percentage’ of respondents with reasonable accuracy. While such tests can act to increase confidence that a questionnaire is measuring what it claims to measure they are not foolproof. For example just because a depression questionnaire can discriminate between patients and controls does not mean that it measures depression well, as the two groups will likely vary in several different ways. Likewise a questionnaire that distinguishes between patients and controls may not be able to identify the (presumably) more subtle differences between depressed and non-depressed healthy individuals, or the range of depressive tendencies within the healthy population. In fact that are a large number of reasons why questionnaire may not be entirely valid, including the following:

Honesty/Image management – researchers who use self-report questionnaires are relying on the honesty of their participants. The degree to which this is a problem will undoubtedly vary with the topic of the questionnaire, for example participants are less likely to be honest about measures relating to sexual behaviour, or drug use, than they are about caffeine consumption, although it is unwise to assume, even when you are measuring something relatively benign, that participants will always be truthful. Worse, the level at which participants will want to manage how they appear will no doubt vary depending on personality, which means that the level of dishonesty may vary significantly between different groups that a study is trying to compare.

Introspective ability – Even if a participant is trying to be honest, they may lack the introspective ability to provide an accurate response to a question. We are probably all aware of people who appear to view themselves in a completely different light to how others see them. Undoubtedly we are all to some extent unable to introspectively assess ourselves completely accurately. Therefore any self-report information we provide may be incorrect despite our best efforts to be honest and accurate.

Understanding – Participants may also varying regarding their understanding or interpretation of particular questions. This is less a problem with questionnaires measuring concrete things like alcohol consumption, but is a very big problem when measuring more abstract concepts such as personality. From personal experience I have participated in an experiment where I was asked at regular intervals to report how ‘dominant’ I felt. As I can honestly say I don’t monitor my feelings of ‘dominance’ and how they change over time, I know that my responses to the question were pretty random. Even if I could conjure an understanding of what the question was getting at, it would be impossible to ensure that everyone who completed the questionnaire interpreted that question in the same way that I did.

Rating scales – Many questionnaires use rating scales to allow respondents to provide more nuanced responses than just yes/no. While yes/no questions do often appear restrictive in terms of how you can respond, using rating scales can bring their own problems. People interpret and use scales differently, what I might rate as ’8′ on a 10 point scale, someone with the same opinion might only rate as a ’6′ because they interpret the meanings of the scale points differently. There is research which suggests that people have different ways of filling out ratings scales (1). Some people are ‘extreme responders’ who like to use the edges of the scales, whereas other like to hug around the midpoints and rarely use the most outer points. This naturally produces differences in scores between participants that reflects something other than what the questionnaire was designed to measure. A related problem is that of producing nonsense distinctions. For example studies sometimes appear where participants are given a huge rating scale to choose from, for example a scale of 1-100 to rate the confidence of a decision as to whether two lines are the same length (2).  Is anyone really capable of segmenting their certainty over such a decision into 100 different units? Is there really any meaningful difference, even within the same individual, between a certainty of 86 and a certainty of 72 in such a paradigm? Any differences found in such experiments therefore run the risk of being spurious.

Response bias – This refers to individual’s tendency to respond a certain way, regardless of the actual evidence they are assessing. For example on a yes/no questionnaire asking about personal experiences, some participants might be biased towards responding yes (i.e. they may only require minimal evidence to decide on a yes response, so if an experience has happened only once they may still respond ‘yes’ to a question relating to whether they have had that experience). Alternatively other participants may have a conservative response bias and only respond positively to such questions if the experience being inquired about has happened regularly. This is a particular problem when the relationship between different questionnaires is assessed, as a correlation between two different questionnaires may simply reflect the response bias of the participants being consistent across questionnaires, rather than any genuine relationship between the variables the questionnaire is measuring.

Ordinal Measures – Almost all self-report measures produce ordinal data. Ordinal data is that which only tells you the order that units can be ranked in, not the distances between them. It is contrasted with interval data which tells you the exact distances between different units. This distinction is easiest to define by thinking of a race. The position in which each runner finishes in is an ordinal measure. It tells you who is fastest and slowest, but not the relative differences between the different runners. In contrast the finishing time is an interval measure, as it provides information relating to the relative differences between the runners. Even when the questionnaire measures something that could be measured in SI units, and is therefore theoretically an interval scale (i.e. alcohol consumption) it is doubtful whether the responses can really be treated as interval because of the problems relating to response accuracy raised above. More pertinently most self-report measures in behavioural science relate to constructs, such a personality measures, that can’t be measured in interval units and are therefore always ordinal. The problem with ordinal data is not the data itself, but the common practice of using parametric statistical techniques with such data, because these tests make assumptions about the distribution of the data that cannot be met when said data is ordinal. Deviations from such assumptions can lead to incorrect inferences being made (3) bringing the conclusions of such studies into question.

Control of sample – this has become more of an issue with the advent of online questionnaire distribution sites like Survey Monkey. Previously a researcher had to be present when a participant completed a questionnaire, now with these tools the researcher need never meet any of their participants. While this allows much bigger samples to be collected much more quickly, it does cause several concerns over the sample make up. For example there are few controls to stop the same person filling in the same questionnaire multiple times. There is also little disincentive for participants to respond with spurious responses, and there is little control over how much attention the participant pays to various parts of the questionnaire. Conversely, from personal experience, I know that sometimes it is hard to complete these questionnaires because there is no way of asking the researcher for clarification as to the meaning of various questions. Finally as the researcher has lost control over the make up of their sample, they may end up with a sample which is vastly skewed towards a certain type of person, as only certain types of people are likely to fill in such questionnaires. These issues existed even before the advent of online data collection (e.g. (4)), but collecting data ‘in absentia’ exacerbates the size of such problems.

Although there are many problems with using self-report questionnaires they will continue to be a popular methodology in behavioural science because of their utility. While it might be preferable for every variable a researcher wants to investigate to be manipulated systematically using behavioural techniques, this is in practice impossible as it would severely restrict what each individual research design could achieve, and would make certain topics effectively impossible to research. Self-report measures are therefore a necessary tool for behavioural research. Furthermore some of the problems listed above can be countered through the careful design and application of self-report measures. For example response bias can be removed by ‘reversing’ half the questions on a questionnaire so that the variable is scored by positive responses on half the questions and negative responses on the other half, thus cancelling out any response bias. Likewise statistical techniques are being devised to attempt to pick out dishonest reporting, a problem that can also be attenuated by ensuring anonymity and confidentiality of responses (e.g. the researcher leaving the room when the participant is completing the questionnaire). Given this it would be wrong to dismiss any findings that are reliant on self-report measures. However whenever you read about research where self-report measures have been used to draw conclusions about human behaviour, it is always worth bearing in mind the multitude of problems associated with such measures, and how they might impact on the validity of the conclusions that have been drawn.

(1) Austin, E. J., Gibson, G. J., Deary, I. J., McGregor, M. J., & Dent, J. B. (1998). Individual response spread in self-report scales: personality correlations and consequences. Personality and Individual Differences, 24, 421–438. http://www.sciencedirect.com/science/article/pii/S019188699700175X

(2) Balakrishnan, J. D. (1999). Decision processes in discrimination: Fundamental misrepresentations of signal detection theory. Journal of Experimental Psychology: Human Perception & Performance, 25, 1189-1206. http://psycnet.apa.org/psycinfo/1999-11444-002

(3) Wilcox, R. R. (2005). Introduction to robust estimation and hypothesis testing. Academic Press. ISBN: 0127515429

(4) Fan, X., Miller, B. C., Park, K., Winward, B. W., Christensen, M., Grotevant, H. D., et al. (2006). An exploratory study about inaccuracy and invalidity in adolescent self-report surveys. Field Methods,18, 223–244. http://fmx.sagepub.com/content/18/3/223.short

The Immune Cell, the Neutrophil – the Good, the Bad, or the Ugly?

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By Kathryn Higgins

Throughout our lifetime our bodies sustain infections and injuries, and the body deals with them by mediating an inflammatory response. This happens by cells within our blood entering the site of infection or injury and carrying out multiple biological reactions. These reactions can kill the microorganism that has caused the infection, but also heal at the site of injury, and hence resolve inflammation. These blood cells are collectively called white blood cells or leukocytes, and there is one in particular, named the neutrophil, which not only helps to resolve inflammation but can also exacerbate the condition further. This has resulted in the neutrophil having a reputation for being both ‘good’ and ‘bad’ in inflammatory conditions.

The reputation of the neutrophil is influenced by many molecules that are released from other cell types during inflammation. These molecules influence the activity of the neutrophil in various ways, either stimulating the cell so inflammation can be resolved or inhibiting a particular function the cell has. The influence of these molecules determines whether the neutrophil is able to carry out its functions efficiently or whether the inflammatory condition will be aggravated further. The biological activities of neutrophils therefore need to be understood to comprehend how they function and how these roles can be modulated to determine what effect this has during an inflammatory response.

Neutrophils form part of the body’s innate immunity which involves a series of defence mechanisms that protect the host from infection and form the early barriers to infectious diseases without relying on the production and expansion of antibodies that form the adaptive immune response. When an infection occurs, the innate immune response is triggered to rapidly detect and destroy the infection. Neutrophils are one of the first blood cells to respond to infection and are recruited from the circulating blood into the tissue by molecules called chemoattractants1. These molecules, released from cells at the site of infection and also from the microorganism, also known as a pathogen, provide a chemical gradient for neutrophils to migrate along, with the highest concentration of these chemoattractants situated at the site of infection, so the cells are led directly to the infected site. Once in the tissue the lifespan of the cell is increased to approximately 1-2 days as opposed to 6-10 hours in the circulation. This is to lengthen the amount of time neutrophils have to carry out their functions and resolve inflammation.

A vital part of the innate immune response is the ability of the neutrophils to engulf pathogens and aid the resolution of infection. This process is called phagocytosis and classifies the neutrophil as a phagocyte, so called after the Greek for ‘devouring cells’. When the neutrophil has entered the infected site and detected the pathogen, the outer membrane of the neutrophil surrounds the pathogen to engulf it and so the pathogen becomes taken up into the cell. Neutrophils contain many granules and these are packed with lots of toxic reagents. Upon engulfment these granules fuse with the pathogen and release their toxic contents, by a process called degranulation, and these contents assist in the killing of the pathogen2.

In addition to degranulation, neutrophils can also kill pathogens by oxidative mechanisms, so called because molecular oxygen is required. This involves a process named the respiratory burst and it is the major mechanism by which neutrophils kill and digest pathogens. During the engulfment of a pathogen into the neutrophil, molecular oxygen is also rapidly taken up. The oxygen is then converted, by a series of chemical reactions, into several toxic compounds such as hydrogen peroxide. Further chemical reactions may occur producing even more potent substances3 and when the pathogen becomes exposed to these various toxic oxygen metabolites the pathogen is digested and destroyed within the cell.

Neutrophils have also been shown to kill pathogens outside of the cell, i.e. extracellularly, rather than engulfing them. This occurs by neutrophils releasing web-like structures of genetic material, called neutrophil extracellular traps (NETs)4. These NETs are composed of fibres that trap pathogens, and have been proposed to contain high concentrations of anti-microbial compounds, such as those contained within their granules, to kill pathogens and prevent the spread of infection. Some bacteria, however, have evolved to counteract being killed by NETs by producing substances that degrade the genetic material that make up NETs, such as Streptococcus pneumoniae5, which is known to be the common cause of pneumonia.

Once the pathogens have been dealt with, and to completely resolve inflammation, neutrophils need to be cleared from the tissue. If the cells do not become removed then all their toxic contents, such as the granule contents and oxygen metabolites that kill pathogens, may leak out of the cell and damage surrounding cells and tissues, which will only make the inflammatory condition worse. For removal, neutrophils firstly need to die. This is by a programmed type of cell death termed apoptosis6 which ensures that the cellular membrane remains intact so these toxic contents are retained within the cell and cannot be released. During this cell death a fatty (lipid) molecule called phosphatidylserine is flipped to the outer surface7. This lipid acts as a signal for tissue macrophages to target the dead neutrophil. Tissue macrophages are another class of white blood cell with a vital role of recognising apoptotic cells. Once the signal has been recognised, the neutrophil itself is then engulfed by the macrophage and cleared from the tissue. It is essential that these apoptotic cells are removed efficiently from the tissue because a delay in their clearance can also increase the chance of their intact membranes becoming leaky.

Apoptosis is therefore a process which needs to be tightly regulated to ensure inflammation is resolved efficiently. If cell death is stimulated too early then the number of functional neutrophils in the tissue is reduced. This would limit the hosts’ ability to fight infection and resolve inflammation. For example, some infections induce neutrophil apoptosis, such as the influenza A virus8 and the Pseudomonas aeruginosa bacterium9 to favour their own survival. In contrast to this, if apoptosis is delayed, as seen with the inflammatory joint disorder rheumatoid arthritis10, the number of circulating cells in the tissue increases, toxic contents may then be released from the cells, and surrounding tissue would be damaged potentiating inflammation further. This contrasting effect of the neutrophil is often referred to as the ‘double-edged sword’ effect, i.e. can be both ‘good’ and ‘bad’ during the inflammatory process, with the damaging effects of the neutrophil quickly out-weighing the benefits. Although neutrophils may often appear to be the ‘bad’ guy in certain inflammatory conditions this is typically due to the influence of other molecules released from surrounding cells. Without this influence the primary aim of the neutrophil is to resolve inflammation, making them overall the ‘good’ guys of the inflammatory process.

References:

  1. Yoshimura, T., Matsushima, K., Tanaka, S., Robinson, E.A., Appella, E., Oppenheim, J.J. and Leonard, E.J. (1987) Proc. Natl. Acad. Sci. USA 84, 9233-9237
  2. Campanelli, D., Detmers, P.A., Nathan, C.F. and Gabay (1990) J. Clin. Invest. 85, 904-915
  3. Albrich, J.M. and Hurst, J.K (1982) FEBS Lett. 144, 157-161
  4. Brinkmann, V., Reichard, U., Goosmann, C., Fauler, B., Uhlemann, Y., Weiss, D.S., Weinrauch, Y. and Zychlinsky, A. (2004) Science 303, 1532-1535
  5. Beiter, K., Wartha, F., Albiger, B., Normark, S., Zychlinsky, A. and Henriques-Normark, B. (2006) Curr. Biol. 16, 401-407
  6. Kerr, J.F., Wyllie, A.H. and Currie, A.R. (1972) Br. J. Cancer 26, 239-257
  7. Fadok, V.A., Voelker, D.R., Campbell, P.A., Cohen, J.J., Bratton, D.L. and Henson, P.M. (1992) J. Immunol. 148, 2207-2216
  8. Colamussi, M.L., White, M.R., Crouch, E. and Hartshorn, K.L. (1999) Blood 93, 2395-2403
  9. Usher, L.R., Lawson, R.A., Geary, I., Taylor, C.J., Bingle, C.D., Taylor, G.W. and Whyte, M.K.B. (2002) J. Immunol. 168, 1861-1868
  10. Ottonelo, L., Cutolo, M., Frumento, G., Arduino, N., Bertolotto, M., Mancini, M., Sottofattori, E. and Dallegri, F. (2002) Rheumatol. 41, 1249-1260

Ancient Humans: Becoming human

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There can be only one

No I’m not referring to Highlander I am referring to species of humans. Out of many species that fall under the umbrella term of the genus Homo we are the only one that has survived- Homo sapiens. The mystery behind this has had religious, philosophical and scientific ramifications over the ages that have been debated to this day. But who were these other humans? And can we really consider them to be human?

From the archaeological record we know a fair bit about these other humans which may be able to tell us just how human they were by identifying sociality, intelligence, technology and culture.

Homo habilis Stringer and Andrews 2005 P. 68

Robin Dunbar found a relationship between a part of the brain known as the neo-cortex and theory of mind. Theory of mind refers to a level of sociality- the first level dictates that person A knows something about person B. The second level dictates that person A knows that person B knows something about person C; and so on. Therefore the higher the level, the higher the capacity for an individual to comprehend what a group knows. This type of intelligence becomes important when we start to consider how a group functions within a landscape; they form social bonds which is crucial for group activity. Seeing this hallmark within primates, Robin Dunbar extrapolated the size of the neo-cortex within extinct humans from archaeological remains, and use it to infer upon theory of mind and sociality. What he found was a general clumping of all the extinct Homo species around the Homo sapiens mark. The lineage that led to the genus Homo diverged 6 million years ago from chimpanzees. The first Homo species that appeared on the scene was Homo habilis at 3 million years ago. It is very likely that by then, H. habilis had the intelligence to understand social situations.

While H. habilis was the first Homo species to make and use tools (which led to their alternative and rather informal name Handy Man), Australopithecus afarensis was actually the first species to do so. A. afarensis was an earlier species that walked on legs as opposed to knuckle-walking, and it is possible that the Homo lineage came from this species. The earliest evidence of tool use on bones comes from Ethiopia dated at 3.39 million years ago where it is known that A. afarensis inhabited this region. Clearly by the time of H. habilis, we start to see the beginnings of a rather primitive form of intelligence that enabled them to form social groups and use their own type of technology, which was known as the Oldowan tool industry.

Nariokotome Boy. Stringer and Andrews 2005 P. 139
Homo erectus

Eugene Dubois, a Dutch palaeo-anthropologist, was in Java (S.E Asia) in 1890 when he found a set of skeletal remains. He had found what was later called Homo erectus. This species was clearly the first member of the Homogenus to have migrated out of Africa. One of the most important finds belonging to this species was Nariokotome Boy found in Kenya in 1984. What was particularly interesting about this find was that the individual was thought to be just a little bit older than 11 years old and, from his remains, it could be seen that he was about 6 foot tall! This is a species that was very well adapted to the hot climate of Africa; H. erectus was tall, gracile and slender with long legs that enabled them to travel for long distances, which ultimately they did.

 

Homo heidelbergensis
Neanderthals

To perfectly complement how H. erectus was adapted to the hot climate of Africa, H. heidelbergensis illustrates adaptations to a cold climate. Likely to diverged from H. ergaster as well (and thus be a sister group to H. erectus), H. heidelbergensis was the last common ancestor of Neanderthals and modern humans. But it was also the first Homo species to move into Europe. The commonly held theory is that H. heidelbergensis evolved into Neanderthals in Europe. As such Neanderthals appeared to be very well adapted to the cold; they were short, stocky and well-built when compared to the tall and more graceful modern humans.

They had a wide distribution across Europe and Asia; from Israel to Wales, and as far north as Siberia and south as Gibraltar. Vast amounts of archaeology have shown that Neanderthals had their own culture and technology, and existed together in their own social groups. But all good things come to an end. By the time the Neanderthals had settled into their life in Europe, at 60,000 years ago, the climate got severely worse. Before the start of the Ice Age at approximately 28,000 years ago, modern humans had already arrived and settled themselves, and the Neanderthals had become extinct.

Cave painting from France
Figurine from Germany

The arrival of modern humans into Europe from 50,000 years ago is part of the next hallmark in our evolution: the Upper Palaeolithic Revolution. This revolution saw a cultural explosion. A wide variety of art has been attributed to the Upper Palaeolithic. Such examples include ornaments, figures and cave art, but it also included technology for acquiring and processing food. While the Neanderthals had their own technology for the same reasons, modern humans had a much more diverse toolkit. But as far as we know, no art found has been associated with Neanderthals.

In 2010, DNA analyses suggested that Neanderthals and modern humans interbred just outside of Africa before modern humans spread around the world. Following on from this, a few other studies have suggested that interbreeding was occurring between other human species, such as between H. erectus, and a possible new human species the Denisovans, and between modern humans and the Denisovans. While many more analyses need to be done to confirm this, this claim has immediate implications as to what we consider a species. A species is defined as a group of individuals that can only reproduce with each other. If Neanderthals and modern humans were interbreeding with each other, then this suggests that Neanderthals and modern humans are the same species, and that we (current modern humans) are descended from this interbreeding. More work however needs to be done. Ancient DNA is a field fraught with difficulties but as DNA technology improves we will have more data to look at.

By now we see a picture emerging as what we could consider as “being human”: the capacity for sociality and intelligence, use of technology and the element of culture. At the same time the lines between these various humans are beginning to blur. If the DNA evidence holds up, as more studies are carried out, then perhaps we should start to consider all of these humans under just one species name and designate each one by sub-species. The archaeological evidence certainly suggests that many of these types of humans had a level of intelligence that meant they could establish technology and culture which appears to be just as different from each other as they are morphologically. We are so willing to find the point in time where we can say “here is where we became human!”  The truth is we can’t. We, Homo sapiens, may have arisen around 200,000 years ago, but humanity could have begun much earlier. So when natural selection and bad luck killed off the other types of humans, it left us- the sole human survivor. This then leaves us with just one question:

For how long, in this changing world, can we survive?

For more information:

  • Dunbar, R. 2003. The Social Brain: Mind, Language and Society in Evolutionary Perspective. Annual Review of Anthropology 32, 163-181
  • Green et al. 2010. A Draft Sequence of the Neandertal Genome. Science 328 (5979) 710-722
  • Stringer, C. Andrews, P. 2005. The Complete World of Human Evolution. Thames and Hudson, UK.
  • Oppenheimer, S. 2004 Out of Eden. Robinson, London

This article was written to complement the presentation “Ancient Humans: Who were they? And who got it on?” that was given on the 5th December 2011 for the Natural History Society. For more details on the author, see http://independent.academia.edu/DanaeDodge

 

Humans as data sources!

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I have recently begun collecting data for an experiment.  Data collection is the ‘bread and butter’ of science, without it there is no data, and therefore no results, conclusions or theories. While scientists can collect data from almost anything, as I am involved in behavioural science the data I require almost always comes from people; volunteers who agree to participate in an experiment. Using human participants (volunteers were previously referred to as ‘subjects’, but this term was dropped because it suggests that the volunteer is ‘subject’ to the experiment, rather than a willing participant) as your main data source produces additional (or at least different) problems to that presented from other data sources. I presume that in natural sciences, materials are ordered from a supplier, and therefore can be (hopefully) acquired to a predetermined timescale at a predictable cost. This is not the case with using participants, whose availability depends on the willingness of the local (normally student) population to submit to your study. Likewise whereas physical data-sources presumably perform reasonably consistently (i.e. putting the same quantity of lithium into the same quantity of water will always produce similar results, as long as other relevant variables are held constant) the same cannot be said for humans. The performance of two participants, tested under identical conditions, can vary drastically, even when the participants are from very similar backgrounds. Similarly an individual participant’s performance can vary widely during an experiment as concentration and motivation fluctuate. These factors produces a large amount of variance in the resulting data that is not due to the experimental manipulations the study is designed to investigate. The consequence of this is that the amount of data that needs to be collected in order to overcome such variance, and therefore provide a valid result, increases.

The variability in human performance also generates the further problem of generalisation. How can you be sure that the participants you have used in your study provide data that can be generalised to humans in general, given that individuals vary widely on how they perform the task? Larger samples (more data collection!) can make a sample more representative, but as undergraduates are usually the easiest source of data, inevitably most studies involving humans utilise samples that are non-representative of the general population to a greater or lesser extent. You could write an entire book on the issues around sampling and generalisation (indeed many have (1)) suffice to say that when you read any behavioural science research, especially that which is weighted towards the ‘social science’ end of the spectrum, it is worth considering the sort of people who may have participated in the research, and how that may effect the results that were found.

There are other, more basic problems with using humans as a data source.  Participants may fail to show up for the study, they may fail to understand what is required of them in ways that you couldn’t predict, they may even not take the experiment seriously, making little effort or deliberately producing nonsensical data. In physical science I suspect the main problem that can occur with an experiment is equipment failure. This is also a danger with behavioural experiments, but ‘participant failure’ is often a more pressing concern.

A final issue with using humans as a data source is that any study involving humans requires ethical approval, meaning that the research design is scrutinized by a committee prior to data collection for anything that might be deemed unacceptable. Ethical procedures are in place for a good reason, as in the past certain scientists were subjecting volunteers to all sorts of unpleasant and/or morally dubious procedures in the name of science (2). However perhaps inevitably ethical checks tend towards the cautious in terms of their application. While for many behavioural and social science research, ethical approval is merely a formality, it can restrict scientific enquiry for those of us that are interested in the facets of human behaviour that can only be evoked through manipulations of the participant’s emotional state or physical comfort.

So, given that I have just spent 700 words complaining about the problems of using humans as data sources,  why have I chosen a career path which relies so heavily on collecting data from humans? Well there are some advantages of performing research on humans. Most importantly humans are (to me at least) the most interesting subject in science. You can keep your chromatography, your mutagenesis and your particle accelerators, nothing they produce will ever be as interesting to me as investigations into human mind and behaviour. The variability in human performance which causes us so many problems is actually the main reason the subject of psychology is so interesting. A second advantage to behavioural research is that it allows you to meet a lot of different people who volunteer for your study for a variety of different reasons. The fact that certain people are prepared to give up their time and submit themselves to the often unpleasant or tedious tasks that make up your research project has helped reaffirm my faith in human nature after years of working in soul-destroying office jobs. Apart form anything else, the actual data collection part of a behavioural study certainly helps to break up a research process which would otherwise mainly consist of reading journal articles and staring at a matrix of numbers on a computer screen.

I’ll be coming to the end of the data collection process soon. I will then have weeks of grappling with the resultant data to look forward to!! As a final plea, if there are any men out there who fancy participating in my research then get in contact, as I still need a few human ‘data sources’ to complete my study!

(1) Rao (2000) Sampling methodologies with applications. Chapman & Hall
(2) See the early chapters of Naomi Klein’s book “The Shock Doctrine” (Penguin, 2008) for a description of some particularly unethical experiments performed in the US.

What is cognitive neuroscience, and why should anyone care?

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I often have trouble explaining to people what I am doing for my PhD. This is not a consequence of the topic being so fiendishly complex that no-one else can understand it. Instead it comes from a fact that the area of study seems to fall between several difference subject areas. When I tell people that I am doing my PhD within the Neuroscience department I imagine this provokes images of test-tubes, microscopes and pipettes, and perhaps associations with genetics, animal testing and stem cells. In reality I have little knowledge or experience of any of these topics, having last done ‘traditional’ lab work while I was at secondary school. If you asked me to dissect something, I would probably run a mile! When I instead say that I work within the psychiatry department this probably brings up an altogether different set of images, of drug therapies, ECT and perhaps of ‘talking therapies’ such as CBT (cognitive behavioural therapy). In fact both the above statements regarding my PhD are true, as the Psychiatry department sits within the Neuroscience department, but neither appear to give an accurate impression of what I actually do.

The best description of my area of research is ‘cognitive neuroscience’, but what does this mean? Cognitive Neuroscience relates to the study of the neural basis of behaviour. Roughly, it bridges the gap between biological sciences, and behavioural sciences such as psychology and psychiatry. It attempts to determine how the brain achieves the legion of processes that it performs – crudely ‘what part of the brain does what’! Cognitive neuroscience has only been seen as a separate area of study relatively recently, partly because the advanced brain imaging techniques which the discipline now heavily relies on have only been developed within the last 30 years (according to Wikipedia the term ‘cognitive neuroscience’ itself was coined in the back of a taxi in 1979!!). However scientists from various disciplines have been trying to understand how the brain functions, using whatever methods were available, since at least the 19th century.

Cognitive Neuroscience relies heavily on work done within behavioural sciences, which have served to define how human behaviour and cognition can be classified into concepts that can be studied. Unsurprisingly therefore, cognitive neuroscience research normally involves the application of a behavioural task which has already been utilised without the use of brain imaging techniques. One question this raises is what does knowing how the brain achieves it function tell us that purely behavioural science does not?  Psychologists have been ably investigating the details of mental processes for well over a century without knowing (or even caring) what part(s) of the brain are involved. The knowledge that spatial processing is largely dependent on the Hippocampus is not necessary for studying the intricacies and individual differences in spatial processing. So what does an understanding of the neural basis of mental processes achieve?

Firstly understanding the neural basis of a mental process can help distinguish between different theories relating to how that process is performed. Behavioural data is often not sufficient to distinguish between competing theories (e.g. whether a particular process is performed in totality, or whether it is split into components processes that are dealt with separately, and whether such component processes are performed in parallel or in series). Neuroimaging data can be used to provide strong evidence in relation to these questions (1).  Secondly cognitive neuroscience can provide insight into areas of cognition that were difficult or impossible to address without neuroimaging techniques. For example much work has been done on trying to understand what the brain does ‘at rest’ (i.e. when no task is being performed, effectively ‘mind wandering’) which can allow us to understand how the brain might work as an self-contained integrative mechanism. As, by definition, non-task related mental processes can’t be manipulated systematically, it is hard to investigate these processes from a purely behavioural standpoint. Similarly neuroimaging has enabled scientists to begin to uncover the neural basis of ‘consciousness’, raising interesting questions about how our experience of the world is constructed (3). These achievements of cognitive neuroscience help elucidate the nature of human thought and behaviour, shedding light on why we act the way that we do. 

On a larger scale, understanding how the brain is able to processes such a large variety of information, and produce such a wide variety of responses, can help guide the design of artificial intelligence systems intended to mimic human abilities, facilitating advances in medicine and engineering. Finally, and perhaps most importantly, knowing how the brain produces certain responses can lead to the development of interventions to alter the functioning of the appropriate brain areas when those responses become problematic (e.g. during mental health disorders). One of the major aims of cognitive neuroscience is to identify the neural deficiencies that mark various psychiatry and neurodegenerative disorders. From this information it becomes potentially possible to identify methods of combating such deficiencies. Indeed biological interventions are being developed that can target specific brain areas, potentially offering great hope for improving the therapeutic treatment of mental disorders.  

References

(1) Jonides et al (2006). What has Functional Neuroimaging told us about the Mind? So many examples, so little space. Cortex, 42, 414-417 http://www-personal.umich.edu/~jjonides/pdf/2006_3.pdf

(2) Van den Heuval & Pol (2010) Exploring the brain network: A review on resting-state fMRI functional connectivity. European Neuropsychopharmacology, 20(8), 519-534 http://www.sciencedirect.com/science/article/pii/S0924977X10000684

(3) Dehaene & Changeux (2011) Experimental and Theoretical Approaches to Conscious Processing. Neuron, 70. 200-225 http://www.sciencedirect.com/science/article/pii/S0896627311002583

Science and cartoons

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Guest post from Caroline Parkin.

Two pieces of news caught my eye today; a new mushroom has been described and named, and Sonic the Hedgehog, a video game character is 20. Read on to find out what the connection between them is.

Opinions are divided, heated debates can be heard in science departments the world over, the bone of contention? Should new genes, species, disease and other discoveries be named in an orderly fashion, or at the whimsy of the discoverer?

The privilege of naming a new discovery has long been the reward for diligence and hard work. Immortalizing oneself or an admired contemporary was the traditional choice.  But more imaginative choices have also been made.

One of my favourites, and close to my heart, are the members of the hedgehog gene family.  The first Hedgehog gene was discovered in 1978 by Christiane Nüsslein-Volhard and Eric Wieschaus, in the fruitfly, Drosophila. If Drosophila lack the gene for Hedgehog, they have a thick coat of spikes (called denticles) that reminded the scientists of a hegehog, and so that’s what they named it. Later, similar genes were found in vertebrates, but instead of there being just one Hedgehog gene, there were multiple, and they needed to be distinguished from each other, two were named after hedgehog species, Indian and Desert, whilst the most famous (and most biologically active) was amusingly named Sonic, after the video game character.

Fruitfly genes provide fertile ground for interesting names, such as the two mutants amnesiac and cheapdate. They’re both have defects in the same gene (called amnesiac), whilst the mutant amnesiac has memory loss, the change that causes the cheapdate phenotype (physical manifestation of a gene), lowers the fly’s tolerance to alcohol. 

Other favourites are; methuselah, which increases the lifespan of flies, named after the biblical figure who lived to 969, stargazermutants look up over and over (due to an affect on the cerubelum) and brainiac flies have much larger brains then normal.

Zebrafish gene names are often imaginative too, such as the class of blood mutants, that were discovered by the Zon lab, which are named after fine wines, such as chardonnay, chablis and merlot (rumour has it that the discoverer of a new gene in the lab is awarded a bottle of the corresponding wine – hence an increase in more obscure and expensive wines as time has gone on!) 

Understandably perhaps, the penchant for amusing names in science seems be dying out, in favour of methodical, structured naming, saving doctors from having to give the unfortunate news, for example, that a patient has a mutation in swiss cheese (which results in holes in the brain, although for the record, I know of no patients that have this mutation!)

 

However, wit amongst scientists has not been lost forever, for today I learnt of a new species of mushroom, discovered by researchers from

San Francisco State University,

that is shaped like a sea sponge, and was therefore named: 

Spongiforma squarepantsii 

after the yellow-marine dwelling-cartoon character.

This makes me happy.  

Caroline Parkin is a researcher based in the MRC Centre for Developmental and Biomedical Genetics at the University of Sheffield. She has her own website on the use of zebrafish as model organisms www.fishforscience.com

Dominant and Recessive Genes In Humans

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As briefly referred to in the previous Genetics blog, for each of our genes we posess two ‘alleles’. One of these alleles in inherited from our father and one from our mother. There can be many different alleles for one gene and it can be completely up to chance, or perhaps luck, what we inherit from our parents. When speaking in general terms about dominant and recessive alleles, we tend to speak about genes as if for each of them there are two different alleles. This is not always, or often, the case, but it sometimes is and makes it much easier to explain this way.

For example, for a particular gene, say the ability to roll your tongue, there is a dominant and a recessive gene. We can call the dominant allele ‘R’ for being able to roll our tongue and the recessive allele ‘r’ for being unable to roll our tongue. Our parents could posess any combination of these alleles: AA, aa or Aa. Then, it is completely down to chance what we inherit from them.

One unexpected example is that the allele for dwarfism in humans is the dominant allele and the allele for normal growth is recessive. This means that if we inherited both of the different alleles for this gene we would show the dwarfism trait.

Below is a table of dominant and recessive traits shown in humans.

Dominant Trait in Humans

Recessive Trait in Humans

A blood type

O blood type

Abundant body hair

Little body hair

Astigmatism

Normal vision

B blood type

O blood type

Baldness (in male)

Not bald

Broad lips

Thin lips

Broad nose

Narrow nose

Dwarfism

Normal growth

Hazel or green eyes

Blue or gray eyes

High blood pressure

Normal blood pressure

Large eyes

Small eyes

Migraine

Normal

Mongolian Fold

No fold in eyes

Nearsightedness

Normal vision

Rh factor (+)

No factor (Rh -)

Second toe longest

First or big toe longest

Short stature

Tall stature

Six fingers

Five fingers normal

Webbed fingers

Normal fingers

Tone deafness

Normal tone hearing

White hair streak

Normal hair coloring

 

When we are speaking about the inheritance of alleles and the genetic make-up of a person with respect to one gene, we use one of two phrases. The first is homozygous, meaning that the two alleles an individual posesses for one gene are the same i.e. AA or aa. The second is heterozygous, meaning that the two alleles an individual posesses for one gene are different i.e. Aa.

By Robyn Bradbury

What Is The Problem With Stem Cell Research? (Part III)

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Stem cell research leads to very strong and different opinions globally, but why? What is it about this incredible tool that allows it to be condoned and appreciated in one country, and considered immoral in others? Well, as with many issues that span the world, the local ethics play a large role in how they are received.

The main ethical argument comes down to how embryonic stem cells are taken. Because they exist around 5 days after an egg has been fertilized, the procedure involves destruction of the early embryo. Understandably, this is an unpleasant thought. However, our UK laws only allow the use of eggs spare from those who have undergone IVF (in-vitro fertilization) treatment, or from donors, it is also possible to source embryonic stem cells from fluid in the placenta and umbilical cord. The eggs from donors are fertilized outside the body, and never put back in. The artificially fertilized embryo is then grown for a maximum of 14 days. When the cells are derived (5 days after fertilisation) they are kept in culture where they can keep replicating and survive for a long time. However, new embryonic stem cells are required usually because culture conditions can lead to the cells gaining adaptations, which basically means the cells we are working with are no longer true to all stem cells. In order for all results to be standardized against other countries and labs, it is important the cells we are working with are the same anywhere else in the world, otherwise new discoveries could just be false results due to lab techniques and conditions.

Regardless of faith, most individuals consider killing humans unacceptable, but the big issue is at what point would you consider the moral status of a human being should be given to the embryo? Some religious sects believe it is at the instant the sperm fertilizes the egg, whilst others believe it is later than this. Some laws use the term ‘moment of conception’ to define the rights of a foetus, however this is ambiguous because there is no real moment, it is a progressive event that is hard to pin point.

It is almost impossible to put a definitive answer on the moral status; before implantation of the developing embryo in to the uterus wall, 14 days after fertilisation, it is common and natural for fertilized eggs to be discarded by the body if the conditions are not perfect, and also some current contraceptive devices work by preventing implantation into the uterus wall. This means early embryos are discarded both naturally and unnaturally already, so is research on them arguably more acceptable than the common wastage?

In order to determine when embryos deserve human rights, many use ideas of individuality and viability to help. In normal circumstances, the early embryo implants into the uterus at day 14. Before this, the egg only has the potential to become a person; up until 14 days, the egg can split in two to form identical twins, or two eggs (fraternal twins) can fuse to develop one person. If one egg can contribute to two people, or half a person, then it follows that the embryo isn’t truly a human with all attributed rights. After 14 days is a different matter. 20 weeks is around the last point that it is legally possible to have an abortion. Before this date it is known that the foetal tissues, including nervous system, are not developed enough for there to be any ability to survive independently. Premature babies can survive if born after around 26 weeks, so by this point their tissues are developed and connected, can respond to pain, and are they are undoubtedly human. Somewhere between individuality and viability lies the truth about when a foetus deserves human rights. We should all make our own opinions, and it is definitely a grey area with no single view right or wrong, but because embryonic stem cells are taken at 5 days, rather than 14, it is becoming increasingly acceptable to generate them for research.

Hopefully you understand this is not a deliberate provocation on the scientists’ behalf, but a necessity to improve the lives of others, and quench a certain thirst for knowledge. As scientists, we are required to be unbiased, and therefore we must accept beliefs and customs of others, and be as open to their views as our own. In my opinion, this is actually one of the most impressive aspects of our society. Britain is arguably the most multicultural, scientifically advanced nation in the world. The laws and restrictions put upon us are designed to reach a logical middle ground, and there are a number of authorities that subject research plans to heavy scrutiny before they are allowed to proceed. This, from some perspectives, may be seen as a travesty against scientific progress, but from another angle it ensures all our research is important, significant and ultimately useful. Without such rules our citizens are put at risk from promises and treatments that are unsubstantially founded. What’s more, these are precious cells and as scientists we have a responsibility to respect such a powerful tool that holds great value in every sense of the word. I personally believe that the cause justifies the means, as the goal for the research is to reduce suffering, but what do you believe?

Another controversial issue concerns a technique called somatic cell nuclear transfer. This is where the nucleus from a human cell replaces the nucleus of an egg, and the new environment changes the human nucleus to a fertilized egg-like state. This is called reproductive cloning, because if the egg were to survive it would result in an exact replica of you. This is an intriguing technique because they can use eggs from animals (e.g. cows), which are easier to get hold of, and then the nucleus that replaces the cow genetic information would be derived from the patient themselves. This leads to production of patient specific embryonic stem cells, and if we were to take the cell from a patient with a genetic disease then we can use the embryonic stem cells this technique generates to improve our understanding of how the disease is characterized, develops, and provide a model to work with for future treatments.

Born in 1996, Dolly the sheep was the first mammal to be cloned using cell nuclear transfer, showing the principle of how adult cells can be made to reverse back to a pluripotent state. However, it isn’t an easy process because often the embryos do not survive – of 239 eggs, Dolly was the only one to be successfully fertilized and live. But it still sparks debate as people worry about cloning humans. The Human Fertilization and Embryology Acts prohibit this, so there is nothing to actually worry about, but it is interesting that the principle of creating human life exists outside of sexual intercourse. Many people consider it ‘playing God’, which depending on your view, it is – but I guess the argument comes down to whether ‘playing God’ is a good or bad thing. Again, if it saves lives, and we have the power to do it (in itself an act of God?), does the cause justify the means? There were reports in 2004 that a well-known lab in Korea had cloned humans, but in hindsight this result turned out to be false and unethical on a number of grounds. Reproductive cloning is a sensitive subject as it opens a can of worms in relation to, hypothetically, whether clones have the same rights, would they be treated as equals, so on and so forth. Even the idea of engineering babies through IVF, to prevent risk of genetic disease, is a minefield of ethical, moral and financial explosives e.g. what if people create their ‘perfect’ children? How will genetically engineered children be treated? Will natural humans be treated worse? Will ‘Brave New World’ become the reality?

We know from examples throughout history, that it is controversial issues that help scientific advances break through. Controversy just implies that society is not decided on a matter, not that the matter is inherently wrong (or right). It proves how our opinions as a race have changed over time, and the mere fact that we can discuss these issues is an achievement in itself. Protesting an opinion improves research, and prevents science becoming stagnant. Science is supposed to be about searching for the unknown and explaining it, but ventures into the unknown can unearth results and predicaments that no one has the foresight to see, whether good or bad. Scientists are the modern day versions of Christopher Columbus; to discover the new world you have to sail off the edge of the map.

 

Dolly’s Cell Nuclear Transfer – I.S.

Nucleus from egg is removed

and replaced with a nucleus of a normal adult cell from Dolly,

the egg can then develop inside uterus as normal, to generate a clone of Dolly

∞

Why Should We Study Stem Cells? (PART II)

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Well, the more they are studied the more they tell us about how our body functions in normal and diseased states, showing amazing potential in a therapeutic sense. In the US, 2009 and 2010 saw the first use of human embryonic stem cells in clinical trials, but they were turned into neural support cells before they were implanted in spinal cord injury patients. This research was performed on animal models first to ensure its safety, and stands as a landmark in stem cell therapy. Currently, this is largely how such therapies are developing; taking an embryonic stem cell and turning it into a more committed cell type that can then be implanted.

Other notions of directly injecting embryonic stem cells into patients to treat disease and degeneration are a premature and scary thought, putting patients at high risk of cancer, and thankfully are not allowed in most countries. As stem cell scientists, we don’t want to promise miracle cures, but we are very much aware of how they can help current strategies against many illnesses. For example, embryonic stem cells can divide forever and create two new cells each time. These divisions are tightly controlled, but cancer shows the same ability without the control. So, as you may see, learning what controls and restricts division improves our understanding of what goes wrong in a normal cell that allows it to switch to a cancerous state, and how we may set about stopping this. Some respected theories even suggest that cancer occurs when an adult stem cell loses control of its ability to replicate. Indeed, it appears that cancer is a natural part of life.

Of course, adult stem cells have been used for decades without being isolated, for example in bone marrow transplants for patients with leukeamia. Because the patient has reduced ability to make white blood cells, they cannot fight infection, so donor bone marrow replaces their own. In the new bone marrow exist adult stem cells – hematopoietic stem cells – that can make all the blood cells necessary to repopulate the body. In recent years, more and more funding has gone into studies on adult stem cells. The main reasons for this are because it does not require taking the early embryo, and bypasses a biological problem that embryonic stem cells have. If we were to take such a cell, and then inject it into another person – either as itself or a more restricted cell type – the human body would mount an immune reaction because it has molecules from a source that it cannot recognize. By manipulating the stem cells that are already within us, the body doesn’t have to cope with an immune reaction at the same time. Many of these studies, despite relatively early, provide a convincing approach towards new therapies, improve our understanding of how our bodies maintain themselves, what can go wrong, and possibly identify stem cell populations as new drug targets.

Mesenchymal stem cells are another type of adult stem cell taken from bone marrow, but another good source is fat tissue. It was found that they could be easily grown in culture, and have the ability to become a wide variety of cells. Due to their lack of ethical controversy, and ease in sourcing, they have become an integral part of tissue engineering and current regenerative therapies, for example there are clinical trials on patients with MS (multiple sclerosis) and coronary heart disease, and have been proved successful in many other diseases and injuries. This fact could mean that mesenchymal stem cells could soon be widely used, for a host of reasons, and in many places. Perhaps you will one day rely on a mesenchymal stem cell based therapy.

Induced pluripotent stem cells are also a new hope for regenerative therapy. These cells would be derived from the individual patient, and then directed into whatever cell types were necessary. Unfortunately, this process is still very inefficient and has a very long way to go before you see any science fiction like organs being transplanted back into us to replace our old ones! However, they do provide a way to generate tissues and systems that can be used as a model for an organ. With this, it is possible to use them to test new drugs and are potentially an alternative therapeutic strategy to embryonic stem cells. They do not stimulate the same intensity of ethical debate, and are currently being used by many labs to see whether they can aid in regeneration of different parts of the body and to understand more about cell fate decisions. Again, these studies can be thought of as preliminary, as scientists are still learning about their differences and problems that are encountered when using cells that have been forced to become stem cells.

This description has barely touched the surface of the research that is out there, but even so, it is obvious and amazing to see just how much power these cells hold and how our fate is inextricably linked with stem cells, both embryonic and adult. They are an essential part of our biological development, and hold key responsibilities in maintaining life. Understanding their influence on our biological world is the next step towards improving it, but Nature does not give up its secrets easily, and has a unique way of dangling the truth behind the smoke and mirrors.

Simple Steps to a Neuron – I.S.

Adult neural stem cell; must give rise to a neural progenitor before being committed to a neuron

Embryonic stem cell; must give rise to a neural progenitor before being committed to a neuron

Induced pluripotent stem cell; fibroblast must be turned into a pluripotent cell, which then needs to gives rise to a neural progenitor before being committed to a neuron

Immature neurons, or support cells, could be targeted (Adult NSC) or transplanted (ESC, IPS) to required regions of the central nervous system

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