Author Archives: Iain Stewart

Credit card diagnoses HIV & Syphilis

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Written by Iain Stewart

An article published in Nature Medicine, 4th August 2011, has shown scientists from Columbia University, New York, have created a new tool for efficient and reliable diagnosis of both HIV and syphilis.

Samuel Sia and his team of researchers have adapted the ‘ELISA’ technique into a portable and cheap procedure that can be used in remote parts of the world, giving results in under twenty minutes. ELISA (or enzyme-linked immunosorbent assay) is a well-known method, routinely used in laboratories, to detect the presence of antigens using antibodies.

Antigens are molecules, which when present in the blood, trigger an immune response from the body. Every cell in our body carries its own antigens, which are recognized as ‘self’, but foreign antigens from bacteria, viruses, and cells that are not our own, stimulate new antibody production.

Sia and colleagues scaled down the recognition of antigens into a plastic tool they term ‘mChip’ (microfluidic chip). All that is required is a microlitre of blood, taken directly from a pinprick, which is then passed through extremely narrow channels in a credit card sized device. The disease antigens are present where the channels form tight loops. When blood from an individual who has the virus flows through these loops, specific antibodies from the blood bind. Next, antibodies attached to silver particles are washed through and bind to the antibodies present, with the result of solid silver loop indicating the patient is positive for the specific disease.

This new tool displays many advantages over the current diagnostic strategies. It is low cost, as the mChip and reagents cost pennies to make. It can diagnose both HIV and syphilis in the same test, taking under twenty minutes compared to previous hours, days and even weeks. Its portable design allows it to be operated at the point-of-care, making it accessible anywhere in the developing world. A microlitre of whole blood is all that is necessary from the patient, while its ease of use requires minimal training for the operator. The result can be read without hi-tech optical equipment, is not open to interpretation, and has been shown to be as reliable as current techniques.

Exposing unborn children to the sexually transmitted disease, syphilis, leads to miscarriages, stillbirths and death of newborns. Fast diagnosis of pregnant mothers, and therefore treatment of syphilis with a single dose of penicillin, can significantly increase the survival of the unborn infant by preventing disease transmission through the placenta. Sia and colleagues’ data suggest 5000 syphilis-related deaths could be avoided in Rwanda alone, whilst the World Health Organisation estimates that the disease is responsible for 500,000 perinatal deaths in sub-Saharan Africa every year. 

As well as the obvious impact this technique could have on diagnosing HIV and syphilis at the point-of-care, this test can be used for pre-screening blood donations, and could eventually be used to diagnose a range of infectious diseases in poorly equipped areas all over the world.

Chin, C. et al. Microfluidics-based diagnostics of infectious diseases in the developing world. Nature Medicine. 4th Aug 2011, doi:10.1038/nm.2408

http://www.nature.com/nm/journal/vaop/ncurrent/abs/nm.2408.html

http://www.who.int/reproductivehealth/topics/rtis/syphilis/en/index.html


credit card sized device.

doi:10.1038/nm.2408

channel loops, scale bar 1mm.

doi:10.1038/nm.2408  

A woman bathes an infant in rural Manara, Tanzania. Taken from www.who.int.

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

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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

∞

What Are Stem Cells? (PART I)

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Stem cells have been an important part of medicine since their isolation from mice in 1981, but in actual fact they have been used far longer than this. Bone marrow transplants for leukaemia and skin grafts for burn victims both rely on the principles of stem cells and regeneration. Even in ancient Greece they were imagined as an essential part of human biology, shown by the story of Prometheus who, as punishment for stealing Zeus’ fire and giving it to man, was bound to a rock and had his liver pecked out by a giant eagle every single day, just to have it grow back each night. Nice.

The term stem cell actually covers different types of cells, and is arguably thrown around a little too often nowadays. They can divide forever and generate new cell types, much like an oak tree can keep on growing, throwing out new branches. This power has made them exciting with respect to repairing damaged organs and for use in developing new drugs.

Embryonic stem cells are defined as being pluripotent, that is to say that if you took one embryonic stem cell it has the capacity to become any other cell type of the human body. These are the roots and trunk of the oak tree, shooting branches off in any direction it needs, whilst each root can make a new oak tree. During gestation, these are the cells that build us; the fertilized egg generates a shell in which the embryonic stem cells grow, they then divide and follow paths to different fates, for example a neuron, or a heart cell. This ability allows one original cell to go on to produce all the cells that we are made of. The same principle applies for all life; we all start off from the same building blocks.

Adult stem cells are pretty much what it says on the tin. They are stem cells that continue to stay in the body even into adulthood. Adult stem cells are the branches of the great oak; they do not under normal conditions make a new tree, but continually sprout new leaves and acorns necessary for the ongoing life of the original oak. They are found in brain, bone marrow, blood vessels, muscle, skin, teeth, heart, gut, liver, ovaries and testicles. The main difference between these cells and embryonic stem cells is their ability to make new cell types. Essentially, adult stem cells are restricted in what cell type they can make, only creating cells down a certain path, for example the neural path. The body does not want teeth filling our arteries, nor intestines sprouting out the top of our head, so cell types are kept limited.

Induced pluripotent cells – or IPS cells for short – are slightly different matter. They are the acorns and cuttings which when replanted can generate a new oak tree. Scientists have found that they can take cells from our skin; force expression of a combination of genes and this reverses the path the cell has taken, reverting it back to a pluripotent stem cell i.e. a cell that can then generate any other cell type. This demonstrates an incredible progress in our understanding of stem cells.

In the next two parts I will give a slightly more detailed introduction to why and how stem cells are used, and the major points of controversy that arise. Hopefully, it will give an insight into the lives of scientists that work on them and help you decide your attitude towards the subject.


Stem Cell Oak Tree – I.S.

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