ofmiceandmolecules

Starting from scratch Sundays: Convalescent plasma therapy

Ebola virus

What is convalescent plasma therapy?

The concept of convalescent plasma therapy involves procurement of blood from survivors of a disease, processing it and transfusing it into patients with the same disease. The basis of it is that the survivor’s blood has antibodies against the Ebola virus that would help the patient recover.

The therapeutic strategy has been around for a while, but has revived due to research into alternative Ebola treatments as there are no readily available drugs or vaccine for the highly contagious and deadly virus. Even though news about Ebola has simmered down, there is still an urgent need to develop a viable therapy as countries in West Africa are still being ravaged by the disease.

What is the science behind it?

The immune response

When the body is infected with a pathogen such as a virus, our bodies naturally mount an immune response against it. This adaptive immunity is an additional line of defense that our bodies have, in addition to our innate immune response, to fight against pathogens we have yet to cross paths with.

Lymphocytes, which are white blood cells, can recognise the invading pathogen and produce antibodies unique to the pathogen. The binding surface of the antibody has a complementary shape to that of the pathogen, which allows the two components to bind together. As a result, the pathogen is destroyed and engulfed by macrophages.

Once the pathogen has been defeated and the patient recovers, immune cells have a ‘memory’ for the pathogen. If the individual is exposed to the same pathogen again, their bodies can respond to the invasion much quicker and more efficiently to hopefully prevent them from falling ill again.

The blood transfusion

Whilst blood transfusion has become a standard procedure, there is a limit on the amount of blood a person can donate each time. Blood can be separated by centrifugation, such that the plasma can be extracted. The benefits of this, as opposed to whole blood transfusion, is that it allows recycling of the red blood cells back to the donor. It therefore increases the amount of blood a donor can donate, and the frequency of allowed donations. Plasma can also be stored for much longer than whole blood.

Historical outlook on convalescent plasma therapy

Emil von Behring published a paper in 1890 describing antitoxins that the body produced to neutralise diphtheria and tetanus. The discovery of convalescent plasma therapy for the diseases secured him the first Nobel Prize in Physiology or Medicine in 1901. Despite the effectiveness of the treatment, it fell out of favour to antibiotics, antiviral drugs and vaccines.

Since the late nineteenth century, the concept has been used for an array of diseases, such as H1N1, H5N1 and SARS, amongst others. Drugs and vaccines superseded convalescent plasma therapy in previous attempts, as they are easier to mass-produce and administer. For example, the availability of antiviral drugs such as Tamiflu rendered convalescent plasma therapy unnecessary for H1N1.

However in the case of Ebola, convalescent plasma therapy is a worthwhile avenue of investigation as drugs and vaccines are unavailable. In the Ebola outbreak of 1995 in the Congo, seven of eight patients treated with convalescent plasma made full recoveries. Similarly, the therapy was used in the Ebola outbreak of 2014. These cases are promising, but further investigation is necessary to probe the benefits of the treatment.

Junin, a hemorrhagic fever in Latin America is treated using convalescent plasma therapy. Furthermore, the 2012 outbreak of MERS-CoV (Middle East Respiratory Syndrome Corona virus) in Saudi Arabia has prompted clinical trials for convalescent plasma therapy as a potential therapy.

So, is it plausible?

In the 2014 pandemic, the therapy seemingly worked on several cases, but there was a lack of scientific method in that there was a lack of control groups, and patients were also treated with other medicine. Thus, further work needs to investigate the efficacy of the treatment, and risk-benefit assessments.

Clinical trials for convalescent plasma therapy has recently started in West Africa to assess its benefits. If the treatment is proven effective, it can be easily scaled up quickly in hospitals and clinics due to its low cost, and can have substantial impact. WHO has deemed experimental therapies ethical for Ebola due to the lack of effective treatments, and has issued guidelines for it. However, implementations of the treatment has to be standardised, as there is the danger of transmitting other diseases such as Hepatitis B and HIV.

Reference: http://www.who.int/mediacentre/news/ebola/26-september-2014/en/

Do we have free will?

Humph, ever wondered about our free will?  Science writer Ed Yong (whom I have had the pleasure of listening to) talks about suicidal wasps, zombie roaches and other parasitic tales that may make you doubt the extent of our free will.

Warning:  Graphic insect images; may want to avert your eyes to pictures and the video of worms crawling out of insects…

Sleep for the sake of your neurons!

credits: Flickr

credits: Flickr

There’s always that student who leaves their work until the day before the deadline, and pulls an all-nighter to start and finish it.  These sleep deprived students build up their ‘sleep debt’ and spends their weekends making up for the lack of sleep.  I know as a student, I have been guilty of this.

It’s time this prevalent student habit stopped because scientists from the University of Pennsylvania and Peking University found that long-term sleep loss led to the loss of brain cells.  The habit may have long lasting physical damage and might not be so harmless after all…

It has been known for a while now that sleep is important.  After all, we do spend a third of our lives sleeping.  No one knows the function of sleep, but it just is needed.  Take for example, how one feels after an all-nighter.  We’re groggy, grumpy, and we can’t concentrate on anything.  Sound familiar?  So it is clear that a lack of sleep affects our brain’s ability to function properly.

Sleep-deprivation has also been implicated as the main contributory factor to people making mistakes and irrational judgments.  The Exxon Valdez oil spill of 1989, the Chernobyl disaster of 1986, the Three Mile Island accident of 1979…you get the picture.  Lack of sleep can cause disasters.

There are numerous theories floating about as to why we sleep, including one arguing that it is the time that our brain is ‘cleansed’.   It was also thought that sleep was necessary for recovery from the day’s activity, or for memory consolidation.  I’ve had the privilege of listening to professor Russell Foster lecture about the circadian rhythm, but for keener readers out there, I’ll just leave a video below of him giving a talk on why we sleep.

 

Sleep deprivation is largely featured in the job description of shift workers, truck drivers and doctors.  The study imitated the sleeping patterns of shift workers in mice, and evaluated the health of neurons that are important for alertness and cognitive function, which are found specifically a part of the brain called locus coeruleus (LC).

It was found that in mice with short-term sleep loss, the neurons have increased SirT3 protein; a protein important for energy production and the protection of neurons from metabolic injury such as free radicals.  On the other hand, in mice experiencing long-term sleep loss, SirT3 is reduced and 25% of neurons died.”This is the first report that sleep loss can actually result in a loss of neurons,” says professor Sigrid Veasey.

So, what does this mean?  Well, the study was done in mice, so it has to be established whether this happens in humans.  Not all people may be affected, so studies on the effect of duration of sleep loss, age, lifestyle and diseases on the risk of neural injury also have to be taken into account of.  “If cells in individuals, including neurons, have reduced SirT3 prior to sleep loss, these individuals may be set up for greater risk of injury to their nerve cells”, Veasey adds.

This piece of research is a step towards developing a drug to help shift workers, although it is a far cry away.  Previous work has shown that loss of LC neurons can accelerate the course of Alzheimer’s and Parkinson’s disease in mice, so further studies also have to be done on the role of sleep loss in these neurodegenerative diseases.

Surely this is a wake up call (har har har, sorry I had to) for students…if only we had better time management skills, eh?

Sniffing a trillion scents

Credits: Flickr

The scent of freshly baked cookies wafting from the kitchen, a salted caramel scented candle burning, and the distinctive smell of a wood fire.  These are a few examples, out of a trillion, of the scents that our noses are capable of distinguish.

10,000 scents.  This was the figure thought to be the number of scents the human nose could distinguish between.  The number was a rough estimate resulting from a paper published in the 1920s.  It was based on theoretical work that made a few assumptions (which turned out to be wrong), but it remained as the figure quoted until now.

A study from the Rockefeller University, published in the journal Science, ‘mythbusted’ the figure of 10,000 and determined that the resolution of the human sense of smell is several orders of magnitude higher than previously thought.  One trillion.  That’s the number of scents we can distinguish. 

“Objectively, everybody should have known that that 10,000 number had to be wrong,” Leslie Vosshall, an investigator in the study, says. For one thing, it didn’t make sense that humans should sense far fewer smells than colors. In the human eye, Vosshall explains, three light receptors work together to see up to 10 million colors. In contrast, the typical person’s nose has 400 olfactory receptors.” 

An odor that is encountered in real life is the combination of an array of different molecules, and is multi-dimension.  The scent of a rose, for example, has 275 components to it, but only a small percentage of the components dominate the characteristic smell. 

 Participants of the study were given three scent mixtures prepared from a set of 128 ingredients, and were asked to identify the mixture that smelled different.  Two of the three mixtures were the same, and the complex scent mixtures had either 10, 20 or 30 ingredients in them.  The scent mixtures presented to the participants imitates the complexity of scents.  

A lot of data analysis ensued, and the researchers concluded that human noses can detect at least a trillion different scents.  It was also found that when ingredients of two scent mixtures overlapped by 51%, it was much more difficult for participants to differentiate between the scents.

Andreas Keller, co-author of the paper said, “The message here is that we have more sensitivity in our sense of smell than for which we give ourselves credit. We just don’t pay attention to it and don’t use it in everyday life.”

Even so, a trillion appears to be a conservative guess given that the experiment narrowed down the astronomical number of scent molecules down to only a mere 128.  In reality, the limits of combinations introduced by the experiment are removed, and much more complex smells can form. 

 I have a new found respect for my nose…

Starting from scratch Sundays: Stem cells

‘Starting from scratch Sundays’ is a new series I would like to test-run for the keener readers.  The concept is to provide a brief, but comprehensive summary of various topics I find interesting.  As a student, I know it is difficult to find a complete introduction to a topic that does not bombard one with dense walls of information.  ‘Starting from scratch Sundays’ strives to be articles of topics in a nutshell.

This week, we start on stem cells.

What are stem cells?

 Stem_cells_diagram

Source: Wikipedia Commons

Everyone has stem cells – from embryos to adults.  They are cells that can generate (scientists say differentiate) into different cell types.  In the image above, the ‘potency’, which is the potential to differentiate into various cell types, of the inner mass stem cells is restricted as development of the foetus occurs.

They can generate cells of a specific function from the circulatory, nervous or immune system to make up the cells necessary for the body to properly function.  Apart from embryonic stem cells (ES cells), adult stem cells exist in various parts of the body to maintain and repair the tissue in which they reside in.  These can be found from the bone marrow to the brain.

What makes a stem cell a stem cell?

Well, for a stem cell to be a stem cell, it has to meet two criteria:

1. Self renewal: the cell has to be able to undergo several cycles of cell division to generate more cells that are undifferentiated.  However, stem cells are generally quiescent, which mean they retain inactivity, and are only triggered under events such as an injury.

2. Potency: the unspecialized cells have the ability to differentiate into different cell types.  There is a sliding scale of potency, ranging from those that can form any cell in the body to those that can only produce cells in the tissue they reside.  For example, a haematopoietic stem cell in the bone marrow can become any blood cell.

So, a stem cell is a cell that can continuously divide and differentiate into different cell types

What about stem cells in the lab?

Both embryonic and adult stem cells can be grown (otherwise known as cultured) in the lab.  There are also cells called induced pluripotent stem cells (iPSCs) that are laboratory produced stem cells.  In essence, an adult cell in the body can be ‘undifferentiated’ using a cocktail of proteins so it reverts its differentiated state.

iPSCs overcome the need for embryos, which has been an ongoing ethical controversy.  Additionally, because they can be derived from any adult cell, patients with a specific disease can be used to generate models of stem cells with the condition.  There has been ongoing research to find simpler ways of ‘reprogramming’ cells.

Below is a video, courtesy of Nature, explaining the ‘Method of the Year 2009’, iPS cells:

Recently in the news, it was revealed that Japanese scientists found a simple laboratory protocol involving soaking skin cells into weak citric acid for half an hour to generate stem cells.  However, it has stirred controversy in the scientific community as no other teams can repeat the experiment with the same results.  The study spurred a four hour press conference in which the team addresses questions on their paper.

What are the potential clinical uses of stem cells?

There has been a lot of research dedicated to finding ways of directing the differentiation of a stem cell into a desired cell type.  What’s the point, you ask?  The ability to manipulate a stem cell to form a specific cell type means that large quantities can be generated from a readily available source that is your body.

This can be useful for stem cell therapies and regenerative medicine, which relies on the implantation of stem cells to replace the patient’s diseased cells and encourage its integration into the body.  A clinical study that will launch in five years was recently approved in Japan for the use of iPSCs to treat eye diseases.  This will involve generating cells of the eye, and implanting them back into the patient so they can function properly as part of the body.

iPSCs prevents triggering of the immune system because of rejection of the cell, as the cell was from the patient.  Currently, stem cell therapies are thought to have a huge potential for treating diseases such as stroke, heart disease and diabetes.

They can also be useful for drug testing, which allows quicker and safer drug development.

Long story short…

Stem cells are invaluable for its therapeutic potential because they can replace dysfunctional or diseased cells.  It could be an alternative to organ transplants, in which demand greatly diminishes the supply, but could also treat diseases like certain types of cancer and even Alzheimer’s disease.

The field is still in its baby stages, but is quickly growing into an important discipline.  However, there is still much to learn and numerous problems to overcome before stem cell therapy becomes feasible as a routine therapy.

The ‘five second rule’ verified by science

Exam revision looms over your head, but the only way to motivate yourself is with M&Ms.  A brightly coloured M&M is delicately balanced the top of each page of the textbook.  Your tired, glazed eyes sweep over the text, trying to cram all the information in…a sentence left…and…done!  You excitedly reach for the blue M&M, but you lose your grip.  It flies in slow motion across the room and lands on the carpet.

What do you do?  Leave it, or deal with it and have the next one once you finish the next page (no, taking another out of the pack is not an option)?  Most people would leap across the room as fast as humanly possible to retrieve their prize. 

The ‘five second rule’ states that any food that has been in contact with the floor for less than five seconds is still safe to eat.  Well, it seems that science supports this excuse.  Under certain circumstances, anyway.  This is devastating news to a germaphobe like me. 

The rationale behind the urban myth is that food that has been dropped for a shorter period of time has fewer germs.  Research from Aston University provided the scientific basis for this urban myth, as they monitored the transfer of common bacteria from different flooring to dry, wet or sticky food. 

They found that time, the underpinning factor of the ‘five second rule’, heavily influences the bacterial transfer.  So the findings showed it is true that food dropped for a shorter time has less bacteria.

The type of flooring and food also seem to be important in your decision of whether to eat that piece of dropped food though.  Carpeted surfaces were the least likely for bacteria transfer, whilst laminated or tiled surfaces were the most likely.  The grace period is also longer with dry foods as opposed to sticky candy or wet foods like pasta.

That said, the data hasn’t been published yet or peer reviewed, so the preliminary findings have yet to be confirmed.  The research should be taken with a grain of salt.  Fecal bacteria hitching a ride on the soles of your shoes may end up on the floor of your dining room. 

Anthony Hilton, the principle investigator of the study, warned “Consuming food dropped on the floor still carries an infection risk as it very much depends on which bacteria are present on the floor at the time; however the findings of this study will bring some light relief to those who have been employing the five-second rule for years, despite a general consensus that it is purely a myth.”

Either way, I’m not playing Russian roulette with germs.

Gecko-inspired reusable ‘self cleaning’ adhesive tape

Image

Photo credit: Flickr

I’m sure everyone has some time or another come across those annoying food packages that claim it is ‘re-sealable’.  All they provide is a flimsy piece of sticker that loses its adhesiveness after one use…if that at all.  Well, fear not, everyone.  Your cookies need not be spilt everywhere.

Researchers from the Karlsruhe Institute of Technology and Carnegie Mellon University took inspiration from the design of the feet of gecko and designed a tape that could withstand multiple uses.  Additional to food packaging and bandages, Metin Sitti, Professor of the Carnegie Mellon University, describes that “such a tape might be applied in the sports sector, in medicine, automotive industry or aerospace technology.”

Why geckos?  Well, they’re agile ninjas on any surface because of their sticky toe pads.  Their toes have tiny hair-like structures called satae that can further branch out into millions of tips called septulae.  The summation of millions of weak van der Waals interactions between the septulae and surface forms the strong grip needed to support the weight of the gecko for it to creepily dart across your room when you’re trying to sleep.

Apart from the amazing ability of being able to hang upside down on the ceiling, the feet of gecko are also ‘self cleaning’.  When the gecko moves, the toes drag across the surface and causes friction that removes some of the dirt particles.  This keeps the feet effective in supporting the weight of the gecko.  The scientists produced a replica of the structures found on the feet of gecko that were able to self clean even after repeated exposure to glass spheres that acted as the dirt particles.

The tape can reliably stick onto surfaces, and remain sticky even after it has been ripped off multiple times.  That’s one step closer to designing the perfect food re-sealing tape!

Alzheimer’s in a blood test?

“Am I supposed to know you?”

The portrayal of dementia in the media such as in ‘The Notebook’ depicts a life of confusion and forgetfulness, rendering the patient helpless and dependent on those around them.  The inability to recognize faces, changes in personality and decline in speaking, writing and reading abilities often manifests alongside the slow, progressive decline of cognitive function.  The most prevalent neurodegenerative disease, Alzheimer’s disease, is difficult to predict, and currently impossible to cure.

Two days ago, Federoff et al published a paper in Nature Medicine describing a blood test for predicting Alzheimer’s disease.  It relies on ten biomarkers, which mean that they are characteristic of the disease, in the blood.  The paper claims this test is able to reliably predict with 90% accuracy the future development of symptoms of dementia in an individual.  Blood tests, as a diagnostic test is ideal as drawing blood is a routine procedure and blood is rather abundant in us.  Now, what is all the fuss about?

The research has a wider implication on therapy development, as the accurate prediction of Alzheimer’s allows targeting of earlier stages of the disease rather than the late stages that current research targets.  It may improve effectiveness in slowing down or preventing onset of the disease, which is highly preferable to the ‘damage control’ strategy of current therapies, as late stage intervention has been argued to be too late for treatment.

This is all fairly exciting news, but the ethics must be kept it mind.  An open letter to the government in England expressed concern regarding screening for Alzheimer’s, as there may be more harm than benefit in the current state of the field.  Why forewarn individuals over the impending onset of Alzheimer’s when there is nothing at present is available to prevent or cure it?  There are also arguments against the screening of healthy people based on the statistics of false negatives and false positives (shown particularly well by this visual piece explaining professor David Colquhoun’s arguments).

The preliminary study also only involved 525 people aged over 70, in which 74 participants had Alzheimer’s.  Only 28 participants developed symptoms.  Further studies involving larger groups of participants have to be done to confirm these findings.

Nonetheless, knowledge is power.  The research has paved a new direction for drug research, and is a remarkable first step toward disease prediction for when therapies are readily available.  Even if it is not immediately useful and accepted in the field, it us still a milestone in Alzheimer’s research, and may prove to be valuable in the future.