[Sciences] My Top 10 Sciences Discoveries of 2014

Here I am, a couple of hours before the end of 2014 and lots of excitement in science this year. Here are my top 10 discoveries that marked me this year. It is surely biased (stem cells, blood-brain barrier) but hey I am a scientist after all. There is no particular ranking, so do not use the numbers as a rank.

Note: I will update this blog post by adding additional contents.

1.STAP Cells

The latest blog post from Dr. Knoepfler on the STAP cells debacle

STAP cells: stimulus-triggered acquisition of pluripotency. This was certainly the buzzword of January. Imagine that. Cell reprogramming (following the Yamanaka protocol) of somatic cells into iPSCs is a daunting experience. It is long, expensive and low yield (0.1%). When the technique came, it brought 30% yield and sounded as easy as prepping kosher-dilled pickles. Yep, just that, plunge the tissue into some acidic bath (that is a scientific iteration of the pickling process) and you get 30% of iPSC-like cells (or STAP cells). Sound as easy as ABC, no? Well indeed it was not. And it turned sour very fast indeed with over 10 labs trying without success. First came some statement similar to “it’s complicated”, then inquiry from RIKEN university in Japan followed by obvious scientific misconduct and paper retraction as the first author failed to reproduce the original data. In addition, the senior author committed suicide. A tragic ending for a flawed study, a “too simple to be true”.

2. The first stem cell clinical trials for retinal macular degeneration

This year have seen the first stem cell clinical trials using hESCs and iPSCs in patients suffering from macular degeneration. Preliminary results are showing a relative safety of the technique (no tumor observed so far) and some reports of improvements in certain patients. It is still not known if such improvement is a “placebo effect” or real effects. Similar studies are ongoing for other cardiovascular diseases and for neurological disorders such as Lou Gehrig’s disease or Huntington’s disease at the Mayo Clinic. However, I would like to remind people that there is yet no stem cell cures or proven stem cell therapies. Please, please, please do not listen to those claiming “stem cell therapies” that are working. There is not such thing and there is not yet any FDA-approved guidelines for such. A lot of labs are working to bring stem cells from the bench top to the patient’s bedside but still a lot of way to go.

3. The gut-brain interactions: the blood-brain barrier as the middleman

Diffusion of an IR-dye across the blood-brain barrier in a “sterile” mouse compared to “pathogen-specific free” mice. Note the fluorescence intensity showing a leaky BBB. Courtesy Karolinska Institute.

This was the most interesting and the fast-pacing rise. Until a few years ago, we mostly believed that the gut microbiota would only affect the GI tract without any incidence on the rest of the organism. I was stunned by two studies: one study showing the impact of microbiota composition in the gut flora on autism-like symptoms (http://www.ncbi.nlm.nih.gov/pubmed/23307560) that shows how the alteration of the flora composition resulted in the display of autism-like phenotype. The mechanisms are unknown but it seems the presence of a leaky intestinal tract may trigger neurobehavioral changes. The second comes from http://www.ncbi.nlm.nih.gov/pubmed/25411471, in which they show that the absence of a gut microbiota results in an increase leakiness of the blood-brain barrier. It took 60 years for neuroscientists to admit the presence of a blood-brain barrier. Hopefully, by 2020, neuroscientists will finally understand how crucial the BBB is for the brain well-being and the salute of treating neurological diseases will only come when they will understand that we BBB scientists are as important as them.

4. Human induced pluripotent stem cells as disease modeling and drug toxicity screening

If one biomedical research field that quickly emerged in the last decade, it is certainly the field of induced pluripotent stem cells (iPSCs). For those who are not aware about iPSCs, this is an important discovery of this century. Once the egg is fertilized, it quickly divide into 2, 4, 8, 16 cells up to reaching a stage called a “morula” stage that ultimately evolve into a blastocyst. This blastocyst will eventually become…YOU! Interestingly, all these cells are called totipotent as they can form any type of cells. These are the classical “embryonic stem cells” that have raised hope and fears among the public.
All of our cells have the same genetic information but what makes a neuron from a muscle cell is the number and types of genes that are ON and OFF. This is what we call the epigenome. By reverse-engineering it, we can bring reverse the clock on these cells to bring them into a pluripotent stem cell stage. Once pluripotent, we can reprogram these cells into any type of cells. This dedifferentiation stage was developed by Yamanaka in 2006 (Nobel Prize 2013) and applied to human cells by Jamie Thomson in 2007. Since then, a lot of effort have been done to differentiate these cells into various cell types including neurons. This open a new perspective as we can now try to understand human diseases in a dish by directly having access to patients cells. And this have been successfully applied in these last five years for different types of neurological diseases. If we have to show a poster-child for personalized-medicine, that would be its first iteration. There are numerous studies showing the ability to differentiate neurons from patients suffering from Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, ALS, frontotemporal degeneration, Dravet Syndrome, Fragile X Syndrome, schizophrenia….
As we are just starting to understand the mechanism of diseases, we can now foresee the possible usage of these cells to identify novel compounds capable to slow or even relapse the disease.

5. The Edna Krabappel and Lisa Simpson peer-reviewed study


This was one of the big bust, especially when you are in the academic field and know the calvary of publishing your manuscript. Getting your study is a long and patient process in which you have to deal with peer-review process, in which other scientists (anonymously) review your study and give their decision to the editor-in-chief about if your study is good for publishing or not.

In the classical model, the journal charges the authors of the study for publishing the study and the readers to access to the full journal. And having access to journals can be very expensive especially if you are in a small university or if you are located in a developing country. Still even with the best peer-review system, there are still flawed study that made it to publication and get retracted (http://retractionwatch.com). Since these last few years, an important step have been done to provide open-access to scientific papers. The authors pay a publication fee (usually higher than the traditional journal) but the paper is freely accessible to read it.

This new model has of course brought some interest for some people seeing “easy money” to be done, by accepting ANY studies, even from fictional characters. The fact that a paper authored by Edna Krabappel and Lisa Simpson filled of non-sense text fillings raise concerns and make a call to establish some guidelines and ways to select the “good open-access journals” from the bad ones. Also this year, the NIH Library of Medicine, the Pubmed portal (a well known scientific articles search engine for biomedical scientists) has launched the Pubmed Commons to provide an open, post-publication review mechanism in which anyone can comment on any paper presented in Pubmed.

I believe this is the first case of many uncovered and we are expecting to see more. It is a time we have to decide if we keep our science straight and well-sounded or if we let hijacked by flawed and manipulated studies.

6. Rosetta Stone and Philea probe

This was the biggest achievement of the European Space Agency (ESA). Can you imagine sending a remote probe, have it land on an asteroid. You have to imagine piloting a RC buggy car through a screen with 10 minutes delay between the time you see the obstacle and the time the command is executed. Imagine you drive your RC buggy see a tree in front of you, send the command to turn right and have to wait 10 minutes to get it done.

If I have one rant to make, it certainly on some trolls that pointed on Dr. Mark Taylor’s shirt and ignored the scientific achievement accomplished. Yes, having this shirt on live broadcasting was a terrible PR move, but putting on that shirt to blame the problem of women in science is wrong. The problem is much bigger than a shirt and those that are putting bars in the wheels of women in scientific careers are not wearing such shirts. We need to re-think about the whole system to better retain women in sciences, set maternity leaves and adapted schedule to have them the possibility to adapt their work to their schedule, tailor the tenure process to take in consideration that women have to deal with two important choices in their life in the same time and should not be forced to choose one  for the other.

Although Philea landed in a wrong place and rapidly died from low battery, it gave us some information. For a moment, I fell in love with Philea, like a real-life WALL-E. I am looking forward to have it back on track and running up soon.

The also interesting projects are the Mars Curiosity roving over the red planet and found some bursting methane (that could be some microbial life) and of course the Pluto mission coming in early this year.

7. Prosthetic arms and cyborgs

As a kid, I always got fascinated by robots, cyborgs and giant mechas. I grew up watching “UFO Grendizer”, “Star Wars”, “Transformers”, “The Terminator”, “The Million Dollar Man”, “Robocop” but also got frightened by “Galaxy Express 999” in which in a distant Earth future, humans have most of all acquired immortality by replacing their biological parts into robotical parts. Those who failed to afford or refused to become cyborgs are considered as sub-humans and hunted as preys.
Human-mechanical interfaces sounded like science fiction 20 years ago. As we have been progressing in neurosciences, we also have considerably improved in mechanical engineering and electronic. We are just assisting in the first trials in which prosthetic limbs are directly connected to the brain surface or capable to transduce electrical impulse from nearby muscles to execute movements. Two trials especially caught my attention: the one depicted in the picture and currently run at John Hopkins University in the Department of Applied Physics. The two robotic arms can sense muscle activity from the chest and transduce into complicated movements. Watch the video it is really impressive to see this man capable to regain functional from lost limbs.


The second one from the University of Pittsburgh allowed a quadriplegic woman to gain control of a robotic arm through a brain-connected interface. Look at the fluidity of the arm, the dexterity. Remember this is a robotic arm connected to the patients brain, it is just  awesome to see the improvement of such discipline over the years.

8. The lady with no “Little Brain” (Cerebellar agenesis)

Source: Cerebellar agenesis Luigi Titomanlio, Alfonso Romano and Ennio Del Giudice Neurology 2005;64;E21 DOI 10.1212/WNL.64.6.E21

Source: Cerebellar agenesis
Luigi Titomanlio, Alfonso Romano and Ennio Del Giudice Neurology 2005;64;E21
DOI 10.1212/WNL.64.6.E21

The cerebellum (or little brain in Latin), is an important piece of the central nervous system. Its function is essential in the locomotion and in the coordination of movements. This is also the primary target of ethanol, the active component of alcoholic beverages (or booze if you like it). Thats why when you are drunk you loose your reflexes and have the typical walking pattern of a drunk person.

We may think that the absence or severe malformation of this organ may significantly impact the locomotor function. Seems not according to a recent study from Fu and colleagues (http://brain.oxfordjournals.org/content/early/2014/08/22/brain.awu239.long). Apart from having trouble to keep an equilibrated statute and some episodes of nausea, the patient appears to have a normal life as she is reportedly married and has one daughter. It shows one thing: the brain appears very plastic and can rewire some of its functions if needed. The most interesting aspect now is how the cerebellar function is re-wired and compensated by the other brain area and which areas?


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