Anatomy of Science

It was a particularly murky day and I was waiting to meet the academic head of our course, Dr Gavin Jell. Exams were looming and there was work to be done but I had been given a task, I was getting this interview. To my eternal joy Dr Jell had suggested that this interview take place in the pub. I like Dr Jell.

An interview with surgeon Jonathan Knowles.

Faster, cheaper and more accurate than any other previously developed method of engineering DNA. CRISPR/Cas9, based on the mechanisms of bacterial defence system, enables scientists to modify and replace genes. The technology was awarded the Breakthrough Prize of 2015 by the Science Magazine and sparked heated public debate on numerous occasions.

Here’s why #CRISPR is still trending in media.

CRISPR was used to edit human embryos

Jonathan Kossoff - Editor

Tania Choreño Machain- Editor

Magdalena Plotczyk - Social Media

Ammar Alsaad - Designer and Writer

Krystal Gayle - Writer and Interviewer

For all Tissue Engineers out there, an Annual Meeting of Tissue and Cell Engineering Society (TCES) is coming up in July. This year the meeting is organised at UCL, giving the university an amazing opportunity to present the scope of its tissue engineering projects. Among the key speakers are Prof. Paul Martin, a great scientist and speaker working on wound healing at the University of Bristol, and Dr. John Sinden, a scientific co-founder of ReNeuron Ltd., the leading clinical-stage stem cell company. Do not forget to submit an abstract before the 6th of May! 

Corneal disease is a major cause of blindness worldwide, second only to cataract, and its epidemiology involves an extensive variety of infectious and inflammatory eye diseases that can also be highly dependent on the geographical area under study. To place the disease into perspective, according to a report by the WHO, there were 45 million individuals worldwide in 2001 who were bilaterally blind and another 135 million that had severely impaired vision in both eyes.

In the last five years the internet has produced a variety of challengers to the traditional model of scientific publishing. Open publishing sites such as F1000 have created spaces where any research can be instantaneously released. Academics have been quietly subverting journal copyright on twitter for several years; using the hashtag #icanhazpdf to request a paper from peers and then deleting the tweet after the paper is emailed to them.

But now a more flagrant assault on the publishing industry has been mounted from Russia. In the last few weeks the website Sci-Hub has gone viral across the internet;tagged as “the Pirate Bay of science”. This repository of 48 million academic papers was founded by neuroscientist Alexandra Elbakyan, in response to her frustration at the difficulties of accessing papers. The website uses software that automatically accesses and downloads papers from a variety of sources to update its repository.Its location makes it unlikely that the website will be taken down any time soon. Elsevier, the world's largest academic publisher,successfully brought suit against the site last year, gaining an injunction from a New York court and forcing the site to change its domain. However, enforcing this judgement in Moscow seems unlikely.

Last May I attended a very interesting discussion between Professor Iain Hutchison and Maggi Hambling at King’s College of London. What could a Maxillofacial Surgeon possibly discuss with a world famous painter and sculptor?

For those who don’t know any of them, Prof. Hutchison is a famous Maxillofacial Surgeon and the founder of an amazing organization called “Saving Faces”. On the other side, Mrs. Hambling is a British contemporary painter and sculptor (her most famous piece is Oscar Wilde’s sculpture close to Trafalgar Square).

Going back to my question and being a surgeon myself, I was trying to grasp the idea, the underlying meaning of sophisticated use of English language and surrender myself to the beauty of the conversation.

 I was constantly thinking about it and only when I let myself go and let the romanticism kick in I had a realization: Surgery is not just another way of saving people but rather a form of ART. YES! That it is! A form of ART! A surgeon creates, manipulates in order to create something, even from scratch. We are sculptors but with a different power in our hands. We create and at the same time help people to ameliorate their living standards!  

Genetically engineered white blood cells used in first-in-man leukemia treatment. Way to go UCL! 

"The technology itself has got enormous potential to correct other conditions where cells are engineered and given back to patients or to provide new properties to cells that allow them to be used in a way we can only imagine at the moment."

- Esmond Lee

Review: 

Invasive procedures is a medical thriller written by Orson Scott Card (think Ender’s Game) and screenwriter Aaron Johnston. Scott, better known for his science fiction writing, won both the Hugo and Nebula Awards for Ender’s Game (now a film), and its sequel Speaker for the dead. I couldn’t help but pick out this novel from one of my favourite science fiction authors for the daily commute. Published in 2007, the novel is set in the not-so-distant future where a brilliant but defunct scientist George Galen tries to guide humanity to a brighter future through genetic enhancement. He devises a virus that can carry specific genes into human cells. Galen sends agents to collect DNA from potential patients with genetic disorders and if suitable, engineers a unique version of the V16 virus as a cure. However, his plan to bring about a medical revolution is shrouded in secrecy and is picked up by defence scientists who trace his steps to avert what they think will be a medical disaster.  

By Andrea Ochoa                        

 Edited by Sparshita Nag  

This weekend I decided to take a small break from my thesis project and join the XIII Symposium of Mexican Students and Studies at UCL where Mexican students from all around UK came to London to share their projects and ideas in round tables, posters and oral presentations. Here are some of the most remarkable events:

“Is science broken?” In this round table, important aspects of how science is currently done were analysed and discussed. We all know that humans are not perfect; therefore, there are some problems that as scientists, we need to address. There is a competition for resources for publishing research and fulfil expectations of the society. This tremendous pressure sometimes unfortunately leads to researchers falsifying their data and resorting to other means of fraud. This compromises the credibility of science. Besides, the conflicts of interests have mixed science with corporatisation in order to publish articles with excellent results to sell drugs and pharmaceutics. In addition, another point to ponder is how difficult it is to obtain objectivity and reproducibility of results, making a difference between exploratory and confirmatory research. Mistakes are intrinsic. There are multiple ways of carrying out an experiment and variables that can affect them that it gets hard to standardize any protocol. Therefore, a justified question could be how exact science could really be? Furthermore, how statistical analyses are applied, and the wrong use and interpretation of p-values is a point of concern. Reproducibility of experiments again gets affected because of the lack of proper controls, not publishing unexpected negative results and the lack of collaboration. After sharing and listening to the different viewpoints, my personal take home message is that it is not that science is broken; maybe how we utilize and interpret it makes all the difference. “Science is just the best thing we have” in order to answer questions and satisfy our curiosity. There are many other things that could be improved in our own labs regarding the way we carry-out our research, multi-disciplinarity and collaboration are key elements as well. Therefore, our part as scientists is to do our best in carrying out research with integrity, so we can perform and publish science that people can actually trust.  

[Participants for the above Round table discussion were: Carlos Cuevas Garcia (University of Nottingham), Angelica Jimenez (University of Manchester), Lucia Magis Weinberg (UCL), Rafael Prieto Curiel (UCL). Moderator: Ana Ramirez (UCL)]

“Violence and criminality in Mexico: the role of gender, education and the brain” by Dr. Feggy Ostrosky-Solís (UNAM). While I was listening to this wonderful talk about psychopaths and sociopaths, and the relation among these disorders with the brain structure I was wishing that Mr. Trump could have been present. One of the first elements of the presentation was to define and state clearly the difference between aggression and violence, psychopathy and sociopathy. Aggression is an innate biological response. Violence is aggression with intention to damage. Psychopathy has a genetic component, while sociopathy is acquired due to the lifestyle and social conditions. Dr. Ostrosky-Solís not only has done an excellent job in analysing how lifestyle and stress during childhood can affect some key parts of the brain that can give rise to socio-pathological behaviour, but she has identified how we can prevent it. According to the 2000 Nobel Prize in Economics James Heckman, the best rate of return of human investment is at the very early stages of childhood. But it is not only in the child that we have to pay attention, according to Dr. Ostrosky-Solís we need to educate and teach the primary caretakers of children: mothers, grandmothers and the likes including schools and the society.

(Therefore Mr. Trump, the criminality problems solution is not building a big wall between USA and Mexican frontier that will be ashes one day and will create more violence, it is investing in education).

 “Re-Shaping our democracy: power and the role of civil society in Mexico” by Dr. Denise Dresser (ITAM). I really don´t have words to describe the perfect way in how Dr. Dresser has described and analysed the political situation of my country. The disappearance of the 43 students in Ayotzinapa in September, 2014 was the starting point of this conference as a reflection of the high level of corruption, impunity, conflicts of interests and specially “high weight of silence” that we are living in Mexico with. Mexico is moving backwards. We are living in a regressive system of extraction without representation, the political class is breaking the law, we don’t have a functional police with good regulations and basic rights being denied. However, even if the Mexico that we dream of is an impossible idea today, it is on us to keep on believing and fighting. To have faith that Mexico could have a real democracy that serves society, where police investigate crimes, where the war against drugs has an end, where corruption is punished. So here I am Dr. Dresser, trying to follow your advice and using this small scientific blog to share the important ideas that I have learned from this symposium and especially from you.    

Thanks to the organizers of the XIII Symposium of Mexican Students and Studies and Conacyt as it has been a very enjoyable experience. 

Signing off

Andrea   

If you want to see the full version of the conferences check out the videos of Omar Hernández Arauz:

--By Sparshita Nag

Well that’s not an uncommon question these days, is it? I’ll start with an example.

Neil and Maya—aged 36 and 34 respectively have been married for 6 years now. Both of them are corporate executives and have predictably stressful work profiles. All is seemingly well in their lives except for one thing. They have not been blessed with an offspring till date. This is in spite of absence of any contraceptive measures on their parts. A visit to the gynaecologist confirmed what they were scared to confront all this while. It was a probable case of infertility. While Maya presented with irregular menstrual cycles, a series of tests revealed Oligospermia/Low sperm count in Neil. “Stress-induced infertility(SUI)” concluded the doctor and advised lifestyle modifications to relieve stress as a panacea to this problem.

Stress and infertility. They sound as unrelated as two words could conceivably be. But statistics suggest that in recent years, this has gained the notoriety of being the commonest cause of inability to conceive. Although one would be tempted to point out that it may directly affect the consummate relationship of a couple, most cases present despite normal relations between the couple. “So how does that work?”, a person unrelated to biology would wonder. Well, that calls for us to focus on the games that hormones like to play in our bodies and their beautiful, balanced interdependence and co-existence. A little perturbation and we turn symptomatic in different ways. Stress induced infertility is the result of disturbance of one such delicate hormonal balance.

In this context, we will be talking about male infertility. The discussion would include two glands in the brain namely the Pituitary and the higher-up authority called the Hypothalamus. Also included would be Adrenal glands located above the kidneys and of course, the male gonad--Testis.

Sperm production or spermatogenesis as it is technically referred to, requires the male sex hormone called Testosterone. This hormone is produced in the Testis from a precursor called Dehydroepiandrosterone (DHEA). This conversion happens under the influence of Leutinising hormone(LH) from the Pituitary Gland in the brain which is in-turn controlled by the Hypothalamus. This constitutes the so-called Hypothalamo-Pituitary-Gonadal (HPG) Axis which is cyclical and follows a feedback mechanism. An excess of any of the downstream components signals the release of the respective upstream component to be suppressed thus retaining the so-called hormonal balance in the body. 

Now, the Adrenal gland seated above the kidneys produces a hormone called Cortisol. It’s secretion drastically increases in stressful conditions. In medical science, the word stress refers to anything that our cells are not made to handle in normal health. And that could range from busy work profiles to a surgery to any illness. This hormone although not a part of the HPG axis, has an external suppressive effect on Leutinising hormone that directly reduces Testosterone production and hence the sperm count.

Can regenerative medicine help? Well theoretically speaking, yes. A possible idea could be to direct stem cells to form sperms outside of the body that can be used for in-vitro fertilization with the egg from the female partner and a normal pregnancy continued provided the female is in good health. Unfortunately, previous research attempts to generate sperms artificially in such a manner have been unsuccessful in attaining complete morphological and functional resemblance to sperms produced naturally in the body. But a lot of work is going on in this area and scientists hope to come up with a solution soon.

It must however be noted that stress induced infertility is technically reversible and does not necessarily require medical intervention. Reducing work stress levels by taking a short sabbatical from work, paying attention to what we eat (yes, fat is another reason for high cortisol levels), maybe initiating a moderately active lifestyle with yoga, brisk walking or zumba sessions could aid in curbing the excessive cortisol secretion to allow the HPG axis to spring back to normal health. Most importantly, we need to cultivate a positive attitude towards life. You see, one way of looking at this is by considering our cells to be infants who look up to their mothers for care and protection. The onus of protecting our cells from external damage lies on us. We are supposed to provide them with a healthy atmosphere within to support proper growth and function. Like the adage goes, “Prevention is better than cure”. Of course we have doctors and medical science to help us. But then again these healthcare delivery professions are limited by what has been found out till date which is in no way enough to cure each and every ailment.

So let us all be good parents to our cells and help them to help us function properly. After all, health matters!

Fries with your cultured beef burger?

Tissue Engineering and the science behind Schmeat

By Andrea Ochoa

 In August of 2013 the professor Mark J Post from the Department of Physiology, Maastricht University in the Netherlands gave a lot to talk about in the news. Not because he discovered the cure for VIH or how to prevent cancer, but for providing a proof of concept that one day could have huge impact on nutrition, health, environment and food.

The concept of “schmeat”, cultured beef or lab burger was born from a petri dish and basic Tissue Engineering techniques.

Tissue Engineering has been defined since 1993 by Langer and Vacanti as: “is an interdisciplinary field that applies the principles of engineering and the life sciences toward the development of biological substitutes that restore, maintain or improve tissue function” [1].

This definition was only thought probably for Regenerative Medicine purposes and there is a big debate to determine if Schmeat could be considered or not as tissue engineering.

Tissue Engineering fundamentals consist in manipulating cells to guide their behaviour through signals and scaffolds. Behaviour could be understood as growth, proliferation, differentiation or production of a specific metabolite. The most common signals used are growth factors that have specific impact on gene expression or cell metabolism. Also it not necessarily has to be in vitro or in a petri dish as many biomaterials are being developed to guide cell behaviour once implanted inside the body.

Going back to the creation of Schmeat, it was created based on muscle-specific stem cells from a cow, they were expanded and differentiated in skeletal muscle cells and fibres [2].

There is a lot of controversy about Schmeat. The first one is because right now could be very expensive to produce (£215,000). However, scalability approaches are being studied [3]. Also why would we prefer Schmeat instead of a juicy sirloin?? Well, because the world population is growing very fast and food security is a concerning issue as well the environmental consequences. Also it will bring several advantages as vegetarians could enjoy meat and bring nutritional benefits to the population, is low-fat and at long term could be sustainable. What do you think?? Would you like to try a cultured beef burger??

 If you want to know what the food experts thought about it, take a look to this video!!

https://www.youtube.com/watch?v=9XqcIkbxxBw

Signing off

Andrea, on behalf of the team

  References

1.            Langer, R. and J.P. Vacanti, TISSUE ENGINEERING. Science, 1993. 260(5110): p. 920-926.

2.            Post, M.J. and Anonymous, An alternative animal protein source: cultured beef. Frontiers in Agricultural Sustainability: Studying the Protein Supply Chain to Improve Dietary Quality, 2014. 1328: p. 29-33.

Being a medic involves more than the simple medicine taught in medical school. What separates a good doctor from an average one is the continuous need to seek improvement. For doctors that includes attending conferences, continuous medical education, and taking up courses to improve their skills. This is especially true for surgeons. As part of the MSc in Surgical and Interventional Sciences we were involved in a great opportunity to take up the only certified microsurgical course in the United Kingdom. This is offered at Northwick Park Hospital in the department of surgical research. The workshop lasted for 5 days of intensive continuous teaching of different types of sutures and techniques in microsurgery for about 7 hours a day. The practical work involved carrying out exercises on rubber models, followed by pigs aorta and then dealing with a rats aorta. It was challenging at first dealing with sutures under the microscopes for long periods but ones skills can be honed with continuous practice. It also involved end to end and end to side anastomosis as well as techniques that involves patches of micro- vessels reaching 2mm in size. Courses like these are essential to any medic whose work involves suturing even if they are not doing microsurgery. Not only does the intensive course teach you the skills involved, but it also teaches you to have patience which is necessary is stressful work environments. The course paves way for advanced surgical skills courses in microsurgery, which is offered at the same center. My classmates and myself highly recommend it for anyone considering a career that involves suturing.

Staying Positive In The Lab

It is Sunday night (or any night for that matter). You sit down to make an outline of the things you have to do on Monday morning. You feel organized, you feel so confident… “Nothing will go wrong tomorrow, everything is prearranged, calculations ready, I will not need to think too hard, 1 2 3 go…”

PUFF… Monday morning it is! Filled with positivity you say good morning to everyone having a smile on your face… You go into the lab “GOOD MORNING GUYS” you shout! Obviously you are the only happy person in there… BUT!!!! You do not let that destroy you mood… Anyway you have everything covered! You are absolutely 100% ready and prepared! Today is the day! You are going to get amazing results…

The day starts and you go to pick up the hundred million things you ordered on Quartzy. And after you have received your order you look something like the picture above…

But still you are happy and you are ready to run your scheduled experiments… Nothing can put you down now… And so you go into the lab to prepare your hood and you see that someone else has taken it…

- “Hey have you booked this hood?” you ask

- “No why?” he murmurs 

- “Because I booked it”

- “Do you need it?”

- “Yes I do” (Like SERIOUSLY? No I booked it for fun… I was thinking of falling in love with it or something… Women in science joke)

- Oh ok I will leave…

All cool, everything is under control and you are now ready to go… you have everything you need…

You cleaned your hood, you have placed everything you need and you are ready to go… BUT nooooo… You forgot to get another DMEM because you use two different ones… You stand up take off your gloves and go ask for one.

Cool now you are 100% sure you have everything you need. On the way you meet one of your colleagues… They look sad and lost and you try to be positive… “Don’t worry everything is going to be ok we will get there” and then they remind you that you have two more weeks of experiments to go… “OMG! OMG! OMG! I am having a panic attack! Two weeks? Two weeks? TWO WEEKS!!!! I have to go seed my scaffolds…” and off you go… And then when you think you are good you make the first mistake… Not enough cells to seed your scaffolds, scaffolds look like they were hit by a truck, you got the wrong media, your pippete is not working… “FAIL!!! BIG FAIL!!!” you think…

Another colleague sees you upset and comes to check on you…

-       “What is wrong?” he asks

-       “Nothing works… NOTHING” you say with a sad voice (ready to scream)

-       “Don’t worry you will get results, it will work”

AND BAM!!!! What you said to someone else before, someone is telling you now…

Day FAIL!

Experiments FAIL!

Cells EXTRA-FAIL!

Today’s Lesson: No matter how positive you are, no matter how organized and prepared you are, when you are in the lab something will fail! And most of the times it will fail BIG TIME!

But do not blame yourself! It is not YOU!!!         

Remember: Anything that can go wrong will go wrong… Murphy’s Law! (Wise man!)

To be continued…

Signing off on behalf of the team,