B cell development: basically a romcom for the ages

I've always thought of our universe as a complicated version of one of the scenes from Men in Black. Will Smith peers into a locker containing an entire world of tiny aliens who think he's almighty because he is larger than them. What if all living things are really just small world's within bigger worlds within gigantic world's : worldception? Think about it: what if Bob the skin cell feels like he is just a cog in the policing machine for the man? Then one day he gets cruelly sloughed off just because you walked into a door. Supposing this is true, it should hardly come as a surprise that our cells' interactions very closely mimic our relationships or perhaps more accurately, a scene from The Notebook. 

Our immune system is a perfect example of the rollercoaster of love. They say that as soon as you stop looking for love it finds you. Well no one looks for disease and it finds our cells all the time. I never promised this would be a good analogy. Never the less the B cells have feelers out all the time, searching for meaning, searching for something to ignite their fire so to speak. Once they spot something they like, much like our version of brown hair or eyes that are as deep of the ocean, they activate. Secrete a bunch of things and start overreacting. Pretty much what happens to humans. 

Now although some B cells don't need any help to get to a happy chaotic stage much like humans, the majority need some company. And occasionally they need matchmakers. Certain cells provide T cells with an antigen or some attractive feature so that when a hunky naive B cell comes along they are ready to turn on the charms. Of course there are external factors at play, and certain factors drive the adonis B cells into different zones of the tissue. Think of the T zone as the awkward dating pool - the mesh of clubs, boring movies, sweaty hands etc. If the B cell doesn't find a T cell that matches what he is looking for he moves on. Likely to a place called the B cell zone. A place really where everyone hangs out and pretends they "don't need no woman" or whatever they tell themselves. In actuality what they are doing is just hoping to survive and go into dirt bike riding or some other crazy hobby until they again get sucked into the T zone. 

If the B cell does find what they like then they get trapped in the dating zone and they form a couple with the T cell. This of course changes both parties; for one once bonded it would be bad if the B cell went back off to scope out the rest of the T cell zone hoping for a more curvy possibly blonde T cell. Not only do they individually become pretty clingy but they strengthen their bond with reciprocal favours; bringing home flowers, washing the dishes, promising to fix the garage door. Eventually they form a synapse or as I like to call it, marriage. They move together out of the awkward dating pool and into their own place. Here they begin to divide and form a happy family called the primary focus. It is here that the sexy slim B cell often changes into a rather large flabby shadow of his former self, the plasma cell. However scattered throughout the home are cells that help provide complements (punny if you are an immunologist) to each of the cells and ultimately their marriage survives and they are average. 

Some B cells, like some people enjoy change and instead venture off into a new location with their partner. Here they change radically excelling in career and producing the best antibodies. Their partners change too. Occasionally there can be too much change and often B cells can no longer recognise the complements or attracting factors. Soon he's too busy working nights to notice Ben his eldest cell just apoptosed. The B cell is now barely himself mutating and hypermutating and now hangs out with his buddies in the dark zone. Sometimes the B cell gravitates back to the light zone once he has matured past his midlife crisis where he will be reunited with his T cell partner. Often the B cell and the antibodies he expresses have changed too little or too much and they must now fight for the affections of his partner or die. I realise this went medieval pretty quickly. 

Okay so perhaps not exactly like the Notebook - but still a better love story than Twilight. 

The PhD condition

I've heard of people spending 8 years finishing their PhD. When I was an overachieving undergraduate I would turn my wet noobish nose at these "lazy sloths of science". I mean clearly, CLEARLY these people were just sitting around the nespresso machine  and had never touched a pipette. Then I met science. Not the kind of science you read about in books, nor the kind in movies where lethal diseases can be vaccinated before the well groomed scientist in the heels rushes out to dinner with Brad Pitt. Science - the mysterious mush of the unknown. And everyday since I have been filled with the uncomfortable thought that it is out to get me.

I think I always knew I would be a scientist. When I was two I asked my dad where the light went when you switched it off. The feeling that I get when people ask what I do is a bit, I imagine, how Rocky Balboa felt when he reached the top of the stairs. I say imagine because I am not so skilled with the running thing, or the walking thing for that matter. " Ooh a scientist" they coo. "So what does that entail? "Then, as I explain enthusiastically I watch their eyes glaze over. But it doesn't matter for I am a scientist!

It was a natural progression then that I would do my PhD and about a month ago, I registered. But as much as I love what I do, I cannot shake the feeling of dread that I do not have what it takes. Science, it turns out is not just experiments and research and questions and answers - all things I am good at. Instead these things are only a tiny proportion of overall career. Much of science is being a glorified hobo begging the likes of Bill Gates for money. Slowly we add accountant to our resume. Not something I even remotely wanted to do with my life.

Then there is the never ending politics. If someone gives you a plasmid ( basically just a tiny nothing snip of DNA) and they are a big shot but did no other work for the project you were working on, they must be an author on your paper while someone else, who probably did a huge chunk of work gets bumped to acknowledgements because they only have a honours or something. Is it fair? Nope. Will it change? Nope. Getting bounced around by huge egos is they way it works and as your research gets into bigger journals so the pressure to bow down increases. Politician. Right, another thing I never studied.

Marketing is another huge part of research. So many Cell and Nature papers show obvious things. Things that are by no means innovative but they are repackaged  in the most amazing story. It's a bit like Shades of Grey. BEST MARKETING STUNT EVER. It's porn in Mills and Boon form; both of  which have been around forever; not innovative just repackaged. Generally scientists became scientists so they could be swathed in the warm comfort of no social contact. Instead we must become advertisers and more and more dolly our science up because bar charts are no longer enough. In fact infographics with 42 keys are the only way to go. Promotions....I can *gulp* do this.

It is not hard work I am afraid of, in fact I revel in it. However no matter how hard one works, it is never enough for the prying eyes of the PhDs  whose whole life is devoted to the lab. They eat there, sleep there, probably don't have a shower very often and then casually claim that anyone who is exercising or going home to a partner/child is simply weak. Having a life is just not okay. So as if all the pressure from the additional careers that we have taken on isn't enough, our own peers are constantly trying to undermine us. It's a  cut-throat world - and you just thought it was like an episode of big bang theory. 

The worst part of all this is that the two year old, the one who was so inquisitive about the world around her, is slowly receding into her shell. She fears speaking out lest her ideas be stolen from her or someone attacks her dreams of discovery. Galileo was killed by the church and I still think he had it easy.  

Tim Noakes-the joke? Or just an unfortunate rhyming name?

Tim Noakes is getting exactly what he wants. His book is sold out. Does he care that he has critics, including his mentor Lionel Opie? Probably not.

Everyone, bar those who are skinny, is hanging on to another pipe dream where veggies are just another thing swimming in butter. Lets think about it logically shall we? No carbs and no fruit. A fair amount of fat and veg. People lose weight. Do we know why? Can the man who developed this form of the actually ancient diet explain the weight loss? No. His form of comeback is actually that doubting Thomases "need to look around and explain how the low-fat ‘healthy’ diet we are currently promoting, is healthy and is not causing the epidemic of ill-health that began in 1980… three years after this ‘healthy’ diet was first promoted globally”. A nice bit of distraction. Why do we need to explain your diet Tim? Isn't that what scientists do? Aren't you supposed to do that bit?

My view on the diet is really neither here nor there. I mean people will do it because their mommies or their aunties have lost 6 kgs. And that's great. I mostly have 2 issues: 1) people are saying "read his book, he explains EVERYTHING". He explains what he wants you to know people. A cookbook, especially not one for sale, or something with revolution in the title is not a good enough source of information on which to base health decisions. Read his journal articles. Yes, you may be an architect or a bank teller and not get it first time round but really try. Or ask your friendly neighbourhood scientist to explain. Anything worth doing is going to take time.
2) The second issue is how this one scientist has managed to once again bring the whole of science under scrutiny. The people that are against his diet have evidence to back them up. He has evidence that his diet works but cant explain the mechanism. This is science. For every 10 references that you find for this low carb diet I can find 10 that say the opposite. Please know that this is NOT because science is unreliable. The aim of science is to refute each claim that is made. All scientists err on the side of caution. It is not "being mean" or "belittling someone someone". This is the only way science can move forward. Basically its a dogma eat dogma world.

And look, Tim Noakes is about to be a wealthy guy. When skinny people everywhere start dropping dead of  clogged arteries or diabetic people start trying to sue him because their condition didnt disappear, you know where he will be? In the Bahamas. With your money.

Cry the beloved country

This week I received some truly awful news. My inner geek pounded her fists, banged her head against a wall and screamed in futility into a fluffy pillow. South Africa is officially the lowest ranked country for science and maths education and the third lowest for overall education out of those involved in the Global Information Technology Report 2014. So that is 148 out of 148 and 146 out of 148 countries, behind Haiti. Haiti, the country devastated by one of the worse earthquakes in a developing country. Fantastic. I honestly feel like my puppy died. My wonderful scientific puppy. 

The government is the predominant party to blame here, but that's the obvious thing. Out of 148 countries we ranked 119th in the ability of our government to procure technology, 105th in the tertiary education gross enrollment rate and 116th in internet access in schools. But I think I'm more depressed by the apathy of students in this country to maths and science.

If you constantly convince yourself that something is too difficult for you, it will always be impossible. Likewise, if you are a parent and you reinforce the notion that maths is an alien language sent to suck our souls, don't be surprised when your kid fails it. For some particular freaky people, maths is the shiz-niz. Maths is the same in every language and in some ways that is really comforting to some. To be honest I can't remember if someone told me that or if it was a particularly cheesy line from Mean Girls. Probably the latter. 

I never had a philosophical relationship with maths. I, like most scientists, even like the man who invented calculus,view it as a means to an end. Maths was mostly developed to further science and unfortunately almost all of our understanding of the world is based on physics. Unfortunately for me, I don't like physics either but diligently I studied, always looking to the bigger picture. One day I knew I would be able to say to random people, "Hello I am a scientist" while wearing a HAZMAT suit in a biosafety level 3 facility. Which you have to admit, is pretty hardcore and a bit more exciting than "Hello, I'm an accountant, look at my spreadsheets".

Every day I learn something new. Every day I am forging ahead with a new exciting idea. Everyday I fit another piece into the puzzle. And its great, truly the best thing ever. It angers me when people say "Oh wow, you are so clever to be able to do what you do, I could never do that." Well to be honest, first I feel flattered then I try to get them to say I'm pretty too. But the bottom line is that anyone can do it, if from a young age they are given the bug of wonder; the urgency to ask questions and never stop asking them just because your parents want to kill you or because there is something bright and shiny on the TV. I also acknowledge the fact that in developing countries we are dealing with way more than just problems in schools. Our society is very broken; filled with needless violence and cultural clashes but that does not mean that we can accept mediocrity. We can not say that because someone got 30% for science they pass. I mean if you know 30% of chemistry, you may drink H202 instead of its non-lethal common counterpart. We can not accept apathy because, lets face it, the rest of the world is laughing at us. 

The message if you are a teenager is life does not end at 15. If you can't go to the one direction concert because you are studying for a maths test, it won't kill you. Another boy band will come along, probably with the same songs in 20 years time. And do you know what? You could ride into that concert on your very own T-rex. Science-it's real. 

If you are a parent, please stop telling your kids that science is hard. Of course it is. Anything worth doing is hard. So is anything not worth doing, like being a street sweeper or cleaning toilets. Science is fascinating. And there is so much more to find. In the great words of Ellie in Up "Adventure is out there, " don't stop your kids from finding it. 

Hemorrhaging fear

20081 Ebola cases in West Africa were recorded on the penultimate day of 2014. A year wrought with misnomer and confusion that exposed the complete folly of first world countries where ultimately there have only been 5 cases. That is a total of 0.02% of the global burden; a burden I might add that was enough to send main stream America into a panic that had at least a handful of people wearing face masks on planes travelling from Detroit to New Orleans 8,746km away from the epicentre of the outbreak.

It took the treatment of 2 health care workers in Atlanta and the deaths of 2400 people in Africa for the American administration to send 3000 members of the US army to help in the fight against the spread in Guinea, Liberia and Sierra Leone. Spain of course greatly contributed to the fight when officials decided to put the dog of an infected health worker down, even when there was no scientific basis for ending Excalibur's life.  It is concerning to me that in an age where as much as 31 percent of the world's demand for bauxite, cobalt, gold, manganese, phosphate and uranium is supplied by Africa, the death of its people was of little concern until their disease breeched the first world. 

Ignorance can best be explained by this gem from Donald Trump

So basically do good things for the world and you deserve to get a deadly disease. It's a wonder Mother Theresa didn't die of tuberculosis. Yes Africa is the source of many zoonotic diseases but that's because there are larger areas of Virgin mother nature that is more habitable than many other places in the world. Slowly but surely we are encroaching on habitats of things we don't understand yet, interestingly not only because of population expansion but ironically because of the human races intense requirement for more of everything. These sorts of outbreaks are not the concern of the people they infect first but of the whole world. This is not the time for selfish behaviour otherwise at the end of 2015 we will have a pandemic out of Africa that kills millions all around the world. Sound familiar?  

A taste of our own medicine

Sitting in a work meeting the other day (yes scientists have those too), we were posed with an interesting question. Would we, as HIV researchers, be willing to take part in one of the many ongoing HIV vaccine trials given the chance? The reaction was immediate, a series of firm shakes of the head swept the room and then a spattering of hurried excuses – “Well, we aren't really the target population, ethics… blah blah *scientific jargon* blah blah.” That got me thinking, why were the very people who design these vaccine candidates so hesitant to become the lab rats to test their means to change the course of history?After all, every scientist wants to leave a legacy and the best way to anger one is to tell them that even if they win a Nobel Prize, they will never be as famous as a 12 year old pop star.

I feel sure that the answer doesn't lie in a lack of commitment to the cause. Our lab represents some of the most determined to end the scourge of HIV. Being in a field that has been working for 3 decades with no translatable success and continuing to search for the proverbial needle in the haystack is disheartening to say the least. Despite this high level of failure, this group of extraordinary science minds continues to untangle the mess that HIV has left for humanity, bolstered by the fact that any meaningful finding could mean saving millions of people.

Could it be the stigma that is attached to the unknown element of HIV research? On posing this question to non-scientisty types, their reaction was one of horror. “But what if you contract HIV? Would you do that for your science?” Clearly there was a disconnect of knowledge there. In HIV vaccine trials they don’t give you a vaccine, inject you with HIV and hope for the best. This seems like an obvious statement but it is amazing what conclusions the mind can make when perceiving a threat. Those people who are recruited are healthy HIV negative individuals and although some cohorts are high risk for HIV, they are given the best information  possible to prevent infection. 

I think much of the uncertainty in the field lies in some pretty disturbing results in recent vaccine trials. HVTN 502 and 505 trials were stopped during immunisation due to futility. However, in one of the trials there was actually a trend over follow up that showed that the vaccine arm had a higher HIV infection rate than the placebo arm- a very depressing result for vaccinologists anywhere. In fact I was at the conference in Barcelona when this whole story was explained and I can tell you that you could hear hundreds of scientists'  hearts breaking in one audible crack. 

Scientists are very practical people. We only deal in facts. Fact 1: the only vaccine that showed any efficacy only protected at 31%, fact 2: we haven't had much functional success in 30 years. So why do we continue hunting for one? Well quite simply put, it is worth it. Humanity is always worth it. So perhaps the unwillingness to test our own outcome is not because we are snobs or hard unfeeling machines but because we are perfectionists. We are always dissatisfied with our progress. Everyday we work to make sure that anyone who participates in any study is as safe as they can be and that their wonderful contribution is fully appreciated. So the next time you walk past a scientist and think that we are all like Sheldon from Big Bang Theory (physicists are a totally different breed!), give them a high 5 or even better a hug (virologists don't get many of those for obvious reasons) - we are pretty cool!