DIY biology anyone? Behold the new species known as the biohacking citizen "scientist"!

I read a rather provocative article today that questioned the very validity of the apparently secretive and exclusive world of big time science, with the clear implication not hidden between the lines that it is finally time to take science back from actual scientists and put it back out there where it belongs - in the hands of Joe Public. "DIY" used to be reserved for the home renovation genre, but not anymore! Seemingly we are entering (or have already entered?) the era of DIY biology, where essentially anyone who wants to can let out their inner scientist and get to work on saving the world. 

There are a lot of equally provocative buzzwords being bandied around in that article, and elsewhere, including "DIY biology", "synthetic biology","bio hacking", "hacking science", "distributed science", "kitchen counter science", "citizen science" and even the somewhat radical-sounding "democratization of science"! I find most of these terms humorous at best, and downright hilarious at worst, but then again, I might be biased, being a fully paid-up member of that elite club known as actual scientists! 

At the risk of sounding trite, I would point out that membership of that club does not come on a whim, but rather is a result of a lifelong passion, a decade of post-secondary school education, and many years of higher-level training and 24/7 living in wonderful laboratories in four different countries in the world. That is how one becomes eligible to be called a professional scientist, as opposed to someone who got trained in an entirely irrelevant subject but who may have an interest in science. Perhaps unironically, most of the proselytising about the future of science being in peril and needing Joe Public's engagement comes from either non-scientists or amateur would-be scientists. I do have a solution for that predicament, but more on that later. 

Don't get me wrong, the sacrifice and dedication aspect is not unique to science - lawyers, doctors, dentists, athletes, musicians and a whole slew of other career choices all involve a similar paying-of-dues period that often takes many years, more dollars than that, and even more sacrifice, to get there in the end. But we do it ultimately because we want to, and the journey of getting there is actually a lot of fun along the way a lot of the time, not least because there is a goal in mind and we are working towards it. To hear radical rallying-the-troops hyperbole with the message that the future of science, drug discovery and medicine should now be in the hands of amateurs comes across as disingenuous, if not potentially dangerous. 

The very concept that it's 2015, people, and science can now become something that the untrained and under-educated can be let loose on, is something I find quite ridiculous on a bad day. My primary question for the DIY biology "movement" is - why?! Is someone truly saying that a bunch of enthusiastic kids (even if they were mentored by one or two established scientists) can take on the world of professional science and beat it at its own game - all from the comfort of the kitchen sink? It's quite a ridiculous concept, and essentially an impossible one. You can access all the software, hardware and wetware you want but when you don't have an understanding of even the basics - it's called tinkering, not science. 

Believe it or not, it takes more than one senior scientist to make major breakthroughs, usually. That senior scientist needs an experienced and skilled team to expand on his/her vision, and in the best teams, that vision comes from more than one person as well. There are technicians, research assistants, grad students and postdocs all contributing to the mix but they all have some key things in common at their respective levels - education, training and experience. There is a reason why they are present in a given lab, and the same progress simply cannot be achieved with a bunch of scientific neophytes even if directed by a genius.

So in my opinion, the mere idea that one can put together a whole bunch of "amateur scientists" (a kinder way of putting it!) around a country or even the globe, with one real scientist at the helm, and expecting to get somewhere fast is dreaming in technicolour.  Anyone who ever has been involved in real, hardcore research usually learns the hard way that the really hard questions are often excruciatingly hard to answer. And that's after two decades of schooling in the theory and practice of science. Ditto any other challenging profession for that matter. No serious scientist would even have the time (or patience!) to take on a challenging project, and populate it with a selection of amateurs. 

I can understand that it might be somewhat disappointing to suddenly wake up at 25 or 30, after hating science in school and avoiding it like the plague, to realise that it actually does appeal and it is what one should have focused on. I get that completely, it's something that essentially happens to us all at some point or another. But in correlation with the DIY biology "movement", if I wake up tomorrow and want to be a musician or a lawyer, I have to realise that I am lacking in both credibility and training. I cannot just suddenly create a DIY law practice or anoint myself as the next big thing - the DIY rock star - without actually picking up an instrument and learning how it works and how to play it!

But, as long as I restrict myself to being classified as someone who like music as a hobby, or as an amateur lawyer type, there is no harm in it. The danger arrives if I manage to persuade others to believe that I have expertise in it, and to part with their hard-earned cash either as an investor or as a fee for my services. Using the music analogy, there is one massive divide between someone who plays in a band with friends in the local pub on a Friday night and someone who gets contracted (and paid handsomely) by a record company to record and tour their music around the globe. 

One is a professional musician and one is an amateur with a hobby. Ironically though, the disparity in skill set and raw talent might not be as massive as one would imagine between the two, in music, but it is that massive in the case of science. If R&D and drug discovery was an easy thing, then we would all own pharmaceutical companies, or pharmaceutical companies would save even more money by hiring a few hundred DIY biologists at a cheaper price than hiring all those stuffy, expensive PhDs. Right?!

Things have changed; communication tools and technological advances have opened up the world to us all, and some of the barriers and walls have come crashing down, which is a great thing. Change is good, and it should be embraced. But change in and of itself does not allow us to break all the rules and it does not mean that the future of science is DIY biology. DIY car manufacturing or DIY aeroplanes, anyone? I can hear someone screaming that you can now print a car (yes, I saw it!) but I doubt that Ford or Ferrari are trembling in their factories.

For now, the DIY biology "movement" is a nice little hobby for non-scientists with an interest in science, nothing more. For it to gain serious traction, and to stop real scientists from snickering over it, the challenge is clear - beat us at our own game, do something spectacular (preferably three times), and you never know, we might just look up from the lab bench long enough to take notice. Until then, most PhDs probably will remain insulted by the very idea that someone who went to art school should be allowed anywhere near or let loose in any real laboratory. 

I have zero problem with enthusiastic amateur scientists, as long as they realise that's what they are, they are kept away from real laboratories in the institutions they dislike, and don't self-promote their agenda with outrageous statements claiming that virtualising the complicated process of R&D is the new way to find blockbuster drugs. Disruptive technologies are one thing, but disruptive claims are another, and if those claims cannot be backed up by data and examples (something real science relies on!) then credibility becomes the issue and they become destructive. 

But you know, there is a real solution to this burgeoning predicament that has arisen at least in part due to the popularisation and vulgarisation of science. Young people everywhere who went in other directions earlier in life are apparently discovering their "inner scientist", and want to get in on the action. I don't blame them, because I have always known that science was the best game in town, and we all do have one thing in common - I have also practised kitchen laboratory science - when I was 9 and got my first chemistry set for Christmas! 

Sadly, there is no shortcut to real knowledge plus great training, combined with seasoned on-the-job experience. For those considering the DIY biology trend, I have a better solution - go back to school and get a science degree, or three - like most current scientists did. The DIY thingy is just that for now - a trend; and although it may be cold comfort to some, a PhD is never going to go out of fashion, and it will remain the de facto passport into the real world club of high-level science. As much as the world has changed, and is changing, trends will come and go, but a great education and solid work experience will never be replaced by mere trends or by enthusiastic amateurs. Science and scientific research indeed make the world go round, but the term "scientist" has to be earned, not simply adopted. 

When a cultured cell begins to become part of the counterculture!

I read an interesting article recently that stated that life science venture capital agencies (such as AmorChem!) consider essentially half of all published research to be unverifiable. While that may initially appear to be a radical (if not outright controversial) point of view, it gained further traction after the announcement by Amgen that they could only reproduce 6 out of 53 supposedly landmark studies on cancer. This further underlined the outcome of an earlier analysis by Bayer, wherein they were only able to repeat the results published in about 25% of some 67 "hot" papers. 

One can hear not only venture capitalists asking what the hell is going on, but the entire scientific community, if not a cynical general public also. That public is subject to the rigorousness and validity (or lack thereof) of major new discoveries, ultimately in clinical trials and at the pharmacy, after that. The fact that an estimated 80,000 patients (2000-2010) were involved in clinical trials based on research papers that were later retracted is a worrying testament to how the public can be impacted by shoddy science. 

So, what the hell is going on? Irreproducibility is the thorn in the side of modern science and medicine, and clearly for such complex matters involving various layers of personnel and scrutiny, there are many possible explanations. At the extreme end there are examples of outright fraud; this does not only mean playing with the data, but has gone as far as egregious manipulation of the peer review process itself such that in certain exposed cases the senior author got to review their own paper - as inconceivable as that seems to a typical scientist. I am not going to try to define what causes a scientist to commit any form of fraud, but you can be pretty sure that "publish or perish", tenure, fierce competition for funds and positions, the clear need to be first, and mere survival are all in the mix somewhere. 

Not to be confused with the satirical take on the emerging reproducibility problem in science, "The Journal of Irreproducible Results", a certain Dr. Ivan Oransky has founded an entity known as "Retraction Watch" whose goal it is to monitor the retraction of scientific publications very closely, and to dig into the dirt and expose the darker side and slimy underbelly of contemporary scientific research. The fact that they recently received a substantial grant from the MacArthur Foundation emphasises that this issue is being taken seriously and support is growing for a closer monitoring of the scientific process. 

Reproducibility is in fact a bit of a dirty word, because often one does not want a competitor being able to repeat something one has done, and then racing ahead like an express train. In case it needs to be said, scientists don't publish to enable anyone else to do what they have done, they publish because they have to, to survive, and because they usually want to be (more) famous. At the risk of bursting anyone's bubble, academic scientists as a pack are more interested in being at the front, leading the pack, and getting the fame that comes with that, than they are in curing a disease. For those trying to get into the club, it's all about getting the papers you need to get a job; rarely anything deeper. But it can become darker, when that need becomes more of a priority than the science itself - even if that's just the reality of life for many trainee scientists who are trying to "make it".

There are a lot of moving parts in a typical research paper, often involving a combination of technicians, research assistants, graduate students, postdocs, and of course, the lab director as the obergruppenfuhrer-in-chief. While it is largely believed that the head of the lab oversees all aspects of the process from lab bench to published paper, anyone who has ever worked in even a medium-sized lab knows just how distant that oversight can be on a weekly or even monthly basis. A senior postdoc charged with "keeping an eye" on the kids is often too busy grinding out their own experiments to monitor the activities of anyone, and are often daily-obsessed with their own urgent need to get a job to get the hell out of there.  

In a typical laboratory, one is by and large left to one's own devices to get the desired data, present it at lab meetings, then compile it into a nice little story - which is where the lab head usually steps in and polishes that story into his/her version of acceptable-for-publication. The entire process only works if the trust that cements it all together is solid and does not have cracks in it due to any one piece of the puzzle not being trustworthy. As precarious as this all may be, I feel in general it works surprisingly well, if we were trained correctly as young scientists in the first place. 

Having spent the greater part of my adult life in life science laboratories in four different countries, it has always been apparent where the majority (i.e. those not derived from fraud) of irreproducible results come from - cultured cells. They are the very workhorse of the modern biology laboratory, and are used by essentially everyone as little models of the human condition. There are also very many variables in the use of the array of cell types at our disposal as biologists, such that I am pretty certain that HeLa cells or 293 cells or COS cells in two labs even in the same institute are unlikely to be identical. 

It's the things that don't go into published papers that make all the difference. Not only do the sources and grades of various chemicals often play major roles in cultured cells' response to them, but the precise practices of handling cultured cells is rarely as published. Typically, when one is publishing a paper involving the use of given cell types commonly used in that lab, and one gets to the dreaded "Materials and Methods" section of the paper draft, what most seem to do is go to the last paper published (by someone else) and simply copy/paste the cell culture details as published. If it's published, then it has to be acceptable, right?!

In this case, it is a "right!" because that culture protocol is what is written in the cell culture bible. However, that is rarely what is practised. Busy people in busy labs rarely seem to rigorously pass their cells at the same confluency each time, will continue to use them even when they overgrew, because if no one else has them in culture it means starting from scratch again and the boss won't be happy with the delay. Ditto when someone leaves trypsin on them for too long, while chatting on the phone. Additionally, when cells are "behaving" nicely, and cranking out the data you want/like, why worry that they have reached an upper passage number that dictates scrapping them and thawing out a new stock?

Cells are "abused" very regularly, and even differences in serum batches and media preparation can play havoc with the true phenotype of a cell referred to by some generic name. It's a huge problem, and one that is almost impossible to police, or at least impossible in the current scientific system. The issue was discussed recently in a new panel put together by the Global Biological Standards Institute in November that focused on cell line authentication - a central factor in a 2013 white paper by the Institute that underlined the need for new standards in the wide arena of preclinical research. Missidentification of cells prior to or during use is rife and therein lies the root cause of irreproducibility issues in modern research.

While the panel all agreed on that, there was less alignment on who should police the issues. One cannot really ask the journals to do it, not least given the fact that the majority of their editors and reviewers (think, peer reveiew) have day jobs, and their in-house editors are swamped with just handling the volume of papers hitting their desks. One can ask the universities and thus their lab directors to do it, but too much policing will definitely impact the freedom that is academia, and established, famous scientists are not going to take close scrutiny by their own university lying down. There will be a definite resistance if the checking gets too intrusive or burdensome. 

I think a variety of stakeholders will have to come together and get new policies and standards introduced into the protocols and practices of using cultured cells, and the means to assess they were adhered to in work that is to be published. The future of scientific research probably depends on it. But it's worth pointing out that a paper containing cellular data that cannot be reproduced is not fraudulent when (as is usually the case) the data was obtained honestly. It may be bad science, or misleading science, but it is not fraud. Fraud is much more insidious and harder to identify/correct, but bad science can be bettered by introducing new policies and standards to which one and all must adhere. Stakeholders will have to introduce an "amnesty" for work previously published, and only investigate work that occurred following the introduction of any such new standards. 

All this fuss over cells and cell culture has been simmering for a long time, and it has been placed on the backburner for many years, but it's beginning to boil over now, and we are all going to have to face it in one capacity or another. We simply must get to a point where F9 cells in a lab here in Montreal are the same F9 cells genotypically/phenotypically as those in a lab in Hamburg. Suddenly, reproducibility will be more the norm, rather than today's irreproducibility. There will be initial resistance and some big hurdles to get over, but if we can get cultured cells to fall into line (i.e. cell lines!) all over the world, then the culture of science is going to experience a major advancement as a result!

Avoiding cancer - it's better to be lucky than good!

I read some very interesting news this week about cancer that brings a whole new meaning to the expression "I'd rather be lucky than good", and how that relates to our chances of falling victim to cancer in our lifetimes. Those odds are already pretty heavily stacked against us, with an estimated 40% of adults predicted to stumble into some form of the deadly disease at some point or other in their lives. 

What is apparently shocking in the article published by Tomasetti & Vogelstein in "Science" magazine this past week is that it essentially debunks the "myth" that we are born genetically predisposed (or not) to (a particular) cancer, and when that is the case and is in combination with the right (i.e. wrong) environmental cues - then we get cancer. This thinking did not change with the sequencing of the human genome, which, although it simplified us in terms of how many coding genes we express, left us as in the dark as before regarding our susceptibility to killer diseases such as cancer. 

Although we have gotten a lot more successful in treating various types of cancer, it remains the #2 killer in North America after cardiovascular disease, and we still understand very little about what precisely causes it. Gaining a firmer understanding of what changes in a previously healthy body that results in that body's cells being instructed to eat the organism alive from the inside out has always been the holy grail of trying to detect and prevent cancer before it gets too tight a grip. 

Whilst cancer research has continued on as aggressively as cancer itself, in spite of many billions of dollars spent on it, there are few certainties about the crossroads between life and death that is cancer. What we do hear most frequently from our doctors is not to smoke, eat a healthy diet rich in fibre, vegetables and fruits, get as much exercise as we can, and sleep deep for several hours a night - all of this is supposed to up our chances of never having to face the grim reaper diagnosis that is cancer. 

And yet we remain bombarded by all sorts of examples that don't fit the hypothesis and hear all the stories about people who spent their entire life "breaking the rules" yet living well into their nineties, while your super-healthy next door neighbour or colleague across the corridor dies at forty-one from cancer. It's often even more shocking when that person's parents are still alive and well, and the family has no history of cancer. There just has to be more going on than good or bad genes and heredity - according to Bert Vogelstein at least. 

The rather startling news from Vogelstein (and Tomasetti) of Johns Hopkins University is that one reason why we may have been digging in the dark with little success is that in about two-thirds of cases, it all comes down to luck. That would be bad luck, of course! The authors report that the frequency of cancers seen in a particular tissue correlates with the total number of cell divisions of stem cells present in that tissue, and it therefore implicates that cell division as causative in the disease. 

Given that random mutations are introduced into our DNA when it replicates, it appears that it is that very randomness and the statistical possibility therein of introducing a negatively-impactful mutation that is at the root of the problem, almost 70% of the time. The introduction of that mutation and its propagation into future generations of daughter cells is presumed to be the mechanism by which the body ultimately turns against itself - all as a result of mere bad luck?! It's an initially bizarre-sounding hypothesis, and yet it explains much that has heretofore confused research scientists and clinicians alike. Bert Vogelstein recently summarised it as follows:

"All cancers are caused by a combination of bad luck, the environment, and heredity."

It's a very provocative statement, and may tempt some to claim that they knew the doctors and scientists were full of it all along, so now they can go back to living their life as they want and taking their chances with the lottery of life and death that is bad luck and cancer. However, even if two-thirds of it does stem from stem cells and bad luck, it is worth noting that the environment is still in there, and you might not want to add a bad environment into the equation of a bad luck mutation and it's chances of causing cancer. 

More research is needed, of course, and we will need to get better at earlier detection and diagnosis of various cancers, as well as identification of those random mutations that are devastatingly consequential in terms of entirely unpredictable emergence of cancer. In the meantime, it looks like we remain stuck with the dreaded treadmill or sidewalk, the chewy fibre and vegetables, and the reluctant putting down of bad habits - if we want to continue to win at and hurdle any bad luck in the lottery of life!