Monthly Archives: January 2013

What a mitochondriac does, in the simplest language possible

As I’m hoping this blog will attract ‘real people’ in addition to those who find this funny, I always wanted to properly explain what my research is about to see what said real people thought of it. (For the record, I am not a real person, as this and this caused me to fall out of my chair. Repeatedly.)

If I were an enzyme, I would be a DNA helicase so I could unzip your genes.

If you are not smiling right now, you are my target audience.

Lo and behold, the gods of the Internet, presided over by the supreme xkcd, have provided the perfect opportunity: a challenge to explain a complex topic using only the 1000 most common words in the English language (in Twitterspeak, this is called an #upgoerfive). To put that in perspective, the only words in your average scientific abstract that overlap with this set are articles and prepositions. While only the best of us can explain rocket science under such constraints, I decided to give it a shot to explain my research on the systematic approaches we take to mitochondrial diseases, the chemical and genetic therapeutic strategies we screen, and the potential intervention points we discover. If that didn’t make sense to you, I hope it does after this:

My job is to study the parts of us that change our food into power that helps us live, understand what happens when people get sick because those parts don’t work, and find ways to make these people better. Sometimes there are wrong letters in the directions our bodies have to change food into power. Since we all need that power to live, people can get very sick and die if their power directions are wrong. The problem is that we don’t know how to fix power directions (or any directions for that matter), even if we know exactly which letters are wrong. Also, different wrong letters can make different things go wrong. In fact, so many other things can go bad when power directions are wrong, that it’s hard to know where to start fixing things and because of that, we don’t have many ways to help these power-sick people. 

This means we need new ways, and to find those we need to understand everything else that goes wrong when someone is power-sick. Figuring out what those other things are is very important but pretty hard, especially because we couldn’t see many of them for a long time and don’t know what they have to do with each other. These days it is becoming easier to see more types of things that go wrong, so we’re trying to put all of them together, understand them as a whole picture, and look for what’s different between power-sick people and power-okay people. Knowing how things are supposed to look can help you figure out how to get there.

There’s lots of stuff out there you can give to sick people that might make them better, but how do we know what would work for power-sick people? We can’t just throw everything possible at them – so instead, we take tiny little parts of them (without hurting them) which also can’t make power out of food very well. Then we try all the ways we can to fix these tiny little parts. If we find ways that work, we try to find out exactly how they work – we look at all the things they do and fit them into our picture. Sometimes this can help us understand better what happens when people get power-sick, and that in turn can show us even more ways around the problem. Our hope is that the ways we find to help some power-sick people and understanding how they work will help many other power-sick people too.

Yay, I get to use real words again! And just in time, as my brain is now jelly. So I’d like to use my last remaining neurons to say I hope that made sense, and I’d love to know what all of you made of it. From my side, it was incredibly challenging but wonderfully clarifying. I would encourage everyone, especially scientists, to try it out on your own projects. In these ridiculously overcomplicated lives we’ve constructed for ourselves, simplicity can be very satisfying.

Putting a timestamp on the end of cancer is just irresponsible

Kicking cancer’s butt is a major reason many of us went into scientific research. Recently, Cancer Research UK launched an online campaign, #ResearchKillsCancer, the jist of which is, “One day we will beat cancer…help us make it sooner.” This includes a brilliantly done set of videos that tells us how far cancer research has progressed, how much work is going into developing cancer treatments, and how they need public support to realize the dream of defeating cancer.

I want to state at the outset that I fully support this initiative. Promoting research to the public via social media and getting people fired up about it is important. Finding ways to catch people’s eye in a world of overstimulation and ever-shortening attention spans and convincing them that scientific research is a worthwhile pursuit is commendable.

But hey, there are exceptions to everything. Like this Facebook picture posted by Cancer Research UK quoting one of their scientists:

My son is 21 and my daughter is 22 and I can pretty confidently say they will never ever have to worry about dying from cancer.

Here is how NOT to promote scientific research.

It is time to raise the tirade flag.

<tirade>

Allow me to summarize the median reaction of scientists to this picture in 4 PG-13 words: Are you kidding me?

They’re not alone. The original Facebook post garnered hundreds of comments from cancer survivors, terminal cancer patients, parents of cancer patients, and Joe 6-Packs alike, a large part of which were dissenting. The consensus: this is a ridiculous, dangerous overstatement. I sincerely hope that his children never suffer from this terrible disease. But what he is insinuating is that no one who is in their early 20s right now will ever die of cancer. For a cancer researcher to put his hand on his heart (or some words on a Facebook picture, which is approximately the same thing these days) and place a finite number (which I can assure you no one in the scientific community has discussed) on cancer’s remaining days is at best incredibly irresponsible. Other suggested adjectives for that mad lib include naive, stupid, arrogant, and dishonest.

For those of you unaware of just how unrealistic this statement is, think Newt Gingrich promising a colony on the moon by the end of his second presidential term before he had even secured the Republican leadership. There are at least two things wrong with that prediction. There are way more wrong with this one. For starters, no one’s life is in the balance over our colonization of the moon or consecutive elections of Newt Gingrich as the commander-in-chief of the most powerful military on earth.

Newt Gingrich on the moon

We can thank our lucky stars for that.

Here are some reasons why this promo is doing more harm than good:

1) Pointless slaughter of the original purpose

The point of #ResearchKillsCancer is to convince people that cancer research is progressing and therefore worth donating to. But if you want people to donate, why talk as if the cure for cancer is a given? This hyperbole is totally at odds with the purpose of the campaign.

I see you got a Diet Coke with that triple meat burger and bucket of fries. Good for you.

Yeah, I let him keep the change, too. I don’t need it.

2) Disappointing the public is bad for science

The astronomical odds against this statement holding true for all of humanity means it will inevitably lead to disappointment, which incidentally is not high on the list of things that science is going for. Hope is great, but false hope is not, especially when you’re literally talking matters of life and death. Disappointment fosters distrust, and distrust prevents good science from getting done by cooling public support, messing with policy-making, and encouraging budget slashing. So do we really need any more ways to disappoint the public? Plenty already think that genomics is a farce because we ‘finished’ sequencing the human genome 11 years ago and we still haven’t cured, like, every genetic disease ever. Heck, we were also disappointed that we didn’t get more out of that. But there’s a very good reason for it.

“So, umm, do we know where the genes are yet?”

3) Biology is complex and unpredictable

I want to spend a bit more time on this point, because I think it’s the most important and misunderstood one. What we learned from the Human Genome Project and everything that came from it applies here: the genome is way more complex than we anticipated. That’s because biology is way more complex than we anticipated. As this great Economist article put it, the HGP was a ‘race not to the finish but to the starting line’. The reality is that we still don’t really know what a ‘normal’, ‘functional’ genome looks like. Differences between individuals matter a lot. Sure, we have thousands of sequences from seemingly healthy people, and encyclopedias of things that the genome could be doing, and lots of ways to measure what it does. That doesn’t mean we can say, ‘if you have genome sequence x, you will be healthy for your entire life; if you have sequence y, you’d better eat carrots to avoid having an aneurism at age 50.’

Bugs Bunny

That’s all, folks!

Nothing would please us more. But that is a seriously long-term goal.

So the human genome is immensely complicated. Now take cancer. Cancer is a disease of the genome. More precisely, cancer is a big BAG of assorted, multicoloured, box-of-chocolate-and-other-unidentified-foreign-candies diseases that involve malfunctions of the genome. Names like breast cancer, lymphoma, leukemia, etc. are only very rough categorizations; it’s becoming clear that fine-tuning these is essential not only for defining prognosis (i.e., your chances of survival) but also for selecting an effective treatment. (Stratifying diseases is an incredibly important improvement to healthcare that I’ll address in another post.) We don’t know what brings about most of these malfunctions, how to treat them, or why so many of them don’t respond to (or more confusingly, do respond and then suddenly develop resistance to) the treatments we spend decades and billions developing. It is absolutely true that research is helping to answer these questions. But every scientist in the world knows that with every answer comes a million new questions. That is the very nature of science – its unpredictability.

Image

PCR is an incredibly simple method for amplifying DNA to detectable levels that involves ~5 ingredients and warranted a Nobel prize. It is an absolutely standard method in biology labs. And there is absolutely no guarantee that any given PCR reaction will ever work.

And PCR is simple biology. When you start tossing unknown genetic variation, dietary choices, family history, epigenetics, environmental influences, stuff like whether your mom was nice to you or how often you eat at McDonald’s, and more invisible factors we can’t even measure yet into the blender, and you don’t know what kind of blender it is or what it’s made out of or what it looks like or how it chops things or what its power source is, then…how do you predict what comes out and what will happen to it in 50 years? We’re getting there, but that is not a straightforward, timestampable problem.

And I hate to disappoint everyone whose heart was instilled with hope after seeing that Facebook post or watching I am Legend, but what all of this complexity pretty much guarantees is that there will be no single ‘cure for cancer’. Magic bullets only exist in Hollywood, Bollywood, and la-la land.

Zombie growling at Will

Even Will looks skeptical.

Last, but not least:

4) It violates the principles of responsible scientific communication

We as scientists have a responsibility to share our knowledge with the public – in fact, the very spirit of science is built on information sharing. While this requires getting people interested in the promise of research, it should never involve unsubstantiated claims. The false promise in that Facebook post is not only misleading and distrust-building, but simply does not reflect what scientists believe. And to pretend biology is not as complex and unpredictable as it is is not only a lie to society, but a disservice to ourselves as scientists.

The goal of science communication: relaying honest, transparent, objective, verified information that represents the relevant scientific community’s accepted stance.

As the inspiration for this post incorporated exactly 0 of those elements, I deem it a science communication fail.

Homer making cereal

It’s like the arrogance ignited the dishonesty.

OK, we can put the flag down now.

</tirade>

I don’t want to appear pessimistic about the potential of research to improve our health. Nothing could be further from the truth – the very reason I became a researcher is because I believed in it, and it’s the reason I’m still here. I truly believe genomics and modern molecular biology have the potential to revolutionize healthcare. And make no mistake, it is happening. We just honestly don’t know when the revolution will be ‘finished’.

If this picture does some good in terms of convincing the public that we researchers are doing our best to understand and treat disease, then that’s just great. But I think the Cancer Research UK videos do a great enough job of that on their own. I do not believe whatever additional hope this picture generated is worth the tradeoff for dishonesty, false hopes, and the inevitable disappointment and distrust that will follow.

I want to emphasize that the folks at Cancer Research UK (including Professor Evan), other cancer research institutes, and cancer-focused research labs worldwide are doing great work. There is no way to measure the amount of effort that goes into tackling that baffling amount of complexity I just described. There are tons and tons and tons of cancer genome sequences being generated in efforts to understand what malfunctions are at the root of these diseases and where the treatment opportunities lie. We are certainly much closer to understanding cancer than we were 20 years ago, due in great part to the affordability of genome sequencing. And I am optimistic that, with enough technology development, datasets, computing power, scientific man- and brainpower, and funding, one day we will get there. But until then, let’s be honest with the public about where we are.

And speaking of funding, we honestly need it. No one goes into cancer research for the money. Help research keep progressing in the UK, Canada, USA, and Germany (feel free to post other countries below!).

Update: While I wrote this, Cancer Research UK posted a response to all the negative reactions, apologizing for upsetting people with these ‘promises’. Their feeling was that the statement struck ‘the right balance between optimism and caution’. While I appreciate their efforts, I disagree with the latter point (the ‘caution’ element is strangely absent); also, the damage has already been done, and unfortunately most people will not read their response.

Why #overlyhonestmethods rocked my weekend

Try doing a Google images search for ‘scientist’ and see what comes up. A series of dishevelled nutjobs with glasses, lab coat, and bubbling flasks full of coloured liquids.

Just don't let him operate any heavy machinery.

This is Dr. Watson. He’s gonna cure that cancer for ya.

While it does make me chuckle, it highlights a sad reality: ‘lay people’, as we scientists like to call them (which, quite frankly, doesn’t help things either), have no idea what we’re really like.

In no way is it at all this.

The answer is not this. Very not this.

We just can’t seem to shake that ‘ivory tower’ association (particularly when some of us work at places with ivory-coloured structures that vaguely resemble towers). And this is a big problem. Associations with madness, superiority, and isolation do not serve us as scientists, to say the least: they only feed public fear and distrust of whatever strange, irrelevant pursuits we’re spending everyone’s hard-earned tax dollars on.

Gosh, I can't even pronounce that!

Fruit fly research in France? That’s despicable!

Why scientific research is worth spending tax dollars on is a topic for an entirely different post. What I want to focus on here is the image that scientists have. Too commonly do my colleagues and I encounter attitudes that scientists are elitist, hyperintellectual, detached cyborgs. I won’t stick my neck out and claim that scientists are entirely free of idiosyncrasies or social awkwardness – there’s a certain level of truth to every stereotype.  But to me, the beauty of this week’s #overlyhonestmethods trend (samples here) is that it illustrates just how much we have in common with non-scientists (even if some of the posts were a bit too specific to be entirely comprehensible).

What it shows is: we’re only human. We’re not omniscient. Sometimes we take shortcuts. Sometimes we do things a certain way because it’s most convenient. Sometimes we don’t have an explanation for why things are done a certain way. Sometimes we forget things or mess things up. Our jobs can make us frustrated, insecure, apathetic, and cynical. But the most important take-home from #overlyhonestmethods is that we have a sense of humour* (a self-deprecating one at that – is there anything better?). And that’s something that can help just about anyone get through the day.

The best part is that Bart is the only one who laughs.

If I could say a few words, I’d be a better speaker.

Honestly, we’re not that different.

*With some unfortunate exceptions.