Can a physicist fix a cell?

I posted this the other day on the Amaral Lab blog, but if you didn't get a chance to see it:

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For those of you who haven’t read the article “Can a biologist fix a radio?” allow me to summarize: physicists and engineers are awesome, biologists are idiots. I could (and at some point, likely will) ramble on at greater length about the litany of problems that I find with the author’s entire premise and conclusions but here I’d like to focus myself a bit more. Of course, you can and should read the article yourself but my one sentence summary is sufficient prior knowledge for the current purpose.

I’m frequently annoyed whenever I hear people citing this editorial as insightful. The fact of the matter is that the author poses an extremely interesting question: how would individuals that were trained in different disciplines approach a novel problem such as understanding or fixing a strange new object (a radio)?

This thought experiment could be really interesting, but unfortunately in its published form this is not the case. Perhaps my real problem with this editorial is that I imagine the thought experiment as if the object of understanding were a strange foreign object – something that no one knows anything about a priori. The radio analogy serves merely as a nice way to ground this potentially esoteric thought experiment.

From this starting point, the author lays out/mocks the potential straw-man-biologist approach: a) get your hands on a lot of these radios, b) take them apart and catalog the pieces noting various qualities, c) remove components and see how the function of the radio is altered, d) shoot radios with a shotgun until they cease to function and try to determine why, etc. To this relatively simple list I would also add that a biologist would most certainly try to understand inputs and outputs. It appears this alien thing functions with electricity so lets send a pulse of electricity through it and maybe we can track where this electricity goes and how that is altered when components are missing. I could go on listing the types of experiment that a humble biologist such as myself would propose, but I would rather ask the question of how would an engineer or physicist approach the problem?

However, the author doesn’t specify in this regard and rather states “we know with near certainty that an engineer, or even a trained repairman could fix the radio”. Oh, we’re talking about actual radios. Literally, the kind of radios that engineers who are required to take electronics classes grow up building and diagramming as part of their training. Not a strange new object for which a radio serves as an analogy. An actual radio.

When the question is framed this way, I submit that an average electrical engineer would do a much better job at fixing the radio than an average biologist. Next you’re going to tell me that if you want to solve an unknown equation, the best people to ask would be mathematicians and not biologists! Or that a biologist wouldn’t be the best person to manage your stock market portfolio. I’d be on the edge of my seat in anticipation of the conclusions of “Can a biologist solve the middle-east peace process?”.

My point here is that this could be an interesting thought experiment were it phrased differently. Its not only that biologists and physicists learn different material in their classes. I believe that to some degree we also learn different ways of thinking and approaching problems, and that the biological education has many shortcomings and biology as a whole has and will continue to benefit from physical scientists. When I sit down with my boss (a physicist) and show him particular data, his mind goes in completely different directions from my own. To some extent this is knowledge of the field and experience publishing, but to another degree I’m sure that these differences are the product of ways of thinking which clearly differ between the two of us. I’m just not sure exactly how we think different, how these ways of thinking are related to particular parts of our education, and whether different means that something is unequivocally better or even better suited to certain types of problems or not.

So how would a physicist or an engineer understand or fix a strange foreign object for which we will use a radio as an analogy? As a lowly biologist, I don’t know the answer to that question, and would love for someone to articulate it. However, let me stop you right now before I’m swamped with comments that physicists and engineers think in “models” and “first principles” and rather than a naive reductionist approach a physical scientist would “think holistically” and blah blah blah. I have no need for this verbal display of scientific pseudo-speak. Give me concrete examples of how a physical scientist would go about understanding a strange foreign object like a radio via experimentation.

Perhaps physical scientists wouldn’t catalog parts and iteratively take out objects and assess the function the way a biologist naively would. But until I hear different, my on-going assumption is that a physicist would build a radio accelerator and hurtle 2 radios at each other at the speed of light to figure out how radios function based on the scatter of the resulting collision. I joke (kind of) namely to make light of the original authors condescending tone to biologists, but also because I wish to point out that the reductionist approach is not even remotely unique to biology. I’m not so sure that the answers I hopefully receive will differ that significantly from a biologist’s prescriptions.

I’m not sure that biology was ever the isolated discipline that some would have you believe, but at very least I wish to make it clear that a lot of physical scientists are currently making great biological discoveries. Of course, so are biologists. And – this is crucial – physical scientists and biologists alike are are failing together in countless areas. Think: every unsolved biological problem. If physical scientists think different, convince me this difference exists within the framework of our little analogy. And if you’re really feeling ambitious, convince me that different is better.
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Decoding dialects key to understanding the language of DNA

Check out the article that I wrote for the Northwestern Science in Society website

How applied is to applied?

First off, I want to say thanks for the education and the living stipend. I'm a graduate student currently funded by you thanks to all of your generous donations to the National Institue of Health by way of the IRS. It is in my best financial interest to tow the party line and say that there is no such thing as to much investment in research and development at the federal level. After all, I'm rather unlikely to convince Pfizer to fund my intellectual curiosity at the basic linguistic structure of DNA, and I firmly believe that scientific research is absolutely essential for economic growth and innovation.

The premise behind funding research at the federal level is that there is little incentive for private companies to investigate basic biological or physical phenomenon for knowledge sake alone. Private companies want to make drugs to cure diseases because they can sell those drugs for profit; elucidating the physical mechanism that a protein uses to bind DNA pales in comparison. In addition to the enriching our understanding of the world around us, which few would disagree is a laudable goal, basic research into the aforementioned mechanism might have unintended applications. The modern internet was born from physicists working at a particle accelerator whose purpose was to investigate the fundamental laws of physics at the atomic scale. No one anticipated it, but the plethora of data and the need to share it spawned the world wide web. This often cited example would likely never have been funded by any company because of the high costs and low odds of payoff.

But, like everything, research funding is far more subtle. The Economist recently held a small debate concerning the nature of public versus private research funding (see here, though the interface is unfortunately clunky to read now that the debate has closed). The first and clearest take home message is that there is no way to delineate basic from applied research.  Research falls on a continuum, and what one person would call basic another would call applied. Can we truly study plant genetics without uncovering applications that lead could lead to drought resistant Genetically Modified Organisms? I was fully convinced by this argument that basic versus applied is a false dichotomy and I was ready to go home with my tail in between my legs. But another debater briefly raised the issue of profit versus non-profit research and I realized this is the real underlying debate and the cause of my unease at funding particular research areas.

The first thing that you must know is that academic science is a very safe endeavor for scientists. Sure, becoming a professor is incredibly difficult and so to is procuring tenure. But compared to the alternative option of starting your own company to fund your research, the financial security of an academic job can't possibly be understated and I would love to hear any debate to the contrary. I don't doubt that a life as a consultant or in the pharmaceutical industry where you work on a research project dictated form above is far safer, but if you want to pursue your own research goals and intellectual curiosity there is absolutely no safer place to do it than under the umbrella of a university. As such, I'm continually baffled that taxpayer money can be used to fund research that is then taken to the private marketplace either by professors starting their own companies or by selling their discoveries to existing companies.

The Economist debate failed truly elucidate this issue, and to this day I can't see any economic justification behind why a professor should have their research funded by the government such that if they fail, they lose nothing but prestige. If they succeed, they can profit wildly and profiting wildly isn't as uncommon as you might think. At my own institution I know of countless professors with multiple spin-off companies or income generating patents. This absurd system is the very same paradigm as 'moral hazard' that banks operate under and that has proven so wildly unpopular (i.e. if a bank fails, the government will bail them out but if they succeed they reap rewards).

You could make the argument that financial incentives are the best way to encourage progress, and I would be the first to agree. But individuals who chose a life in academia have either done so out of intellectual curiosity or at very least out of safety. They could have founded their own companies, procured their own venture capital, profited if they succeeded and been forced into bankruptcy if they failed. This is the capitalist model that I so ardently support. But instead they chose the safety net of academia where they can study their own research whims as long as they can convince taxpayer funded agencies that there is some remote benefit to it.

My hope, is not that we decrease federal research funding for the sciences. Quite the contrary I think that research funding should be greatly increased. But the dirty little secret that any honest scientist will tell you is that a lot of research funds are poorly spent either on frivolous projects or on financing public risk for private gain. Developing better funding strategies that re-align incentives and payouts by keeping the taxpayer in mind will add to the pool of money available to non-profit driven scientists who will continue to produce ever-more novel and exciting research that benefits everyone.

Communicating complexity

I'm terribly lazy these days so here is yet another re-post of something that I posted over on my lab's website (which can be found here) a few days ago. Apparently self-plagiarism is all the rage these days anyway.  


Many of you know that I frequently tirade about the value of good presentation and writing skills, and the complete lack thereof in the scientific world, so here is a bit more to add on to that pile:

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I study cancer. Except, of course, that I don’t.

But if you’re a friend or family member of mine, there are pretty good odds that I’ve told you that I do. Before you judge me too harshly, let me assure you that I’m not a con artist using the prestige of a cancer researcher to attend gala dinners and pick up lingerie models. Rather, my reason for lying about what I study has a perfectly logical, age-old explanation: laziness.

What I actually study is the relationship between the coding sequence of a gene and its rate of translation by ribosomes into a protein product, as well as the evolutionary pressures that shape and constrain this relationship —worst elevator pitch ever.

The great majority of the population has no idea what a ribosome is. Or that proteins are the effector molecules that carry out virtually all of the vital processes of life. This poses a problem for me as a biologist, when in the middle of Christmas dinner or at a smoke-filled karaoke bar I get asked, “what do I do?”. Biology. Bacteria. DNA. How about them Yankees? Cancer.

Understanding your audience is one of the first rules of both writing, and speaking. Or if it isn’t, it should be. Most graduate students aren’t taught how to adapt their sales-pitch to a ‘general’ audience. Add in the constraint of brevity and most of us resort to superficial descriptions of our research that everyone will understand but that hardly begins to describe the actual work that we do. Hence: cancer.

Answering the question: ‘what do you do?’ without resorting to the extremes of jargon is a challenge that all scientists—and dare I say: people—should accept. Even short conversations in a crowded bar can lead to academic growth as we take the time to understand our research enough to communicate it clearly and concisely. The added benefit of course is that in doing so we also get to convince people, whose taxes we rely on, the breadth and importance of research.

So in case you were wondering:

I study the language of DNA.

I study how the language of DNA affects the production of molecules within the cell.

I study how the language of DNA can predict the production of molecules within the cell.

I study how the language of DNA developed over evolutionary time and how we can possibly exploit the grammar of this language to better target disease and and synthesize pharmaceuticals.

It’s not perfect, but I’m working on it. And I’m sure glad that a lot of other people are studying cancer in the meantime.
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NIH is the new Pirate Bay, and its about time

This week, congress officially shelved the 'Research Works Act'. This bill was proposed late last year and its main point was banning federal agencies from mandating that federally funded research be made publicly available. This bill stands in direct opposition to the recent trend of open access publications and prior mandates from the National Institutes of Health (NIH) that all research funded by them be made freely available to the public. From the taxpayers' perspective, it is logical that federally funded research should be made publicly available to those that helped to fund it. Imagine a different scenario where the Centers for Disease Control and Prevention paid 100 million dollars to produce 'Contagion', gave it away to Warner Bros, and allowed them to charge $12 a ticket for viewers to go see the film in theaters. It is a ludicrous proposition, and precisely what the NIH mandate is tries to prevent.

So why would anyone want to limit access to research? Its entirely obvious, but this is where parallels to copyright infringement, media piracy, and SOPA/PIPA emerge. One of the major headlines to come out of this relatively short debate was the 7,500 strong researcher boycott of Elsevier - a journal publishing company that initially sponsored the bill and was subsequently pressured to withdraw support, thus ending the bills hopes of proceeding. As a company which publishes scientific research at a considerable cost, it is in Elsevier's interest to prevent their content from being distributed freely. Even as a child of the internet age that has come to expect that all of my media content be free, I can sympathize with this concern.

Creating and distributing music costs money and so to does creating and distributing research. It's not to say that garage-band musicians who independently distribute can't make a profit, and scientists who publish on sites like arXiv can't readily distribute their research. But big journals, like big record labels and film studios, clearly distribute research broadly. More importantly, they also add value to the research by facilitating the peer review processes at a considerable financial cost. In the same way that musicians and film-makers have to deal with increasingly open access to their content (though it doesn't mean many have not tried, and failed, to fight this) so too must the publication companies. Their efforts should thus be focused more on how to change their business model to adapt to this ideological shift, which clearly journals can clearly do - other publication groups including Nature and the PLoS are doing just that and came out in opposition to this bill.

Lastly, a powerful lesson to take home from this kerfuffle is that we scientists, in our own nerdy way, are  just like musicians (I like to think of myself as the Jay-Z of systems biology). We are the producers of content and we have the power to choose where we publish - and it need not always be the highest impact factor journal. When publishers do something that we disagree with, we can and should choose not to support those decisions and thus not publish with them. Their prestige is little more than a product of our collective perception of their prestige. Boycotting journals, like boycotting artists, record labels, banks, or stores whose policies we disagree with can lead to real change. This case is a perfect example of that.

--Adam Hockenberry

Sources:
Slate here and here
Nature here 
Scientific American here,
and the NY Times here.

Benefits of higher education

So I try to avoid re-posting as much as possible but this chart is just to good to pass up. One of the most common-threads that runs through pretty much every scientific discipline/department/university at the graduate school level that I have been exposed to is that of complaint. No matter where you are, you can never seem to lose points by talking about how flawed the academic system is in terms of how much graduate students and post docs get paid, length of working days, shortness of vacations,  how small our chances of finding gainful employment are, etc. 

While I'm all for making improvements to a system that I see as being far from perfect, I never quite understand the jaded graduate student trope and more frequently get annoyed at it. At some point in their education, everyone seems to feel like they were lied to and that they didn't sign on for x, y or z. I'm sure most of those individuals are people who didn't necessarily think through the choice of graduate school adequately, and my sympathy is non-existent for them until convinced otherwise. 

Yet, there are undoubtedly others who took their time and made a career decision to continue their education rather then doing so simply out of inertia/apathy. For those individuals, I hope this chart is a pleasant reminder. 

Feel free to call me out when I come whining to you in a few more years time, but until then look at the numbers. High school education pays. Undergraduate education pays. Graduate education pays. All the terrible sacrifices that we make now and make us question our life decisions should be contextualized at least every now and then by the fact that education is a rational economic decision in addition to the numerous difficult-to-quantify benefits. 

Of course, business majors undoubtedly drag these numbers up but humanities and liberal arts majors probably drag them down (sorry guys) leaving scientists and engineers somewhere in the middle.

While I made this post about graduate school in particular, the benefits for graduating high school and attending university are even more striking. So for those individuals whom the graduate school argument seems a bit esoteric, I hope there is a take home message in here for you as well. 

I couldn't possibly argue for the intangible benefits of higher education enough, but take solace that if your sole goal is increased income and job security you will find both with increased education. 

It's a bit of a side issue but I can't seem to throw a rock without hitting a journalist/blogger/academic complaining about the sky rocketing costs of undergraduate or professional education. While I'll never make the argument that our system is perfect and that we couldn't/shouldn't make adjustments to control costs and make education more accessible, I will make the argument that the benefit that can be gained over a life time is substantially more then the cost you'll pay upfront or with loans. 

Even an absurdly expensive $50,000/year education will likely pay itself off several fold over a lifetime. Does that mean it should cost $50,000/year? Or be free? Or cost substantially more? These are arguments for another day but I'd love to hear them.

see the original posting at: http://www.bls.gov/emp/ep_chart_001.htm

Fact finding and conspiracy mining

Well it has been > 3 months since my last posting, and still I'm 13 days late on what I wanted to write about. But here goes:

If, like me, you read copious amounts of news, then you couldn't have possibly avoided reading numerous articles about the 10th anniversary of September 11th. "This is supposed to be a science blog" you may be telling yourself, and you'd be right to do so. I have no intention of turning this into a political blog/post/argument, but the two most interesting articles I read (at Slate and Popular Mechanics) were of scientific relevance so I thought it worthy of discussion. 

Plain and simply, the articles that I cited lay out the arguments against 9/11 conspiracy theorists. I think that we're all by nature susceptible to conspiracy theories (Moon landing, JFK, etc.) and perhaps that susceptibility stems from the fact that some of them are actually true. Perhaps. But how do we uncover the real truth? Therein lies the scientific question.

Think what you may about the facts of the 9/11 conspiracy theorist case, either for or against U.S. government involvement and/or prior knowledge. I don't aim to convince you either way. What I do aim to convince you of, is a gigantic flaw in the conspiracy theorist way of thinking. Namely, by refuting facts that support the predominant opinion, you strengthen the case for the minority opinion. 

Allow me if I may to generalize the case so as not to break down the minutiae of 9/11. A historical event occurred, and A and B represent multiple narratives as to how it unfolded. The best route to the truth would be to lay out all of the facts, and to conclude the most probable course of events. What conspiracy theorists do, however, is start with the assumption that B must be true. And rather than strengthen facts supporting B, casting doubt on the facts that support A must automatically lead you to conclude that B is indeed correct. Refutation of null hypothesis, however, is only useful when you have carefully enumerated all the null hypothesis (C, D, E, ...). In a complex system such as 9/11, this would be impossible and rather than refute explanations, the only way to 'prove' a historical truth is to bolster your hypothesis with facts. 

Another great flaw of conspiracy theorists is that they know their opinion before looking at the facts and are thus able to support their opinion against any mountain of facts by casting doubt. Scientifically, this is unacceptable. Medical trials for instance, are predicated on the fact that individuals do not know whether they have received treatment, and those who analyze the data are also blind as to who received a drug and who didn't. While this system has its own flaws, the crucial point is that people who analyze data evaluate facts without prior knowledge. If the doctor analyzing data on whether his drug worked knew the identity of who received the drug and who didn't, it would be tremendously easy to spin the data to prove the result that he wanted to see, most likely that the drug he discovered works wonders! 

We find this unacceptable scientifically, and it should be unacceptable logically. Of course, its impossible not to have an opinion on matters of political importance. So we all approach facts with a certain bias, but those whose opinions I trust most are those who clearly try to limit their bias and be as objective as possible. Sometimes its not so obvious to tell the difference, but sometimes its glaringly obvious.

Perhaps the truest test is to envision what amount of facts it would take to convince someone to change their mind. If all of those facts, purely imaginary at this point, could be twisted and refuted to fit the opinion that they purport to refute, it becomes obvious that nothing will change some people's minds; their opinions, are thus, of little significance to me. 

A healthy dose of skepticism is a fantastic thing, and I'm always glad that people are digging for truth and not accepting what their government tells them. I just hope they can recognize that truth when they find it, even if it doesn't support their preconceived opinion.