Oscillator

What is “boyish” anyway?

There’s been a lot of news today about a new study (that I can’t find online yet), reporting that prenatal phthalate exposure can make young boys act more “feminine.” Phthalates are chemicals found in some plastic products that have been shown to affect the endocrine system in rats, mimicking the effect of exposure to estrogens. The new study found that “Boys exposed to high levels of these in the womb were less likely than other boys to play with cars, trains and guns or engage in “rougher” games like playfighting.”

I don’t doubt that exposure to endocrine altering chemicals is bad for developing babies of all sexes and genders. Others (mostly from the plastics industry) have pointed out problems with the study’s experimental design, statistics, and uncontrolled variables that are definitely necessary to look into before making any definitive statements about the data being presented.

My biggest problem with this study, however, is how it defines gender so narrowly, or rather that it defines gender at all based on arbitrary behaviors. The very idea that behavior can have a “gender”, that some play activities can be “masculine” while others “feminine” is so restrictive and completely ignores the enormous social aspects of gender development and the very definitions of gender in our culture.

What does it mean to act “feminine”? Are boys who don’t like playing with guns less “male”? Are girls who engage in “rougher” games less “female”? By defining “masculine” and “feminine” in such limited terms, the study maintains and promotes a narrow set of behaviors that society deems appropriate for girls and boys. As part of a scientific study, this definition is even more dangerous, because it gives socially constructed notions of “masculine” and “feminine” a basis in scientific “fact”, naturalizing and enhancing the argument that boys and girls are meant to do different things.

Phthalates likely do affect hormone levels, and hormones probably do affect behavior in some way, and studying how chemicals may affect us in order to prevent harm is very important. However, how our genes, our hormones, and our chemical, social and cultural environment affect the development of gender differences is much too complicated for a study of 74 boys and their toys guns.

Exactly what I was thinking

about the article “A Universal Truth”, but more thought out and well-reasoned. Sheila Jasanoff’s response, “Lessons for Science Envoys”, makes many excellent points about the traps that we can fall into when discussing a “universal” anything in the context of diplomacy. One of the best I think focuses on the misconception that more science necessarily means more progress:

But just as more food does not necessarily solve the problem of global hunger, so too more science cannot be expected to solve the basic problems of development. Technical knowledge and skills are indispensable for problem solving, but answers can be only as good as the processes that defined the problems.

My other favorite point is that science is not the entirely objective search for “universal” truth that the previous article states, but that scientists are subject to the same social, economic, and cultural forces as everyone else. I think she makes the point by asking what kind of science is going to be promoted in the proposed scientific diplomacy

Which versions of science and technology will our expert ambassadors carry when they travel abroad: science for the people or science for profit and power? Will American science serve the democratic humility of smokeless cookstoves, waterless toilets, and community clinics or the autocratic hubris of nuclear technology, genetically modified miracle crops, and pricey cancer drugs?

I hope that with this kind of attitude science and diplomacy can both benefit from this program.

Truth and Beauty

Paul Krugman’s recent NYTimes Magazine article, “How Did Economists Get It So Wrong?” starts with criticizing economists for confusing beauty for truth in the simplified mathematical models of market economies. I’ve been thinking a lot about “beauty” and “elegance” in science since overhearing a discussion of synthetic biology where someone said that it would be possible for scientists to come up with a more “elegant” solution to biological information processing than already exists in evolved living systems.

In science (particularly physics), elegance is defined as mathematical simplicity. Here’s a fun TED talk by Murray Gell-Mann all about it beauty and truth in physics:

I think that systems biology is driven by a similar underlying principle; the idea that there is an underlying beauty to living systems that can be explained by simple, beautiful equations. Synthetic biology has been described as the “electrical engineering” to systems biology’s “physics” and I think it’s mainly for this reason. Synthetic biology aims to take the “fundamentals” from systems biology and turn them into an engineering discipline, where the simple equations that govern living systems can be used to design new ones.

Unfortunately, I think the notion that there is underlying simplicity in biological systems is flawed. This is demonstrated best in the work of that most famous physicist turned biologist, Francis Crick. Crick discovered the “central dogma of molecular biology,” a beautifully simple description of how heredity works, where DNA can replicate itself, is transcribed into RNA, which can then be translated into proteins that make up the functions of living cells.

His discovery was tremendous, but in the decades since Crick coined the phrase, the uni-directional, dogmatic simplicity has turned into a chaotic jumble. RNA can make DNA, RNA can act like some proteins, proteins can alter how genes are expressed and how RNAs are processed and more, and there are likely many more complicating factors that have yet to be discovered. In a way, it’s still beautiful, but it’s definitely not simple, and all of these complexities definitely make synthetic biology very challenging, but also fascinating in terms of what we can learn. By trying to understand why even the most successful synthetic biological systems fail to behave exactly as predicted, we may be able to more deeply understand the complexity inherent in biological systems and realize that stripping it away is counterproductive. We’re lucky that so far the failure of oversimplified biological models, unlike the consequences of sticking to oversimplified economic models, only really hurts the graduate students working on the project.

Control Theory

Synthetic biology is about control. Control of cells, control of biological systems, control of genes; understanding how cells control themselves so that we can do it too, in ways that we find useful. As such, synthetic biology isn’t particularly a new idea (we’ve been trying to control our “animal nature” for quite some time…), it’s just that recent technological breakthroughs in gene sequencing and synthesis have made control at a fundamental, molecular level seem just within our reach.

Since going to the FBI conference “Building Bridges Around Building Genomes”, where public safety and national security issues around the possible dangerous uses of synthetic biology technology were discussed, I’ve been thinking a lot about how the idea of control plays into our view of nature and the study of biology, and how all of these ideas are affected by cultural/historical forces. Law enforcement is about control in a way as well, and in recent years much of the focus at the FBI has shifted from responding to crimes to preventing crimes. A significant amount of time at the conference was spent discussing terrorism, and how terrorist organizations in the middle east have expressed interest in using synthetic biology to create terrifying biological weapons. Terrorism is scary, primarily because it is something that we can’t control. Terrorist cells are constantly evolving and adapting to how we can respond to them, changing in ways that we cannot easily predict and cannot easily shut down.

Sound familiar? Bacterial cells are constantly evolving, adapting to whatever chemical warfare we can throw at them, and generally being terrifying. The antibiotics which sixty years ago were seen as the beginning of a new era of control over nature have turned bacteria into a force that in many cases we cannot contain. The focus on synthetic biology as a threat, especially as a terrorist threat, becomes more interesting when thought of in this context. Biology is scary because it evolves in ways we can’t predict, and terrorists are scary because they evolve in ways we can’t predict, but somehow the idea that we can control biology in such a sophisticated way as to create even scarier biological threats with relatively minimal effort is something that is emphasized.

I don’t think synthetic biology will be successful in achieving its goals until the emphasis changes from control to cooperation (maybe this goes for US geopolitical goals as well, but that is not my area of expertise). Can we work with living systems in order to achieve something useful? Can evolution and the unpredictability in living systems be another tool in the synthetic biology “toolkit” instead of something that needs to be eliminated?

Synthetic Biology and the Scientific Analogy

Scientists love analogies; they make it easier to discuss and understand complicated systems in terms of things that are familiar to many people. Synthetic biology is still trying to define itself, but the analogy that prevails thus far is synthetic biology:biology/life::electrical engineering:physics. With the data from decades of biological research, we can put together novel biological pathways and maybe even whole genomes, creating new living “circuitry”.

Since the industrial revolution, Nature has been seen as both a source of resources to be used and shaped into human invention, but also as somewhat of a machine itself, something that has parts that can be systematically understood and then used as a tool [1]. As technology has developed to embrace the digital machine, our analogies for Nature and specifically biology have changed with it. In synthetic biology we have DNA as “software”, genes as “parts”, biochemistry as “logic gates”, all the way up to cells as computers and networks [2].

With this kind of analogy in place, synthetic biology can make “devices” that behave like toggle switches, logic gates, diodes, or oscillators, and even develop real computer software to help build living circuits like you would electronic circuits. This intertwining of biology and electrical engineering has almost moved beyond simple analogy, that biological molecules are electrical components (I too am guilty of this) and that progress in synthetic biology will mirror progress in computer engineering in the 20th century.

This analogy is useful, and certainly interesting, but is it limiting? Biology does a lot of amazing things that computers can’t (yet?), and vice-versa. There are some people working on cyborg interfaces between computers and cells as a way to take advantage of both (see the Harvard 2008 iGEM project, for example) but in a lot of ways cells and computers are not alike in what they are, what they do, and how we interact with them (and that’s ok). I think most importantly, this kind of analogy doesn’t really take into account the basic science implications of synthetic biology as a tool.

I’m not sure if we need an analogy at all, but the one that I like the best is synthetic biology:biology::synthetic chemistry:chemistry from Brian Yeh and Wendell Lim’s 2007 Commentary “Synthetic biology: lessons from the history of synthetic organic chemistry” [3].

Chemical synthesis of organic compounds in the mid 1800’s shattered the notion that there is something magical about the chemicals that make up living systems. Most importantly, synthesis led to enormous insights into the physical structure of molecules. Despite the very limited knowledge of chemistry that existed at the time of the first synthetic projects, attempts at creating molecules opened up new avenues for learning about chemistry, with obvious implications for how we make drugs, dyes, plastics, food etc.

We may be at such a turning point now. There is a lot that we don’t know about how cells work, but attempts at synthesizing rudimentary biological pathways will possibly allow synthetic biologists to better understand how cells work, and will very likely develop many useful technologies and research tools along the way. In the end synthetic biology may redefine biological engineering and the study of biology into something uniquely different.