Books About Molecular Biology

If I were starting a career today, I probably wouldn’t go into computer software. Software is really “over”, mostly it is rehashing old concepts for new platforms—and the only business model appears to be snooping, selling advertising, and rigging financial systems.  Ick!

Instead, I would probably go into nanotechnology or molecular biology (which can be the same thing), or something in that arena. This stuff is both the Next Big Thing technologically and an area with abundant opportunities for “blue water” scientific discovery—a wide open ocean to explore, with no maps and no other ships in sight!

As Richard Feynman famously said, “there’s plenty of room at the bottom”.  And, if you can manipulate individual atoms, you can perform black magic.  These days, we can definitely manipulate molecules and atoms, sometimes one at a time.  So, watch out!

Molecular level mechanisms are operating at a very fundamental level of the physical world, not far removed from many basic forces. But what a world!  Our everyday intuitions are all wrong at the molecular scale: things happen fast, things happen slowly, things are strong, things are weak.  Most of all, things are noisy!  So much is going on, it is a deep challenge to understand even simple systems.

Of course, nature has been doing nanotechnology for a billion or three years, all over this planet (and probably everywhere else).  There is so much we don’t know, so much we haven’t even tried to look for, in the natural world.  You’d have to be a very poor scientist to not make fundamental discoveries in molecular biology.

We humans are natural systems, built up of myriad molecular machines and systems. And these are fundamental to human nature, even to everyday macroscopic behavior and social relations.  And there can be surprising connections between molecules and behavior, and behavior and molecules.  If we don’t understand these things, we don’t understand ourselves at all.

And if we can learn to fix and optimize them, we may be able to perform magic.  Clean energy!  Interplanetary travel!  Prevention of disease!  Hell, even immortality!

Let’s check out a sample of recent popular science books  that captures the excitement.

The “Moral Molecule”

Zac, Paul J. 2012. The Moral Molecule: The Source of Love and Prosperity. New York: Penguin.

Zac’s book recounts his research on oxytocin, an important and ancient bio-molecule common to almost everything with a nervous system, including you and me.  Zac, an academic economist, brings a very real word and large-scale perspective to bear on this molecule, investigating the biochemistry of social relations, sex, religion, and economics.  In this book he paints the fascinating picture of what he terms, “The Moral Molecule”, through substantial experimental evidence (plus abundant plausible speculation).

The essential science here is: oxytocin is a molecule present in many species, including humans.  It is associated with nervous system, and appears to have distinct behavioral effects, which Zac summarizes as engendering “trust”:  the opposite of “fight or flight”, an openness to being close to others. When the body releases a flood of oxctocin, people (and presumably lobsters, voles, et al) experience feelings of safety, friendliness, trust, etc.

Evolutionarily, this molecule appears to have developed to be associated with sex and nursing the young: these are behaviors require tender, caring relationships to succeed.  This is one of the ways animals can modify normal defensive and aggressive behaviors (vital for survival) to create a limited circle of “trust” within which breeding can occur.

In humans, this often triggers a flood of endorphins, which produces great pleasure.

The story is much more complex, of course.  It is not just that oxytocin can trigger behavior, behavior can trigger a release of oxytocin, producing chains of mutual causation. In particular, various pro-social behaviors may cause the release of oxytocin, which creates feelings of trust, comfort, and empathy; which leads to more pro-social behavior, and so on.  In humans, release of oxytocin often triggers a flood of endorphins, which produces great pleasure, further reinforcing the behavior.

The reverse can happen as well: hostile or violent behavior suppresses the release of oxytocin, which decreases feelings of comfort, reducing trusting behaviors. These behaviors may also release endorphins, though, so they may be reinforced.  (Human behavior is complex, so is brain chemistry.)

Frankly, the brain chemistry is pretty boring in itself. What makes this book interesting is how Zac ties these basic links to real world interpersonal and social interactions, as well as religion, health, and prosperity.  Now, I have to say that most of the claims about pro-social behavior, and the links with many positive outcomes have been made many times by others.  For example, we know that people who have solid and positive interpersonal relationships are happier and live longer.  We are not surprised that weddings make people happy, and we are also not surprise that severe abuse, neglect, or stress can have permanent emotional effects.  We’re not even surprised at links between sex and religion, or that mutual trust in a community is the key to prosperity for the whole community.

However, Zac is able to tell a story of how oxytocin, specifically, behaviorally triggered releases of oxytocin, explains and ties these macro phenomena to brain chemistry.  This makes many of these earlier observations less mysterious, and certainly less mystical, but also confirms what we really alerady know is the right way to behave and organize society.  Assuming that Zac’s suppositions are more or less correct, then we know that, for example, lots hugs will make you happy and healthy, and will contribute to a much happier and healthier life for everyone. This is true because it is how humans have evolved to work.

“Oxytocin, then, is not only tied in with the brain mechanisms that make us pro-social and morel, it is also tied in with the mechanisms that make us happy by activating the elements in the HOME circuit, dopamine and serotonin.  Fulfilling relationships make us happy, and as psychologists and epidemiologists have been demonstrating for many years, being happy makes us healthier. Oxytocin reduces cardiovascular stress and improves the immune system, a neat trick for a tiny and ancient molecule, causing us to live not only happier, but longer.”  p. 207

I especially liked the book because of Zac’s hard-headed empiricism, and somewhat adventurous experimentation.  Please read the book and his other articles to see how he has explored these very interesting questions, and how he supports his claims. I have to note that parts of Zac’s book are pretty speculative, drawing conclusions far beyond what he can empirically prove at this time.  But it is a good story, with at least some solid science, and the promise of more science to follow.

I also found that his work meshed with other work that had completely different goals, but similar, converging results.  You’ll find Zac’s work cited by McGonigal, who is interested in why games work, and how to use them to fix the world.

McGonigal, Jane. 2011. Reality is broken: why games make us better and how they can change the world. New York: Penguin Press.

You’ll also find his work connected to The Neighborhood Project, which is basically trying to make better cities through various interpersonal interventions.

Wilson, David Sloan. 2011. The Neighborhood Project: Using Evolution to Improve My City, One Block at a Time. New York: Little, Brown and Company.

Any and all of these folks could be wrong.  Just because it is a good story, doesn’t mean it is true.  But when I see quite a few people arrive at similar conclusions from different directions, then the story starts to be convincing.  So maybe we are getting somewhere.

Life’s Ratchet: Molecular Machines

Hoffmann, Peter M. 2012. Life’s Ratchet: How Molecular Machines Extract Order from Chaos. New York: Basic books.

Moving from human behavior, happiness, and prosperity, let’s consider how life really works, and how life can exist at all.

Hoffman tackles the very basic questions of “what is life?” and how does it work.  It is now apparent that all life is, at base, molecular machines, which have evolved for billions of years, and which exist in a chaotic, random storm of thermal motion. How can organized, purposeful behavior emerge from what is, at the molecular level, such a chaotic storm of thermal noise?  Throughout the history of ideas about biology thinkers have argued about the roles of “chance and necessity”. Hoffman explains some current answers to this question.

In order to understand the basic principles of life, it is necessary to look at a very small scale, the scale of molecules.  At this scale, we can actually see molecular “machines” that are not “alive”, but which combine together create living systems.  Notably, we can see the same molecular machines across many different organisms, combining to build up vastly different macroscopic organisms—just as one would expect from an evolutionary process.

At this scale things are weird and different from the human-scaled world we intuitively understand.  First and foremost, the molecular scale is dominated by the “thermal storm”, the constant random rattling of molecules, Brownian motion. Hoffman points out that this thermal storm is analogous a 15,000 mile per hour hurricane blowing constantly—and in all directions at once!  How can anything survive, let alone come to be, in such a violent environment?  And, for that matter, how can we learn to understand this world?

Basically, things work at this level because of the properties of chemical bonds and molecules, especially the geometry and folding of proteins and other polymers. Though the lifetime of a molecule may be very short, there are bazillions of them being born and dying every second, so molecular systems can be “stable” for long periods of time.

Hoffman’s discussions of specific molecular machines are particularly interesting. For example, he explains what is known about several “walking molecules”, such as myosin and kinesin, which transport molecules in the cells of many animals. The molecules are moved by attaching to the payload, and “walking” along molecular membranes—wow! There is even video of the process,

Kodera, Noriyuki, Daisuke Yamamoto, Ryoki Ishikawa, and Toshio Ando. 2010. “Video imaging of walking myosin V by high-speed atomic force microscopy.” Nature no. 468:72–76.

Just as interesting, Hoffman tells about the contemporary methods used to gain these insights, which are awe inspiring. Trapping and tracking individual molecules with lasers and microscopes!  Phew!

One of the critical principles of molecular machines is the importance of the folded shape of complex molecules, and how the shape changes dynamically when molecules bind.  Walking molecules “walk” by a cycle of changes triggered by (random) attachment of ATP and ADP molecules.  As the molecules attach to specific sites, the molecule warps and bends, detaching, grabbing ATP, releasing ADP, and so on. These changes happen in response to the random flow of molecules and energy, but they create a more-or-less determined sequence:  the molecule “ratchets” through a cycle of states, to “stride” along a membrane.

Sometimes these complex and sophisticated symphonies of molecular machines are offered as evidence that life could not possible evolve spontaneously without some kind of “direction”. On the contrary, Hoffman says, we now know that life “uses chaos” rather than resists it, which is the only way life could possibly develop.

“Looking at molecular machines has made me realize that evolution is the only way these machines could have come to exist. As we have seen, life exploits all aspects of the physical world to the fullest: time and space, random thermal motion, the chemistry of carbon, chemical bonding, the properties of water. Designed machines are different. They are often based on a limited set of physical properties and are designed to resist any extraneous influences. The tendency of molecular machines to use chaos rather than resist it, provides a strong case for evolution. Why? If life started by itself, without a miracle, then life had to start at the molecular scale. The ability of life to somehow incorporate thermal randomness as an integral part of how it works—as opposed to giving in to the chaos—shows that life is a bottom-up process. A top-down design would have avoided the complications of thermal motion by making the fundamental entities of life larger, so they could resist the molecular storm more easily. “ p. 226

These studies are not only at the edge of known science, they are clearly fundamental to some of our most important questions about the universe.  For instance, nothing in Hoffman’s tale is in any way unique to Earth—it must happen everywhere in the Universe.  The same types of molecules that have built up life on Earth likely exist everywhere in the Universe, though, of course, the specific set of molecules might come out different.  But life at the molecular level must exist everywhere.

This work is also at the cutting edge of technology.  Hoffman’s arguments make clear that the way to create biotechnology is to follow nature’s way, evolving self-assembling collections of molecular machines.  Top-down design of micro-machines is not likely to succeed.

Synthetic Biology

Church, George, and Ed Regis. 2012. Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves. New York: Basic Books.

Where do we go with this knowledge? Church and Regis write about one of the key technological directions: “synthetic biology”.  With our new-found understanding of molecular biology and the ability to read genomes, it is possible to deliberately  write artificial genomes, to create new forms of life, that have amazing properties. In short, we can create organisms to solve our most pressing problems through the processes Nature uses.

A simple example of synthetic biology are genetically engineered bacteria that generate drugs or other useful chemicals.  This is not science fiction: today most medical insulin is produced by genetically modified E. coli bacteria. And soon, many petrochemicals may well be replaced by similar synthetic biological sources.

C & R outline the basic techniques of synthetic biology:  manipulating DNA to create custom biochemistry. Basically, mixing and matching what Nature already can do, to create something new.

There is considerable discussion of efforts to commercialize these technologies.  Their discussions of business models and legal issues are poorly written, and basically boring for me.  But there are important nuggets of experience:  so many fabulous, can’t miss, free-money-from-sunlight, ideas have failed.  It’s not so easy to get from a cool lab experiment to a successful industrial technology.

C & R present their own views on privacy of genetic data, which, if I understand them correctly, they aren’t terribly worried about.  Aside from their obvious vested interest, I can see their point:  does it really make sense to worry about “owning” your genome, when so much is at stake if the information can be used.  And, honestly, with the cost of genetic analysis crashing, it will soon be trivial to read anyone’s genome just as you can snap their image.  At that point, arguments about “privacy” enter a different level.

C & R are also leading lights in the DIYbio movement.

Wohlsen, Marcus. 2011. Biopunk: DIY Scientists Hack the Software of Life. New York: Penguin.

As a Fab Labber, I’m surely in favor of “establishing a vibrant, productive and safe community of DIY biologists”.  Of course, one does have visions of “some guy” messing around with DNA in his garage—what could possibly go wrong?  But that cat is out of the bag, so the only question is how to make it safe and open to the public good.

Archea, The Third Domain

Friend, Tim. 2007. The Third Domain: The Untold Story of Archaea and the Future of Biotechnology. Washington, DC: Joseph Henry Press.

Finally, we return to the natural world, part of which is all around us but sometimes nearly unknown—especially at the very smallest scale.

For many years, life was theorized to belong to two broad groups, … and … (which includes plants, animals, and us).  In the 1970s Carl Woese (who died in December 2012) used new DNA reading technology to show that there is a third group, now know as Archaea.  Whoa! A whole ‘nother domain!

This ancient branch of life lives and thrives today, in many cases at the “outer limits” of what we consider survivable.  Many Archaea are extremophiles, adapted to live in high temperatures (boiling hot volcanic springs), cold temperatures (Antarctic ice), dark (deep cracks in the Earth) and poisonous (volcanoes) and oxygen free (slowly digesting the wreck of the Titanic). These guys could live on Mars, or the moons of Jupiter, but some are found right here, alongside everyday microfauna, in ponds and even in human saliva.

It is interesting to read about the ongoing exploration of natural microbes, which is only possible now that we can sequence and process DNA and RNA.  Something like 10,000 microbes have been identified by science, out of many millions of species that probably exist.  Since most microbes can’t be cultured (i.e., we don’t know how to make them grow in captivity), they can be identified only through DNA fingerprinting and genetic engineering.

Microbes are interesting scientifically, because they are the dominant species on Earth, and probably everywhere else in the Universe.  It’s fair to say that all human life depends on microbes, quite possibly in ways we don’t even know about.

Microbes are also interesting because they are highly evolved molecular factories—assembled from molecular machines, “life’s ratchet”—capable of “eating” many sources of food, and creating many materials from those foods.  They exploit exotic energy sources, including chemical and thermal energies not based on photosynthesis. Some hate oxygen, but love methane, cyanide, arsenic, and other (to us) toxins.

Who knows what valuable and life saving chemistry may already exist in some microbe, if only we know how to duplicate it?  And who knows what they may already be contributing to human health and disease?  Do they work with or against known pathogens?  Are some diseases caused by normally undetected Archaea? Are some diseases prevented or cured by undetected Archaea?  We really need to know.

The book recounts several “expeditions” in some detail.  Exploring the newly evolved ecosystem that is consuming the Titanic on the floor of the North Atlantic.  Hunting intestinal microbes in the insects of Costa Rica (intestinal microbes are there to digest “difficult” food—insects in the rain forest encounter a huge variety of different “foods”).  Sampling the volcanic mud in Yellowstone.  Sampling the Harlem Meer in Central Park.

Biology is Destiny (Molecular Biology, that is)

Freud was talking about something else.  What I’m talking about is the rapidly developing understanding of biology at the molecular scale, which is teaching us the basic lessons of what life is (it is, in fact, molecular machines), how it works, and how it has evolved.  These findings are broad reaching, because the molecular machinery is universal, and likely to exist everywhere in the Universe.  For sure, we humans are built of molecular machines, and, in fundamental ways, human society and economics are macro-scale results of molecular chemistry.  And we are learning how to Do It Ourselves, to create molecular machinery to do whatever we want.

Honestly, this is bigger than the last “big thing” (networked computers)—much, much, bigger.  Though, I will take pride in the fact that much of what we have learned about molecular biology would not have been possible without the computers and software I helped create.

Check out these books, it one heck of a story.