Probable Impossibilities, page 7
Some observers place synthetic biology within the larger context of our exponentially advancing technology in general and the need for restraint. Richard Hayes, a social and political advocate and former executive director of the Center for Genetics and Society in Berkeley, says, “We’re at or very near a cusp in the history of humankind. It’s no longer a question of the pros and cons of this one new technology or that particular application. I believe we need to take a huge, deep breath, take a big step back and give ourselves the time and space within which to assess where we are, how we got here and where we want to go, along the entire set of social, political and technological dimensions. We need to draw lines. If we allow scientists to create a single living cell, for example one very effective at pulling CO2 from the atmosphere, why not allow creation of two-celled organisms that do so even more effectively, or of 200- or 2,000-celled organisms that remove pollutants from the ocean? Why not fish-like or rat-like organisms that possess certain human cognitive abilities and can be trained for many useful purposes? And if that’s OK, why not allow the creation of human-ape hybrids to perform even more useful tasks?”
Certainly, there are safety issues. In the early 1970s, Paul Berg at Stanford University produced a hybrid loop of DNA containing DNA from two different organisms, a virus called SV40 and the common bacterium E. coli. Berg was planning on inserting this human-made recombinant DNA back into E. coli. When concerns were raised about the unforeseen consequences of creating an organism never before seen in nature, Berg suspended his experiments. At that point, the U.S. National Academy of Sciences appointed a committee to study the safety issues of recombinant DNA research. After the committee published its report in 1974, the scientists recommended a worldwide deferment on certain kinds of recombinant DNA research until the risks were better understood. “There is a serious concern that some of the artificial recombinant DNA molecules could prove biologically hazardous,” wrote the committee. Today, forty-five years later and with guidelines in place, recombinant DNA technologies have been enormously useful in producing new vaccines, protein therapies such as human insulin, blood-clotting factors, and gene therapy.
A more recent development occurred in 2010, when J. Craig Venter and colleagues created a set of genes that were a variant of already existing bacterial genes and then inserted them into a bacterium that had had its own DNA removed. The synthetic genes then took over the bacterium. The accomplishment triggered a presidential investigative commission, under President Obama. In its report, titled “The Ethics of Synthetic Biology and Emerging Technologies,” the commission wrote: “The Venter Institute’s research and synthetic biology are in the early stages of a new direction in a long continuum of research in biology and genetics. The announcement last May [of Venter’s achievement], although extraordinary in many ways, does not amount to creating life as either a scientific or a moral matter…In order to provide benefits to human conditions and the environment, the Commission thinks it imprudent either to declare a moratorium on synthetic biology until all risks can be determined and mitigated, or to simply ‘let science rip,’ regardless of the likely risks…The Commission instead proposes a middle ground—an ongoing system of prudent vigilance that carefully monitors, identifies, and mitigates potential and realized harms over time.”
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In 1981, several years before his death, the great theoretical physicist Richard Feynman did an interview for the BBC television program Horizon, in which he was asked a question about his Nobel Prize. Feynman’s reply: “I don’t see that it makes any point that someone in the Swedish Academy decides that this work is noble enough to receive a prize—I’ve already got the prize. The prize is the pleasure of finding the thing out, the kick in the discovery, the observation that other people use it [my work], those are the real things…” Jack Szostak, too, has a Nobel. And he is undoubtedly aware of many of the theological, ethical, and philosophical aspects of his work. He is also aware of the medical and business opportunities of synthetic biology in general. (In the 1990s, he and two colleagues founded a start-up biotechnology company to produce new kinds of proteins. “Although the company was not a business success, it was a very interesting and educational experience,” he recalls.) But what drives Szostak and many other basic scientists—what keeps them up late at night in the lab or at their work desk, so that they can think of nothing else, sometimes to the neglect of their family and friends—is what drove Feynman: “the pleasure of finding the thing out.” How did life begin on our planet? What did the first replicating cells look like? How do we create a living thing from nonliving material, life from nonlife—a squirming, growing, evolving, reproducing thing from simple chemicals? Few questions could be more profound. Yet it is not only the profundity of the questions. It is the primal pleasure of finding things out, and the incomparable thrill of being the first person to understand something about nature.
As I talked with Professor Szostak about his research, despite the quiet of his voice I could hear the passion. In his autobiography, he wrote these words about his work to create primitive replicating molecules (which he calls modified nucleic acids or genetic polymers): “It is thrilling to me to see people in my lab developing new approaches to the synthesis of modified nucleic acids, but the suspense is almost unbearable as we await the results of template-directed polymerization experiments. From our current vantage point, it is not clear whether there will be many solutions to the problem of chemically replicating genetic polymers, or just one, or none, but in any case it is an exciting quest.”
There is one significant way in which Szostak’s pleasure in science differs from Feynman’s. As a theoretical physicist, Feynman worked alone. By contrast, Szostak and most biologists today work in groups, surrounded by a team of graduate students, postdocs, and other colleagues. It is a more social enterprise. And that companionship provides Szostak, and other higher life-forms, with an additional pleasure. Near the end of my visit with Professor Szostak, he summed up the last decade: “What I love doing the most is talking to other colleagues, students, and postdocs. One of the best things about having a lab is helping young people develop.”
MIND
One Hundred Billion
I’ve always been struck by the fact that the number of neurons in our brain is about equal to the number of stars in a galaxy: one hundred billion. The first reflects the architecture of one unit of consciousness, a mind, and the second one unit of glowing cosmic matter as seen by a giant being. Perhaps we should not make much of this coincidence. Still, it reminds us of our place in the cosmos, just as Copernicus and Darwin reminded us and reconfigured that place.
Not only are we cosmic material. We are the precise material made in stars. Our atoms, our particular atoms, one by one, were forged in the nuclear reactions of stars, then hurled out into space in the explosion of those stars, to swirl and condense millions of years later into planets and ultimately into single-celled organisms and ultimately into us human beings. We are literally part of the cosmos. Contrary to widespread belief, there are not two kinds of material in the cosmos—inanimate material, like rocks and water and planets and stars, plus a second kind of material, the animate, endowed with some supernatural, transcendent essence. There is only a single kind of material, made of atoms. Rocks, water, air, trees, human beings—all are constructed of the same atoms.
Still, it is stunning that a mere assemblage of atoms can produce the exquisite sensation of our consciousness, feelings of love and anger, self-awareness and self-reflection, memory, painters and philosophers and scientists. How is that possible? The British philosopher Colin McGinn has argued that we can never understand consciousness because we can never get outside of our minds to do the analysis. We are necessarily trapped within three pounds of moist gray matter, thinking and perceiving within that constraint. Whether McGinn is right or wrong, we certainly must acknowledge that any discussion of the physical cosmos is predicated on our perceptions, our language, the instruments we build. And any discussion of our personal experience with the world must include memory and the vagaries of memory. For us human beings, our minds are necessarily part of our description of reality. We study other animals, plants, nuclear reactions, cell division, DNA, planets, stars. And we ourselves are always necessarily involved with such studies, because we cannot think outside of our minds. Thus it seems natural that the scientist and mathematician Pascal, when contemplating the infinitely small and the infinitely large within the cosmos, included human beings in the same paragraph. But, as I have said before, that infinity is not to be feared. Rather, it is to be embraced. We are part of it.
Many years ago, I took my two-year-old daughter to the ocean for the first time. We parked our car some distance away, beyond sight of the water, and then walked across a broad sandy area, passing sand dunes, shells of crabs, piping plovers that ran and stopped, ran and stopped, ran and stopped. Eventually, we climbed over a sandy hill. And there was the ocean, stretching on and on until it merged with the sky. It was my daughter’s first glimpse of infinity. For a moment, her face froze. Then she broke out in a big smile.
Smile
It is a Saturday in March. The man wakes up slowly, reaches over and feels the windowpane, and decides it is warm enough to skip his thermal underwear. He yawns and dresses and goes out for his morning jog. When he comes back, he showers, cooks himself a scrambled egg, and·settles down on the sofa with the Essays of E. B. White. Around noon, he rides his bike to the bookstore. He spends a couple of hours there, just poking around the books. Then he pedals back through the little town, past his house, and to the lake.
When the woman woke up this morning, she got out of bed and went immediately to her easel, where she picked up her pastels and set to work on her painting. After an hour, she is satisfied with the light effect and quits to have breakfast. She dresses quickly and walks to a nearby store to buy shutters for her bathroom. At the store, she meets friends and has lunch with them. Afterward, she wants to be alone and drives to the lake. Now, the man and the woman stand on the wooden dock, gazing at the lake and the waves on the water. They haven’t noticed each other.
The man turns. And so begins the sequence of events informing him of her. Light reflected from her body instantly enters the pupils of his eyes, at the rate of ten trillion particles of light per second. Once through the pupil of each eye, the light travels through an oval-shaped lens, then through a transparent, jelly-like substance filling up the eyeball, and lands on the retina. Here it is gathered by one hundred million rod and cone cells.
Cells in the path of reflected highlights receive a great deal of light; cells falling in the shadows of the reflected scene receive very little. The woman’s lips, for example, are just now glistening in the sunlight, reflecting light of high intensity onto a tiny patch of cells slightly northeast of the back center of the man’s retina. The edges around her mouth, on the other hand, are rather dark, so that cells neighboring the northeast patch receive much less light.
Each particle of light ends its journey in the eye upon meeting a retinene molecule, consisting of 20 carbon atoms, 28 hydrogen atoms, and 1 oxygen atom. In its dormant condition, each retinene molecule is attached to a protein molecule and has a twist between the eleventh and fifteenth carbon atoms. But when light strikes it, as is now happening in about 30,000 trillion retinene molecules every second, the molecule straightens out and separates from its protein. After several intermediate steps, it wraps into a twist again, awaiting arrival of a new particle of light. Far less than a thousandth of a second has elapsed since the man saw the woman.
Triggered by the dance of the retinene molecules, the nerve cells, or neurons, respond. First in the eye and then in the brain. One neuron, for instance, has just gone into action. Protein molecules on its surface suddenly change their shape, blocking the flow of positively charged sodium atoms from the surrounding body fluid. This change in flow of electrically charged atoms produces a change in voltage that shudders through the cell. After a distance of a fraction of an inch, the electrical signal reaches the end of the neuron, altering the release of specific molecules, which migrate a distance of a hundred-thousandth of an inch until they reach the next neuron, passing along the news.
The woman, in fact, holds her hands by her sides and tilts her head at an angle of five and a half degrees. Her hair falls just to her shoulders. This information and much, much more is exactingly encoded by the electrical pulses in the various neurons of the man’s eyes.
In another few thousandths of a second, the electrical signals reach the ganglion neurons, which bunch together in the optic nerve at the back of the eye and carry their data to the brain. Here, the impulses race to the primary visual cortex, a highly folded layer of tissue about a tenth of an inch thick and two square inches in area, containing one hundred million neurons in half a dozen layers. The fourth layer receives the input first, does a preliminary analysis, and transfers the information to neurons in other layers. At every stage, each neuron receives signals from a thousand other neurons, combines the signals—some of which cancel one another out—and dispatches the computed result to a thousand-odd other neurons.
After about thirty seconds—after several hundred trillion particles of reflected light have entered the man’s eyes and been processed—the woman says hello. Immediately, molecules of air are pushed together, then apart, then together, beginning in her vocal cords and traveling in a spring-like motion to the man’s ears. The sound makes the trip from her to him (twenty feet) in a fiftieth of a second.
Within each of his ears, the vibrating air quickly covers the distance to the eardrum. The eardrum, an oval membrane about 0.3 of an inch in diameter and tilted 55 degrees from the floor of the auditory canal, itself begins trembling and transmits its motion to three tiny bones. From there, the vibrations shake the fluid in the cochlea, which spirals snail-like two and a half turns around.
Inside the cochlea, the tones are deciphered. Here, a very thin membrane undulates in step with the sloshing fluid, and through this basilar membrane run tiny filaments of varying thicknesses, like strings on a harp. The woman’s voice, from afar, is playing this harp. Her hello begins in the low registers and rises in pitch toward the end. In precise response, the thick filaments in the basilar membrane vibrate first, followed by the thinner ones. Finally, tens of thousands of rod-shaped bodies perched on the basilar membrane convey their particular quiverings to the auditory nerve.
News of the woman’s hello, in electrical form, races along the neurons of the auditory nerve and enters the man’s brain, through the thalamus, to a specialized region of the cerebral cortex for further processing. Eventually, a large fraction of the hundred billion neurons in the man’s brain become involved with computing the visual and auditory data just acquired. Sodium and potassium gates open and close. Electrical currents speed along neuron fibers. Molecules flow from one nerve ending to the next.
All of this is known. What is not known is why, after about a minute, the man walks over to the woman and smiles.
The Anatomy of Attention
Every moment, our brains are bombarded with information, from without and within. The eyes alone convey more than one hundred billion signals to the brain every second. The ears receive another avalanche of sounds. Then there are the internal fragments of thoughts, conscious and unconscious, racing from one neuron to the next. Much of this data is random and meaningless. Indeed, for us to function, much of it must be ignored. But clearly not all. How do our brains select the relevant data? How do we decide to pay attention to the beep of a smoke alarm and ignore the drip of a leaky faucet? How do we become conscious of a certain stimulus, or indeed “conscious” at all?
For decades, psychologists, philosophers, and scientists have debated the process by which we pay attention to things, based on cognitive models of the mind. But in the view of modern scientists, the “mind” is not some nonmaterial and exotic essence separate from the body. All questions about the mind must ultimately be answered by studies of physical cells, explained in terms of the detailed workings of the hundred billion neurons in the brain. At this level, the question is, How do a group of neurons signal to one another and to a cognitive command center that they have something important to say?
“Years ago,” the neuroscientist Robert Desimone told me during a recent visit in his office, “we were satisfied to know which areas of the brain light up under various stimuli. Now, we want to know mechanisms.” Desimone directs the McGovern Institute for Brain Research at the Massachusetts Institute of Technology. Youthful and trim at age sixty-two, he was casually dressed in a blue pin-striped shirt, with only the slightest gray in his hair. On the bookshelf of his tidy office were photographs of his two young children; on the wall was a large watercolor titled Neural Gardens, depicting a forest of tangled neurons, their spindly axons and dendrites winding downward like roots in rich soil.
In an article published in the journal Science in 2014, Desimone and his colleague Daniel Baldauf reported on an experiment that shed light on the physical mechanism of paying attention. The researchers presented a series of two kinds of images, faces and houses, to their subjects in rapid succession, like passing frames of a movie, and asked them to concentrate on the faces but disregard the houses (or vice versa). The images were “tagged” by flashing them at two different frequencies—a new face image every two-thirds of second and a new house image every half second. By monitoring the frequencies of the electrical activity of the subjects’ brains with magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI), Desimone and Baldauf could determine where in the brain the images were being directed.
