Regenesis (7 page)

In 1980 commercial DNA synthesis services were available, at the going rate of $6,000 for a small amount of product, only about ten nucleotides long. They were used either to find valuable genes in cellular RNA or to synthesize them. By 2010 we could make a million 60-nucleotide oligos for $500. Just as the global appetite for reading DNA seems insatiable—growing a million-fold in six years and still increasing—the appetite for DNA synthesis, or “writing,” will probably grow similarly and go in many unexpected directions. Since DNA in cells is very long-lived (billions of years), we might want to preserve the whole Internet in the form of DNA molecules. This would be the ultimate backup, made possible by converting the Internet's 0s and 1s to the DNA molecule's
As, Cs, Gs
, and Ts, and synthesizing the molecules accordingly. The Internet Archive contains 3 petabytes (10
¹⁵
) of data, and is expanding at the rate of 1 petabyte per year. This granddaddy of all backup copies would cost $25 billion, an amount that is not out of the question, but bringing that cost down by three to six factors of ten would be desirable. Because of its very small size, launching copies into space and icy moon polar craters could be very inexpensive.

Today, oligonucleotide chips are becoming the lifeblood of synthetic biology. However, spatially patterned light and ink-jet printers can be used to make objects as complex as patterned cells. Various options exist: (1) the cells themselves can be shot directly from ink jets, (2) scaffolding proteins can be deposited in such a manner that the cells self-assemble onto those proteins, or (3) the cells can be assembled onto photo-reactive scaffolding and then selectively stabilized or released by light. These and other methods hold the potential of making synthetic and even personalized
tissues and organs suitable for testing pharmaceuticals—and ultimately for printing copies of whole organisms.

As we go forward we will be seeing more hybrid inorganic/organic systems. Our children already inherit our mechanically augmented biology, in the form of cars, smart-phones, hearing aids, pacemakers, and so on, and these devices have become increasingly integrated into our daily lives; indeed, many people would find it hard to live without them. Since the 1980s we have added recombinant DNA-based parts to our bodies in the form of insulin, erythropoietin, monoclonal antibodies, and other medically useful substances. The addition of complex synthetic biological systems to this mix will ultimately blur the distinction between life and nonlife.

Reading the Most Ancient Texts
and the Future of Living Software

The greatest story ever—the story of the genome—continues through the Archean geologic era, which started roughly 3,500 million years ago. The name “Archean” stems from the Greek
arche
, which means “the beginning.” (The same ancient Greek term also refers to the keel of a boat, the part from which everything else rises.)

Back in the Archean, the earth scarcely resembled the planet that exists today. For one thing, there was no free oxygen in the atmosphere, which consisted largely of gases such as methane, ammonia, hydrogen sulfide, and the like, a lethal mixture for humans. For another, the earth at that time was hot, with average temperatures exceeding 130 degrees F. This was heat from the planet's molten core, produced during the earth's accretion, frictional heating arising from denser materials sinking to the planet's center, and heat from radioactive decay.

During the Archean one of the most important and dramatic events in the history of the planet occurred: the rise of life on earth. Early life took the form of single-cell organisms (and colonies) lacking a distinct,
membrane-bound nucleus, the primary examples of which are bacteria, archaebacteria, and photosynthetic forms (like cyanobacteria). That life originated during the Archean means that metabolism, reproduction, and DNA all arose during this period.

The appearance of DNA some 3,900 million years ago makes it the most ancient of all ancient texts. Ancient texts of other types are still revered today, including the 5,000-year-old Yi Ching (2852–2738
BCE
), the Bhagavad Gita (Hindu, oral Sanskrit 3137-1924
BCE
, written Sanskrit 400
BCE
), the Qur'an (Islam, 630
CE
, written in Arabic 650-656
CE
), Tipitaka (Buddhism, 580-543
BCE
, written in Pali in 30
BCE
), and the Bible. These texts are widely translated (in up to 2,200 dialects), widely printed (3 billion copies), read, interpreted, downloaded (1.4 megabytes), and even memorized. The Torah has 304,805 Hebrew characters and in the centuries since the original, ascribed to Moses (1444-1280
BCE
or Josiah's 620
BCE
revision), the number of “mutations” worldwide is only nine (among the Ashkenazi, Sephardi, and Yemenite lineages), all of which are considered to be a result of minor spelling differences that do not impact meaning.

The original ancient text is written in the genomic DNA of every being alive today. That text is as old as life itself, and over 10
³⁰
copies of it are distributed around the earth, from 5 kilometers deep within the earth's crust to the edge of our atmosphere, and in every drop of the ocean. A version of this text is found in each nucleated cell of our bodies, and it consists of 700 megabytes of information (6 billion DNA base pairs). It contains not only a rich historical archive but also practical recipes for making human beings. For such a significant text, its translation into modern languages began only recently, in the 1970s.

Other naturalistic, geological, and astronomical resources can also be considered ancient texts. We surmise that the ancient texts written by humans, as well as the texts of natural data, are all transmitting profound truths that are not intrinsically contradictory. We try to align and weave these various threads to help us understand the past and the future.

Because the engineering of that most ancient text, the genome, takes place at the cellular and subcellular levels, it's important to understand the cell and its workings in some detail. In fact, it would be nice to know exactly what it's like to
be
a cell. But is it possible, even in principle, to know such a thing?

In 1974 the American philosopher Thomas Nagel published a mind-stretching essay that became an instant classic, “What Is It Like to Be a Bat?” The piece was an attempt to understand the subjective character of a conscious experience that is fundamentally different from our own. Nagel found that his ability to do this was rather limited. He tried to imagine having webbed arms, hanging upside down by his feet in an attic, navigating through the air and catching insects by echolocation, and so on. “In so far as I can imagine this (which is not very far),” he said, “it tells me only what it would be like for
me
to behave as a bat behaves. But that is not the question. I want to know what it is like for a
bat
to be a bat.”

Certainly we are more like bats (which are, after all, mammals) than we are like cells, and so if it's difficult or impossible to know what it's like for a bat to be a bat, it's going to be an uphill battle to know what it's like for a cell to be a cell. But let's at least give it a try.

First, some history. Cells were supposedly discovered in 1665 by British physicist Robert Hooke, who saw them in thin slices of cork. What he actually saw, however, were not living (or even dead) cells but rather a network of tiny holes arranged in the honeycomb-like structure characteristic of cork, the bark of a dead tree. He thought these small cavities resembled a monk's or prisoner's cell, hence the name. At most, then, Hooke can be credited with coining the term that was later applied to cells in the modern sense.

Genuine living cells were first seen by the Dutch linen draper Anton von Leeuwenhoek through the microscope lenses that he ground as a hobby. (He first used them to examine the quality of cloth samples.) Through his lenses Leeuwenhoek saw one-celled protozoa, blood cells, sperm cells, and many other “animalcules,” as he called them. In 1683, pressing against the limit of his ability to discriminate the fine structure of this microscopic underworld, Leeuwenhoek saw bacteria (derived from
tooth scrapings), and he vividly described and drew relatively accurate pictures of them.

It wasn't until much later, in the mid-1800s, that the foundational laws of cell theory were stated. In 1837 German botanist Mathias Schleiden made the generalized assertion that all plants are made of similar units called cells. Two years later his physiologist friend Theodore Schwann extended the same claim to animals. Finally, in 1855 the pathologist Rudolf Virchow stated the capstone principle of cell theory, which he expressed in Latin as
omnis cellula e cellula
, which means “all cells arise from cells.” (The phrase is reminiscent of Pasteur's
omne vivum ex vivo
—
all life from life—and likewise seems to embody a vitalist position.)

In general, cells are small objects. Bacteria range from 0.5 to 750 microns, human cells from 5 microns to 1 meter in length. (A micron is a millionth of a meter; for comparison purposes, a human red blood cell is about 5 microns across.) The longest cells are nerve cells, or neurons, some of which stretch from spine to toe. The very tiniest bacteria, members of the genus
Mycoplasma
, are less than a micron long. The physical volume taken up by a
Mycoplasma
bacterium is evidently the smallest amount of space that will accommodate all of the metabolic machinery necessary for life, or life as we know it, so far, here on earth.

There's one big division in the overall cellular universe: some cells exist only as entities embedded within other cells of the same type, for example, muscle cells or brain cells; other cells exist as free-floating entities by themselves, for example,
E. coli
cells or yeast cells.

What we might call an average or generic cell is composed of eight major classes of polymers: polynucleotides (like DNA and RNA), polypeptides (like collagen and vancomycin), polyketides (like fats and tetracycline), polysaccharides (like cellulose and starch), polyterpenes (like cholesterol and rubber), polyaminoacids (like lignin and polyalkaloids), polypyrroles (like heme and vitamin B12), and polyesters (like PHA, PHV). First in importance are the nucleic acids, DNA and RNA, which contain the genetic information, the software of life. This software runs the cell in as literal a sense as a computer's operating system runs the computer. It directs the formation of proteins. It contains the cell's own recipe,
the complete instruction set necessary and sufficient for making another nearly identical cell. The cell is not controlled by its genome exclusively, but also by its environment, its history, and the choices that the cell makes in response to these. Emergent behaviors arise as a function of the cell's being greater than the sum of its parts individually.

Second, cells are made of proteins, which constitute some 20 percent of a given cell by weight. The term “protein” comes from a Greek word that means “primary” or “first thing,” and a typical bacterium may possess several thousand different types of them. The proteins perform most of the cell's housekeeping, self-repair, and other workaday tasks. Some of them, the enzymes, or biological catalysts, are shaped with distinctive clefts or pockets that assist in certain chemical reactions. Structural proteins have ends that attach themselves to surfaces to provide rigidity and support to compartmented cells. Transmembrane proteins allow selected types of molecules to enter or leave the cell. Since we are made up of cells, proteins are another thing that cells and humans have in common.