Holly Lindem (photoillustration); Gene Burkhardt (styling)

Key Concepts

• Researchers have found a way that the genetic molecule RNA could have formed from chemicals present on the early earth.
• Other studies have supported the hypothesis that primitive cells containing molecules
  similar to RNA could assemble spontaneously, reproduce and evolve, giving rise to all life.
• Scientists are now aiming at creating fully self-replicating artificial organisms in the lab­oratory—essentially giving life a second start to understand how it could have started the first time.

Every living cell, even the simplest bacterium, teems with molecular contraptions that would be the envy of any nanotechnologist. As they incessantly shake or spin or crawl around the cell, these machines cut, paste and copy genetic molecules, shuttle nutrients around or turn them into energy, build and repair cellular membranes, relay mechanical, chemical or electrical messages—the list goes on and on, and new discoveries add to it all the time.

It is virtually impossible to imagine how a cell’s machines, which are mostly protein-based catalysts called enzymes, could have formed spontaneously as life first arose from nonliving matter around 3.7 billion years ago. To be sure, under the right conditions some building blocks of proteins, the amino acids, form easily from simpler chemicals, as Stanley L. Miller and Harold C. Urey of the University of Chicago discovered in pioneering experiments in the 1950s. But going from there to proteins and enzymes is a different matter.

A cell’s protein-making process involves complex enzymes pulling apart the strands of DNA’s double helix to extract the information contained in genes (the blueprints for the proteins) and translate it into the finished product. Thus, explaining how life began entails a serious paradox: it seems that it takes proteins—as well as the information now stored in DNA—to make proteins.

On the other hand, the paradox would disappear if the first organisms did not require proteins at all. Recent experiments suggest it would have been possible for genetic molecules similar to DNA or to its close relative RNA to form spontaneously. And because these molecules can curl up in different shapes and act as rudimentary catalysts, they may have become able to copy themselves—to reproduce—without the need for proteins. The earliest forms of life could have been simple membranes made of fatty acids—also structures known to form spontaneously—that enveloped water and these self-replicating genetic molecules. The genetic material would encode the traits that each generation handed down to the next, just as DNA does in all things that are alive today. Fortuitous mutations, appearing at random in the copying process, would then propel evolution, enabling these early cells to adapt to their environment, to compete with one another, and eventually to turn into the life-forms we know.

The actual nature of the first organisms and the exact circumstances of the origin of life may be forever lost to science. But research can at least help us understand what is possible. The ultimate challenge is to construct an artificial organism that can reproduce and evolve. Creating life anew will certainly help us understand how life can start, how likely it is that it exists on other worlds and, ultimately, what life is.

Got to Start Somewhere
One of the most difficult and interesting mysteries surrounding the origin of life is exactly how the genetic material could have formed starting from simpler molecules present on the early earth. Judging from the roles that RNA has in modern cells, it seems likely that RNA appeared before DNA. When modern cells make proteins, they first copy genes from DNA into RNA and then use the RNA as a blueprint to make proteins. This last stage could have existed independently at first. Later on, DNA could have ap­­peared as a more permanent form of storage, thanks to its superior chemical stability.

Investigators have one more reason for thinking that RNA came before DNA. The RNA versions of enzymes, called ribozymes, also serve a pivotal role in modern cells. The structures that translate RNA into proteins are hybrid RNA-protein machines, and it is the RNA in them that does the catalytic work. Thus, each of our cells appears to carry in its ribosomes “fossil” evidence of a primordial RNA world.

Much research, therefore, has focused on understanding the possible origin of RNA. Genetic molecules such as DNA and RNA are polymers (strings of smaller molecules) made of building blocks called nucleotides. In turn, nucleotides have three distinct components: a sugar, a phosphate and a nucleobase. Nucleobases come in four types and constitute the alphabet in which the polymer encodes information. In a DNA nucleotide the nucleobase can be A, G, C or T, standing for the molecules adenine, guanine, cytosine or thymine; in the RNA alphabet the letter U, for uracil, replaces the T. The nucleobases are nitrogen-rich compounds that bind to one another according to a simple rule; thus, A pairs with U (or T), and G pairs with C. Such base pairs form the rungs of DNA’s twisted ladder—the familiar double helix—and their exclusive pairings are crucial for faithfully copying the information so a cell can reproduce. Meanwhile the phosphate and sugar molecules form the backbone of each strand of DNA or RNA.