Philosophy

Current Work On The Origin Of Life

Major experimental and theoretical advances are being made to understand the origin of life. It is reasonable that within one or two decades we shall have made at least self-reproducing and evolving "protocells."

Before Pasteur, there was no problem of the "origin of life," which sprang forth after any rain in rotten logs. Then Pasteur famously showed that "life only comes from life." But then how did life ever start?

Search for an answer began in earnest in the 1930s and 1940s with the postulate of a "primitive soup" of organic molecules.

But whence this primitive soup? Stanley Miller in the 1950s made a major discovery. He mixed simple organic molecules in a retort with electric sparks and obtained a modest number of different amino acids, the building blocks of proteins. This unleashed an intense effort in "prebiotic chemistry," yielding the abiotic synthesis of many of the small molecules of life. Since then it has been recognized that infall of "carbonatious" meteorites on the early Earth might have populated the primitive soup as well.

Wonderful results, these. But how did molecular reproduction possibly start?

All readers will know the beautiful double stranded helix of DNA and its cousin, RNA. In the 1960s, early workers were convinced that life must be based on what is called "template replication" of molecules such as DNA or RNA, where each single strand, as template, specifies the sequence of "nucleotide bases" in the complementary strand, A,T,C and G in DNA, A,U,C, and G in RNA.

Famous biochemist Leslie Orgel of the Salk Institute was perhaps the foremost scientist in this effort. He hoped that a single template strand of RNA, say AGGUCCUA, linked together by what are called 3'-5' phosphodiester bonds, could line up free nucleotides in a test tube, A lining up its complement, U, C lining up G, etc, then without an enzyme to catalyze, or speed up, the formation of new phosphodiester bonds, the second strand nucleotides would link together, and then the two strands would separate, and cycle in a self-reproduction process.

Over 40 years later, this hopeful idea should have worked, but it has not yet worked for a largely known variety of good chemical reasons. It may still work however.

The next era has been the RNA World era. It was discovered several decades ago that RNA in cells could act as catalysts, like protein enzymes, these "ribozymes" could speed up chemical reactions. Many were very excited, for RNA also carries genetic code information in cells as well, and here a single polymer, RNA, could act as an enzyme and catalyze reactions and also, maybe, come to carry genetic information.

The main line of work in the RNA World has been an attempt to evolve from a "library" of many random RNA sequences, one that could catalyze the copying into a second strand, of any RNA sequence, including itself. Such a molecule could be a self reproducing molecule, called a "ribozyme polymerase."

This too has not worked yet.

In 1971 I proposed a third idea. Here molecular reproduction is not based on template replication, but on a set of molecules linked by a set of reactions, in which the very same molecules are candidates to catalyze the very same reactions. Then obviously, it is conceivable that a set of molecules could jointly catalyzes one another's formation in what I called a "collectively autocatalytic set," forming itself from some sustained "food molecule species" in the environment.

It turns out that in sufficiently diverse chemical reaction mixtures, say of small proteins called peptides, so many reactions are expected to be catalyzed by the peptides in the reaction mixture, that a collectively autocatalytic set of peptides emerges. If this view is right, the emergence of molecular reproduction is to be expected.

Simple versions of this idea have in fact worked. For example, Reza Ghadiri at the Scripps Research Institute made the first single peptide that catalyzed the formation of a second copy of itself by gluing (ligating) two fragments of a second copy of itself together to form the entire second copy of itself. Ghadiri showed conclusively that molecular reproduction does not need to be based on DNA or RNA or similar template replication. Even peptides can do it and without template replication.

Ghadiri's post doc, Gonen Ashkenazi, now at Ben Gurion University Israel, constructed a nine peptide collectively autocatalytic set, where each catalyzes the ligation of two fragments of another peptide among the nine, into a second copy of that other peptide. Here NO peptide catalyses its own formation, the set as a whole catalyzes its formation. Calling catalysis of a reaction a "catalytic task," Ashenazi's nine peptide set achieves a Task Closure, all the reactions that require catalysis by some member of the set, are catalysed by some member of the set.

At present, Gunter von Kiedrowski has made collectively autocatalytic DNA sets, and Gerald Joyce has made collectively autocatalytic RNA sets, in addition to Ghadiri and Ashkenazi with peptide sets.

Further, Luigi Luisi has made what are called liposomes, derived from lipids in water that form "bilipid vesicles." Luisi and students showed that these liposome could grow in surface area and volume of enclosed water and divide.

Roberto Serra has shown theoretically that a dividing collectively autocatalytic set contained in a dividing liposome will synchronize the two division cycles. And Eors Szathmary and colleagues have shown in theoretical work that such systems are capable of open ended evolution.

The way seems open to create experimental protocells that reproduce, evolve and even co-evolve.

Is this life? It is probably only the precursor for several reasons: 1) Real cells link spontaneous and non-spontaneous chemical reactions into thermodynamic work cycles, the analogues to a car engine cycling. 2) Protocells need to discriminate "food" from "poison" and "act" accordingly in a complex environment to survive. Achieving these is beyond immediate reach.

Finally, should we achieve evolving protocells, how contemporary cells, with DNA, RNA, and proteins whose sequences are encoded by the genetic code in RNA molecules copied, "transcribed" from DNA molecules, remains much of a mystery.

I conclude that the progress is substantial and we can hope for protocells, perhaps even evolving and co-evolving, within 20 years.

Comments

 

Please keep your community civil. All comments must follow the NPR.org Community rules and Terms of Use. NPR reserves the right to use the comments we receive, in whole or in part, and to use the commenter's name and location, in any medium. See also the Terms of Use, Privacy Policy and Community FAQ.

Support comes from: