EMBARGOED FOR RELEASE: 5 JUNE 2000 AT 09:00 ET US

Contact: Jeffrey J. Sussman
[EMAIL PROTECTED]
212-895-7951

Weizmann Institute
New theory on the mystery of the origin of life proposed by Weizmann
Institute scientists
New model based on lipid molecules

REHOVOT, ISRAEL--June 5, 2000-- One of the greatest mysteries, which
continuously fascinates many scientists worldwide, concerns the way by which
life emerged on primeval Earth. The accepted notion is that prior to the
appearance of living organisms, there was a stage of chemical evolution,
which involved selection within inanimate chemical mixtures. This is thought
to have eventually led to the crucial moment, when self-replicating
molecules arose. As self-replication is a most fundamental characteristic of
living entities, such an event is often defined as the birth of life.
Self-replication of molecular systems is often viewed in the context of
information content. Many scientists believe that life began with the
spontaneous emergence of biopolymers, such as proteins or RNA, where
information is stored in the sequence of chemical units. Experiments
mimicking the conditions on Earth billions of years ago have shown how such
chemical units, e.g. some of the building blocks of proteins and RNA, could
appear spontaneously. Yet, the emergence of proteins or self-replicating RNA
molecules remained enigmatic.

This started Prof. Doron Lancet of the Crown Human Genome Center in the
Weizmann Institute of Science, and his students, Daniel Segre and Dafna
Ben-Eli, on a journey leading to alternatives to proteins and RNA. They have
developed a model, suggesting a new route for the origin of life, based on
lipid molecules. This model is described in an article published in a recent
issue of the Proceedings of the National Academy of Science, USA.

Lipids are oily substances, known as chief ingredients of the cell's
membranes. Lipids have two different aspects - one hydrophilic
(water-attracting), and the other hydrophobic (water-repelling). They get
readily synthesized under simulated prebiological conditions, and because of
their bipartite nature, have the tendency to spontaneously form
supramolecular structures made of thousands of molecular units. This is
exemplified in lipid assemblies (micelles), which have even been shown to be
capable of growing and splitting in a fashion reminiscent of cell
replication. Yet a critical question was left unanswered: how could lipid
assemblies carry and propagate information?

The model proposed by Lancet and colleagues offers a solution. They surmise
that early on, lipid-like compounds existed in a very large diversity of
shapes and forms. They show mathematically that under such conditions, lipid
assemblies could contain almost as much information as an RNA strand or a
protein chain. Information would be stored in the assembly's composition,
i.e. in the exact amount of each of its compounds, rather than in a sequence
of molecular "beads" on a string. A useful analogy would be that of perfume:
the information – the scent as discerned by receptors in the nose – depends
on each ingredient's proportion in the mixture, but the order in which
aromas are added is unimportant.

Thus, the authors argue, heterogeneous lipid assemblies may be thought of as
having a "compositional genome". They further demonstrate how a droplet-like
lipid assembly, when growing and splitting, could manifest a form of
inheritance. Their computer simulations show how a compositional genome
would be handed down with some fidelity to the offspring assemblies. A
crucial aspect of the model is how such molecular inheritance is made
possible. In present-day cells, the replication of information-containing
DNA is facilitated by protein enzyme catalysts. In the early prebiological
era, catalysis could be performed by the same lipid-like substances that
carry the information. Molecules already present inside a droplet would
function as a molecular selection committee, enhancing the rate of entry for
some, and rejecting others.

Lancet, Segre, and Ben-Eli designed a computerized simulation that shows
how, based solely on physiochemical principles, lipid droplets with
idiosyncratic compositions accrete, grow, split, self-replicate, accumulate
compositional mutations, and get involved in a complex evolutionary game.
Importantly, it is entire assemblies, with their complex mixtures of
relatively small molecules that are replicated.
This differs from the older models, in which a single, long RNA polymer is
what gets copied. The scientists' model makes very few chemical assumptions
and derives a rich molecular behavior reminiscent of life processes. It
therefore has the potential of constituting the long-sought bridge leading
from the inanimate world to that of living organisms.

This research has already attracted considerable interest, and was quoted in
the recently published new edition of the classic book Origins of Life by
Freeman Dyson from the Princeton Institute of Advanced Study. The next
important question to be answered: how could lipid droplets undergo the
numerous transitions needed to lead to living cells as we now know them? In
this sense, the study marks the first footfall in a long journey to come.

###

Professor Lancet holds the Ralph and Lois Silver Professorial Chair in
Neurogenomics. Professor Lancet's research is supported by The Ebner Family
Biomedical Research Foundation, Israel; The Henri and Francoise Glasberg
Foundation, France; The Alfried Krupp von Bohlen und Halbach Stiftung,
Germany; La Foundation Raphael et Regina Levy, France; Dr. Ernst Nathan Fund
for Biomedical Research, USA; The Kalman and Ida Wolens Foundation,
Corsicana, Texas and The Wolfson Family Charitable Trust, England.



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