Transcript if chemists are so smart, then why don`t they make a living system?

What化学家能告诉我们
Can Chemists Tell Us
About
the Origin of Life?
生命的起源在哪里吗?
Richard N. Zare
Department of Chemistry
Stanford University
Stanford, CA 94305-5080 USA
Chemists claim to be able to make
any molecule … …
OK -- if chemists are so smart,
then why don’t they make a living
system?
What Do We Mean By Life?
Respond to stimuli
Capacity to grow
Capacity to reproduce
Driven by chemical energy
How Did Life Begin on Earth?
1. Supernatural Explanations:
“Creation myths”
2. Spontaneous Generation:
“Nonlife  Life” is a natural
process
3. Panspermia: “It all started
somewhere else.”
Primordial Broth?
1871 -- Darwin suggests that simple chemicals in
“warm little ponds” might spontaneously form
organic compounds in the presence of energy
from heat, light, or electricity from lightning
strikes. These organic compounds could then
have replicated and evolved to create more
complex forms.
1953 – Miller and Urey synthesize amino acids
by passing sparks (lightning) through a gas
mixture of ammonia, methane, above a pool of
water.
The RNA World?
1980’s -- Thomas Cech and Sidney
Altman showed that some RNA
molecules can act as enzyme-like
catalysts.
RNA was assembled by chance, and
was then able to fill twin roles as both
enzyme and hereditary molecule in
the runup to life.
“Networks of synthetic pathways that are
recursive and self-catalyzing are widely
known in organic chemistry, but they are
notorious for generating side products,
which may disrupt the reaction system or
simply dilute the reactants, preventing
them from accumulating within a
pathway.
The important feature necessary for
chemical selection in such a network,
which remains to be demonstrated, is
feedback-driven self-pruning of side
reactions, resulting in a limited suite of
pathways capable of concentrating
reagents as metabolism does.”
James Trefil, Harold Morowitz, and
Eric Smith, American Scientist 97,
206 (2009).
How To Search For Origins
Consider the automotive transportation system in China.
If you wanted to explain this system in all of its complexity,
you would not ask whether cars led to roads or roads led to
cars.
It would be more productive to consider the state of
transport in preindustrial China and ask how primitive foot
and horse trails that must certainly have existed had
developed into paved roads and so on.
We need to look for multi-step processes with feedback,
which may have occurred in the past.
Setting The Stage
The story of life begins with the
origin of the Solar System.
Scenario for Star and Planet Formation
n~104-105 cm-3
T~10 K
0.1 pc
Cloud collapse
100 AU
Planet formation
t=0
Factor 100
smaller
outflow
n~105-108 cm-3
T~10-300 K
infall
Protostar with disk
t~106-107 yr
Solar system
1 AU = Sun – Earth distance ; 1 pc ~ 2x105 AU ~3x1018 cm
t~105 yr
t>108 yr
Geologic Time
D. W. Deamer, “The First
Livings Systems: A
Bioenergetic Perspective,”
Microbiology and Molecular
Biology Reviews, 61, 239
(1997).
How Did Life on Earth Begin?
The details of the beginning of life on Earth remain
obscure.
All that scientists can say with certainty from the
geological record in Precambrian rocks is somewhere
between the origin of the Earth around 4600 million years
ago and the appearance of the first simple fossils about
3450 million years ago the crucial steps from nonliving to
living matter happened and cells began to populate the
Earth.
Scientists also believe that all life has a common origin.
Three-Dimensional
Architechture of Molecules
Chirality = Handedness
What Are the
Facts of Life?
Life as we know it requires
homochiral biopolymers:
RNA
DNA
Proteins
Polysaccharides
…from P. Frank, W. A. Bonner, and R. N. Zare, “On One Hand,
but not the Other,” in Chemistry for the 21st Century, eds. E.
Keinan and I. Schechter, Wiley-VCH, Weinheim, 2001, pp. 173208.
Two Problems:

Establishing an initial
enantiomeric excess (e.e.)

Amplifying a small e.e. into
a dominant e.e.
Origin of an Initial e.e. on Earth

Is it Intrinsic?

Is it Fluctuational?

Is it Extrinsic?
Is Chirality Intrinsic?
In 1966 Yamagata argued that parity
violation energy differences (PVED) would
account for the asymmetric appearance of
biomolecules on Earth.
PVED is on the order of 10-18 to 10-15 kJ/mol
for molecules composed of light elements,
which should be compared to RT at room
temperature (2 kJ/mol).
Is Chirality From Chance?
Testing a Fluctuational Origin
Left-Handed and RightHanded Quartz Crystals
Quartz: An Experimental Test
of Fluctuational Chirality
The distribution of chirality among quartz
crystals within the Earth is extremely close to
50:50.
For example, in the largest study to date, of
27,053 naturally occurring quartz crystals,
49.83% of them (13,481) were found to be
left-handed, and 50.17% (13,572) were found to
be right-handed.
The most appealing fluctuation
hypothesis seems to be that the
cells all of one handedness ate
those of the opposite handedness.
Experiments on
Chiral Induction
Testing an Extrinsic Origin
A Twist of Fate?
Left and right circularly polarized light
(CPL) is not absorbed equally by any two
enantiomers.
Hence, CPL from an external source is able to
engender asymmetric stereoselection thereby
leading to a small e.e.
A Twist of Fate?
On Earth, light from the sun can exhibit
weak (ca. 0.2%) left circular polarization at
sunrise and right circular polarization at
sunset.
These differences would sum to zero over
a completely flat Earth. Where the terrain
is tilted, however, a net circular
polarization of light could result.
Such an explanation cannot be ruled out
but does sound like special pleading.
A Twist of Fate?
Cronin and Pizzarello found a chiral
excess of L-amino acids could be
extracted from the Murchison meteorite.
These include nonbiogenic L,L-2-amino2,3-dimethyl pentanoic acid, which has
two chiral centers.
Chiral Amplification
Many ways are possible!
Example: Autoamplification by polymerization
1957 -- Wald proposes that the secondary -helix
structure of a polypeptide chain should bias the
selection of amino acid enantiomers toward
homochirality as polymerization progresses.
Soon thereafter, abundant verification of this
suggestion follows.
1997 – Eschenmoser elaboration
Chiral Amplification
Another example: Autoamplification by partial
hydrolysis
Partial hydrolysis of mixtures of nonhomochiral
leucine peptides cause the preferential
hydrolysis of those components of the mixtures
that were enantiomerically more random.
Bonner (1991) proposed that partial
polymerization - partial hydrolysis steps, driven
by environmental dry and wet cycles, lead to
homochiral biopolymers on early Earth.
Chiral Amplification
Chiral Amplification
R. Breslow and M. S. Levine, “Amplification of
enantiomeric concentrations under credible
prebiotic conditions,” Proc. Natl. Acad. Science
USA 103, 12979-12990 (2006).
Solutions with as little as 1% enantiomeric
excess (ee) of D- or L-phenylalanine are
amplified to 90% ee (a 95/5 ratio) by two
successive evaporations to precipitate the
racemate.
Sequestration of Chirality
Once chirality is induced and amplified
by some mechanism, the excess must
be preserved.
J. V. Smith and co-workers have suggested
the uptake of organic molecules within the
micron-sized, three-dimensional, cross-linked
network of pores found to exist within the
top 50 microns, or so, of weathered feldspar surfaces.
A 2.5 km2 granite reef is estimated to contain
possibly 1018 "catalytic microreactors, open by
diffusion to the dynamic reservoir of organic
molecules ... but protected from the dispersive
effects of flow and convection" as well as
protected from the high flux of ultraviolet
radiation impinging on the early Earth.
(a)
(b)
SEM images of weathered (001) surfaces of alkali
feldspar fragments (Scale bar 5 µm.) (a) Fragment
from gravel, showing the beginning of formation of
etch pits; (b) a highly weathered Shap feldspar from a
peat soil, inhabited by at least three varieties of rod
and disc-shaped bacteria.
Plutonic Love?
1981, F. Westheimer stresses the important
and universal role of phosphorus in
biochemistry.
This fact hints at the origination of life as
Life on the Rocks!
Hydrothermal
Deep-Sea Vents
Marine scientists (late 1970’s) discover
ecosystems, the energy source of which is
chemical synthesis by bacteria. Associated
with the midoceanic ridge and rift systems
where the thin plates of the earth's crust
are spreading, creating vents. Seawater
seeps through. The resulting plume is often
black because mineral particles precipitate
when hot vent fluid and cold seawater mix.
Hydrothermal
Deep-Sea Vents
The Rocky Road to Life?
A hydrothermal origination of life within
porous weathered granitic materials
potentially solves an apparent contradiction.
Polyphosphates in biochemistry are
ubiquitous as contrasted both to the relative
rarity of crustal phosphate and to the
insolubility of native calcium phosphate
(apatite: Ca5(PO4)3X, (X=F,Cl)) and consequent
low average concentration (ca. 2 µM) of
dissolved oceanic phosphate.
Does Life Require
a Volcanic Eruption?
Most phosphate in the primordial crust must have
been sequestered in nearly insoluble calcium
phosphates or basalts and weathering produced
only dissolved monomeric phosphate. But volatile
P4O10 is known to be a component of volcanic gases.
P4O10 hydrolyzes to polyphosphates and
trimetaphosphate. Moreover, aqueous phosphoric
acid is known to efficiently polymerize into
polyphosphates under conditions of temperature
(250 - 350 C) well within those attained within
hydrothermal vent systems.
A Possible Synthesis:
Life starts in weathered granite reefs near hydrothermal
vents using organics from Earth and from space.
This hypothesis solves problems of:
(1) early Earth atmosphere composed of CO2 and N2;
(2) hostile surface bombardment and UV irradiation;
(3) capture and concentration of dilute organics and
capture by vesicles;
(4) locale for catalytic synthesis and polymerization;
(5) scarcity of phosphorus in a usable form;
(6) source of energy to drive biogenic chemistry;
(7) need for multitude of microreactors to promote a rich
evolutionary biogenesis.
What This Talk Was NOT About:
Past, Present, Future?
Concluding Remarks I:
The universe appears to be self-organizing
across all length scales. Evidence of
self-organization is obvious in the selfassembly of atoms from quarks and leptons, in
the building up of the periodic table by the
organization of electrons in shells and
subshells, and even in the life cycles of stars.
The origin of life has been regarded as
emerging from chemical self-organization of
one type or another. To find an answer to the
question "What is life?” it is imperative to
answer the question: "From whence life?"
Concluding Remarks II:
At the heart of life, as we know it, are homochiral
biopolymers.
This lecture has considered three questions:
(1) how an initiating enantiomeric excess was
generated on Earth,
(2) what sort of amplification mechanisms might have
been able to transform that small enantiomeric
excess into the homochiral arrays found in
contemporary biomolecules,
(3) how such biopolymers might survive to become
incorporated into living systems.
Concluding Remarks III:
In the course of exploring this question, I have
outlined what might have happened. I hope
this outline might inspire a series of
experiments and eventually evolve into a
workable model for this process.
The question of the origin of life is among the
most profound questions asked by human
minds. I dare to imagine that during the 21st
century a more complete answer to this
question will be found to this great mystery.
Closing Thoughts:
If you feed someone, you have less food for
yourself.
If you give someone knowledge, you gain
knowledge for yourself!
Everyone wins!