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Prebiotic Soup--Revisiting the Miller Experiment [biogenesis]
Science Magazine ^ | May 2003 | Jeffrey L. Bada and Antonio Lazcano

Posted on 11/02/2003 10:30:46 AM PST by PatrickHenry

"Isn't life wonderful?" sang Alma Cogan and Les Howard in their almost forgotten 1953 hit. That same year, Stanley L. Miller raised the hopes of understanding the origin of life when on 15 May, Science published his paper on the synthesis of amino acids under conditions that simulated primitive Earth's atmosphere (1). Miller had applied an electric discharge to a mixture of CH4, NH3, H2O, and H2--believed at the time to be the atmospheric composition of early Earth. Surprisingly, the products were not a random mixture of organic molecules, but rather a relatively small number of biochemically significant compounds such as amino acids, hydroxy acids, and urea. With the publication of these dramatic results, the modern era in the study of the origin of life began.

Since the late 19th century, the belief in a natural origin of life had become widespread. It was generally accepted that life's defining properties could be understood through physico-chemical characterization of "protoplasm," a term used to describe the viscous translucent colloid found in all living cells (2). Expressions like "primordial protoplasmic globules" were used not only by scientists but also in fiction, from Gilbert and Sullivan's Pooh-Bah in The Mikado (1885) to Thomas Mann's somber imaginary character Adrian Leverkühn in Doktor Faustus (1947). But few dared to be explicit, even in novels. Questioned about the origin of life, a chemist in Dorothy L. Sayers' novel The Documents in the Case (1930) states that "it appears possible that there was an evolution from inorganic or organic through the colloids. We can't say much more, and we haven't--so far--succeeded in producing it in the laboratory."

Some were willing to fill in the details. At the turn of the 20th century, many scientists favored the idea of primordial beings endowed with a plant-like (autotrophic) metabolism that would allow them to use CO2 as their source of cellular carbon. However, some scientists--including A. I. Oparin, J. B. S. Haldane, C. B. Lipman, and R. B. Harvey--had different ideas (3). The most successful and best-known proposal was that by Oparin, who, from a Darwinian analysis, proposed a series of events from the synthesis and accumulation of organic compounds to primordial life forms whose maintenance and reproduction depended on external sources of reduced carbon.

The assumption of an abiotic origin of organic compounds rested on firm grounds. In 1828, F. Wöhler had reported the first chemical synthesis of a simple organic molecule (urea) from inorganic starting materials (silver cyanate and ammonium chloride).

After a large body of research on the synthesis of simple organic compounds accumulated in the 19th century (see figure above), W. Löb achieved the chemical syntheses of simple amino acids such as glycine by exposing wet formamide to a silent electrical discharge and to ultraviolet light (4).

These efforts to produce simple organic compounds from simple reagents heralded the dawn of prebiotic organic chemistry. However, there is no indication that the scientists who carried out these studies were interested in how life began on Earth, or in the synthesis of organic compounds under possible prebiotic conditions. This is not surprising, because the abiotic synthesis of organic compounds was not considered to be a necessary prerequisite for the emergence of life.

From the 1950s, chemists were drawn toward the origin of life. Driven by his interest in evolutionary biology, Melvin Calvin tried to simulate the synthesis of organic compounds under primitive Earth conditions with high-energy radiation sources. He and his group had limited success: the irradiation of CO2 solutions with the Crocker Laboratory's 60-inch cyclotron led only to formic acid, albeit in fairly high yields (5). Miller's publication 2 years later showed how compounds of biochemical importance could be produced in high yields from a mixture of reduced gases.

The origin of Miller's experiment can be traced to 1950, when Nobel laureate Harold C. Urey, who had studied the origin of the solar system and the chemical events associated with this process, began to consider the emergence of life in the context of his proposal of a highly reducing terrestrial atmosphere. Urey presented his ideas in a lecture at the University of Chicago in 1951, followed by the publication of a paper on Earth's primitive atmosphere in the Proceedings of the National Academy of Sciences(6).

Almost a year and a half after Urey's lecture, Miller, a graduate student in the Chemistry Department who had been in the audience, approached Urey about the possibility of doing a prebiotic synthesis experiment using a reducing gas mixture. After overcoming Urey's initial resistance, they designed three apparatuses meant to simulate the ocean-atmosphere system on primitive Earth (3). The first experiment used water vapor produced by heating to simulate evaporation from the oceans; as it mixed with methane, ammonia, and hydrogen, it mimicked a water vapor-saturated primitive atmosphere, which was then subjected to an electric discharge (see the figure below). The second experiment used a higher pressure, which generated a hot water mist similar to that of a water vapor-rich volcanic eruption into the atmosphere, whereas the third used a so-called silent discharge instead of a spark.

Miller began the experiments in the fall of 1952. By comparison with contemporary analytical tools, the paper chromatography method available at the time was crude. Still, after only 2 days of sparking the gaseous mixture, Miller detected glycine in the flask containing water. When he repeated the experiment, this time sparking the mixture for a week, the inside of the sparking flask soon became coated with an oily material and the water turned a yellow-brown color. Chromatographic analysis of the water flask yielded an intense glycine spot; several other amino acids were also detected. Experiments with the second apparatus produced a similar distribution and quantities of amino acids and other organic compounds, whereas the third apparatus with silent discharge showed lower overall yields and much fewer amino acids (primarily sarcosine and glycine).

After Miller showed the impressive results to Urey, they decided to submit them to Science. Urey declined Miller's offer to coauthor the report because otherwise Miller would receive little or no credit. Knowing that a graduate student could have a difficult time getting a paper like this published, Urey contacted the Science editorial office to explain the importance of the work and ask that the paper be published as soon as possible. Urey kept mentioning the results in his lectures, drawing considerable attention from the news media.

The manuscript was sent to Science in early February of 1953. Several weeks went by with no news. Growing impatient, Urey wrote to Howard Meyerhoff, chairman of AAAS's Editorial Board, on 27 February to complain about the lack of progress (7). Then, on 8 March 1953, the New York Times reported in a short article entitled, "Looking Back Two Billion Years" that W. M. MacNevin and his associates at Ohio State University had performed several experiments simulating the primitive Earth--including a discharge experiment with methane wherein "resinous solids too complex for analysis" were produced. The next day, Miller sent Urey a copy of the clipping with a note saying "I am not sure what should be done now, since their work is, in essence, my thesis. As of today, I have not received the proof from Science, and in the letter that was sent to you, Meyerhoff said that he had sent my note for review."

Infuriated by this news, Urey had Miller withdraw the paper and submit it to the Journal of the American Chemical Society. Ironically, at the same time (11 March), Meyerhoff, evidently frustrated by Urey's actions, wrote to Miller that he wanted to publish the manuscript as a lead article and that he wanted Miller--not Urey--to make the final decision about the manuscript. Miller immediately accepted Meyerhoff's offer, the paper was withdrawn from the Journal of the American Chemical Society and returned to Science, and was published on 15 May 1953.

On 15 December 1952, well before the Miller paper was sent to Science, K. Wilde and co-workers had submitted a paper on the attempted electric arc synthesis of organic compounds using CO2 and water to the same journal. They reported that no interesting reduction products, such as formaldehyde, were synthesized above the part-per-million level. This result supported the surmise of Miller and Urey that reducing conditions were needed for effective organic syntheses to take place. Surprisingly, when the paper by Wilde et al. was published in Science on 10 July 1953, it did not mention Miller's paper, although the authors did note that their results had "implications with respect to the origin of living matter on earth."

Miller's paper was published only a few weeks after Watson and Crick reported their DNA double-helix model in Nature. The link between the two nascent fields began to develop a few years later, when Juan Oró demonstrated the remarkable ease by which adenine, one of the nucleobases in DNA and RNA, could be produced through the oligomerization of hydrogen cyanide (8). It would eventually culminate in the independent suggestions of an "RNA world" by Carl Woese, Leslie Orgel, and Francis Crick in the late 1960s and by Walter Gilbert in 1986.

The impact of the Miller paper was not limited to academic circles. The results captured the imagination of the public, who were intrigued by the use of electric discharges to form the prebiotic soup. Fascination with the effects of electricity and spark discharges on biological systems started with the work of L. Galvani in 1780 with frog legs and the discovery of "animal electricity." And an everlasting impression was left in the public's imagination by Mary W. Shelley's Frankenstein (1818), in which Eramus Darwin gained a place for his advocacy of therapies based on electric discharges.

Although in 1953, few envisioned the possibility of Frankenstein monsters crawling out of Miller's laboratory vessels, the public's imagination was captivated by the outcome of the experiment. By the time that the results were corroborated by an independent group 3 years later (9), the metaphor of the "prebiotic soup" had found its way into comic strips, cartoons, movies, and novels, and continues to do so. In Harry Mulisch's novel The Procedure (1998), one of the central characters encounters disaster while paving his way to the glittering halls of Stockholm for achieving the artificial synthesis of life from a primitive soup.

But is the "prebiotic soup" theory a reasonable explanation for the emergence of life? Contemporary geoscientists tend to doubt that the primitive atmosphere had the highly reducing composition used by Miller in 1953. Many have suggested that the organic compounds needed for the origin of life may have originated from extraterrestrial sources such as meteorites. However, there is evidence that amino acids and other biochemical monomers found in meteorites were synthesized in parent bodies by reactions similar to those in the Miller experiment. Localized reducing environments may have existed on primitive Earth, especially near volcanic plumes, where electric discharges (10) may have driven prebiotic synthesis.

In the early 1950s, several groups were attempting organic synthesis under primitive conditions. But it was the Miller experiment, placed in the Darwinian perspective provided by Oparin's ideas and deeply rooted in the 19th-century tradition of synthetic organic chemistry, that almost overnight transformed the study of the origin of life into a respectable field of inquiry.

[Illustrations and footnotes in the original.]


TOPICS: Culture/Society; Miscellaneous; Philosophy
KEYWORDS: abiogenesis; biogenesis; crevolist; earlyearth; evolution; millerexperiment; originoflife
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To: Loc123
I have never seen a plausible scenario to explain why all organic matter (or almost all) is L and not D.

There are two non-conflicting ideas of which I am aware personally concerning why biological proteins are L and sugars are D. The main one is that the first replicator happened to be made of L stuff, so the L-handedness basically won the race to self-replication. The L-replicators then formatted the pre-biotic soup to L-handedness by the simple act of copying themselves.

Another point is that L- and D- isomers have slightly different energies because of the handedness of the weak force. The "biological" form of a molecule tends to correspond to the lower of the two energies.

181 posted on 11/05/2003 6:17:19 AM PST by VadeRetro
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To: Ogmios
Whose behavior?
182 posted on 11/05/2003 6:41:59 AM PST by bondserv (Alignment is critical.)
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To: Admin Moderator; Jim Robinson
To: bondserv

So, will you answer my question? Were you defending the behavior of ALS and his buddies, or not?

That's all I wish to know, is their behavior defensible, and are you defending it?


177 posted on 11/04/2003 10:06 PM PST by Ogmios

Is FR a tabloid ... liberal rag --- rat's nest republican snake hole ?
183 posted on 11/05/2003 7:21:39 AM PST by f.Christian (( Alpha - Omega Design - Architecture ... designeduniverse.com --- Science3000 ! ))
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To: f.Christian
I was noticing the harassment as well. Course, it's pretty much par for the course for some people here.
184 posted on 11/05/2003 7:30:12 AM PST by Michael_Michaelangelo
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To: Michael_Michaelangelo
The liberals are running the schools ... higher education --- writing history - science ...

calling Christians on the FR vermin ---

I call them the ... rat's nest republicans - caucus !
185 posted on 11/05/2003 7:33:43 AM PST by f.Christian (( Alpha - Omega Design - Architecture ... designeduniverse.com --- Science3000 ! ))
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To: f.Christian
Darwin, Design & Democracy IV: Responding to the AAAS Decree Against ID
http://www.intelligentdesignnetwork.org/june_symposim.htm ^


Posted on 11/05/2003 5:29 AM PST by truthfinder9


All day Saturday, November 15, 2003

Most of science is an objective search for the truth.

However, the Board of Directors of the American Association for the Advancement of Science (AAAS) seems to abandon that concept when the discussion turns to the question of our origin. Only one answer is allowed - naturalistic evolution.







http://www.freerepublic.com/focus/religion...97/posts?page=3


To: LiteKeeper


Take away people's guns (( hard )) on the FR is a no - no ...

take away their minds (( easy )) via evolution --- must - must !

Why would the 1st matter ... skip it ?


4 posted on 11/05/2003 8:28 AM PST by f.Christian


186 posted on 11/05/2003 8:33:17 AM PST by f.Christian (( Alpha - Omega Design - Architecture ... designeduniverse.com --- Science3000 ! ))
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To: PatrickHenry
So, if scientists are successful at "creating" life, does that mean that that life came about because of "Intelligent Design"?
187 posted on 11/05/2003 8:39:25 AM PST by Theo
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To: f.Christian
http://www.freerepublic.com/focus/f-religion/1015097/posts
188 posted on 11/05/2003 8:39:27 AM PST by f.Christian (( Alpha - Omega Design - Architecture ... designeduniverse.com --- Science3000 ! ))
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To: Michael_Michaelangelo
I was asking a very simple question and he was dancing around it.

I will assume that he does indeed defend such behavior since he is unwilling or unable to answer the question.

Asking for a yes or no answer should not be that difficult.
189 posted on 11/05/2003 9:23:51 AM PST by Ogmios (Since when is 66 senate votes for judicial confirmations constitutional?)
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To: Ogmios
I believe we are at an ethical impasse.

This has been an excellent tutorial, for that I thank you.
190 posted on 11/05/2003 9:57:46 AM PST by bondserv (Alignment is critical.)
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To: Theo
So, if scientists are successful at "creating" life, does that mean that that life came about because of "Intelligent Design"?

It would mean that life is such an easy step for organic chemistry that mere humans in a lab could do it. This would suggest (not prove) that -- contrary to the claims of some theolgians -- such matters do not require, much less prove, the activities of a deity.

I'm not interested in dancing around with you about the multiple meanings of "intelligent design" which are inherent in your post.

191 posted on 11/05/2003 10:03:44 AM PST by PatrickHenry
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To: VadeRetro
Thank you for the reply.

First, about energies. Are you completely sure that L is less energy? Because chirality is not like normal isomers in that it is just different in configuration, and not bond repulsion (why cis is more energetic than trans in certain bonds).

If this were the case (that L is less energetic) it would not only refute your first explaination (that it simply won the race), but it then need to be correct for sugars as well.

Now onto your first explanation. The problem here is this: there is no reason why there weren't equal or mostly equal concentrations of both, most likely in a heterogeneous mixutre. Therefore, there is no reason why the region where magically self-replicating matter occurred wouldn't have sparked BOTH L and D at the same time, thus making them equally competitive and likely. Given the relative infinite of energy (to those little molecules), any energy disparity between L and D would be irrelevant and not a selective factor.

This is why the problem is such a conundrum--there is no reason why L won over D. There were unlimited resources relative to the "organisms" or pre-organisms. There was unlimited space to expand (else neither would have flourished). It is as if something arbitrarily picked one of the two.

However, the magical "starlight" transformation in space that I talked about does account for the disparity--hence why it is mainstream, in the very least.

I don't believe, as you apparently do, that evidence supports automatic qualities on nature (IE the "race to self-replication" implies it was a forgone conclusion that "something" would do it).

192 posted on 11/05/2003 4:28:31 PM PST by Loc123
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To: PatrickHenry
That is certainly one way of looking at it.

However, you would need to observe the processes required to synthesize that life. If it were totally beyond what is believed to have existed, or even could have existed, it would imply intelligent design.

By your logic, the fact that computers exist--increasingly with relative ease--than that proves they are natural creations. However, we know that there is no way computers could naturally arise--mostly due to thermodynamics and entropy--but also due to the incredibly force it takes to create them.
193 posted on 11/05/2003 4:31:48 PM PST by Loc123
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To: Loc123
Me in 191:
"[I]f scientists are successful at 'creating' life ... it would mean that life is such an easy step for organic chemistry that mere humans in a lab could do it. This would suggest (not prove) that -- contrary to the claims of some theolgians -- such matters do not require, much less prove, the activities of a deity. "

You:
That is certainly one way of looking at it. However, you would need to observe the processes required to synthesize that life. If it were totally beyond what is believed to have existed, or even could have existed, it would imply intelligent design.

My point is that traditionally, theologians have marveled at the existence of life, and have frequently declared that its very existence is a miracle. Evolution may have happened naturally, many of them admit, but the initial appearance of life is such an impossible thing that it must be the miraculous act of a deity.

That's not a new idea. It's very traditional. And many science-minded folk have suggested that it's a trap, because if life is ever created in the lab (by mere men) then the central miracle which sustains many theological systems will be in jeopardy.

Now, sensing that the "miracle" of life is soon to be created in a mundane lab by mere lab rats -- and not by gods and angels -- we can observe an almost instinctive moving of the goalposts. Now you want an exact replication of the conditions on earth billions of years ago. And you will then insist on perfect proof that those were indeed the young-earth conditions, etc. Endless objections will be raised. All of this is expected. Every time an alleged "miracle" is demonstrated to be a natural occurence, those who need miracles will squeeze and spin and dance as much as necessary to still find a miracle -- that is, an event not yet explained or demonstrated.

However, even if the first time the "non-life to life" trick is done the conditions don't mimic those on the young earth, it will nevertheless be momentous, because the trick will have been done. Without supernatural intervention. All the rest will be in the nature of mere sweeping up.

By your logic, the fact that computers exist--increasingly with relative ease--than that proves they are natural creations.

There are analogies, bad analogies, and truly awful analogies. I'm afraid yours is in the last group.

194 posted on 11/05/2003 4:57:16 PM PST by PatrickHenry
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To: Loc123
First, about energies. Are you completely sure that L is less energy?

Dr. Alexandra McDermott was looking at the weak force angle a few years ago. She says, "Life's handedness may be a feature of fundamental physics, a result of selection by the weak force, which makes L-amino acids very slightly more stable."

L-aminos work with D-sugars and vice-versa, but I think I've read that D-sugars are lower energy than L-sugars as well.

Now onto your first explanation. The problem here is this: there is no reason why there weren't equal or mostly equal concentrations of both, most likely in a heterogeneous mixutre.

Initially, a pre-biotic soup would have been a racemic mixture of L- and D- aminos, L- and D- sugars, yes. A complex, self-replicator molecule forms. It is either made of all L- aminos and D- sugars or the reverse. There's a fifty-fifty chance of getting what we got. Dr. MacDermott's weak force hypothesis means that maybe the thumb (God's thumb?) was slightly, slightly on the scale in favor of getting what we got.

195 posted on 11/05/2003 5:18:47 PM PST by VadeRetro
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To: PatrickHenry
Don't think I believe we will ever synthesize life; contrary to your beliefs, the more we learn about origins the more unlikely it seems they were abiotic. I was merely stating how really precise conditions in a lab (I'm talking REALLY precise) would imply a definately HUGE improbability that life is automatic given reasonable circumstance. You must differentiate minor improbability with near-infinite improbability (or a really high improbability).

In fact, there is good reason to think that the Lord created this universe with a set laws of physics that could be self-sustaining given the right agent. Though I believe the evidence on origins supports this position less than the uniqueness of life.

On my "truly aweful analogy"-- this is a conservative forum, so why do you use liberal tactics? Insulting something without evidence is quite infantile, wouldn't you agree? Please show me where my analogy fails.
196 posted on 11/05/2003 7:17:02 PM PST by Loc123
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To: VadeRetro
I truly applaud you for your research and time.

However, I still detect the same unresolved flaws.

Say L proteins AND D sugars are at a lower energy and thus preferred by chemistry/physics. That still doesn't explain why one type got preference in the formation stages. This is due to the massive amount of energy and resources present in any abiogenesis model. Therefore, the selection of the lowest energy would not exist until much, much later--a point in which perhaps having a higher bond repulsion could allow D to bind with more complex atoms.

And Dr. McDermott's hypothesis doesn't address my concerns with the racemic problem. McDermott, or you, say that there is a 50-50 chance of either L or D acheiving self-replication. But why? They are racemic, local--they are exposed to the same stimuli. So why do all local (or even some or one) L molecules get self-replicating ability and the neighboring (by nano meters) D molecules not receive this endowment? As you said, this incredibly unlikely happening would definately imply a God to inhibit the neighboring D proteins.

Also, if you are going to say the difference was magically calibrated to the difference that that "weak force," I will preempt this by reminding you the massive amounts of energy bombardment present, their variable intesities, as well as the sensitivity of organic molecules.

You are a wonderful debater, by the way.
197 posted on 11/05/2003 7:26:19 PM PST by Loc123
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To: Loc123
Say L proteins AND D sugars are at a lower energy and thus preferred by chemistry/physics. That still doesn't explain why one type got preference in the formation stages.

I flip a coin. It might have come up heads or tails, but it came up tails. That might not explain WHY it came up tails, but it did have to be one or the other.

And Dr. McDermott's hypothesis doesn't address my concerns with the racemic problem. McDermott, or you, say that there is a 50-50 chance of either L or D acheiving self-replication. But why? They are racemic, local--they are exposed to the same stimuli. So why do all local (or even some or one) L molecules get self-replicating ability and the neighboring (by nano meters) D molecules not receive this endowment? As you said, this incredibly unlikely happening would definately imply a God to inhibit the neighboring D proteins.

Do you know how OlestraTM, the no-calorie fat works? You can't digest it at all because it's all made with the "wrong" isomers. L-aminos only form chains with L-aminos (and D-sugars). D-aminos only form chains with other D-aminos and L-sugars. You can't have a complex molecule of L-aminos, D-aminos, L-sugars, and D-sugars. So a complex molecule able to catalyze its own formation--i.e, a self-replicator, is either of the handedness we know as "biological" or its mirror image.

Now, natural processes have been making and tearing down racemized aminos and sugars at some near-equilibrium rate. However, a self-replicator of one handedness--the only one so far in existence--starts taking molecules of one handedness out of solution as it copies itself. That will tilt the former equilibrium toward the replicator's handedness in a runaway process. The replicator formats the soup. There's nothing unlikely unless that initial replicator was spectacularly lucky. (No one knows the odds one way or another.)

You are a wonderful debater, by the way.

Well, thanks! I just wish some of my evo buddies had my patience. (/sarcasm)

198 posted on 11/05/2003 7:43:28 PM PST by VadeRetro
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To: Loc123
I was merely stating how really precise conditions in a lab (I'm talking REALLY precise) would imply a definately HUGE improbability that life is automatic given reasonable circumstance.

Nobody knows, with enough precision to produce a meaningful statistical probability calculation, how life came about, so nobody knows what the odds were against it. "Precise" does not necessarily imply "accurate".

199 posted on 11/06/2003 1:45:49 AM PST by donh (1)
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To: VadeRetro
Good example with the Olestra TM.

However, my main point is still unaddressed (as you honestly admitted). Why did only 1 type receive this ability in a racemic mixture given the conditions I layed out? You say it "did have to be" one of the two, but there is no reasoning for this, given the relatively infinite amounts of energy and resources being given to earth at that time (if that weren't the case then NO complex molecules would be able to form for thermodynamic/entropic reasons).

If somehow magically this were the case, I could hypothetically see how L type would get predominant. However, the problem of the 'why?' is insurmountable and therefore any theorizing given the amount of data we know is fantasy (IE without evidence). And that is why panspermia (or its equivalent for self-replicators) is the best explanation since it actually has evidence to explain chirality--that the amino acids are L type on those space bodies. Although it doesn't explain why......
200 posted on 11/06/2003 12:57:09 PM PST by Loc123
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