"Charles Darwin did little experimental science. He did make several descriptive studies of barnacles and worms and some experimental studies about how species spread through seed dispersal and other processes. Yet his masterpiece, On the Origin of Species by Means of Natural Selection, contains neither a single mathematical equation nor any report of original experimental research. Yet he formulated a great scientific theory."
Stephen Meyer - Signature in the Cell p139
Sunday, March 28, 2010
The Axe-Meyer Axis.
This is an attempt to state more clearly what I tried to say before...
How is Axe's published work relevant to ID?
Past posts for reference:
I was thinking...
J.Mol.Biol- 2000 -301-585-595
Controversial paper
Appearance of design
Making a functional protein from scratch is difficult. This is relevant in two situations(a) In a prebiotic soup making a protein to help stabilise or increase the function of a precellular replicon.
(b) after the origin of life the development of a brand new structural or functional protein which enhances the reproductive capacity of the organism.
The following argument is my version of what Stephen Meyer says on p206 and following in Signature in the Cell.
Most functional proteins are over 150 amino acids long. The average is estimated at around 300 amino acids long. With 20 different amino acids a protein 150 amino acids long gives a very large number of possible sequences - 10195 (which is a pretty big number)
Firstly in a prebiotic soup with an abundance of amino acids there are a number of possible ways in which amino acids can link up- however to get a folding protein we need peptide bonds. The probability of forming a peptide link is about 1 in 2.
To get a 150 amino acid molecule with peptide bonds the whole way along will be a probability of 1 in 1045.
Secondly in a prebiotic soup there will be 2 optical isomers of each amino acid. All the functional proteins in nature use only L isomers.
To get a 150 amino acid molecule with only L isomers the probability is also 1 in 10 45.
Thirdly there are constraints in terms of the exact order of amino acids that will produce a protein that can fold into a globular shape with the possibility of having a function.
Fourthly there are constraints in terms of the exact order of amino acids that will produce a protein that has a function.
The fourth issue was investigated by Robert Sauer in the late 1980's at MIT. Cassette mutagenesis was used to examine the tolerance to sequence change at a number of locations in a variety of proteins.
The results showed that the probability of acheiving a functional sequence in several small proteins was very low. In other words there are very few different combinations of amino acids that allow the function to be maintained.
The chance of hitting on one of these by chance was about 1 in 1063.
Doug Axe was interested in Sauer's work and began to wonder if he had underestimated how much protein sequences can vary and still retain function.
He developed a more rigorous mechanism to test this. The results in a paper published in 2004 were particularly important. On the basis of these results Axe was able to demonstrate that the ratio of functional sequences to non functional sequences for the enzyme beta-lactamase was 1 functional sequence to every 1 x1077.
Axe's work also allowed him to calculate the probabilities of finding any functional sequence amongst the possible sequences. This was done by looking at the probability of sequences being able to form stable folds (a necessary pre-requisite for stable 3D structure)
On the basis of his work he calculated the ratio of sequences able to form stable 3D structures to those which were not able to as 1 to 10 74.
A comparison of these odds:
The odds of finding a 150 amino acid sequence able to fold into a stable 3D shape is equivalent to finding a single marked atom out of all the atoms in a a billion Milky Ways (that is the galaxy[this is the star system rather than the chocolate bar] rather than the chocolate bar)
These are unpromising odds to say the least.
For a functional protein in a prebiotic soup the odds are considerably worsened.
For a complex of functional proteins occuring at the same time the odds are also considerable worsened.
The odds of a 150 amino acid protein with stable 3D shape in a prebiotic soup is 1 in 10 to 164 this is well below the entire probabalistic resources of the entire history of the entire universe.
How is Axe's published work relevant to ID?
Past posts for reference:
I was thinking...
J.Mol.Biol- 2000 -301-585-595
Controversial paper
Appearance of design
Making a functional protein from scratch is difficult. This is relevant in two situations(a) In a prebiotic soup making a protein to help stabilise or increase the function of a precellular replicon.
(b) after the origin of life the development of a brand new structural or functional protein which enhances the reproductive capacity of the organism.
The following argument is my version of what Stephen Meyer says on p206 and following in Signature in the Cell.
Most functional proteins are over 150 amino acids long. The average is estimated at around 300 amino acids long. With 20 different amino acids a protein 150 amino acids long gives a very large number of possible sequences - 10195 (which is a pretty big number)
Firstly in a prebiotic soup with an abundance of amino acids there are a number of possible ways in which amino acids can link up- however to get a folding protein we need peptide bonds. The probability of forming a peptide link is about 1 in 2.
To get a 150 amino acid molecule with peptide bonds the whole way along will be a probability of 1 in 1045.
Secondly in a prebiotic soup there will be 2 optical isomers of each amino acid. All the functional proteins in nature use only L isomers.
To get a 150 amino acid molecule with only L isomers the probability is also 1 in 10 45.
Thirdly there are constraints in terms of the exact order of amino acids that will produce a protein that can fold into a globular shape with the possibility of having a function.
Fourthly there are constraints in terms of the exact order of amino acids that will produce a protein that has a function.
The fourth issue was investigated by Robert Sauer in the late 1980's at MIT. Cassette mutagenesis was used to examine the tolerance to sequence change at a number of locations in a variety of proteins.
The results showed that the probability of acheiving a functional sequence in several small proteins was very low. In other words there are very few different combinations of amino acids that allow the function to be maintained.
The chance of hitting on one of these by chance was about 1 in 1063.
Doug Axe was interested in Sauer's work and began to wonder if he had underestimated how much protein sequences can vary and still retain function.
He developed a more rigorous mechanism to test this. The results in a paper published in 2004 were particularly important. On the basis of these results Axe was able to demonstrate that the ratio of functional sequences to non functional sequences for the enzyme beta-lactamase was 1 functional sequence to every 1 x1077.
Axe's work also allowed him to calculate the probabilities of finding any functional sequence amongst the possible sequences. This was done by looking at the probability of sequences being able to form stable folds (a necessary pre-requisite for stable 3D structure)
On the basis of his work he calculated the ratio of sequences able to form stable 3D structures to those which were not able to as 1 to 10 74.
A comparison of these odds:
The odds of finding a 150 amino acid sequence able to fold into a stable 3D shape is equivalent to finding a single marked atom out of all the atoms in a a billion Milky Ways (that is the galaxy[this is the star system rather than the chocolate bar] rather than the chocolate bar)
These are unpromising odds to say the least.
For a functional protein in a prebiotic soup the odds are considerably worsened.
For a complex of functional proteins occuring at the same time the odds are also considerable worsened.
The odds of a 150 amino acid protein with stable 3D shape in a prebiotic soup is 1 in 10 to 164 this is well below the entire probabalistic resources of the entire history of the entire universe.
Thursday, March 18, 2010
The appearance of Design.
The universe itself and living organisms in particular have the appearance of being designed. Human intelligence from very early times has concluded from this appearance of design that there must be a designer.
Darwin’s theory was an alternative seeking to explain the appearance of design without an actual designer.
In terms of biology ID writers suggest three key areas for investigation that interest me.
1. The origin of life itself.
2. The origin of new functional proteins
3. The origin of interdependent proteins where multiple proteins are fine tuned for a particular function and all are required simultaneously for minimal function.
With regards to area 1 I am interested in working through Stephen Meyers recent book – Signature in the Cell.
With regards to area 2 the key research is the investigation of the relative quantities of functional to non-functional proteins amongst all possible proteins. How easy is it to produce an entirely new functional protein? I am not talking about variants within a protein family but the production of an entirely new structure with a new function with no amino acid sequence homology to any other functional protein.
One way to investigate this is to ask how easily protein structure and function degrades when you change one or more amino acids around the active site of an enzyme or elsewhere in its structure.
This gives an increasingly clear picture of the size of the islands of protein functionality in the vast ocean of possible protein amino acid sequences.
It is this kind of experiment that Doug Axe did at Cambridge.
Some previous posts on this:
How big is the hole?
I was thinking..
Axe's paper
Axe's paper
Which Golf Course?
Darwin’s theory was an alternative seeking to explain the appearance of design without an actual designer.
In terms of biology ID writers suggest three key areas for investigation that interest me.
1. The origin of life itself.
2. The origin of new functional proteins
3. The origin of interdependent proteins where multiple proteins are fine tuned for a particular function and all are required simultaneously for minimal function.
With regards to area 1 I am interested in working through Stephen Meyers recent book – Signature in the Cell.
With regards to area 2 the key research is the investigation of the relative quantities of functional to non-functional proteins amongst all possible proteins. How easy is it to produce an entirely new functional protein? I am not talking about variants within a protein family but the production of an entirely new structure with a new function with no amino acid sequence homology to any other functional protein.
One way to investigate this is to ask how easily protein structure and function degrades when you change one or more amino acids around the active site of an enzyme or elsewhere in its structure.
This gives an increasingly clear picture of the size of the islands of protein functionality in the vast ocean of possible protein amino acid sequences.
It is this kind of experiment that Doug Axe did at Cambridge.
Some previous posts on this:
How big is the hole?
I was thinking..
Axe's paper
Axe's paper
Which Golf Course?
Wednesday, February 24, 2010
JBS Haldane on the origin of Life
If the minimal organism involves not only the code for its proteins, but also twenty types of soluble RNA, one for each amino acid, and the equivalent of ribosomal RNA, our descendents may be able to make one, but we must give up the idea that such an organism could have been produced in the past, except by a similar pre-existing organism or by an agent, natural or supernatural, at least as intelligent as ourselves, and with a good deal more knowledge.
J. B. S. Haldane;
Data needed for a blueprint of the first organism, 1951.
Published posthumously in S. Fox (ed) The origins of prebiological systems and of their molecular matrices,
Proceedings of a conference at Wakulla Springs, Florida, 27-30 October 1963
Academic Press. New York 1965, p12.
Does anyone know anything about the context of this quote?
I have this page with some other quotes of JBS Haldane.
J. B. S. Haldane;
Data needed for a blueprint of the first organism, 1951.
Published posthumously in S. Fox (ed) The origins of prebiological systems and of their molecular matrices,
Proceedings of a conference at Wakulla Springs, Florida, 27-30 October 1963
Academic Press. New York 1965, p12.
Does anyone know anything about the context of this quote?
I have this page with some other quotes of JBS Haldane.
Tuesday, December 01, 2009
The proof of the Truth is in the citation index…
A lost letter I came across in the historical archives dated November 30th 1871
Dear Gregor,
One of the hallmarks of science is that it is fruitful. A good scientific paper will usually lead to much work along the same lines, work that confirms and extends the results, and work that produces more new ideas inspired by the paper. Although citation counts are not completely reliable metrics for evaluating scientific papers, they do give some general information about what papers are considered important.
Pea factorization advocates like to point to lists of “peer-reviewed publications” advocating their position. Upon closer examination, their lists are misleading, packed with publications that are either not in scientific journals, or that appeared in venues of questionable quality, or papers whose relationship to pea factorization is tangential at best. Today, however, I’d like to look at a different issue: the fruitfulness pea factorization work. Let’s take a particular Pea factor publication, one that was trumpeted by a religious nutcase as a “breakthrough”, and see how much further scientific work it inspired.
The paper I have in mind is your paper Experiments on Plant Hybridization, which was published, amid some controversy, in the relatively obscure journal Proceedings of the Natural History Society of Brünn in 1865.
What I want to do here is look at every scientific publication that has cited your paper to determine whether your work can fairly said to be “fruitful”. I used the ISI Web of Science Database to do a “cited reference” search on your article. This database, which used to be called Science Citation Index, is generally acknowledged to be one of the most comprehensive available. The search I did included Science Citation Index Expanded, Social Sciences Citation Index, and Arts & Humanities Citation Index. Even such a search will miss some papers, of course, but it will still give a general idea of how much the scientific community has been inspired by your work.
I found exactly 0 citations to your paper in this database. Of these, counting generously, exactly 0 are scientific research papers that cite you approvingly!
I hope that you will see how foolish it is for religious nutcases to pretend to be involved in real science and that you will content yourself with simply growing peas and singing hymns in your monastery.
Yours scoffingly,
Jeff
Dear Gregor,
One of the hallmarks of science is that it is fruitful. A good scientific paper will usually lead to much work along the same lines, work that confirms and extends the results, and work that produces more new ideas inspired by the paper. Although citation counts are not completely reliable metrics for evaluating scientific papers, they do give some general information about what papers are considered important.
Pea factorization advocates like to point to lists of “peer-reviewed publications” advocating their position. Upon closer examination, their lists are misleading, packed with publications that are either not in scientific journals, or that appeared in venues of questionable quality, or papers whose relationship to pea factorization is tangential at best. Today, however, I’d like to look at a different issue: the fruitfulness pea factorization work. Let’s take a particular Pea factor publication, one that was trumpeted by a religious nutcase as a “breakthrough”, and see how much further scientific work it inspired.
The paper I have in mind is your paper Experiments on Plant Hybridization, which was published, amid some controversy, in the relatively obscure journal Proceedings of the Natural History Society of Brünn in 1865.
What I want to do here is look at every scientific publication that has cited your paper to determine whether your work can fairly said to be “fruitful”. I used the ISI Web of Science Database to do a “cited reference” search on your article. This database, which used to be called Science Citation Index, is generally acknowledged to be one of the most comprehensive available. The search I did included Science Citation Index Expanded, Social Sciences Citation Index, and Arts & Humanities Citation Index. Even such a search will miss some papers, of course, but it will still give a general idea of how much the scientific community has been inspired by your work.
I found exactly 0 citations to your paper in this database. Of these, counting generously, exactly 0 are scientific research papers that cite you approvingly!
I hope that you will see how foolish it is for religious nutcases to pretend to be involved in real science and that you will content yourself with simply growing peas and singing hymns in your monastery.
Yours scoffingly,
Jeff
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