Saturday, January 27, 2007

Possible Pathways for the evolution of intracellular transport.

In his book “Darwin’s Black Box Behe made the claim with regards to the cellular transport systems that:
"A search of the professional literature and textbooks shows that no one has ever proposed a detailed route by which such a system could have come to be."

Some commenters here have argued that Behe is being intentionally deceptive they argue that there is an abundance of published material – shelf loads of it - that give a clear outline of how a pathway transporting a newly synthesized protein to an intracellular compartment could arise.

Some suggestions were given as to where I should start – (I acknowledge that they were probably hurriedly put together sources by scientists who are very busy doing more important work than arguing with me and I do appreciate the attempt to provide me with the references.)

This is sequence comparisons in the myosin superfamily looking at homologies between the different types of myosin molecules in different organisms.
This is the attempted production of a phylogenetic tree comparing different types of myosin molecule.

The Richards and Cavalier Smith Nature paper is similar and suggests that the most primitive eukaryotes had three types of myosin from which all eukaryotic myosins come but that does not really help me.

This gives 111 delightful titles but not really what I am after. They are mainly phylogenetic trees and studies of sequence similarities. Behe accepts that there are an abundance of this kind of study.

What I am after is a simple step by step process whereby a single transport system from protein translation completion to function in a separate compartment can arise. It does not have to be a DVD of the process happening just a suggestion of some of the useful steps along the way.
I am thinking of the kind of thing that Matt Inlay produced in response to Behe’s Immunology chapter (here) or Nick Matzke’s response to the flagellum chapter ( here)

Tony’s scenario:
This problem concerns the way proteins are targeted to the mitochondria. These organelles (again, they’re shown in your diagram) are responsible for supplying a major fraction of the cell’s energy needs. They are distantly descended from free-living bacteria that began a symbiotic relationship with an early eukaryote. As part of that evolutionary history, mitochondria still retain a small genome which encodes a few of the proteins required by the organelle. However, over evolutionary time there has been a general drift towards more and more mitochondrial genes being transplanted to the nucleus. Mitochondrial proteins produced from such nuclear genes somehow have to get to their correct organelle. How do they do that? It turns out that such proteins contain, right at the start of their amino acid sequence, a so called ‘targeting signal’ made of about the first ten or so amino acids and which docks with import machinery in the mitochondrion. A mitochondrial gene newly transplanted into the nuclear genome must acquire this signal or it risks turning into a pseudogene. So how easy is it to acquire a functioning targeting signal? Some years ago a clever experiment was performed to find out. It’s a neat example of how our intuitive ‘gut feelings’ about these issues can lead us badly off-course. The scientists took a gene for a mitochondrial protein, then replaced its normal targeting signal with random DNA sequences sized to encode between about ten and thirty amino acids. They then determined what fraction of these random sequences acted as functioning mitochondrial targeting signals for the protein.What do you think the answer was? One in ten million? Or some other Dembski number perhaps? Actually, they got a remarkable 3 to 5%! Subsequent work with more truly random and uniformly-length sequences increased this estimate still further. Evidently, it’s almost ridiculously easy to evolve working targeting signals. One more point is worth making here. Because the results were so striking and the way the experiment was conducted was so elegant, this work is rather well known in the field. It was published in 1987 – almost ten years before Behe wrote his book. Yet he tells us with a straight face that no experiments have been done to address the evolutionary origins of protein traffic!

Tony’s point here is that the ID code for the mitondrial car park is pretty easy to forge. The fellow checking the ID’s is a pretty sloppy fellow and a great variety of ID sequences will do.

However let us imagine that this putative mitochondrial gene is the very first one to complete the journey into the cell’s genome. Let us also assume that the appropriate insertion of DNA occurs of the correct length and with the approximately correct sequence. Is this all that is required for the newly made protein to find its way into the mitochondrion? Is it just a single rough ID sequence that is needed or are other modifications required in the mitochondrial genome and elsewhere in the cell?

Friday, January 26, 2007

Molecular Meccano

Described by some researchers as a strange form of molecular “lego” and by others as “molecular basket weaving” the beautifully shaped propeller like molecules of clathrin have a crucial role in the cell’s internal distribution network. Another description in the literature is “groovy” which I think is about right! A single clathrin complex is made up of 3 light chains together with 3 heavy chains

to form the propeller like structure called a “triskelion” meaning three-legged.
These 3 legged units can be attracted to a membrane by a variety of different molecular structures on the surface of the membrane. As they are attracted they begin to associate

and as they associate they begin to bend the membrane inwards. The structure grows to form a complete and beautiful basket or cage around a little blister of membrane which is eventually pinched off to form a separate bubble inside the membrane.
At this point the clathrin complexes can be removed and reused elsewhere.

The diagram below is adapted from here (thanks to Dr. Tony Jackson)
A Quicktime Movie is here showing the assembly of a clathrin coated vesicle. (You may have to wait a little time for it to load.)

A Flash animation of the budding off of a clathrin vesicle is available here.

Wednesday, January 24, 2007

Intracellular Transport systems

There are two types of living cells that we know of on earth-
1. Prokaryotic cells:

2. Eukaryotic cells [from the greek word karyon meaning nut or kernel – prokaryotic meaning “before a kernel” and eukaryotic meaning “with a true kernel” – the kernel being the nucleus of the cell.]

Eukaryotic cells not only have a “kernel” the nucleus but they have a goodly number of other internal compartments inside the cell too.

There is the complex structure of the onion like “endoplasmic reticulum” around the nucleus, there is the “golgi apparatus” looking like a pile of plates ready for a feast, there are the mitochondia looking like sausages out of some crazy sausage machineand there are the lysozymes- the waste recycling plants of the cell.

These different compartments each have their special function inside the eukaryotic cell.

The problems of transport are therefore much more complicated in the eukaryotic cell than they are in the prokaryotic cell.

It is these traffic problems that Behe mentions in chapter 5 – (From here to there) of “Darwin’s black box

He first uses two analogies to explain the problem he is seeking to elucidate.

1. The delivery of urgently needed vaccine to an area of the country where there is an outbreak of a highly infectious viral disease. If the correct vaccine arrives at the correct location then lives can be saved- if not lives will be lost. Behe then imagines a film director making a film called “epidemic” in which the vaccine labels get muddled – This situation is similar to the situation inside a cell he argues when the transport system breaks down- death is the result.
2. He then imagines a robotic space ship exploring space with its battery crusher compartment, its library, its master machines and so on- This imaginary space probe is then compared to a cell

He then asks…. Is this analogy real?

This is illustrated using a protein he calls “garbigase.” A temporary copy of the relevant section of data from the DNA library is made- the messenger molecule. This messenger molecule passes to a nuclear pore- a tiny little door in the wall of the kernel. Proteins in the pore recognise the molecule in a process analogous to a challenge of identity with a secret password being given and the pore opens. In the cytoplasm a master machine the “ribosome” begin the process of converting the linear coded data into a 3D machine- in a process which biochemists have aptly named “translation” to make part of a brand new gleaming machine.

Diagram of translation:
Diagrams of a ribosome:

The first part of the machine to be made is a special combination code which quickly and neatly sticks to a code “hood” (signal recognition particle) causing the translation process to pause. The hooded new machine then locates a docking site in the surface of the onion. The docking process un-pauses the translation process and the newly made full length machine – a baby garbigase molecule - is fed into the inside of the onion compartment. As it passes into this new compartment the special code sequence to gain its safe entry is clipped off and a large carbohydrate molecule is bolted onto it.

Special proteins then cause a bubble of the onion wall to form and this pinches off into a separate little bubble containing molecules of the new garbagase protein. This little package then moves to another compartment called the Golgi apparatus and joins with the wall of this new compartment.

This kind of process happens two more times as the enzyme passes through several compartments of the Golgi apparatus. Another carbohydrate group is added to the enzyme and this is then trimmed by another enzyme leaving an special code MI-6 molecule.

In the final compartment of the golgi apparatus 3 blade propellor proteins snap together in a patch forming a bubble making cage. Within this bubble there is a MI-6 checker protein that binds to MI-6 pulling it into the bubble before it buds off. On the outside of the bubble is a tiny rabbit-SNARE protein that binds only to a tiny rabbit- proteins on the surface of the final compartment to which this little bubble is journeying.

Once the final docking process has completed further special membrane fusing proteins join the bubble to the wall of the waste disposal compartment so that it becomes part of it emptying its contents into its final destination.

Monday, January 22, 2007

A very controversial paper!

Doug Axes’ work was controversial even as he was carrying it out. It was funded by an Institute that never under any circumstances funds anything but misguided PR material- The Discovery Institute. When another researcher in his lab pointed to the Discovery Institute's agenda and suggested that Axe be asked to leave, Prof Fersht refused. (New Scientist article)

It was controversial when it had been published with Dembski hailing it as a peer reviewed publication which supported his arguments.

Axes’ work has continued to be controversial with the set up of the Biologic Institute and his announcement that he does consider his work as supportive of the ID view.

Ed Brayton (here and here) thinks that the Journal of Molecular Biology accepted a paper in which the author got the title of his paper to mean the opposite of what his results suggested!

“The 2000 JMB paper did not show "severe sequence constraints" at all. It showed quite the opposite, that you could make massive changes in the sequence of amino acids in an enzyme, knocking out 10, 20, even 30 amino acids at a time, without completely destroying the function of the enzyme. It showed that you could make 10 substitutions at a time with only a negligible effect on the enzyme's function. And this is "severe sequence constraints"? Not even close.”

The title according to Ed should not have been “Extreme functional sensitivity to….” But Extreme functional INsensitivity to…” I immediately thought that the fact that the paper’s author and the papers reviewers made such a monumental error and that Ed managed to come to the rescue and point this out was rather odd to say the least. That it managed to get through the JMB peer review process without anyone noticing that the title was saying the opposite of the results seems quite remarkable to say the least! Perhaps it was a simple printing error?

Matt Inlay critiques the early claims that Dembski made for this research. Interestingly Matt Inlay does not mention that Axe got his title wrong.

Arthur Hunt likewise does not mention that Axe got his title so completely wrong and argues that of all the values for enzyme functionality in possible sequence space the lower ones give easily attainable rates in bacterial populations. However the much smaller populations in larger animals still present difficulties for explaining the origin of their unique proteins.
(Interestingly Arthur Hunt mentions that Douglas axe helped him with early drafts of this essay.)

Hunt present the enzyme activity as hills with a wide or narrow base. The size of the base of the hill indicates the likelihood of finding a functional protein by random mutation.

Personally I like my golf course analogy better which turns the diagram upside down. (here and here)

Abstracts of Axes Papers: here and here

Heaven and Earth

ID was one of the subjects under discussion on the Heaven and Earth programme.
Prof. Mark Walport (Director of the Wellcome Trust) spoke against ID maintaining that:

"Evolution is truth now... there is huge anounts of experiment evidence to back it up."

Dr Alistair Noble spoke in defence of ID:

"Intelligent design is a very ancient idea going back at least to the Greeks - It maintains that there is evidence for design in the universe. The constants of physics are finely tuned for life and this looks like design, complex systems are necessary for life and these look designed above all the coded information locked into DNA looks designed."

Former Education Secretary David Blunkett "helpfully" added that ID is “just a much more sophisticated version of creationism.”

Simon Barrow, of "Ekklesia" dismissed ID as a “mistaken religious ideas” and “a political and religious problem”.

Dr Noble responded by distingishing ID from creationism in the following way:

“the difference between intelligent design and creationism is that they have very difference starting points. I would want to insist that the starting point for intelligent design is scientific observation.”

Friday, January 12, 2007

Intelligent Design and Evolution have the same status as scientific theories.

Royal Holoway University of London are hosting a debate on the above proposition on 21st February at 5.00pm.
Steve Fuller graduated as a sociologist and then studied the history and philosophy of science and has focused on the writings of Thomas Kuhn and Karl Popper. He describes himself as a secular humanist.

He has commented on the Dover judgement (in which he was a witness) here.
He has explained how he became involved in the ID debate
A brief outline of a previous debate with Jack Cohen is

Lewis Wolpert is a developmental biologist who was made a Fellow of the Royal Society in 1980 and was awarded the CBE in 1990. He was for 4 years Chairperson of the Committee for Public Understanding of Science. He is a well known rationalist.

Given that we have a rationalist debating a secular humanist this hardly looks like a standard religion versus science debate!

Saturday, January 06, 2007

Abiogenesis and the 2nd Law of Thermodynamics.

Previous related posts:
Andy MacIntosh and the 2nd Law.
The idea of unintelligent Abiogenesis.
Is Abiogenesis Falsifiable?

This post is based on Walter Bradley’s chapter on “Information, Entropy and the Origin of Life.” In “Debating Design” Edited by Ruse and Dembski and published by Cambridge University Press.

Walter L. Bradley was one of the authors of “The Mystery of Life’s Origin.” which remains as the best selling advanced level text on the Origin of Life.

Bradley states that the second law of thermodynamics (2lot) and the theory of evolution are two of the three major scientific discoveries of the nineteenth century with Maxwell’s field equations for electricity and magnetism being the third. He is intrigued that the theory of evolution and the 2lot appear to be in conflict. The 2lot suggests a progression to disorder from order, from complexity to simplicity. Evolution involves progression to increasingly more complex forms of living organisms.

Erwin Schroedinger noted that living systems are characterized by highly ordered, aperiodic structures that survive by drawing “negentropy” from their environment and feeding on it! Today we recognise Schroedinger’s ordered structures as the complex biopolymers of protein and nucleic acids.

Living organisms use information stored in these biopolymers to resist the pull of the 2lot towards equilibrium. They are able to store information, to replicate with minimal information loss and they are able to feed on “negentropy.”

The existence of these three abilities allow us to understand how living organisms can continue to exist without violating the 2lot but the difficulty is understanding how these three abilities came to exist without violating the 2lot. This is the greatest mystery in science. At the heart of this problem is the difficulty of explaining how the complex specified information within these biopolymers can originate.

Bradley discusses the significant quantities of Shannon information that are stored in cytochrome c and in the E.coli bacterial chromosome.

At best the 2lot gives a very small yield of unsequenced polymers that have no biological function. The sequencing required for function is not facilitated by the 2lot.

Bradley then goes on to discuss the various origin of life scenarios that have been proposed in the light of the problem of the need for information and the pressure of the 2lot towards disorder.

He concludes: The origin of life seems to be the ultimate example of irreducible complexity. I believe that cosmology and the origin of life provide the most compelling examples of Intelligent design in nature. I am compelled to agree with the eloquent affirmation of design by Harold Morowitz (1987):

“I find it hard not to see design in a universe that works so well. Each new scientific discovery seems to reinforce that vision of design. As I like to say to my friends, the universe works much better than we have any right to expect.”


Thursday, January 04, 2007

The 2nd Law of Thermodymamics and Abiogenesis.

I commented on William Crawley’s “Sunday Sequence” and its aftermath here.

William Crawley has put several posts up following this. “Finding Darwin’s God” a piece on Ken Miller. Richard Dawkin’s letter to the Guardian. A piece on Andy Macintosh. A piece on the letters defending Andy Macintosh. Andy Macintoshes reply. Since then William Crawley has chosen Richard Dawkins as his Blog’s Person of the year. He has linked to a Salon interview with Ron Number’s the author of “The Creationists” and blogged on the letter from senior academics defending TiS.

Clearly William Crawley has a more than passing interest in the brewing "Biological Origins War" in the UK.

I was very interested in the exchange between Richard Dawkins (RD) and Andy MacIntosh (AM) and its aftermath. RD clearly thought that he was on to a big hitting winner with AM mentioning that the 2nd Law of thermodynamics rules out an unintelligent origin for biological information systems. RD seemed to be keen that Leed’s University should take action against one of its professors speaking in this way about a subject that is clearly within his own area of special competence- thermodynamics.

I got the impression RD really wanted AM to say something like “The 2nd law of Thermodynamics means that evolution is impossible.” RD could then show watertight evidence for micro-evolution and initiate a national UK science day of laughter at the silly creationists. However this is not what AM actually said. He has further clarified his position with a comment which has been published on William Crawley’s blog.

This is what he said:

Now that the 2nd law has had time to work on the Turkey this Christmas . . . maybe a few words are in order on thermodynamics and living machinery which I spoke about on the Sunday Sequence program on Dec 10th. I don't usually enter lots of blog discussions, but I see that you are having quite a debate here, so perhaps a word is in order from me. I do not on principle enter into any ad hominem attacks or respond to such against me. They do not add weight to any arguments and it is the science which is important.

The reason of course why this subject of origins will not go away is that there is a scientific case, whether Dawkins likes it or not, which is a challenge to the neo-Darwinian attempts to explain life in terms of common descent. It is a straightforward case of testable science versus the modern evolutionary ‘just-so’ story telling. Scientists like myself who believe in Creation have no problem with natural selection. It is simply the natural equivalent of artificial selection. But natural selection has no power to create new functional structures. It does not increase information and does not build machines which are not there already (either fully developed or in embryonic form).

The principles of thermodynamics even in open systems do not allow a new function using raised free energy levels to be achieved without new machinery. And new machines are not made by simply adding energy to existing machines. This was the point at issue in the programme of Dec 10th. Intelligence is needed.

And this thesis is falsifiable. If anyone was to take an existing chemical machine and produce a different chemical machine which was not there before (either as a sub part or latently coded for in the DNA template) then this argument would have been falsified. No one has ever achieved this.

I suggest that all the listeners read again if they have not done already, the excellent book by Wilder Smith called 'The natural sciences know nothing of evolution'. It is available on Amazon.

Clearly this kind of argument has been bubbling around for some time since Wilder Smith raised it. I do not think that when scientists of the standing of AM and Granville Sewel (University of Texas El Paso) are willing to stick their necks out over this that it can simply be dismissed as "showmanship bluffing" to a willing audience.

It is a also a subject which has also been raised by Walter Bradley (2004) "Information, Entropy, and the Origin of Life" pp 331-251 in Dembski and Ruse (eds) "Debating Design" Cambridge University Press.

I became interested in the concept of entropy in my A-level Chemistry classes but I really have only a very basic understanding of the concept. It seemed to me however that the 2nd Law of Thermodynamics ruled out the idea that matter is eternal.

Those who believe that life originates without intelligence argue that all that is needed to produce life is energy plus matter plus lots of time. They tend to argue that the demonstration that this is true is the fact that life is here on earth!

AM, Wilder Smith, Walter Bradley,Granville Sewell and others clearly have the conviction that this formula is flawed and something else is needed.

Energy + Matter + Time + ? = Life (with its computer like information system)

The needed ingredient they say is a plan, an idea…intelligent design.


Tuesday, January 02, 2007

Prominent Academics support Truth in Science.

Previous posts on "Truth in Science":

It has emerged that 12 prominent academics wrote to Tony Blair and Alan Johnson, the education secretary, last month arguing that ID should be taught as part of science on the national curriculum.

They included 1. Norman Nevin OBE, Professor Emeritus of Medical Genetics, Queen's University of Belfast, 2. Antony Flew, formerly professor of philosophy at Reading University; 3. Terry Hamblin, professor of immunohaemotology at Southampton University; 4. John Walton, professor of chemistry at St Andrews University, 5. David Back, Professor of Pharmacology at the University of Liverpool; 6. Steve Fuller, Professor of Sociology at Warwick University; 7. Mart de Groot, Director, Retired, Armagh Astronomical Observatory; and 8. Colin Reeves, Professor of Operational Research at Coventry University,,2087-2524442_1,00.html