I saw no mention in the EMBO article of the ~45 or so variants of one particular prion gene (as of a few years ago when the work went non-public). The one implicated in vCJD. Sequencing was deemed 'important' to Britain's public health services so that relative susceptibility to prion-flipping could help map the course of their Mad Cow epidemic. Only one variation has thus far succumbed to the disease, they figure some of the other variations will start coming down with it at any time.

Seems that despite the vital functions prions serve, human beings have a high tolerance for variation in the genes that code for them.

I'm glad to see the work has been ongoing, because the very idea of a pathenogenic protein that operates by flipping the fold configuration of the host's normal prions is rather amazing. There are other proteins that actually function by alpha-beta switching, though they're ephemeral compared to indestructible prions. Interestingly, it's in the brain that these protein dimers serve focused consciousness functions, and in the brain that prions encode long term memory or (when flipped) make it go away.

With the sequencing of the human genome, we were amazed how few "genes" there were. Few people were willing to admit that perhaps vast amounts of information are being stored outside the genome.

One paper from the IEEE which analyzes the linguistic properties of cells is slowly arriving at this conclusion. See (link courtesy RBH):
Two Operative Concepts for the Post Genomic Era

The first successes in cloning experiments and stem cell "reprogramming" have already demonstrated the primordial role of cellular working-space memory and regulatory mechanisms,which use the knowledge stored in the DNA database in read mode.

We present an analogy between living systems and informatics systems by considering : 1) the cell cytoplasm as a memory device accessible as read/write; 2/ the mechanisms of regulation as a programming language defined by a grammar, a molecular algebra; 3) biological processes as volatile programs which are executed without being written; 4) DNA as a database in read only mode. We also present applications to two biological algorithms : the immune response and glycogen metabolism.

The prion anomal is thus a degree of experimental support for the view offered in the above paper, with the cell's cytoplasm having information bearing qualities.

I think "Coperincan revolution" is an appropriate metaphor.

Say that this phenomenoa is real and that ingested or injected amino acid sequences can insert into an indigenous "sister" protein, alter its shape and ultimately alter its function. (I have no doubts this is what causes BSE etc.)

Now say via ID research we decipher a genome as we could a computer code. Could we then, as we do with computer codes, synthesize a genetic patch, inject it into an affected organism, that would insert into a mutated sequence that is producing an abnormality, and correct it?

For example sickle-celled anemia is a change in one amino acid sequence. Why couldn't we, once we have the mechanism figured out, correct that genetic abnormality, as opposed to treating the symptoms of SCA with pharmaceuticals?

Salvador, by proteins lead to genes you mean by reverse transcription?

Yes, that is correct. On the surface the phenomena of reverse-transcription may seem trivial, but for those who have worked on von Neumann self-replicating automata theory, one realizes it is an interesting problem. Consider the frame-shift and reverse-direction reading methods of transcription…..

Because the system is essentially self-referencing and recurrsive, there has to be a higher degree of design. And with what seems to be the movement toward epigenetic inheritance, this will become more significant.

In other words, the gene is only a first-order approximation of how information is represented and stored. I think we will discover and distributed architecture of information storage. I believe there are genotype-phenotype recursive loops that store information. This is a highly efficient computation storage technique when compactness is one of the design constraints.

When I heard that the intron splicing was recursive, I began to thing what we are seeing is some sort of computation going on. I think we are seeing enormous amounts of sophisticated computation going.

It's too early for anyone to say anything definitive, but I do think the claim of a "copernican revolution" is appropriate.

Salvador, by proteins lead to genes you mean by reverse transcription? How is this protein-to-genes route? I cannot imagine how you could get from protein to mRNA to DNA. Or do you mean indirectly? I'll read into 'infinitely recursive loop'. An irreducible system is the last thing we need.

Although the possibilities of proposed mechanisms and AI are enormous, we have to see if they fit in the straight-jacket of evolution. It would be almost neodarwinistic to assume that all theoretical possibilities are also biologically possible.

I agree with Lynn Caporale that all the information is in each single cell. That it can come out is another thing. Because of the limited set of genes we have, it's amazing how much complex behavior can come out it. Wouldn't you then conclude that memory for instance has to be very simple.

The central dogma was not so much wrong as it was incomplete. James Shapiro views the genome as basically a hard drive which can describe most of creature's features, but like a computer system, it is not complete in and of itself.

Mathematicial Douglas Hofstadter was bewildered at these recursive construct in biology. Engineers and students of Artificial Intelligence (AI) will recognize these recursive constructs and see them as an irreducible holistic constructs.

A lot of AI software is written this way (recursion is the order of the day). Biotic systems thus have an internal intelligence designed in them. Lynn Caporale said we should not underestimate the intelligence within a single cell. An entire human being, after all, comes from a single cell, so all the intellligence of our minds is shown to be compacted in a single cell.

The prion anomaly I think will lead us to see that biotic reality is a very sophisticated AI program, a living intelligence. Biology and evolution have some capacity for self-redesign, just as our minds help us to adapt, learn, and change…..

Salvador

I discussed with Francis Crick the problem of irreversibility of information transfer from nucleic acids to proteins. Although he was ready to accept some kind of reversibility between DNA and RNA through retroviruses, he was adamant about the absolute irreversibility of the RNA−protein road: "Nature could not proceed in another way."

I think Crick had a real engineering perspective. I still think he is basically right about the frozen accident hypothesis of the genetic code. (The problem for some is that it doesn't fit in the neodarwinian way of thinking). Here as well, he refers to the mechanistic consequence of reversing the central dogma. Apart from short-term effects of proteins as informational molecule, has it viability in the long run? Is it stable enough, how would it behave in evolution?

Biologists need to get used to the idea that there is no end in sight when it comes to new insights and scientific breakthroughs…

We maybe should start to solve the evolution of the fundamentals first before speculating about long-term potentiation and memory. Without evolutionary mechanism, it just another tool in the neodarwinian toolbox. Anything goes. Throw in some neutral evolution and you can explain how a horse can evolve to fly. More variables, more possibilities.

BTW, Long-term potentation is another field that needs regular hyped articles in important journals to hide to fact that they do not have a clue how memory works.

Yes, a great article. Another illustration of why phenotype cannot be reduced to genotype.

Sal