You Read The Da Vinci Code? Now Watch the Compugen Code

You like to go to the movies? I do, too, and some of those that I have enjoyed fall within a genre of treasure hunt films, including Romancing the Stone, National Treasure and The Da Vinci Code, just to name a few.

The Da Vinci Code? If you read the book or saw the movie based upon the novel, you will recall how Robert Langdon, a professor of religious symbology, deciphers a series of puzzles and anagrams, solves a murder, eludes would-be killers, possibly finds love, and discovers that the "Grail" is buried beneath the pyramid of the Louvre, all within the course of days. The Da Vinci Code is of course fictional. I would suggest that there is a real-life treasure hunt being pursued for almost a decade, involving the deciphering of billion-year old riddles, which can be watched as it systematically unfolds: how life "works" on the molecular level.

When did the real treasure hunt begin? Perhaps you remember many years ago the excitement surrounding the discovery of a single gene and the scientific value attributed to its occurrence. But now consider the value of the discovery of a single gene today, without knowing the proteins and peptides it can generate and without any clue how to modulate its activity. The mystery of life is far more complex than anyone imagined some 20 years ago, and almost all the corporations who initially joined in this treasure hunt have long since abandoned the pursuit.

Given my love for movies, I believe an analogy to the situation existing when the treasure hunt began can be drawn to the "tutsi fruitsi ice cream" scene of The Marx Brothers' A Day at the Races (http://www.youtube.com/watch?v=9LBIsDBC848). Watch as Chico sells Groucho the code, ZVBXRPL, for the winner of the next horse race. Groucho soon discovers that without the Code Book, which Chico then sells him, he cannot decipher the code. However, understanding the Code Book, requires – at a price – the Master Code Book, which requires the Breeders' Guide, which requires the Jockeys Manual, which ultimately leads, at great expense and much frustration, to a losing horse.

Unlike other companies that joined and then abandoned the chase, Compugen has persisted in its pursuit of this elusive quarry, discovering on the way that there are no shortcuts and that each of the interlocking pieces of the puzzle is as intricate as the next. Examples of the pieces of the puzzle: correlated mutations, intramolecular segment interactions, large scale genetic variation, pseudogenes, protein folding, cleavage sites, viral piracy and antisense. The code is not binary, i.e. the basis of life is not found in a series of "0s" and "1s", as in computer science. Rather, four nucleic acids – adenine ("A"), cytosine ("C"), guanine ("G") and thymine ("T") - provide the building blocks for all our DNA blueprints, which encode our RNA, which translate into proteins, many of which cleave into peptides. Similar, however, to computer science which was spawned by man, the language of life is also mathematics.

Compugen's treasure hunt began with a better understanding of alternative splicing. Whereas once it was thought that for every gene there is one protein, Compugen correctly predicted that a little known phenomenon known as alternative splicing, whereby one gene gives rise to more than one protein, was far more prevalent than commonly thought. Ultimately, Compugen would discover that this phenomenon occurs in more than 80% of all human genes. But this was hardly enough to provide an understanding of life at the molecular level, which requires the integration of additional biological phenomena, resulting from billions of years of mutation and evolution.

Further evidence of Compugen's progress? Pseudogenes, ancient relatives of known functional genes, have lost their protein-coding ability and were tossed into the category of "junk DNA". In 2006 Compugen announced that its predictive methodology had been shown to use pseudogene sequences as blueprints for new gene variants and, thus, novel transcripts and proteins, resulting in new therapeutic candidates.

But the discoveries involving pseudogenes were still only the beginning. Peptide therapeutics, among the hottest fields of drug discovery today, were facilitated by new technologies for their synthesis. However, peptides, which are protein fragments, cannot be predicted without knowing protein cleavage sites. Compugen mapped both the human proteome and peptidome, and created new discovery platforms, e.g., the GPCR peptide ligand discovery platform (2007), providing access to a host of new peptide therapeutic candidates which can be discovered on demand.

The DAC Blockers platform (2008)? Proteins fold and sometimes assume disease associated conformations. Compugen, as the result of its evolutionary knowledge involving the loci of mutations, is able to predict peptides, which can bind with the protein at the appropriate location and prevent the folding of the protein.

The ultimate objective of Compugen's treasure hunt? That's obvious: You. I'm not referring to the blue eyes or blood type that you inherited from your parents. Rather, I am asking why you don't tolerate penicillin, or why you suffer from IBD? Why are you aging faster or slower than your peer group? Are you destined to become ill with lung cancer even if you don't smoke? More to the point, why are you different from every human being that ever lived, and how might it be possible to intervene to ensure you a healthier, happier life with a new crop of diagnostics and therapeutics premised upon rational scientific prediction?

The Compugen Code? A small group of the world's top scientists, including persons who spent many collective years in the Israeli army breaking secret codes, are now busy deciphering the secrets of life. This is a project infinitely more complicated than the plot of The Da Vinci Code, nevertheless significant progress has been made, as evidenced by cutting edge discovery platforms and promising therapeutic and diagnostic candidates used to validate these platforms. No one is dying in the chase after life's secrets, and there is no crazy albino monk hot on the trail of Compugen's scientists, but take the time to read their story and watch for the discoveries as they are periodically reported. Chances are you will find this real-life thriller even more fascinating than that of Dan Brown.

If you follow the Compugen Code, you are not going to discover the burial site of Mary Magdalene. On the other hand, you just might be able to learn the secrets of a code extending back billions of years and perhaps touch, depending upon your theological orientation and outlook, something divine.

[As noted in prior blog entries, I am a Compugen shareholder, this blog entry is not a recommendation to buy or sell Compugen shares, and in mid-September 2009 I began work as a part-time external consultant to Compugen. The opinions expressed herein are mine and are based on publicly available information. This blog entry has not been authorized or approved by Compugen.]