In an article titled "Life Is Complicated" in Nature 464, April 2010, Erika Check Hayden explores the frustration many biologist are experiencing with the realization that the genome is becoming more complex than they could of imagined. To illustrate the depth of the problem, the article states "Instead, as sequencing and other new technologies spew forth data, the complexity of biology has seemed to grow by orders of magnitude." Notice the term "orders of magnitude" indicating a vast amount of interactions and elements they were not expecting. Certainly, with the discoveries of new complex genetic interactions with RNA's, signal transduction pathways, proteins and the accompanying cascade of those interactions, this is not a surprising reaction. Jennifer Doudna, a biochemist at University of California, Berkeley adds, "It seems like we're climbing a mountain that keeps getting higher and higher,"

The article states that the crux of the regulation problem is "that a regulator gene codes for a regulator protein that controls transcription by binding to particular site(s) on DNA." A vastly simplified description of what happens follows: 1) A request for a protein is generated by the cell. 2) That request is translated into the RNA operating language of the nucleus through signal transduction pathways. 3) The request for a particular protein is interpreted by the RNA operating system which must generate the local machinery that locates copies and edits the appropriate gene via RNA's and existing protein elements. 4) The needed RNA's are first located and copied, forming a variety of small RNA's, si RNA.s, etc. These work in conjunction with proteins to form the transcription factors and a host of other functions. 5) The above mechanisms work upon the formatted data base that I call the DNA hard drive to extract, copy and check for proper information. 6) Regulation (as biologists call it) is more like the process of locally enabling those volumes and clusters of the genome where the requested gene resides. Next, it is important to locate the proper gene and then, precisely identify and align the copy mechanism to the initiation start site. 7) Once the copy of the gene needed is made (mRNA), it is edited by the spliceosome (a highly complex and specific process in itself) followed by the addition of the cap and poly A tail transforming the mRNA into a biological bus analogous to the data bus of a computer system. The mRNA then travels through the nucleus pore complex towards its destination (the protein building factory). 8) More than one copy of the same gene may be necessary (such as building the filament of the flagellum) enabling repeated copying processes to continue on the same gene, regulated by the system.

Basically, this is a multi-integrated process that is orchestrated by the cellular operating system, just like windows or Linux orchestrates the processes on a computer. The article goes on to describe how "systems biology" can help to make sense of the added complexity. However, this hasn't been the case "So far, all these attempts have run up against the same roadblock: there is no way to gather all the relevant data about each interaction included in the model." I believe that this is because they are following the wrong paradigm. Structural isolation of gene modules is not what one would expect from random undirected processes of evolution. Instead, the creation of boundary conditions around gene modules (transposons, gene clusters) is what one would expect to see if an organized rule based process is applied to a generic database. In our experience, this formatting is a product of design. We see such structures in multiple drives and volumes as seen in hard drives and in subroutines and libraries in software programming. What appears to be regulatory system interactions may be the visible execution of the cellular operating system, or bio-BIOS occurring in the nucleus.

Dr. Michael Mann, the Penn State climatology professor and 2007 co-winner of the Nobel Prize for his environmental leadership is fed up--and who can blame him?

Several months ago a YouTube video, Hide the Decline, was released that he alleges damaged his reputation by suggesting that he falsified climate change data. The makers of the video temporarily removed it but have now released another video--only in this one Dr. Mann's image has been removed.

Of course, scientific truth is not decided by the popularity of Youtube satire, but by evidence. The first paragraph of a New York Times article claims that a UK Parliamentary panel found that there had been no misrepresentation of climate change data.

Interestingly, later in the article it is mentioned that this was only the result of listening to one day of oral testimony. Two additional, and more detailed, investigations are scheduled. It seems that the panel's advice that, in future, scientists allow their critics to see all their data and that they do not stonewall investigations is apt.

So what is integrity anyway? On page 84 of his book, Dr. Johnson points out that the root of integrity is "integer," which to a mathematician is an unfractionated whole. Various internet sources give phrases and words such as sound, unbiased, consistent, or adhering to ethical and moral principles. Wikipedia points out that, in popular culture, "in an absolute context, the word "integrity" conveys no meaning between people with differing definitions of absolute morality."

But, of course, science and technology do strive to find absolute truths. If we mix all the colors of light, we get white light; if we mix all the colors of pigment, we get brown pigment. The question is, do scientists and engineers strive to find the truth? After all, when one's actions, results, or conclusions have uncomfortable implications, it is not always easy to maintain scientific integrity. AITSE believes that science should be based on evidence, not mere consensus, political, financial, or even religious (theistic or atheistic) considerations. But, this sounds a lot easier than it is in practice.

Therefore, one of AITSE's next projects will be to gather a group of experts to talk about just this subject--scientific integrity. In particular, we intend to gather data for a book highlighting stories of scientific integrity (or lack of it) and write curriculum detailing how it can be practiced. If you have an example or expertise to share, we would be happy to hear from you!

Of course, the listed side effects of cholesterol-reducing agents vary depending on the source. The pharmaceutical manufacturers, the Mayo Clinic, and even the FDA seem to think that the side effects are mild and rare. Others feel they are rather more serious; one site even suggested that over 90% of people taking statins develop serious muscle pain. It appears obvious that the motive for advocating prescription of statin drugs for those who do not have high cholesterol might be financial. But, maybe I am wrong. Perhaps this is a good idea.

These days much health care is preventative. People take medications to prevent osteoporosis, have a mastectomy to prevent breast cancer (if they are positive for the gene), and are vaccinated to prevent viral infections, even by agents that they are unlikely to encounter. But, my opinion is that one should always weigh the health risks of any therapy against the possible health (not financial) benefits. In the case of prescribing statins to those who do not have elevated cholesterol levels, I am not convinced that this has been adequately accomplished.

In closing, as always, Caroline, thank you for your past gifts and support. It is a fact that AITSE cannot function in its efforts to educate to increase scientific understanding and integrity without contributions. Please consider helping us with a special donation or a commitment to give on a monthly basis. Please make checks payable to AITSE and send them to PO Box 15938, Newport Beach, CA 92659. Alternatively, you can now donate on line through PayPal or credit card at www.AITSE.org.

Sincerely,