Are Terrorists That Dumb?

Terrorists are most likely like spies. At least one would think they would or should be. Spies have been around for a real long time, a real long time. The Persians had spies in Greece some 2500 years ago. So it is nothing new. Spies, and one would suspect Terrorists, communicate amongst one another and they would most likely do so in some secure manner, not say sending emails on some well known site or planning in an open "chat room". But perhaps they are really that dumb.

There is an article in Science which has alleged "experts" applauding the current administrations massive tactics of seeking these folks by examining what is in plain sight. In fact they state:

“I can tell you that this kind of thing is extremely effective,” says Alex Pentland, a computational social scientist at the Massachusetts Institute of Technology in Cambridge who has studied phone networks.

Now being told by someone from the Media Lab is not really that comforting to me but perhaps it may be somewhat truthful. I would not know what their basis is. The article continues:

The first step, Uzzi says, would be to map who calls whom—with each person represented by a point or “node” and each person-to-person link represented by a line or “edge”—to create a simple  communication network. Next, the analyst would study details of calls—their frequency, duration, and timing—to determine how closely connected each pair of people is. This step breaks the  communication network into smaller, overlapping social networks. The third step would be to study  the dynamics of a social network, to see how activity ebbs and wanes and the network evolves. The  fourth step would be to try to correlate the dynamics of the network with external events, 

This assumes the "plain sight" scenario. If we take spies as the example, they have two options; hide in plain sight and be totally covert. When in plain sight you must be transparent, not attract attention, and be as if you were a sleeper. You could not stand out, you don't communicate, and you must fit in with everyone else. If you are covert than you stand apart and in this case you must use secure and covert means of communicating. Thus codes, secure comm links, such as wireless HF digital links, so that no one knows just who you are calling.

The use of the above techniques work well in commercial applications where people volunteer their information and have no desire to "hide". We can find that people say on Staten Island order more Pizza deliveries per 1,000 HH than any other area in the US and further that they have the greatest BMI in the US as well.  But if we had some Chinese espionage agent I doubt that they would call the Embassy to transmit data. I would think.

I can recall all the means and methods of WW II and those in the Cold War, so why would they not be employed? Can we really detect those hiding in plain sight. Perhaps, but the Fort Hood terrorist was shouting out his plans and no one ever paid attention? What happened there. He apparently even gave presentations that should have alerted a Mall Guard. 

Thus the issue is less the value than the very rights we would expect.  As for Congress and its overview, I have found that all too often those providing oversight just do not have a clue technically so what good does it do. 

I am still in favor of human intel, people, people where the action is. Again, just sitting in that bar in Istanbul, the coffee shop in Algiers, the shops in Islamabad. Words, accents, clothing, shoes, packages, hair cuts, people meeting, those are the tools on intel, and the ability to have a keen insight into the obvious. 

The Philadelphia Chromosome

The book by Wapner, The Philadelphia Chromosome, is simply perfect. It is a wonderful balance of science, personalities, inventions and medicine. It flows smoothly, giving the reader the opportunity to catch up each time a new step is taken. The topic is simply the best example of how we are beginning to understand cancer in a detailed manner, thus allowing us to develop therapeutics to treat cancer, turning many from death sentences to chronic disease. The focus of Wapner’s book is CML, chronic myelogenous leukemia. This is a blood cancer where the white cells start changing and slowly increase and then in a blast crisis cause total collapse and death. This is the story of how it was understood what caused it and how to stop it.

She takes the discovery of the Philadelphia chromosome and walks the reader step by step to the acceptance and use of imatinib. I remember a colleague in Vienna, Austria, who in 2002 came down with CML, at a young age, and I had been following the imatinib development and after a few calls it was possible to get him on the therapeutic and he survived. This tale has some many coincidences, most positive, that makes its telling almost mandatory to best understand where cancer therapeutics is progressing today.

The tale presented by Wapner is fairly straightforward; it is a mixture of science, luck, coincidence, and human nature.

The first part of the book takes us from the early 1950s through the mid-1980s, where we go from not understanding to having a somewhat clear scientific comprehension of both the problem and a remedy. The first part moves through the following:

1. Using an innovative way to look at chromosomes the 1959 discovery of a chromosomal alteration indicates that a hematological cancer, CML, presents with this abnormality. A short end on one chromosome and longer end on another were observed. This is just six years after the Watson and Crick paper.

2. Recognition of a cancer generating gene.

3. Recognition of the fusion of two chromosomes

4. The understanding of how protein kinases work via the src gene from chicken sarcomas. In fact on p 47 the author describes this process and she does a superb job in highlighting what will become a significant key in the overall development of imatinib.

5. The discovery of the Abelson gene, abl, and its relationship to cancer. On p 63 the author relates how Abelson was berated in 1969 by physicians and the president of AACR, the cancer research society. Frankly at that time cancer was the realm of the surgeon, who often just cut as much as possible and often doing more damage than good.

6. The new Gag/Abl protein, namely the fusion seen on chromosomes is identified as the fusion of two genes. The author on p 72 has a wonderful description of this insight.

7. Gag/Abl causes cancer. On p 83 the author discusses the work in David Baltimore’s lab in the early 80s. At the same time they found abl had come from chromosome 9 and was transported to chromosome 22 attached to gag.

8. The tale of Drucker and his persistence and dealings with Ciba Giga, eventually to be Novartis starts at this point. Here we see the drive of pushing, connecting, developing, and frankly persevering with a positive result. It was recognized that the Gag/Abl fusion product was the driver of CML and that the driver of that was ATP and ATP found a connection point on the protein. Then if a new molecule could bind and block the ATP the gene effects, namely cancer, could be blocked. Thus starts the second part of the book.

The second part of the book is much less linear and shows the complexity afoot in the pharma world. Even though Drucker, and at this point many others, saw the path forward, it was necessary to engage the pharmas and their massive powers as well as their bureaucracies. Thus, we have the tale of this part. The author does a superb job of giving some light on the development and testing of therapeutics. One walks away seeing the most bureaucratic part the pharma and the FDA and Government entities almost acting as sideline players at best.

The infighting in the pharmas, the conflicts between development, marketing, toxicology, and management is a wonderful tale, typical of so many large institutions. The lesson from part one is the brilliance of the dedicated researchers, that from part two is one wonders how any therapeutic is ever developed. In today’s world it would take fifty years to approve aspirin!

Wapner’s book presents great history but it begs the question of the future progress. Although that was not the intent of Wapner, she sets up the question quite nicely. She shows how research and development proceeded from the 1950s through the end of the century. I would argue that we are at the beginning of a new paradigm of development, and it is not clear if the institutions are all that prepared to deal with it.

There are several drivers which make the future even more interesting.

First the communications over the period of 1959 through 2002 were driven most often by personal contact, journals and conferences. Today the Internet spreads results and data around the world instantaneously. The chance occurrences are increased orders of magnitude.

Second, as we look at kinases we now understand them first as intracellular networks and pathways and secondly as distributed spatio-temporal systems. This means that we are moving from the world of bench researchers and their singular focus to the “engineer” and their systematic approaches. Cancer is viewed as an unstable multidimensional system. Fortunately there are many tools and expertise to deal with such a paradigm.

Third, and this is an exceptionally critical change, we have multi-national participation, with explosions from countries like China.

One is starting to see more and more of the fundamental work arising from not just the US and Europe but Asia. These three factors will most likely be accelerators for the tale told by Wapner. However she also contains the cautionary tale of the Pharmas and the regulatory bodies, oftentimes the brakes on progress. That will most likely be the challenge to realizing true progress on cancer.

The future may very well be driven by the observations of Eddington and Einstein:

“It is also a good rule not to put too much confidence in the observational results that are put forward until they are confirmed by theory.”  Arthur Eddington

“It is quite wrong to try founding a theory on observable magnitudes alone. It is the theory which decides what we can observe.” Albert Einstein

The two quotes frame the changes which are occurring in the understanding of cancer. The tale by Wapner was initially data driven, there was not model, it had to be constructed. Now, we have models, we understand pathways, we understand where they fail, and thus result in cancers. We have the models and thus hopefully we can make better and faster sense of the data. Wapner sets the path to best understand that progress.

Genes and the Left Wing

Apparently the left wing bloggers have determined that Justice Scalia does not "believe" in evolution. One of the left wing bloggers, who in my opinion is all too often a bit over snarky states:

The text goes on just like that: simply summarizing molecular biology. That’s right, Justice Scalia can’t confirm these details with his knowledge (valid) or his belief (um, what?).

Can't he hire a clerk to teach him molecular biology?

 Now let us examine just what this complaint seems to be.

Justice Scalia states:

I join the judgment of the Court, and all of its opinion except Part I–A and some portions of the rest of the opinion going into fine details of molecular biology. I am unable to affirm those details on my own knowledge or even my own belief. It suffices for me to affirm, having studied the opinions below and the expert briefs presented here, that the portion of DNA isolated from its natural state sought to be patented is identical to that portion of the DNA in its natural state; and that complementary DNA (cDNA) is a synthetic creation not normally present in nature.

Now one should note several things. First belief is a legal term of art, and before commenting the Justice indicated that this is a complex issue which may not have been fully illuminated. Second, and this is critical, Scalia unlike the one who crafted the opinion, uses the correct term for cDNA, complementary DNA, not what we have commented in before. Thus Justice Scalia is spot on in both delimiting his knowledge in the complexity of the issue and secondly in using the correct term.

Thus unlike the left wing bloggers he appears as is so often the case to be correct, and the left wing bloggers just wrong. So what else is new?

Women and Lunch

Some day I must cross the border and visit one of my former students who is Ottawa and at the same time visit Frances Woolley. Today she writes a long blog about men and women having lunch together. Now since I am old enough to be her father perhaps I may be able to shed some light on the situation. That man and woman thing.

You see when I grew up it was during WW II and there were few men around. The world as I saw it was controlled and managed by women, mother, grandmother, aunts, cousins. The men I intuited were sent off to war and some never returned. I even envisioned that the women made all these choices, after all even all my teachers were women and the girls often got the best grades. There were indeed very few men. I was the minority, and there always was that concern about what happened when you grew up.

Now segue to the late sixties, I am teaching at MIT, my first major assignment, the Sophomore Electronics course. Never saw a woman in class, and then there in the front row was a real woman. Yes, I made the mistake of asking if perhaps she was in the wrong class. Today that question would have you drawn and quartered but then it was trying to be polite. No, she replied, she was a Biology major and she wanted to learn electronics, a laudable goal I thought. From that point I never asked again and the numbers grew exponentially.

By the late 1980s I had accumulated a few female students, and I would travel back and forth, but the thought that there could be any issues never crossed my mind, nor my wife's. You see I still had my WW II memories, and now their were colleague, not students. I knew their families, their spouses, and eventually even their children. They were professionals and after years still are. I have even assembled cribs for my student's children, and perhaps they may be told later in life of such a heroic event. Namely my doing anything really mechanical!

Now Frances writes:

As a person becomes professionally more established, too, new challenges arise. Is it okay to go out to for dinner with a co-author in another city? To go out drinking with a former supervisee? Nick Rowe, in his position as Associate Dean, will go out for drinks with the (male) Dean. But is it appropriate for a female Associate Dean and a male Dean to go out drinking? 

Drinks and dinner, well it all depends. In the context of normal professional relationships I see no problem, in the context of how it "looks" it all depends. Are there predatory individuals, yes and I have seen them, but I suspect that it is they that often look askew at others. In New York today there are no second glances, no issues with such meetings. Then again I feel safe with age, there being nothing more disarming than being perceived as grandfather.

So Frances, whenever I get to Ottawa I would love to have a drink, and I will bring my wife and my former student, of course assuming she can get a baby sitter.

The Myriad Decision and cDNA

The Supreme Court states:

They can also synthetically create exons-only strands of nucleotides known as composite DNA (cDNA). cDNA contains only the exons that occur in DNA, omitting the intervening introns.

As NCI states:

The next step is to convert the mRNA back into a DNA molecule in the test tube. This can be thought of simply as reversing what went on in the cell when the gene DNA was switched on and mRNA was made by base pairing. This is a two-stage process. First, each mRNA is copied into a new DNA strand using base pairing to form a mRNA-DNA duplex. Next, the mRNA is chopped up and removed, and the DNA strand is used to make a second DNA strand. This double-stranded DNA is called complementary DNA or cDNA. Thus, each cDNA in the test tube originally came from a specific mRNA in the cell.

But in the MIT cDNA course they call it complementary DNA, NOT "composite DNA (sic)" Even Wikipedia uses that term. It is amazing this is on page 1 they make this massive fundamental mistake. Any AP Biology High School student knows this. One wonders who crafted this document.Perhaps that is what is wrong with our Government.

Lions, Tigers and Bears

I live less than 20 miles from the southern tip of Manhattan as the crow flies. It is in the most densely populated state in the US. We have red fox and coyote in the neighborhood, not to mention deer, rabbits, chipmunks, turkey, and the squirrel. But we now have a bear, yes, a 200 pound bear walks across my driveway at night eating up whatever we have left behind.

Now it is not that I have anything against bears, we have one in New Hampshire, but this guy likes my daylilies, my precious hybrids. Do I call Christie? What will EPA say? And yes he did check out my car...hopefully he does not decide to take a ride.