Friday, March 30, 2012

Somewhat Terrifying: Loss of Identity

The Guardian has a frightful article on what is happening in the Internet, in my opinion the arrogance of the bot creators have a logic which one cannot follow.

As part of the Esc and Ctrl series, Jon Ronson recently published two videos on Comment is free in which he confronts a spambot version of himself and accuses it of stealing his identity.

These European Professors are in my opinion clearly cyber terrorists but also seem in my opinion to be grossly illogical. They seem to have the problem that in Twitter world the use of one's real name is verboten, yes they teach in Germany. Identity is a key element of existence but one must listen to these characters, they are truly unreal.

What do they have, they have bots which steal identities and then create cyber identities that are sent out into the Internet. It states:

We're at a turning point in the development of the internet. Bots, like any other scientific innovation, can be used for benign or malign purposes. The identity issues that Ronson raises are only the thin end of the wedge

The creators have a problem with the Wall Street algorithms which perform real time trades, and they allege are at the core of their lost earning, and this is the apparent underlying prime reason that they are sending bots out to destroy individual identities. For these creators they believe that attacking third parties is a way to make public their message. The logic is hardly compelling to say the least.

It is essential to listen to this interview. Ronson is clear and logical but the creators of the bots in my opinion seem totally incoherent. They jump from conclusion to conclusion with no logical connectives. The issue that by using Ronson's name and picture and creating a bot to tweet things that may make no sense to things which could be defamatory is their way of sending out a complaint about Wall Street. There is in my opinion a direct disconnect from reality here, something is truly wrong.

The fear is that our future may very well be in the hands, or worse, the minds of people like this. Ronson did a wonderful job by collecting their logic and lack thereof on video. It should be viewed by many because it establishes the mindset in my opinion of a total nihilism. The loss of logic in a world where anyone can go out and defame with impunity.

Of all the things which one could be concerned about, this is one of the most serious. Loss of identity. There are those stealers of our selves, thieves of the persona, who then take and contort and then present it to the world as if it were us. They take glee in such an act, and have applied a set of disconnected logic which can only in my opinion be called bizarre!

Thursday, March 29, 2012

Keen Insight into the Obvious

I am always amazed that studies are done, and done again, demonstrating the obvious. Being obese will almost always result in Type 2 Diabetes. Loosing weight and moving will almost always mitigate against Type 2 Diabetes.

Now in a NEJM article the authors conclude:

Weight loss and improved fitness slowed the decline in mobility in overweight adults with type 2 diabetes. 

So what is new here? Nothing really. They conclude:

Among overweight and obese adults with type 2 diabetes, an intensive lifestyle intervention led to a relative reduction of 48% in the severity of mobility related disability, as compared with diabetes  support and education. This effect was mediated by both weight loss and improvement in fitness. Group differences that favored the lifestyle-intervention group were most striking in the severe- disability category. However, as shown by prevalence rates in the good-mobility category during all  4 years of the study, participants in the lifestyle-intervention group also retained higher levels of  healthy functioning than those in the support group. The proportion of participants with the highest  level of functioning at baseline in the support group was generally stable until year 3 and then  declined. By contrast, in the lifestyle-intervention group, there was an increase in the prevalence in  the good mobility category by year 2, and rates never fell below baseline.

Reuters also published a piece on this result:

The lifestyle changes helped mobile people stay that way and eased severe mobility problems in others, at least over the short term. Lead author .... , said the trends show the importance of encouraging people to get their weight down and exercise sooner, rather than waiting until they develop problems getting around.

But all of this was clinically well known. Perhaps another study is supposed to demonstrate something. The only way to stop the obesity epidemic is to do what was done with cigarettes, tax it. Unfortunately none of the Republican advisors want to do that; one wants to tax gasoline out of existence and the other wants to have the Government mandate all health care, none of which addresses this issue! And the Democrats, well they seem to be even worse. Just watch the costs explode.

Engineering Health Care: And a Bird!

What the Supreme Court arguments show is that Washington is NOT Cambridge and neither is New York. In Cambridge one can go back and forth from the Academy to the home in the suburbs and rarely see reality. In Washington it is a continuous political battle. In New York, for better or worse, it is just money, nothing person, and you win or lose, at least until Washington stuck its head in. You see New York is still driven by Dutch individuality and capitalism, Cambridge by Puritan aloofness and exceptionalism, and Washington by the slime of politics.

Now the NY Times has a piece on one of the MIT Profs who spent his career pushing for a dream, a theoretical dream for health care. Now dreaming up a scheme with models is a far cry from designing a system and assuring it works. It is ivory tower economics versus engineering. This is why we are in such a mess, economists and the ivory tower. Their "ideas" just fails to meet reality.

As I have argued, universal coverage is essential, but the devil is in the details. We have models which work, auto insurance and even home insurance. The characteristics are simple:

1. Universal, yes one just can't seem to get around it. There should be an uninsured pool just in case.

2. Individually procured, NOT through an employer or third party.

3. Minimal required coverage primarily for catastrophes, and of a form where an individual can then add on.

4. Rates determined solely by variation of life style choices, you smoke you pay, you are fat you pay, but no variance for those with hereditary and the like diseases.

5. Skin in the game, you can have even oil change covered but it costs, otherwise you pay out of pocket.

6. Regulation, yes regulation, of the insurers.

7. Government support if incomes are too low. Cannot seem to get around this.

Now I had done a detailed financial model showing how this would efficiently work. I also argued along the line of changes in the means and methods of health care. As did hundreds or thousands of others. Yet the Times believes that there was a single voice. Pity they so all too often neglect the facts.

Wednesday, March 28, 2012

Reduction in Cancer Deaths and Politics

The CDC issued a new release summarizing a published report, requiring what appears to be a substantial fee, strange for a taxpayer funded work. Yet the conclusions indicated a significant reduction in both incidence and mortality.

Specifically it states:

The Report to the Nation was first issued in 1998. In addition to drops in overall cancer mortality and incidence, this year's report also documents the second consecutive year of decreasing lung cancer mortality rates among women. Lung cancer death rates in men have been decreasing since the early 1990s.

Colorectal cancer incidence rates also decreased among men and women from 1999 through 2008.  Breast cancer incidence rates among women declined from 1999 through 2004 and plateaued from 2004 through 2008.  Incidence rates of some cancers, including pancreas, kidney, thyroid, liver, and melanoma, increased from 1999 through 2008. 

Melanoma has a long tail since most cases are sun induced but take substantial time to progress so that is not unexpected. Pancreas may very well be linked to obesity and the inflammatory response that results. What was once a rare form of cancer has seen a rate of increase paralleling the increase in obesity. The same may be true for renal carcinomas since they are well established as having linkages to Type 2 Diabetes as well as obesity. Thus the increases are most likely obesity linked.

The release continues:

“In the United States, 2 in 3 adults are overweight or obese and fewer than half get enough physical activity,” said John R. Seffrin, Ph.D., chief executive officer of the American Cancer Society. “Between children and youth, 1 in 3 is overweight or obese, and fewer than 1 in 4 high school students get recommended levels of physical activity. Obesity and physical inactivity are critical problems facing all states. For people who do not smoke, excess weight and lack of sufficient physical activity may be among the most important risk factors for cancer.” 

 We have been arguing this for years. We indicated the scope in our book on Health Care and our book on Obesity. The irony is that one of Romney's senior economic advisors rejected any Government attempts to control this epidemic while at the same time recommending a $1.00 a gallon added tax on gasoline. That approach is as bad as or worse than the current Administration's mess. But then again they are all filled with Harvard economists.

The fact is that technology can fix the gas problem but that people's behavior must be controlled to fix the cancer and other obesity related problems, just as those smoking related have been shown to have been fixed. We now have almost banned smoking everywhere, why not try that with obesity?

Monday, March 26, 2012

Genes and Patents

This case is interesting and now very much worth following. The Washington Post states:

The Supreme Court on Monday threw out a lower court ruling allowing human genes to be patented, a topic of enormous interest to cancer researchers, patients and drug makers. The court overturned patents belonging to Myriad Genetics Inc. of Salt Lake City on two genes linked to increased risk of breast and ovarian cancer. ... The case is Association for Molecular Pathology v. Myriad Genetics, 11-725.

 It will be interesting to see if pathways will have similar standing since in many ways they are the next step in creating ways to control cancers. Just a thought.

Sunday, March 25, 2012

Would You Buy a Used Car From This Man?

In the FT an opinion writer states:

Economic forecasters divide into two groups. There are those who cannot know the future but think they can – and then there are those who recognize their inability to know the future. Major shifts in the economy are rarely forecast and often not fully recognized until they have been under way for some time. So judgments about the US economy have to be tentative. 
Now I read his paper which he and a west coast academic are circulating and it is one of those if and if and if documents with models which would not pass muster in any good engineering school, but read the words.  The conclusion, no forecaster ever has a good forecast. Yet then he asks us to believe his recommendation of what will make the future better ... is that not a forecast, and has he not already denied any valid forecast, thus why should we believe him now.

That is the problem with academics, especially economists, the write all too often as if they understand reality and then in the next breath ask us to suspend it.

America's First Socialist: TR

Recall that TR made the following in Osawatomie, Kansas on August 31, 1910:

Nothing is more true than that excess of every kind is followed by reaction; a fact which should be pondered by reformer and reactionary alike. We are face to face with new conceptions of the relations of property to human welfare, chiefly because certain advocates of the rights of property as against the rights of men have been pushing their claims too far. The man who wrongly holds that every human right is secondary to his profit must now give way to the advocate of human welfare, who rightly maintains that every man holds his property subject to the general right of the community to regulate its use to whatever degree the public welfare may require it. 

The New Nationalism, inspired by Croly, a founder of the Progressive The New Republic, assisted TR in this speech.  TR truly believed that property rights were no longer there, they were destroyed by his contention that the community can regulate them, whoever the "community" is, and for TR it was him and his followers. This was a decade before Lenin, before Stalin, this was the basis of the election of 1912.

Now a hundred years later we reflect on the same issues as the case before the Supreme Court in many ways resonates with the philosophy of TR. Just a thought!

The Republican's Left Winger:Pigou

Energy Policy has become a euphemism for back door tax increases. The Pigou Tax is its leader. Tax the poor, let the rich ride. It is the most regressive tax ever and it make cap and trade look tame. Cap and Trade is a Democrat creation, typical, a Rube Goldberg Government controlled means to reduce gas consumption. Pigou is pure taxation in its intent and execution, tax the life out of it.

But as I have indicated before, the tax takes money from the open economy and places it in the hands of Government, read waste. That is the major concern. Taxing something out of existence does work, painfully, and at times usefully, look at smoking. But it destroys individual wealth at the benefit to politicians. They redistribute. But also gasoline consumption is highly inelastic. Even more so for those on the low end of the economic spectrum.

But the left wingers always see Government as the proper beneficiary of peoples hard work As is stated in Barrons:

Harvard University economist Greg Mankiw, currently an advisor to GOP presidential hopeful Mitt Romney, has long been an advocate of a $1-per-gallon gas-tax hike phased in over 10 years (Romney won't countenance the tax). Absent the tax, politicians resort to crazy, Obama-like schemes to achieve the same end of reducing our dependence on foreign oil supplies.

Yes the same Republican that brought you  health care by law in Massachusetts has an advisor bringing you not cap and trade but a simple $1.00 a gallon INCREASE in your transportation, and just where does that $1.00 go, to the coffers of the same folks in DC that caused the mess. This is a solution? So now where is the difference in these candidates? Harvard Law, mandated health care, taxing the poor for energy .... ? They are starting to look an awful lot alike.

The key problem is defining the issue and then seeking a solution. An economics based solution is but one of many, and that usually entails a tax. On the other hand if the problem is using too much foreign oil, then there are two technical solutions; get more energy from the US itself and/or improve efficiency. These are engineering solutions. Having the Government choose winners or losers in this domain is insane as we again see with the current Administration. However using the heavy hand of economic solutions, mandated taxes, is based upon belief and not facts. The Chinese leadership is dominated by engineers, almost to the extent of banning economists. Perhaps they know something we do not. And oh yes, they have no lawyers.

Friday, March 23, 2012

Community Colleges

Science has an interesting Editorial on Community Colleges. Having just attended one, I retook Organic Chemistry 50 years later, I thought my comments might have some weight.

The author states:

In the 2009 American graduation initiative, President Obama enthusiastically highlighted the importance of community colleges—publicly funded 2-year institutions—for meeting the projected growth in jobs requiring a college degree. Increasing the number of college graduates earning science- and math-related degrees depends on these institutions increasing workforce preparation through science, technology, engineering, and mathematics (STEM) education. Community colleges are accessible, affordable, diverse, and flexible, and thus well positioned to meet this need. However, the current demand for courses far exceeds capacity, thereby calling for more government, business, and local resources to support these institutions.

and she then continues:

 Community colleges can play a pivotal role in preparing under-represented students for STEM careers. People of color will make up 45% of the working-age population in the United States by 2030, up from 18% in 1980. According to the U.S. National Academies, they “embody a vastly underused resource and a lost opportunity for meeting our nation's technology needs.” Community colleges currently enroll more than 50% of undergraduate Hispanic students and about 45% of African American and Asian undergraduates. Among those currently holding a baccalaureate or master's degree in science or engineering, 55% of Hispanics and 50% of African Americans attended a community college. For immigrants pursuing the American dream, community colleges are a vital resource. They provide English language instruction, citizenship preparation, job skills, and assistance in navigating American bureaucracy. 

 My observations are somewhat in line but with some variance. I speak of a New Jersey CC and one in a somewhat upscale county. The students were a real mix, about 50% female, about 25% minority, Asian and Hispanic, and many returning to college or seeking a low cost path to their last two years. Thus this was an alternative path and a valuable one. It allowed them to attend college near their residences at a fraction of what it would cost.

The teaching was good, albeit at a High School level, the instructor always "warning" students, and yet he was competent and engaged. Yet he lacked what one would find at a first class university, namely engagement with the students. But he was not at a first class university, yet the material paralleled the MIT class material. Thus basically the student would have the book exposures. The Labs were twenty years old or older, the equipment was quite aged, computers ran Windows 95 in the Lab, and the techniques were also at best High School. Yet the resources were limited.

The students were for the most part intelligent, motivated, accomplished. Yet they lacked the vision that would be necessary. It was not their problem, the school did not provide it. What was missing was the nexus with what a professional does. At MIT a Freshman can do research with a top class researcher. At CC there is no such opportunity. Instructors are competent but they just teach, and try to seek other income as possible. The mindset of what real research is one cannot find.

The students learn technique not technology, and especially no science. Science is the art of asking questions having the expertise to frame the answers. The CC provides technique, and that is the shame. It clearly is a step above High School, but it is run as a High School. I do not blame them, yet the opportunity is there to expand the plane to provide the insight, namely seek stronger industry ties, seek out retired researchers and academics as adjunct advisers, and open the doors to those who are accomplished. The Administration of the CC is more politically oriented than academically, that to me is the challenge. The students are fertile ground, it should not remain fallow.

Cancer: An Evolving Puzzle

Several recent papers have been published on the details of cancer genetics which make the understanding a continuous process of complexity. Let me first provide a brief précis of how we have progressed to this point:

1. The clone. It has been asserted that almost all cancers begin with a single aberrant cell, the clonal source. From this one cell we have generate everything else. One single cell then replicates in an uncontrolled manner.

2. The Vogelstein Paradigm: The Vogelstein Paradigm (VP) states that the clone is created in some predictable sequence of gene changes and that these changes can be detected and perhaps blocked.

3. The genetic profile: This concept uses the wealth, also excess, of gene mutation data available from microarray analysis to determine “profiles” for various cancers attempting to gain prognostic information as well as “individual” profiling for treatment. In many ways the micro array tool provides “too much data”, akin to the comment in Amadeus when the Emperor was asked about Mozart’s music, and he remarked “too many notes”. Namely the wealth of data is essential but the ability of the human processor is not quite up to it yet.

4. The pathway model: In this case we use pathways as a means to understand what is going wrong in a cell by cell basis. Then we try to block aberrant pathways to have the tumor no longer function as it has to that point. We have argued that this approach has a strong core, namely a model which can be verified and improved, but at the same time it lacks two major factors; (i) is does not deal with intercellular communications well enough, (ii) it does not deal with the issues of what causes the loss of gene activity and homeostasis well enough.

Now there have been several papers in NEJM discussing results on several cancers, kidney and AML, acute myeloid leukemia. Combined they tell and interesting tale. I have already commented on the kidney paper by Gerlinger et al but will add to it in this analysis.

As Gerlinger et al state:

Multiregion genetic analysis of four consecutive tumors provided evidence of intratumor heterogeneity in every tumor, with spatially separated heterogeneous somatic mutations and chromosomal imbalances leading to phenotypic intratumor diversity (activating mutation in MTOR) and uniformity (loss-of-function mutation in SETD2 and PTEN). Of all somatic mutations found on multiregion sequencing, 63 to 69% were heterogeneous and thus not detectable in every sequenced region. Heterogeneous patterns of allelic imbalance were found in all tumors, and ploidy heterogeneity was found in two tumors. Therefore, we found that a single tumor-biopsy specimen reveals a minority of genetic aberrations (including mutations, allelic imbalance, and ploidy) that are present in an entire tumor.

Thus with this study we see significant genetic variability. The sequencing of genetic changes and the expectation of clonal consistency seems to be at variance.

In contrast, to justify the clonal progression, as Walter etal state regarding AML:

A unique aspect of the biology of leukemia is that hematopoietic cells freely mix and recirculate between the peripheral blood and the bone marrow. Clones that persist and grow over time must retain the capacity for self-renewal. Mutations in new clones must confer a growth advantage for them to successfully compete with ancestral clones. The result is that these secondary-AML samples are not monoclonal but are instead a mosaic of several genomes with unique sets of mutations; this mosaic is shaped by the acquisition of serial mutations and clonal diversification. Similarly, recent analysis of de novo AML samples with the use of whole-genome sequencing showed that relapse after chemotherapy is associated with clonal evolution and acquisition of new mutations. Analysis of individual cancer cells may reveal additional layers of genetic complexity. Recent studies of B-cell acute lymphoblastic leukemia have shown that serial acquisition of cytogenetic abnormalities in that disease most often occurs through a branching hierarchy and only rarely follows a simple linear path…. Our study has several clinical implications. First, the distinction between the myelodysplastic syndromes and secondary AML currently relies on manual enumeration of bone marrow myeloblasts, a standard that is subject to interobserver bias but nonetheless drives major decisions about treatment for patients with small differences in myeloblast counts. Ultimately, identifying the patterns of pathogenic mutations and their clonality in bone marrow samples from patients with myelodysplastic syndromes should lead to greater diagnostic certainty and improved prognostic algorithms.

Neither studies presented intracellular pathways models which could be verified as state machines leading to malignant processes nor did they provide any basis for the genetic variations observed. These two factors will be essential in a better understanding of these diseases. However we see strong hematopoietic clonality and non-hematopoietic non-clonality.

The question one may ask is: does the cancer cells as they progress in a metastatic manner do so in a random ever changing manner unconnected from one another or is there some rational basis for the changes in a manner in which the cancer has become an alter-organism in the human host? Is cancer a “slime mold” atop the human?

ACA, Medicare, and the Stupidity of Government

It is always useful to see the provision of Government controlled health care through one's own lens. Now I am one of the few who try not to get sick, and to that point I watch diet and exercise especially watching blood glucose. To wit, I record each day for the past ten years fasting and post prandial glucose, weight, food intake, etc. Ten years of daily data, never a miss, truly. It is plotted, managed, watched, just to be certain we keep from getting Type 2 Diabetes. You see I am my own petri dish.

CMS stated to me in their correspondence:

A claim for blood glucose test strips was filed with NHIC, Corp. (NHIC) and an initial determination was performed on January 7, 2011. The clEiim was found unfavorable because similar items were already provided...The reconsideration case file included a Reconsideration Request Form,  re-determination Request Form, Medicare remittance, physician's order, delivery ticket, and clinical

Our Medical Review Panel, consisting of a nurse and a physician, has reviewed the submitted
documentation and decided that payment cannot be allowed for blood glucose test strips....

In addition, there was no progress notes submitted for review current to the date of service. The one submitted establish progress note is after the date of sen/ice in review and cannot be used ... Medicare, the patient's medical record must contain sufficient documentation of the patient's medical condition to substantiate the necessity for the type and quantity of items ordered and for the frequency of use or replacement (if applicable). The information should include the patient's diagnosis and other pertinent information including,

When I turned 65 the Government took over control of my glucose monitoring. I could not buy the tabs anymore, the Government, some physician and nurse, yes some unknown nurse, said my 10 years of daily data were not proof that prevention works. I even sent them my book on Obesity and Type 2 Diabetes! For CMS, it appears, I must gain 50 or more pounds and have HbA1c in excess of 7.0 before they would allow me to buy it myself. Well thank God for Amazon, they sell them and I buy them, and I stay well! And thank you Government, for the ACA, you really created a monster. Happy Second Birthday.

But to the most strange part is the recent NIH News, stating that intervention and prevention works, namely I am doing the right thing.

They NIH state:

Prevention programs that apply interventions tested in the landmark Diabetes Prevention Program (DPP) clinical trial would also improve quality of life for people who would otherwise develop type 2 diabetes. The analysis of costs and outcomes in the DPP and its follow-up study is published in the April 2012 issue of Diabetes Care and online March 22 at 

The DPP showed that lifestyle changes (reduced fat and calories in the diet and increased physical activity) leading to modest weight loss reduced the rate of type 2 diabetes in high-risk adults by 58 percent, compared with placebo. Metformin reduced diabetes by 31 percent. These initial results were published in 2002. As researchers monitored participants for seven more years in the DPP Outcomes Study (DPPOS), they continued to see lower rates of diabetes in the lifestyle and metformin groups compared with placebo ( Lifestyle changes were especially beneficial for people age 60 and older. 

The economic analysis of the DPP/DPPOS found that metformin treatment led to a small savings in health care costs over 10 years, compared with placebo. (At present, metformin, an oral drug used to treat type 2 diabetes, is not approved by the Food and Drug Administration for diabetes prevention.) The lifestyle intervention as applied in the study was cost-effective, or justified by the benefits of diabetes prevention and improved health over 10 years, compared with placebo. 

 So NIH wants prevention but CMS, that is Medicare prohibits prevention, or at least that nurse in Tennessee says so. Remember my fear of some bloated GS 9 denying coverage! Well she is in Tennessee. And she is a contractor!

The stupidity of CMS, the intent should be prevention, not waiting until the disease takes over. I even wanted to pay out of my own pocket, denied. Back to Amazon! Thank you Dr. Bezos! Perhaps Amazon could open a full service Medical practice as well. The of course DC would send in  the thugs and shut it down, perhaps even send in EPA!

Thus with the new ACA, on one hand they deny prevention and on the other hand they praise the need for prevention. In case anyone has noted this happens all the time with big Government. And we are only 2 years into this mess!

Research Publications: A Coming Evolution or Revolution

We have been commenting on the many new outlets for publishing technical results as the Internet expands. The old Academic world of peer reviewed articles may in many ways be creating its own demise for a variety of reasons.

Let me remark on a few. First why have peer reviewed journals:

1. Credibility: These journals were created to ensure credible results by having them reviewed by peers. Namely the reader had some semblance of safety that what was presented was correct. However we know that often that is not the case. Fraud is as bad in professional journals as in many other outlets so that safety net is not really effective.

2. Dissemination: Having a professional journal published and available at a library meant that one could access it. Even some almost 50 years ago I did searches, handed in cards and in a week or so got copies of the articles. I rarely ever sat with the journal itself. Today of course it is rare if I even know where they are. I used to keep my old NEJM, but they are all on line and all I get to look at are the ads. Same with JAMA, Science etc. Where possible I use on line access.

3. Citation and Credit: In the academic world your rank is based often on how many times you have been cited. Go to Google Scholar, look at your publications, add up the citations, and that is a measure of your rank. But not so fast. Today almost 90% of the articles say in IEEE publications are many authored, and I mean many, a dozen is not uncommon. So who did the work. Fifty years ago they were single authors so we knew who did the work.

4. Critique: Journals allowed professionals to write comments and have them published thus serving as an ex post facto means of vetting the results. Today we have instant comments on line, albeit in some cases from unknown individuals whose remarks we have not value of.

Thus the reasons for having journals may be fast disappearing. There are a few recent articles in the Scientist regarding this issue. The first looks at open access papers, journals such as PLOS  PLOS is an online fee to publish not fee to subscribe journal. No paper, peer reviewed and the author pays to publish, a nominal amount. This in many ways is the road to the future.

Second, the other issue is that Academies are making faculty research available on line. Again the Scientist states:

Academic publishers are currently up in arms about the Federal Research Public Access Act (FRPAA)—a bill that has the perfectly reasonable goal of making publicly funded research available to the public that funded it. Tom Allen, president of the American Association of Publishers, described it rather hysterically as “intellectual eminent domain, but without fair compensation.” Why are he and his colleagues so desperate to retain the current business model? By any objective standard, academic publishing is a very strange business indeed. It became established at a time when all publishing was on paper, when duplication and delivery were demanding problems, and when publishers provided an important service to researchers. Now, as the Internet is dramatically changing other forms of publishing, academic journals seem stuck in the 1980s, with results both comical and disastrous.

The extreme costs of journals may force many to seek PLOS type approaches. Moreover providing White Paper works in progress, rather than the full peer review process is also a trend which I have used. If people know you, they can judge, in addition they can understand the work in progress model and at the same time one establishes precedence.

Thus perhaps there will be a transition from the old form journal, through an on line journal and with an real time work in progress approach as well.

Sunday, March 18, 2012

Reinventing History

The recent book extolling the old Bell Labs has had a few reviews on Amazon and I was interested to see what folks said. As I had noted in an analysis of the work, namely that Bell Labs was and is a bit over rated, I noted a review on Amazon which stated:

This led to the greenest of recruits learning at the feet of masters like Bardeen or Shannon. Most importantly, you were free to pursue any idea or research project that you wanted, free to ask anyone for advice, free to be led where the evidence pointed. Of course this extraordinary freedom was made possible by the immense profits generated by the monopolistic AT&T, but the heart of the matter is that Bell's founders recognized the importance of focusing on long-term goals rather than short-term profits. They did this by gathering bright minds under one roof and giving them the freedom to pursue their ideas. And as history makes clear, this policy led not only to fundamental discoveries but to practical inventions greatly benefiting humanity. Perhaps some of today's profitable companies like Google can lift a page from AT&T and channel more of their profits into basic, broadly defined, curiosity-driven research.

Gertner's highly readable book leaves us with a key message. As America struggles to stay competitive in science and technology, Bell Labs still provides the best example of what productive industrial research can accomplish. There are many lessons that modern scientific organizations can learn from it. One interesting lesson arising from the cohabitation of research and manufacturing under the same roof is that it might not be healthy beyond a point to isolate one from the other, a caveat that bears directly on current offshoring policies. It is important to have people involved in all aspects of R&D talking to each other. But the greatest message of all from the story of this remarkable institution is simple and should not be lost in this era of short-term profits, layoffs and declining investment in fundamental research: the best way to generate ideas still is to hire the best minds, put them all in one place and give them the freedom and money to explore, think and innovate. You will be surprised how much long-term benefit you get from that policy. As they say, mighty trees from little acorns grow, and it's imperative to nurture those little seeds. 

Let me examine the facts which the reviewer so nimbly ignores:

1. Google can lift a page from AT&T and channel more of their profits into basic, broadly defined, curiosity-driven research Now as I have shown many times ATT charged its customers for the Labs, and profits had nothing to do with it. Profit was a return on invested capital plant. The more inefficient and costly the plant the more profit. It would help if the reviewer had some basic knowledge of whence he spoke on this point.

 2. greenest of recruits learning at the feet of masters like Bardeen or Shannon. Most importantly, you were free to pursue any idea or research project that you wanted, free to ask anyone for advice, free to be led where the evidence pointed  Shannon worked almost alone and the hallowed halls of Murray Hill were off limits to almost all. As freedom, most staff had projects and were limited strictly.

3. Bell Labs still provides the best example of what productive industrial research can accomplish Bell Labs is an example for no reality that exists. It was an artifact of a monopoly. The productive research leads to products that are economically viable in a competitive domain. That was never a Bell Labs concern. Just look at the black dial telephone.

4. One interesting lesson arising from the cohabitation of research and manufacturing under the same roof is that it might not be healthy beyond a point to isolate one from the other, a caveat that bears directly on current offshoring policies Let me consider the Andover wireless plan as an example. The system engineering was done at Holmdel, and some at Whippany but manufacturing was done at Andover. The Bell Labs staff there supported manufacturing.

5. the best way to generate ideas still is to hire the best minds, put them all in one place and give them the freedom and money to explore, think and innovate The best way to generate new and innovative products, things people will buy and use, it to get the best people but in an open and competitive market where abject terror from competitors drives results, results which generate cash flow, positive cash flow. It also destroys bad ideas and bad management. The suggestion made by the reviewer is one found in a dream world lacking any foundation in reality.

Frankly as I had discussed  based upon my experience the intent was to spend as much as possible because it went into the costs which were paid to the monopoly and in addition to lock up patents to ensure the monopoly. And it was Government sanctioned. There was no Darwinian survival of the fittest as we find in the venture and real world. It was a monopolist political world driven by maintaining control and killing off any potential competition. But I suspect the author of this review has no knowledge of the facts, just some idealistic view of what they think reality should have been.

In contrast, Bob Metcalfe writes in the WSJ an interesting contrast and somewhat balanced. Metcalfe states:

Mr. Gertner, besides celebrating forgotten figures and seminal discoveries, wants us to re-evaluate our contemporary assumption that innovation can only be brought about by "small groups of nimble, profit-seeking entrepreneurs." Think big, the author urges. "To consider what occurred at Bell Labs, to glimpse the inner workings of its invisible and now vanished 'production lines,' is to consider the possibilities of what large human organizations might accomplish."

Mr. Gertner grew up in the glow of Bell Labs headquarters in Murray Hill, N.J., and certainly romanticizes the place. Like many before him, he exaggerates the numerator of Bell Labs while ignoring the denominator. With almost limitless support from its monopoly benefactor, Bell Labs grew to employ more than 25,000 people. So was Bell Labs cost-effective? You will not find the answer in Mr. Gertner's eulogy.

The author also makes the common mistake of confusing invention with innovation. Mr. Gertner credits Bell Labs with inventing the silicon solar cell in the 1950s. If only they had finished the job. Solar energy remains uneconomic today, more than half a century later—invented but not innovated. Likewise, Bell Labs in the 1960s poured its money and reputation into an early form of videoconferencing, PicturePhone, which flopped when deployed.

Brilliantly stated.  They never finished any job I saw them attempt. The solar cell is a great example. They wanted the patents and the rights to keep others out! The idea that one should look at numerator and denominator is critical. There were a few brilliant producers but then again the Bell Labs as the only game in town for those working in telecom sucked up the best talent it could find and in many ways warehoused them so that nothing could be created. It was not until 1982 and the AT&T breakup that the dam broke!

Bob continues:

Mr. Gertner suggests that society would do well to re-create more Bell Labs. But trusting research to corporate monopolies is problematic in two ways. First, their money comes from overcharging customers by using monopoly power. (If you doubt that AT&T was overcharging, ask some old-timers how our mothers urged us to phone home after we arrived safely up at college—"Call, but hang up after letting the phone ring three times"; actually completing the call was too expensive.) Second, a corporate monopoly has little motivation to disrupt a market that it already dominates. AT&T had to be forced, starting in 1968, to let the nascent Internet connect to its telephone network; "Ma Bell" resisted every step of the way. 

 So true! The Internet screw up, the modem, and the list goes on. Bell Labs was in my opinion based upon my experience a bloated machine designed to suck money from rate payers and to block any and all innovation.

The irony of the Metcalfe review is that when one scans through the comments most of those opposing Bob do so based on the assumption Bob is an academic. Bob invented the Ethernet and started and grew 3 Com. Bob is the example of good R&D, not Bell Labs. Those who commented without knowing this just exposed in my opinion based upon my direct experience their gross incompetence in understanding the entrepreneurial world.

But even more chilling is the thread that large centralized R&R, such as Government sponsored R&D is the best way to go. In reality it is the worst. Just look at DoD. For years they had all home brewed designs until the industry outpaced them. The typical cell phone of today is better than any DoD design over the years and at one millionth the cost. It is a shame that so few understand the entrepreneur. It is more of a shame that the often run the country!

More on PSA

The recent NEJM article purporting to show that PSA screening saves lives has all sorts of issues, as do almost all of these. I noted some of this in an earlier posting but let me continue:

They state:

The principal screening test was measurement of the serum PSA level with the use of the Tandem-R/Tandem-E/Access assay (Hybritech). A positive test result, defined as a PSA value of 3.0 ng per milliliter or higher, was an indication for biopsy in most centers. Sextant prostatic biopsies were recommended for all men with positive test results; lateralized sextant biopsies4 were adopted in June 1996. Some exceptions to these procedures have been described previously.

That level of 3.0 is better than most, it is lower and has a higher false alarm rate and also higher detection probability on the ROC.

They continue:

The median screening interval was 4.02 years. A total of 6963 prostate cancers were diagnosed in the screening group (cumulative incidence, 9.6%) and 5396 in the control group (cumulative incidence, 6.0%), with approximately 1000 additional cases of prostate cancer in each study group, as compared with our earlier analysis

Here is a problem if one reads this correctly, namely it was too long a screening period.

Again the question to be asked is what PSA level and what screening interval yields the best if any survival. Then one can check the costs.

The issue is really also one of looking at PSA as a progression over time including % Free as well.

Now a Reuters report has some interesting comments:

Dr. Otis Brawley, chief medical officer of the American Cancer Society, said the European study is actually eight studies in eight countries, and only in Sweden and the Netherlands did PSA testing significantly reduce the risk of death from prostate cancer. "Screening saves lives if you live in the Netherlands and Sweden, but not the other six places," he told Reuters Health in a telephone interview. One factor that may have skewed the Swedish data, he said, is that men who were screened were treated at an academic medical center, while men in the control group who developed cancer were treated elsewhere in the community. That alone might account for the lower mortality rate in the PSA population. In all, there were 299 prostate cancer deaths in the screening group compared to 462 in the control group that was not screened. Brawley said PSA testing is being widely promoted because "there's a huge profit in screening and treatment" for prostate cancer, even though most studies have failed to show that screening saves lives.

Strange in my opinion for ACS to advocate against screening,  as they seem to be saying above.

Type 2 Diabetes or Just the Flu?

In a recent Cell article the senior researcher argues that he has identified that he has a gene for Type 2 Diabetes and after such a discovery he finds that after a year of monitoring he has actually shown signs of Type 2 Diabetes. Then after dieting it goes away. Really?

The details on the subject were:

Monitoring of glucose levels and HbA1c revealed the onset of T2D as diagnosed by the subject’s physician (day 369, Figures 2A and 2C). The subject lacked many known factors associated with diabetes (nonsmoker; BMI = 23.9 and 21.7 on day 0 and day 511, respectively) and glucose levels were  normal for the first part of the study. However, glucose levels elevated shortly after the RSV infection (after day 301) extending for several months (Figure 2D). High levels of glucose were further  confirmed using glycated HbA1c measurements at two time points (days 329, 369) during this period (6.4% and 6.7%, respectively). After a dramatic change in diet, exercise and ingestion of low doses of acetylsalicylic acid a gradual decrease in glucose (to 93 mg/dl at day 602) and HbA1c levels to 4.7% was observed. Insulin resistance was not evident at day 322. The patient was negative for anti-GAD and anti-islet antibodies, and insulin levels correlated well with the fasted and nonfasted states (Figure S2C), consistent with T2D. These results indicate that a genome sequence can be used to estimate disease risk in a healthy individual, and by monitoring traits associated with that disease, disease markers can be detected and the phenotype treated.

Now the patient did not have a high BMI but did have two viral attacks. As is well known obesity effects an immune like inflammatory response, chronically, and a viral attack has an acute response, yet both will effect an increase in blood glucose, often not suppressed by insulin in those with the potential for Type 2 Diabetes.

The problem with this patient is shown in Figure 2D where the blood glucose is measured, in somewhat of a random manner and where HbA1c is also shown. The problem is as follows. HbA1c reflects red cell glucose uptake and red cells last for 90 days and thus to reflect an elevated HbA1c one would expect an elevated level for 90 days, or at least for 45. That is not the case for this patient on the upside or on the down side. Also the glucose spikes as one would expect to find in acute inflammatory diseases or use of steroids and the like. In addition to do this properly one should be measuring fasting blood sugar and two hour post prandial and accounting for such exogenous factors as travel, stress, and excess carb intake. None of this was done.

The author and patient in question was interviewed and he states:

"I was not aware of any type-2 diabetes in my family and had no significant risk factors," said Snyder, "but we learned through genomic sequencing that I have a genetic predisposition to the condition. Therefore, we measured my blood glucose levels and were able to watch them shoot up after a nasty viral infection during the course of the study."

As a result, he was able to immediately modify his diet and exercise to gradually bring his levels back into the normal range and prevent the ongoing tissue damage that would have occurred had the disease gone undiagnosed. 

The question is was this Type 2 Diabetes or the flare seen in those with low insulin control when in an acute inflammatory state. Could one use a steroid to induce this and then watch blood sugar rise equally as well, and perhaps use that as a diagnostic. After all we use a classic glucose tolerance test to measure insulin response.

How does one define Type 2 Diabetes? Is it low insulin response? Or is it HbA1c above say 6.0? Is it the "potential" for the disease or the disease. The problem here in my opinion is that the author and patient in question may have crossed the line by saying if you have a genetic predisposition then you have the disease. A very slippery slope in my opinion.

Saturday, March 17, 2012

The Impact of Full Gene Testing on Health Care Costs

In a recent JAMA article the author attempts to show the potential for genetic analysis on a per patient basis as a means to reduce health care costs.

We have argued that advances in genetic tests and analysis can result in advances in three areas:

1. Determining predispositions and the attempt to mitigate the disease states.

2. Determining the specific abnormality or malignancies and assessing treatment protocols accordingly.

3. The establishment of genetically oriented treatment methodologies.

However we are looking at two extreme situations:

First the understanding of basic genetic causes of disease inherited or set as a predisposition state. For example the heritability of Marfan or Huntington's. Also the predisposition for certain cancers.

Second, genetic changes in somatic cells to assess the state of a malignancy, such as breast cancer or prostate cancer.

The problem is twofold:

First we know some but hardly all genetically inheritable traits. In fact we are just starting to understand them. In a sense we are in year 1 of say a Framingham study for these issues and the time to determine what they are is lengthy.

Second, in the case of cancers, we need to understand the dynamics, and as recently shown in an earlier post from a NEJM article, the complexity of cancer genes from cell to cell is not understood. 

The JAMA article states:

Several steps are needed to realize any potential beneficial effect of genomics on the cost of health care. First, the development of effective clinical decision support is needed so that patients and clinicians use genomic test results appropriately. Such decision support already is available for several tests and should become a US Food and Drug Administration requirement for the introduction of new targeted therapy with a companion diagnostic test. Second, information systems need to be adapted so that genomic information can be stored efficiently and accessed indefinitely. Given its rapidly declining cost, whole-genome sequencing is likely to become the dominant model for germline genetic testing and can provide substantial efficiency assuming that test results can be stored and reliably accessed in the future. Third, professional and patient advocacy organizations need to develop guidelines about how to manage genomic information unrelated to the clinical question of interest, in order to minimize the evaluation of clinically irrelevant genetic variation and wasted health care dollars. Fourth, genomics can only reduce costs if the aggregate cost of testing is lower than the cost of the health care interventions that are used. 

I would argue that there are many steps needed beyond these. First, most physicians lack a true understanding of these issues. For example as I have indicated a urologist may perform a prostate biopsy and find highly disseminate HGPIN and then 9 months later perform a saturation biopsy in anticipation of a malignancy and find none. Why? Surgeons generally do not ask those questions, for them the patient has become a lucky end point. But why? What has genetically reversed what is assumed to be irreversible?

We need to establish large data bases readily accessible by professionals to be worked upon an jointly shared. Leverage of this type is essential. Closed data will result in slow progress, open and shared data is essential.

China and the US Debt

China Daily provides insight into China's current and near term dealings with US Debt.

It states:

China increased its holdings of US Treasury securities by a slight $8 billion to a total of $1.16 trillion in January after cutting the purchase for five consecutive months, according to data released by the US Treasury Department on Friday. But analysts suggested the move doesn't signal a reversal of China's efforts to diversify its foreign exchange holdings and reduce its exposure to dollar assets. China remained the largest foreign creditor of the United States among the overall foreign net buyers of US financial assets in January. But Japan, as the second-largest holder of US Treasuries, is closing in on China after boosting its holdings by $21 billion to $1.08 trillion in January. China had been moving away from US Treasury bonds since July, continuously cutting its holdings by a total of $163 billion by December. By the end of last year, China had reduced its holdings of US debt by $8.2 billion compared with the previous year, the first time it had reduced the amount year-on-year since 2001.

 Now China has over $1 T in US debt which is a substantial sum. The slowing down of their purchases reflects two things. First internal stress within China. Second concern over the US debt situation in general.

This will be a careful issue to watch in the next six months as we approach the election.

Happy Saint Patrick's Day

Come and tell me Sean O'Farrell tell me why you hurry so
Hush me buachaill hush and listen and his cheeks were all a glow
I bear orders from the captain get you ready quick and soon
For the pikes must be together by the rising of the moon

By the rising of the moon, by the rising of the moon
For the pikes must be together by the rising of the moon

Come now tell me Sean O'Farrell where the gath'rin is to be
At the old spot by the river right well known to you and me
One more word for signal token whistle out the marchin' tune
With your pike upon your shoulder by the rising of the moon

By the rising of the moon, by the rising of the moon
With your pike upon your shoulder by the rising of the moon

Out from many a mud wall cabin eyes were watching through the night
Many a manly heart was throbbing for the blessed warning light
Murmurs rang along the valleys like the banshees lonely croon
And a thousand blades were flashing by the rising of the moon

By the rising of the moon, by the rising of the moon
And a thousand blades were flashing by the rising of the moon

There beside that singing river that dark mass of men was seen
For above their shining weapons hung their own beloved green
Death to every foe and traitor! Forward strike the marching tune
And hurrah, me boys, for freedom, 'tis the rising of the moon

'Tis the rising of the moon, 'tis the rising of the moon
And hurrah, me boys, for freedom, 'tis the rising of the moon

Well they fought for poor old Ireland
And for bitter was their fate
Oh what glorious pride and sorrow fills the name of ’98
Yes thank god instill our beating hearts in manhoods burning loom
Who would follow in their footsteps at the rising of the moon

At the rising of the moon, at the rising of the moon
Who would follow in their footsteps at the rising of the moon

Wednesday, March 14, 2012

PSA Debate Continues

We all remember the discussion that the Government declared PSA tests as not effective. It was the same group which wanted to do away with mammograms. Most likely the same group which wants to do away with health care for anyone over 65, the current team in Washington that is.

Well NEJM just reported a different tale.

Here it is:

Namely it does save lives! Eureka, that is what we have been saying for the past four years, and now we have the data in spades.

Here is the test:

The principal screening test was measurement of the serum PSA level with the use of the Tandem-R/Tandem-E/Access assay (Hybritech). A positive test result, defined as a PSA value of 3.0 ng per milliliter or higher, was an indication for biopsy in most centers. Sextant prostatic biopsies were recommended for all men with positive test results; lateralized sextant biopsies were adopted in June 1996. Some exceptions to these procedures have been described previously.

 Yes a PSA cutoff of 3.0, not 4.0, and sextant biopsies. Today we would use 14 cores at a minimum, and saturation in many cases, say 24 cores, although it increases morbidity to a degree.

The end point was:

The primary end point of the trial was prostate-cancer mortality. We evaluated deaths among men in both the screening group and the control group in whom prostate cancer was diagnosed (including cases that were first diagnosed at autopsy), regardless of the official cause of death, as described previously. Data on overall mortality were collected by linkage to the national registries. Each trial center followed the common core protocol and provided key data to the joint independent data center every 6 months. The independent data monitoring committee received updates every 6 months according to a predefined monitoring and evaluation plan.

They conclude:

The controversy regarding screening for prostate cancer has been renewed by the publication of the draft report of the U.S. Preventive Services Task Force, which after a literature-based analysis of benefits and harms recommended against the use of PSA testing in asymptomatic men. The report has been discussed in several Perspective articles in the Journal. Clearly, the issue can be resolved only on the basis of evidence that considers both the advantages and disadvantages of screening, data that are not available at this time. Our study shows that the absolute effect of screening on the risk of death from prostate cancer increased in the intention-to-screen analysis from 0.71 to 1.07 deaths per 1000 men at a median of 11 years of follow-up, as compared with the initial results with a shorter follow-up period.

Clearly there is a benefit but clearly as I have previously stated they did not ask the correct question, which is:

"What should the PSA level be by age, race etc so as to have a decrease in survivability by some factor x?"

Notwithstanding, there is a clear benefit.  The details of the benefit are yet to be determined but the conclusion is that the USPSTF conclusion is in error. The "Death Panel"'s conclusion is just that. And we have just begun!

Tuesday, March 13, 2012

China to Raise Prices on Rare Earths

The rare earths are major ingredients in our high tech society and China is the worlds major supplier, mainly because the US decided to shut down its production for environmental reasons. Now China is going to charge for their environmental costs as reported in China Daily:

The era of cheap rare earth supplies from China is doomed to end as the country tightens control over the precious resources out of environmental concerns, Chinese lawmakers said on the sidelines of the parliamentary session. China has been supplying enormous quantities of rare earth products to the world. However, environmental costs were not included in the pricing of the commodities, said Liao Jinqiu, an economist at Jiangxi University of Finance and Economics. "The exploitation of rare earths should be further integrated, and a rare earth industry chain must be forged so as to ease the environmental pressure created by excessive extraction," said Liao, also a deputy to the National People's Congress. China is believed to have abundant reserves of rare earth metals, a group of 17 elements that are vital for manufacturing an array of high-tech products, including cell phones, wind turbines, electric car batteries and missiles.  China now produces more than 90 percent of the world's rare earth products, but its reserves only account for about one-third of the world's total.

 China is being both prudent and controlling in this action. However the use of rare earths is increasing in our high tech society and total costs should be reflected but at the same time this may open the window for the US to reconsider the fact that we have an equal amount of rare earth reserves as does China.

In many ways the rare earth issue is a microcosm of the oil issue, we have both, but we refuse to prudently use them and place the burden on others, yet at an ever increasing cost.

Monday, March 12, 2012

More Details on Employment

Let's start with the two publicly supported elements; Government and Health and Education. State and Local Govt have declined, with the blip back in 2010 due to the Census and H&E continues to explode. This frankly is a bad omen, these are not "productive" elements in the sense that they are paid from true productive elements.

The above are the actual productive worker force and we see a true depression across the boar with recovery in mining and Durable Manufacturing.
On a per Pop basis we show the above which demonstrates the reduction. Namely we normalize all jobs by the total population and this shows growth only in H&E. That is an upsetting trend.

We show the percents by category from April 2005 to the present by sector. Government, H&E and professional show increase. All others declined.

The above demonstrates the actual percent changes. Mining is a small sector so we can disregard it. In summary things are really getting worse.

Saturday, March 10, 2012

MIT and Numbers

In a recent post by the MIT News group the author quotes a speaker at an MIT conference as follows:

“There is a huge disenfranchisement going on, due to our voting laws,” .... said. “And I think to fight that we have to build a conversation with Latino leaders, because we’re both being disenfranchised.” .... students, he noted, have found in studies that in Los Angeles, Miami and New York, “at least 30 percent of the taxpaying adult voting-age population can’t vote because of immigrant status. If you add in ex-felons who can’t vote … you’re at nearly 50 percent of the [urban] population.”

Now if I do a back of the envelope calculation what is being said is as follows:

1. Take New York City...

2. The 30% of the voting age population is an illegal alien

3. 20% of the voting population is a convicted felon.

Yikes, that means that every other person is either a convicted felon or illegal! I have lived here for 70 years, yes I know of a few convicted felons, a few, and I grew up on Staten Island, home to the Genovese family, nice folks but some convicted felons amongst them, and my father and grandfather were police officers, but 20%, that means in an 8 million population we have with us 1.6 million felons! It just does not add up. We just do not have that many prisons. As for illegals, that would be 2.4 million, and there I have another problem. 200,000, maybe 500,000 but not 2.4 million! Where do these numbers come from? And this is MIT, and an MIT Press Release. Would someone at MIT check the facts?

Friday, March 9, 2012

Employment: Good News and Bad

The ghost of Romer still haunts the halls of power. The above is the current unemployment, 8.3%, as announced, and her predictions from January 11, 2009. As we have argued for more than three years now our friendly economist seems as if she could not hit the side of a barn with her predictions. But back to California.

The above shows the level of variance which is clearly growing.

This details the growing variance in some detail. Now to the overall stats. We use the SA non-farm stats.
The good news seems to be an increase in percent employed albeit at best a small amount and at worst an anomaly. Secondly the unemployment using the 2006 base has dropped below 12% for the first time. This should be the true measure.
Employment and population seem now to be in lock step. This curve above shows the loss of the 2008 recession but it also shows no recovery.

Unemployed seems to be decreasing bu the concern is still the workforce as a percent of population, a slight dip again.

Wednesday, March 7, 2012

The Challenge of Cancer Genetics

In the current NEJM there is an interesting article on the heterogeneous nature of cancer cells. Namely in examining renal carcinoma the authors clearly demonstrate the genetic complexity of cancer cells, namely that the cells express a wide variation in genetic changes, the focus being on mTOR.

The authors state:

Multiregion genetic analysis of four consecutive tumors provided evidence of intratumor heterogeneity in every tumor, with spatially separated heterogeneous geneous somatic mutations and chromosomal imbalances leading to phenotypic intratumor diversity (activating mutation in MTOR) and uniformity (loss-of-function mutation in SETD2 and PTEN). Of all somatic mutations found on multiregion  sequencing, 63 to 69% were heterogeneous and thus not detectable in every sequenced region.  Heterogeneous patterns of allelic imbalance were found in all tumors, and ploidy heterogeneity was found in two tumors. Therefore, we found that a single tumor-biopsy specimen reveals a minority of genetic aberrations (including mutations, allelic imbalance, and ploidy) that are present in an entire tumor.

This is a very powerful conclusion. Namely just sampling a single cell is inadequate. Moreover it will become essential to have a dynamic system model which can project the nature of the changes, namely what comes first and then what causes the progression.

The optimism of finding genetic markers which can be used for treatment are made more complex by this somewhat obvious finding. It is obvious from the models of cancer as a complex system, but not obvious from what was known before. That challenge will be to establish models for explaining these changes. The challenge will also be to explain what role the cancer stem cell plays here as well.

Monday, March 5, 2012

A Very Interesting Experiment

In the late 1960s I taught 6.02 at MIT which was the core electronics course for incoming EE students. I had some 350 students and many sections which were handled by Instructors, some were even Associate Profs. So we had a high power group. Now each lecture was planned to the micro second, better than any Shakespeare play.

Now MIT is offering 6.002x, an on line version of this course almost 50 years later! So I enrolled. What the heck, can I still do this stuff, it is a bit of an FCC exam as well. But what is more interesting is the questions from the students! I am amazed, the flow of misunderstanding from across the world! Since it is free I would suggest that one enroll if for no other reason than reading the real time commentary.

Now for me some comments:

1. The lectures are a bit shaky, not fully structured as we did those 50 years ago, but I guess things change.

2. The lab is cumbersome at best. It finally works but not ready for prime time.

3. The problem sets are trivial, but unless you really pay attention you get killed in sloppy addition and subtraction. Here 50 years does make a difference, we are so dependent upon spread sheets.

4. The text is in my view overly verbose and lacks motivation, but that is style.

It will be interesting to follow along. Great idea any way!