Did Anyone Ever Take Geography?

New Guinea was a major front during WW II. MacArthur landed on the northern side, I recalled from the exploits of my father's Destroyer records at the time. Today New Guinea is split down the middle. The West is Indonesia and the East is Papua. The interior is impenetrable. Abot 2 to 3 meters from the waterline one can no longer see the fingers on an out stretched hand, the growth of vegetation is so great.

Yet in all the news channels they indicate Papua as the West! Just check Google maps, please, someone! I am totally amazed at the general incompetence of the news media. Really guys! It is just Grammar School geography!

This is reflective of the general competence or lack thereof of both our media and our education system. I had this in the 5th grade with Sister Rosita. As did the Public School colleagues.

Why not try this one out on the Candidates, even the former Secretary of State!

Reinterpreting Pearl Harbor

I have to admit that being alive during WW II and with a father in the Pacific the position taken by Japan still rings loudly. Thus in reading Abe's somewhat self serving piece in The Syndicate I was a bit taken aback.

For example he states:

With the Manchurian Incident, followed by withdrawal from the League of Nations, Japan gradually transformed itself into a challenger to the new global order that the international community sought to establish after such tremendous sacrifices. Japan took the wrong course and advanced along the road to war.  

The Manchurian Incident was a massive invasion and occupation by Japan of China's territory resulting in the massacre of thousands in Nanking. 

Then he states:

More than one hundred years ago, vast colonies, possessed mainly by the Western powers, stretched across the world. With their overwhelming supremacy in technology, waves of Western colonial forces surged toward Asia in the nineteenth century. There is no doubt that the resulting sense of crisis drove Japan to pursue modernization. Japan established a constitutional government earlier than any other country in Asia, and preserved its independence throughout. The Japan-Russia War gave encouragement to many people under colonial rule from Asia to Africa. 

But was that an excuse for the assault on Pearl Harbor, for the Death Marches, for the abject slaughter?

Abe, in my opinion, writes a classic "on the one hand and on the other hand" piece. Japan had defeated Russia. Japan then occupied land mass after land mass, gathering up natural resources it needed in its attempt to defeat the United States.

Abe continues:

We will engrave in our hearts the past, when Japan attempted to break the deadlock it faced with force. Upon this reflection, Japan will continue to uphold firmly the principle that any disputes must be settled peacefully and diplomatically, based on respect for the rule of law, and to reach out to other countries in the world to do the same. As the only country to have ever suffered the devastation of atomic bombings during war, Japan will fulfill its responsibility within the international community, aiming at the non-proliferation and ultimate abolition of nuclear weapons. 

I recall the writing from my father's shipmate which recorded today, as they prepared in the Aleutians for an invasion of Japan and sure death, that the men who had survived Japanese attack after Japanese attack and seen hundreds of their shipmates dismembered by Japanese shells, just sit in tears on the deck of their Destroyer, knowing that the end of the horror was near. Regrettably it was Hiroshima, and Nagasaki, but the end was quick, and the lives lost significantly attenuated.

Perhaps Japan may someday come to the point of recognizing that it really was not on the one hand and on the other, but that they made a terrible error. Yet it is this understanding that should be understood by all, for such errors, as can be self justified, can be repeated. The consequences of nuclear weapons are a horror mankind must avoid, and that means an acceptance of consequences, not an attempt to justify, no matter how slightly.

Interesting Work on Mabs

Monoclonal antibodies are a class of antibodies which on the one hand reflect a response to a specific antigen and on the other hand can activate the immune system to respond to the cells presenting to that antigen and have them eliminated if possible.

Back in the mid-1960s when I first came across the clinical use of antibodies what was frequently employed was gamma globulin, a massive amount of mixed IgG, immunoglobulin G, from many people and it was somewhat tried as another treatment for a variety of disorders including some cases of mumps. However the specificity of IgGs and the other immunoglobulins had not yet been ascertained.

As this identification progressed it became apparent that specificity of the antibodies could perhaps be a tool to attack certain disorders, including cancers. This then led to many examinations of ways to produce large volumes of specific antibodies. The result was the development of monoclonal antibodies. Simply this is the chimeric combination of antibodies developed to attack a specific target and a vehicle cell that had immortality to bind this product to so it became a small factory for production. From this came, after a significant amount of effort, the monoclonal antibody, and in turn the new therapeutics ending in –mab.

The work of Marks, The Lock and Key of Medicine, is an effort to tell this story. It starts with some of the early researchers in the UK who persevered to get some of the initial samples available and the ever changing dynamic of researchers and clinicians. As with so many efforts of this type, there is an ever challenging set of steps that the researchers and the clinicians go through, some winning and some losing. The early days of the late 1960s, when in the practice of medicine little was truly understood but the tools for the researchers were coming on quickly.

The author takes the reader through the many individuals and the many crises and victories as they progressed. The book focuses on the many individuals and their steps in developing MABs and the ultimate commercialization of them and their application to human therapeutics.

As we progress we have seen basically four classes of Mabs. They are: murine or mouse versions with therapeutics ending in –omab, chimeric murine and human Mabs with the ending –ximab, the humanized Mabs ending in –zumab, and finally all human Mabs ending in –umab. Mabs are now one of the arms in treating a variety of diseases from cancer to arthritis and colitis. At the same time they have become “big pharma” and the author takes the reader through this process in some detail.

Overall, the book and an excellent articulation of the people, the conflicts, the achievement, and the institutional progress. From that perspective is an excellent contribution.

On the other side it would have been more helpful to have provided some simpler introductions to Mabs and the immune system. For a well-educated reader this is an interesting tale of scientific and clinical development. It does lack a feeling of personal involvement. The description of the individuals is in my opinion quite arm’s length and unlike other works of similar genre this is a discussion of facts and events and dates.

What I especially missed was the recent explosion of applications. For example in advanced melanoma there is the use of Mabs and pathway control therapeutics such as BRAF inhibitors and MEK inhibitors. This raises the issue of how does one see a blending of these two or are they not so complementary. On the other hand there are certain cancers such a prostate cancer which may be so complex and changing at such a rapid rate that Mabs would just not work. It would have been useful for the author to have contributed some substance to the debate.

Overall, again, this is an excellent book albeit for possibly a smaller community of engaged readers.

More on PCORI

PCORI has now exceeded $1 B in funding as a result of the ACA. One should examine the projects. Its head recently stated in an email:

We've just marked a major milestone here at PCORI - topping $1 billion in funding approved for research projects and other initiatives that will help patients and those who care for them make better-informed healthcare choices. 

 

We're proud of these investments, all of which support our mandate to advance comparative clinical effectiveness research (CER), studies of what works best for whom under which circumstances. All of our awards are approved by our Board of Governors and reflect ongoing input from patients, family caregivers, clinicians, and other stakeholders from across the healthcare community. All directly fulfill our mission to both improve the quality and relevance of evidence available to clinical decision makers and the methods used to see that this evidence is reliable. And all ensure that we live up to our name by supporting research addressing the questions and concerns of patients and other stakeholders.Two-thirds of our awards to date, nearly $680 million, support studies of the effectiveness of two or more approaches to care focusing on outcomes that matter to patients

 

However when one tries to examine what may actually have been accomplished it seems in my opinion to be fairly empty.  Needless to say they will continue to burn $500 M or more each year, a sum which frankly could be much better spent elsewhere.

Calories are Calories?

In a recent NIH study there was an attempt to demonstrate that fat calories were more effective in adding body fact than carbohydrate calories.

The procedure was as follows:

The researchers studied 19 non-diabetic men and women with obesity in the Metabolic Clinical Research Unit at the NIH ..... Participants stayed in the unit 24 hours per day for two extended visits, eating the same food and doing the same activities. For the first five days of each visit they ate a baseline balanced diet. Then for six days, they were fed diets containing 30 percent fewer calories, achieved by cutting either only total carbs or total fat from the baseline diet, while eating the same amount of protein. They switched diets during the second visit. 

They conclude:

“Our data tell us that when it comes to body fat loss, not all diet calories are exactly equal,” .....“But the real world is more complicated than a research lab, and if you have obesity and want to lose weight, it may be more important to consider which type of diet you’ll be most likely to stick to over time.”  

Now there are several issues here:

1. The sample is much too small

2. The duration time is much too short

3. The switching is in the middle of a metabolic change which takes possibly weeks, not hours to adapt.

4. The key issue is the definition of a calorie. Namely if we measure 3500 Kcal = 1 pound, then how do we differentiate at all?

This is not in my opinion a study of any value for the above and many other reasons.

Ginkgo and Hiroshima

Seventy years ago Hiroshima was bombed. Some nearly 20KT yield uranium device fell some 30,000 feet and exploded several thousand feet above the city. The result was a massive ring of destruction. Surviving that was a few century old Ginkgo trees, tress which themselves had survived some 250 million years[1]. As a symbol of survival the Ginkgo has great standing. As we look backwards and then again look forward one thinks of these Ginkgos.

Some twenty five years ago I took a handful of Ginkgo nuts from the trees at the New York Botanical Garden. I placed them in my pocket, stink and all, and let them sit in my refrigerator to cold stratify over the winter and then planted them in my seed beds. Up they came and now twenty five years later I have one female tree filled with Ginkgo nuts. The legacy of 250 million years goes on. The hardy tree may survive us all, in some way shape or form, since its seeds will be transplanted elsewhere, to grow again.

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[1] http://www.bbc.com/news/uk-england-manchester-29920359 and http://kwanten.home.xs4all.nl/hiroshima.htm