Book Review: Dr. Folkman’s War

Saturday, May 18, 2002


Read “Dr. Folkman’s War: Angiogenesis and the Struggle to Defeat Cancer” by Robert Cooke. Dr. Judah Folkman while working in a navy lab in 1961 noticed that strangely, tumors do not grow unless they manage to recruit blood capillaries to provide them with a lot of blood to nourish their growth. After a period of 40 years this intriguing observation has blossomed into a multibillion-dollar industry in the biomedical arena racing towards possible cure for cancer. Since Folkman happened to be Chief of Pediatrics Surgery in the Boston Children’s Hospital (rather than a cancer researcher), the established cancer research fraternity refused to seriously look at his proposals/research/results and consistently scoffed him off until the 90’s..!

As you may know, the standard treatment for cancer is removing the tumor by surgery and/or killing the cancerous cells either by chemotherapy or by radiation. So the establishment has been all along focused on fine-tuning the Maximum Tolerable Dosage (MTD) of toxins or radiation that can be administered to kill the cancer cells while avoiding the killing of patient in the process (since a large number of non-cancerous cells also get killed in this shotgun approach). The Angiogenesis approach is to simply cutoff the needed blood supply to the cancer cells so that they can never grow beyond microscopic levels. People with microscopic cancerous tumors can live a long and peaceful life. Since this type of cancer management does not affect any normal cells, it is has very little or no side effect..!

Another well-known problem in cancer treatment is the appearance of secondary tumors once the primary tumor is surgically removed. As long as the primary tumor is in the system you don’t see too many secondaries in most of the patients. The traditional treatment is just to hope that the intervention is timely and pray that the cancer has not spread to other parts of the body yet. But in many cases once the primary tumor is removed, a whole slew of secondaries appear all over the body. Folkman’s team hypothesized that the primary tumor, in addition to releasing a chemical to invite and recruit blood capillaries, must also be releasing some other factor that keeps the secondaries at bay and limits their growth. Again cancer establishment threw out this idea asking what the hell does a pediatric surgeon know about the pathology of cancer cells that oncologists don’t already know. One of the main problems Folkman faced was that these factors are so small in quantity that no one could quickly separate them to demonstrate their effect. But in the last few years they have. Book details all the trails and tribulations Folkman went through to get funding for his research, establishment of his labs, all the fights he had to put up to fend of bad publicity, etc. What is nice is that it is not a biography of Folkman but a chronicle of the development of Angiogenesis as an accepted, recognized field of study solely developed and pushed into the lime light by Folkman.

He is portrayed as a very affable researcher, grooming his research associates well, constantly giving them credit for what they have contributed, free spirited researcher deeply committed to his work, willing to talk to anyone who is interested, etc. This seems to be quite true since every report/documentary I have seen mentions these aspects of his nature. The factors his team has isolated called angiostatin and endostatin are in clinical trials at this point in time. There are several more in the labs now since the U.S. Govt., NSF, American Cancer Society, etc. recognize this approach’s potential in treating, managing cancer. Pretty interesting. You can see a PBS documentary on this topic at http://www.pbs.org/wgbh/nova/cancer/program.html

While working on these issues, he has developed a polymer that is porous enough to releases chemicals stored on one side to the other at extremely slow rates. Since neither he nor Harvard wanted to patent anything (as they felt it is against the spirit of academic research), the idea was put into public domain and has been used very effectively in the Norplant contraceptive..! (If you don’t know about Norplant, read up on the web. It is a very neat application of this polymer.) BTW, Harvard no longer has that “not-patenting-anything-ever” policy. How sad. :-(

Updates on November 26, 2011
Dr. Folkaman passed away in 2008. Avastin, which is a drug developed based on Angiogenesis theory received its first approval in 2004 for combination use with standard chemotherapy for metastatic colon cancer. While at one point it was also approved for breast cancer by the FDA, the approval was revoked on 18 November 2011.

Book Review: Complexity

Saturday June 8, 2002

I bought this book called Complexity: the Emerging Science At the Edge of Order and Chaos by M. Mitchell Waldrop off the shelf of a book store without having heard about it before. It turned out to be a very good read. The field of complexity studies how individual entities like a cell or a stock or a human being join other such entities and with each entity functioning independently, still manage to evolve as a coherent whole system (like a biological being, national/international level economy, societies and civilizations respectively). Despite the second law of thermodynamics, how do these systems evolve into a more coherent order is indeed an intriguing question. This book discusses the research efforts that are ongoing in this field and the formation of The Santa Fe Institute in New Mexico to study such phenomenons. Naturally understanding the emergence of complex systems from smaller independent entities will have wide implications anywhere from population control, stock markets to formation of stars and galaxies, etc. The way the book is written, neatly mixing the details about the formation of the institute, research efforts that are ongoing, all the interesting characters that are involved in the process, the prose itself, etc. makes it delightful. Each chapter starting from a new point (instead of continuing the discussion from where the previous chapter ended) delineating a different thread relevant to the discussion and eventually all the threads crossing each other's path via the institute, was also quite nice.

Wide ranges of organizations like Citibank, NSF, DoE, etc. are funding the institute. Citibank for example, is interested in understanding the economies of different smaller countries. Apparently a whole lot of their investments based on old, traditional models of economic theory (that denounces "Increasing returns" type ideas and insists that supply will always be equal to demand) went bust and so they are trying to see if this complexity model can give them a better, more realistic projection. This idea of forming an institute that will work across fields in itself is quite interesting. Invariably research efforts funded by govt. funding agencies and university departments are quite narrowly focused in one small area. In order to go the other way, this institute has a philosophy of securing funds for the whole institute and then getting interesting people from various fields to come and work together in the institute on problems that span multiple subject areas obviating the need for the researchers to write grant proposals and secure their own research money. This method of operation, though harder to implement and monitor, ensures that researchers don't get stuck in a narrow area stipulated by the funding agency.

Next picked up "Fresh Blood: The new American Immigrant by Sanford J. Ungar. Heard a brief interview of the author couple of years back on Good Morning America or some such program. Since then thought I should read this book and kept it on the list. Finally bought a copy. Seems to be an interesting write-up about contributions new immigrants make. It is based on individual anecdotes, interviews as well as statistics. Will see how it turns out.. :-)

Book Review: The Case for God

Monday December 27, 2010

After reading a few books like The God Delusion by Dawkins, wanted to read some good literature covering counter-points. Didn't want to read books like "Purpose Driven Life", etc. but something more academic and nuanced. So, ended up buying Karen Armstrong's “The Case for God” I have been hearing about for a while. Though the title could be interpreted to mean how she is going to make a case for God, book is more of a study of how human beings always manage to come up with the concept of God irrespective of the era or the geographical area they belong to. You might have heard this famous quote attributed to Blaise Pascal about how human beings have a God shaped vacuum in their soul. It is listed in this book as well. While it captures the point well, it does appear to be an incorrect quote (see http://theconstructivecurmudgeon.blogspot.com/2006/05/incorrect-pascal-quotes.html). The first 300 pages of the book covers Paleolithic age's Unknown God moving from 30,000 BCE to 1500 CE while the next 300 pages cover 1500 CE to present discussing the Modern God. 

I felt a marked difference in the writing style between the two halves. Language in the first half was stuffy. To cite an example, here is a typical sentence: "Even though the Council fathers went to such lengths to enforce dogmatic orthodoxy, their prime concern was to promote regular liturgical observance to enable the laity to transform the old external, communal rites into genuinely interior devotion." Couldn’t she say “The Council fathers tried to calm the public by focusing into following rituals”? But the second half was a lot easier to read. This could be due to the fact that I personally didn't know a lot about the first half material while I was familiar with the second half content. Still, it did feel like two different people wrote them.

I was glad to see her covering Hinduism as well. Though it is one of the major religions in the world, Western scholars usually not well versed in Eastern religions routinely skip/gloss over it focusing only on Christianity, Islam and Judaism. Though her coverage of Hinduism lacks depth comparatively, it still is more balanced compared to other writers.

Read the book while I was on vacation in India last month. During that time came across a Tamil book titled “KadavuL” (means simply “God”) while just browsing shelves in a book store. It had a collection of articles, essays and columns writer Sujatha had written over a period of 10+ years (1993 to ~2004). There is a large overlap between the two books in the material discussed (not implying any kind of plagiarism anywhere). Between the two I actually found KadavuL lot more engrossing despite it being a collection and not one massive piece of work as Case for God is. Though most of the articles in KadavuL were written for less erudite audience, Sujatha had done a wonderful job of presenting this complicated material spanning vast areas in a very easily accessible narrative. Both books have traced various forms of religions and how God had to be brought into explain most naturally occurring phenomenon in the past and how as science demystifies nature, the need for God’s hand has been dwindling over the centuries and particularly in the last few decades.  

In the second half of the book, just like Sujatha, Karen discusses how quantum mechanics, Heisenberg's uncertainly principle and other such developments in science had made people realize that beyond a point nature cannot be understood fully. This realization has obliterated the confidence people once had that eventually anything and everything will be logically explained obviating the need for higher level powers to explain what we can’t understand. Lot of theologians and ancient Hindu religious writings have argued the same w.r.t. to knowing God as well. Both authors point out similarities in this convergence that is intriguing. There are areas of disappointment in Karen’s narration where she seems to stretch things to suit her convenience. For example, when mentioning Hilbert’s set of 23 problems in Mathematics, she implies (in the beginning of Chapter 11) Hilbert said that when these problems are solved, we’d have a complete understanding of the universe..! In all other material I have come across, Hilbert listed those as interesting problems in Math for people to work on. I don’t remember any assertion by him beyond that. Even if she is not an expert in Mathematics, I am surprised that the editorial process didn't catch/correct these assertions. I also noticed as to how she has avoided naming any fundamentalists she despises/looks down upon but limits herself to naming atheists like Dawkins, Hitchens, etc. that should be safe to do. :-)

Talking about God, have you heard what a dyslexic agnostic does lying on the roof top staring at the starry sky?

He wonders if there is a doG. :-)

Book Review: The God Delusion

Saturday, March 21, 2009

Read “The God Delusion” by Richard Dawkins a while back. I remember reading that Dawkins suggested this idea for a book to promote atheism to his agent around the year 2000. It got rejected initially since publishers didn't believe that there will be a market. When W. became president of USA, the pendulum had started swinging quite a bit towards the religious right that around 2004 it appeared like an opportune moment to write this book. Subsequently when it came out in 2006, it became a best seller and has garnered a lot of attention in the pop culture, being used even in the popular cartoon TV show Family Guy..! Basic argument in the book is that belief in any kind of supernatural God promoted by religions is nonsense and it always leads the world towards conflict and hatred towards each other. Dawkins strongly opposes even lighter versions of religion saying while it may appear harmless and altruistic, it only softens people up aiding and abetting a few to move further into religious extremism, suicide bombings and so on. Having grown up in Southern India where a famous atheist in the last century encouraged his followers to attack priests and demolish temples, I was wondering if Dawkins' argument will apply in the other direction as well, i.e. while preaching atheism may be harmless, it might prep a few extremists who may move further and turn violent. Obviously he is not encouraging violent demolitions of churches and synagogues but only a cerebral move towards a more rational, non-religious, logical, scientific world. 

Overall the book feels more like a collection of articles on this topic rather than one tightly written book. This may be excused since he had to touch upon various areas and topics to be comprehensive. Him being an evolutionary biologist, there is a lot of content related to evolution that are borrowed from his various other books. This perhaps indicates how difficult it is to be consistently creative and come up with original ideas.)

He talks about Einstein's use of the word God, and ideas like God could be a set of equations, etc. right at the beginning to say that is not the God he is talking about. His discussion is about the supernatural omniscient God who created the world as religions (particularly Christianity, Islam and Judaism) promote. He spends enough pages to answer arguments like there is an innate need for God in human beings, religion is what gives us our moral compass, etc. In case you haven't heard of Hauser's Denise's Dilemma, you can read this link. Hauser's idea is that we have a moral compass that is innate which has nothing to do with religion since people of all religion and atheists respond to these thought experiments the same way. Dawkins then dove tails to propose that the cynical religious argument "there are no atheists in fox holes" could possibly be countered with, "there probably are no atheists in prison". :-)  In addition he also asks if people will lead a moral life only if there is a God watching over them, doesn't that mean that they are only sucking up to God due to fear and are not righteous by themselves.

I was thinking along the lines of the amount of time/energy/resources that have gone into religion and wouldn't we lose it all if we simply get rid of every form of religion..? He acknowledges this point on his own towards the end saying we should treat, preserve and cherish it just as part of human history (like Egyptian pyramids for example). Though this book may not convert anyone anytime soon, it is a good read.  

I wrote about his documentary "Root of All Evil?" a while back. Got some good responses. While the Channel 4 link is still there at http://www.channel4.com/culture/microsites/C/can_you_believe_it/debates/rootofevil.html the Google video site that offered the video for download no longer exists. That documentary pretty much covered the content of this book as well. BTW, his website http://richarddawkins.net/ looks so cluttered and silly. I think he needs to hire a new webmaster. :-)

22 pens for one signature..!

Thursday, March 25, 2010

In U.S. whenever a new law need to be enacted, first the congress & senate vote on it to approve. It then goes to the president for signature. When the president signs the bill, it becomes law. Instead of treating the bill signing process simply as a procedure that need to be completed, they usually make a ceremony out of it. TV cameras record the event and broadcast it so that politicians can talk about the virtues of the newly enacted law and how it will help people. As part of this ceremony, the president gives the pen used to sign the bill as a memento to the individual(s) who worked hard for getting the bill through.

 

When a big bill like the health-care legislation gets signed, the ceremony becomes even more pronounced. With so many people involved in getting the bill passed, there are so many people who want the pen..! Solution? President signs the bill using multiple pens. :-) For the health-care legislation passed last Tuesday, there were apparently 20 people who deserved the thank you gift. President Obama wanted a pen for himself and they needed one more for a museum. So, he signed his name just once (see the picture below) using 22 different pens..! Individual pens were used to sign just a fraction of one letter in his name..! This sounded silly to me. I am not sure how many of these pens are going to end up in eBay in the next few years. :-)

 

Similarly there is a custom of sending the U.S. national flag that flies on top of the Capitol Building inWashington D.C. to dignitaries around the world as a memento. You can imagine how it would be nice for someone to own a flag that flew on top of that building for a whole year. But again, this idea need to be leveraged fully and so the system goes into "mass production". There are workers who tie a new flag to the pole, hoist it, let it fly for 5 minutes, pull it down, replace it with the next flag and repeat the process throughout the day..! This dilution again cheapens the idea for me. It would be much nicer to use just one pen for each bill and one flag per year and perhaps keep it in some museum if they need to be preserved.

 

Still treating such physical objects as treasures sounds similar to Bollywood movie fetish where heroes and heroins hold on to some clothing or hair clip, etc. of the loved one pining over it. I was quite amused few years back when the British Museum turned down a collection of her used hand bags ex-PM Margaret Thatcher tried to donate suggesting that they should be displayed as treasured exhibits. :-) To a small extent I can see some symbolic value in preserving one pen used to sign a big law that touches the lives of several million people. But used personal handbags..?!?!

My brush with law (i.e. Jury Duty :-)

May 6, 2009

I was summoned to serve as a juror in a civil case in a state county court. As you may know, the U.S. constitution guarantees the right to a jury trial in most cases.The 7th amendment provides this right for civil cases. Countries like India abandoned the jury trial model decades back with the understanding that peer jury not specifically trained to provide judgment in complicated cases may botch justice. The practice of serving justice varies country by country. Some allow jury trial for extreme criminal cases alone, some allow if the defendant wants one, etc. You can read lot more about it at http://en.wikipedia.org/wiki/Jury_trial. About a decade back I have expressed my doubts about how well are public qualified to deliver verdicts setting aside emotions & prejudices. American friends have pointed out that while that may be arguable, it should generally be more difficult to buy off dozen jurors compared to one judge. 

Now having sat through a case and delivered a verdict, though it may not be flawless, I do think the system works well. Of course if the underlying society has problems like corruption, citizenry not taking its civic responsibilities seriously, unresolvable hostility between different tribes/communities that form the country, etc. any type of justice system can still fail whether it is a judge or a bench or a jury delivering a verdict. But in this case it was a positive experience.

Case was about a traffic accident. An 80 year old lady who is the defendant had rear ended a 24 year old lady who is the plaintiff in a stopped intersection in 2004. Defendant immediately agreed that it was her fault. It was just a fender bender and both of them drove away with no injury, no air bag deployment, no ambulance transport, etc. Insurance company seems to have paid to get the mildly damaged bumper fixed. Now 28 year old plaintiff is suing the 84 year old defendant claiming that the accident subsequently resulted in a back injury causing recurring aches that is precluding her from starting up a bakery thus demolishing her life long dream. Both sides presented physician testimonies discussing her injury. They all said that her X-rays, MRI and bone scans taken within few days of her injury does not show any issues. So, the injuries became subjective since nothing could be proven objectively. Plaintiff had gone through several rounds of treatments and had reached MMI (Maximum Medical Improvement) state couple of years back, meaning there is no additional medical treatment possible to make her feel better. Just to be on the conservative side, her physician had recommended that she should do light duty work that will not involve lifting more than 20 lbs of weight.

Though she had completed a 1 year culinary college course in 1999, plaintiff has been working only as a part time waitress earning about $7000 a year. She has not made any progress towards starting her own business though her father testified on the stand that he was going to support her starting the bakery business with financial help. She is living in her mother's house paying rent to her mother. Because of this back injury, she claimed that she had to give up on the idea of starting her own bakery and finished a course to become a medical billing/coding clerk. But she didn't pursue that avenue either though that would have got her a job paying about $33,000 a year in the county where we live. Her reason for not following that career is that it requires her passing an exam for which she has to pay $300 fee and buy books for $70. Though her father was willing to support her financially even to start a business, she didn't want to ask him for $370 since she didn't want to be a financial burden..! So she continues to work as a part time waitress earning the same $7000 a year even now. 

Her lawyer brought in a vocational rehabilitation expert who said that due to her injury her productive work-life horizon will be cut short by about 7.8 years. Considering the fact that medical clerks could earn a median salary of $33,000 in the county, he computed her loss of income in her life time as $257,000. He then added an additional $72,000 for benefits employers would normally provide (P.F. or 401K type retirement savings, etc.) and said her losses are about $329,000. So, they wanted that money (or some part of it) + additional award for non-economic damages such as pain & suffering, humiliation, quality of life loss, etc. 

Fourteen jurors were selected for this case where 12 of us were the required jury and two standby. All 12 of us were from the same county, 5 women and 7 men. We were repeatedly instructed not to discuss the case even amongst ourselves until the final closing arguments were completed by both sides and our charges were handed over to us asking us to start the deliberation. To make sure the process is not tainted, each time anyone of us had to use the toilet, we were escorted by the court clerks. No one in the court including plaintiff, defendant, their attorneys or others (except the judge and court clerks) would even greet us each day. We had to hand over the notepad we were given to take notes to the clerk before we leave the court room even if we are to get it back in the adjacent jury room which was just 50 feet away. The whole process was intentionally designed to be very deliberate and slow thus boring at times as we all agreed. Still, I was quite impressed as to how seriously and sincerely all 12 of us followed the rules to ensure that the process is not compromised in anyway. 

Today when we were finally given the charge asking us to deliberate the evidence and provide our verdict as to how much the awarded damages should be, the speed with which we all unanimously agreed on the verdict surprised us all a bit. Within minutes we all agreed that award for loss of wages should be zero since she was not handicapped in any measurable way that would preclude her from earning what she was earning anyway. Even if she wanted to open a bakery, she could get someone else to do any occasional heavy lifting required. But if she becomes a medical biller/coder/transcriptionist, there will be no need for any heavy lifting anyway.

But since the defendant had conceded that the accident was her fault, the judge said we must provide an award for the second part, i.e. non-economic damages such as pain & suffering. Can you guess how much we awarded her..? Correct answer is $370. Hopefully she got the message. :-)

Even though most of the jurors were probably not college educated, and even though several hours of physician testimonies we heard involved enough medical details, functional capacity test results, etc., I was impressed as to how things were broken down and presented so that anyone with common sense can assess the validity of the plaintiff's claim. It was interesting as to how all the jurors with differing economic/work backgrounds still had similar values and had identical take on plaintiff's outlook. Even though I wouldn't agree with couple of them on their views on politics, gun control, etc, we could easily see eye to eye. Since this is a civil case (unlike criminal cases), unanimous verdict is not required. As per Pennsylvania law, 10 out of 12 jurors agreeing on the verdict would have been sufficient. But ours was unanimous. I am sure other cases can be lot more complicated, verdicts may not come out easily, etc. But many of us expected at least some argument for a while before we reach consensus. But there was no need for any. 

For having served 3 days on this case + 1 day for jury selection in early April, I was paid $62.88 for my services ($9 per day for first 3 days and then $25 for subsequent days + mileage). I don't have to do this at least for another 5 years. Though I wouldn't want to do this over and over again, over all it was a very interesting, positive  experience.

Book Review: Guns, Germs & Steel

Saturday, January 21, 2006


When my son turned one, we had a get together in which an acquaintance mentioned "Guns, Germs & Steel: The Fates of Human Societies" by Jared Diamond which won the Pulitzer Prize in 1998 in the General Non-Fiction category. It sounded interesting and so I bought the book before he turned two. Couple of friends borrowed the book from me and returned it unread taking up few months. I think I started reading it when he turned 3 and finished it just now. Arjun is going to be 4 next month..! Time to take a class in speed reading. :-)  

In about 450 pages, the author analyzes as to why the world turned out the way it is today. The subject material is similar to another book I read a year back called "The Wealth and Poverty of Nations: Why some are so rich and some so poor" by David S. Landes. But compared to Landes, Diamond’s arguments appear more coherent and focused. The main thesis behind the book is that the advancements or lack there of in various countries/continents/societies is not due to innate abilities/inabilities of the human beings living there. Rather it is a result of the environment. In other words, you can’t say that people of one race are more intelligent/dumb than others. 

He argues that compared to Africa or New Guinea, the Eurasia had a clear head start due  to the number of native flora and fauna that could be domesticated. I liked the way in which he had analyzed the domestication process starting with every known plant species (about 200,000) and then filtering out poisonous ones, difficult to replant plants and then sorting them by the size of the pulses (bigger the better from productivity point of view), nutritional value, etc. to arrive at the couple of dozens of plants that serve the food needs of the entire world. Similarly, he has analyzed the animal species as well to sort out which ones could be domesticated to help human beings in their transport, farming, food, and other needs. At least for the past 2000+ years no new animal has been domesticated perhaps goes to show how clean and complete this process is. Once flora and fauna domestication occurs, the idea of developing more complex societies come into the picture since comparatively efficient food production will allow a society to live in close proximity developing a dense population that can in turn support armies, develop weapons, go through various infectious diseases and eventually develop immunity (after scores of people die of a given disease, only those who can survive reproduce thus becoming immune to that disease as a society from that point onwards). When a society with these advantages encounter another one which is sparsely populated (like native Indians) and so never had to deal with infectious diseases that spread in dense populations, the Guns (i.e. weapons), germs (carried by the invaders) as well as steel (i.e. all sorts of technological advantage) work in favor of the densely populated society, helping it conquer the other. 

Using several examples and statistics, he shows that if people of Africa had been in Eurasia, the end result will still be similar with people from Eurasia being dominant over a long period of time since whoever lives in a continent with flora/fauna head start will eventually start dominating the rest of the world. In addition, (as other books have argued before), states that the north-south spread of the African continent Vs. the East-West spread of Eurasia works against Africa since climate change over North – South is much more pronounced creating huge barriers for the spread of plants/animals domesticated in one part of the continent to other. 

Diamond does take his space explaining related material also in enough detail. For example, he spends couple of pages explaining how carbon dating works though he could have easily presumed that readers will get that information elsewhere. 

Analysis of this kind gives you sort of an egoistic satisfaction since it seems to neatly explain the entire human history in one book (similar to standing on top of a hill when the elevation helps you comprehend the topology of the landmass lying beneath). So, towards the end I was turning a bit skeptical wondering can we be really sure. Then read the epilogue where Diamond back peddles a bit discussing the role of ‘historical science’ and how its experiments can not be identical to the way physics experiments are conducted and so you can only analyze what has happened and explain the present scenario and predict general trends but can not precisely say how things will proceed next at the micro level. For example, if the truck driver who hit Hitler’s car in an accident few years before WWII had been a bit slow and ended up killing him, lot of things in world history might have turned differently. Along similar lines, "Why Europe..? Why not China..?" could be explained by a few Chinese leaders making few specific decisions that prevented China from going out and colonizing most of the world. Once he concedes these points, though the results are no longer very tidy (similar to the book by Landes), the overall thesis becomes much more acceptable. Good, long read. :-)