Fun with biology for weekend entertainment!

 We are often caught up in clips/news/forwards that are pushed by social as well as mainstream media that are mostly one or two minutes/pages long about things that are not going to matter much after a week or two To make sure our attention span is not monotonically getting atrophied, I nudge next gen youngsters in my circle to regularly read/listen/watch/focus on material related to ideas/research that span time & space, since that is what is going to have significant impact on societies in the longer term. I'd list the concepts behind mRNA vaccine or how High NA-EUV Lithography system works, as couple of such examples that took more than a decade to develop, with work spanning across a dozen countries/companies. 

To pull us back from the non-stop "Breaking News" cycle that mostly pumps out trivial stuff that is not going to matter next week, one approach suggests imagining a newspaper that gets published only once in 50 years. If you are the editor of that newspaper, what will you put out as the headlines (both good & bad) for the new issue going out next week?

Thinking along such slow lines, wanted to provide few good pointers I came across in the realm of biology.

Within the human body, we know blood flows all around, providing the needed nourishment for different body parts to function. Still there is a serious barrier at the brain that doesn't allow most things to get through. Here is an interesting article that nicely explains the blood-brain barrier.

Similarly, when a foreign body (e.g. a germ) enters our body, we know there is serious defense mechanism in place to fight it off. But when an expectant mother is carrying the baby, the fetus should normally be treated as a foreign body, as it has different blood type, DNA, etc. and so should be fought off by the mother's body. This doesn't happen. Why? It is because of the placenta, which is now understood to be a much more complicated organ than it was previously thought of. This Radiolab podcast does an excellent job of discussing this topic. A closely related article discusses discusses possibility of microbiome existing in human brain. 

On a somewhat related note, saw a nice video titled Post Human that talked about using our skin cells to create stem cells that can then be goaded to become egg & sperm cells, so that one can potentially have one's own baby without the need for another partner's sperm or egg. While this is one form of cloning, the documentary is not about cloning at all but about developments in biology (e.g. growing a baby outside the womb, developing a digital model that can be used to experiment drug or surgical procedures to see what will work for the real patient) in multiple areas that could be around the corner. https://youtu.be/88DPXE1thw4

If such things are possible, will it be possible to grow the human baby totally outside a woman's womb? That is the "What if?" question being explored in this Netflix movie, where in the near future, babies go through gestational development in a pod, provided by a private company. You can rent the pod, choose various options by paying for them, and use a crypto key to unlock the pod during the birthing process. While the concept is nicely explored, ending is just meh. https://youtu.be/rGMx_7oAeUM

Going back in time, Netflix also has a new movie titled Joy, that presents the development of IVF tech in the 1970's.

https://youtu.be/Ix8Hzwc81XA

Robert Edwards & Patrick Steptoe, the pioneers that brought Louisa Brown (the first test tube baby) to this world, have written a book titled "A Matter of Life". It is one of the first non-fiction book I read in English, way back in the 1980's and so vividly remember, which is what this movie is about. Just like the way we are worried about the unknown repercussions of CRISPR based editing of human genome today, in the 1970s, there was massive opposition to IVF, since church, public and even the scientific community (including James Watson of DNA fame) were all worried that this is going against nature, that may produce Frankenstein monsters! 

Let me know how many of these pointers you were able to explore and what you found interesting or if you have pointers for me. 

Not so well disguised Book Reviews!

A while back I heard an interview of Nina Kraus on the radio discussing her book titled "Of Sound Mind - How our brain constructs a meaningful sonic world" that emphasized the importance of the sense of hearing, that we don't take as seriously as vision. The pun in the main title was amusing, making the book name stick to my mind. As I age, there has been some age based deterioration in my own hearing as shown in the chart below, and so I wanted to dig into this area a bit more to see if there is anything for me to do/practice to slow down or reverse the trend before I am forced to go for hearing aids, etc. in the future (very similar to what I was doing with CGM - Continuous Glucose Monitoring). 

In a totally different context came across the old Pulitzer Prize winner "The Soul of a New Machine" (when straplines for book titles were not in vogue!) by Tracy Kidder that came out in 1981. Though I have heard of it, never picked it up, though it was considered a classic in computer science world. Decided to order a copy. Since I read these two books back-to-back, my usual triggers, comparing the authors' writing style, their background and how the material was presented were all swirling around in my mind. 

Just for fun, I first asked ChatGPT to write a book review in my style for the Soul of the machine book. I could do that by pointing it to my blogsite that has archives of my previous reviews so that it can learn. Here is the exact prompt I gave, and the review it wrote. This is to see how close its writeup is compared to how I felt. 

My prompt to ChatGPT: Write a book review for "The soul of a new machine" by Tracy Kidder in the style of Sundar Vedantham using book reviews posted at https://sundarvedantham.blogspot.com 

Here is what it came up with:

I was expecting it to write a review exactly like what I'd have written (i.e. if I copy/paste and send it out as my review, no one will know the difference). But it interpreted the prompt to mean that it should mimic someone else writing the review, referring to my style (hence the "as Vedantham would ask" lines). While it did manage to write prose that is similar to how I may write, actual takeaways were quite the opposite to what I felt reading the book! I have read couple of other books in the past, with major expectations that turned out to be duds for me. Along those lines, despite this one being a Pulitzer Prize winner, I didn't find it very engaging. Being a 4 decade old book, perhaps it hasn't aged well. It is written by the author Tracy Kidder who is a writer (i.e. not computer scientist). He was invited to hang around the design team of a computer company called Data General, as they were designing a new Mini-Computer (similar to DEC's PDP-11) called Eclipse. 

Data General was a badass computer company in the 70's. It was known for aggressive sales techniques, bold advertisements (look up "They Say IBM’s Entry Into Minicomputers Will Legitimize The Market. The Bastards Say, Welcome." advertisement that never actually went out) and so forth. While the DG's efforts & style were unique and heroic compared to IBM type companies at that time, to me Kidder kept sounding like a total outsider (perhaps because I am an insider) who was trying to sound like an insider, explaining geeky technical details of computer design in not so easy to understand prose for common audience. Author who is not a techie trying to sound like he is very tightly integrated as part of the tech team, describing how he was in the lab, went fishing with the tech leads, ate dinner with them, describing everything in first person singular (I did this, I asked him, my wife said) sounded odd. Reminded me of Carly Fiorina, when she became CEO of HP, putting up her picture next to Hewlett & Packard in their corporate office. It made HP engineers giggle since they didn't see her as an equivalent techie that deserved to have her portrait next to the founders, both of whom had passed away! Kidder certainly didn't go that far. But more of an observer style reporting in third person might have come across better. Perhaps it is just me. If you have read it and consider it a classic, educate me as to what I am missing and what impressed you so much.  

OTOH, Kraus is a Prof. at Northwestern University, running a lab called Brainvolts for decades, guided about 30 PhD students and has written just this one book that captures her lifelong work spanning decades. While this profile matches that of some very good books I have read in the past, I found Kraus' prose unnecessarily technical for a mass audience book. Here is an example, "Their hearing threshold did not change, but the way the auditory cortex responded to sound changed, reflecting a disorganized tonotopic pitch-processing mechanism". Takes a while to get used to her discussing the differences between afferent (moving upstream from ear towards brain) and efferent (moving downstream) in such language elaborately. I often complain that books usually contain walls and walls of text but instead should sprinkle around many more figures & pictures to help illustrate the discussion. While I was delighted to see Kraus using a lot of pictures, I found many pictures that didn't add much value. They felt so unnecessary, perhaps only helping to increase page count nudging it towards the 300-page mark, which is typical for books of this kind (this one is only 267 pages long). In addition, there were several pictures reused with permission from somewhere else. Probably the originals were color pictures that were meant to be seen in larger format. Rendered in B&W, small format portrayal in this book, things written inside those images by hand were hard to read and so again were annoying. 

But once we get past those annoyances, this book nicely covers the importance of good auditory capacity we should strive to retain for our mental health. Kraus writes in first person, talking often about her family, children, husband, mother, and students. In this case, since it is all her research, it does sound appropriate, at least to my ears. She covers the subject from multiple angles, the ear-brain functionality that enables us to hear & comprehend sound, bird songs, poverty are just few angles she takes up. Often when you dig into any specific areas of research, you unearth very interesting facts and nuances that are not intuitive. Kraus does a lot of research by measuring midbrain electrical signals that can be measured from our scalp (FFR - Frequency Following Response), that she uses as a point of departure to study the effects of sound on autism, aging, and so on. Here are some such findings Kraus talks about:

- Both musicians and athletes are better at hearing & understanding speech under noisy conditions. But the brains of the musicians amplify the signal (i.e. speech) to understand what is being said better, while athletes suppress the noise to reach the same level of understanding. 

- Plants are able to "hear" or are sensitive to sound. Her team demonstrates it using a pot that has two diverging legs at the bottom. Since plants grow their roots towards the area where water is found, without really providing water, but by creating the sound of water, they are able to observe the root growing towards that leg of the pot!

- Marine lives thrive near coral reefs that have a lot of activity reflected by the level of sound. By playing marine sounds through speakers near dead coral, we are able to attract more fish and other marine beings to settle down in that area, helping the area revive!

- Being a practicing bilingual and performing music of any kind are two areas that really help. 

- I have attached a 7 min long radio interview she gave. Near minute 6:30 see how by measuring the electric signals on the scalp as our brain listens to a piece of audio (few seconds of music, in this case) we can even recreate the audio back. 

I went for an audiology exam recently. The plot below shows my left/right (blue/red respectively) hearing thresholds. This is typical age-related hearing deterioration at different frequencies. 

I did do well on speech audiometry, word recognition tympanometry, and other such tests. Bur from previous test results completed couple of years ago, I can see a 5db drop in most frequencies. Kraus points out how if we see bleary road signs, we won't blame the highway department for installing fuzzy signs but get our eyes checked but when we don't hear well, we blame the noise around us and don't rush to get our ears tested! As we lose hearing slowly, as almost all of us will as we age, conversations become difficult. We slowly become apprehensive and hesitant about annoying others by asking them to repeat what they said. We then start to avoid interactions and tend to become more and more isolated leading to depression. We may also see this behavior in our own family elders. Simple fixes are getting tested by an audiologist to track any deterioration over time, learning a new language, playing music, avoiding excessive noise that can damage our ears, getting the right kind of hearing aids, and so on. I am planning to put these ideas into practice in my life. Do check out the Brainvolts lab website that has interesting short videos, papers, tests. If you won't pick up this book, you can search for her name online and listen to interviews/talks.

Book Review: Accelerating India's Development by Karthik Muralidharan

I was listening to Amit Varma's The Seen and the Unseen, long form podcast when I came to know about this author. Karthik Muralidharan's first two appearances on that podcast series where he discussed education and healthcare in India were domain specific and were excellent. Third one that is five hours long discussed the Indian state, its faults and short comings and ways through which it can be improved considerably. When that episode aired two years ago (in 2022), KM was working on this book. Since it piqued my interest, asked my friend Sanjay to buy it, read it and then give it to me when I went to India last summer. Sanjay did the first and third part but did the second only partially, since this is an 800-page tome! Now that I am done, I can give it back to him to finish reading. 😀

Muralidharan is an academic who went to grad school in the US and is a faculty at UCSD but also has done a ton of field work in India, working with various state governments, NGOs (Non-Governmental Organizations) and academic institutions. Since this book titled Accelerating India's Development - A State Led Roadmap for Effective Governance, distills everything he had learned and gathered over the last two decades, it is panoramic, comprehensive and impressively detailed. Though it spans 800 pages, the last 200 pages are notes & references, leaving a good 600 pages for us to read, in very accessible language. 

Initial chapters set out the current status and the problems that need to be solved. When India got its independence from the British 77 years ago, many thought it may break apart into dozen different pieces due to its diversity in people, culture, languages, religion, wealth and geography. While the union has endured, thriving as the world's largest democracy, there are still humungous problems in service delivery, lack of trust in the government & politicians, corruption, poverty and so forth that need to be solved. General apathy or disillusionment among the citizenry is quite common making such problem solving quite difficult. 

After setting up that background, with a lot of facts, data and charts, Muralidharan goes around breaking several myths and presents current problems & status from different perspectives. Couple of examples:

- Western scholars or even people in India tend to compare current conditions in India with developed countries as they exist today to complain how bad the situation in India is. Author points out that countries like the US initially became democracies where only a very small minority (i.e. white men) had the ability to vote, and the state was able to provide the guarantees and services that small voting block desired (e.g. land rights). With that initial trust built, more citizens could be enfranchised slowly (e.g. women, blacks), over the decades, if not centuries. With raising tax revenue in the same period, additional services like education, health, etc. could be provided by the government. This ladder of starting small, delivering a small set of services, gaining the trust and slowly expanding the tax base, capacity and services worked in the histories of developed countries. But in case of India, right off the bat, everyone in the country was enfranchised from the beginning as the constitution was written when India got its freedom in 1947. But the state had no tax revenue or other needed capacity to deliver so many things like food, jobs, education, healthcare, defense. etc. the citizenry expected from the government! This led to distrust, resulting in people cheating on taxes, moving to private services for their education, healthcare needs, preventing the state from ever acquiring the capacity or ability or trust to deliver all the expected services. When we look at India's evolution in this light, we may not bad mouth the country so much. 

- Indian citizenry often feels that most of the government funds are swindled by corrupt politicians and bureaucrats. The author argues that a pie chart of funds not reaching the intended goals, shows only 13% swallowed by corruption, while the remaining 87% loss is due to poor and ineffective/inefficient implementation. If we can tweak the system to eliminate inefficiencies even a little, it may have 10X improvements in deliveries! As the deliveries and services improve, corruption may start to go down on its own. Thus, there is a lot of hope for fixing the system. 

- There is a general perception that there are way too many Indian government employees. But in reality, there are only 16 public employees for every 1000 citizens in India, while the number is 57, 77, 138 and 159 respectively in China, US, Sweden and Norway! This shows that the number of public servants per capita are one of the least in the world for India! Even the limited state capacity (e.g. police) is used to provide services for the rich and powerful (e.g. VIP escort) rather than ensuring the safety of ordinary citizens.

After several chapters of such interesting juxtaposing of facts, book gets into ideas for improving the system area by area. Since the suggestions are not just armchair analysis but are tested in field, author is keenly aware of what is practical. He focuses on changes that can be implemented by politicians with their eyes on the next election that they need to win. Hence many suggestions are ones that are especially low hanging fruits that can be picked with minimum effort and expense. While many of the suggestions are worth discussing, to keep the review short, we can summarize them as follows:

- Everywhere focus in India to improve services is on allotting more resources but not on measuring outcomes. Thus, when it comes to education, a school may get 10 computers. But since the school principal will be in deep trouble during audit if a computer is found missing, he will tend to keep it under lock and key ensuring its safety, though this may result in a situation where students don't learn much from it. Every ministry/secretory/NGO continues to ask for more funding for their pet area. But simply improving efficiency by ceding a lot of control to local entities may solve a lot of these limited resource issues. Book cites China and Vietnam as two countries that have improved quality of education delivery without increasing the teachers' salary. Particularly China that is often seen as a very strong centrally controlled country, is cited many times for the level of decision making, budgeting, spending that is taking place at the local government level. 

- In a field trial, the author worked with an Indian state government to setup a calling center with minimal expense. They then used it to contact end recipients of a government grant to check if they got the disbursed money. While doing this, they advertised this process of checking widely to the bureaucrats that are the intermediary, delivering the funds to the state's citizens. This apparently eliminated most of the swindling and the money reached the intended recipients properly. Thus, implementing some such small but highly visible check may make a dramatic difference in the quality of service delivered. 

- Since firing ineffective government workers may not be easy, author suggests hiring new interns to assist existing employees on a contract basis for 3 to 5 years. Government employees won't object to this since they are getting extra help. The temporary employees will work better since the carrot of a small percentage of them becoming permanent later could be dangled in front of them. Many who don't become permanent can apply for another temporary term or would have at least gathered valuable skills they can use elsewhere to get gainful employment. Over the years, quality of service should improve considerably with older inefficient employees retiring.

There are many more such field-tested ideas for healthcare, court system (that is creaking under the backlogged case load), agriculture, policing, and so on that are all worth exploring. Author argues that many of these ideas can be implemented with results starting to show up within about four years. Since Indian elections are held once in five years, politicians can wade into these ideas with the hope of being able to take credit for the positive results during the following election cycle. Book focuses more on what can be done at the state level, rather than at the central/federal govt level, since the needs of the Indian states vary widely. This approach will allow more customized solutions that could be tried out quickly at a smaller scale at the state level. If they are successful, other states can adopt them. If not, they can tweak the programs and iterate to perfect them. He cites the example of Illam Thedi Kalvi  (Education at your door step), a program pioneered by the state of Tamilnadu during the Covid pandemic to ensure children got access to enough schooling at their home, that turned out to be a great success. This approach makes each one of the 28 Indian states smaller labs that can move more nimbly. 

In more than one section, including the last chapter, author talks about the Aadhar biometric ID system India has implemented, as a poster child for excellent solution development that is customized for India and deployed in such massive scale for the first time in the world. Such initiatives manage to prove naysayers within India, who think India can't innovate at that scale, wrong. The Unified Payment Interface (UPI) is the next innovation that has leap frogged many other developed nations' systems in being developed, deployed and being operated smoothly on a massive scale. Both of these solutions are now being exported to other countries. This is used to illustrate the point that due to its size and scale, solutions being put together for India can potentially help the world as well. Thus, book concludes that though it may appear daunting, there is a lot that could be done to smoothly to accelerate India's development. 

There is not much to say that is negative about the book. Language is simple, areas covered are comprehensive, ideas are presented for central, state, local governments to try out, bureaucrats and individual citizens to take up, and corporations and NGOs to contribute. While one can complain about the length of the book (800 pages), the scope seems to warrant it. Even if you are not interested in India particularly, if you are a policy geek like me, it might be an interesting read. I am also sure many ideas presented will be applicable to several other countries in the world. If you don't have the time and patience to read the book, you can atleast consider listening to the podcast episode where many of these ideas were first discussed. 

Book Review: The Song of the Cell by Siddhartha Mukherjee

Fiction writers publishing several dozen books in their lifetime may reflect how prolific they are and fertile their mind is. But if non-fiction writers publish several dozen books, I tend to look at them with some skepticism since individual books offer very little (i.e. low Signal-to-Noise ratio, as we say in communication engineering). On the other hand, I find well-written large books that provide comprehensive view of a given field, written by experts that worked in that field for several decades and produce just couple of books in their lifetime, so amazing and engrossing. Mukherjee's first two books, belonged to this category. The Emperor of All Maladies, and The Gene, were both excellent. He did say after writing the first book that he'd never write another book, since he had put down everything he knew about his field in his first book itself (which won him a Pulitzer). But then he found enough material to write the second one (The Gene) and couple of years back published this third book titled, The Song of the Cell: An Exploration of Medicine and the New Human, that delves into biological cells. I am grateful that real researchers like him (a practicing oncologist) sit down and write such books. Though I struggled with the initial couple of chapters, subsequence chapters are really well-written and so this is certainly worth a read. 

After discussing the passing of a cancer patient in the introductory chapter, book rolls back centuries & even millenniums to start from as far back as AD 129, to talk about the Roman physician Galen and his teachings about anatomy. It then quickly moves up to 16th and 17th century when investigators started looking at specimens through initial versions of microscopes to be mesmerized by the new worlds that seem to exist there. Though progress has been accelerating as each century rolled by, how much early discoverers/investigators learned & documented about cell biology is still quite impressive. As we come into the 20th century, there are large chapters/sections that view different side of biology and medicine, using the lens of a cell. The IVF section really tickled me, since the book "A Matter of Life", about the first "test tube baby" by Bob Edwards & Patrick Steptoe was one of the very early non-fiction books I read, circa 1983. I was starting to read material just to whet my curiosity (i.e. they weren't prescribed by anyone or needed for any course I was doing) and so I still remember a lot of details vividly, that were cross referenced here. 😊

Naturally, there are many sections in this book dedicated to cancer research, as it is close to the author's heart & work, while also covering many areas such as AIDS, immunotherapy, insulin generation, pandemic and even DBS (Deep Brain Stimulation) techniques being tested as a way to cure serious depression. (I should note that the author's own fight with serious depression is eye opening and humbling, since it is discussed sincerely and not for scoring some brownie points.)

When I read such books, I really wish I can remember/recall all the details that I come across. While I certainly don't have eidetic memory, the section on T-cell posed quite a challenge in this regard. Since it is not really my domain, paragraphs that read as, "In contrast, a majority of peptides derived from pathogens outside the cell (and a few from the cell's interior that end up in the lysosome) are presented by class II MHCs. These are detected by a second class of T cells, called CD4 T cells." were difficult to grasp and retain. I was starting to think that Mukherjee's lucidity I enjoyed in his previous two books is missing now. But once I got past these chapters, I could see the author being back in form. Lines like "I tuned the microscope off and an inner light flickered on" (while learning about stem cell growth) are all over the book, neatly illustrating the author's capacity for good writing & metaphors (he compares antibody to a “gunslinging sheriff” and a T cell to a “gumshoe detective”, explains that bacterial protein can make precise edits to the human genome that it’s as if “it can change Verbal to Herbal in the preface to Volume 1 of ‘Samuel Pepys’ Diary’ in a college library containing 80,000 books.”). Fun reading.

Daily news is alarming & depressing these days. Anti-immigration sentiments seems to be on the rise along with polarization everywhere. In this environment, reading books like these restores your hope and confidence in humanity on the whole. How scientists do painstakingly slow work across space & time, paying no attention to national borders to push our understanding of how cells work and how they use the knowledge subsequently to design drugs & solutions to cure the humanity of its ailments is truly humbling. I wish some of the readers of this email will (or have already) read this book so that I can talk about many spectacular ideas like how neurons transmit information by both electrical and chemical means, the enormously complicated details of stem cells and so on, to get more clarity. Learning about how in 2007, a Japanese scientist named Shinya Yamanaka created stem cells from a mouse tail fibroblast should make anyone of us giddy, since it is so brilliant and reveals so many secrets that were buried deep in the annals of cell biology. I can similarly go on and on about the role of stem cells in skin wound healing (page 350), how we learned the role of pancreas and so on that are all equally engaging and amusing.   

But in addition to the complaint about some sections being harder to comprehend and retain fully, I do have couple of additional items to whine about. I often complain about books not having enough illustrations. While this book has some illustrations, the authors/editors have focused on reproducing decades & centuries old original drawings as is, in many sections. While it is exciting to see original drawings, they don't help much in conveying the knowledge well, since the old drawings are fuzzy and often confusing. I wish there were clearer, newer drawing that are easier to comprehend. Another minor nit is related to so many quotes that appear at the beginning of each chapter. One pertinent quote that matches well with the chapter's content increases the quality of writing (I did that for each chapter in this one book I have published and hoping to do the same for my second book as well). But having multiple quotes at the beginning of each chapter that are not that tightly related to the chapter contents, makes it look like the author is trying to show off and impress readers with his literary erudition, without adding much value to the discourse.

I sincerely hope all my friends who are either physicians or working in the medicine/pharma R&D will read this book so that we will have a ton of stuff to nerd out on homeostasis. 😎

Landed in India today for two weeks of vacation/work mix. Looking forward to picking up another good book, perhaps in Tamil, during this break.

Regards.

-sundar.

 

Continuous Glucose Monitoring

If you are diabetic or heard enough about Continuous Glucose Monitoring from the media/friends already, you can skip this post completely. 

Last time I went for a routine medical checkup/blood work, the numbers showed me as one who has just reached pre-diabetic stage. If you are not familiar with this diagnosis, it is nothing too alarming, as millions of people all over the world live in this state for decades. The medical industry's guidance at this stage is to "just watch", meaning no medication or change in lifestyle required. They will keep testing once a year to see if we actually become diabetic, after which medications will be prescribed. To me, this doesn't make sense, since this is the time to dig into the data to see what changes we can make in our diet and exercise routine so that the A1C numbers don't continue to trend up. Though things like reducing weight, exercising more and eating less carbs will all help, since each individual's metabolism is different, getting lot more data about our particular body/food/exercise habits to see what we can easily to tweak to go back to normal state is what made sense to me. 

To gather a lot of data, bought a Freestyle Libre CGM (Continuous Glucose Monitoring) system, that has a sensor that you attach to your body and a reader, using which you can read your blood glucose level in a second, whenever and as many times as you want. Till two weeks back, getting a CGM in the US usually required a doctor's prescription, whereas in other parts of the world, you can purchase one OTC (Over The Counter). The US FDA changed the rule couple of weeks back allowing OTC sales in US as well. Hopefully it will bring the price down. While there are a lot of models, types, version, the one I bought costs roughly $100 for the reader and $30 for the sensor that works for two weeks (exactly, to the minute). I got a second sensor, in case I mess up while putting on the first one. But it was easy to put on and so I have a spare one now, that someone else can use later. 

You can find a lot of details about CGM online, and in YouTube videos. But here are a few photos/video explaining what I did.

https://photos.app.goo.gl/2q2qfHiXDTfPAoLV7 

The Abbott Labs that sells this particular model wants you to create an account, and upload all the data to their cloud, so that they can analyze and give your results/recommendations. Since the EULA wants you to allow them to own/use the data however they want, forever, I felt uncomfortable and went through the painful process of entering all the data into a spreadsheet and doing the analysis myself. If you don't mind giving away your data, you can download apps available online, and use the provided USB cable to easily transfer the data to get the analysis done online. 

This reader also has the interface to take glucose blood test strips to provide you the reading, though I didn't use it myself. There are newer versions of the device, where using the Bluetooth interface, data can be directly transferred to your phone and then on to the cloud, etc. I intentionally used a low-tech version where the reading stays in the handheld reader, that is about the size of pager, with a very easy to use, single button interface.

The sensor actually measures the glucose levels in the Interstitial Fluid rather than in the blood hemoglobin but is considered pretty accurate, since the reader can use a formula to covert (i.e. estimate) it to blood glucose level. 

I took about 20 to 25 readings each day for the past two weeks and so have about 300 readings. The sensor you attach to your body does gather the glucose data continuously and so even if you don't read it so many times, when you do, it will transfer all the data to your reader. You can see it in the graphs the reader plots & shows you (see photos). But since the reader screen size is small, and since I wasn't transferring the data to the cloud, I am depending more on the 300 manual readings I took and recorded on a spreadsheet with notes on foot/activities. (See update 1 below.)

Observations made are applicable mainly to me, since the reason to go through this process is to get a better understanding of our own specific (i.e. one person) metabolism. Still, I am listing a few salient points I gathered, since these insights may be useful for others to follow or may indicate the value & surprise findings you derive by going through this exercise. I defined my "normal range" of glucose reading as 70 to 120 mg/dL.

- Eating a cup of plain white Raman noodles (without adding any vegetables, proteins, flavors, etc.) causes a glucose spike close to 200. I used this as a baseline to test couple of theories.

- Eating the same plain noodles, preceded by a small salad, flattens the spike, limiting it to about 150. 

- Eating the same plain noodles, followed by 20-25 minutes of moderate exercise (like brisk walking), flattens the spike, limiting it to about 150. 

- White rice eaten with Sambar/rasam/butter milk (typical south Indian lunch/dinner) causes a spike close to 200.

- Preceding the identical meal with a small salad keeps it under 150. 

- Alternately replacing white rice with cooked bulgur wheat or brown rice eliminated the spike.

- Eating a small salad or protein, seems to coat/occupy your intestine preventing any subsequent carb/sugar from being quickly absorbed that seems to cause a spike. 

- Eating 1.5 slices of toasted whole wheat bread OR just one cup of south Indian rava uppuma caused a sharp spike. I think white bread would have caused even a bigger spike. 

- I tried all types of food (Mexican, Italian pasta, pizza, black coffee, coffee with milk & sugar, fruit smoothie, pistachio nuts), different type of exercise (walk, jog, weights, stretches/sit-ups) and took readings to see how/what I can optimize to prevent spikes.

There are articles like this one that argues why common public should NOT do CGM, and how spikes after eating different food is quite normal, as long as the glucose level comes down on its own in the following hour. I do understand those points and my levels do come down. Still, being an engineer, I prefer & tend to measure, analyze, debug and fix issues before they become a crisis. I am hoping to use the collected data to modify my diet & exercise routines to see if I can go back to being normal (instead of pre-diabetic) next time I go for a checkup. If I can do that, I'd have gotten my money's worth, and this process will be in line with my goal of living a healthy life as long as I can without resorting to chronic daily medication just to lead a normal life. Will tell you how it goes after 6 months or 1 year. 

If you are already an expert and have pointes for me, drop me a note.  

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Update 1: Weeks after writing this post, I did manage to upload all the data to Abbott without giving my personal details to remain anonymous. It showed about 1700 data points gathered by the reader, instead of the mere 300 I had. It also did a really nice analysis and gave me a 16-page PDF that is much more comprehensive than mine.)

Update 2: It's been 7 months since I started making tweaks to my diet & exercise routines. Dropped few pounds, did more exercise, ate salad (with Apple Cider Vinegar) regularly before most meals, replaced white rice with brown rice, etc. So, wanted to see if all this had the right impact. When I asked my PCP (Primary Care Physician) for an A1C test, I was told that US health insurance will allow only one A1C test per year (as part of annual blood work) since I am not diabetic and so I can have one only in the next calendar year. I didn't want to wait till January 2025 and so bought a home A1C test kit and did the test myself. It showed my new Hemoglobin A1C percentage number is 5.4. This is better than my 2016 number of 5.5! Since then, it has always monotonically increased. Though home test may have accuracy issues, since this number is even better than my 8-year-old reading, I think I can safely conclude that the last 8-months of tweaks are working. I don't need to lose any more weight but will stick to ongoing diet & exercise routines. Hopefully I can confirm the numbers next year when I get the annual blood work done. 

For engineers, there is no better buzz than seeing a specific fix you put in addressing a bug in the system. 

If you are interested in this topic, consider listening to this one podcast episode about Novo Nordisk:

https://www.acquired.fm/episodes/novo-nordisk-ozempic

Book Review: Chip War by Chris Miller

This book titled Chip War - The fight for the world's most critical technology by Chris Miller came out in late 2022 and became a best seller quickly garnering a lot attention. Since I keep yapping about semiconductors all the time, many friends, including my own team members who have read the book kept asking me if I had read it. Since I am slow reader, who still haven't learned to skim through a book perfunctorily, I remained reluctant to pick it up. I thought it may not have a lot of new material for me to learn, as we have been living this history for the past few decades. But the noise about the book was getting deafening, with our own CEO interviewing the author, and various news media outlets incessantly talking about it. So, decided to pick it up from the local library. While I should honestly say there wasn't a ton of new information for the semiconductor industry oldies like myself, I thoroughly enjoyed the read. It felt similar to watching a good movie you liked for the second time! If you are not in the semiconductor industry, I will highly recommend this book as the material is written in an extremely accessible prose covering lucidly not only the old history but the current status and how critical this technology is for the entire world.

Author is not an industry expert but an academic, who teaches international history. Since he has taken the time and put in the effort to grok a lot of material, conducted a ton of firsthand interviews, the story arc has come out very well, bearing his international history background as the overarching signature. Most of the individual chapters are only 4, 5 pages long, while the total book spans a respectable 350 pages. Starting from cold war days, the invention of integrated circuits, book chronicles how this technology originally invented in the US, was taken over by countries like Japan in the 80's forcing companies to reinvent themselves. There are several stories and personalities from Intel since it is a quintessential part of the world's chip industry history. While in the late 80's it looked like US has totally lost the leadership, US companies managed to out invent everyone else, bringing the leadership back to the US for couple of decades. But the subsequent developments, such as the emergence of TSMC that prints chips for most of the world, has reshaped the world and this market. Countries like Russia and China see the importance of being a leader in this domain from both military and civilian national requirements but haven't succeeded in becoming serious players so far, despite a lot of government push, deluge of subsidies and even industrial espionage. While most people in the world think of chips as some commodity similar to potato chips (i.e. fungible, gets produced somewhere and used somewhere, without the locations mattering much), the pandemic that resulted in chip shortage that brought things like automobile production lines to a halt, helped the world realize how smoothly this supply chain has been running in the background.

Though US controls many choke points such as high-end chip design software, currently the manufacturing prowess to produce the most advanced chips sit with TSMC and Samsung. Our company Intel Corp is trying to catch up, working with companies like ASML that manufacture the machines needed to make these cutting-edge chips. Building each generation machines and factories costing literally tens of billions of dollars involving extreme specialization makes this cutthroat competitive world a difficult one to survive. Just take a look at this one short video our company has put out to see how complex the technology is. If you pay attention to the process of generating the UV light that doesn't exist naturally, you will see why the effort we need to go through and the technology that need to work flawlessly to print the next gen microchips is truly mind boggling. If you don't ask. "Are you kidding me? Is this for real?", you weren't paying attention. 

While I am tempted to write a lot more, I am trying to keep this short and will highly encourage those who are not working in the field of semiconductors to reach this book to understand the breadth and importance of this field. Same recommendation for new young engineers in this field as well! 

Time to go back to The Song of the Cell by Siddhartha Mukherjee that I am only halfway through! 

Book Review: Outlive by Peter Attia

This book titled "Outlive - The Science and Art of Longevity" came out just last year (2023) and seems to be making waves. My friend Sanjay Padubidri recommended it and so picked up a copy from our local public library. Since it is a fairly new book, it came on a two week loan, instead of the usual 3 week period. Though at 410 pages, it looked like a big book, it was an easy read and yes, it could have been shorter in length, like this book review. 

Attia is a practicing physician and has written this book with Bill Gifford, though pretty much every line is written in first person singular mode. Classifying and giving names to everything is a common practice in the US these days. In that tradition, he starts off discussing medicine as Version 1.0 (medieval practices like blood letting, etc.), 2.0 (current version that focuses on issues after they show up) and 3.0 (where a lot of treatment is preventative). Then spends a lot of pages talking about the "the four horsemen" of ailments that pain us as we age, viz. metabolic issues like diabetes, heart health issues, cancer and neurological issues like Alzheimer's. Second half of the book dives into measuring everything possible, finetuning our routines (in eating, exercising, sleeping) to prevent or delay these ailments from slowing us down, so that we can "Outlive" them into a happy, healthy old age. 

Books gets into the details of each area (e.g. functions of various genes, enzymes, hormones) and also adds a lot of personal stories about patients he treated, how he was so ignorant and over the decades learned his lessons and so on. While these makes it all very easy to read as there is not a lot of difficult concepts that you need to remember, it also feels like very many pages could have been eliminated, including sections meant for his humble bragging. On the positive side, certainly liked the fact that he is not pushing any one wonder drug or diet or practice that will solve everything but is evangelizing a comprehensive approach of moderation on multiple fronts (diet, sleeping, exercising, taking needed medication). The overall takeaways are presented in an easy to remember fashion and so it is worth a read, though it may not be necessary to buy and keep a copy. Last round of annual check up I had showed me as mildly pre-diabetic. Based on what Sanjay was telling and this book is suggesting, thinking of getting a CGM (Continuous Glucose Monitor) for a month or two to get a lot of data. This should help me tweak whatever I can in diet/exercise to continue my general goal of living a healthy happy life as long as I can, without having to take chronic medication. Will see how it goes. Looks like many such "lifestyle gurus", he is also making an industry out of this with a website where he is posting videos, podcast, book, patient sessions, etc. Though there is nothing wrong with any of that, it reminded me of another writer mildly making fun of an Indian Swamiji pushing spiritualism, who has established an equivalent of a mega church that takes Mastercard and Visa for their services! 

Enathu Naadaga Vaazhkkai

For my non-Tamil speaking friends, this email's subject line might have sounded odd. It is because it is the transliterated title of an old Tamil book. It means something like "My Life in Drama" as in stage plays. It can also be understood as "My Fake Life". Pun is certainly intended by the author. Thought will write a note about this Tamil book, for many interesting reasons. 

I came across this book in an article I was reading on the Tamil magazine website solvanam.com. Since it sounded interesting and is readily available to download as a public domain PDF version, started reading it. This is supposedly an autobiography written by a legend in Tamil stage plays, called T.K.Shanmugam, who lived from 1012 to 1973. You can read a quick excerpt about him at 

https://en.wikipedia.org/wiki/T._K._Shanmugam

It was written/published more than 50 years back and appears to be based extensively on the daily diary he had kept. So, it read more like a series of diary updates rather than a cohesive thesis or a well put together story. Every couple of paragraphs or page had a subsection title, as each one talked about a particular event or activity, without too much of a continuation from one subsection to the next. After a few pages I was getting a little tired with the flow and the prose. But then realized I actually need to step back to understand the overall ideas in the book on my own, rather than depending on what the author is saying page by page. Once this realization set in, I started enjoying the read. 

I was intrigued to note that even after using English as my first language for the past 3+ decades, I could read a book in Tamil much faster than I can one in English. Granted this book is certainly light reading, compared to something like Francis Fukuyama's Political Order and Political Decay. Still, this book is more than 560 pages long and I was able to read it in 2-3 days. You can either say my Tamil is still much better than English or perhaps my English will never improve to be any good till the end of my life.  

The author TKS had joined a company when he was just 5 years old and had started performing. He has written about his life as a traveling performer and subsequently as a theater company owner, spanning 50 years from pre-independence British colony India days to the post-independence Republic of India years. Similar to traveling circus groups that were popular during the first half of the 20th century in the US, there were these theater groups that were popular in India, particularly in the southern state of Tamil Nadu. Each one of these companies had a long name something like Madurai Saraswati Ghana Vinoda Nadaga Sabah. Many companies had the Madurai prefix, which refers to a famous temple town in Southern India that was historically known for poetry, literature and theater. They felt it gave them an aura of credibility, irrespective of whether they are originally from Madurai or not! 

Each group probably consisted of close to about 100 people, that constituted of actors, musicians, stage designers, organizers, accountants, cooks, managers and so on. Owners who invested money, traveled with the group and managed day-to-day affairs or employed managers and stayed in their home bases. These groups used to put together a play that could be based on one of the Indian mythologies (such as The Ramayanam, Mahabharatham or a subplot from one such mythology), or based on historically popular brave Indian kings & queens or based on contemporary societal issues that were on the forefront in those days. These groups are often called "Boys Company". Many even had that term in their company names. It actually indicated that most of the actors in these companies were 10- to 20-year-old boys. It is amazing to realize that 12, 13-year-old boys memorized hundreds of pages of dialogues and songs and then performed as full-fledged actors on these theater productions, playing both male and female roles. The tutors in the company used to teach them how to sing and act. Newbies will start performing small roles and depending upon their abilities, graduate to bigger roles, finally ending up with the lead roles on multiple plays. They are often required to memorize lines (author refers to "lines" as "paadam" in Tamil, which means "lesson") for both hero and heroine roles as they may be required to switch roles depending upon the play/company/actor availability & requirements! Those who play female roles routinely used to grow long hair to make the makeup part easier to complete. While they did employ few women actresses, since keeping young women in payroll and taking them around had its own complications and safety issues, they preferred men (or actually boys) playing female roles.

Similar to circus companies in the US in those days, these companies used to move from one town to another every few weeks. Once a town is picked, they will find a stage for which they will pay rent, find a big house where most of the company members would stay (this is referred to as company house) and start practicing. Food will be cooked and provided by the company to all the employees on a daily basis. These stage plays will start around 9:30 p.m. and we'll go on till 2:00, 3:00 a.m. in the morning, thus lasting about 5 to 6 hours or even more! It is common for these young actors to even sleep in between and then wake up to return to the stage to finish off performing their roles. Shows will not be held on weekends but more on weekdays. Audience used to finish their work and then head over to these temporary theaters to see these elaborate shows. 

There were a lot of very intriguing and interesting facts that are sprinkled around the book. For example, it was customary to print notices with interesting hook lines, exclaiming why a particular character that is part of the play is laughing or crying and encouraging people to come and see the show to find out the answers. When the company TKS belonged to moved into a small town (circa 1923), they were told that in that town there are no printing presses to print anything and so it is not a practice to distribute notices to advertise the play. The author TKS being a 11-year-old boy, was afraid to ask the elders in the company as to how else would they advertise the play in that town. But he subsequently comes to know that outside the building where the show was being performed, half a mile away, there was a marked location to explode loud firecrackers. Around 7:00 p.m. they would explode 3 firecrackers that would send out loud booms, heard by people in the nearby towns and villages in the next 5-to-10-mile radius. This will serve as an advertisement and notification that a drama company is in town performing plays. Hearing these loud booms, people will walk over or come in small carriages to the location, buy the ticket and watch the play that runs through the night. 

In the early days, there was no electricity. So, they used what are called Petromax lights. Since even these are expensive, they used to have just 4 such lights. One in front of the theater, one in the back where actors were putting on make-up and two on the stage to light the stage up. That's all the lighting they had for the big production! Author talks about difficulties they had walking from company house to the building where the show was taking place in the dark, in unpaved village mud paths, worried about animals or snakes attacking them! Usually, one elder in the company will carry a lantern and lead the walk, while everyone else will just follow that person walking in the dark. Sometimes plays used to be staged in the middle of the ground, with people sitting around (like amphitheater) as well. As the decades passed by, they moved on to more solid stages, electric lighting and lot of stagecraft involving electricity, elaborate pulley systems to show mythological characters flying, floating on clouds and so on. It was also customary to stop the play before the final scene, to allow local patrons/village heads to come and give presents (like gold medals) to the actors and then continuing with the last scene to complete the play. Picture of the book's cover page shows TKS with four different looks. He is in the middle with glasses, performing as the Hindu God Krishna on the left, as a king/warrior and as a female Tamil poetess named Avvaiyaar on the right. Since his performance in this role was so spectacular and the play was such a big success, he was given the title "Avvai" and so was known as "Avvai Shanmugam". 

Since these were the 1920s, 30s and 40s, the growth of this industry is quite closely tied up with Indian freedom fighting movement to get freedom from the British, promoting societal values such as women's education, widow's remarriage and so on. Author write with so much of exuberance about seeing national leaders & freedom fighters such as Gandhi, Nehru, Rajaji, singing in front of them, interacting with many others. Since motion pictures were also showing up to compete in the entertainment realm, these companies, actors, and owners were often involved in producing movies based on their plays. In many years/towns, collections for the shows used to be so bad that they need to frequently move to find greener pastures or switch shows from one to the next within a day to try to make more money. If the movies they produced were successful, they plowed the profits back into these productions. Many of the political parties in Tamil Nadu having understood the power of this mode of mass communication, routinely used this medium to promote their ideas and principles. Many of the show authors subsequently became political leaders, and Chief Ministers of the state. Since one division of the political party considered themselves as rationalists who were atheists, they were often opposed to productions based on Indian mythologies with Hindu Gods. Still the drama companies and the atheist politicians got along, tolerating each other as they were also often staging plays that tried to push the society in the right direction that they both could agree on.

It was amusing to see practically every name the author mentions (as actors, musicians, writers, tutors, supporters, that would run into hundreds) has their caste name listed as the name's suffix. This was very common in those days and was practically a mark of respect, though it sounds so anachronistic today! Another amusing thing I noted about the names were the double initial. In the state of Tamil Nadu in India, there is no concept of family name. Each one is given a name (my name was Sundararajan) that will be preceded by the first letter of the father's given name (in my case Vedantham) as the person's initial (and so my name in school certificates were V. Sundararajan). Occasionally my classmates (or even my Dad) used to have two initials, referring to their hometown, etc. My Dad's official name is A.D.Vedantham, where A refers to the town where he grew up in (Ariyakudi) and D refers to my paternal grandfather (Desigan). In my school days, out of 30, 40 kids in my class, usually a couple will have two letter initials. But practically every person this author refers to (including himself) had two initials! 

There is so much more to write, such as the ease with which TKS and three of his brothers, learned different languages to bring in plays from other languages in India, how they wrote down occasional English dialogs in Tamil, memorized and delivered them precisely earning kudos, so many jokes (someone's hair piece coming off exposing the boy playing girl), dangers (stage props falling down occasionally injuring actors), difficulties (local mafia asking for a cut in collection without which they won't let the production go on), the immensely satisfying literary (Shakespeare like) Tamil poetry and songs they wrote/sang, new drama conferences they conducted and prizes they instituted to nurture the trade and so on. I was also amazed to hear that each show they put together was done only after receiving proper written permission from the author and for each show performed, they provided royalty to the author. This is especially impressive, since Indian movie stories were often copied from Hollywood or other places without any copyright attribution in the 1980's, which is getting corrected now, since anything produced anywhere in the world is visible everywhere else. 

When I was growing up, movies had mostly taken over and so stage productions had dwindled and morphed considerably. I have seen many live historical/mythological/contemporary productions. But they used to be just one show performed with the support of a local cultural association, not a 25 or 50 day runs conducted by the show's own company. In the 80's these shows became mostly contemporary comedies that were cheaper to produce. These are still on since there is no Broadway type shows permanently being staged in India though different Indian states still have smaller production houses staging plays. But I do fondly remember couple of big historical productions of this kind I have seen in the late 1970's that were really impressive with their elaborate costumes, sets and magic tricks performed on the stage (e.g. to show a ghost, they will have smoke going up on the stage, on which they will show slides or projection of a ghost, etc.). 

Write back about equivalent practices/shows/customs you grew up with or have heard of during the last century wherever you live.