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Introduction

"Who are you? Where are you from?" Two questions everyone is asked sooner or later in life. They're harder to answer than you might think. Most people answer the first question with a sentence or two about what they do. "I'm an airline pilot. I'm an army officer. I'm a lawyer. I'm a plumber." And so on, a puppet, a pauper, a pirate, a poet, a pawn and a king, to quote a famous blue-eyed performer. (He didn't write those lyrics, though. He'd have probably said he was a singer.) But who was Frank Sinatra, not "what did Mr. Sinatra do"?

Okay, I'm going to tackle that one. (No, silly, not about Frank Sinatra!) I'm a philosopher. Somewhere in my attic there's a piece of paper proving it. It's the document my graduate school gave me after I finished writing my first book, which was a dissertation "in partial fulfillment of the requirements of the degree of Doctor of Philosophy." It was all about organic chemistry, which was an amazingly useful subject to study. It may not have been read by more than a half dozen people, half of whom were on my thesis defense committee, two others being my late parents who through no fault of their own wouldn't have understood it at all, and the sixth being yours truly because when you write a book, you read it so many times you get sick of it. But yes, it was useful because it taught me how to think and to put a story together, although that's an art form still requiring a lot of honing. I could have said "I'm a chemist." Or, to give it more depth, "I'm a medicinal chemist who worked on developing drugs for serious diseases." Both are true, but that's what I do, or at least did for several decades. It's not who I am. The advanced degree doesn't say "Doctor of Chemistry" or even "Doctor of Science." Those accolades belong to honorary recipients who may have achieved certain notable accomplishments in their lives, and more power to them. No, it says "Doctor of Philosophy" which suggests I've qualified as a philosopher. Take that, Plato, there are lots of us out there. Let's chat if we ever meet in the afterlife.

On to the second question. Where are you from? All I can say is it's been one long adventure for this nomad. When I was much younger, I really struggled with the concept of "from." Was it where I was born? Was it where I lived, or where my family lived? I conducted an exercise recently to help me record all the places I hung my hat in the last six and half decades, and there turned out to be more hat stands than you'll find in your average pop-up millinery. My birthplace was in the only city in Great Britain that's on an island - not counting the whole joint of course (trivia gem). That's Portsmouth, on the south coast of England. I lived there for a grand total of seven months in one stint, five more in another, so a year in total. Is that enough to say where one is from? I don't think so. Then again, for the next seven years, we moved another eight times, different towns, a couple of different countries, less than two years in any of them. More countries and locations followed over the next decade until the family settled in the USA. I stayed there a while too, living on either coast and in the middle as well. A half dozen more "home towns" if one tallies up all the different zip codes. And finally, a peregrination across the International Date Line and the Equator. On the north side of the Southern Ocean, this rolling stone came to a blessed halt and gathered moss. Home at last. Melbourne, Australia. It's not where I was born. It's not where I spent the other scattered two thirds of my life but it's where I belong. It's my answer to the question.

But let's come full circle, shall we? Back to "That's Life" by Dean Kay and Kelly Gordon. Sung by Ol' Blue Eyes, but he wasn't the first, and I'm going to plump for David Lee Roth as the surprising best. Personal opinion: at the end, "Dave" declares not that he's going to roll himself into a big ball and die. Instead he sings that he will roll himself into a big ball and FLY! That's much better! For me, I haven't been a puppet etc. but many years in the pharmaceutical industry, one way or another, have yielded many valuable lessons. Some of which I'll no doubt allude to in this blog. This occupation has also given fancy to a number of insights and ideas for fiction. No, not highbrow literature or the type of prose that critics would regard with frenzied enthusiasm. Many critics feel honor-bound to live up to the word itself and do nothing but criticize anyway. Perhaps rolling themselves into big balls and dying when there's nothing left for them to find fault with. No worries. If readers pick up a paperback in a used bookshop, an airport display, fish it out of an online shipment, or download it onto an e-book reader, and enjoy the stories, that's good enough for this old hack. It's fun writing them, and if you say "don't give up your day job" I won't be offended. Because the same has probably been said to any number of us. That's life, and being positive is to fly.

Hall of Fame

That's an odd title, but like many ideas, it came to me while waking up a wee bit earlier than intended. The first baseball player I ever heard of, about 60 years ago, shares the same name as mine. He pitched for the Baltimore Orioles, won more games than any other in the 1970s, never gave up a grand slam, and made it into the Hall of Fame in his first year of eligibility. It got me thinking. To be considered for the Hall of Fame as a pitcher, you often have to have won at least 300 games in the major leagues (Or, like my namesake, win multiple Cy Young and Golden Glove awards). As a batter, it helps if you amass 3,000 career base hits, or, for instance, have a long career with an overall batting average of 0.300 or more. See a pattern? A lot of threes. When you think about it, though, "hitting 300" for a career means you manage to get on base (outside of being walked either intentionally or due to the pitcher's inaccuracy) thirty percent of the time. And that's really, really good. Tough gig, pro baseball. Seventy percent of your attempts result in the umpire giving you the thumb and sending you back to the dugout. Try again next time, batter. The guy on the mound has it a bit easier. Even if he starts spraying it all over the shop there'll be a specialist in the bullpen who can come in and save the day. Sometimes.

When I first arrived at graduate school to study synthetic organic chemistry, one or two of the more experienced sloggers (yes, graduate school is a slog) would say something like "If you can get ten percent of your experiments to work, you're doing well." Wow. That suggested ninety percent of them go south. That percentage is a lot worse than a good professional baseball player's bad trips to the plate. Natural product synthesis, which was always considered the most useful discipline in organic chemistry serving to educate those seeking a career in the pharmaceutical industry, is very challenging. You're presented with a target, complex molecule that you have to build from scratch, otherwise known as starting materials available for purchase via a chemical supply house. You have to design a way to make it through dozens of sequential steps. Each of these can fail at any time, requiring a return of sorts to the drawing board, literally. To make a long story short, making one of these natural products might be enough to earn a graduate student a PhD. Often, even getting part way is enough. Whole teams of students are occasionally assigned to build a single molecule, so complex might the target be.

Hall of Famers in the natural product synthesis world include famous academics, for example Elias J. Corey, Nobel Laureate, 1990. (Same year as the bloke in the first paragraph entered Cooperstown in a different discipline.) They can count many dozens of former students who have gone on to be well-deserving of recognition in their own right, one way or another. All, however, will testify as to how challenging their tasks would have been. Using a ten percent success rate, that would mean one would need to perform a thousand experiments to complete a ten-step sequential synthesis route. Three experiments a day would mean about three years of work to get the job done. Gee whiz, there's the three factor again. Funny, that.

Yes, the arithmetic is simplistic but it's one of those curious little parallels. More on the intricacies and challenges of making natural and unnatural products later, but there's another way to look at this entirely, and it's this. No experiment fails if it is performed. That means the senior, jaded students battling the elements to complete their advanced degree programs could have been viewing their success rates pessimistically. Why? Because when you conduct an experiment, you learn something new. You may not get the result you were hoping for, but you still get a result. That revelation will provide guidance in one of three ways. (1) Hooray, everything turned out the way you hoped, and you can move on to the next step. (2) Oh, crap. This was not the right thing to do. You've destroyed the goodies. You have learned not to do this again, and that's very useful information. (3) Hmm. Looks promising but needs a tweak here and there. You're on the right track though. The common thread here is that you've asked a question, and you've received an answer. You ran an experiment and discovered something new. That is not a failure. It is a success. And the Hall of Fame, whether Cooperstown for baseball, Canton for American football, Cleveland for rock and roll, or Stockholm for chemistry, physics, physiology and medicine, and literature, is full of success. (I won't mention economics or peace because no one seems to have gotten them right or the world wouldn't be loaded with debt or conflict, but that's a topic for another rant.) That's life, and thinking in terms of success is to fly.

He's in the drug business

About 25 years ago I had occasion to fly from San Francisco to Montreal in order to meet with corporate collaborators. We had these face-to-face meetings about three times a year, rotating between the aforementioned sites and one in West Point, Pennsylvania. (Readers might be able to figure out which companies were involved). In between these summits, we conducted three-way teleconferences in boardrooms at our respective facilities. These events were fraught with technological hurdles. At first, we thought it would be nice to have everyone piped in by the video technology of the day. Note: it wasn't anywhere as good as Teams or Zoom even, and while Skype wasn't yet in its infancy, it probably worked better. Routinely, we would spend anywhere between 30 and 60 minutes overcoming the inability to see each other or project slides so remote viewers could see our presentations on screen. During these fiddly manipulations, sound and/or vision would invariably cut out when the bandwidth choked. After several iterations of this aggravating recurring phenomenon (which never coughed up the same problem we'd fixed before, therefore thrusting all of us and our IT experts into fresh paroxysms of frustration) one of us had a bright idea. Instead of attempting to display our presentations on screen, let's completely dispense with the video and instead restrict ourselves to a three-way conference call. Prior to the meeting, all slides and materials would be circulated at least a day in advance so that everyone had a chance not only to peruse the data, but formulate questions without having to fight a losing battle against the Internet. Lo and behold, it worked well. Everyone had a copy of the slides to make notes on, and all presenters needed to say to orient the audience was say "Slide X" or "Next slide." Soon that too became unnecessary because everyone was in sync with the flow. It may not have had a major effect on the project's progress as a whole, but it sure simplified the communication. The take home message is that sometimes the best solution isn't the most technologically advanced. I'll come back to that some other time, because it has all sorts of implications in healthcare.

But at the risk of digressing (oh, dear. Too late...). This very same project was one I was leading on the smaller partner's side, so I was responsible for pulling together the lion's share of our sub-team's slides to present at one of the actual face-to-face meetings, where we all got to see each other's body language and get a sense of individuals' tastes in assorted meals and beverages throughout the two-day event. The program was reaching an intriguing stage of its development, and we were all excited about where it could lead. (Side note, we wanted it to lead to successful clinical trials and ultimately to a marketed drug, if that wasn't obvious). The San Francisco team had to change planes in Edmonton, Alberta, before boarding an internal connecting flight to Quebec. And that's where I made a mistake for the first (and stupidly not the last) time. It's an oddity, perhaps, that customs and immigration services between the US and Canada are in the latter country. When flying from the northern nation to the southern one (can't speak for Alaska, never been there) you actually pass through border control when you're still in the Canadian airport. It's as if the post-security section of the terminal is technically on US soil. Saves a bit of time, admittedly, because when you land back in the States, it's as if you've flown in from Chicago, or Boston, or LA etc. Straight into a domestic terminal. But going the other way? Yes, you're in Canada too when that happens, and if you're not careful, you could get a whole slew of questions you hadn't anticipated.

Edmonton was where I made the silly mistake of telling the truth. "What's the reason for your visit to Canada?" said the border control officer. "I'm here for a conference." Not a lie. A conference is where one confers. I've used it many times when being asked to enter countries all over the world, often when giving talks or presentations at conferences. But it can also mean discussions among interested parties, and you only need two people to make a conference. This officer wasn't buying it. "What's the conference about?" he asked. "A project collaboration with our partners," I said. "Where do you work?" I told him the company name and its location. "What do you do?" he followed up with. "I'm a chemist." BOOM! (No, that sound didn't go off. It was an airport. Not a good place to say "Hi" to your pal named Jack.) Up went the red flag. Chemists are bad. Organic chemists are really bad. They made a show about one a few years back called Breaking Bad. "What kind of chemist?" He was looking through my passport and his screen, and glancing sideways at his colleague, who looked to be about to give one of my co-travelers and colleagues the hairy eyeball himself. "I'm a medicinal chemist." A bit of clarity. Next question please? "What are you working on?" For crying out loud, I can't tell you! It's proprietary. Not in the public domain! For the joint project team's eyes only! Shoot, what am I going to say, I wondered. "We're developing a treatment for osteoporosis." Good thing I didn't say joint and bone disease. They might have taken the "joint" part out of context and given me a full cavity search next. I was beginning to wonder if I was going to be asked to whip out my presentation and give it to them. Instead the guy smirked at his buddy. "This guy's in the drug business." He handed my passport back. I thanked him and remarked "If I'd said that to you, you wouldn't be laughing."

The next couple of times I traveled to Montreal, irrespective of route, I always got singled out and grilled, coming or going. The assorted forms you need to fill out when entering or leaving certain countries require you to state your occupation. That's when I learned my lesson. I stopped putting "chemist" on the form and replaced it with "Biotech Research." It was like night and day. A couple of times I'd get a question flying into LAX or London, like "what do you do back home?" and I'd say "cancer research" (again, perfectly true, collaboratively). No longer was I the evil meth lab suspect. More like "Cool. What kind of cancers? We need help with such and such." "Working on it," invariably brought a nod of appreciation. That's life, and doing something to help people is to fly.

Indiana James and the Equation of Doom

Wrestling with troubling equations was made tremendously easier with the advent of the pocket calculator in the early 1970s. Until that point we had to rely on log tables, algebraic transformations by hand, and of course slide rules to help crunch the numbers. Significant figures be damned: more than three was a luxury. How the astronauts of the 1960s coped with traveling to the Moon has always been a monumental triumph of computation. That achievement was personified by the extraordinary skills of Katherine Johnson, the closest thing to a human computer there was in those days. It's said that John Glenn himself wouldn't trust the actual computers' projections of his first orbital trajectories until Mrs. Johnson checked them by hand. Roll on a few years and the very first electronic four-bangers came on the market. These delighted many who were fed up with sliding cursors back and forth over ever-stiffening 12-inch and 6-inch slide rules whose scales required a magnifying glass to read otherwise. Including myself, as I progressed through high school math. The added advantages of scientific funcions like trig, logs, roots, and (gasp) exponential notation and memory spurred me on to upgrade from my Sinclair Cambridge to a Sinclair Oxford 300 (go ahead, look those ones up if you dare!) The latter kept me going into college, where the arrival of a Texas Instruments TI58 along with its programmability and statistical capabilities was the next leap. It was my companion through graduate school in the great state of Indiana. There I made two more discoveries. One was that I didn't need most of the functions any more, especially anything involving hyperbolic trigonometry. Esoteric delights like Poisson and Weibull distributions were of no interest. Occasionally I stumbled across a Student's t test, but beyond that, most of it had no application in my world. Still, it's one thing to need a capability, entirely another to know you have it should the need ever arise. Which brought me to the second discovery, Hewlett-Packard and Reverse Polish notation. As in 3 enter, 4 plus, gives you 7. Easier than 3 + 4 equals, gives you the same. It's like Marmite for Brits. You either love it or hate it. In my case I took to it like a duck to water, and now I struggle to use calculators that don't use RPN, as it's called. I started collecting HP calculators, some for use of course, others simply because I liked them. Scientific, graphic, financial, you name it. I still have several, despite having sold many on eBay (yes, there's a market for vintage models). The one thing that struck me about a particular example was that it had not only scientific functions built in, but also financial ones as well. Then there was the gold standard HP12C, first marketed in 1981, and still going strong 45 years later. Had all the useful financial functions but sadly lacked the scientific ones, or at least sines and cosines and stuff. What a silly oversight, but there it is. And that's what brought me to realize what's at the root of the world's economic problems. It's the equation of doom, and it's the same one that's built into every HP12C, HP17BII+, and even the newer models other manufacturers push out to high school and college kids. It's called the TVM equation, or time-value-of-money.

Why is this equation so heinous? Here's my answer, and I'm sticking to it. Put in simple terms, it can be written as PMT x 100 x (1 - (1 + I / 100) ^ -N) / I + FV x (1 + I / 100) ^ -N + PV where PMT is the payment amount, FV = future value, PV = present value, I is the interest rate, and N is the number of compounding periods. Financial calculators all have these buttons that allow you to solve for any one of the variables given the other four, and it's an amazingly useful feature if you want to know how much you can afford like a mortgage or a car loan, or, for example, how much interest you'll make when saving. There are derivatives of this equation and other terms like net present value, internal rate of return and the like, involving uneven cash flows etc., not to mention subtleties regarding whether the mortgage calculation is performed in Canada, but I won't go into that here. What I will point out is the notion of amortization. This is what happens when you take out a large loan and need a long time to pay it back. Imagine, for instance, that you buy a house for a million dollars. (Yes, that's getting quite realistic these days, if not a painful thought.) Forget the down payment and finance the whole buck. Over a standard 30 year mortgage, paid monthly, with an annual interest rate of 6%, your payments are: (thanks to my trusty HP Prime!) $5995.51. Per month. Over 360 months, that adds up to $2,158,383.60. More than twice the amount you've borrowed. The interest payments alone are more than the principal. Even with a 4% interest rate, your total interest payments add up to $610,694.00. And with an 8% interest rate (the horror...) you'd pay $1,641,554.00 in interest alone. Money literally thrown away, the only beneficiary being the lender. But what's worse is the staging of the payments. They are front-loaded in the interest portion, such that in the first year of our 6% interest rate example, you only knock off $12,280.17 of the principal. $59,665.95 goes towards the interest. Sixty grand a year, tossed aside. Think about it. If 6% were charged on top of a million bucks, that would be an extra sixty grand you'd pay. Total. Wouldn't that be nice? But that's not the way things are done. In the amortization schedule, you have to keep paying for 21 years out of the 30 to see the principal on the loan drop below $500,000. You've already paid a shedload of interest by this point. $978,960.72 to be precise. Almost a million bucks and you still have another half a million left on the principal over the next nine years, although it will diminish more quickly now. See the problem?

Aha. That's why everyone is in debt. I'm not talking banks, but many individuals and especially nations. If it takes the average household 30 years to pay off the biggest debt it's likely to incur, how can one expect a country to solve its own debt burden within a single election cycle? Answer: It can't. And this is why virtually every large economic powerhouse, and a whole bunch of the smaller ones, are deep in the red. One hears words like trillion-dollar national debt, interest in the hundreds of millions, or billions. (That raises the question no one ever seems to answer: to whom is all this interest owed, who determines the interest rates in the first place, and who's actually making money off it?) Frankly it doesn't matter, because all they ever seem to do about it is agree to spend more money they don't have in the first place, or print more, throwing terms around like quantitative easing, and so on. They try to claw some of it back by the only means they can think of, such as taxes, but does that help? The short answer is no. It never works. No country has ever taxed itself into prosperity, and the reason behind it all is the blasted TVM equation. It's destined to cause the imbalance. (Irony. Equations are supposed to balance....)

There was a pretty famous tax collector, a bloke called Matthew. Oddly enough, a book he once wrote, at least in the King James translation, chapter 6, verse 12, he reports: "Forgive us our debts, as we forgive our debtors." Various denominations of the Christian faith use words like trespass(es) to replace "debt(or)s" in the Lord's Prayer, but perhaps Matt's account (or was it his reformed accounting practice?) was on to something. We'll never solve the debt problem when the TVM equation of doom is at work, because it totally shafts those who owe money. That's why it's really, really good to avoid debt as much as possible. Let's face it, the powers that be haven't figured it out yet, but when we find ourselves no longer beholden to lien holders, we can sleep better and worry a whole lot less. That's life, and getting out of debt is to fly.

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