My interest in chemistry was stoked early on, as a consequence of my rabid pre-medical drive from the time I knew what a career was. I went through several small commercial chemistry sets before discovering that, at that time, chemical supply houses would ship pretty much anything to anyone, even if the combination of chemicals ordered together made it quite clear what the intended use was. By the time I was 12 or so, I had quite a sophisticated lab occupying half of my bedroom closet, and was spending the majority of my paper route money on chemicals, glassware, and documentation.
In addition to performing experiments that I found in books and articles, I also developed very respectable recipes for rocket fuels, low explosives, gunpowder, and the like. As I'm unfamiliar with the Statue of Limitations for some of our exploits, you'll have to imagine the kinds of things a bright 13-14 year old chemistry fanatic with access to anything might think up.
For instance, everyone knows that a major gunpowder ingredient is potassium nitrate (KNO3, saltpeter). However, after much experimentation, I found that potassium perchlorate (KClO4) was a far better oxidant, giving a much faster-burning powder without sacrificing stability (although the jury is still out on that stability thing...).
Fortunately, I had an almost instinctual knowledge of what things would be stupid to do, like grind up all the solid chemicals put out for the day's experiments, as a kid in another chemistry class actually did. The experiment concerned oxidation, and had several oxidants set in a hood, along with a series of reductants. You don't have to know much chemistry to predict what would happen if you mixed all of these solid chemicals and ground them in a mortar & pastle. Or the things that were just stupid, period - like the kid who put several ice cubes in a beaker into a dessicator, because the experiment called for - can you guess? - dry ice. I swear this is true.
During my junior high experiences, I learned a great amount of theoretical and applied chemistry, so that when I took high school chemistry as a junior, it was not particularly difficult. In fact, at that point, I'd never had a class I enjoyed so much. Part of it was the teacher - old Alden Smith was not only a dynamite, animated, humorous teacher, but became my advisor, and urged me to excel in chemistry in a supportive but challenging way. I knew I was going to love taking chemistry, but Smith stoked my interest and enthusiasm way more than it had already been. The other part was the awakening, in me, of a true love of chemistry and its challenges in a way that was unique and mystical for me. I'm sure I'd have said I was already turned on when I got there, but I didn't know, yet, what the word really meant.
A bunch of us (7-8) in Smith's class expressed an interest in taking AP (Advanced Placement) Chemistry, which was usually offered every other year, as demand dictated. We were disappointed to learn that there was literally no space in the schedule for it. However, we spoke to the teacher, who bargained with the administration until we arrived at a solution. We could have our AP Chemistry class, which would meet three times per week....at 7am!
When the teacher brought this to us, I think he expected a negative reaction - what high school kids want to be at school an hour early? - but we thought it was perfect! Most chemists are morning people, and we knew the building would be very quiet then. So, the seven of us developed a friendly but fierce competition, trying to best each other on each exam.
It's hard to describe how fierce academic competition can stay supportive and friendly, but my observation is that our little community of scholars was like my later community of competitive runners. We knew that when one person does well, everyone around them tends to do better. We knew how to psych each other up by analogy with sports classes.
It's no use trash-talking your competition, and even kids with high gpas don't feel right about using their academic prowess as a battering ram. (They'll be taught all of that later, I know.) Because, when the contest starts, it's each person against a fiendishly clever, diabolical exam written by experts with decades of experience.
By the time we all took the took the SAT advanced chemistry test in the spring, I think we were competing with each other as much as the exam. Evidently, our friendly pushing of each other paid off, as three of us scored a perfect "800" on the SAT advanced test - usually a rare event! (Modesty prevents me from saying that I got one of the 800s. (YES!!! ;-)
In college, I double-majored in pre-medical studies and chemistry, and by the time my senior year came around, I'd taken all of the required courses for both majors, and was taking electives. Two excellent electives - one in each major - were offered simultaneously, so the decision point came quicker than I'd expected.
When I thought of which class I'd rather sit in for a semester - Comparative Anatomy (cutting up various creatures' guts and comparing the bloody entrails) or Advanced Inorganic Chemistry (learning new theories of inorganic bonding then doing laboratory exercises illustrating the concepts!) - clearly, it was no contest at all! Chemistry won. Easily. And I've never regretted that decision for even one second.
I earned an M.S. in organic photochemistry from Central Michigan University in 1977, winding up with an overall GPA of 3.97 (it was a single-hour "B" in a class in which no "A"s were awarded ;-( ), enabling me to get a trip to Northwestern University - I only applied to two schools - Northwestern and M.I.T. - and after taking a trip to each, it was clear that Northwestern was the place I really wanted to attend for my Ph.D. work.
CMU had (as far as I know, it still exists) a program where all of the graduate classes were taught in the evening, each one meeting once per week for around 3hrs. This program had two halves, or "tracks", and each year, one track was taught at CMU and the other at nearby Dow Chemical Co., and its ready and steady pool of graduate school candidates. The following year, the tracks offered in the two locations were switched. The benefit to the Dow folks was that they could complete the M.S. degree in two years and not have to travel to the granting institution.
I was honestly surprised that Northwestern University wanted me to interview there before finalizing any admission decisions. Not that I ever thought I was the candidate from heaven, although I knew that I knew my stuff and I had the grades to prove it. Also, M.I.T. had accepted me sight-unseen the previous week. I wasn't nervous or apprehensive; I figured that if I got into MIT, NU was a likely bet, too.
In the event, the interview was quite low-key, and I had a great time, especially meeting professors whose work I'd known for years. From the start I got the feeling they wanted me there, but had to do the interview for reasons I never did learn. I'd already given my "interview seminar" many times, and had it down cold. The following day, I got a call from the Chair of the Chemistry Department at NU, offering me the position! I accepted immediately, whereupon he chuckled, saying "That - is the right answer!" I felt dynamite. I was about to feel even better.
All entering chemistry graduate students at NU must take a series of placement exams authored by a subcommittee of the ACS. Each exam is highly detailed, cunning in its offered but incorrect answers (extracted from decades of wrong answers by test-takers), long (3 hrs), and almost unbelievably intense. For the organic chemistry exam, there were 150 questions to answer in those 180 minutes. For three of the five exams, Northwestern chemistry faculty felt they weren't sufficiently rigorous, so they added a specially-designed addendum to the ACS tests. They did not, however, extend the allotted time for the exams.
Out of 47 entering students, after the exams were all graded and evaluated, only three students were found to have no undergraduate liabilities. Three (yes; I was one of them ;-). Buoyed by this, I looked over the syllabi for the three required courses that all new organic graduate students must take, and thought that I could pass the final in all three, if needed. As it was, I took my class materials from several CMU graduate chemistry classes and visited the profs for the three classes - and was excused from all three!
About the pressure of being a first-year grad. student in an institution the caliber of Northwestern: Nine of the 47 entering graduate students (20%) were gone by the end of the first year. As is typical, only two left involuntarily; that is, they couldn't maintain the required gpa even though they wanted to stay. The others decided that the ongoing pressure was more than they could or wanted to handle, and were unable to envision putting in four to six grueling years in pursuit of their Ph.D.s.
Anyway, I wound up working with Professor James A. Marshall, who was a major reason I wanted to attend NU so much, and is one of the brightest and most insightful chemists I've still ever met. I went in to talk to him about his research during the first month that fall, and although very personable, he was confused, he said, because new students usually did their advisor selection during the second trimester, after their three required fall courses were done (and the grades recorded). I told him that not only did I have no undergraduate deficiencies, but that I'd spoken to the three professors teaching the three initially-required courses for organic students, and all three had excused me from their classes, saying that my attendance would be a waste of everyone's time.
With a intrigued smile, Prof. Marshall invited me to sit down and talk about a total synthetic project he wanted to begin, to test a reaction he had developed earlier. Before long, I was really into the rhythm of coordinated laboratory research, arriving at the lab around 6am and never leaving before 10pm. In fact, my primary remembrances of graduate school are 1. total poverty, and 2. incredibly hard, long work with little time for anything else.
After two semesters' time on the synthesis project, Marshall and I agreed that it was going nowhere, so he asked me about taking on a project that had a reputation in the lab for being extremely difficult and a real loser. Not being one to turn down a major challenge, I said "Sure!". It was a project in basic research, preparing compounds with highly-strained, physically buried double bonds and then investigating their reactivity.
The project actually proceeded very smoothly, after I demonstrated that the prior grad. student has mis-read an important NMR spectrum which invalidated Marshall's publication on the new synthetic method. He was not at all happy, but I scored some major points and gratitude with him for quickly uncovering the error and thus avoiding his compounding it by trying to build on an erroneous result. I put a lot of intellectual effort and input into the project, and the results turned out to be in excellent agreement with the theoretical results we anticipated we would encounter at the outset.
During my third year at Northwestern, at about the usual halfway point, I reached a logical conclusion to a huge section of the project I'd been working on, and went to speak with Prof. Marshall about what extensions we should be examining. After reading my summary of the conclusion of the previous section and then talking with me at some length, he leaned back, gave me a trademark Marshall smirk, and said "Well, I think it's probably about time for you to start writing."
WHAT??!! It took a few seconds for his words to sink in, to comprehend what he was saying. He was going to let me graduate in three years! Wow! But - I knew I wanted to go into academia, and the good academic jobs are typically advertised a year ahead of the position's starting date and filled by mid-winter. It was March already, so I knew the chances of landing a good academic position I wanted were slim.
As is typical for most graduating PhDs, I applied for the three types of positions I could envision: universities that offer the Ph.D. degree, universities that concentrate on undergraduate education through research but also feature an M.S. program, and pharmaceutical companies. Although gratified that I managed to get offers from all three categories, none of the institutions was really what I wanted.
As it turned out, the charismatic founder of Aldrich Chemical Co., Dr. Alfred Bader, had visited Marshall several weeks before, and evidently asked if he had anyone graduating soon whom he could recommend. Marshall strolled over to my lab bench and asked if I wanted to meet and summarize my research for Dr. Bader. I jumped at the opportunity, not yet knowing that Marshall was springing me early. Dr. Bader made a very seductive pitch for an open position he had at Aldrich, which did indeed sound fascinating, so I thanked him and told him that I'd be in touch when I graduated. Well, upon learning that I'd be available the following fall, I started thinking about Aldrich.
The position they wanted me for was as the Principle Investigator for a synthetic group they had under contract to the National Cancer Institute (NCI), preparing proven anticancer drugs that were needed in large quantities for animal studies. The responsibilities sounded very much like an academic position, so I figured it would make a great, high-paying post-doc experience. After my interview trip, they made me a very attractive offer, and after a second trip, I accepted.
Following graduate school, I put in over three years with Aldrich Chemical Co., the largest specialty chemical supplier in the world. During the first 1.5 years, I ran a five-person synthetic group contracted to the NCI, preparing 100g quantities of potential antineoplastic drugs which had already demonstrated promise by giving positive results in screening tests against cancer cell lines in vitro.
Once these in vitro tests are confirmed to be valid and positive, the NCI then moves on to in vivo screening, using mice with known cancers. For that, the 10-15mg quantities used for cell studies won't do, and our typical request was for 100g - analytically pure, of course. After nearly two very successful years in this position, the Aldrich upper management decided they wanted me more in the "Aldrich operation" as opposed to a tangential contract group.
My last period at Aldrich was as Manager of the Pilot Plant, Aldrich's largest synthetic facility at the time, where we prepared compounds in reactors between 22L glass flasks and 500 gallon reactors in quantities ranging from several hundred grams to a ton or more. About half of our business was "catalog service", i.e., preparing compounds that sold from the catalog in sufficient quantities to warrant their synthesis on large scale.
The other half was comprised of custom syntheses, usually of pharmaceutical intermediates for new projects at large pharmaceutical companies. This was enjoyable and challenging work, as we usually had to quote on syntheses which we had never done before; the opportunity for large profit margins was counterbalanced by the chance of disastrous loses, should the synthesis fail at any step. It was stimulating and engrossing work.
In one great transaction, Searle requested 10kg of a certain compound, and upon looking over the published synthesis and the batch notes from earlier syntheses done at Aldrich which had run into problems, I decided to have the Ph.D. working for me try a drastically shorter workup that seemed very workable to me. I quoted the compound based on the literature synthesis, with a nice markup, but when the shortcut worked out so well, our markup on the 10kg batch became over 20:1!
As often happens, Searle's pilot investigations worked very well, and they continued to come back for larger and larger quantities (getting better and better pricing), and because of our breakthrough, when they finally returned for a ton (1000kg), our markup was still over 5:1 - Searle and Aldrich were both very happy, and the compound turned out being Aldrich's #1-selling chemical (measured by sales dollars) for that year. Unfortunately, Searle's final scaleup in a 10,000gal reactor failed badly, and we never saw another order. (Actually, when a pilot project reaches the 10,000gal reactor stage, the pharma usually takes the synthesis back to their plant.)
But I wasn't teaching and I wasn't doing original research - the life of a research-oriented academic to which I felt an ever-stronger calling. So, as my 30th birthday loomed closer, it was clearly time to move to academia if I was going to do it at all, so I started sending out resumés for assistant professorships. I was quite sure I wanted to be at a school with a master's, but not a Ph.D. program; regardless, I figured I'd apply to both types (as my M.S. adviser reminded me once, "You can't turn down a job you haven't been offered."). Omitting the gory details, when it was over, I had three offers each from PhD-granting universities and PUIs (predominantly undergraduate institutions, including those with master's programs); when the comparing and contrasting was over, I wound up at Eastern Illinois University.
The academic lifestyle clearly suited mine, and I rapidly rose through the ranks, earning promotions and tenure several years early on the basis of exceptionality (usually in the area of Research; sometimes in Teaching). I established large, diverse web sites to support my various classes. Each class had its own site, with main page, syllabus, score data (high, low, average for each quiz/exam; current state of the curve), supporting handouts, and other supplementary material, and an archive of all the quizzes and exams I'd given in the class since the web project began (about 1998). The archive was extremely popular, not only because it gave a good idea of what future tests might be like, but I also provided blank copies of the quiz/test in addition to the key. That way, a student could download a few blank quizzes and go through them to check their current comprehension.
A notable feature on my academic main page is the collection of link libraries listed (and linked) at the bottom of the page. This link also appears on the thblack.com index page. When I became interested in a topic, I would gather web (and other) citations to it in specific directories on my PC, in a format I can readily use to find a certain piece of information very quickly. More often than not, I found that it filled an informational need on the web that no one else has done, or perhaps had not done as deeply as I have. I then HTMLified the page, uploaded it to my site, and linked it appropriately.
So far, there are eight link collections: Group Handbook (from the research group), Medicinal Chem. (for the layman, great links about drugs, illnesses, pill I.D. etc.), Links for Organic Chemistry Students (for students in any organic chemistry class), RSD/CRPS-Chronic Pain (concerning Reflex Sympathetic Dystrophy (RSD), a horribly painful nerve illness that's widely under reported; I've had it for 16+ years), Links for Researchers in Organic Synthesis (great for anyone in an organic synthesis lab), WebTools (links for the web page developer and creator), Modeling/Animation (covers modeling and 3D representation of molecules; a large link collection for those into computer simulation of molecular shapes, calculation of molecular energies and other characteristics of the species, modeling of drug-receptor interactions, etc.), and MedChem. Links (a large collection of links to upper-level subjects in medicinal chemistry such as PD-PK, computer modeling of pharmacophores, rational drug design, QSAR, etc.).
One of the biggest challenges at a master's level department like EIU is to identify research projects that are important, exciting, fundable, and publishable, but not so hot that a large research group at a high-powered research institution with an army of postdocs is going to blow you away during the first year....
I was fortunate in that I arrived at EIU with two projects that I had good reason to believe were ideally suited for the position I'd accepted. One of them had been almost serendipitously discovered during my tenure running the NCI synthetic group. We knew that it was novel and potentially very useful if its generality could be demonstrated, but since Aldrich does no research, we had no time to chase it down. However, I felt that it had tremendous potential, and we knew for a fact that it worked from the NCI work - not only did it work admirably, but it functioned just as well on a 400g scale as on 50 milligrams!
The other project was the topic of the original research proposal I had to write as part of my graduate program. Not only did Prof. Marshall like it very much, but two members of my thesis committee (before whom I had to orally defend the proposal, without the psychological benefit of the presence of Prof. Marshall, who was replaced on the committee for this specific purpose) opined that it would definitely be fundable in a competitive grant program. So, although I had no published preliminary experimental results to point to, the expert opinions of the Northwestern professors were good enough to give me the confidence to submit it to a "starter" program for new professors.
As it turned out, these two synthetic projects formed the basis for my research programs during my entire 22-year career at EIU, along with a few other things that turned up along the way. I'll describe them in layman's terms, such that a relatively intelligent non-scientist should be able to follow them easily. One is called "PBF Chemistry", or "The Blue Reaction"; the other is known as "beta-Lactone Chemistry" (more correctly written as β-Lactone) or "The Chemistry of Strained Rings".
It is a major undertaking to form a research group, populated with smart, enthusiastic research students. Fortunately for me, the other organic professors at EIU hadn't done any real research for years, and organic chemistry is a wonderful discipline in which to attract and involve students. In fact, I had two students approach me at the start of my second semester! They got a third student to join us, and my fledgling group was up and running. A proposal I'd written during my first semester was unexpectedly funded, so we were incredibly solvent (!) with $18,000 to use in our investigations.
Rather than including a long narrative detailing the activities and successes of my research group, a much better appreciation of this exciting, vibrant, self-starting group of student researchers can be had by perusing our group website, whose composition was maintained by group members (after I lent them much technical assistance).
In addition to inventing new synthetic reactions, we also explored potentially new drugs; the most recent project was aimed at the treatment of neonatal apnea, which is the sudden cessation of breathing in neonatal infants and is the major contributing factor in Sudden Infant Death Syndrome (SIDS). The pulmonary system is the last to develop in mammalian embryos, so if one is born prematurely, its pulmonary system will be underdeveloped. This project was undertaken in collaboration with an EIU pharmacologist, Prof. Kip McGilliard, who not only had developed a very clever in vivo model of the syndrome; he also developed an excellent set of structure-activity relationships (SAR) on the molecular family (the xanthines, of which caffeine is the most well-known member) on which we focused our synthetic efforts.
Other projects on which we published quite widely involved extensions of our β-lactone work into the large family of β-lactams (the pharmacophoric moiety (the part of the molecule responsible for its biological activity) of the penicillin and cephalosporin antibiotics) and on the synthesis of several pharmacologically active natural products or their primary carbon skeletons using our β-lactone methodology. Naturally-occurring medicinally active compounds whose synthesis we investigated and usually accomplished included andirolactone, heritol, a series of Streptomyces lactones, and diazonamide A.
During 20+ years of operation, the Black research group published about 50 peer-reviewed articles and book chapters, gave many dozens of invited seminars at major research universities, attracted over $1 million in extramural research support, and involved nearly 130 talented research students, who stayed with the group between one semester and nearly three years. My involvement with and guidance of this fantastic group is the single most wonderful memory I have from my teaching career.
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