Graduating My First PhDs

It’s been far too long since I’ve written a blog post, but I think I have a good excuse: I’ve been focusing on getting tenure. It’s been a 5-year, assistant professor roller coaster ride. But the ride is nearly over. Weirdly, it feels like just yesterday, but also a lifetime ago, that I shared my experience during the job search, wrote my memoir of a first year assistant professor, and captured our first year in lab with a time-lapse camera. My tenure package is submitted and my external letter requests are out. Thankfully, my group has been very productive and we’ve published some really solid science. I’m optimistic about tenure and it is honestly a relief to have my portion of the process behind me.

My tenure timeline also coincides with the bittersweet experience of graduating my first PhD students. While I am not a fan of ceremonies for the sake of ceremonies, I can get behind the pomp and circumstance surrounding a PhD graduation. I sat through two different 3-hour graduation ceremonies, one for the College of Arts & Sciences and one for the College of Engineering, and it was worth it. It isn’t every day that you get to be a central part of a centuries-old tradition. I hooded my students, just as my advisor hooded me, and his advisor before him, in a chain that dates back to the earliest Ph.D.’s over 500 years ago. While the thesis defense is typically anticlimactic, the Ph.D. hooding ceremony has a formal grandiosity that’s well-earned following 5 years of dedicated effort.

I have mixed emotions about losing (err…graduating) my first students:

• My students certainly earned their ‘Dr.’ title
• I’ve contributed the growth and development of some truly exceptional scientists and I look forward to seeing what they accomplish next
• I got to hood my first PhDs!
• I got to wear my most expensive outfit (hood + gown = ~$1,000)
• My lab now has room for more new students
• I have several new connections entering the academic and industrial communities
• It’s time. There isn’t much more they can learn from me
• Now that I have academic progeny, I’m more motivated to add my information to my graduate and postdoc advisors’ academic family trees

• I lost fifteen years of combined practical lab knowledge in a weekend
• Now that they are especially good at writing papers, they are leaving
• I had more time with these students while creating our lab than I will probably have with any others. I am going to miss them
• I am not entirely sure that all of our instrument and account logins and passwords have been handed down
• They each have their own unique skills. While some of these skills will be replaced by new students, others are irreplaceable


In preparation for their departure I contemplated two questions:

1) How do I commemorate my students time in lab?

I really wanted to do something tangible and long lasting to commemorate their time in my group.

Approximately five years ago we started Photo Friday by sharing one photo of our research every week on our Twitter and Instagram accounts. Since then, my group has captured some truly remarkable images. One was selected as C&EN’s 2015 Chemistry in Pictures photo of the year. This included a spread in an issue of C&EN and a grand prize award of a DSLR camera.

My wife and I liked the photos so much that we decided to incorporate them into our home decor. We found an online printing company to create 8” x 12” metal prints of our favorite photos. The number of prints grew and below is a photo of our current collection.

Each photo has its own story. For example, the second photo down on the far right was included in the TOC image of our first corresponding author paper.

So, in a kind of wonderful but unintentional way, we happened upon a way to commemorate my students: we asked them to sign their work. On the back of their photo is I asked the students to write their name, signature, degree, and year of graduation.

2) How do I keep track of them after they leave FSU?

Two years ago, at the Fall 2016 ACS meeting, I organized a special symposium to celebrate the 75th birthday of my postdoc advisor, Thomas J. Meyer. The event included three days of presentations and a dinner for both the speakers and all Meyer group alumni (AKA The Meyer Mafia). Part of my organizing duties involved contacting and inviting as many alumni as I could find. Thankfully, Prof. Meyer’s secretary had an excel spread sheet containing over 150 names spanning more than four decades. While it was not comprehensive, and some of the email addresses and webpages had long-since died, the list was impressive and very helpful nonetheless. The symposium and birthday party were ultimately a huge success. The proceedings even helped populate a book, aptly titled The Ru(bpy)3 Legacy, commemorating Prof. Meyer’s impact on the research community and his students. The book also included a list of all his academic children and their current affiliations.

The symposium allowed me to meet, face-to-face, the people behind the papers I had read for years. It also made me very reflective. How was I going to keep track of my students? Over the course of 4 or 5 years you spend hundreds of hours in meetings together, exchange thousands of emails, and learn a hundred little details that you might not even recognize. For example, I can identify who’s about to enter my office based on the rhythm of the steps coming down the hallway. The advisor / student relationship can sometimes be a love-hate but hopefully it is still deeply rooted in mutual respect. And while we (mentors/advisors/professors) don’t always show the impact students have on us (I for one am an emotionless robot) the bonds of a quality mentor-mentee relationship run deep.

It is for this reason that I am going to do my best to collect private email addresses and current affiliations. My hope now is that they will continue to contact me and update me on their major milestones. It is always a pleasure to hear from Hanson Research Group undergraduates who’ve moved on (even though they have only been gone for a few years). In the future I will look forward to hearing from my newly minted PhD students too.

By June 18, 2018 0 comments Chemistry Art, fun

2050 – A world without plastics

An experimental bit of writing – be nice 😉


The 20th centuries wonder material had turned into a blight of biblical proportions. The world was awash with plastic. From obvious fragments of polystyrene packaging, to polyethene shopping bags, and discarded PVC furniture to the microscopic micro-fibres shed from our polyester clothing during every wash. It accumulated in great, becalmed garbage patches in the middle of our oceans or washed up as vast invasions of flotsam, where it was consumed by wildlife, mistaking our discarded packaging for food.

Meanwhile the currents and geological forces abraded the jet-sum into tiny fragments that found their way into, well everything. Our cheap, durable and omni-present material had reached every corner of the globe, it had became part of the very fabric of the planet. Geologists coined a new type of sedimentary rock; plastiglomerate – part plastic pollution part stone.

For decades the litter had been building. The obvious detritus featured on every street corner, beach and country park. It became part of the scenery, we got used to it, ignored it, or mildly complained, whilst making sure we kept hydrated by sipping from our water bottles, that we clutched like life-support systems.

Then almost two decades into the 21st century the zeitgeist shifted. Seemingly triggered by the haunting image of pilot whale grieving her dead cub. The narrator blamed plastics. Our blinkers fell away, and we noticed the plastic as if it had just been dumped on our doorsteps. Unlike the invisible carbon dioxide, ravishing the climate and the oceans, we could point at this culprit.

Almost overnight plastic packaging became universally distasteful. Shoppers curled their lips when offered a plastic punnet of mushrooms and then stripped of the useless artificial skins from their purchases before dumping them in front of the supermarkets. Companies raced to see who could strip the plastic from their products the quickest. Listicle blogs sprang up providing tips on how to throw the ultimate plastic free dinner party. And, much to children’s dismay, drinking straws disappeared from cafes across the land.

Politicians were as quick to jump on the bandwagon, keen to cash in on the voters’ new plastic outrage, they vilified cotton buds, toothpicks and wet wipes.

But all this outrage, bans and boycotts was just tinkering around the edges. One small island’s war on drinking straws did little more than remove a mole hill from the mountain of the world’s plastic waste. Something much more radical was needed.

Gaia had the beginnings of an answer. She was used to cleaning up detritus. Over millions of years the myriad of micro-fauna have found biochemical ways to harness the resources from organic dead matter. But plastics had only been around for a few decades. So microorganisms simply hadn’t had enough time to evolve the necessary biochemical tool kit to latch onto the plastic fibres, break them up and then utilise the resulting chemicals as a source of energy and carbon that they need to grow.

Or so we thought.

But deep within a Japanese rubbish tip, devoid of organic matter on which to feed, evolutionary pressure had selected an organism with a new feeding strategy. Nature it seemed, had quietly made a start on tackling our plastic plague. Somewhen, in the recent past, a bacteria had undergone a random mutation and a protein that normally allowed the bug to feed on fats had been converted into one that empowered it to digest plastics.

Not that the plastic waste was noticeably decomposing. The bacteria wasn’t up to the scale of the job. After all, it was a mere evolutionary infants, taking the first tentative bites of a new food, still unequipped to make full use of it. It might have been decades or longer before anyone noticed the rubbish was rotting. Or maybe some other natural pressure may have been to much for the new species. It could so easily have gone extinct before anyone ever became aware of its existence.

But for Prof Yoshiharu Kimura’s eureka moment. Struck by an inspiration particle, it occurred to him that the obvious place to look for a plastic eating organism was in the heaps of rubbish. For five years he hunted through 100s of samples of soil, sludge and stagnant water seeping out of tips and recycling plants. Then, back in the lab, he painstakingly tried to grow something, anything, by feeding his soup of organisms little more than ground up polythene bottles. Miraculously, in just one dish a single bacteria flourished, multiplied and thrived. Soon he had a viable culture. Professor Kimura had found the needle in the plastic stack. He called it Ideonella sakaiensis.

For a while people were mildly interested, there was a flurry of pressproclaiming the solution to the plastic problem may have been found. But soon the excitement died down, for this was still two years before the dead whale cub was beamed into homes around the world. And so the newly discovered I. sakeienis slipped from the folk mind. That was until, a second breakthrough came. Perfectly timed, on this occasion, coinciding with the new anti-plastic movement. Professor Kimura had been happily sharing his cultures with scientist far and wide, and and one group had accidentally genetically engineering the protein that empower I. sakeienis to be a much more efficient plastic digester. In those 24 months they had done what nature might have taken centuries to achieve. The bacteria hit the headlines. They showed the world that by taking what Gaia started and combining it with 21st century biotechnology we could at last tackle the plastic problem of our own making.

Genetically modification of organism, vilified for decades as the technology that would destroy our ecosystems, suddenly became the answer to all our worries. Folks who had ripped up experimental GM crops, fell over each other in their efforts to support genetically enhanced plastic munching microbes. After all, the plastics were unnatural and evil. And so, they reasoned, it was perfectly acceptable (at least in this case) to utilise GM bugs to clear up our mess. It might even be that we were just giving nature a helping hand, it was possible that some organisms might even have made a start on the plastics in the oceans.

The great cleanup began. Governments and eco-charities around the world throw money at the problem. What started with the odd publication here and there became a torrent of papers describing newly discovered and genetically enhanced bacteria, fungi and even worms. All equipped with an arsenal of plastic eating enzymes. Soon concerned citizens got in on the act. School science fairs featured projects dreamt up by keen children attempting to breed plastic-eating creatures, the maker movement got involved, as they discovered home bio-hack kits could be used to tinker with microbes molecular machinery.

By 2022 we had identified thousands of organisms, both naturally evolved and artificially enhanced, equipped with the molecular and mechanical machinery required to set to work on our poly-materials. In just a few more years the impact was tangible. Recycling plants quickly harnessed the new biotech boom to turn rubbish into fuel and chemical feedstocks used to create, amongst other things, fresh virgin plastics. Plastics production and recycling had at last become a truly circular economy. It even became economically viable, with the help of solar powered drone barges, to sweep up the great ocean garbage patches.

The oceanic rubbish rafts shrank, plastics slowly rotted on our beaches, reports of plastiglomerate dwindled. There was a collective sigh of relief.

Except it wasn’t just the rubbish the new breed of bugs were eating. Once out in the wild they were unable to distinguish between refuse and infrastructure. Whether the plastic-munching organisms escaped from the recycling plants, the amatuer bio-hackers’ sheds, or just naturally evolved, we can’t be sure.

The world was once crisscrossed with polythene pipes delivering gas and water to homes and industry. PVC insulated electrical cables and sheathed the world’s fibre optic communication networks. The many uses of plastics were incalculable. At its peak 350 million metric tonnes of plastic materials produced annually had formed the fabric of not just our single use packages, that we so quickly discarded, but also the very structure of our civilisation. And now that fabric rots like so much soft-wood.

By May 8, 2018 3 comments opinion, science news

Chemistry Blog needs you!

Poor old chemistry-blog, its being going since 2006, but its been a bit neglected of late. So as it approaches it’s teenage years, (13 in May!) we felt it could do with a new lease of life.

So we’re blowing the dust off the old thing and inviting a new generation of writers, chemists and chemistry enthusiast to join the venerable network.

If you fancy contributing to the site then drop us a line (email, twitter or the comments are fine) and let us know why you’d like to write for the blog and a little bit about your background (280 characters will do!).

Over the years we’ve covered  everything from data manipulation, plagiarism to a fair bit of larking around.  In case you need any reminders here’s a few of our highlights (in no particular order, and having polled exactly one person).

Over to you!

The Rules

Alleged Data Manipulation in Nano Letters and ACS Nano from the Pease group

What’s in Lemi Shine? – UPDATED

Something Deeply Wrong With Chemistry

By April 21, 2018 2 comments Uncategorized

The chemistry of William Gibson’s Neuromancer.

Ninsei, courtesy of Vincenzo Natali via twitter.

Note: minor edits made due to incorrect usage of “amphetamine” to refer to crystal meth. This was a typographical error and some explanation has been added to that paragraph for clarity’s sake. My apologies. -N

I recently purchased a new hard copy of William Gibson’s first novel (and sci-fi classic), Neuromancer. I make no secrets about this book being my favourite of all time, and I’ve even got an ongoing project wherein I’m composing a musical companion to the book (progress is slow). While there have been rumours of this book getting made into a movie for at least 10 years now, the project seems permanently stuck in development hell. But the same could be said of Altered Carbon several years ago, and look where we are now!

Apart from inventing the term “cyberspace” and predicting virtual reality long before it became commonplace, Neuromancer also contains some interesting tidbits of chemistry. Being a chemist myself, specifically one in the pharma industry, these little nuggets of scientific prose jump out at me, and quite pleasantly Gibson (for the most part) does a good job of using them appropriately. I wanted to examine the pharmaceutical elements of the book, which are almost entirely used by Case and Peter Riviera, its two biggest junkies.

Octagons: “dex”

Dex is a shorthand name for dextroamphetamine. Anyone familiar with the structure of methamphetamine will recognize that it is almost the same molecule–it’s simply missing one methyl group. To be even more specific, dextroamphetamine is a single enantiomer of amphetamine.

In chemistry, molecules that have the same chemical formula are known as “isomers” of each other. This broad term means that the constituent atoms are the same in number and composition, but that the molecules themselves are different in structure in some way. There are many sub-classes of isomer, one of which is enantiomer. This term refers to molecules which are mirror-images of one another, but which cannot be superimposed. The easiest analogy for this would be your hands. Hold them up so that your palms face you and your pinky fingers touch. Ignoring minor differences, they are clearly mirror images of one another. But now turn over your right hand. Your thumbs point the same way and your hands could overlap, but they clearly are not superimposable: your knuckles bend in different directions, your palms face different ways, and so on. These are enantiomers. Likewise, look at dextroamphetamine and levoamphetamine:

Dextroamphetamine (left) and levoamphetamine. Note that Dextroamphetamine is actually the S enantiomer, but is named for the direction in which it rotates polarized light.

Dextroamphetamine (right) and levoamphetamine. Note that Dextroamphetamine is actually the S enantiomer, but is named for the direction in which it rotates polarized light.

The dashed bond on each hydrogen indicates that it is projecting away from the viewer. The only difference in structure between these two molecules is the “chirality” (which comes from the Greek word for hand, transliterated roughly as “kheir”) of that carbon center connecting the benzyl, methyl, NH2, and hydrogen.

Interestingly, dextroiamphetamine (which is in fact the S-enantiomer!) is the more active of the two in the human body, with effects including increased concentration, CNS stimulation, and in higher doses, euphoria and libido enhancement. Street amphetamine methamphetamine (crystal meth, or simply meth) is almost always a mixture of the two enantiomers of methamphetamine, because isolating a single enantiomer usually requires more advanced equipment, more time, and more money. The same is true of amphetamine, which back when it was still either legal or commonly encountered as a street drug (often known as benzedrine, or “bennies”) was usually had as a racemate. Enantiomerically pure dextroamphetamine is used in drugs for narcolepsy and ADHD. Most people are probably familiar with the drug Adderall, which is a 3:1 mixture of dextroamphetamine and levoamphetamine. There are other drug products which use different ratios, the most well-known of which is probably Dexedrine, which is a 100% dextroamphetamine sulfate formulation.

Thus, when Case takes “Brazilian dex”, he is quite simply imbibing a powerful CNS stimulant that has been known for decades and used by everyone from beat poets to fighter pilots and college students.

Case’s new pancreas & the plugs in his liver

Early in the book Case undergoes a highly invasive (though mostly unspecified) set of surgeries to allow him to “punch deck” and resume his career as a virtual reality hacker. During this surgery he has a “new pancreas…and plugs in [his] liver” installed, which make him incapable of getting high on cocaine or amphetamines (including his beloved dex). How involved the pancreas is in the metabolism of these drugs is not known to me, but presumably the plugs in his liver would do one (or all) of the following things:

  1. Severely amp-up his body’s production of monoamine oxidase (MAO) which is the primary mechanism for the metabolism of amphetamines and other psychoactive alkaloids like phenethylamines and tryptamines;
  2. Up-regulate expression of cytochrome p450 (CYP450) enzymes in the liver, which are probably the most important class of xenobiotic-metabolizing enzymes, using oxidation to modify foreign compounds and make them more excretable;
  3. Up-regulate his body’s production of esterases, which as it happens are the main enzymes responsible for the first line of cocaine metabolism and elimination;
  4. Some other type of hand-wavy metabolism-altering or endocrine-altering thing.

MAO is a frequent culprit in the lack of oral bioavailability of alkaloid drugs. Dimethyltryptamine (DMT) for instance, has almost no oral bioavailability because MAO-A is abundantly present in the digestive tract and oxidizes it before it can be absorbed into the blood stream and carried to the brain. Ayahuasca, a South American traditional entheogenic drug, involves ingesting DMT along with a MAO inhibitor, which allows the powerful and profound psychedelic experiences used in shamanistic rituals, all with the relative convenience of an oral administration (YMMV). In Case’s world this particular bit of homebrewed combination therapy wouldn’t be necessary since almost everyone uses “derms” to dose themselves, meaning the gastrointestinal levels of MAO wouldn’t be a concern as the drug would go straight to the bloodstream.

CYP450 is another one that you may come across from time to time. It is responsible for doing the lion’s share of xenobiotics in the human body. These enzymes are highly concentrated in the liver, and generally deal with drugs in one way: oxidation. What this does is (very generally) to become more water soluble, allowing excretion via the renal system and urinary tract. One reason you may have heard of it is that a certain blockbuster drug named Lipitor has some unusual contraindications. People taking this drug (which is a statin inhibitor) are told not to ingest large quantities of grapefruit. The reason for this is that grapefruit and grapefruit juice contain a relatively potent class of CYP450 inhibitor called furanocoumarins, which causes the Lipitor to hang around in the body unmetabolized (and therefore performing its intended function) longer than it should, which can cause problems. CYP450 is also produced in the pancreas, relevant to the current discussion.

Esterases are again a liver-localized family of enzymes that–you guessed it–cleave esters. Cocaine is primarily metabolized by esterases in the liver to produce benzoylecgonine, which is identical to cocaine except for the cleavage of the methyl ester:

Cocaine (left) and benzoylecgonine.

Cocaine (left) and benzoylecgonine.

A less prevalent but still important transformation is the cleavage of the benzyl ester to produce ecgonine methyl ester. Both of these modifications are quite rapid, and responsible for cocaine’s notoriously short duration of effect: roughly 30 minutes after insufflation. While the metabolites hang around for longer, they don’t possess cocaine’s “desirable” effects. Cocaine is also metabolized to a lesser extent by enzymes like CYP450 to produce metabolites with -OH groups on the phenyl ring.

So the “new pancreas and liver” thing is actually not completely outlandish, though of course we get nothing else by way of in-depth explanation, so we can chalk this one up to the vagaries of good science fiction writing: just enough to make it seem doable without so much detail that it begins to fall apart.

Riviera’s cocktail

We’ve already discussed cocaine, and most are probably familiar with its effects, even if not first hand. meperidine, however, is probably better known by its trade name Demerol (or possibly its alternate name pethidine). Meperidine is an analgesic synthetic opioid, though it bears no resemblance to naturally-derived opioids like morphine, heroin, hydromorphone (Dilaudid), or codeine, all of which containe the characteristic fused ring structure at their core (we’ll get into the structures later on in the post). Meperidine and other synthetic opioids are so named simply because they also bind to the opioid receptors in the brain.

This means that meperidine is, like other opioids, an analgesic sedative and CNS depressant. It is commonly used in labour for pain management (administered primarily via IV, and not by epidural).

So as the Finn says, Peter is a speedball artist. He mixes cocaine with an opioid to get his desired blend of highs, much like some people choose to mix heroin and cocaine. And as Peter says, “If God made anything better, he kept it for himself.”

Similar to dex, this is a pretty pedestrian drug reference, but it’s still nice that Gibson gets it right.

Avoiding SAS: scopolamine

When Case makes his forst foray into space with Molly, Peter, and Armitage, he suffers from space adaptation syndrome, or SAS. Basically a nice way of saying motion sickness coupled with weightlessness and your guts being in positions they’ve never been before. So like anyone who experiences these symptoms, he uses a transdermal scopolamine (L-hyoscamine) patch.

This one is actually the least imaginative (or most grounded in reality) of the bunch, because these exist now, and have for years. Scopolamine is used to treat motion sickness and is typically used as a transdermal patch. This is because its oral bioavailability isn’t great (less than 30%), and the patch allows a slow release over the course of three days, very handy if you’re on a boat and know you won’t be leaving for a while.

The kink here, though, is that scopolamine belongs to the class of drugs called tropane alkaloids, of which cocaine is also a member. The name “tropane” refers to the bicyclic nitrogen-containing core at the center of these molecules. This can be seen below at left, on its own, and in cocaine (second from left), atropine (second from right) and scopolamine (right).


Tropane (left), cocaine (middle left), atropine (middle right), and scopolamine.

So if Case is incapable of getting any effects from cocaine, would he really be able to benefit from scopolamine’s inhibition of the muscarinic receptors? The answer would appear to be “No” if we take into consideration the most likely ways in which Case’s endocrine and hepatic system have been juiced up. As previously mentioned, cocaine’s most prevalent routes of metabolism are via esterase cleavages of the methyl and benzoyl groups. Scopolamine’s benzoyl group shuold be similarly susceptible. Also, since, unlike cocaine, scopolamine does not possess a methyl ester on its tropane ring, another principal path of metabolism appears to be via CYP450 enzymes in the liver which remove the N-methyl group, making it more water soluble.

So in this particular case, it seems like Gibson may not be correct. Scopolamine most likely would not be able to get past Case’s boosted xenobiotic metabolism. The consolation prize, however, is that he was probably quite right that “the stimulants the manufacturer included to counter the scop” almost certainly wouldn’t, either: they’re probably things like ephedrine or pseudoephedirine (both amphetamines, interestingly these ones are diastereomers of each other), or possibly phenylephrine (structurally very similar to pseudoephedrine).

Case’s angry fix: beta-phenethylamine

While visiting Freeside, Case decides he wants to get high, really, really badly. Luckily he meets a woman named Cath, who happens to be almost permanently dusted on something she calls “beta-phenethylamine”. Case tries a taste and it does the trick not once, not twice, but three times throughout the remainder of the novel, albeit accompanied by hangovers so grievous that it’s a wonder Case makes it through dinner and a show, let alone the cyberspace run of a lifetime.

Here Gibson quite clearly took artistic license with his chemistry, and I don’t necessarily blame him. Beta-phenethylamine refers to an extremely broad class of compounds (of which amphetamines are the best-known members), similar to how “tropane alkaloids” does. The beta-phenethylamine core can be seen below:



This simple arrangement of atoms is such fertile ground for psychoactive compounds that the late, great chemist Alexander Shulgin wrote a book on it. Other well-known compounds in this class include mescaline, MDMA, and the 2C-X series of drugs (where X can be substituted by bromine, iodine, an ethyl group, or even a thioether). So one might be inclined to think that this vagueness allows Gibson to cover his bases without getting painted into a corner, chemically speaking.

Alas, any and all compounds in this class would almost certainly not be metabolized any differently than an amphetamine, as they all have that tricky NH2-CH2-CH2-phenyl skeleton, which is a prime target for MAO. Based on what we’ve assumed about his surgical enhancements, Case almost certainly would not get wasted on this drug or any in its class.

Sorry, Case.

Peter’s downfall: the meperidine hotshot

As we mentioned before, Peter is a speedball artist. One of the drugs he uses is called meperidine. Meperidine is relatively easy to synthesize, and as we know still sees a lot of use in modern times. A drug that is perhaps less known, however, is one of its structural isomers, called MPPP. You can see the two structures below (meperidine at left, MPPP at middle left).

Meperidine (left), MPPP (middle left), MPTP (middle right), and MPP+.

As you can see, very similar. But the subtle change in the ester configuration results in different reactivity under certain circumstances. In brief, MPPP is very easy to decarboxylate by overcooking it or exposing it to moisture (or even better, both). In addition, MPPP’s penultimate intermediate is the free alcohol, which can easily dehydrate. When either of these things happens, something called MPTP is produced, seen above at middle right. MPTP is more correctly called N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, as Molly chants out late in the novel.  MPTP itself is oxidized by MAO in the body to form MPP+ (N-methyl-4-phenylpyridinium) seen at right. Both MPTP and MPP+ are neurotoxins, but MPP+ is the stronger of the two, being highly toxic to dopamine neurons in the substantia nigra of the brain.

A very unfortunate and imprudent graduate student in the 1970s (1976 to be exact), Barry Kidston, self-injected a preparation he had made of MPPP (at the time a legal “designer drug”) which apparently had gone slightly awry, and almost immediately began exhibiting symptoms akin to those of Parkinson’s disease (one in which dopamine is present in chronically low amounts in the brain).  His symptoms were successfully treated with L-dopa (a known treatment for Parkinson’s) for a time. His case was not unique; in fact this phenomenon was observed several more times and a book was written about it by the neurologist who helped to treat some Bay-area addicts with these same symptoms as late as 1982. Interestingly, MPP+’s chloride salt is still used today as a herbicide under the name cyperquat. As for Kidston, he seemed rather determined in his drug use, and was found by his parents catatonic and drooling on September 4th, 1978.  After a brief stay at home, he left, and promptly overdosed on cocaine, which finally proved fatal.

Unfortunately for Gibson, the decarboxylation side reaction to produce MPTP only occurs in the synthesis of MPPP, and not in that of meperidine. The carboxyl group in meperidine is connected to the piperidine ring via its carbonyl carbon, as opposed to the oxygen as in MPPP. This means that if it hydrolyzes, it simply produces the free acid. It can be exceptionally difficult to get this type of structure to decarboxylate, so much so that there are numerous publications with it as their aim.

This is not universally true: THC, perhaps the most commonly-imbibed illegal drug in the world, is actually a decarboxylated product of THCA, tetrahydrocannabinic acid, which is how most THC is found in plants. This decarboxylation is facile, requiring only heat and time. But meperidine is not THC, and such reactions tend to be very sensitive to specific moieties in the molecular structure (in THCA’s case, the phenol -OH adjacent to the carboxylic acid in question).

So in this case Gibson unfortunately got the chemistry very slightly wrong. This can easily be forgiven: such structural isomerism has tripped up many a fledgling chemist, and indeed, sometimes even the pros get it wrong.

As for all the effects of MPTP, Gibson totally nails it. It absolutely does cause Lewy bodies or similar structures to form in the substantia nigra of the brain, its symptoms are like Parkinson’s disease, and it would almost certainly result in death if used for an extended period of time with no treatment. One has to wonder, though, if Peter would notice that he was being poisoned or not. Cocaine, the kicker in his speedball concoction, is a dopamine reuptake inhibitor, which in the short term might counter-act the effects of the MPTP. In the long term however (and we’re talking years probably) cocaine is suggested to contribute to the onset of Parkinson’s. Barry Kidston apparently noticed the effects of his own mistakes almost immediately, and it’s not clear exactly when Peter starts taking the poisoned drugs in the first place. So this is a big old “who knows?”


Overall Gibson does better than most would. He gets the chemistry about half right, and does a bit of handwaving in a few parts. He even steps into some pharmacology and doesn’t do too badly.

I’d be willing to bet that a lot of this is owed at least in part to his known penchant for dabbling in drugs in the past, but no matter where it comes from, it’s pretty impressive.

Just one more reason why this book remains my favourite of all-time, and why I recommend that everyone read it. Not that I need any more reasons.


This post was adapted, expanded, and improved from an earlier post on my personal blog.

By April 16, 2018 15 comments Uncategorized