Org Prep Daily

August 30, 2017

Breaking Bad in South Florida (7)

Filed under: Uncategorized — milkshake @ 10:58 pm

This is a work of fiction. Names, characters, businesses, places, events and incidents are either the products of the author’s imagination or used in a fictitious manner. If you find any resemblance to actual persons, living or dead, or actual events, deadly or lively, or actual molecules, carbons or heteroatoms, it is purely coincidental.

Part 7

(here is Part 1, Part 2, Part 3, Part 4, Part 5, Part 6, Part 8)

The company became more dull and quiet place after our old CEO was deposed and the biologist friend fired. We were wrapping up old projects; there wasn’t much drive to do new things until we had funding to go to clinic. The research director urged us to use up all remaining vacation time and transfer nothing to the next year.

A major cleanup of the satellite lab where our CEO used to make drugs took place in December: The Canadian chemistry colleague did it all by himself one early morning. He found some previously overlooked hand-written experimental notes that our CEO left behind, he got rid of that incriminating evidence. My colleague also threw away a whole bunch of new surplus glassware – maybe thousand USD worth of flasks – and also the empty MBraun THF drying columns stored there for repacking with new sorbent. When I asked him why he threw out all that good stuff without telling me (as I could have found some place for it), he flipped out: it was none of my effing business, and that he did not tell me because he did not want my help.

The director cautiously mentioned once that maybe we should start updating our resumes if we don’t see any new major investments coming in by the next summer. It was a half-truth like everything he says – as I understand now. There was a board meeting at the end of November which confirmed our research director as the new CEO. At the same time they already made plans complete with the list of people, to shut down the company research if the financial situation did not improve by the next meeting in 3 months time. Of course they kept this secret until the last moment. I think my Canadian chemist friend learned about these plans and that we were getting rid of the satellite labs and offices. He was very worried but he couldn’t tell me.

Another curious thing happened right after the board meeting. The company hired HR external consultant in early December “to help us with the management transition” – and she wanted to interview me. She was apparently asked by the Board of Directors to write a report based on a “strict confidentiality of the interviewed employees”, to identify any hidden problem within our company…

I wasted two hours with the HR consultant at the nearby hotel where she was talking to the employees – we had a cautious waltzing-kind of conversation: I outlined how our former CEO was buying precursors and cooking drugs at the company and that he recruited the student technician to help him with MDMA scaleup, she was nodding and taking notes, and the next question she asked without blinking was if I was ever aware of anything illegal at the company. Obviously she already knew and that is why she was asking me the same question for the second or the third time if she did not get the answer she needed. At the same time she was encouraging me and making quick leading comments whenever she liked what I was telling her. I backed out of that interview: it was clear that someone at the Board retained her to spin the story and provide an alibi if the scandal became public. I told the HR consultant that I knew our CEO was cooking drugs for more than a year and I could share a lot more about it with anyone who wanted to know. She did not want to know.

Meanwhile, our business development guy was giving optimistic pep talks how things are going to pick up real soon, early next year. Our research director was traveling quite a bit and always telling us he was going to see prospective investors, talking to the banks and VCs. The management actually used to shun the VC money before – they said they couldn’t get a decent long-term deal with VCs and they preferred rich private individuals  instead. (Some of them seemed rather clueless about biotech and research. We used to have private tours quite often – we would get a reminder to set up large scale experiments and adopt busy lab activity to make us look more impressive to the visitors. The big polymerization reactors with elaborate monomer manifolds in my hood were the spot around which the visitors usually congregated and listened to the show-and-tell by our CEO. We used to joke about putting up signs “Scientists are not pets – Respect their wildness” and “Fed scientist is a dead scientist”).

In early January 2016 our company finally settled the whistleblower retaliation/wrongful termination legal action brought by my biology friend, out of court, with a good amount of cash. It was pretty sketchy because our research director did not tell the attorney representing our company about the drug scandal – he prefered the company lawyer to be totally oblivious during the settlement negotiations. I did not realize that if the company lawyer knew more, she wouldn’t do it – she would have to recuse herself for client conflict because she used to represent the family of our former CEO.

I took most of what went on in the last two months actually as a hopeful change, quite a cleanup. I also started on a new exploratory project we wanted to do for a long time, and it was great –  I thought that I did not have to worry about all that nastiness with the illicit drug coverup anymore.

I did not get to finish the new project: I suppose it is a pretty sure sign when you have to haggle with your research director about purchasing a pack of NMR tubes that he does not want to order for you (or explain that you aren’t gonna need them anyway). We did one last liquid He fill with our NMR magnet – all chemists plus our research director, working and joking together, relaxed – I can still picture it. The helium fill went smoothly and it was very peaceful.

 

reality

August 26, 2017

Breaking Bad in South Florida (6)

Filed under: Uncategorized — milkshake @ 2:24 am

This is a work of fiction. Names, characters, businesses, places, events and incidents are either the products of the author’s imagination or used in a fictitious manner. If you find any resemblance to actual persons, living or dead, or actual events, deadly or lively, or actual molecules, carbons or heteroatoms, it is purely coincidental.

Part 6

(here is Part 1, Part 2, Part 3, Part 4, Part 5, Part 7)

I learned that the biologist was fired the day after it happened – it was done so quietly. The research director came to talk to me, he knew that we were friends. He gave a long explanation: stubborn, not a team-player, already slated for downsizing but they had to speed it up when he tried to sabotage our clinical candidate by unauthorized animal experiments reportable to the FDA…

I went to see the biologist friend after the work. He was coping well, a little excited and angry, and on his first day of unemployment he already got a lawyer. We drank beer and cursed the management. My friend was afraid to use the CEO illicit drug-manufacturing angle: After all, it wasn’t the reason why they fired him. We heard some rumors about our CEO having sketchy friends – we did not know why he was making Ecstasy or if there was any connection to the organized crime so maybe it shouldn’t be used in the lawsuit. But when I spoke with the biologist two days later again, he warmed to the idea and he asked me to take pictures of the bottles of precursors left in the satellite lab that our CEO used for making drugs.

I went back to the company that night with a camera and started snapping the pictures of precursors. The camera autofocus was crappy and it was quite hard to make out the little print on bottle labels in the resulting photos. Also, I couldn’t find some of the more incriminating precursors like methylenedioxy benzene (though I did find few bottles of the other stuff) and I begun to change my mind about providing evidence for a lawsuit against my employers even though I volunteered to do it. It was clear to me that pictures of few precursor bottles won’t make a convincing case about the illicit drug manufacture, there would also have to be a detailed chemistry explanation and a witness deposition about the misuse of these materials as drug precursors. I would have no control over these photos, how they were going to be used during the lawsuit or the settlement negotiations – the photos would show the management that my friend is getting some help from among the chemists. I was already under the suspicion of our research director. I realized that to keep my job I needed to betray my friend, and do it soon.

So I sent a brief e-mail message to the CEO on Friday in the early morning hours, asking him for an urgent meeting and when he arrived I breathlessly reported that my biologist friend was going to sue the company for wrongful dismissal and he is also gathering evidence about the illicit drug manufacture. I enjoyed pointing out to him how badly he compromised himself and I urged him to settle the case. The CEO was visibly shaken and said that he could probably write a check under the table, for tens of thousands – but not for hundreds of thousands – from his own fortune. Then he shook my hand, hugged me and said he would remain forever grateful.

I could rationalize this now and try to make myself look better but I did it for selfish reasons: I thought I could keep my job. I did not want my friend to use the drug manufacturing scandal to destroy the company if things got out of hand. I figured his legal action (whistleblower retaliation / wrongful termination) wouldn’t be hampered if the management learned about it couple days in advance: they already made the mistake of firing him right after his research presentation – not much that they can do about it now… I also stopped by to see my friend, to tell him that I already ratted him out to the management and that the CEO was willing to pay him off. (The reaction wasn’t good. His wife asked me to never come back).

The research director took me aside when he returned next Tuesday, he grilled me about every detail I could remember about the incoming legal action but I did not know much to tell him. He looked very concerned while I tried to impress him how badly they needed to settle. The next day the chief business officer (who was based in a different city and visited the company infrequently) also chatted me up and gently probed me about my job satisfaction and my friendship with the biologist.

For a while I thought they bought it. The CEO looked happy and relieved and was now very friendly. Then he suddenly stopped showing up at the company. The research director looked stressed and very busy though I had one lunch conversation with him during this time – he mentioned that our CEO was unable to bring in more money for the company from his family fortune. He was also telling me about the university police investigation and the near bust of the student-technician buying the precursor in February 2014. When I pointed out that the technician actually worked for our CEO and the private drug manufacture project started more than a year before that – as he should well know because he set up the lab for it – the research director did not even pause and conceded it was his personal failure that he refused to believe the rumors about our CEO; it sounded quick and practiced.

Two weeks later, the research director called a meeting and announced that the CEO was taking a personal leave and won’t be coming back. He made it sound all rather mysterious, along the lines of a serious illness and family matter. Later we found out that our CEO checked himself into a rehab upon recommendation of his lawyer and he was ordered in no uncertain terms to stay out of town. Our research director became the new CEO.

I think our research director had the CEO ouster prepared for a long time already and the threat of the lawsuit just prompted him to act – to immunize himself should the drug making scandal become public. He did it, most likely, by outing the CEO to the university where we were renting the lab space (and where his wife was a vice-president for research integrity, a high-ranking official in the presidents’ office hierarchy). I think the university leadership in turn made absolutely sure to keep the reopened investigation under wraps by using their political clout. These are only my speculations – it was done in a hushed way and we didn’t learn any details.

Our CEO stepped down and disappeared into a rehab, the Board of directors was told a very sanitized version of the story and all was good again: No public investigation, no indictments, no fuss. We were back in business under the quietly effective management of our research director.

Sliva1 Credit: Jiri Sliva

August 24, 2017

Breaking Bad in South Florida (5)

Filed under: Uncategorized — milkshake @ 6:45 pm

This is a work of fiction. Names, characters, businesses, places, events and incidents are either the products of the author’s imagination or used in a fictitious manner. If you find any resemblance to actual persons, living or dead, or actual events, deadly or lively, or actual molecules, carbons or heteroatoms, it is purely coincidental.

Part 5

(Here is Part 1, Part 2, Part 3, Part 4, Part 6)

Maybe I should make a little detour here and tell you about what our company was doing when not dabbling in the street drug manufacture – it is quite important to the story.

The main purpose of the company research was to formulate cancer chemotherapy agents into injectable therapeutic nanoparticles. We developed polymers composed of a random peptide sequence with lipophilic aminoacid residues and connected to a long polyethylene glycol chain. These polymers are bio-compatible and when dissolved in water they form pseudo-solutions composed of small fairly uniform micelle nanoparticles. They are acting like surfactant – with a greasy core and a halo of water-loving PEG chains projecting outside. When you have some lipophilic, poorly water-soluble drug that you want to formulate for intravenous infusion, you would dissolve it in organic solvent and add it to the micelles: the drug is going to partition itself into the micelle greasy core and after evaporating or dialyzing away the solvent you got an injectable formulation of a drug that is “solubilized” by being taken into the polymer nanoparticles.

Quite a few research groups developed this kind of system based on a polymeric excipient. A formulation like this is not stable and quickly unravels in the presence of plasma proteins. Our claim to fame and fortune was to include a metal-coordinating region in the polymer chain and finish the drug formulation by adding a small amount of Fe(III) salt: the added iron salt acted as crosslinker, it tied together the previously loose chains by metal atom coordination and we obtained stabilized micelles with the drug encapsulated inside. The nanoparticles could survive in the circulation and release their cargo gradually thus improving the drug residence time. The strength of used iron chelator is pH dependent and becomes weaker at lower pH and there is plenty of lactic acid in tumor sites. Tumors also have a voracious appetite for iron (with so many transferrin receptors on the surface of cancer cells) and their vasculature tends to be more leaky for the nanoparticles so there is an opportunity for improved delivery of a drug to the tumor sites with such iron-stabilized micelle drug formulation: The micelles make it to the tumor site, they preferentially fall apart there and the cancer cells get higher and more prolonged exposure to the chemo agent than they would get with a less elaborate formulation.

The controversial results with our technology came when I proposed and helped to develop an improved version of the polymer with stronger iron-binding properties. With the new polymers we saw the tumor mass discolored with iron that was part of the formulation, the tumor mass became visible on MRI and there were dense particles present in tumor cell vacuoles visible on electron microscopy. The company claimed that we can now observe the stabilized nanoparticles as they were making their way inside the tumor cells and releasing their drug cargo inside the cell.

There were few problems with this claim: 1. We had no proof that the high-contrast particles seen on EM and MRI were the original nanoparticles making their way inside the cell. A more likely explanation would be that cancer cells gorge on iron present in the formulation and they can protect themselves from the overload by stashing away the excess iron in vacuoles in a form of iron oxide particles that are highly visible and ferromagnetic. We did not try to look closely enough to be able to distinguish what were these particles. 2. There was no direct proof that our nanoparticles could survive their journey in the bloodstream and make it to the tumor site in one piece, as claimed by the company. We also couldn’t tell a micelle loaded with a drug from a micelle where the drug had already leaked out while it circulates in the bloodstream, and again we did not try to look very hard. 3. In fact, we had no way of distinguishing the free drug in circulation from the drug still loaded in the nanoparticle since any method used to analyze blood samples invariably destroyed the nanoparticles. You would “observe” a better drug residency times that way if you are combining together the concentration of free drug plus drug resting inside the nanoparticles and you cannot tell them apart.

I did not pay much attention to the biology, formulation or PK data analysis initially – I was interested mostly in making the polymers in high quality, trying to fix the numerous manufacturing problems. I hoped that after ten years in business the research director knew what he was doing. (He did: his plan was to sell the company at the first opportunity to the unsuspecting buyers.) But my biologist friend convinced me to look closer at the presented data and the story about the technology that our management was making and I noticed there was quite a bit of hand-waving that connected a perfectly sound research on how the drug was formulated with the results we were getting from the test animals implanted with xenografts and then treated with our formulations. We were blind as to the fate of the loaded micelles and their exact release mechanism, and the management probably should not have been making some of the claims in the absence of hard direct evidence.

My biologist friend was with the company for over 8 years, and he was clearly the most driven and most creative biologist we had, and the most skeptic one too. He would always run the controls on his controls, to make sure he wasn’t fooling himself – he came to believe that the entire subfield of therapeutic nanoparticles is polluted by sloppy science and irreproducible results. He blamed not only the difficulty of analyzing the nanoparticles in vivo but said it also originated from the wishful thinking, the socio-economics of postdoc academic labor and the relentless grantsmanship getting in the way of doing good science. He thought too many research groups were cherry-picking data to support their favorite notion without really asking the hard questions and this was the main reason why the nanoparticle field stagnated and so few approved drugs came out of it.

This biologist was always working on the periphery, on a sort of “woulnd’t it be nice also” kind of side-projects that were underfunded and received little chemistry support at our company. I was puzzled why the management did not have him on the clinical candidate formulation instead, with all his inventiveness and drive. The research director’s explained to me that my friend was “not a teamplayer”.

One of the side-projects that this biologist was doing was targeting: the idea of decorating the nanoparticle surface with ligands binding to receptors present on the surface of cancer cells. As our micelle was quite elaborate, fragile and not easy to follow in vivo, he developed a stand-in for a micelle, a toy model, a form of PEG-coated quantum dots of a similar size that can be easily studied in vivo because they are stable and highly fluorescent (you can even follow them in the circulation within a live animal if you use near-IR emitting Qdots.) He worked out all kinds of interesting details about the targeting problem and wanted to publish it. He also convinced himself that the micelle story the company was pushing was cartoonish and that the nanoparticles should not get inside the tumor cell if they looked anything like what the company was claiming.

When his targeting research project got cancelled in the summer of 2015 and my friend was finally put to work on the formulation with which we were going into clinic, he used some of his new analysis techniques and quantum dot-derived insights to have a more detailed look at our micelles. What he found was not encouraging: The drug was leaking from the “stabilized” micelle quite readily (on the timescale of minutes) once injected into a mouse, and the micelle itself was aggregating with blood plasma proteins. His work with cell cultures also supported a conclusion that the drug leaked from the micelles first and only then got inside the tumor cell, and not as a part of the intact nanoparticle. He did a FRET pair study with our nanoparticles – again, the leak out was rapid in undiluted plasma.

When my biology friend presented his data, there was a great deal of consternation among the chemists. The data indicated that there might be serious trouble ahead with our clinical candidate, and maybe even with the entire technology platform… In the meeting room after he finished we immediately started discussing fluorescent probes that would help us to clarify whether the problem was real and if it was, whether it was manageable with what we had, and if it was conceivable that the leakage problem was specific to the particular drug with which we were going into clinic (the drug did have a hydrolytic stability issue, the hydrolyzed ring-opened form was more polar and already known to leak out of the nanoparticles). Our research director cut the discussion short with saying that he was not surprised and that he suspected as much based on the animal data, and that he will carefully consider what will be the next step.

This was on Friday noon. Our research director then set up one-on-one lunch meeting with our biologist for the next Monday. This lunch meeting did not happen because our biologist found himself downsized already by 9:30 am that Monday morning. He received two months of severance for his eight years with the company – and he just had a newborn son and his ailing wife was at home with the kid. The research director also told him that his study the on quantum dot targeting wasn’t going to be published even though the company wasn’t interested in it anymore.

This happened to him after our management had been pooping on his work for years already and cancelling his projects every time he got some promising results, and now they were firing him for the work they asked him to do, in order to suppress his data. And he recently had to endure more than eighteen months of having our CEO for a neighbour – the CEO was using a lab located right behind his office desk, stinking up the place and cooking drugs like a maniac. The biologist wasn’t really given any other choice but to go after the company.

stablemicelle

August 23, 2017

Breaking Bad in South Florida (4)

Filed under: Uncategorized — milkshake @ 6:28 pm

This is a work of fiction. Names, characters, businesses, places, events and incidents are either the products of the author’s imagination or used in a fictitious manner. If you find any resemblance to actual persons, living or dead, or actual events, deadly or lively, or actual molecules, carbons or heteroatoms, it is purely coincidental.

Part 4

(Here is Part 1, Part 2, Part 3 Part 5)

It is pretty certain that our CEO did manufacture some ecstasy before the fire in February 2014. Even as he was deleting his NMR files, he was careless with the temp files stored in the console and he occasionally also left his NMR sample tube in the magnet. My cranky senior chemistry colleague told me that he saw his spectra and that he even re-run NMRs on some of the samples he found after the CEO. Clearly, there was MDMA even if the purity wasn’t great, maybe 80-85%. We could only speculate how much the CEO managed to produce – but couple months before he was into the final stage already, with methylamine and Al foil reductive aminaton, and he was doing the preceding Wacker oxidation step with oxygen gas. (The research director bought an oxygen tank and regulator for our CEO so they weren’t using benzoquinone anymore.)

My own guess is that the duo – our CEO with the technician – probably wasted most of the precursor, the one kilo of methylenedioxy benzene that the CEO bought the summer before (and had to retrieve from the DEA), and they needed more. But even with all their bumbling attempts they would have produced at least something useful from it, to get our technician excited enough to try ordering the precursor through the university purchasing system. It is only my speculation. Either way, the university confiscated the new bottles and our CEO wasn’t going to buy the stuff again, not after these two very near busts.

When he moved back to his lab after the fire, for a while he was spending less time there, his previously feverish MDMA work slacked probably due to lack of starting material. He also had some problems with his back injury so running long experiments wasn’t easy for him physically. But he was still working in the lab and continued to be interested in drugs: One day I noticed two new unopened bottles from TCI – we rarely used this chemical supplier but our CEO somehow felt it was easier to order from them since they did not ask too many questions. (At least that is what he told to our technician who shared this great insight with my old cranky chemist colleague.) The new bottles contained m-methoxy phenylacetonitrile and bis(2-chlorethyl)methylamine hydrochloride, aka nitrogen mustard mechlorethamin.

I recognized that this stuff was a material intended for making ketobemidone or some other similar pethidine opioid analog. I went to the CEO and explained what could happen if he spilled even a tip of spatula of that water-soluble nitrogen mustard blister agent around the balances and left it there without cleaning up the spill – I asked him to never bring that shit into our main chemistry lab. And he did not; it stayed unopened until we departed from the company.

The next thing I remember, our CEO ordered materials for making synthetic tropane alkaloids, namely cocaine, and left it in shared storage cabinets in his lab. He got a big bottle of acetonedicarboxylic acid, and also 2,5-dimethoxytetrahydrofurane. But only the bottle of acetonedicarboxylic acid was opened: my senior chemistry colleague later told me that our CEO was fruitlessly trying to make monomethyl ester of acetonedicarboxylic acid and he did not manage to avoid its decarboxylation during workup and so he wasn’t getting anywhere. But he was still trying, more than half year after the very near bust by the police. At this point I just walked to our research director and gave him an ultimatum – I was leaving for Germany, to oversee a technology transfer to our GMP manufacturing partner and when I am back I want this private project to be over, clean and gone.

And it worked – I came back from the trip and the clandestine drug work had already ended. But just before my departure to Freiburg, the CEO came to me and said in a hurt voice that he was always my biggest supporter at the company and that I should think twice before crossing him… (Even after the two near busts, the ass-covering research director had to tell the CEO that it was me who was now forcing him to stop.) And so, by the end of November of 2014 the drug making at our little company finally came to close. Only the coverups and screwups kept piling on.
__________________________________________________

I have good memories of the first half of 2015. The clinical candidate we bought with the small virtual biotech had atrocious manufacturing problems but I did manage to come up with a reasonably scaleup-friendly alternative route and the management loved it. I was also scaling up intermediates for another clinical candidate project and was told that soon we should have money to do a GMP campaign and go to clinic.

Then all of sudden without warning, the management fired my friend – the best biologist at the company – and they did it because they disliked data he produced. His results flew in the face of the simplistic descriptions of our technology as advertised to the prospective investors and buyers, and the management wanted to suppress the findings. On Friday morning meeting, he presented his unfavorable data about our clinical candidate and by the next Monday morning he was already made redundant.

I don’t know if our management considered the one minor problem when firing the biologist and censoring his study: that his office and biology lab space was adjoining the satellite lab where our CEO was cooking drugs; my friend had a front-row view of what went on in there. He was going to use it now against the company. And his wife was a lawyer – before the maternity leave she used to be a partner at a major law firm suing insurance fraudsters on behalf of the insurance companies. It was gonna be awesome.

 

USF4

 

August 22, 2017

Breaking Bad in South Florida (3)

Filed under: Uncategorized — milkshake @ 4:47 am

This is a work of fiction. Names, characters, businesses, places, events and incidents are either the products of the author’s imagination or used in a fictitious manner. If you find any resemblance to actual persons, living or dead, or actual events, deadly or lively, or actual molecules, carbons or heteroatoms, it is purely coincidental.

Part 3

(here is the Part 1 Part 2, Part 4)

By the summer of 2013, our CEO switched to making methylenedioxybenzene (1,3-benzodioxole) by alkylating catechol with dichloromethane in DMSO. He was failing every time – the air oxidation of catechol in the presence of base at high temperatures proved challenging for his techniques. (I had to keep re-buying expensive 4L bottles of DMSO for my project that he was taking from our lab and consuming at the rate about one bottle per experiment… The CEO asked me why DMF did not work when he tried it to replace DMSO; he did not know DMF is unstable at reflux and even more so in the presence of K2CO3.) So I still had some reasons to hope that he would give up.

But our CEO grew tired of his attempts to prepare methylenedioxybenzene for his private MDMA project and he decided to buy the stuff from TCI. It alarmed me to see two half-liter bottles of methylenedioxybenzene suddenly in his lab – I informed my chemistry colleagues who freaked out too. This already got too far along the synthetic route to MDMA, and there was a chance he would manage to finish, maybe throw an Ecstasy-tasting party at his home, with the guests ending up in hospital. The purchase of a flagged precursor was a loud shout to the law enforcement to come and visit our company…

Little did we know that our CEO ordered these bottles of methylenedioxybenzene for delivery to his parents house, DEA intercepted the delivery and invited him to their Tactical Diversion Squad at the District Office, to kindly explain why he needed it. Our CEO put on his best act for the DEA agents (to this day, they are still pretty sore about it), describing them in detail his revolutionary drill bit boron doping hardening technology essential to his father’s business. Then he collected his confiscated kilo of precursor, brought it to our company and proceeded to brominate it.

_________________________________________________________________

He was getting close. Worse still, the expected management change – the IPO or takeover – wasn’t going to happen. Instead, it was our company that acquired another even smaller and more troubled virtual biotech that went belly up, apparently for their phase 1 clinical candidate completely unrelated to our company technology, in some kind of a complicated share exchange+debt deal, and our management stayed on to run the joint company. (I later learned that the people who brokered this deal and collected their finders fee actually helped to fleece us, by hiding serious problems. Our top management missed important things when performing the due diligence. But that’s another story.)

What really alarmed me was that our CEO bypassed the last remaining unpleasant step he struggled with, by obtaining a red-flagged precursor. The CEO also recruited the student technician working for my senior chemistry colleague, to help him watch over his reactions while the merger-related issues kept him away from the lab. And the technician was anything but a normal person: He was an Adderall-addled emo kid, a bullshitter and kiss-ass. He was also very interested in making drugs. (He never learned to read structural formulas but he loved to rant about random stuff like isoelectric point to impress girls). Now that it became management-sanctioned project run by our CEO, he was more than happy to help watching over distillations and with cutting aluminum foil for the amalgamated Al reductions. (Due to his obsessive behavior when on amphetamine, he was apparently very good at cutting Reynolds foil: in one sitting he could make drawers full of Al foil strips).

This was enough – how many times did I tell this dude not to involve himself in the clandestine project. I’d explain him what it was about – ten year sentences, snitching and paranoia – but he couldn’t resist the glamor of being Heisenberg, and he also hoped to earn extra cash from it. I went to my senior chemistry colleague to complain he should watch over what his technician guy has been doing for the CEO in the satellite lab. Unfortunately my cranky senior colleague really liked his technician, he took this as affront, went to the research director and told him I was oppressing his poor guy, and it was me who got berated and told to stay away. (It even ended up in my performance review)

By the end of year the enthusiasm of our technician somewhat faded, he hoped for loads of money for his extra foil-cutting work but was pretty disappointed when he got only a 1000 USD Christmas bonus check. He grumbled, “that he could go and tell things.” But he must have reconsidered since by February 2014 he was already back and ordering methylenedioxybenzene precursors himself, apparently through the university ordering system, and using his student ID – as if somehow that made the purchase less conspicuous. At which point the university police came looking for him – to interview him about the drug precursor. But they did not catch him because he just left due to family emergency: his father supposedly suffered a heart attack (although now I somewhat doubt it) and while he was away with his family, he received a message from the company and from the university to keep his mouth shut and never ever come back. (He later tried to blackmail the company by approaching the other two co-founders that were no longer with the company but they were not interested in his story, and the company management quickly put an end to it).

So this was already the second time we came very, very close to being busted, the university and the company management covered it up, not for the last time, and we did not learn about it until much later.

_____________________________________________________

Just right at the same time, we also had a big fire in the main lab.

I used to believe it was an accident but now I see the timing as pretty suspicious. Apart from very nearly destroying the main lab (we had tanks with ethylene oxide, hundreds of liters of ether, heptane, THF etc, many gas tanks) the fire made it possible for our management to remove the precursors in the satellite lab in hurry. The flooding from sprinklers put the computers in the office out of commission – it erased the chemical inventory database and the ordering system was unavailable.

The drug investigation was done by the campus police in conjunction with the Department of research integrity and compliance presided over by the wife of our research director (he married the university vice-president). And the conclusion of the official inquiry was that a junior junkie student misused the satellite lab of our little company without the management knowledge. Perhaps he was ordering sketchy chemicals and making who-knows-what in the dead of the night but neither the company nor the university wanted to press the charges in order to avoid bad press.

And the fire itself was declared a poor housekeeping issue, not a safety violation. The university signed on this, our management vehemently lied to the police and all was good again.

We did not know about the circumstances of unhappy departure of our young student technician. We were instructed never to contact him so we figured that our student technician left on bad terms but the drug precursor investigation was kept from us, we were sent home immediately after the fire for the entire week while the flood and hazmat-related problems were handled. Apparently the drug investigation was done at the same time…

The week after we were already very busy: The fire disaster almost wiped us out, the official story was that an unsecured big beaker filled with ether placed into a common household fridge saturated the fridge with vapors and it exploded in the early morning hours when no-one was around. A big explosion that shook the building and pushed the drywalls by few inches, the door from the fridge flew across the the entire lab, bounced from the cement floor, narrowly missed our NMR magnet and broke the hurricane-proof window. Kilo bottles of diphosgene and butyllithium strewn across the room and got charred from fire (fortunately our 3kg inventory of diphosgene did not break), flood and soot was everywhere.

I have somewhat perversely happy memories of the fire aftermath. We were without a functioning lab for almost a month but the destroyed benches and fridge and cabinets got replaced at a record speed. It was an unpleasant work – every piece of glassware was soot covered (the main fire and smoke source were the safety blast shields stacked on top of the fridge that exploded – the shields were blast-proof but highly flammable), every single item had to be cleaned and moved to storage and then brought back – but I was impressed by the newfound friendliness and sense of solidarity among my colleagues and by the energetic actions of our management. Everyone was working hard to get the office and labs up and running. Our clothes were perhaps blackened with soot and the floor was still wet but it was harmonious time. Incidentally, the technician was gone & not missed, and the CEO drug lab was now used for temporary storage of all the stuff from the main lab while it was rebuilt and refurbished, so no more MDMA for the duration.

At the end of March 2014 we went happily back to our rebuilt lab, with a gleaming new oversized bench that gave us so much space for the instruments, and wider corridors that made the deliveries and rolling dewars of liquid nitrogen much easier. And our CEO returned back to his lab, now emptied of the stored things, and he started cooking again.

MOERDIJK-BRAND-CHEMISCH BEDRIJF

Breaking Bad In South Florida (2)

Filed under: Uncategorized — milkshake @ 1:02 am

This is a work of fiction. Names, characters, businesses, places, events and incidents are either the products of the author’s imagination or used in a fictitious manner. If you find any resemblance to actual persons, living or dead, or actual events, deadly or lively, or actual molecules, carbons or heteroatoms, it is purely coincidental.

Part 2

(Part1Part 3)

I repeatedly tried to intervene with our CEO, to talk him out of his MDMA scaleup project. At first, he promised that he would wrap it up soon and stop – but he didn’t. The next attempt at conversation, he would ya-ya-ya me, and the third time he just told me to buzz off and mind my own project. When I appealed to him that he was drawing attention and there were many rumors within our little company, his reaction was “the people who spread the rumors should really watch out”. Clearly, this wasn’t the door to push.

I also tried our research director, I would go and start by saying that there are problems with the stuff the CEO is doing, he stinks up the lab with methylamine all the time so people in the adjoining office are complaining and it is unpleasant to walk into that lab and look for the chemicals stored there… The research director interrupted me and said he would handle it himself. (I think he put a better waste container there for the CEO). Next, I brought up a large expensive piece of equipment that our CEO crushed by stuffing his flasks into my base bath – so I got instruction to set up a new base bath for the use of our CEO, the ruined custom piece went back to Chemglass for repairs and everyone carried on just as before. When our research director questioned why I am ordering so many large flasks, pumps, mechanical stirrers and other equipment, I explained that our CEO was taking them from our lab to his, trashing many of them so we had to replace – and this reliably silenced the otherwise stingy manager, he asked no more and had the stuff ordered…

My conclusion – and not only mine – was that the research director knew enough that he did not want to know more, quite aware whom he owed his #2 position at the biotech company, complete with oversized paycheck (triple of our average scientist salary) and all the prestige that goes with it. I think he became fond of his big house with a big indoor pool, flying first class everywhere, driving brand new Mercedes SUV and Lexus, ordering exotic scotch and vintage wines by the case (with company as the receiving address, it often arrived to our lab and sat there on a pile of boxes with the lab solvents and glassware). The research director was in his late thirties, a similar age as our CEO, and about to become very rich if the sale or IPO of the company came through. He wasn’t going to screw it up. And even if he was waiting for someone to come to him with a proof of illegality to stop our CEO, I was pretty sure he would go and sacrifice that poor schmuck to shield himself. (Tomas says you are cooking ecstasy – is that really true?)

I thought up a little ruse: The hood space in our labs was limited; all it would take was to fill the hood in the satellite lab. We could definitely use another chemist since we had more projects than people and I knew an excellent Swiss-American chemist who needed a job. So I talked to my chemistry colleagues, and to the research director and got his approval. All were impressed with the job candidate resume (a Pfizer and Scripps jobs, he worked for prof. Seebach at ETH) and I think they immediately caught on the real reason why I was doing this. They asked me to meet the candidate and set up his job interview. So I went to lunch with the guy, to find out when he could come to interview. Then I received a message that we needed to save money and the interview was to be postponed by few months. (When I tried again few months later, after yet another meeting with the job candidate, I was told the interview is cancelled outright because our CEO does not approve. They were jerking us around.)

Here I should probably explain why I did not run away from this company, with all the shenanigans and deceit around. I thought we were doing an excellent research and just our CEO got off the rails, and we could be a happy little company again – if only there was some way to make him stop or make him leave. The projects that I was working on were interesting and rewarding: not exactly high-level chemistry but the execution had to be immaculate. (10L Schlenk-like reactors with insane level of exclusion of moisture and oxygen). I learned new techniques used by organometallic chemists, and even devised some of my own that allowed us to accomplish this in a humid Florida summer without a glovebox. There were practical problems to solve on kilo scale, and once you found the right reaction conditions it was satisfying to see the progress. We basically inherited a technology that was in stage of a concept when I came aboard and it had so many difficult problems that the practical implementation was impossible but we fixed it and our new improved versions seemed so practical, the material quality was pristine and I had great enthusiasm about the company future… By the time this unfolded I already made key improvements to almost every aspect of our chemistry methodology, the managers kept flattering me how tremendous were my contributions, etc. It was the kind of process development projects I always wanted to do. And we had pretty good working conditions for a small company – while they did skimp on the office area the lab space and equipment was first rate. It was a great place to work until it wasn’t.

__________________________________________

By the summer of 2013 the situation settled into new abnormal. Our CEO was puttering away in his lab trying to figure out the best way to cook MDMA. Meanwhile, the chemistry colleagues did not keep this secret – just as I hoped they couldn’t: my Canadian roommate-colleague and the student technician went drinking with biologists one evening and it took about two shots for them to start unloading. Other biology colleagues, long suffering in office next to our smelly CEO lab soon learned what went on there and came to me to ask for explanation. I mean, when you have a bare-chested CEO sprinting across the parking lot in his undies, people do take a notice. (The CEO had a large-scale reaction runaway, a splash of very irritant material on him and all over the wall. Since there was no safety shower he thought he would undress and run to his car and drive home. The reaction mix turned black on air so there was a light silhouette of him left on the darkening splashed wall that had to be re-pained. The unfortunate vacuum pumps nearby remained black for good).

It had unreal sitcom-like quality: while everyone in the company including the intern in the formulation lab was cracking the Walter White jokes, our CEO heroically pushed on. It is now clear that as far as our CEO was concerned, this was his company, he kept giving it cash injections from his family fortune so he did not think twice before turning it into his private chemistry club. In fact, the company existed as a vanity project and the cancer research we were doing was a vehicle for him, to be a biotech CEO and co-founder right out of the grad school, and to impress his older siblings and cousins. The promised success was taking too long to arrive and after 10 years he was getting bored, his failing attempts to sell the company or bring it public probably did not help his self-image. So he needed to become a badass chemist too, to impress himself and perhaps someone else too with his product…

For a short time, it looked like our CEO was finally about to change his project – he asked me about LAH workup, a reaction step that wasn’t on the MDMA route. Soon I found my missing bottle of oxalyl chloride in his hood next to a half kilo of indole and a big bottle of dimethylamine solution – so now he was also making tryptamine hallucinogens… Apparently our CEO was not pleased with the DMT chemistry very much, I remember him bringing a thick brown ooze, his crude product, to our lab to take the NMR, the stuff was giving off a revolting indolic smell. I think he stopped working on DMT because the material turned out too air and light sensitive for his mad skillz and he did not manage to purify it. It also smelled like a fossilized colostomy bag – it lingered on clothes.

After the DMT interlude, the next thing our CEO came up with was an alternative route to safrole and MDMA, starting from catechol. He bought a 5 kilo tub of catechol, 3 kilos of Mg turnings, NBS and bromine we already had kilos from an old project, and a 2.5 liter flask of allyl bromide. It looked like his updated plan was to turn 4-bromo-methylenedioxybenzene into Grignard, alkylate it with allyl bromide and use the produced safrole in the established MDMA route from Rhodium archive. He gathered precursors sufficient to produce kilos of MDMA. And it was a realistic plan.

 

USF2

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