Org Prep Daily

September 8, 2017

Breaking Bad in South Florida (10)

Filed under: Uncategorized — milkshake @ 3:26 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 10

(here is Part 1Part 2Part 3Part 4Part 5, Part 6, Part 7, Part 8, Part 9, Aftermath)

A week after I spoke with the university chief compliance officer, the DEA got back to me – a senior special agent called me up and asked me to come for an interview the following week.

I had couple more calls that day: In the morning, an unexpected conference call – some university officials and lawyers urgently needed to hear the complete story of manufacturing MDMA and DMT at the company. I did not get to meet them, they did not invite me to talk to them in person afterwards. I don’t even have their names. The second call came from DEA, to set up the meeting. Then I got several frantic calls from the company lawyer – she was trying to find out what the hell just happened. Our research director never told her about illegal drugs: she had been handling the company terminations for several months already, oblivious… I explained the lawyer she really needed to speak with the research director and I wasn’t going to take part in any company-run self-investigation. The following day, the lawyer sent me a Cease and Desist letter to keep me from talking to the university and the law enforcement. I wished her good luck trying to sue me for talking to the DEA, and I suggested that she should excuse herself due to a client conflict.

The trigger for all this sudden activity was an e-mail that I wrote to our research director. The subject line: “Today is your special day! Wednesday 23rd is a perfect day to resign.“ My e-mail mentioned the university EthicsPoint misconduct submission line and also the possible involvement of his wife in the previous university investigations of our company. I sent it at 7 in the morning. At 10 am, the university officials were calling me already, then the DEA called an hour later to set up the meeting, and finally the company lawyer.

I did not realize that the university was coordinating its actions with the company and the DEA: Our research director already informed the university about the drug-manufacturing operation, to push out the CEO and to whitewash his own role in the drug ring. Our research director became the new CEO, and the university conveniently overlooked that he set up, supplied and maintainined the lab that was making illicit drugs for almost 2 years…

Now that I talked to the chief compliance officer, I became a new source of problem. At first, it was wait-and-see. (If EH&S found safety violation serious enough to push the company off campus, maybe the affair would go away. At least that was the unofficial deal we worked out with the chief compliance officer). But I was impatient, writing e-mails about going full expose. Our research director panicked after reading my e-mail on 23rd, he run to the university for help and provoked this sudden response. DEA contact people were asked to go-ahead and interview me because it wasn’t possible to delay it much further and the university really did not want to reopen its own inquiry into this scandal – they knew there were things they did not want to find out.

At the time, I did not know enough about the three previous investigations of our company – every one of them a cover up – so I underestimated the role played by the university: it wasn’t just one high-ranking official who helped to protect the good name of the university (and perhaps shielded her husband from criminal investigation too). By now, it was the presidents office, the leadership of a major university calling in political favors and going through the State Attorney office and “comparing the notes” with the DEA, trying to avoid a scandal that would tarnish the university and its biotech incubator, and implicate one of their own in the previous cover up. The university and our company were in the same boat.
_______________________________________________________________________

I met two special agents from DEA District Office Tactical Diversion Squad on Thursday, last week of March 2016 at 11am. They were pleasant, charming, understanding. Right off the bat they offered me an unspecified but large amount of cash if I worked for them as a paid informant: they said I was perfect because of my background in setting up synthetic labs. I politely turned that offer down – I thanked them but it wasn’t the right career path for me.

We walked a short distance over to a nearby shopping mall. Sitting in front of an entrance to Macy’s, we talked for about 90 minutes (I was nervous about the DEA building and I also wanted a decent cappuccino while interviewed – it was the first time I went to the law enforcement to turn someone in.) Later we moved back to the federal building where the officers were going through their case files, writing few comments on the margins. I think we spent about two hours together – my long-winded story probably kept the agents hungry during their lunch time.

Surprisingly they did not ask me in detail about the precursors, their dates of purchase and their quantities, even though diversion of precursors for drug manufacture was very much within their field of investigation. This alone should have made me suspicious of the whole interview. Also, I told the officers where we could find the evidence in the company records, if they wanted to build the case based on the precursor purchases. And my senior chemistry grouchy colleague actually saved an NMR sample with MDMA produced at the company – it should be still in the fridge. But the DEA officers were not interested in getting a search warrant – They said the company was cooperating (about which I had serious doubts).

What they really wanted to know was who were the sources that could confirm my story, and any photographic evidence I might have. They warned me that their investigation will proceed in a slow methodic way and I should not expect any criminal charges any time soon. Maybe never. But they assured me that the culprits will get a kick in their pants, should not be able to continue in their position at the company and the university. And certainly they should not be able to buy any listed precursors in the future or obtain DEA permits for controlled substances. That was good enough for me – after all, I wasn’t really trying to get anybody thrown in jail, and I did not like the idea of having to testify in court or be called in front of a grand jury. I would have been satisfied with our research director stepping down and the company moving off campus.

I must say the officers looked just as I imagined them, after watching Breaking Bad: no-nonsense, cautious, savvy. But the DEA facilities were pretty run down – lots of empty offices with battered police precinct-like metal desks and chairs. The oversized office space was cluttered but deserted and gave impression of neglect.

Not much happened in the following months. The unusually slow pace of interviewing witnesses – maybe one interview every few weeks – was worrying me: I though the DEA was giving too much time for the company to do a damage control. I did not expect the current employees to talk to the DEA but several already laid-off people also didn’t, or claimed a total ignorance. I originally suspected maybe the DEA was slow-boating the case because they were using our former CEO (or maybe the research director) as an informant-provocateur, the same thing they offered to me but signed them with help of a sealed indictment against them. I imagined there must be some big gangster case they don’t want to compromise by blowing the identity of their informants, etc. The reality was more mundane: The DEA agents were asked to run errands for the university.

From the phone conversations I had with the DEA over the last year, I learned few details about the previous company investigations and I figured out what made the DEA special agent rather grumpy about this case: We were just “a bunch of knuckleheads and clowns, only interested in keeping our nice jobs and paychecks” for not going to the DEA before the first cover up. The DEA agents were not learning any substantially new details from anyone, or building a case that had a chance to go to court – the only reason they were wasting time interviewing us was to patiently handle some neurotic unemployed scientists, making sure no one makes a tantrum in public… I sensed that they would have loved to have the case prosecuted to the hilt: unlike the garage meth labs, the Ecstasy busts in US are exceedingly rare – and a professionally equipped superlab operating from within a biotech company on university campus would be a stuff of legend. And they sure have no love for a privileged punk with a PhD making fools of them and getting away with it. I think they were thwarted, and directed to mind the university reputation above anything else.
___________________________________________________________________________

No one was charged. The company continues renting the office and lab space at the university research incubator, not really doing any research since shutting down the labs in 2016. EH&S performed a lab inspection, found few minor problems and wrote a mild citation. Unofficially, the company was warned by the university to never use the biotech incubator labs for a dangerous scale up manufacturing again. The polymerizations are technically challenging and some hazardous starting materials are tightly regulated – it is really difficult to contract out the entire manufacturing process to a CRO. My guess is that the company will need to build its own manufacturing facility, away from the densely populated areas.

The university did some house-cleaning – they made the wife of our research director to resign from her post of vice president for research integrity and compliance in the summer of 2016. Our technician from the formulation lab whom she hired after the layoffs, to work in her department, was pushed out too – he only found out when he saw his own position advertised on the university job bulletin board. He was completely innocent and he never got a chance to defend himself, the university canned him just for his association.

The company lawyer resigned, nominally for a client conflict but really for being misled and manipulated. The company soon hired a new law firm – more cautious and more expensive. The Chief Medical Officer left without explanation and removed the company association from her online CV. Also the business development guy who was at my termination interview have left – he developed a serious drinking problem, and it got worse at the end of March 2016. He had a heart attack recently, and died… He was a great person I admired: A self-made man and a military pilot. I think the sleaze did not originate with him, he found out about it too late to bail out – it probably pushed him over the edge.

morce

 

September 3, 2017

Breaking Bad in South Florida (9)

Filed under: Uncategorized — milkshake @ 12:27 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 9

(here is Part 1Part 2Part 3Part 4Part 5, Part 6, Part 7, Part 8, Part 10)

When I received the settlement documents from the company, I saw they did a quick job: there were typos, only two months of medical, instead of a temporary job extension at a reduced pay it was a straight separation, with a severance paid out in installments over a period of four months. The pay amount was the only thing that remained from our agreement, the rest was something else. The lawyer who drafted it had no clue. It was actually the same company lawyer who negotiated with the biologist fired couple months before – and our research director again did not feel like telling her about all the drugs that the management used to cook at the company, or the promises he just made to me…

I called the research director and protested that this wasn’t what we agreed on. He pretended like he did not see the documents – he assured me “he wasn’t trying to sneak this one on me”. Then the second version of documents came: it was the same text just with the typos corrected. I was supposed to apply to COBRA to get my medical and the company would reimburse it maybe later. The research director explained that he was working hard to come up with the agreement that “encapsulates” what we discussed on the dinner meeting on Monday. He just thought it expedient not to keep his word even though we shook hand on it. Instead, he proposed to have another meeting to renegotiate.

Meanwhile I saw that the Mac I got from him was trying to upload massive volumes of data to the cloud – it was tying up the connection and filling up the computer memory. (I did not have the net connection at home set up yet, I just ordered it and the Verizon guys were taking their sweet time so I was temporarily using a free login guest account on wifi radiating from a retirement community nearby; their connection was frail and slow). Then I noticed someone was reading an unopened message from my laid-off colleague in my private gmail account – and he tried to mask it by deleting the message and emptying the trash bin. So I checked the security settings: the Mac was set on enabled remote access and the firewall was down… I had pretty good idea who was reading my private e-mails and trying to upload my files to find out if I had any interesting piece of evidence on my computer. The offer about consulting and working from home was probably a ruse from the beginning, to have me take the backdoored Mac.

I changed my passwords, disabled the auto-backup cloud uploads and the remote access. I wrote the research director that it was difficult to take seriously anything he promised, and I was not slighted as he implied – not even surprised – but getting progressively more tired of everything that happened with the company and the role he played in it, as he kept making the same mistakes and excuses over again. And if we meet and try to reach a new agreement it should be final this time and not re-interpreted, modified or encapsulated.

To which I got a reply from the research director that he was cancelling our meeting and the deal was off. It was time for the lawyers. Instead, I went to war.

_________________________________________________________________________________

At this point it wasn’t about money anymore: I wrote to the research director and the business development guy explaining that the research director needs to resign from his role of a CEO – and I promised to do my part to get the company raided by the police and pushed out of the campus if he does not step down soon.

I also informed my freshly laid-off colleagues about the negotiations with the company. Some of them reacted with a surprise – they only got two weeks of severance – but they were hurt and not in a fighting mood: if anything, they were more angry with me that I got a better offer (and did not take it – because they would).

Next I called the DEA – they asked me to come over immediately but I wanted to meet some officer who investigated our company before, for repeated attempts to purchase the Ecstasy precursors. They said they would find out who that was and call me back. It took few days for them to do that.

I also paid a visit to the Chief compliance officer at the university: We had a long evening meeting and he promised to help. I knew his boss was the wife of our research director so it was tricky for him; she was the university vice-president for research integrity and compliance. I hoped he would not go to her straight away if I explained how much the whole affair stank. And I think he didn’t – but it is likely that he talked to someone else, in the university president’s office.

The university chief compliance officer was quite taken aback by the stories of drug cooking at our company – and he wanted to have absolutely no part in investigating it. He was saying it was a job for the police. So I also described some of the mishaps and close calls in our manufacturing, the risks of running kilo-scale polymerizations of ethylene oxide in a sealed glass reactor without automated cooling backup, without a burst disc and even without a reaction temperature internal thermometer. I mentioned the hectoliter volumes of flammable solvents in the lab and the nature of work with potassium metal, KH and diphosgene. We had no specialized safety training or sensors for detecting ethylene oxide leaks as required by the regulations. I showed him a picture of myself in a gas mask standing next to a 15L reactor full of concentrated HCl and heavy metal complex – parked next to a fume hood because we lacked a walk-in hood for the reactor.

Now we were on the same page. The university chief compliance officer told me that the fire safety people at the university were still having nightmares about our manufacturing lab ever since that fridge explosion and fire in March 2014. He said he would talk to EH&S at the university and he was pretty sure these safety violations alone should be enough to get the company kicked out of the research incubator. He said he would write the report using anonymous online EthicsPoint submission to the university, and he would do it by himself because he knew what to put in there to have the right effect. So he wrote it and I never saw his report.

sergey-kolesov-little-black-dress

September 1, 2017

Breaking Bad in South Florida (8)

Filed under: Uncategorized — milkshake @ 2:56 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 8

(here is Part 1, Part 2, Part 3, Part 4, Part 5, Part 6, Part 7, Part 9)

The Board of Directors met on Thursday, the last week of February 2016. Our research director did not stop to chat in the chemistry lab as he would usually do after these long meetings.

The next Friday morning I almost missed my termination interview when I showed up two hours late for it. But I was lucky, the managers were waiting and still willing to see me. (An experiment the night before was taking a long time – eventually I had to turn off the distillation, leaving it unfinished, past midnight). When I arrived to work, my colleagues were already mostly gone and the labs deserted – all quiet. Our grandmotherly administrator said that the boss needed to see me right away. There was a firmness in her voice that did not make it sound like a birthday surprise bonus check or the stock options that the previous CEO promised to me but then forgot, two years ago.

Still, I did not realize it was the grand finale until on my way there I saw a colleague walking back with an empty box in her hands, sobbing. I kept the squad waiting a little longer and helped my colleague to pack her books and papers, we carried it to her car. It gave me time to compose myself. (I even thought about just driving off without ever returning to the office but the result would have been the same and I did not like the idea of the company collecting and packing my belongings.)

So there was our research director with the business development guy waiting seated in a stuffy little office – and they looked heartbroken but they had no other choice and they were giving us two weeks of salary plus two months of medical as a severance if I please sign the papers right here at the dotted line. I told them they were way too generous and I couldn’t possibly accept their excellent offer: they should take their severance papers and please themselves in whichever way they find enjoyable.

I just figured that the list of people being laid off was probably put together three months ago, the HR consultant was already “helping with the transition” at the beginning of December last year, and the main factor that earned me the membership in the layoff club was that I made the CEO and the research director stop their illicit drug manufacture at the company. I explained that I was happy to fight the company with everything I got. The next thing they tried was the offended pose, to show me their indignation and they accused me of blackmailing them. The business guy taunted me about not having any evidence that there were drugs cooked at the company.

I walked out of that meeting and the research director run after me and brought me back to his office and he said that perhaps they should be able to work out some consulting arrangement since I was so tremendously valuable to the company. Before I even finished packing my box, the research director wrote me two e-mail messages to my gmail address (my company e-mail account already stopped working) and he attached consulting agreement proposal and he wanted me to stop by at his office, to see me again on my way out. He also set up a dinner meeting with me the next Monday.

____________________________________________________________________________________

Here is the Standard Model of corporate downsizing: The first principle is to keep all preparations secret till the last minute to better catch the subjects unaware what is about to happen so that they don’t sabotage the company or gather kompromat; ideally they should be off-guard even as they are sitting down with the “exit specialist”. Next, it is important to try to have them sign the prepared papers that they are accepting the severance and will not sue the company – this is best done by applying mild pressure while the subject is still shell-shocked. After that, you just get those bums out of the building, one by one, escorting them gently but firmly to control the unpleasant scene. The layoff theory stipulates that it is important to downsize on Friday (or better yet, on the last day before Christmas) because the ex-employees will have more time to exhaust themselves with anger and beer, and get depressed. After a weekend or holiday they will be less likely to return to the company with a shotgun. I don’t know how well the theory worked in my case but I did relax over the weekend and I was genuinely looking forward to the meeting on Monday.

On Monday night, our research director brought me the nice widescreen Mac that I was using at the company: he already prepared it by removing the company files but leaving everything else – it came installed with Chemdraw and MS Office so that I could work from home. He handed it to me in the restaurant parking lot.

I wasn’t keen on his vague consulting agreement where the number of work hours depended on the company whim. I wanted to see the exact income figure, the medical plan, my obligations laid down in a clear language. In the end, we shook hands on a fixed-term four-month extension contract: 3 extra months of salary spread over 4 months, with four months of continuing full medical coverage. I would be working from home. (There was actually plenty of research results to write up for publication and patents so this wasn’t a sinecure but a real job, and the company actually did something similar once before – to accommodate our colleague who had to be in Vancouver with his family).

I thought this package wasn’t great given the circumstances but I did not want to fight or deal with the lawyers – I thought it was reasonable enough: I could interview for a new job and still remain employed for a little longer, and I wouldn’t have to worry about medical insurance in the meantime. This convenience alone had a value for me. We could even remain on friendly collegial terms… So we shook on it and I was relieved. One huge problem solved, or so I though.

2eajifc

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”).

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 cover up 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 going to 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

« Newer PostsOlder Posts »

Blog at WordPress.com.