Intro - Sofie (Host):

What do AuDHD and biopharmaceuticals have in common? 

[Music]

Welcome to this month's episode of the Disabled Scientist podcast. 

I'm your host, Sofie, an autistic researcher, and I'll be introducing you today to John, a validation engineer with autism and ADHD. 

Just to let you know, this was my first recording and the audio was imperfect, but I hope you stay to listen because I particularly enjoyed this conversation with John. 

Let's get on with the show!

Sofie (Host):

So, John, what is autism and ADHD? 

John (Guest):

Autism and ADHD is like having very organized piles of your belongings spread throughout your house. 

I have a need for order and logic and sense, but extreme difficulty manifesting that in my life, though it is ordered chaos. 

Sofie:

Yeah. What does it mean to you? 

John:

What it means to me is having a lot of difficulty communicating with stuff. 

Certain people, I tend to have to use a lot of energy, not only kind of mask certain behaviors that might make the social interaction more difficult, but to pay extra attention to their body language to try to discern what they're saying and what they mean. 

Because I noticed that people have a tendency to kind of bury that information and only give you what they want you to know, but on the other hand, to have a easy and fun time connecting with people who have a similar neurotype to my own. 

Sofie:

That makes sense. You mentioned masking there. What. What does that mean? 

John:

I think a lot of people in the community will observe certain behaviors like stimming or things that bring comfort, but to people who have no experience with those kinds of behaviors seem odd. 

And it can introduce grit, friction, into one's social interactions. 

So, for example, I was sitting at my desk this week, and it seems that ADHD medication addresses some of the symptoms that I have on the ADHD side, but pronounce some of the autistic symptoms. 

So I was holding my mouse with one hand and just stimming on my own beard, just touching, running my fingers through my beard unconsciously while I'm trying to read. 

And I had to grip a pen in my left hand to keep from touching my face while I'm trying to read my documents. 

Now, realistically, I don't think anybody around me is really paying attention to me. 

Maybe out of the periphery because everyone's busy working, because for me, it is calming to run my fingers through my beard and keep it to a particular shape, but for others around me that I need to put on an appearance of blending in and not standing out for that type of behavior. 

Sofie:

So. Mm. What are the potential consequences of standing out?

John:

So far that I've seen in the biotech industry and I've heard it described as Boston style mafia -  

Sofie:

[Laughs] Okay! 

John:

Interactions. So in order to get things done effectively, you need to know a guy who knows a guy who knows a guy who knows how to solve the problem. 

Sofie:

Yeah. 

John:

So the effectiveness of your social network at work is tied to your own effectiveness as a person. 

If you're able to do a favor for a person, you can go back to that person later and say, hey, I need help with X. 

Remember I helped you with Y. Y. So if you start to build yourself a reputation where you're an odd person, it may make other people less wanting to work with you. 

And when you need to work through someone to get something done, whether it's, you know, sign a document or to partner with you on a project, that level of social cohesiveness that you've built with another person really impacts your output. 

There's that kind of soft skill effectiveness that plays into your work output and to struggle with that can spell doom for your career. 

It's really one of the things I'm most afraid of because I'm certain that given time and training I can do whatever. 

On the technical side, that's no problem. But can I lead a meeting? Can I bring a group of five people together because I need help with something? 

Can I convince people that I'm, I know what I'm talking about. 

These are the kinds of things that don't come natural to me. 

Sofie:

Have you spoken to any of your colleagues about having ADHD or autism? 

John:

No. 

Sofie:

No. 

John:

So the position that I'm in at the moment, my contracting organization has been hired by this large biotech firm to provide so many number of people for a particular project. 

And as a contractor, I'm not really ingrained with the larger employer. 

The advantage of having someone as a contractor rather than an employee is that you don't have to shell out further benefits and so forth. 

And it's easier to reduce staffing when the project is over. 

Right. So if I did anything to put a target on me saying that I may not be a potential good fit for a long term role at this company, they you don't have to out and out say we're terminating you because you're ADHD and autistic, they can really say whatever they want. 

So to open up to my colleagues about that, it's unfortunate, but it wouldn't really serve me in the long term. 

Yeah, I would rather, at least in this particular role that I'm in day under the radar and masked and just let my work show for itself instead of opening up to my co workers about my condition and making things ultimately more difficult for myself. 

Sofie:

Have you had bad experiences in the past? 

John:

I mean. Yes. So I worked for another company for a long time and I tried to move up out of the department that I was in into an engineering role. 

And I would apply internally to jobs at this company. 

And when I would talk to senior engineers, they would tell me that I was definitely qualified. 

Whatever work that I had done outside of my regular role supported my candidacy for those roles. 

And I would interview for them and then I wouldn't get the promotion. 

Sofie:

Right. 

John:

So now I was a little bit more open about my neurotype at that particular company. 

I can't say for sure because they won't say it out loud, of course, but I think that may have influenced their hiring decision or some particular struggles that I may have had. 

The- The tenure that I had at that company that saw me go through, I- I came into that company knowing I had an ADHD diagnosis. 

And it was while I was at that company that I attained the autism diagnosis and started work within that framework to kind of improve my social interactions at work to be more effective as a. 

As a leader, as a communicator in general. Because I would tune my communication style to something that would work for me, which ended up being too blunt, too black and white, too cut and dry for the average person. 

There's an incredible amount of utility that you can get padding your communication through for allistic consumption, let's say. 

Sofie:

Yep, that makes sense. 

John:

So playing that up a little bit made it a lot easier to interact with coworkers at large. 

Sofie:

It sounds like getting an autism diagnosis was helpful for you, even though it didn't necessarily change things in your previous workplace. 

It means that you've been able to develop skills that you can bring to your new workplace. 

John:

Yes. There's another saying that goes that you can't fix a problem you don't know about. 

And let me be clear, I don't view my neurodivergence as a problem; I never have. 

Sofie:

No. 

John:

But looking at it from a, how do I make this work for me so I can interact with people who are different from me? 

That was the angle that I was able to adopt once I knew that as previous to that, it was just I didn't seem to get along well with people and I didn't really know why, I didn't understand. 

Sofie:

Yeah. 

John:

And knowing that there's at least some cause was helpful because I was able to strategize and to change the way that I interact with others because it's strange to seem to get along really well with some people and not at all with others when I didn't really think that I was acting differently with one group to the next. 

Come to find out that some people get it and some people don't. 

Sofie:

Yep. I've ended up surrounded by neurodivergent people and it, you know, by accident, essentially I'm happier for it. 

But yeah, some people get it and some people don't. 

John:

I agree. Yeah. I. I know that engineering and STEM does have a tendency to attract people who are neurodiverse. 

So far in my experience, it seems it depends on your engineering specialty. 

I think were I to go into automation engineering, where people interact with code more than one another, I think it would skew more towards neurodiverse where validation, where I'm at now, there's teamwork and then working with regulators. 

So there's a lot of social aspect. But I think that it's definitely a growth opportunity for me, so I'm happy where I'm at. 

Sofie:

Yeah. I think now's a good time to ask. Could you explain what your job involves as a validation engineer? 

John:

Our task is to provide a body of work that shows that the equipment that we're responsible for is fit for use for production of drug substance. 

When we bring on a new piece of equipment, it goes through a series of tests to ensure that the equipment is fit for its intended use. 

And we're responsible for maintaining the validated state of the equipment. 

As the equipment runs, we will generate data based on the equipment's performance. 

When we're going after maintaining the validated state of that equipment, we will pull deviation records and data and impact assessments and establish if there are any trends of the equipment where it may be going out of specification more consistently, that there's some problem with the validated state of equipment or not. 

It's a challenge to prove a negative. 

Sofie:

Okay. Yes. 

John:

Trying to prove that something is not wrong. 

Sofie:

Yeah. 

John:

So we produce a report saying everything is fine with the equipment and here's why. 

And depending on how critical the equipment is, we have to would have to do this more or less often. 

But in any case, when regulators come calling, they can see that we've been doing our due diligence to make sure that the equipment works, that it produces the results that we need it to and that everything is in an acceptable range. 

Repeat forever or at least until decommissioning where we're no longer responsible for the validated state of the equipment because we're not using it to make stuff to put into people. 

Sofie:

Yeah, that's interesting. That's really. That sounds like really important work. 

John:

I like it. 

Sofie:

You like it? 

John:

So you remember what I said about needing order or wanting order? 

Yeah. The validation kind of speaks, I think, to the autistic, neurodivergent mindset, where you have black or white thinking. 

Something is generally compliant or not compliant. 

And if it's not compliant, that's a problem. If it's compliant, that's fine. There's very little gray area afforded to pharmaceutical manufacturing, and for good reason. 

Sofie:

Yeah, that sounds good to me. I'm also autistic, and I very much struggle with gray areas. 

That's pretty much one of the hardest parts of navigating a new work environment for me, is trying to figure out, trying to make sense of the ambiguities and the gray areas. 

John:

Yes. There thankfully, is very little that's ambiguous. 

Once you grasp the scope of a system, there's very little left to ambiguity. 

Ideally, the more ambiguous a biopharmaceutical process is, the more dangerous it is, so that ambiguity is kept to a minimum. 

Their people may be ambiguous, and that is another animal, but the work itself is very clear. 

Sofie:

Could you give me an overview of making biopharmaceuticals? 

John:

I can. 

Sofie:

Ooh. 

John:

So biopharmaceutical processing is the process of using living cells to make medicine. 

One of the earliest examples I'm familiar with is using horses to produce diphtheria antitoxin. ‘

Sofie:

Wow. 

John:

Because the animal had a large blood volume, they were inoculated and then had the antitoxin harvested from their blood. 

In the 1980s, some scientists accidentally discovered a selection factor available in a particular mammal cell, the Chinese hamster ovary cell. 

This was a pivotal development in biopharmaceuticals, and I'll explain why. 

When you have a selection factor in a mammalian cell, there's two critical things going on here. 

First is the selection factor. The scientists accidentally discovered that they could make cells that were deficient in DHFR [dihydrofolate reductase], a particular enzyme, and they can build what's called a plasmid and encode that plasmid for the ability to produce DHFR and also the ability to produce your protein. 

Of interest, once this plasmid is programmed with those two aspects, it can be transfected into these DHFR deficient cells. 

Any cells that survive have uptaken this genetic information that they can produce DHFR and survive, but will also produce your protein of interest. 

Just like a computer program, it's encoded for both of those things. 

So that is a selection factor. The other critical aspect is the fact that these are mammalian cells. 

Previously to this point, the research was only able to utilize selection factors in E. Coli or yeast. 

And while there are some simple molecules that can be produced quite effectively from those cell lines, when you start moving up into more complicated proteins, you encounter glycosylation. 

Glycosylation is sugar molecules on the outside of proteins. 

The body will read these sugars and if they are missing, the body will reject that. 

Sofie:

Ah

John:

So because we're able to have a selection factor in a mammal cell now, we can make much more complicated protein based and immunoglobulin based medications. 

So starting from these transfected cell lines, you can grow and culture a larger volume of these cells. 

And you will then move your cell volume up from a small volume to, you know, maybe less than a liter to 100 liters in a bioreactor, to 2,000 or 15,000 liters of cell culture media. 

Sofie:

That's a lot! 

John:

When you- yeah, the volume can be quite large. 

The cell may not be terribly effective at producing a large amount of the protein of interest.

Sofie: 

Ah, okay. 

John:

So it, once you've reached the end point that you want to get to, you sort of kill the cells and send it off to harvest. 

Because these cells were alive, they have a lot of host cell protein because the host cell needed protein to survive. 

And there's only one protein in particular that you're after, so you can run it through a centrifuge, which will separate larger solids. 

And after centrifugation, you will collect up your centrate and you'll move into chromatography. 

Protein chromatography is performed on what's called resin. 

It kind of looks like sand. 

Sofie:

Okay. 

John:

This is, it's a packed bed of finely engineered sand. 

Chromatography is the process of separating proteins by their fundamental properties. 

The first fundamental property that large scale chromatography generally works with is affinity for a particular binding site. 

So as you load your protein onto your column, the protein will bind its binding site to the binding site engineered on the resin. 

It's not perfect, however, because there will be some competing proteins that also bind on that binding site. 

But generally, what we call affinity chromatography has a 99% clearance rate of host cell proteins. 

So we're starting with a large clarification step. 

So the fundamental properties you'll look at first will be Affinity. 

Next will be your ion exchange, meaning what your isoelectric point of your particular protein is. 

And then hydrophobic interaction chromatography, which separates based on how hydrophobic that particular protein is. 

So by the time you finish those three steps, you've isolated your particular protein from all the other host cell proteins. 

You're working with a pure protein culture that is your drug product. 

Once you're finished with chromatography, you'll run the protein through viral filtration. 

Viruses will be filtered out and everything from viral patient on will have extra precautions to make sure that you don't introduce any environmental virus into the protein. 

You'll move from that to ultra filtration and diafiltration. 

The purpose of ultra filtration is to reduce the volume of your protein product. 

Whether it's for fill and finish or to ship. You want to have a smaller volume to work with. In addition, you'll have diafiltration where your protein is in background buffer A. 

You run diafiltration to put it from 100% buffer A to 99% buffer B, 1% buffer A. 

Because for buffer that you use through your last step of chromatography and viral filtration may not be the buffer you want to inject into people. 

And after diafiltration, you would move into bulk fill where you put the protein into containers to be shipped off to a fill finish facility where it can be prepared to be administered to people. 

So that is an overview of how biopharmaceuticals work, at least in the specific case of mammalian cell lines making nicely glycosylated drug product to be administered to people. 

Sofie:

Wow, that's really interesting. And so essentially your job is making sure that those machines, the processes that you've just described, are safe and are doing what they are supposed to be doing. 

John:

Yes. 

Sofie:

How did you end up doing this sort of work? 

John:

So I spent a long time as an operator for a biopharmaceutical manufacturing concern, so I would actually run the equipment. 

When I was in college, I took college courses on cell culture and purification, so I got to get hands on equipment experience doing this thing. 

Now, after being an operator for a long time and stubbornly trying to move up within the same company, I decided to respond to every headhunter on LinkedIn until somebody was willing to give me a engineering job in life sciences. 

And I worked that contract for a year. I commissioned a few chromatography skids and a bioreactor. 

I did a great job. I got great references from that. And that is how I ended up where I am today. One of the people that I worked with on that project is now my supervisor. 

Sofie:

That's very cool. What are you hoping to move on to next? 

John:

I would like to continue in validation engineering for time. 

So I get the full experience of validation engineering and I could see myself either continuing with that or moving on to more project work. 

It's really more about the availability of work and roles than preferences at the moment. 

I don't particularly have enough engineering experience where I can specialize, and I don't think I would really want to. 

I would rather have a broad base of knowledge than a specific one. 

So after becoming pretty well versed with validation, it's going to depend on what kind of work comes my way, I think. 

Sofie:

Cool. So you're pretty happy. It sounds like you're pretty happy doing what you're doing now and you want to continue doing that. 

But once you've got a bit more experience, you're quite open to where you go next. 

John:

I can't stand not learning things. Yeah. If I have a lull where I'm not really learning or developing or growing, I'm going to rapidly get bored. 

So I need more learning, I need to continue growing. 

I need more stimulus in order to stay interested in what I'm doing for work. 

I was miserable at the end of my manufacturing career because it was all the same, except for the few moments that I got to participate in projects and assist the engineers because I wasn't learning anything new. 

I would train other people with what I know, but I wasn't developing whatsoever. 

So, right. There may come a point where I'm just not learning anything new and that is the time where I start wanting to move on. 

I think the practice of engineering has enough for me to learn and I. I know that I have a ton to learn in this profession, so I think I'll have hopefully a long career ahead of me and continue learning for as much of that career that I can. 

Sofie:

And that sounds like an excellent place to end this off. 

Thank you so much for coming and talking to me today. 

John:

Yes, thank you for having me. It's a pleasure. 

Sofie:

I really appreciate it. 

Outro – Sofie:

Thanks again to John for coming on the show. I really valued hearing his experiences. 

I would love to speak with more people with roles in technology, engineering and mathematics. 

You can find the Disabled Scientists podcast on bluesky at disabledscientists.com and I can also be contacted by emailing: podcast at disabledscientists dot com. 

Thanks for listening. 

Bye. 

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