Creating a New World With a Molecular Genetic Pathologist


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SS 178: Creating a New World With a Molecular Genetic Pathologist

Session 178

Dr. Jason Rosenbaum is a molecular genetic pathologist and a fellowship program director at the University of Pennsylvania. Does he hunker down in the basement and let the machines do all of the work for him?

To find out more about this field, check out the Association for Molecular Pathology. For more podcast resources to help you along your journey to medical school and beyond, check out Meded Media.

Listen to this podcast episode with the player above, or keep reading for the highlights and takeaway points.

[01:04] Interest in Molecular Genetic Pathology

Jason became interested in molecular genetic pathology while he was interviewing for anatomic pathology and clinical pathology residency, which is often done as a combined residency of four years. During the interview, the program director asked him if he had ever considered molecular pathology. It turned out she was right because, given his background and interests, he was a great fit. From then on, he was committed to putting himself in the best position possible to get a molecular genetic pathology fellowship.

“Pathology is the practice of medicine that deals with specimens. Molecular genetic pathology is specifically the part of pathology that deals with genetic testing.”Click To Tweet

The field is broader than most people think in the sense that it’s not just necessarily human genetics, but it’s also about infectious disease. And it’s not just inherited genetics, it’s oncology. It’s essentially any test that might be returned from DNA or RNA sample that falls under the umbrella of molecular genetic pathology, and increasingly lately, some protein-based testing as well.

Molecular genetic pathology is taking anything out of the body and sequencing it to get to a genome to figure out how it’s made and what it consists of. And it’s not necessarily sequencing. It’s really based on the clinical need. They have sophisticated testing methodologies depending on what question is being asked.

[05:19] New Technologies and Findings

The field proper is about 20 years old and the technology keeps getting fancier and more elaborate. It’s a big part of what the job is – adapting to new technologies and new findings.

“The job of the molecular pathologist today is not necessarily very similar to the job of a molecular pathologist in 2015.”Click To Tweet

The first human genome was sequenced and published about 20 years ago. I really believe that medical school shouldn’t be four years. It should be more than four years now. Because every year, we’re learning so many new things.

And yet we’re cramming it all into the same four-year timeline and of medical schools. It just boggles my mind. And Jason agrees on this. He adds that in a lot of ways, medical school education ought to be longer.

[08:01] Biggest Myths or Misconceptions Around Molecular Genetic Pathology

The general stereotype in pathology is that they don’t care about their patients or that they’re antisocial. Those are some of the more insidious stereotypes. Jason illustrates how they have a different way of interacting with patients. They serve a discipline in the same way as radiology or pulmonology where communication and collaboration skills are needed to do their job.

Specifically, with molecular pathology, one of the biggest misconceptions is that the machine does all the work that you can just put the DNA in. Then the machine just tells you everything there is to know about the DNA. That is fundamentally not true. There’s a lot of technical understanding and interpretation that goes into most tests they do.

[09:55] Traits to Become a Good Molecular Genetic Pathologist

Jason stresses the importance of adaptability to become good in this field. For instance, the pandemic has put a premium on molecular testing. When more than a year ago, almost nobody would have thought that molecular pathology would have needed to shift itself so dramatically to viral testing in unprecedented ways.

And so there’s a dramatic need to scale up viral testing and the need to accommodate new testing and screening and new reasons to test viruses. Essentially, new clinical justification has really put a premium on molecular pathology.

[11:26] Typical Day

It’s a very collaborative discipline so a typical day for him would involve a fair number of meetings, either between multiple molecular pathologists. For instance, between molecular pathology and anatomic pathology, or between molecular pathology and microbiology, or molecular pathology and oncology, to name a few. But there are a lot of groups that need to be consulted and communicated with. And so, any given day involves a lot of meetings. 

In terms of the clinical work, it depends a bit on what essay is coming out on a given day.

Jason specializes in high throughput sequencing, which is what most people would refer to as the next-generation sequencing. And those essays require quite a bit of interpretation, quality control, etc.

On a day where he signs out, he might spend most of his time reviewing data and making sure all the T’s are crossed and I’s are dotted and all the mutations are detected. Then he writes up the report with those kinds of tests when not teaching.

[13:37] Typical Cases

Jason says this is going to depend on your particular practice environment. He’s at a very large academic medical center where they have eight or so different molecular pathologists. They divide up the work according to their interests and skills. And so, Jason does most of the next-generation sequencing. Then someone else might mostly do infectious disease.

But for a community molecular pathologist, the bread and butter stuff is going to be single-gene assays, relatively straightforward infectious disease testing, and lab management. They also deal with quality control issues making sure assays are performing within tolerance. For molecular pathologists, they’re routinely developing and bringing on new assays into the lab.

[14:52] Taking Calls

Jason doesn’t take calls. If any, the call issues for most dedicated molecular pathologists are pretty minimal. A lot of molecular pathologists are splitting their service work and maybe they’re also covering transfusion. Their call is going to look a lot like a microbiologist call.

[15:30] The Training Path

After you complete medical school, you do a pathology residency. The typical route, which would be anatomic and clinical pathology combined, is going to be a four-year residency program. Some people in academics will do just one or the other, which only makes it a three-year residency program. And then you do a one-year fellowship in molecular genetic pathology to get you credentialed as a molecular pathologist.

Now, that being said, it’s more and more common among pathologists to do a second fellowship. Things that are typically combined with molecular pathology – hematopathology being the most common, as well as cytopathology, transfusion, or any other pathology subspecialty can be added on.

'Adding on additional training is becoming more than the norm in pathology.'Click To Tweet

[17:20] What They’re Looking For in Program Applicants

For the molecular genetic pathology fellowship at their program, Jason says they favor people who are clearly committed to molecular pathology, as a field unto itself. And so, it’s not that having another fellowship is going to count against you or anything like that. But somebody wherein just from looking at their CV, you could see they’re committed to molecular testing in contrast to some other discipline.

They also look for data science or programming, or even formal bioinformatics training. Even as an amateur or a hobbyist, they find this valuable in an application because there are so many tools now so they need to rely on some understanding of software and data.

'Technology is already a big part of molecular pathology and, at least at large institutions, it's already spreading out into other parts of pathology.'Click To Tweet

Jason believes that it’s only a matter of time before the data scientists become important in more patient-facing parts of medicine, although it’s already important in radiology.

[20:06] Message to Future Primary Care Physicians

Genomics is complex and the technology they use to interrogate genomics is also complex. And so, Jason wishes that non-genomic experts would appreciate that the test results they put out are not as simple as the data they’re used to seeing from a basic metabolic panel or a chemistry panel. Since those only have a few numbers and each value can be understood in detail.

The data they work with is often massively larger, even for a single patient. For example, the medium-sized tumor sequencing panel that they run for solid tumors covers 152 genes. That’s about half a million base pairs of the genome. And that’s a lot of data every time you sequence a patient.

There’s often some tension between the expectation on the part of the person receiving the report that they are “just going to get a simple answer” and the reality that they have quite a lot of data.

”The human genome, in particular, the cancer genome can be quite complex. And sometimes there just aren't any simple answers.”Click To Tweet

[22:26] Is There a Possibility to Sequence Someone at Birth?

Jason adds that their fairly modestly sized panel covers half a million base pairs and the entire human genome is 3 billion base pairs. So there are a lot of genes they don’t understand at all. There’s a lot of the genome where they don’t understand its function and the mechanisms of regulation.

“There are a lot of genes we don’t understand at all… there can be mutations that can alter pathways, and our understanding of any of that is fractional.”Click To Tweet

The genome is only the start of it because the genome is transcribed into the transcriptome, and those transcripts are translated into proteins. And at each of those steps, there are modifications that can occur. There can be mutations that can alter pathways, and their understanding of any of that is fractional.

So he can’t say it’s impossible they could sequence somebody at birth and have some sense of what might happen to them biologically. But it’s a long way off before they can actually have a very good understanding of what’s going to happen to an individual.

[24:18] What He Wished He Knew Before

Jason wishes he had known the field existed, that way, he had more time to prepare and think about how he was going to get into the field. Good thing we have podcasts like this to share some of the more esoteric fields.

Before, he actually had no idea his field was even a thing. Had he known about this earlier,  the greatest benefit to him would have been to have some lead time, rather than finding out on the residency interview that molecular genetic pathology was a field.

One of the key things about this podcast is exposing students very early on to all these different niches so that you can start exploring passions to lead you to these fields. 

[25:35] The Most and Least Liked Things

Jason likes building a new test and deploying a new test, and knowing that the test would still be helping people even when he’d already stop practicing. He likes seeing the return on investment that the field presents.

On the flip side, what he likes the least is how other practitioners don’t appreciate the value they bring. And how they underestimate the sophistication of what they’re doing.

He also admits that he misses having consistent patient contact. He’s not some hermit living in a basement but he does find meaning in providing patient care and having that direct patient feedback is one of the things he misses.

[27:48] Final Words of Wisdom

If he had to do it all over again, Jason would still be in this field 1,000%. His career went in unpredictable directions. And he ended up somewhere great. And he feels grateful and lucky that he and the field found each other.

'I don't understand why everybody isn't going to be a molecular pathologist, except for the fact that people just don't know about it.'Click To Tweet

Finally, he wishes to tell students out there who are maybe just learning about molecular genetic pathology for the first time that any hurdle can be overcome. You might not get the MCAT score you want, or not match exactly in the program you want. Maybe a rotation goes poorly for you. Whatever it is, it’s not the end of the world.

Jason started his career as an MD/Ph.D. because he originally wanted to do bench science. And his Ph.D. didn’t work out in a spectacular way. So there was a time he thought he would never be happy in his career. But he found a way forward and it found him.

'No matter how bad it seems, it can get better and things can work out. You just have to keep at it and keep trying to find the best path forward for you.'Click To Tweet

Links:

Meded Media

Association for Molecular Pathology

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