Meet Dr. Colm Collins!

Episode Transcript
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Speaker 1 (00:00):
Hi, I'm Alicia and I'm Robin and you're listening
to Bowel Moments, the podcastsharing real talk about the
realities of IBD Serve on therocks.
This week we talked to Dr ColmCollins.
Dr Collins has a PhD inintestinal immunology and is
currently an assistant professorat the Conway Institute of

(00:20):
Biomolecular and BiomedicalResearch at the University
College Dublin.
Prior to that, he was anassistant professor at the
University of Colorado.
He is a research scientistworking on finding new
treatments for inflammatorybowel disease and has a special
interest in cannabis.
That started with his time inColorado, so we talked to him
about doing research in cannabis.
We talked to him about gettingresearch funding and the

(00:42):
challenges there and the supporthe received from the Crohn's
and Colitis Foundation.
We talked to him abouttranslating science for lay
people and patients to helpeducate them on all the exciting
things that are happening.
We talked to him about what'son the horizon and what might be
new in inflammatory boweldisease treatments, and we
talked to him about what it'slike working with animal models
of inflammatory bowel disease.
Dr Collins is a laugh riot, sowe really enjoyed our time with

(01:04):
him.
We know you will too, cheers.

Speaker 2 (01:10):
Hi, everybody Welcome to Bowel Moments.

Speaker 1 (01:11):
This is Robin.
Hey guys, this is Alicia, andwe are absolutely delighted to
be joined by yet anotherinternational guest.
I am very excited to talk tothis person, Dr Colm Collins.
Welcome to the show.

Speaker 3 (01:21):
How's it going?
Nice to meet you.

Speaker 1 (01:23):
Nice to have you on the show.
So we are going to get to youand who you are and get to know
all about you very, very soon.
But our first veryunprofessional question for you
is what are you drinking?

Speaker 3 (01:32):
Well, despite the fact that I'm Irish and I didn't
want to push the racialstereotype too far, I'm actually
coming down with a bit of acold, so I figured hot whiskey
is the way forward.
So I've got a whiskey with somelemon.
Lemon's obviously full ofvitamin C and that's very good
for boosting your immunity,fighting infection.
And then it's got clovesstudded into it and again the
cloves provide that analgesiceffect but also help clear my
throat a little bit so I cantalk to you guys more

(01:54):
comfortably, and obviously it'smostly hot water.
Then, after that, we had asmall dash of cooking jams.

Speaker 1 (01:58):
All right, that sounds good here's all.
Yes, robin, maybe you need that, maybe I do, maybe I do.

Speaker 2 (02:03):
I am having coffee, but while we were doing the
setup, I had my husband, matt,swing in here and put a splash
of bourbon in it, so I'm havinga little coffee with bourbon.

Speaker 1 (02:12):
I am also having bourbon Robin.
Hey, here's a bourbon cinnamonsimple syrup, old-fashioned.

Speaker 3 (02:19):
I love that you should stick a couple of slices
of apple in there.
A couple of slices of apple inthere.

Speaker 1 (02:23):
you're away there you go, I might have to run
downstairs real fast and putsome apple in there.
But well, cheers guys.

Speaker 3 (02:30):
Cheers.

Speaker 1 (02:31):
Dr Collins thank you so much for being on the show.
Next question for you Tell usyour IBD story.
What made you become part ofthis community?

Speaker 3 (02:38):
Well.
So it obviously started when Iwent to college.
So someone suggested to methey're like you know, if you're
going to go to college, youreally should experiment with
drugs.
And so I said, okay, fairenough, makes sense.
Studied pharmacology andabsolutely just loved it.
You know, I was fascinated by.
You know how complex it wasmaking drugs and how to get them
to where they need to go andthen how to make them do what
you want them to do.
So I did that and I loved it somuch that I stayed on and a PhD

(03:00):
in GI diseases.
So looking at it sounds prettyglamorous, but I was looking at
cramping and diarrhea inchickens and at that point I
thought, right, well, Wait,that's what makes it glamorous.

Speaker 2 (03:12):
It's specifically that it's chickens.

Speaker 3 (03:17):
I didn't mean to interrupt you, but I had to,
like I mean so chickens areconstantly infected with stuff
like salmonella andcampylobacter, bacteria that we
would normally get really sickfrom, and yet they're somehow
completely immune to it.
So we really wanted tounderstand how they managed to
do that.
But, like I said, it soundspretty glamorous.
But then so at the time my thengirlfriend she's now my
ex-girlfriend, or my wife, as Ilike to call her so my wife she

(03:38):
was working in Baylor College ofMedicine and she said, oh, you
should come out here and youshould interview for a job.
And cause she's like I reallylike it here and it's amazing,
and you know it is, it's anamazing center for research.
But I met with a very nicegentleman called James
Rusalovich who's at TexasChildren's and he said look.
He said you know, it doesn'tmatter where you work in the in
the U S, you're going to Texasand the only downside of living

(03:58):
in Texas is you've got to gofrom your air-conditioned house
to your air-conditioned car toyour air-conditioned place of
work.
And I thought, brilliant, I'llgo look at a job in Colorado,
because that's kind of halfwaybetween the two.
And so I did.
So I interviewed for a job inColorado.

(04:20):
I worked for a physicianscientist called Jesus Rivera
Nieves and he was amazing.
He was working in the lab fourdays a week and then seeing
patients on the fifth day, andit meant that he was really,
really at the coalface in termsof looking after patients with
pretty severe IBD.
So you know it was a referralcenter and so they were getting
all the worst possible cases.
So, jesus, his enthusiasm justblew me away, like he couldn't

(04:41):
help but get excited about it.
To a certain extent it was likebeing locked in a room with a
really bouncy ball.
You know that you're constantlykept on your toes.
You're kind of forced to getbetter, forced to move quicker.
You know you're probably goingto come away with some bruising,
but yeah, generally I'd say itwas easily one of the most
enjoyable periods of my life.
You know, working with peoplelike Owen and Josh and Megan and
Matt, it was just amazing.

(05:08):
And I just got engaged with thisIBD research process and then
from there I got a researchfellowship award.
So that was from the Crohn'sand Colitis Foundation and
they're incredible.
They can just kind of suck youin, so you get funding from them
and then they say, okay, wegave you some money.
We'd like you to spend that tocome to a meeting that we're
hosting.
And so you go along to thismeeting and it's amazing.
It's like the Oscars for IBDresearch.
It's like all the big namesfrom clinical research, from
translational research, you nameit, and these people are just

(05:29):
hanging out, having a couple ofdrinks, having a chat and
they're saying, oh yeah, you'redoing that experiment.
Well, here's the 10 ways I'vetried it and here's the way that
might work best for you.
And it just cuts down so muchon the learning curve, it just
makes it so much easier and itjust really accelerated my
research and it just I loved it.
It was amazing.
And then the other thing that'snice about the foundation is
that they're so engaged inpatient education and patient

(05:51):
engagement that as soon as I gotback to Colorado, having you
know.
I'd obviously been on someone'sradar and I got a call from our
Rocky Mountain chapter from ayoung gentleman called Jeremy
Stern.
So Jeremy was like he's likefive foot five, ginger hair, but
he's got his personality.
That's like the size of themile high stadium.
Like I don't mean ego, I meanpersonality.
This guy was just insane.

(06:12):
He would, he would have youdoing stuff and you kind of felt
like you know he was doing, youwere doing him a favor, even
though you were coming away withway more than what you put into
it.
You know, like he'd say, hey,colm, you know we'd like to host
a lab tour, so we'll havepeople come around your lab, is
that okay?
And the next thing he'd show upwith 30 people, he'd be fully
catered, he'd be all organized,everything done.
And you know we'd give a littlebit of a tour and explanation.

(06:33):
And you know that doesn't fail.
When I do it it'll fail by thetime it gets to the clinic
pretty much 90%, but anyway.
So realistically I'm looking atthis going.
I don't know if I want to seethe faces of the people who I'm
constantly disappointing.

(06:53):
You know I get enough of thatat home.
So even still, I was like okay,I'll do this.
And I was blown away because Imet people who had lived with
this disease and they didn'tneed sympathy or support or they
were just rocking it Like everyday was a new day and they were
super excited.
They were like, oh cool, youknow, it's great to see people
working on this.
And you're like, wow, I'mreally bad at it.

(07:14):
And they're like, no, no,that's fine, like at least
you're trying.
So you know, for me were like,oh yeah, I've tried this, I've
tried this, I've tried this.
This kind of worked, this onlykind of worked sometimes.
But it also gave me this whichI never thought I would get, and
I was like, wow, geez, I'm likea taken notes going.
This is immense.
Like you know, the books don'ttell you all of these patient

(07:34):
experiences and how these drugsactually make you feel, as
opposed to just, this is apercentage drug in this context.
So for me that was huge, allright.
So then research, fellowshipthat went really well.
I was happy enough.
Like I said, it was probablythe most productive time of my
career.
I had no kids, it was easy,things were nice.
But then again, where thefoundation really kind of steps

(07:55):
up is, so they supported me forwhat's called a career
development award, so that wasabout 2012.
And we're talking big money now,right, so this is like $300,000
for a three-year research grantand in and of itself, that
seems like a huge investment forrelatively little return in
terms of I'm a one scientist,one-stop shop.
But actually the way it worksis it's much smarter than that.

(08:15):
So what they do is they haveyou apply for this funding and
then you get feedback, and thefeedback's coming from people
who are absolute experts in thefield, right, and so they can
tell you here's all the thingsyou're doing right, here's all
the things you're doing wrong,here's the reasons why it's good
, here's what's bad about it,here's how you can make it
better.
And so the feedback you getit's not like oh yeah, we're not
giving you the money.
End of story, best of luck,goodbye.
Instead you get then is youknow, it makes you way more

(08:45):
competitive at a kind ofnational level, because you've
had this kind of incubatorsystem where you're being
coached and corrected andprodded and poked and got into
the right kind of areas, whichmeant that when I went to look
for NIH funding you know thatwas I mean I don't want to say
it was easy, right.
So the funding rate's probablyabout 20%, but still I had a
huge advantage going into thatbecause I'd already gotten the
support from the Crohn's andColitis Foundation.

(09:06):
So I walked in, got that andnow all of a sudden their
$300,000 investment turned intothree quarters of a million of
federal dollars to spend on thesame problem.
Right, we're still dealing withtreating IBD, but now all of a
sudden we're getting federaldollars to do it instead of just
foundation bonding.
So you're basically looking attaking every dollar that the
Crohn's Colitis Foundationinvests and that converts to

(09:27):
$3.50 if you include the federalfunding.
Except that I was even able togive back some of the money that
the foundation sponsored intothe final year because of
overlap with the new grant.
So that was huge.
That's not just great from anIBD community perspective,
that's just great business endup and through that, because I

(09:49):
was involved in that stage.
Then I got involved with peoplewithin the foundation who were
really keen to kind of helpprogress careers of junior
investigators, help todisseminate knowledge and break
down barriers to communicatingor collaborating with people
within our field.
Like that's normally adifficult thing to do to walk up
to someone who you idolize andsay, hey, can I get you to come
to my lab and help you with myresearch?
Whereas, because the foundationjust cuts through all that kind
of hierarchy and says we justwant this to happen, we want the

(10:11):
results, we want it now, wewant you to focus on getting
this done.
It just breaks down all thatkind of resistance and it makes
the process so much simpler.
So I remember that there was aVP of research at the time
called Marjorie Merrick, andMarjorie was just this
incredible person to watch.
So it was like watching thismajestic lion just parading
through the savannah, right, onthe one hand, she's incredible

(10:33):
to watch.
Right, she's incrediblyefficient.
She just cuts through all thenonsense, gets things done,
breaks it all down, but at thesame time, in the background, in
the back of your mind, you'rethinking I never, ever want to
be on her bad side.
You know what I mean.
So through that process then Ihad, you know, people coming out
to our lab.
You know, meet someone who's atthe foundation meeting, and
they go oh yeah, no, we're doingthis experiment all the time.

(10:53):
You know, don't waste your timelearning how to do it.
Why don't you just fly out toNorth Carolina We'll show you
how to six months and this kepthappening the whole way through
and it was all because thefoundation just put us together.
I wouldn't say that's their onlyjob, because obviously they do
a lot in terms of patientsupport and patient education.
And we see that and they do aton of work in terms of

(11:14):
physician education right,because things are changing so
fast within the field.
New drugs come out, but alsothe drugs that we already have.
We're changing the way they getused.
We change the order in whichyou use them and who gets what.
Then that's all changing allthe time and they really make
sure that physicians who are onthe ground you know PCPs and you
know referral centers and stuffall have the same level of
knowledge when it comes to whatthe best kind of case scenario

(11:35):
is.
And actually I saw you had AlanMoss on your show last week, so
I obviously want to mentionthat because Alan's actually an
alumnus of the Conway Institute,where I work in UCD.
So clearly you know he wastrained in the Conway so he
knows how to operate with afairly constrained budget.
So I would say, if you'refeeling being supportive,
especially this holiday season,if I was putting smart money, I
would invest in that foundation,not just because you know, I

(11:58):
think it's a great effort, butalso because I think it's where
the smart money goes, like, evenif you hate, if you absolutely
hated people who hadinflammatory bowel disease,
right, and all you cared aboutwas this is the most expensive
disease there is and I want myinsurance premiums to go down
I'd stick my money on thefoundation simply because you
know that when the time comesthat a cure is found, they'll

(12:19):
have their fingerprints all overit.

Speaker 1 (12:21):
Wow, I'm pretty sure that anybody who hates Maybe
they hate listening, maybethey're trolling us, I mean a
download Alicia.

Speaker 2 (12:36):
a stream is a stream.
We need the numbers, that'sright.

Speaker 1 (12:40):
We'll take it.
So funding is limited.
So how do you prioritize whatyou're going to research?
I mean you started out withchickens.
Obviously that involved it.
How do you prioritize what'sgoing to be the best way to use
limited resources?

Speaker 3 (12:53):
So for me there's always been a theme right.
So intestinal disease is areally tough target because
there's no all or nothing, right, you can't shut it down
completely, your intestinalimmune system, because there's a
kilogram of bacteria in there.
They're just waiting to breakdown the barrier and invade and
cause damage and cause infectionand stuff like that.
So you can't shut it off.

(13:13):
You know, like if you've got aninfection in the eye you can
quite easily say, right, let'sjust blow this wide open, kill
every single living thing.
That's not eukaryotic and it'llbe fine.
But you really can't do that inthe gut because then it affects
digestion and it affectseverything else.
So for me I've always looked atways to just modify existing
pathways.
So know, we started withretinoic acid, looking at how

(13:34):
vitamin a can in effect immuneactivation and immune and immune
cells traveling into the gut.
You know, as a way to say,right, well, if we can shut that
down or turn it down a bit,we'll still have natural
immunity present in the gut.
But now all of a sudden it'snot quite as rapid and so then
that's spread into.
You know, targeting microRNAs.
So microRNAs are just reallyshort RNA sequences and they're

(13:57):
perfectly designed.
I mean, this is literally whatthey're designed for.
They're not on-off switches,they're just dimmers on an
existing system, right?
So they're just designed totweak things up and down in a
very kind of controlled manner.
And so we did a study a fewyears ago where we looked at a
specific micro RNA calledMira106A.
They're all named for reasons Idon't know, but it was a

(14:19):
perfect target in that we knowit's increased with IBD patients
, it's increased in the gut ofan IBD patient.
We know it responds to TNF.
So TNF, or tumor necrosisfactor, which is what, like
Remicade and Humira and Simsia,they're all designed to target
TNF.
So we know that's important.
And also we know that itsuppresses natural or
anti-inflammatory cytokinecalled IL-10 or interleukin-10.

(14:41):
And so the idea was okay.
Well, if it goes turned onduring inflammation and it
suppresses anti-inflammatorysignaling, then all we have to
do is silence it and we canhopefully develop a treatment.
And it worked really well inmice.
Now those mice never thanked usfor curing them, but we did all
the time.
So we cured it a couple ofdifferent ways.
We cured it, we knocked it out,we deleted it genetically and

(15:03):
then we also used a lentiviralvector to silence that specific
microRNAs or microRNA.
Problem in reality is that thedelivery of those drugs is very
difficult, so it's not certainlyready for clinical use,
unfortunately.
But like again, the theme kindof stuck with me that I liked
this notion of taking endogenoussystems and making turning them
up or turning them down, ratherthan turning anything on or off

(15:23):
.
So from there then I switchedto looking at excuse me, alpha-1
antitrypsin.
So this is another protein thatyou find a lot in your
bloodstream and we saw thatpatients were losing a lot of it
.
You know.
Same with lactoferrin.
So lactoferrin is another onewhere you know this was used as
kind of a biomarker is oh, youknow, we can measure lactoferrin
in your stool and see how muchyou're losing and that tells us
how much bleeding internally youare or you have going on within

(15:44):
the gut and how absorptive your, your colon is and how you're
covered, how you're copingreally with your inflammation.
But that's all people thoughtit was.
They were like oh yeah, this isa good biomarker, but that's it
.
And I kind of went well, hangon, if you're losing a ton of it
and it's kind of important,what about we put it back?
Would that be helpful?
And so again, that's what wedid.

(16:12):
We said, right, well, we madewith a friend of your drug, but
we stuck that into mice.
And again same thing.
We made them totally better.
Again, we've patented that.
We haven't moved it intoclinical trials yet, but the
hope is that at some point we'llget there.
And then, most recently, Iswitched gears a little bit and
I started working on a drugyou've probably not heard of,
called cannabis.
And so cannabis actually thereason why cannabis does

(16:35):
anything is because our body hasa natural what we call
endocannabinoid system, right?
So there's a system within ourbody that responds to chemicals
that our body produces, calledendocannabinoids, like
anandamide and 2-AG, and theseare natural signaling molecules
within your body and they canturn stuff on and off and they
can affect your nerves and theycan affect stuff on and off and
they can affect your nerves andthey can affect your immune
cells and they can affect awhole range of different aspects

(16:56):
of your body.
And that's kind of whatcannabis plant hijacks.
It kind of hijacks that system.
So anandamide, for example, itcomes from the Sanskrit for
blissfulness, because it givesyou that like warm, kind of
fuzzy feeling.
So they often say that peoplewho runners, runners who like go
running for whatever.
I don't know why.
It just blows my mind.
But if you're into that sort ofthing, runners get this weird

(17:17):
high from running.
I think I don't think it's justlike a sanctimonious I'm better
than you kind of thing.
I think it's a.

Speaker 1 (17:22):
It is a physiological response and that response
might be a little bit ofsanctimony in there too probably
a little bit of both, I wouldhave to say yes right?

Speaker 3 (17:30):
well, basically they, they produce increased levels
of anandamide and that's whatgives them that blissful feeling
, that's what makes them feelgood.
And so we were interested incannabis because I was working
in Colorado, which you may ormay not know is one of the
founder states when it comes tothe green, the green rush, but
we were.
I was working specifically inchildren's hospital in Colorado
and we had, I think, a third ofour adolescent patients.

(17:51):
So there was a study by acolleague of mine, ed Hofberg,
and he showed that a third ofpatients who are kind of 13 and
up were using marijuana.
And we were like, oh, that'shuge.
So we wanted to understand,first of all, why, why on earth
would you use this?
And, second of all, what'sbeneficial, because if it is
great, we can certainly engagethat.
But really we just wantedinitially to understand what's
happening.

(18:11):
And so it turns out there's alot of good reasons why you
might want to use marijuana,right?
So for people who haveintestinal disease, which is
often associated with gut painor visceral pain, in fact, it's
the number two cause ofintestinal pain there is, after
gastroenteritis, where you'vegot an infection.
Ibd is the second most commoncause of visceral pain right and

(18:31):
that's pretty severe.
And the problem with pain forpatients with IBD is that you
can't treat it.
You can't treat it with aspirinor ibuprofen because those
drugs cause more tissue damage.
They prevent that protectivemucus within your gut from
forming and that makes diseaseworse, and so that's a no-no.
At the same time, opioids notreally a great option either,
because you've got, you know,that affects bowel motility, so

(18:52):
you're susceptible to gettingthings like toxic megacolon,
which sounds like a transformerbut it's actually.
It's actually pretty severe.
Definitely want to avoid that.
But overall, you know, and it'saddictive and you know there's
and you're at risk of gettingthis kind of hyperalgesia where
basically the more more opioidsyou use, the more pain you feel,
and so there's a lot of reasonswhy you want to avoid that.

(19:18):
And we know from studies by aguy called Daniele Piemelli.
He showed a few years ago thatif you prevent the breakdown of
natural cannabinoids within thebody, that you get a decrease in
this visceral pain.
So you can actually suppresspain with cannabis-like
compounds, and so the same istrue if you use marijuana.
It looks like you can certainlysuppress that visceral pain to
a certain extent, which istotally understandable.
And if that's all it did, Iwould advocate wholeheartedly

(19:39):
for people to use it, but it'snot all it does.
So another nice feature forcannabis, if you're interested,
is it increases your appetite,right?
So we know this.
You know people go for themunchies and think this is a
great thing, and to a certainextent, for IBD patients, I want
to say I don't want to say it'strue, but they're not wrong.
So there's a big issue withpeople who have IBD that they
don't want to eat.
Because if you're having bowelmovements 10 times a day and
everything you eat comes with aside order of visceral pain,

(20:02):
then you're inclined to eat lessoften.
That sounds like a pretty poordeal.
The flip side of that is, ifyou can eat more and improve
your appetite, then that helpsyou boost your immune system, it
helps you fight infection, ithelps you control your disease a
bit better, it helps to manageyour stress levels.
There's a whole load ofbenefits from eating more and
from recognizing that you've gota decrease in nutrient

(20:24):
absorption.
So, if anything, you need toeat even more than a person
who's not suffering fromintestinal disease.
There was a paper, actually aguy called Mark Garrick, who's a
former colleague of mine andhe's not the only author on the
paper, but anyway, mark's thefirst author on this paper, but
it's basically a clinical.
It was from the Red Journal.
It was a clinical paper lookingspecifically at how cannabis is
beneficial or not for IBDpatients, all right.

(20:46):
So they talked about it in thepaper.
They talked about the painissue, they talked about
appetite, but what they didn'treally talk about was intestinal
inflammation, right, and how itaffects that.
And so for me that wasobviously that's super important
because you know, yay, great,if you can get rid of the
visceral pain, that'd bebrilliant, so long as it's not
doing more harm than good.
And so a few years ago there wasa couple of studies by a really

(21:06):
talented scientist called TimnaNaftali, and so Timna showed
that she did two differentstudies now quite small studies,
but in two studies using eithercbd or cannabidiol or thc,
which is one of the other activeingredients of cannabis that
patients who use marijuana fortwo weeks and had crohn's
disease saw a significantreduction in pain, a significant
decrease in motility and bowelmovements, but what they didn't

(21:27):
see was any kind of improvementin their uh, what we call kind
of empirical measures of diseaseright.
So whether it was in the bloodor in their stool or you know
anything empirical measures ofdisease, right?
So, whether it was in the bloodor in their stool or anything
where there was no questionabout it, and so that was kind
of a red flag to us that itdidn't seem to be having a
protective effect.
But again, that's fine as longas it's not doing any damage.
Except that a couple of yearslater there was a paper by a

(21:49):
Canadian group, by a guy calledMartin Storr, and what Martin
showed was actually that forpatients who were using cannabis
for six months or more, theirlikelihood of having surgery
went up five times, five fold,like five times higher.
And that's huge.
Now you'd argue that, okay,maybe this.
It's skewed in that people withprobably more painful and more
severe disease might be morelikely to use cannabis.

(22:09):
And this wasn't a prospectivetrial, wasn't like hey, if
you're, you want to, you know,enroll.
This was just kind of aretrospective study, looking at
people who use cannabis andlooking at whether or not they
went on to need surgery.
But even still, a five-foldincrease in surgical risk is
huge, right.
So that's a big deal.
We always think of surgery asbeing kind of the worst case
scenario.
So anything that inflects theresults, that much it's got to
be very-.

Speaker 2 (22:30):
Wait, I have to stop you right there.
I have to stop you, surgery isnot a worst case scenario.
It is a treatment option.
I just want to put that outthere.
We always say that on the show.
We've had several surgeons onhere, so surgery is not a worst
case.
Last resort.

Speaker 3 (22:45):
Actually there was a paper from a group in the UK who
recently said that actually,especially for ulcerative
colitis, that surgicalintervention early, like almost
immediately, was probably thebest outcome for patients.
But sorry, I'm specificallytalking about Crohn's disease in
this case.
But yeah, so avoiding surgeryseems like a good option.
And so that made us kind ofwork on what's the cannabis

(23:05):
doing at a cellular level that'schanging this disease
susceptibility, right.
So we started looking at Tcells, which are a subset of
immune cells within the gut thatare known to not only make the
disease worse but they persistand they last a long time, and
they're the ones that kind ofcause the chronic nature of the
disease.
And so, even if the diseasegoes away and those t-cells move
out of the gut and they moveoff somewhere else, they'll go

(23:27):
to the, to the joints, andthey'll cause all right, you
know, arthritis type pain.
Or they'll go to the eyes andthey'll cause inflammation of
the eyes, like uveitis, orthey'll cause skin diseases like
pyoderma gangrenosum orerythema nodosum, diseases that
we always associate with IBD butare kind of triggered by the
intestinal disease.
They're secondary or what wecall extraintestinal

(23:49):
manifestations, right, and sothat's all driven by T-cells and
a kind of memory that theT-cells maintain.
And so what's all driven byT-cells and that kind of memory
that the T-cells maintain?
And so what we found is that ifwe take cells just in isolation
and we stimulate that cannabispathway within those cells, then
our cells develop the munchieseffectively, right?
They start sucking in sugarlike they can't stop.
They just take on a load ofsugar and it completely changes

(24:09):
their outlook, right?
So instead of doing whatthey're supposed to do during
infection, which is theyproliferate a load, they get
loads of T-cells, they kill offthe infection and then they die.
Right, that's what you want.
You want a system where, ifanything goes wrong, the
response is really fast.
You get this massive immunecell activation, those immune
cells totally engulf whateverinfection arrives and resolve it

(24:30):
, but then they die.
And the last part's just asimportant, right?
You still want them to diebecause you don't want them to
survive, because they'll only gosomewhere else and do more
damage, right?
They're like English soccerfans.
So really, what you want tohave happen instead is you want
them to divide and proliferatebut then die off, and
unfortunately, because of thecannabis, because they take on
so much sugar and they startreducing proteins that will

(24:50):
allow them to survive muchbetter and much longer.
Now, all of a sudden, you've gotthis immune system that can
last and last and last, and soif it's triggered
inappropriately, like we seewith patients who have IBD, it
will persist and it will reoccur, and so those patients might
feel fine initially, but whentheir next flare comes they've
got more T-cells on boardalready that are primed and
ready to go, and they will justtrigger this much more severe

(25:13):
flare up when the secondinfection comes, and that's
already part of it.
So it turns out your T-cellsalso have signals that send it
to different locations, right.
And so we've seen drugs likevedalizumab, which is a drug
that targets T-cells fromtrafficking into the gut, and it
does so by blocking thisintegrin or surface protein
called alpha-4-beta-7.
And so we know that's reallyimportant for gut homing,

(25:35):
because if that, elizabeth worksand it works in about 20% of
patients then that pathway hasgot to be important, right.
And so one of those kind ofside effects that we saw when we
started stimulating ourselveswith cannabis-like compounds is
that now, all of a sudden, thatintegrin, that alpha-4-beta-7,
starts coming up a lot, muchhigher than normal than you
would see on normal immune cells, and that's a problem too,
because that means now you'reshifting more cells into the gut

(25:57):
.
It's a double-edged sword,because in one way it helps us
to understand how is it that inother diseases it looks like
cannabis might beanti-inflammatory, right?
So if you've got arthritis oryou've got MS or you've got
something else, it looks likeit's protective and it's
anti-inflammatory.
But it could be.
What's actually happening isit's driving your cells into the
gut and once they're in the gutthen your other diseases might

(26:18):
calm down.
But now your intestinal diseaseis primed for when the next
infection comes.
And certainly there's evidencethat we've seen from monkeys.
So there was a study looking atkind of a monkey version of HIV
and what they found is if theygave monkeys marijuana and it
meant that their disease wentway down, so their viral and
viral loads dropped offsignificant, because what was
happening was all those t-cellswere being forced into the gut

(26:41):
and, as a result, werecontrolling the virus much
better, because that's generallywhere hiv lives.
So yeah, so basically there'swe think we see the same thing,
that we can and, moreimportantly, we can now start
blocking that pathway.
Right now that we know kind ofthe cannabinoid pathway is
important in the immune system.
What my lab is working on nowwith our collaborator, a guy
called Dave O'Connell.
We've developed what Dave, forreasons I don't understand,
calls SHRIMP.

(27:02):
These are selective humanreceptor-modifying peptides, or
SHRIMP.
But the point is, the plan isthat they will target the
cannabis system and they willstart to reverse those kind of
symptoms and stop T-cells fromgoing to the gut and stop them
from persisting.
So that's kind of where we'reat.

Speaker 1 (27:22):
So out of curiosity for the other disease states
like, say, you have multiplesclerosis and you're using
cannabinoids to control your MS,but it's driving all the
T-cells into the gut.
Do we then see people who endup with GI issues?

Speaker 3 (27:32):
Not necessarily, because if you think about
inflammatory bowel disease,you've got to have a whole bunch
of risk factors combinedtogether to actually develop the
disease.
So, for example, it's notenough that you've got the right
genetics to develop disease,because we know that twins,
they're only about 40%likelihood of them both having
it.
It's not enough that you livein a developed country, because

(27:53):
obviously there's a whole bunchof people living in developed
countries who don't develop it.
But equally we know that if youlive in sub-Saharan Africa, the
chances of you developing IBDare also pretty low.
So it's obviously there is anenvironmental factor.
We just don't fully understandwhat it is.
And then we know that there's atrigger.
So it doesn't matter what thetrigger is, whether it's butt
chugging, alcohol or a viralinfection or whatever it is.

(28:15):
Any of those things can triggerdisruption of the intestinal
barrier, which allows bacteriato get across that barrier, and
that triggers an immune reaction.
So there was an amazing study bya scientist in the UK called
Fiona Perry a few years ago andshe tested every single T cell
that patients and controlindividuals had within their gut
and the idea was that theyexpected to see that people who

(28:38):
had IBD would have this group ofimmune cells that were
recognizing a specific thingright, so that they'd had one
particular infection that allthe IBD patients had all been
exposed to, and it was whattriggered their disease and
that's what made them differentfrom regular people.
And it turned out that that'snot true at all, that the things
that an IBD patient's immunesystem sees are exactly the same
things as someone who doesn'thave IBD they see exactly the

(29:01):
same things, their T-cells areidentical and the only
difference is how they respond,where they could respond and say
I see this, it's fine, I'm notgoing to freak out, it's not
like a peanut allergy that Ineed to lose my mind over it.
Instead, ibd patientsautomatically see something and
think oh my God, this isterrible, it shouldn't be here.
I've got to trigger this hugeinflammatory response and I've
got to clear out this issomething that's totally safe

(29:22):
and normal.
But yeah, so driving cells intothe gut alone is not enough.
To trigger intestinal diseaseis the long-winded way of saying
that.

Speaker 1 (29:29):
Thank you.
I appreciate the long-windedexplanation.
Right, thank you, I appreciatethe long-winded explanation.
I definitely have questionsabout the butt-chugging alcohol
comment.
We're going to come back tothat, I think.
Yes, we're going to come backto that one.
When you've been doing thisresearch, have there been any
differences in how it's consumedSmoking versus edibles, versus?
Is there a difference?
Because obviously we know thatcigarette smoking is not good

(29:50):
for people with Crohn's disease,but yet some people with
ulcerative colitis it can besomewhat helpful for them.
So how does that work?

Speaker 3 (29:57):
Yeah, so it's a really tough one, right?
So first and foremost, we'lltalk about the cigarette smoking
issue.
So this was done withadolescents or kids in
children's hospital and so wevery much discouraged them to
smoke.
But that said, there are yeah,so there's huge difference.
So we were struggling in thatwe couldn't power studies big
enough to look at the differencespecifically between, let's say
, oil and edibles and vaping,which would be the three options

(30:20):
I think that we would probablyreach for.
I do have a fun anecdotal storyabout a patient who was vaping
marijuana.
Although it turns out so, it'snot advisable, it turns out
again, not having known this,it's not advisable, if you're
immunosuppressed, to vape yourhomegrown marijuana, which is a
very specific problem to have.
So the reason I say this isbecause we had a patient who was

(30:42):
vaping his marijuana andobviously vaping doesn't heat up
marijuana as high as, say,smoking would, right, so you're
not burning anything, so you'reheating it to a much lower
temperature and actually thetemperature that you heat it at
changes the phytocannabinoids orthe chemicals that come out of
the cannabis, and so some ofthose are anti-inflammatory and
some of those are probablypro-inflammatory and some of
those are kind of inhibitory andsome of those are stimulatory.
So it gets really tricky.

(31:03):
Like there's 106, I thinkdifferent active ingredients in
a regular cannabis plant, whichis another reason why medicinal
marijuana is a bit of anightmare, right, because it's
not really practical.
It's not just that, say, someof the components are pushing
one way and some of them arepushing the other way.
There's what we call allostericmodulators, so there's drugs

(31:23):
within the cannabis plant thatdon't even target the receptor
that triggers cannabis responses, but it binds somewhere else
and it changes the kind ofstructure of the cannabis
receptor.
And now more else, and itchanges the kind of structure of
the cannabis receptor and now,all of a sudden, drugs bind
better or they bind less, moreweakly, like it's.
It's way too complicated tofind any real therapeutic
benefit from a plant like that.
When there's you know, there's106 different things pushing in

(31:45):
different directions, it's veryhard to find which one is being
beneficial, which one's not.
But yeah, so he wasimmunosuppressed, which is fair
enough, right?
If you had a, you had a recentflare, you're automatically put
on steroids and they always saywith your steroids or with your
anti-TNFs or whichevermedication you're on, you're at
risk of infection because we'redeliberately suppressing your
immune response.
And so in an average healthyindividual, if they were exposed

(32:08):
to aspergillus or anaspergillus fungal infection and
they'd be able to fight it offright, your immune system can
just deal with it, kill it,problem solved.
But because this individual wasimmunosuppressed and vaping and
also growing his own marijuanabecause obviously, at least in
the state of colorado, if youbuy marijuana it'll be screened
for aspergillus and you won'tget fungally infected marijuana

(32:28):
on sale as a kind of a theyrecognize it's bad for business.
So so this individual, becausehe was growing his own, managed
to get a fungal infection in hismarijuana and so the
combination of vaping andimmunosuppression and fungal
infection ended up he had to goto hospital because he couldn't
breathe because he had this hugepedunculated is the word they
use pedunculated growth in histhroat which was basically at
the point it was almost cuttingoff his airways.

(32:50):
So the answer is don't do that.
But after that then, in terms ofvaping, is probably better than
edibles, just because ediblesare very difficult to track
right.
So different people respondvery differently and at very
different rates, whether it's,you know, some people are very
high metabolizers of it andit'll clear their system quite
quickly.
Other people, they might takeeight or six, you know, six or
eight hours before they'll evenfeel any kind of response to

(33:11):
cannabis edibles.
And it depends on what you'veeaten, it depends on what's in
your stomach.
So, in terms of dosingdeliberately or consistently,
it's definitely not a good wayto go, whereas vaping at least,
you know pretty quickly how muchyou're getting.
People tend to be good aboutstopping at a reasonable cutoff
point.
There was a study by KenHutchison and Cinnamon Bidwell,
two scientists working in CUBoulder.

(33:33):
They were amazing, right, sothere was loads of regulations
about bringing cannabis oncampus right, because we're
talking federally fundeduniversity campuses who were
like, yeah, we don't want to beanywhere near this.
Like, federal dollars andcannabis do not mix.
So these guys came up with thisincredible solution of they
developed a bus, right, so thebus would drive to your house.
You smoke whatever you want tosmoke, get in the bus, they do

(33:55):
blood samples, they dopsychological testing, you name
it and they could have you jumpin and out of the bus four or
five times over the course ofwhatever you were doing.
And it was amazing because itmeant they generated a whole
load of data and actually forcannabis research.
That's a major problem, right.
Access to patient informationis a huge problem when it's a
federal crime, most of you knowin most parts of the.
But what they were to show wasthat we were really concerned,

(34:15):
right, because people were usingthings like wax and shatter and
what we call very highconcentration THC type products.
But it turns out that peopleonly there's only a certain
amount that they want, anybodywants, and then they just shut
off and they ended up reaching,even though they'd get there a
lot quicker because they'reusing a much more high potency
cannabis.
They'd still reach the samelevels overall, but I digress.

Speaker 1 (34:37):
Listen, I'm a social worker, so I'm going to preface
my question because I wouldimagine working within a
children's hospital system.
You learn that a child is usinga drug that is legal in the
state but not federally legal.
What are the reportingrequirements of that?
And like and truly that means,like when you're designing
research using cannabis, likeyou can't necessarily recruit

(34:57):
children right, like how doesthat work?

Speaker 3 (34:59):
You, can you just wait outside the school?
No, I'm just kidding, youdefinitely don't do it.

Speaker 1 (35:04):
Take this lollipop, kiddo, come join me.

Speaker 3 (35:09):
No, so, right, well, yeah, so when we started, so
actually, it gets worse, right.
So the money we were investingin our research in cannabis was
actually state-sponsored funding.
So when Colorado brought in thelegalization of marijuana, they
said, right, we'll cap the taxrevenue that we earn.
And they really underestimatedwhat the tax revenue was going

(35:29):
to be.
Right, they didn't realize justhow popular it would be.
So they ended up generating somuch extra revenue and they
realized they couldn't keep it.
They'd already agreed inadvance that they wouldn't keep
the excess.
So they asked people okay, well, what do we spend the money on?
And the consensus was, well, wewant more research, right, we
want to understand what thecannabis does.
And so I was lucky to be partof a clinical trial that was
based off that kind of state taxwindfall.

(35:51):
But it was a major issue inadvance, like we talked about.
Like, one of the studies thatwas proposed was to look at
transfer of cannabinoids fromthe mother to the fetus in utero
right, and, yeah, you know,hugely important.
But you now put that mother ona list of federal criminals who
are subjecting an unborn childto cannabis, right?

(36:11):
So that's not okay, and so thatwas definitely panned.
We were lucky in that we wereable to get a dispensation.
We certainly weren't advocatingfor cannabis use, but equally
we weren't trusting people totell us if they were or were not
using cannabis.
So we tested them.
We tested serums or theirbloodstream and we looked for
there's a number of cannabinoidsthat can last quite a long time
within your body, within yourblood, so we could test those.

(36:34):
We confirmed that anybody whosaid they were using cannabis
was actually using cannabisfairly regularly and likewise we
didn't have any cases of peoplewho denied using it but
actually were.
So that was fortuitous.
But yeah, we had to get aspecial dispensation to say,
right, we're putting together alist of federal criminals, is
that okay?
And in all cases, the parentswere also actually part of the
medicaid, part of the I don'twant to say treatment decision,
but they're part of the process,right?

(36:55):
So the parents were all awareand they were providing the
cannabis for their children, sothey were fully aware of what
was going on.

Speaker 2 (37:00):
So there was nothing shady about it everybody who
listens knows I'm from louisianaand I know at one point,
working with the family, likethey had considered like just
moving their whole life tocolorado after it became legal
because their child was so sick.
They were like at wit's end.
They did not know what to doand so they were willing to do
anything, and moving to Coloradoso that their child would have
access to this was one of thethings that they had discussed.

(37:23):
So I feel like you know youcan't make these parents
villains, because they reallyjust want to be better.

Speaker 3 (37:29):
Yeah, if you do anything if you think about even
the, even the best treatmentsonly work in kind of 20 to 40
percent of patients.
So you're kind of rolling adice already.
And if they do work, some ofthem take, you know, three or
four months to get work to startworking effectively and
consistently right.
So you know, in the meantime,absolutely right, a patient
parents are.
You know, we, we spend ourwhole lives trying to protect

(37:50):
our kids and trying to make surethey're never in pain or never
discomfort, or never unhappy or,you know, never wanting for
anything, and so, yes, you cantotally see why that would be a
port of call and there's noquestion that it makes people
feel better.
The concern is that in reality,it's making your disease worse
and so when it comes aroundagain, you're going to flare
much worse and you're going tohave a much more severe disease.

(38:10):
But, yeah, no, it's a tough calland, like I will say so, we had
another study running in thehospital that was looking at
seizures and this was a hugecomponent of it.
Right, people moving toColorado so that they could be
part of the study, andunfortunately, what they found
actually is that moving toColorado had a much bigger
impact on seizure frequencyreporting than the actual

(38:30):
cannabis did.
Because if you change yourwhole life and you uproot
everything and you move to adifferent state, then yeah,
that's going to be a you'regoing to want to see and you're
going to have confirmation biasin that scenario.
So you want to see, you want tosee it being worthwhile, but I
mean, there's always kratom.
You know I'm joking, don't everdo that.

Speaker 1 (38:47):
Well, I guess what I was curious, like, if part of it
is just moving, is it?
You know, like, how do you takeout some of the factors of like
, does altitude or the you knowthe lack of oxygen?
You know it's like, how doesthat play into this?
Like, how do you sort ofcontrol the variables if, yeah,
that is part of it where you getsomebody who's entirely
uprooted their life andcompletely changed?

Speaker 3 (39:06):
And there's no doubt so like there's a.
There's a scientist in Coloradocalled Sean Colgan, and Sean is
just like.
He has built a career lookingat hypoxia and how hypoxia
regulates intestinalinflammation, and there's no
question that it's reallyimportant.
And so if you live somewherehigh altitude, then obviously
you know that increasesexpression of those proteins, it

(39:26):
changes your bloodstream, itchanges a lot of your physiology
, and so there's no doubt thatit affects your disease, not to
mention you're also movingsomewhere that's incredibly high
, also incredibly dry, right.
So National Jewish Hospital inColorado, in Denver, was a
respiratory center, and thereason they were so successful
is partly because people moveinto Colorado to seek medical
treatment for respiratorydiseases.

(39:46):
We're also getting 10% humidityat most, and that completely
changes what you're breathingLike.
You come live in Dublin whereit's 90% humidity on a good day
and that's barely getting above10 degrees Celsius or 40
something Fahrenheit.
You know we're breathing inmoisture all the time.
That's probably full of Godknows what else, whereas in
Colorado there wasn't any ofthat.

(40:07):
He says.

Speaker 2 (40:09):
I can relate to that being from Louisiana also.

Speaker 1 (40:12):
Well, yeah.
And Houston, right, he says Ican relate to that, being from
louisiana also.
Well, yeah, in houston, rightsame thing.
It's like the inside of anarmpit.
It's awful right.
Sorry, houston, love you.
But I'm curious, like, doesthat level off over time?
Like does staying in one placelike so?
Yeah, sure, when you first movethere it's like this big,
drastic change.
Does that then increase overtime, because your body gets
used to it, like that's?
I just like what's the?

Speaker 3 (40:30):
no, you mean you stay , you stay.
Uh, evolved to live in thataltitude, like so much so that
I'd fly down to sea level andI'd be like running around going
crazy.
I used to have a sister who'sshe's nearly six foot tall.
We go for walks every now andagain.
Uh, when I came home I shouldbe like, yeah, let's go for a
walk, and like I'm five foot six, so every step I take sorry,
every step she takes, I takingtwo steps.
But I remember when I movedback from Denver, walking along

(40:53):
which I was chatting, and sheeventually was like, can you
just stop talking?
But I was like, well, yeah, I'mnot used to this low altitude.
It's amazing.
Babies born in Colorado have amuch longer umbilical cord
because they need.
There's just not enough oxygengoing around, so they need extra
oxygenation just to survive.
There you are now.
Useful fact.

Speaker 1 (41:12):
I mean I'm going to definitely pull this out at a
party someday.

Speaker 3 (41:21):
Right, when I moved out there I joined a group of
people who we were called theMucosal Inflammation Program, or
MIP, but everybody used torefer to us as mostly Irish
people, because there was like11 Irish postdocs working
together.
And so my very first day I wastold we were on the 10th floor,
this high rise, and I was toldhey, colin, we've got a meeting
upstairs, we've got to go withit, we've got to go, we've got
to hurry, we're already late,we've got to go.
So I was like, oh shit, byfirst day this is not a good

(41:45):
start.
So I went tumbling up thestairs behind, opened the door
to find a circle of mycolleagues standing there in
hysterics.
Because when I got to the top Irealized not only was I out of
breath but I wasn't getting anyoxygen to recover.
So I thought I was dying, likeI could not breathe.
I couldn't.
The more I breathed, you know,the worse I was doing.
I was absolutely horrified andthey thought this was hilarious.

(42:08):
Apparently, this is like riteof passage for Irish people
moving to Colorado.
That hilarious.
Apparently, this is like rightof passage for irish people
moving to colorado.
They are, they were horriblepeople horrible people listen.

Speaker 1 (42:16):
If you're listening to the show, you know who you
are.
Has there been any researchabout how the microbiome may
change with butt chuggingalcohol?

Speaker 3 (42:23):
uh, so why?
I should preface this by sayingthe reason I brought up that is
because, yes and no, we do itall the time.
I, honestly, we do it all thetime in mice.
I should start with that.
I should really have startedwith that.
So, in mice, if you give theman enema of, so actually, no,
I'll be a bit more scientificabout it.
So we were interested in humandisease.

(42:43):
We don't really care aboutcuring mice, we're really good
at that.
We do it all the time.
We wanted to be able to curehuman disease, but there's rules
about right, there's a bunch ofdrugs you can't just give to
humans, right, it's not safe.
So our compromise was okay,we'll take mice, we'll give them
a human immune system and thenwe'll test our treatments on
those, because we're sort oftesting human immune responses,

(43:04):
albeit still in a mouse, right,and so that's actually pretty
straightforward.
So you take patient blood fromIBD patients, you spin out the
immune cells that you want, youinject them into a genetically
modified mouse strain that cantolerate a foreign immune system
.
You basically wipe out theirown immune system, but it takes
three or four weeks, right, andthen they establish this immune
system.
That's all human and, evenbetter than that, it's

(43:26):
individual to the patient.
You got it from right.
So your patient, mary, whatever, this is Mary's immune system,
but now it's in six differentmice.
So we can tell Mary, this drugworks in your immune system.
But the last part of theprocess is you need to actually
trigger intestinal inflammationin those mice, and the way we do
that is with erectile enema ofethanol or alcohol.
And so what alcohol does is itjust breaks up the barrier

(43:48):
between intestinal epithelialcells.
It just kind of separates thatbarrier out and it allows the
bacteria to get across the gutand into the underlying tissue
and that triggers immuneactivation and it triggers
intestinal inflammation.
And now, all of a sudden, youknow my friend Mary, I can test
all the treatments that arecurrently available to Mary and
I can say Mary, at least in mice, this drug worked best for your

(44:09):
immune system.
And the hope is that at somepoint we'll be able to transfer
that into standard clinicalpractice, right, the idea being
that we could tell everybody inadvance this is the drug that's
going to work best for you,because right now the way it
works is patients get out, youknow, put on Remicade.
All right, we'll try that forthree months.
If it doesn't work, we'll stickyou on Vedalizumab.
If that doesn't work, we'llwait another three months, we'll
stick you on something else.

(44:30):
If that doesn't work, we'regone.
And the problem is the longeryou leave it, the worse the
disease gets, the moreuncomfortable it is for patients
, but also the more difficult itbecomes to treat.
Patients become recalcitrant orresistant to treatment because
they've failed on multipledifferent treatments.
So the idea is that if we canidentify what works best right
off the bat or before, ideally,you get treatment, then we can

(44:52):
streamline that whole processand we can get you on the right
treatment right away.
But that's somewhere in thefuture, I think.
Hopefully.

Speaker 1 (44:58):
Hopefully not too far in the future, though that
gives me a little bit of hope.
Do you have to give the micecolonoscopies?

Speaker 3 (45:05):
We can do.
It's actually really tricky.
It's tricky.
So I worked with a cliniciancalled Ed DeZotenoten who was an
expert in doing colonoscopieson children, which are like
really big mice, so he wasbrilliant at showing us how to
do the colonoscopy part of it.
But it turns out children andmice are not the same, because
children they toot, whereas micedon't.
So if you fill a child full ofair, then you can ask them to

(45:27):
just blow it back out again, andthey might even find that quite
funny.
But if you ask a mouse to do it, it can't, and so there's
always a risk that you'llover-inflate the mouse and
you'll be left with aballoon-shaped mouse.
So for that reason we don't doit.
It's also not super helpful,right?
So at the end of our studies wetend to have to euthanize the
mice anyway, because they'retreatment and we really want to

(45:51):
know if it works.
So what we end up doing iseuthanizing the animals and then
removing their gut, theirintestinal tissue, and looking
at that without having to do thewhole colonoscopy part.
But yeah, they don't like beingover-inflated.

Speaker 1 (46:02):
No, I assume that was probably the case, but also I
just was thinking of like aBarbie colonoscopy scope.
To like go in the tiny mouth.

Speaker 3 (46:13):
We've got one, and so actually my wife my wife's an
ibd researcher as well and soshe's more interested in the
intestinal epithelium, like howthat barrier works and how it
breaks down and how it recoversand how it heals, and so what
they were looking at when theywere using those scope for was
to to generate a little injury,so to generate like a small
pinch, pinch the biopsy out andthat leaves a little hole behind
, and it means that then you cango back in a week later and see

(46:33):
where the hole is and see howmuch it's healed and actually
they're doing that in patientsas well, and they can even
tattoo around the hole, so youknow exactly where the hole was,
and so you can be able to goback in and be like, oh yeah,
that's where the damage was andnow it's all better.

Speaker 1 (46:53):
When you're doing something like a lab tour and or
patient education, because youare literally like bench
research mice not necessarily ascientist, that who also treats
patients.
Tell me how, taking what you doand sort of breaking it down in
a way that makes sense for forthe lay people of the world, how
like, how easy is that whenyou're sitting and doing like
educational pieces?

Speaker 3 (47:06):
Yeah, it's really tough.
And actually now, now that Irun a lab and I have students
working with me, it's one of thethings I kind of teach them
early on is to have it.
You know, there's no point indoing research if nobody hears
about it, and there's no pointin trying to help patients if
they don't know you're doing itlike if they don't get the
benefit.
Right.
And so we do a lot of work onhow to get rid of jargon out of
what we're saying and how tosimplify communications, but at

(47:28):
the same time, you know, if youreally want to understand what
you're doing, the best way to dothat is to not rely on
scientific terminology, to breakit down into its simplest form
and say, right, it's doing thisor it's doing that.
Scientists are constantlyworking towards improving our
communication skills because,you know, we recognize that it's
becoming an increasinglyimportant part of our job.

(47:49):
Right, there's no point indoing research if you can't
share it with people.
If I can find something thatyou need to know and I don't
share it with you, then I mightas well not have found it in the
first place.
But when it comes to lab tours,it's actually it's really
refreshingly simple.
So we bring people in and weshow them.
Here's our microscope here.
These are tissue slides.
We've got a tissue on therethat looks like it's from a gut.

(48:10):
It is, but it's not a human gut, it's a mouse gut, but it looks
, you know, very similar, likeso much so that we work.
We work with pathologists whospends most of his time looking
at humans and when he looks atmouse stuff he's like, yeah,
it's the same, like it's similar, sort of sort of appearance.
But it's funny.
Like things like a centrifuge.
Right, we would use centrifuge40, 50 times a day and we don't
even think about it.

(48:30):
And we've got people come inthe lab and they're watching us
doing stuff, doing, you know,setting stuff up, and they see
us drop something in thecentrifuge, stick it on, walk
away, come back and we'veseparated out blood from serum
or we've, you know, somethinglike that.
And they're like, oh, my God,that's amazing.
And you're like, wait what?
It's a centrifuge.

(48:55):
You know we use liquid nitrogena lot.
And again they're like, oh, wow, that's so cool.
And you're like, wow, you know,the stuff that we take for
granted all the time, was thisstuff that the patient's already
interested in?
And really they don't.
They've never been overly likeoh, why are you doing your
experiment this way?
Or why are you doing thisBecause they recognize that
that's not their expertise.
So really what they want to knowis are you excited about it?
And when they see how excited Iget and they see how excited my
students get, that's enough forthem.
They're like okay, you know youreally care about our disease
and you know you don't have to,but you do and that's that's

(49:17):
kind of a win-win.
And then for us, obviously inthe back of our mind, we're
always thinking like I amfailing you all of the time,
like every time I put my iPad inthe wrong place, or every time
I press too hard on somethingand it breaks, or like you name
it, the stuff I do wrong is just, the list is endless.
But every time I do that I'mlike you know, that was an
option for me to be helpful andI've failed, and it's hard not

(49:40):
to forget that.
But then you meet these people.
They're like, yeah, we don'tneed your help, like we're doing
really well.
I mean they're as a patientgroup.
Ibd patients are incrediblyresilient and, you know,
positive, overwhelminglypositive.
You know I remember a patientsaying to me one day.
She was like oh yeah, you knowI've failed Remicade, I've
failed Adalimumab, I've failedsomething.
You know listing off all thedrugs that haven't worked.

(50:00):
And I've had you know thisnumber of centimeters in my
intestine removed and you knowhow are you doing and it was
like you know it.
Just they just take a kick andkeep on ticking, like they just
do not stop, like these peopledon't need your sympathy, they
just need you to be working hardand you know that's they're
happy enough and that worked,like for us.
That was really tremendouslyreinforcing to know that you

(50:23):
know at least we care and we'redoing the right thing and that's
all you can hope for.

Speaker 1 (50:26):
In looking at your research or research or the
other people like that, are kindof working in the field with
you.

Speaker 3 (50:38):
Is there anything that seems really exciting,
really like hopeful, at themoment?
It is tough.
For a good period recently it'sbeen the opposite.
So we've gone from a stagewhere you know there were new
drugs coming on the market allthe time, right so 10 years ago,
when we had like Eustekinumaband all these other new drugs
that were coming out in rapidsuccession and basically every
clinical trial or a whole loadof clinical trials.
We're looking at all these newmedications and that was really
really exciting time.
And I think with the advent ofbiosimilars, that's really

(50:58):
killed off a lot of thatinvestment in new therapies for
IBD, because so much of theclinical trial work is had to
focus on.
You know, is this biosimilarthe same as the other one?
Is it an equally effective?
Is it doing this, that and theother?
And I think that's reallysucked up a huge amount of
resources in terms of patientswho are enrolled and in terms of
investment that was availableinto a field that doesn't offer

(51:20):
a huge benefit.
So, yeah, it's hard not to benegative about that.
Is their future going to bebrighter?
Yeah, I think this, you know,if you look at the cancer field
and the developments they'vemade with CAR T-cells, where
they basically take your T-cells, re-educate them and modify
them and re-inject them.
I think that's probably wherewe're going to see IBD therapies
go in the future.
I think the technology to dothat is very much available.

(51:41):
So I think that's not far away.
Right, that's going to comequick enough.
But, yeah, no-transcript able toget to that point and it's

(52:21):
probably more of an insuranceproblem than the biology and the
science tells us that it'sbetter to use multiple different
treatment options.
And that's one of the thingswhere right now, there's a huge
hope.
Right, we've got anti-TNF drugs, we've got integrin blocking
drugs, we've got IL-12, il-23blocking drugs, we've got S1P

(52:42):
inhibitors, we've got JAKinhibitors.
We've got way more differenttypes of medications than we've
ever had, but we're not doingenough to combine them together
and seeing if we give you a drugthat has all of those things
combined, would that beeffective on everybody and
wouldn't that be worth having,because insurance companies
won't pay for that.
So even if it's lowerconcentrations of all the drugs
and it's less side effects,there's a bunch of upsides.

Speaker 2 (53:01):
Colm, it has been so entertaining to talk to you and
informational, but we've beentalking for a long time and it's
time for us to ask the lastquestion.
So what is the one thing youwant the IBD community to know?

Speaker 3 (53:11):
The one thing I think is please, even though cannabis
might make you feel better, beaware that it's making your
disease worse and don't do it.
And I appreciate that's comingfrom a place where I don't
suffer from a chronic diseaseand so I do have the luxury of
saying you know, even that'ssomething that makes you feel
better, you shouldn't be doingit, but really it will make your
disease worse.
We have a lot of evidence thatsays that it is going to make

(53:33):
your disease worse, so pleasedon't do it.
And if you don't have IBD,don't do it till you're over 25.

Speaker 2 (53:38):
I will add for the cannabis part don't do it.
But if you're going to do it,make sure that you talk to your
doctor about it or at least letthem everything that you're
taking, drinking, eating,whatever because it's going to

(54:02):
affect your disease course.
So if you're going to do it,make sure that your doctor knows
you're doing it For sure.

Speaker 1 (54:04):
Collin, thank you so much for being on the show.
This was, like Robin said, somuch fun to talk to you and this
is also where sometimes I wishlike we weren't on mute and we
use the video because we werelaughing a lot and you can't
actually hear it.
So for those of you who thinkwe don't have a sense of humor,
I promise we were laughing, justwe were muted.
So thank you so much for comingon the show and spending your
Friday night with us.
We really appreciate that.

(54:25):
And thank you so much toeverybody else for listening and
cheers guys, Cheers everybody.

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