Latest / Voices of Otolaryngology / A Spice, a Patent, and a Purpose: One Surgeon's Path to Cancer Prevention

Transcript

A Spice, a Patent, and a Purpose: One Surgeon's Path to Cancer Prevention · Voices of Otolaryngology

0:01
Welcome to the Voices of Otolaryngology podcast series, where we spotlight
0:05
diverse perspectives and insights within the field of otolaryngology.
0:08
I'm your host, Rahul Shah.
0:10
Let's jump into it.
0:12
Welcome to the Voices of Otolaryngology.
0:15
Boy, am I excited.
0:16
I have Cherie-Ann Nathan, who I got to work with on the Executive Committee
0:21
of the Academy and also on our board.
0:23
Cherie-Ann, welcome.
0:26
Thank you for having me, Rahul.
0:28
I love that you're in the scrubs.
0:30
So you must have been in the O.R.
0:32
procedure office today.
0:34
Where are you?
0:34
You're not in your business suit.
0:36
So you're out there working today?
0:39
I'm. Yeah, I'm in my office right now, but I love that
0:44
I have the WIO scrub cap on
0:47
in honor of WIO.
0:49
That's right. Women in Otolaryngology.
0:51
This month of March, we're highlighting some of the leaders
0:54
and Doctor Nathan,you're a founder of WIO, is that right? Yes.
0:58
Very fortunately, I can count myself in the, as a founder.
1:02
And I'm amazed at how this organization has grown.
1:06
Yeah, so, so am I.
1:08
Do you remember what year the founding year was?
1:12
Oh. I think like 15, 16 years ago.
1:16
So 2010, 2009?
1:18
Around that time. Yeah.
1:21
What has impressed
1:23
you most during that time about WIO,
1:27
and the women in otolaryngology, the impact you all have made.
1:30
Has this met your expectations?
1:32
Exceeded your expectations?
1:35
You know, I think it's exceeded my expectations.
1:38
Because every year at our annual meeting when we have our get together,
1:43
I'm always amazed to see we need a larger and larger room,
1:49
to host our event because it's gaining so much momentum.
1:53
I love, the various, you know, activities of WIO,
1:59
and how would they have helped through their grants.
2:03
And just the networking opportunities and, really,
2:07
all the leaders, in WIO have done an amazing job.
2:11
You know, I forgot.
2:12
Shame on me.
2:13
I know you extremely well as a reader of your articles,
2:17
as a fan of yours, and then working with you on the board.
2:21
But I forgot to let you introduce yourself, Doctor Nathan.
2:24
How about you introduce yourself?
2:25
Let everybody know where you're broadcasting from
2:27
and the various roles you hold.
2:28
Please, Doctor Nathan...
2:30
Thank you.
2:31
So, Cherie-Ann Nathan, and I am currently, chair,
2:37
professor and chair at LSU Health
2:39
Sciences Center in Shreveport, Louisiana.
2:43
And I also serve as Director of the Head Neck Cancer Program.
2:50
And, yeah,
2:53
mostly do head and neck surgery.
2:56
are known as one of the most prominent research surgeon/scientists in our field.
3:02
When did you start your research?
3:04
Go, go way back now.
3:05
When did you start it?
3:06
As a junior faculty member?
3:08
Fellowship residency? When did you start it?
3:11
No. I actually started my research career in 1988.
3:15
When I came on a scholarship from India to Johns Hopkins.
3:20
I was frustrated with our recurrence rates of head and neck cancer in India,
3:24
and came to Hopkins to see how it was treated and work in a research lab.
3:30
And realized it was the nature of the disease
3:33
and the recurrence rates were just as high here.
3:35
And what was it back then?
3:37
What was the recurrence rate that frustrated you?
3:40
Ballpark.
3:42
You know, for
3:42
locally advanced stage disease it's almost 50 to 60%.
3:46
And now of course back then we didn't have the HPV positive.
3:50
And HPV negative.
3:51
But for HPV negative it's still around greater than 50%.
3:56
So let's go back 1988.
3:59
You're a surgeon scientist
4:01
from India and said, you know the recurrence rate is too high 50-60%.
4:05
We can do better.
4:07
So you went to Hopkins and you found the same problem.
4:11
And then let me use my own word.
4:13
You had the arrogance to think
4:16
research would solve it.
4:18
I mean, you took on a huge problem, right?
4:20
I mean, that's amazing.
4:23
Yeah.
4:23
I mean, you know, I realized,
4:26
the only way one could make progress or help for
4:29
patients is really research and I saw what the Hopkins
4:33
faculty did back then and how they were so persistent,
4:38
with what they did and how research really was very slow process.
4:43
Moving something from bench to bedside could take years and years.
4:47
And sometimes, I mean, you never made it right
4:51
and made a change in your patients lives.
4:54
But I think I've been fortunate.
4:56
I haven't given up on that.
4:59
Passions and persistence of mine.
5:01
And, I know we're here to talk about curcumin gum,
5:05
but I do have, another project that has worked really well.
5:10
Inhibiting the mTOR pathway.
5:15
And our phase two clinical trial.
5:17
That looks very promising.
5:19
So, you put that as a placeholder.
5:20
You're going to talk about both of those in just a second.
5:23
But I want to go back to 1988.
5:25
So here you come as this surgeon and saying,
5:29
well, what were you saying to yourself?
5:30
I'm going to bring down the recurrence rate.
5:33
I'm going to solve the world.
5:34
Or was it I'm going to ask a hypothesis and try to get a grant funding?
5:39
I'm just trying to get into your mind 30, 40 years ago.
5:42
Were you looking at incrementalism
5:43
or were you looking at a huge transformational change?
5:47
What were you thinking back then in the late 80s, early 90s?
5:51
Yeah, no.
5:52
You know, at that point, really, Rahul, when I first came to Hopkins,
5:56
it was just to see how head and neck cancer was treated and do some research.
6:00
And I was going back to India where they were holding my residency position.
6:05
I only completed six months of residency.
6:08
I didn't even dream of getting a residency in the US
6:12
because I was a foreign medical graduate.
6:14
So I had no real plans
6:18
except like maybe try for a residency and see what happens.
6:21
And I was encouraged by the Hopkins faculty.
6:25
But then once I made it into a residency program,
6:28
and especially once I started as faculty, I realized this is my passion.
6:34
This is what kept me here to do research.
6:37
I never expected that I would my research
6:40
would ever moves to the bedside, but I knew I was going to try.
6:45
And I knew it was going to be incremental and may not even happen, but
6:50
I was going to keep working on projects till I knew I could answer my question.
6:55
And where did you do your residency?
6:58
At UCSD.
7:00
UC San Diego.
7:02
And then from there, where did you go?
7:04
And from then from there, I moved to LSU, Shreveport, and I moved here,
7:10
you know, just for one year to convert my J-1 Visa
7:14
to my green card and was plans were to move back to San Diego.
7:18
So interestingly, I didn't even negotiate
7:21
for lab space or a package because I came here
7:26
planning on one year, get my green card and then look for my real job.
7:29
And here I am 30 years later.
7:32
Yeah, your real job was right there.
7:34
When you were going through, did you do fellowships or that was not compulsory?
7:39
I did do a fellowship in Head and Neck at UCSD,
7:43
I stayed on for a year and did a Head and Neck fellowship.
7:47
So a junior faculty member at LSU,
7:50
which was your temporary but then permanent home.
7:53
What was your early hypothesis?
7:55
Do you remember your first couple of grants?
7:58
What were you trying to look at?
7:59
Yeah, so, you know,
8:02
I started talking to molecular biologists at LSU
8:07
and explained the problem that we have this high recurrence rates
8:10
and our recurrences are really at the surgical margins.
8:13
A lot of them are local recurrences, right?
8:16
Oral/tongue cancer.
8:17
And we spend these hours and hours in surgery,
8:21
with neck dissections and then microvascular reconstruction.
8:24
And it's very frustrating
8:26
that our local recurrence occurs within the first two years.
8:29
And so my hypothesis was at the molecular level.
8:34
We were leaving cells behind in these surgical margins
8:37
that were not identified histologically or were destined to,
8:43
undergo malignant transformation to invasive cancer.
8:48
And at that time, Wayne Koch’s group from
8:51
Hopkins had looked at p53 mutations in the surgical margins and found
8:56
when p53 was mutated in these tumor free surgical margins,
9:01
those patients recurred.
9:04
So I didn't want to be one more studying p53 or Cimic.
9:08
And I ran across this molecular biologist, Doctor
9:11
De Benedetti, who overexpressed eIF-4E,
9:16
a translation factor in normal cells and it became cancer.
9:20
And so I said “can you look at my tumors
9:23
and tumor free surgical margins, for 4E?”
9:28
Because maybe it will be overexpressed and we can see what happens.
9:32
And I have I know my answers
9:35
should be short, but, I want to tell you this story
9:39
about my very first patient at the VA, who had larynx cancer.
9:44
And I sent this lab, my tumor and surgical margin, and he looked at 4E
9:51
and found that 4E was overexpressed in the surgical margin.
9:55
And I thought maybe he contaminated the samples.
9:59
But two months later, this patient recurred at that surgical margin,
10:03
and I was like, wow, maybe this is not a coincidence,
10:07
and then started to give him more of my tumors and a tumor free margins.
10:11
And that's how this hypothesis evolved.
10:15
And this was basic science.
10:18
You were taking,
10:20
surgical.
10:22
Yeah. You were taking from patients. And he was looking at it. Right?
10:25
It wasn't a model.
10:26
It was an ex vivo.
10:27
It was, it was from patients?
10:29
It was from patients.
10:30
And he was looking at their tumor samples
10:35
using Western blots.
10:37
And then you became grant funded at a quite significant level.
10:40
What were those grants looking at?
10:44
I do want to give a shout out.
10:45
My very first grant was a co-grant from the Academy.
10:49
And, since I said I hadn't, you know, got any funding from my institution
10:54
when I first started.
10:55
And so, my very first grant
10:59
after the Academy’s grant was I got some preliminary
11:03
data was an R 21, NCI grant,
11:08
and basically that was to study tumor and surgical margins and look at
11:13
what would the downstream effects of this AKT/mTOR pathway, when,
11:18
it was overexpressed in surgical margins
11:21
because angiogenesis plays a
11:24
very important part in tumor progression.
11:28
And downstream of this pathway was VEGF and FGF.
11:32
Both important angiogenic factors.
11:34
So we studied those in the margins as well.
11:38
And that was the very first NIH grant.
11:41
What year was this? Ballpark.
11:42
That was, I think in 2004.
11:48
So you're rattling off - Sorry, it was 2000.
11:52
You're rattling off VEGF, etc..
11:54
And people now take it as mantra in the textbooks.
11:58
But back in the early 2000s, it wasn’t clear.
12:01
Works such as yours paved the way: Judah Folkman others right with angiogenesis.
12:07
So what you're doing was off the beaten path.
12:11
I owe
12:12
a lot for Judah Folkman, of course, who was the one who, you know,
12:17
came off with the VEGF story and angiogenesis.
12:21
But I clearly,
12:23
use that, you know,
12:25
in my hypothesis and looked at the downstream of things.
12:29
Amazing.
12:29
So then how long did you continue that body of research inquiry
12:33
before you branched off into the two things that we wanted to talk about today?
12:37
When did you then pivot into that?
12:39
How long did you tell the VEGF story?
12:41
Through the NIH funding?
12:44
Yeah.
12:44
So, VEGF was just one of the factors downstream.
12:48
It was more the AKT/mTOR pathway.
12:51
I then started working with companies.
12:54
Wyeth and Novartis were making, mTOR inhibitors.
12:58
Did the first clinical trial,
13:01
with Temsirolimus from Wyeth,
13:05
looking at, you know, how these patients,
13:08
with head and neck squamous cell cancer where they could inhibit this pathway.
13:13
And then more recently, using the oral formulation
13:17
of Novartis’ drug, Everolimus, which is an mTOR inhibitor,
13:22
completed, multi-institutional clinical trial.
13:26
We have 13 institutions across the country.
13:29
And the results look really promising.
13:33
Patients were
13:34
given Everolimus or a placebo as adjuvant
13:38
after completing their definitive therapy and being free of disease.
13:43
And we found a significant difference in two year progression free survival
13:47
in patients, who had HPV negative tumors.
13:51
So we're very excited about that.
13:54
And that's one of the main projects I’ve worked on.
13:57
And that came from this 2004 early funding.
14:01
And now it's almost two decades later.
14:03
Is that right? That's the most contemporary work.
14:06
Yes, absolutely.
14:08
And where do you plan to take that now?
14:10
You've done 13, sites multicenter study.
14:13
What's the next step of that?
14:15
Is it really getting out to the general population?
14:18
Where do you all see that?
14:20
Yeah.
14:20
So that was a phase two trial.
14:23
And it included both HPV positive, HPV
14:26
negative, p53 “wild-type” unmutated patients.
14:30
It however progression
14:33
free survival was significant only for the HPV negative.
14:37
So now we are planning on a definitive
14:41
phase two trial just for the HPV negative patients.
14:46
And I'm going to keep them on Everolimus for two years
14:50
to look at whether we made a difference in progression free survival.
14:54
How does that drug work?
14:55
Is it IVs at oral?
14:57
How is it? it's given as an oral formulation.
14:59
And that was one of the big advantages over Wyeth’s stem Sirolimus,
15:03
because they had to come in every week for an IV formulation.
15:08
But most of our institutions, you know, our patients,
15:11
travel from so far being tertiary centers.
15:15
And so the oral formulation makes a big difference.
15:18
Is a daily, weekly, monthly?
15:21
It's daily, 5mg to 10mg.
15:24
Daily.
15:25
Yeah. I just want to educate my peers.
15:27
I'm not familiar with the drug, so it's always nice to educate our listeners.
15:31
What are some of the side effects to look out for if they have a patient
15:34
being treated for head and neck HPV negative using this?
15:40
Yeah.
15:40
So interestingly the side effects are minimal.
15:44
They can be one that one of our patients got hHyperbilirubinemia.
15:49
You can have thyroid effects.
15:51
You know, hypothyroid, hypothyroidism,
15:55
some skin reactions, but really not significant problems.
16:00
Mucositis, but much less than chemotherapy
16:04
and even less than the EGFR inhibitors.
16:08
I've never made such a discovery or contribution in anything in my life.
16:12
Tell me the truth.
16:13
Do you sit there
16:14
looking at the bottle and you're like, oh my God, this is the coolest thing ever?
16:18
Could you have thought 22 years ago that a hypothesis
16:22
would lead to somebody taking an oral pill that helps
16:25
their tumor free survival?
16:28
No. And I feel, you know, fortunate and still, till
16:32
the definitive trial is done, I,
16:35
but, you know, think it's too good to be true.
16:39
But if it does work, that would make my dream
16:43
come true, because that's what brought me from India to the US.
16:46
What does the preliminary data show?
16:49
I don't.
16:49
And, so what you've published is the 13 sites.
16:53
Yeah. That's what you published.
16:55
What does that show, briefly? Can you summarize that?
16:58
What is the, statistical significance?
17:00
What's the elevator pitch from that study?
17:03
Yeah.
17:03
So patients with p53 mutated tumors were HPV negative,
17:08
when they were randomized to placebo
17:11
versus Everolimus as adjuvant therapy.
17:15
There was a significant difference in two year progression free survival
17:20
for patients who got the Everolimus drug compared to placebo.
17:25
And what is that rate?
17:26
The, progression free survival.
17:29
What is that number?
17:30
So the significant difference was almost as low as, I think .03
17:35
That was the p value.
17:36
But what was it in terms of months or years?
17:39
In terms of patients got this drug only for one year after.
17:43
So the progression free survival was, you know, just a few months.
17:47
But it was significant because,
17:50
once we stopped the drug, then they started recurring.
17:54
And that's why in this next trial,
17:56
we're going to put them on Everolimus till they’ve progressed.
18:00
Or have, you know, significant side effects.
18:03
And really in breast and renal cell carcinoma,
18:07
patients have been on Everolimus for for many years.
18:11
And we know the drug Sirolimus,
18:14
which is rapamycin, is given in transplant patients.
18:17
And they stay on in it for years and years.
18:20
So our hope is as long as they don't develop resistance to the drug,
18:25
they can stay on this till they develop progression.
18:29
Very well said. So that's wonderful. What
18:33
people suggested I
18:34
speak to you about was curcumin, if I'm saying it correctly.
18:37
So how did you go from that to curcumin?
18:42
Are they two separate paths?
18:43
Actually there's quite a bit of overlap here because,
18:49
you know, there's two problems, right?
18:50
We have in our patients, the recurrence is either
18:55
because we're leaving cells behind that have already undergone dysplasia
19:00
or some pre-malignant change and is going to progress to cancer.
19:05
But also in our early stage patients
19:08
we follow them for life because of second primaries.
19:11
So the cigarette smoke has caused pre malignant changes in the entire mucosa.
19:17
And even though you've cured one cancer, you're getting
19:19
you could develop a second primary.
19:21
But having moved to Louisiana, also, Rahul,
19:25
people chew tobacco over here, and I saw a lot of Leukoplakia.
19:30
And Leukoplakia is extremely frustrating because often
19:35
it's like widespread and you can’t, you know, excise it or laser it.
19:39
And you know that, you know, many of these are going to progress to cancer.
19:45
Earlier in my career,
19:46
I was asked to participate in a COX-2 inhibitor
19:52
trial for patients with pre malignant disease Leukoplakia.
19:58
And that's when I started getting interested in, you know,
20:03
what do we do for patients with Leukoplakia?
20:06
Or have chewed tobacco
20:07
and are going to develop Leukoplakia, to prevent progression?
20:11
And I realized during that COX-2 trial,
20:16
that many drugs had worked - the retinoids had worked.
20:20
That was done by MD Anderson.
20:22
COX-2 to a degree work.
20:25
But the problem was patients when they came off these drugs,
20:30
the pre malignant lesions reappeared and then often progressed to cancer.
20:35
What year was this? What year was this?
20:38
I would say, golly, I think that trial was around 2008, maybe?
20:45
I could be - Perfect. Thank you very much.
20:47
Thank you. About 15 years ago.
20:48
Please go ahead. Yeah.
20:49
So, you know, that's when I started thinking
20:53
if there was a nutraceutical or a food substance
20:56
that they could stay on for forever, then maybe,
21:00
you know, that would be an interesting concept.
21:04
And having grown up in India, of course, I knew about turmeric,
21:09
but I also read around the time, how curcumin had started
21:13
gaining interest in the NCI as a chemo preventive agent. So
21:18
hold on just a second.
21:19
Hold on.
21:19
I want I want to our other colleagues to know what do you mean about turmeric?
21:22
Educate our non folks that don't know about turmeric,
21:25
tell us about turmeric and then make the link to curcumin.
21:29
So turmeric is
21:31
what Indians use for their cooking.
21:35
It's actually known as the Indian gold because in the Hindu culture,
21:40
you know, turmeric is associated with wealth, prosperity, fertility.
21:46
So actually during Indian weddings, there's the Haldi ceremony and,
21:51
you know, turmeric plays a really important role,
21:55
but it's also been used in Ayurvedic medicine
21:59
as an anti-inflammatory, as an antioxidant.
22:04
I don't think in Ayurvedic medicine it was ever considered
22:07
an anti carcinogenic agent, but,
22:12
I know, studies have been done
22:14
looking at, in India,
22:17
people eat turmeric all the time.
22:21
And they found there was, the incidence of colon cancer, I think, in India.
22:25
So what do you mean? They eat turmeric?
22:26
They use it for cooking?
22:28
So they put it in their food.
22:29
They use it for cooking.
22:30
It's what gives, the curry the yellow color. So,
22:36
that's, but it's
22:38
curcumin is a component of turmeric.
22:42
And curcumin itself.,
22:45
you know, is a polyphenol, and it has curcumin.
22:49
It's it has
22:51
bisdemethoxycurcumin, and demethoxycurcumin.
22:55
So it's got three ingredients, but curcumin is the most
22:59
important component of tumeric.
23:02
So in 2009 or 10 you're making dinner for your family and you make curry.
23:09
You say yellow curry.
23:10
And then you ask yourself, wow, this could help with cancer.
23:14
Was that the watershed moment in your kitchen, or is that too idyllic?
23:19
Too idyllic.
23:22
In my kitchen
23:23
I'm just trying to get the meal done, not thinking about science.
23:27
So how did you make this connection?
23:28
So what were you just curcumin flew into your head?
23:31
How did you start thinking about it?
23:33
Yeah, when I realized it's got to be a food substance, and I, realized
23:38
that curcumin was being used for prevention of colon cancer,
23:42
people had started talking about it, and the reason it worked for colon cancer
23:47
is because it sits in the gut,
23:50
that leads the into intestines.
23:53
It's the local contact, mucosal contact, that really helped with delivery.
23:59
So one of the biggest problems of curcumin in is its bioavailability.
24:03
It's not absorbed well.
24:06
And because of the hepatic first hepatic bypass
24:09
a lot of it gets either sulphonated or glucuronidated.
24:14
And so free curcumin in the blood is not easily available.
24:19
And that's one of the main reasons it has not worked.
24:22
So I really just extrapolated what I had heard about
24:26
prevention of colon cancer to the oral cavity and said,
24:31
hey, if it's working better for colon cancer compared to any other cancers,
24:36
maybe if I made had a local application
24:40
of curcumin for all these pre malignant
24:43
lesions, Leukoplakia - So then you came up with a paint?
24:47
How would you get local application?
24:49
What was your idea?
24:50
I was like so how do we you can't just eat curcumin.
24:54
It's extremely bitter right.
24:56
You know if people put extra turmeric in your food, the food is bitter.
25:00
So I started to research and found there was this company, Sabinsa,
25:05
who made a micro granular formulation of curcumin, for studies.
25:10
But I said, okay, so that's not a powder, it's these encapsulated granules.
25:15
So I first contacted this company and the very first study
25:18
I actually did, and got an R 21 for, was this micro granular formulation
25:25
where patients put curcumin micro granules in their mouth.
25:29
Both healthy volunteers and head/neck cancer patients.
25:33
And I looked at the serum levels using HPLC and found
25:38
it was much higher than previous clinical trials
25:42
that had used capsule historic controllers.
25:46
And then when I realized these micro granules were not really working
25:50
well on these cancer patients of mine, as well as my normal -
25:54
What do you mean, micro granules?
25:55
They were eating them or swish and spit.
25:57
What were they doing?
25:59
So they were taking a teaspoon of these micro granules.
26:03
They were like little pellets, little beads
26:05
and just keeping it in their mouth till they either swallowed it.
26:08
I see, as long as they could.
26:10
As long as they could in contact with their tumors, for the tumor patients.
26:16
So then I said, hey, what about taking this a step further?
26:21
And why not try to make a curcumin chewing gum.
26:24
So they’re chewing it, moving it around in their mouth.
26:28
Maybe they'll get rid of the habit of chewing tobacco
26:32
because - So you made you made a chewing gum?
26:35
So yeah I contacted - What does your mother think about this?
26:39
I know you've told me about your mother.
26:41
So does your mother know you went 18,000 miles away and you made a chewing gum?
26:47
You know she does.
26:48
But I don't know if she knows details about it.
26:50
And I don't know much about my science.
26:52
Oh, my gosh, what is that?
26:54
Oh, this is the chewing gum.
26:56
The curcumin chewing gum, for which we actually have a patent.
27:00
So, I contacted a pharmacist in town, and asked him
27:04
if he would make a chewing gum with me.
27:06
When was Doctor Nathan? What year?
27:09
The chewing gum?
27:11
We got the patent in 2011 or 2012.
27:19
So now you've been using it for ten, 15 years.
27:21
What are the results?
27:23
The gum took much longer.
27:25
The first time we made the gum was in 2018.
27:28
Fine. So six-eight years.
27:30
What do the results look like?
27:32
Results were
27:33
really exciting in terms of the concept.
27:37
So of can we get higher curcumin levels
27:42
both in, you know, in the serum using HPLC
27:47
and can we basically affect
27:51
some of these cytokines or chemokines that cause tumor progression?
27:56
So what we did find was
27:59
we basically Rahul, we took ten volunteers and we asked them to chew gum.
28:05
They were given, asked to chew the gum
28:08
6 or 8 times, then pack it in the mouth
28:11
in the buccal mucosa and leave it there and then chew it again.
28:15
So they did this for 30 minutes, two grams of chewing gum.
28:20
And then they did another
28:22
30 minutes of an additional two grams of the curcumin chewing gum.
28:26
And then we drew blood at the baseline, one hour, two hours and four hours.
28:32
And what we found was we had a significantly higher level
28:36
of the levels of curcumin we got in the blood compared
28:40
to, you know, the capsular formulation.
28:44
And we also found we were able to decrease
28:49
TNF alpha, CXCL1.
28:52
These are all important factors that cause cancer progression,
28:56
including VEGF and FGF.
29:00
These androgenic factors.
29:02
So I think there's a lot of good mechanistic reasons as to why
29:08
this may work.
29:09
If we can now run this production of this chewing gum.
29:15
So have you used it on patients?
29:18
Not yet on patients.
29:20
We use the microgranular on patients, which was also the locals concept.
29:25
But we have not used the gum on patients yet.
29:29
How does it taste?
29:31
So, Very good.
29:33
And this is a peppermint, chewing gum flavor.
29:38
We tried various flavors and peppermint
29:41
worked best with the turmeric tastes.
29:44
So I'm an otolaryngologist in Washington, DC, and I want to use it.
29:48
Can I go to Amazon and type “Cherie-Ann gum”?
29:50
What do you call this?
29:54
It's not got a name yet.
29:55
Just curcumin chewing gum.
29:58
It's, We haven't started marketing.
30:00
We are looking really for companies to try to market this.
30:06
You know, I the trial got completed in 2019, right before the Pandemic.
30:11
And then,
30:13
you know, like, we all know, a lot of things came to a halt.
30:16
But we’re, again, trying to see if we can market
30:20
this and get a company interested in making this chewing gum for us.
30:24
What is the toxicity?
30:26
You know, some, some amount is good,
30:31
perhaps curative, but too much could be toxic.
30:34
What?
30:35
What does the data show on serum levels and curcumin, i.e.
30:38
turmeric at high, high levels. Does it get toxic?
30:43
So the maximum dose that has
30:45
been tried, is up to 12 grams.
30:49
For a lot of the studies, 8 to 10 grams have been used,
30:53
our trial used four grams and there was no toxicity seen.
30:58
Like I said, other trials to all the way up to 10 to 12 grams.
31:03
However, for those who are allergic, there are some people
31:06
who have GI irritation from turmeric.
31:10
You know, or if they are on blood thinners,
31:13
it can interfere with, levels of that.
31:16
Those patients, or even healthy volunteers were not included.
31:20
That, of course.
31:21
You must be so excited by the potential.
31:25
I am I but, you know, I think it's,
31:29
not easy taking it from bench to bedside, but I think it's even harder
31:35
going through the marketing process and getting a company,
31:39
you know, to work with you on any inventions.
31:42
So we we'll see. We'll see where this goes.
31:46
I wonder,
31:48
the mic drop moment you will feel when you step off the plane in India
31:52
and you see someone throw that curcumin gum in their mouth.
31:55
it's better that they throw the curcumin
31:58
gum than the betel nut that they chew.
32:01
Tell, tell, tell our listeners what you meant by that.
32:03
What is the betel nut? Tell them that.
32:06
So the betel nuts is, this nut that has,
32:10
a very, significant carcinogen.
32:14
I think it's called arecna.
32:16
But they chew it in this leaf.
32:19
It's called paan, and they chew it with tobacco, and
32:23
I don't know, all kinds of other toxic substances.
32:27
It's red in color.
32:28
And, you know, I think you see it
32:32
because people tend to use it all over the place.
32:35
And, I remember the first time I saw a patient,
32:39
I thought it was a tumor in the buccal cavity.
32:43
And all of a sudden, this tumor moved over to the other side.
32:46
And I realized they had parked this betel nut in their mouth,
32:51
but interestingly, you know, tobacco chewing that, that's the same.
32:55
And,
32:57
I know there are pockets even
32:59
within the US where people still use the betel nut even over here.
33:03
So yeah, that was 40% of our malignancies
33:07
in India, of the head and neck are because of betel nut chewing.
33:11
So we're nearly out of time and I'd love you to perhaps impart
33:16
some of your energy/excitement/inquiry to the next generation.
33:20
When we talked about WIO, the WIO leadership asked me
33:24
to do a podcast with you.
33:26
And now I know why.
33:28
I have found this very entertaining and exciting.
33:31
And your research inquiries contagious.
33:34
What do you tell those residents?
33:36
Early career scientists that are out there?
33:39
How in the world do I get from a core grant to a chewing gum?
33:43
How do I get from a core grant to Wyeth and Novartis, and a
33:47
drug that people are taking?
33:50
Yeah.
33:50
You know, I will say, if you are passionate about something,
33:55
follow your passions.
33:57
Secondly, don't give up.
33:58
I think we all get, you know, our summary statements
34:02
from grant reviews and, you know, you think,
34:07
oh my God, there's no way I want to put in another grant.
34:11
This is not even doable.
34:12
But, the reason we give up easily is we can always go back to the clinic.
34:17
They can always go back to surgery.
34:18
Unlike the PhDs, who keep trying.
34:21
And so I would say never give up.
34:24
Keep trying.
34:24
It works.
34:26
Get started with the Academy core grant.
34:29
I mean, that's not only where I got started, but that's where I met
34:33
so many other WIO, you know, surgeon-scientists.
34:39
Carol Bradford and myself got the grant at the same time.
34:43
it's more lucrative. You know, you said it's easy.
34:46
I can go back to clinic, but it also, financially sometimes is more lucrative.
34:50
The path that you and Doctor Bradford, and others have chosen
34:53
sometimes is not, the instant gratification.
34:57
Do you know?
34:58
And if you don't know,
34:59
you don't have to answer this over your career, from the core
35:02
grant to today, what has been your success rate with grants?
35:06
Try to add it all up.
35:07
Numerator, denominator. What has been your success rate?
35:10
You might not even know, but what is it been?
35:13
I don't know if I can talk about success rate,
35:15
but I will say from 2000 until
35:19
last year I have been NIH funded.
35:22
I've had R-21s and then R-01s after that.
35:25
But you my point is you failed. You didn't always get them.
35:28
I have failed every single time.
35:30
I have always got my grant on the last try.
35:34
I failed on this last R-01 I've just submitted and I have to now
35:38
go in as a new grant.
35:40
So I have never been fortunate the first time around.
35:45
The second time around when we were allowed to try three times.
35:48
So yeah, I think just don't give up.
35:52
It all works out.
35:53
So you have failed more than you've been successful, but yet
35:56
you've been continuously funded for almost 26 years, two and a half decades.
36:01
And I owe a lot
36:02
to my collaborators, my multi-PIs.
36:05
So that's my other recommendation to everyone is always reach out, see
36:10
who else is working in the same field and, you know, reach out to them.
36:14
People are so helpful.
36:16
And, having strong collaborators definitely makes a difference.
36:21
And for full disclosure, I did not allow Doctor Nathan to list
36:25
all her collaborators and co-PIs I asked her to just to keep it to herself,
36:29
but it would have taken, probably 20 or 30 minutes for her to thank everybody,
36:33
but I didn't want to do that.
36:34
So she does represent Team Science.
36:36
Can I acknowledge one person?
36:39
And it was really my lab manager,
36:43
who died of pancreatic cancer
36:48
when she was 40 years old, and was the first publication
36:52
on curcumin was Cheryl Clark, who died of it and, you know,
36:57
very interestingly, she was one of the normal volunteers
37:01
where I was looking at serum cytokine levels.
37:04
So in the blood and the years after she died,
37:07
when we kind of looked at the data and what's looked at, I don't know,
37:11
we looked at the normal volunteers and the names.
37:15
We found that her VEGF level was 10,000 times
37:20
higher than other normal volunteers and realized,
37:24
oh my God, she must have had cancer when she was a normal volunteer, you know?
37:29
And it's just, I have her hanging over here in my office.
37:35
That's Cheryl Clark, my first lab manager, who started me on the Curcumin
37:40
Project itself.
37:42
Amazing story.
37:43
Amazing.
37:44
Thank you, Doctor Nathan, for sharing your time with us, your insights
37:48
and your inspiration,
37:48
and acknowledging your lab manager and the personal story behind our work.
37:53
Thank you so much. You for having me.
37:56
Bye I We hope today's episode sparked some fresh ideas.
38:01
If it resonated with you, please subscribe and share it with friends.
38:04
Have thoughts or suggestions?
38:06
Use the feedback form in the show notes.
38:08
We'd love to hear from you.
38:09
And don't forget to follow us
38:10
on social media for highlights, behind the scenes content and updates.
38:14
Thanks for listening. See you next time.