Funding for To The Contrary provided by the E Rhodes and Leona B Carpenter Foundation the Park Foundation and the Charles A Frueauff Foundation.

The messager RNA is very cheap.

The technology is is very affordable, very quick, and very cheap.

A body's own T-cells are stimulated to seek out specific cancer cells and bind to them and inactivate them.

Intro Music Hello, I'm Bonnie Erbé.

Welcome to To The Contrary, a discussion of news and social trends from diverse perspectives.

This week, the Faces of innovation.

Five Americans who overcame obstacles and turned scientific discoveries into useful products are being honored with the inaugural Bayh-Dole Coalition American Innovator Awards.

It's named for Senators Birch Bayh and Robert Dole, the creators of this bipartisan effort.

The goal is to encourage more life saving advancements.

Two of the honorees are women, Dr. Carol Mimura who we will hear from later in our program and Dr. Katalin Karikó is being honored for her work on mRNA, a medical innovation Americans know about because of the COVID 19 pandemic.

Welcome, Dr. Karikó Thank you for having me here.

It's very good to have you here.

We know about mRNA because of the pandemic, but you were working on it for years before we ever heard those initials.

How did you get involved in that issue?

The messenger RNA was discovered more than 60 years ago.

So it is a medicine which was not created by us with nature created.

We just copy nature.

And so that in the 1990s, in the beginning, I was working or started to work with mRNA.

Prior to that, in the late seventies and eighties, I was working with RNA, which was not messenger RNA but and other type of ordinates.

So this is I started the work at the University of Pennsylvania of Messenger RNA and tried to use it as therapy.

Are there many women who and girls who are interested in the sciences in Hungary?

And how does that compare with what you have found about women in science in the United States?

I think that both places, girls are interested in science.

but it is in the United States is much more difficult to stay on track because in Europe, like for example, I work with recently at BioNTech companies, the the father, daughter.

There's not just the mothers.

Fathers can leave the job and they are not missing out on significant time.

For me it was also important for me when I had my daughter that we had affordable, high quality childcare.

So if the government is listening, I think that that's how we can keep women in science and they can advance.

Now, during communist rule in Hungary, many women and girls were pushed into the sciences.

Why?

And was it a successful strategy?

I don't think that they were pushed.

You know, it was they were interested in the you know, you get the opportunity to study there.

And I just recently heard that several universities around here, I get the award or honorary degree.

They started to accepting women in the 1973.

You know, like I was I was surprised because, you know, in Europe, there is longer tradition that women would go to higher education.

And tell us how you first came to be interested in, believe in Messenger RNA while you were in Hungary.

I mean, in Hungary, I just learned about the messenger RNA later I studied.

in the 1990s when the Human Genome Project started.

I thought that more people might have aches and pains that genetic disease and for aches and pains, maybe we can use messenger RNA and that there are no permanent changes in the genome is needed.

But, you know, people, as they discover new genes and they associated with mutation to some disease, everybody was focusing on delivering correct genes and the gene therapy was in the focus in the nineties when the 1990 started and ended up the Human Genome Project 2000.

You know, it sounds to me coming from an American perspective that you were that women and girls interested in the sciences almost have it better in Hungary.

So why did you come here?

I started to work and work like a postdoc, like I get my PhD in Hungary in and working in, synthesizing RNA chemically.

But we had limited funding and, you know, I lost support, financial support.

So I tried to find a job in Europe.

But there, you know, as I was behind the Iron Curtain, I was not eligible to apply for different scholarships to go.

And so I couldn't get there.

And so I came here to Philadelphia, Temple University, and you first learned about messenger RNA when you were a student.

Tell me about that.

Messenger RNA was discovered in 1961.

Actually, I was born in 55, so at the age of six years, I was not reading nature.

I couldn't see the English up until I was 18 years old.

But, you know, in the school, in the high school, we learned about messenger RNA and the and then when I joined the team and got my Ph.D. in 1978, my supervisor actually synthesized part of the messenger RNA with colleagues collaboration in the United States.

So I learned more about messenger RNA from some of the team there in Hungary.

How involved were you in, if at all, in working to find a vaccine against the COVID 19 virus?

The invention which I did, we together with my colleague Andrew Weissman, at the University of Pennsylvania in 2005.

So we did this a long time ago.

But my focus was always to use messenger RNA for therapeutic purposes, you know, for treating a patient with heart failure or stroke.

But what happened is that the conventional RNA was very inflammatory.

So we discovered that how we can make messenger RNA not inflammatory, and that was seems for therapeutic purposes.

What was a twist was there that it happened, that it was better for vaccine.

And we with colleagues here at the University of Pennsylvania already tested on animal studies whether it is the mRNA is a good vaccine.

And I started to work ten years ago at BioNTech in Germany.

So I moved to Mainz, Germany.

And then as vice president and later as senior vice president, we developed I was responsible for mRNA for theraputic purposes.

So like coding for antibodies and for treatment.

But I also signed up for Pfizer and in 2018 we started work with them to develop vaccine for influenza.

And it was, you know, just happened that two years later, all of the sudden we had the other writers and changing the template.

It was you know, it was very quick because you just had to change the template, which you generate the messenger RNA.

And so that's why it was ready so quickly.

As you might remember, January 11, you know, the information and with Moderna, which also use invention, we did we do Weissman at Penn, they already March 16, they already injected the first volunteer.

I remember during the COVID infection period and before there was a virus, before there was a vaccine, when it finally came out, I was thinking, my God, this just happened at lightning speed.

How do you feel about that?

I mean, that it was probably at the time had to be the if not one of if not the only, you know, vaccine that protected people from a virus invented so quickly after the virus came into being.

How did you feel about playing a major role in that?

I mean, for me, it was not so unexpected, you know, because so many technology was coordinated in sequencing the viral cluster, for example, in China, because the sequencing, which was discovered in 1972, they gave the Nobel was not it was everywhere you could sequence then are also, you know, spreading the news that the sequence is available on Twitter or, you know, the scientists are developing, for example, companies who could generate the genome.

So 20 years ago, if it happens, everybody needs a package from Wuhan to start to make a vaccine.

Now the information was sufficient because this other technologies were already ready.

And also that the very many animal studies with the same construct were already tested and together with Pfizer already, we were just ready to start the human trial because for the influenza.

But so this was for other people seems overnight.

But if I can tell you that for decades overnight I was working and during the weekend and with colleagues, you know, then there would be would people would know that if this happened because so many different field, so many people worked diligently for years and years, you know that.

Or I remember moving to the United States in 1985, 86, we started trial for HIV.

So, you know, that whole big problem was that we didn't have any this test.

So everything was contaminated for the blood pool.

You know, now everybody has at home COVID test.

It was instantly was available.

So so many detection, the treatment, everything because of the technologies.

When you were at the University of Pennsylvania, you had to fund or find funding for your research.

Was that difficult?

Did it was it sort of a pushback that you, in other words, pushing you back in your schedule in terms of getting the research done?

Yes, it was difficult for me to get funding in these days.

I read about what could be the reason I came from a country with a university never heard.

I never had a famous sponsor and then coming up with the stupid mRNA, who cares?

So I never get funding in this academic setting.

So when we first realized the usefulness and we established with Drew Weissman a company I applied for a funding as a small company grant to from the taxpayer, and then we received that money for showing that this mRNA is useful to treat anemic people.

But we and then Moderna we proposed that and we did.

We presented and demonstrated that injecting a tiny amount of messenger RNA coding for the editor wanted the animals hematocrit increase.

They make more red blood process.

So we demonstrated that messenger RNA can be useful and the biologically relevant product protein can be produced.

And the importance is that the messenger RNA is very cheap.

You can every RNA is the same for nucleotides, just different order.

So this technology is very affordable, very quick and very cheap.

So we were very happy to do Weissman, my colleague that.

It would be affordable for everybody.

Thank you, Dr. Kariko.

Dr. Carol Mimura is also a Bayh-Dole honoree.

Dr. Mimura is a central figure behind immunotherapy, a treatment that revolutionized cancer care.

Hello, Doctor, and thank you for joining us.

Hi.

What a pleasure.

It is to be here.

Well, and congratulations on your award in lay terms for the audience.

Please tell us what immunotherapy is exactly.

Immunotherapy is used to treat cancer.

It uses the patient's own immune system to seek out and destroy cancer cells.

Immunotherapy is a huge and growing field and is now used to treat more than 18 types of cancer.

Hmm.

Amazing.

So, I mean, what exactly?

Again, in lay terms.

So I shouldn't be asking.

If you tell us in medical terms, nobody, nobody, including myself, is going to under the vast majority of the audience is not going to understand.

But how do you train?

Normally the immune system goes out and attacks a disease, right?

That's right, invaders.

But with this particular approach, a body's own T cells are Unleashed, if you will, or stimulated to seek out specific cancer cells and bind to them and inactivate them.

And what do you have to do chemically to get them to do that?

Well, you want to know what particular part of a cancer cell surface you want to target with this treatment.

And so, you know, in the laboratory, people find the particular things on the surface of the cell to be targeted by the T cells to make it more specific than just a general T cell attacking of any cell.

So it's sort of like a magic bullet or a tumor specific treatment.

Of the 18 kinds of cancer that it can treat.

Now, what are the the biggest ones, the most widely kinds of cancer being contracted, but that, you know, being that Americans are coming down with?

Well, this was the very first treatment ever approved by the U.S. FDA to treat phase four melanoma, advanced skin cancer.

And, you know, before this treatment, many, many people were dying of skin cancer.

With this treatment, patient survival times have been dramatically elongated, and it's just a great, great thing for medicine.

But also other solid tumors such as breast cancer, prostate cancer are also being treated with immunotherapy.

And you might know that former President Carter was also treated with an immunotherapy.

Okay.

And how do you have any data?

Do you have widespread enough data yet together an idea of how much more successful this is than the traditional therapies, surgery, chemo, radiation?

Yes.

Survival times with immunotherapy, sometimes in conjunction with surgery, chemotherapy and radiation are longer than without the treatment.

And initially, patients were living six months longer, and in some cases, patients are still alive years after the start of the treatment.

So it's a wonderful thing.

And you ran into a fair amount of resistance from the scientific community, did you not, when you were trying to bring this to market?

Yes, because when the invention was discovered, it appeared to attack and shrink cancer tumors in mice, but it was not known if it would work in humans.

So the idea of stimulating a patient's own immune system, recruiting your own immune cells to target a tumor specifically and slow its growth sounded so much like a miracle cure.

But it wasn't known at the time.

If it if this immune stimulation would create unintended harm such as nonspecific autoimmunity or an autoimmune disease disorder, you may know that some of the autoimmune disorders are rheumatoid arthritis or Addison's disease when the body's own immune cells mistakenly attack its own healthy tissues.

Right.

Sure.

And as I recall from work we have done in the past, women are much more likely to contract autoimmune diseases than men.

As I recall, this was true anyway when we did this story a decade or more ago that they were about twice as likely to have autoimmune issues.

All the more reason to have to attack to create very specific treatments that don't do unintended harm.

What doesn't get discussed a lot publicly by doctors and and medical experts is that even though you chemo and radiation are the and surgery are the best tools that we have had up until now.

The side effects can be horrible.

Can can really make the quality of life for some people I've talked to not worth living through.

What about the side effects from immunotherapy?

Well, as I said earlier, the chemotherapy in particular can have unintended consequences because it kills all fast growing cells, even though we would like it to kill only fast growing tumor cells, it can create other damage in the body.

But immunotherapy, as I said, is very specific to the cell that the T cell is targeting in order to bind to and and slow the growth of a specific tumor.

So how do you I'm sure you've spoken with or I assume you've spoken with patients who've been through immunotherapy, what kinds of side effects do they experience?

There is a body of literature out there that shows, you know, what can happen with any particular treatment.

One problem with assigning a given effect on a body to one treatment is that many treatments are often used sequentially.

So if a person has already had radiation and then is treated with immunotherapy in order to mop up, if you will, every last remaining circulating cell, it's hard to know if a side effect is due to one or the other of treatment.

However, we do see that using both several of these treatments together is better than only one.

And you talked about earlier, I asked you about the skepticism from the scientific community, and many medical experts were afraid that it might induce autoimmune disease.

What exactly did you have to do to get around that?

I had to really believe in the inventor, Jim Allison, who ultimately won a Nobel Prize for this discovery despite being faced with skepticism in the scientific and medical community.

And it was really just believing in him as a person and believing in the science.

I mean, he showed me photos of the mice tumors before and after treatment and after treatment, They were dramatically shrunken.

So, you know, the the prospect of of having a cancer treatment that could treat many types of cancer was well worth the investment.

But as was this brilliant and dedicated and doggedly determined scientist.

Please describe your role in all this.

You said you're not an M.D..

So what role did you play in the discovery of immunotherapy?

Well, I'm a trained biochemist and I use my background in biochemistry and business to bring discoveries that are made at UC Berkeley to the market.

So I work in use at UC Berkeley in a field called Technology Transfer.

And UC Berkeley professors and other researchers make groundbreaking discoveries and inventions that solve important problems and create solutions for all of us.

And we are bridging that gap and translating basic discovery into products and services that can help people.

And that was what convinced the medical community to allow the use of of immunotherapy.

No.

So because even though there was this wonderful promise and a reason to invest in both Dr. Allison and the technology and the patents required to commercialize the technology, much more had to be done because universities are academic institutions.

We train students and publish research, but we don't have faculties to make those products from our discoveries.

Or we and we don't have sales forces to sell the products.

So we patent inventions and license the patent rights to companies for commercial who then commercialize the inventions and then sell the products and services to customers.

But finding a company to develop a product was difficult because most companies said what?

Unleashing T-cells to fight cancer?

That sounds like it will never work.

I don't know why the patient wouldn't die of unspecific autoimmunity before the tumor shrinks, so and this is because companies spend well over $2 billion and more than ten years in research and development to bring a new drug to market.

So they make such expensive and long term investments with the hope of selling a successful product.

At the end of the day, but without having confidence that a successful product could be launched someday.

Most companies simply did not want to take that risk.

You can see why, it's a huge financial risk.

Tell me how long you think it might be before immunotherapy is the first kind of therapy given to cancer patients as opposed to sequentially after more traditional treatments?

And is that being done in some cases already?

It is being done in some cases already.

But but I mean, on a widespread basis or how long before it's the you think it's the treat, it's the first treatment of choice for all all patients with the 18 kinds of cancer that it can be used to treat.

Yeah, no doubt it's a specific decision between a patient and his or her doctor.

And the stage of cancer and other factors that have to go into the treatment regimen.

Thank you so much, Dr. Mimura Thank you for your work and thank you for your time.

That's it for this edition of To the Contrary.

Keep the conversation going on our social media platforms.

Reach out to us at to the contrary.

Visit our website.

The address on the screen.

And whether you agree or think to the contrary.

See you next week.

Outro Music Funding for.

To the contrary provided by the E Rhodes and Leo B Carpenter Foundation.

The Park Foundation.

And the Charles A Frueauff Foundation.

Youre watching PBS.

Funding for To The Contrary provided by the E Rhodes and Leona B Carpenter Foundation the Park Foundation and the Charles A Frueauff Foundation.

The messager RNA is very cheap.

The technology is is very affordable, very quick, and very cheap.

A body's own T-cells are stimulated to seek out specific cancer cells and bind to them and inactivate them.

Intro Music Hello, I'm Bonnie Erbé.

Welcome to To The Contrary, a discussion of news and social trends from diverse perspectives.

This week, the Faces of innovation.

Five Americans who overcame obstacles and turned scientific discoveries into useful products are being honored with the inaugural Bayh-Dole Coalition American Innovator Awards.

It's named for Senators Birch Bayh and Robert Dole, the creators of this bipartisan effort.

The goal is to encourage more life saving advancements.

Two of the honorees are women, Dr. Carol Mimura who we will hear from later in our program and Dr. Katalin Karikó is being honored for her work on mRNA, a medical innovation Americans know about because of the COVID 19 pandemic.

Welcome, Dr. Karikó Thank you for having me here.

It's very good to have you here.

We know about mRNA because of the pandemic, but you were working on it for years before we ever heard those initials.

How did you get involved in that issue?

The messenger RNA was discovered more than 60 years ago.

So it is a medicine which was not created by us with nature created.

We just copy nature.

And so that in the 1990s, in the beginning, I was working or started to work with mRNA.

Prior to that, in the late seventies and eighties, I was working with RNA, which was not messenger RNA but and other type of ordinates.

So this is I started the work at the University of Pennsylvania of Messenger RNA and tried to use it as therapy.

Are there many women who and girls who are interested in the sciences in Hungary?

And how does that compare with what you have found about women in science in the United States?

I think that both places, girls are interested in science.

but it is in the United States is much more difficult to stay on track because in Europe, like for example, I work with recently at BioNTech companies, the the father, daughter.

There's not just the mothers.

Fathers can leave the job and they are not missing out on significant time.

For me it was also important for me when I had my daughter that we had affordable, high quality childcare.

So if the government is listening, I think that that's how we can keep women in science and they can advance.

Now, during communist rule in Hungary, many women and girls were pushed into the sciences.

Why?

And was it a successful strategy?

I don't think that they were pushed.

You know, it was they were interested in the you know, you get the opportunity to study there.

And I just recently heard that several universities around here, I get the award or honorary degree.

They started to accepting women in the 1973.

You know, like I was I was surprised because, you know, in Europe, there is longer tradition that women would go to higher education.

And tell us how you first came to be interested in, believe in Messenger RNA while you were in Hungary.

I mean, in Hungary, I just learned about the messenger RNA later I studied.

in the 1990s when the Human Genome Project started.

I thought that more people might have aches and pains that genetic disease and for aches and pains, maybe we can use messenger RNA and that there are no permanent changes in the genome is needed.

But, you know, people, as they discover new genes and they associated with mutation to some disease, everybody was focusing on delivering correct genes and the gene therapy was in the focus in the nineties when the 1990 started and ended up the Human Genome Project 2000.

You know, it sounds to me coming from an American perspective that you were that women and girls interested in the sciences almost have it better in Hungary.

So why did you come here?

I started to work and work like a postdoc, like I get my PhD in Hungary in and working in, synthesizing RNA chemically.

But we had limited funding and, you know, I lost support, financial support.

So I tried to find a job in Europe.

But there, you know, as I was behind the Iron Curtain, I was not eligible to apply for different scholarships to go.

And so I couldn't get there.

And so I came here to Philadelphia, Temple University, and you first learned about messenger RNA when you were a student.

Tell me about that.

Messenger RNA was discovered in 1961.

Actually, I was born in 55, so at the age of six years, I was not reading nature.

I couldn't see the English up until I was 18 years old.

But, you know, in the school, in the high school, we learned about messenger RNA and the and then when I joined the team and got my Ph.D. in 1978, my supervisor actually synthesized part of the messenger RNA with colleagues collaboration in the United States.

So I learned more about messenger RNA from some of the team there in Hungary.

How involved were you in, if at all, in working to find a vaccine against the COVID 19 virus?

The invention which I did, we together with my colleague Andrew Weissman, at the University of Pennsylvania in 2005.

So we did this a long time ago.

But my focus was always to use messenger RNA for therapeutic purposes, you know, for treating a patient with heart failure or stroke.

But what happened is that the conventional RNA was very inflammatory.

So we discovered that how we can make messenger RNA not inflammatory, and that was seems for therapeutic purposes.

What was a twist was there that it happened, that it was better for vaccine.

And we with colleagues here at the University of Pennsylvania already tested on animal studies whether it is the mRNA is a good vaccine.

And I started to work ten years ago at BioNTech in Germany.

So I moved to Mainz, Germany.

And then as vice president and later as senior vice president, we developed I was responsible for mRNA for theraputic purposes.

So like coding for antibodies and for treatment.

But I also signed up for Pfizer and in 2018 we started work with them to develop vaccine for influenza.

And it was, you know, just happened that two years later, all of the sudden we had the other writers and changing the template.

It was you know, it was very quick because you just had to change the template, which you generate the messenger RNA.

And so that's why it was ready so quickly.

As you might remember, January 11, you know, the information and with Moderna, which also use invention, we did we do Weissman at Penn, they already March 16, they already injected the first volunteer.

I remember during the COVID infection period and before there was a virus, before there was a vaccine, when it finally came out, I was thinking, my God, this just happened at lightning speed.

How do you feel about that?

I mean, that it was probably at the time had to be the if not one of if not the only, you know, vaccine that protected people from a virus invented so quickly after the virus came into being.

How did you feel about playing a major role in that?

I mean, for me, it was not so unexpected, you know, because so many technology was coordinated in sequencing the viral cluster, for example, in China, because the sequencing, which was discovered in 1972, they gave the Nobel was not it was everywhere you could sequence then are also, you know, spreading the news that the sequence is available on Twitter or, you know, the scientists are developing, for example, companies who could generate the genome.

So 20 years ago, if it happens, everybody needs a package from Wuhan to start to make a vaccine.

Now the information was sufficient because this other technologies were already ready.

And also that the very many animal studies with the same construct were already tested and together with Pfizer already, we were just ready to start the human trial because for the influenza.

But so this was for other people seems overnight.

But if I can tell you that for decades overnight I was working and during the weekend and with colleagues, you know, then there would be would people would know that if this happened because so many different field, so many people worked diligently for years and years, you know that.

Or I remember moving to the United States in 1985, 86, we started trial for HIV.

So, you know, that whole big problem was that we didn't have any this test.

So everything was contaminated for the blood pool.

You know, now everybody has at home COVID test.

It was instantly was available.

So so many detection, the treatment, everything because of the technologies.

When you were at the University of Pennsylvania, you had to fund or find funding for your research.

Was that difficult?

Did it was it sort of a pushback that you, in other words, pushing you back in your schedule in terms of getting the research done?

Yes, it was difficult for me to get funding in these days.

I read about what could be the reason I came from a country with a university never heard.

I never had a famous sponsor and then coming up with the stupid mRNA, who cares?

So I never get funding in this academic setting.

So when we first realized the usefulness and we established with Drew Weissman a company I applied for a funding as a small company grant to from the taxpayer, and then we received that money for showing that this mRNA is useful to treat anemic people.

But we and then Moderna we proposed that and we did.

We presented and demonstrated that injecting a tiny amount of messenger RNA coding for the editor wanted the animals hematocrit increase.

They make more red blood process.

So we demonstrated that messenger RNA can be useful and the biologically relevant product protein can be produced.

And the importance is that the messenger RNA is very cheap.

You can every RNA is the same for nucleotides, just different order.

So this technology is very affordable, very quick and very cheap.

So we were very happy to do Weissman, my colleague that.

It would be affordable for everybody.

Thank you, Dr. Kariko.

Dr. Carol Mimura is also a Bayh-Dole honoree.

Dr. Mimura is a central figure behind immunotherapy, a treatment that revolutionized cancer care.

Hello, Doctor, and thank you for joining us.

Hi.

What a pleasure.

It is to be here.

Well, and congratulations on your award in lay terms for the audience.

Please tell us what immunotherapy is exactly.

Immunotherapy is used to treat cancer.

It uses the patient's own immune system to seek out and destroy cancer cells.

Immunotherapy is a huge and growing field and is now used to treat more than 18 types of cancer.

Hmm.

Amazing.

So, I mean, what exactly?

Again, in lay terms.

So I shouldn't be asking.

If you tell us in medical terms, nobody, nobody, including myself, is going to under the vast majority of the audience is not going to understand.

But how do you train?

Normally the immune system goes out and attacks a disease, right?

That's right, invaders.

But with this particular approach, a body's own T cells are Unleashed, if you will, or stimulated to seek out specific cancer cells and bind to them and inactivate them.

And what do you have to do chemically to get them to do that?

Well, you want to know what particular part of a cancer cell surface you want to target with this treatment.

And so, you know, in the laboratory, people find the particular things on the surface of the cell to be targeted by the T cells to make it more specific than just a general T cell attacking of any cell.

So it's sort of like a magic bullet or a tumor specific treatment.

Of the 18 kinds of cancer that it can treat.

Now, what are the the biggest ones, the most widely kinds of cancer being contracted, but that, you know, being that Americans are coming down with?

Well, this was the very first treatment ever approved by the U.S. FDA to treat phase four melanoma, advanced skin cancer.

And, you know, before this treatment, many, many people were dying of skin cancer.

With this treatment, patient survival times have been dramatically elongated, and it's just a great, great thing for medicine.

But also other solid tumors such as breast cancer, prostate cancer are also being treated with immunotherapy.

And you might know that former President Carter was also treated with an immunotherapy.

Okay.

And how do you have any data?

Do you have widespread enough data yet together an idea of how much more successful this is than the traditional therapies, surgery, chemo, radiation?

Yes.

Survival times with immunotherapy, sometimes in conjunction with surgery, chemotherapy and radiation are longer than without the treatment.

And initially, patients were living six months longer, and in some cases, patients are still alive years after the start of the treatment.

So it's a wonderful thing.

And you ran into a fair amount of resistance from the scientific community, did you not, when you were trying to bring this to market?

Yes, because when the invention was discovered, it appeared to attack and shrink cancer tumors in mice, but it was not known if it would work in humans.

So the idea of stimulating a patient's own immune system, recruiting your own immune cells to target a tumor specifically and slow its growth sounded so much like a miracle cure.

But it wasn't known at the time.

If it if this immune stimulation would create unintended harm such as nonspecific autoimmunity or an autoimmune disease disorder, you may know that some of the autoimmune disorders are rheumatoid arthritis or Addison's disease when the body's own immune cells mistakenly attack its own healthy tissues.

Right.

Sure.

And as I recall from work we have done in the past, women are much more likely to contract autoimmune diseases than men.

As I recall, this was true anyway when we did this story a decade or more ago that they were about twice as likely to have autoimmune issues.

All the more reason to have to attack to create very specific treatments that don't do unintended harm.

What doesn't get discussed a lot publicly by doctors and and medical experts is that even though you chemo and radiation are the and surgery are the best tools that we have had up until now.

The side effects can be horrible.

Can can really make the quality of life for some people I've talked to not worth living through.

What about the side effects from immunotherapy?

Well, as I said earlier, the chemotherapy in particular can have unintended consequences because it kills all fast growing cells, even though we would like it to kill only fast growing tumor cells, it can create other damage in the body.

But immunotherapy, as I said, is very specific to the cell that the T cell is targeting in order to bind to and and slow the growth of a specific tumor.

So how do you I'm sure you've spoken with or I assume you've spoken with patients who've been through immunotherapy, what kinds of side effects do they experience?

There is a body of literature out there that shows, you know, what can happen with any particular treatment.

One problem with assigning a given effect on a body to one treatment is that many treatments are often used sequentially.

So if a person has already had radiation and then is treated with immunotherapy in order to mop up, if you will, every last remaining circulating cell, it's hard to know if a side effect is due to one or the other of treatment.

However, we do see that using both several of these treatments together is better than only one.

And you talked about earlier, I asked you about the skepticism from the scientific community, and many medical experts were afraid that it might induce autoimmune disease.

What exactly did you have to do to get around that?

I had to really believe in the inventor, Jim Allison, who ultimately won a Nobel Prize for this discovery despite being faced with skepticism in the scientific and medical community.

And it was really just believing in him as a person and believing in the science.

I mean, he showed me photos of the mice tumors before and after treatment and after treatment, They were dramatically shrunken.

So, you know, the the prospect of of having a cancer treatment that could treat many types of cancer was well worth the investment.

But as was this brilliant and dedicated and doggedly determined scientist.

Please describe your role in all this.

You said you're not an M.D..

So what role did you play in the discovery of immunotherapy?

Well, I'm a trained biochemist and I use my background in biochemistry and business to bring discoveries that are made at UC Berkeley to the market.

So I work in use at UC Berkeley in a field called Technology Transfer.

And UC Berkeley professors and other researchers make groundbreaking discoveries and inventions that solve important problems and create solutions for all of us.

And we are bridging that gap and translating basic discovery into products and services that can help people.

And that was what convinced the medical community to allow the use of of immunotherapy.

No.

So because even though there was this wonderful promise and a reason to invest in both Dr. Allison and the technology and the patents required to commercialize the technology, much more had to be done because universities are academic institutions.

We train students and publish research, but we don't have faculties to make those products from our discoveries.

Or we and we don't have sales forces to sell the products.

So we patent inventions and license the patent rights to companies for commercial who then commercialize the inventions and then sell the products and services to customers.

But finding a company to develop a product was difficult because most companies said what?

Unleashing T-cells to fight cancer?

That sounds like it will never work.

I don't know why the patient wouldn't die of unspecific autoimmunity before the tumor shrinks, so and this is because companies spend well over $2 billion and more than ten years in research and development to bring a new drug to market.

So they make such expensive and long term investments with the hope of selling a successful product.

At the end of the day, but without having confidence that a successful product could be launched someday.

Most companies simply did not want to take that risk.

You can see why, it's a huge financial risk.

Tell me how long you think it might be before immunotherapy is the first kind of therapy given to cancer patients as opposed to sequentially after more traditional treatments?

And is that being done in some cases already?

It is being done in some cases already.

But but I mean, on a widespread basis or how long before it's the you think it's the treat, it's the first treatment of choice for all all patients with the 18 kinds of cancer that it can be used to treat.

Yeah, no doubt it's a specific decision between a patient and his or her doctor.

And the stage of cancer and other factors that have to go into the treatment regimen.

Thank you so much, Dr. Mimura Thank you for your work and thank you for your time.

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