(waves crashing) (car horn blares) (motorcyle engine rumbling) - [Kayte] Okay.

(mellow music) - Baby, it's come unstuck and it's pulled out.

I'm trying to push it back in.

I would like some more tape.

I dont know why they don't have plastic tape in this place.

(mellow music continues) (mellow music continues) - [Nurse] So you're going off to sleep.

Okay, sweet dreams.

We'll look after you.

- Thank you.

(machine beeping) (waves crashing) (jet ski rumbling) (upbeat music) (phone buzzes) - [Announcer] You still have time to purchase a raffle ticket for a young lady who has liver cancer or works for Bay County.

Her name is Kayte Hollingsworth.

And if you don't buy a ticket, that's okay.

At least say a prayer for this young lady and her family.

- [Kayte] Hi.

(indistinct).

if you look at me, I'm healthy.

It's only if you have a CT scanner that you know I have cancer.

Four years ago I had just terrible stomach pain.

I knew something was very wrong and I went to the emergency room.

While I was there, everything got better and I actually considered leaving the emergency room because it felt better and I didnt wanna go back and find out that it was something silly.

So I told my friend that had taken me that I wanted to leave and she convinced me to stay.

She said, “You know, this is the second time that you've had really bad stomach pain in the last week” They did an ultrasound and the doctor came in and he's like, “You have a liver tumor.” And up to that point, the thought cancer had not even entered my mind.

A couple of weeks later I found out that I had fibrolamellar hepatocellular carcinoma, something I'd never heard of before.

The first thing I did when I got home from the hospital was google fibrolamellar to find out what it was.

- [Presenter] Fibrolamellar hepatocellular carcinoma.

- [Presenter 2] A rare cancer of the liver that only affects 200 patients worldwide each year.

- [Presenter 3] 1 in 5 million in the population at large.

usually kids and young adults.

Currently there is no direct cure.

- [Kayte] And the first result that I had was a case study from Japan of a young man who went to the emergency room.

They find out they had fibrolamellar and within a couple of days he was dead.

And I literally went and I stuck out in my lip and I looked down and I cried like a, a like a little child that just lost their candy bar.

And I, I just bawled.

- When Katye was first diagnosed, we were about five months out from being married.

We'd been together for several years but we were not yet married.

(mellow music) Dealing with it, it's been hard, you know, from day one there's no textbook on her disease.

So the first chemo she was on, it was the easier one we've had to deal with.

More recently, the chemos she's been on have been more difficult.

- We've tried everything, you know, I've done chemo, I've done surgeries, I've done radiation.

And it just progressively got worse and worse.

And I asked my doctors and they said, I'm sorry but we don't have anything that is going to cure you.

They had basically sent me home to die.

I was 23 years old.

- [Announcer] Kayte Hollingsworth has to go to India in order to get the treatment.

- [Announcer 2] Katye, God bless you.

I know I'm ready for the fireworks.

Whos ready for the fireworks?

(audience cheering and clapping) - [Kayte] For a while I was really in a sad mindset, (fireworks crackling) but right before Thanksgiving last year, all that changed.

(audience cheering) (fireworks crackling) - [Cecilia] It's amazing how it all happened.

You know, somebody who knows somebody who knows somebody is basically how this came to be in Katye's life.

- Hi, my name is Kayte Hollingsworth.

I live here in Panama City, Florida with my husband Jake and our two dogs and a cat.

I can only find a few people on the internet who are still fighting, who are still alive to fight.

And then I was added to the Facebook fibrolamellar support group.

That's how I met this friend, Tal.

- [Tal] When I was first told that I was terminal, I felt like I was being kind of put out to pasture.

I was being put in this box and as they're going to very humanely, you know, make me feel comfortable as my life ends.

When people who know me and have any sense of what I've been through have someone in their lives that gets sick they often will call me and I'll tell them to talk to Howard I wouldn't be alive today if it wasn't for Howard Simons.

(phone ringing) - [Howard] Good morning, this is Howard Simons.

(phone ringing) Good morning.

Hello.

What is the symptom?

So what's your, what's your symptom?

But let me look it up online, okay?

Hello, Sir?

Right, so you just pull it out and then you put it straight into the new one.

Does it work in broil?

Or it doesn't work in bake or broil?

Oh, okay, it doesn't light up or anything?

Okay.

Hello, this is Howard Simons from appliancetimers.com.

I'm just returning your call.

As a human being, I have a general policy of trying to help people who call me And so they could call me up, it doesn't matter what it is.

Right?

Just a minute, please.

Most of my life, I never had any particular interest in medicine.

In the medical world, I'm a nobody.

A completely uncredentialed person.

I have an appliance timers rebuilding business in Toronto.

Do you have a separate touch pad or is it integral to the board?

Originally when I started doing it, it was because 10 or 11 years ago a friend of mine was diagnosed with acute myelogenous leukemia.

Basically my friend was dying, so I started doing research.

I always have enjoyed problem solving, so it was just sort of a thought, well let me see if I can help him out.

Now this coincided with the ease of research provided by the internet.

So this allowed me to read journal articles and things online.

Of course in the past this would've been impossible.

My friend had a particular mutation in his leukemia and you know, I had noticed there was a drug which got approved for kidney cancer.

And so I thought, oh well now that it's approved for kidney cancer, it could be used off label for leukemia.

So I contacted my friend's wife, suggested that she ask the doctor and then he said, “Yeah, it looks like a good idea, you should try it.” At that point I realized that it's obviously not that difficult to come up with decent ideas that these guys haven't thought of, right?

So I figured, well this is something, you know, maybe I could achieve something in this area.

(phone ringing) Good morning.

- [Tal] A lot of people might wonder how you come to trust the advice of this outsider.

You know, he is, he's not a doctor, he is not a PhD.

- [Howard] Have you tried to get the wiring diagram?

- [Tal] But you know, when he tells you something and you're not quite sure, he'll just tell you, well, if you want to look at it yourself, this is where I got it from.

And these are articles in peer reviewed medical journals, which I think doctors are supposed to read, and I don't know, sometimes maybe they don't have enough time, but I don't know where Howard finds the time, but he does.

- I enjoy doing it and I think of it as my job, even though, you know, I don't get paid or anything, but it's just what I do.

You know, what I do for a not living, right?

- [Tal] And guess what?

I'm not the only time that he saved somebody.

- [Stephanie] You know, when you're diagnosed with stage four pancreatic cancer and you have to tell your children that you're not going to live to the summer, you will do everything possible to survive.

- [Howard] Stephanie, she heard about me through a mutual friend.

- I phoned Howard, he gets the basic information and he calls me back in 20 minutes and he says, “I've just spoken to a surgeon in London and I've just spoken to Kjell Oberg in Sweden, and they're interested and they want your files."

And I remember thinking, oh my god, this guy's a nut.

So I said to Howard, “Howard, if you don't mind me asking, why are these doctors talking to you?” And he said, “I have their cell phone number and I call them and they take my call.” - The thing is that doctors are highly specialized.

If you're a professional then you have a particular job and you have to do that.

But that doesn't matter to me because I, I do whatever I want, If you wanna cure cancer, you have to think of all the characteristics of cancer, all of the way cancer can avoid getting killed, and then you have to think of the biological characteristics of the cancer, and then look for the solutions.

You have to think about everything all the time.

The prognosis is utterly dismal for this patient.

No one can argue that there's any decent idea for treating such a person, right?

In the case of Katye, because she has a liver full of cancer, she really should have a completely new liver.

Unfortunately, surgeons are not allowed to give a liver transplant in this case, right.

- [Dr Fuchs] The real problem with transplantation for fibrolamellar is that there are cancer cells lurking in the body outside of the liver.

And that's not gonna be fixed with the transplant.

Right now in medical centers, the standard treatment after a liver transplantation is that something has to be done to prevent organ rejection because the immune system does not recognize and then wants to attack the liver.

So these patients are on lifelong immunosuppressive drugs to prevent rejection.

The fundamental problem is that if the patient is on lifelong immunosuppression, the drugs will suppress the ability of the immune system to fight any cancer outside the liver and the risk of the cancer coming back is high.

- Hi, my name is Katye Hollingsworth.

I live here in Panama City, Florida with my husband Jake and our two dogs and a cat.

- There's certain things that bother me more than anything, one of which is people who believe that things are true because of authority.

- Right now doctors don't have a cure.

So what we do is we'll try one chemo and once that chemo stops working, we'll go onto the next.

The problem is eventually we know that all the chemos will stop working.

- There's a very conservative culture that's endemic in this whole process with Katye, you know.

- Its terrifying to feel so alone and feel like you have this rare freak of nature cancer that no one knows anything about.

The doctors don't know anything about.

And so last year, when the hospital, gave me a bottle of 240 Percocet that the doctor had sent me home to die with.

At that point I made the decision, the doctors are not in control, I'm in control.

- [Howard] Oh, hi, how are you?

- [Kayte] When he answered his phone, I've never met anyone like him.

- The amazing thing is Howard can explain it to me to the point where I actually understand what he's talking about.

That sort of, it makes the scary things not quite seem so scary.

- But this approach could be highly effective with anti-tumor effect from the bone marrow transplant.

My idea for Katye, something that was never done before is essentially a liver transplant from a living donor combined with the bone marrow transplant from that same donor, which is like moving the immune system from one person to another person and therefore the patient become tolerant to the organ.

And that is critical for two reasons.

First of all, tolerance to the liver gets rid of the permanent need for immunosuppressive drugs.

And the second thing is that bone marrow from a different person provides a new immune system, which then also has the capacity to kill cancer cells that might be outside of the organ that you're transplanting, which would protect against relapse and essentially completely heal the person.

and not only for fibrolamellar, Theoretically, all kinds of other types of cancer.

Right.

Now, if we can prove this procedure to be effective, this approach could actually, you know, cure a very substantial number of people.

- [Kayte] And so like my mind is blown, I'm taking notes but I just had that sensation of like, this is it.

This is what I've been waiting for.

- [Jake] They talked for hours.

You know, I just asked her like, who was that guy?

And she just said, “it's one of Tal's friends.” And I was like, “Is he a doctor?” And she said, “No.” I said, “Well he sounded like he knew more than any of your doctors you've had.” She said, “He did.” - [Howard] Most of the people I help are, you know, like stage four cancer patients who have been told there's nothing for them.

In such a case, you know, you have to do something that's unproven.

But because of the very restrictive authority of the idea of something called evidence-based medicine, it is extremely difficult to get people to do something that's unproven.

But I believe in medicine-based evidence, not evidence-based medicine.

- [Katye] Honestly, one of the biggest things to make this happen, is Howard and his philosophy about calling people he's never met.

(bicycle bell rings) He has the guts to call the world's top doctors as if he's, you know, peer to peer.

- I don't see any reason why an intelligent person wouldn't want to discuss a good idea.

What I did was I got on the phone and got two of the best doctors in the world to do it.

The first time I spoke to Slavin, he was the head of bone marrow transplantation at Hadassah at the time.

I didn't have his phone number so I found Hadassahs phone number.

I phoned up their switchboard and I asked to speak to him and they put me through to his cell phone.

(phone buzzing) Dr. Slavin is perhaps the most creative bone marrow transplant doctor in the world.

I said, “Hello Dr. Slavin, I have an idea that I want to discuss with you.” I didn't even tell him my name.

I was a random human being.

- [Dr Slavin] Howard is very smart.

Hes read all my papers and he knows them by heart.

- And then I said, "You know, the liver cancer ... wouldn't it be a good idea to transplant the liver and induce tolerance with the bone marrow transplant from the same donor” He said, “Absolutely it should be done with all organs.” And we had this whole tolerance induction festivity.

Now I should mention that people had been writing about inducing tolerance with bone marrow for a long time, mostly Slavin.

So in that respect, what I came up with wasn't original.

The only thing that was truly original about my idea was using it as a treatment for liver cancer.

Okay, bye.

And actually this was before I knew anything about Kayte.

It was strictly just playing with ideas in my mind.

So this was just serendipitous anyway.

It wasn't like I was out looking for people.

When I phoned Slavin, he couldnt care less who I was He heard an idea and he liked it.

But that's very rare.

He's probably the only person I've ever met like that.

- [Dr Slavin] If I keep doing what everybody's doing, if I know ahead of time, it will fail there will never be progress.

I went to college to study medicine and I always dream about curing cancer.

Oncology at that time was based on a concept, the more, the better, more radiation, the better, the more chemotherapy the better.

And I thought if that cured patients, fine, but it doesn't.

So I thought instead of trying to do more dangerous hazardous procedures, I'd rather do smarter procedures.

So all my life I come up with ideas that are outside the box.

Unfortunately, in general, doctors are very resistant to new ideas.

They just like to do what somebody else is doing, what the textbook says.

It is surprising.

I mean, you go for example to American Society of Clinical Oncology.

The auditoriums are full like ants and you ask yourself, “what is new?” Very little.

They ask you to prove before you do the first patient.

But you must do it in order to see that it works.

So many years later, cancer remains one of the leading causes of death worldwide.

For me, this is war.

You can see it's a complex program.

If the patient accepts bone marrow cells from the donor, he becomes tolerant of the liver.

The other element, which is maybe even more interesting is to use somebody else's immune system to fight against cancer.

- [Tal] The second part of this plan was actually one of the things that Howard arranged for me.

In my case, there was no liver transplant because they were able to remove all the tumors from it, but I still probably had cancer outside the liver.

So I was given donor immune cells for my brother by Professor Slavin in Tel Aviv, basically getting my brother's immune system and my immune system to cooperate for a time to kill cancer.

- [Slavin] This is like biological warfare against cancer.

- For Katye, we need someone who's DNA at least half matched because the closer the match is, the more likely you are to be able to induce tolerance.

(upbeat guitar music) - One of the worst things about this surgery is we need a living donor and it has to be one of my brothers.

- That's why I'm so stressed out.

I've spent hours and hour googling medical journals and I had to do a lot of looking inside myself and asking myself, can I ask my brothers to risk their life?

Press it, it records.

See if I can fix this.

Took a while to get up here and I stepped on a thorn and it hurt.

A lot.

Im being a big dork but I dont care.

Do you know what I dreamed last night?

I always wanted to be something, I always said I wanted to be “they” like, Id always say, “Oh they do this”, you know, “They're in control”, “They do that.” And I was always like, “Who is they?” Like, I wanna be “They”.

When I was in college, I took psychology because I wanted to be like a behavioral therapist.

I was planning on going to graduate school and possibly getting my PhD and I wanted to get married and have babies.

I wanted everything.

It's gonna be cool.

Watch!

Really!

Seriously!

- [Robert] I see you, Kayte.

Since she was a small child, she has been very independent and very strong-willed.

- [Cecilia] She was the child th always looked for a solution.

- And she always said, “I'll do it myself.” Even one time, she was about maybe two years old, she stepped off the dock, went in the water and all you could see were her little eyes shining.

She was probably that far under water.

Jumped in, got her out and by George, she was upset because I helped.

She looked at me straight in the eye and said, “Dad, you going to pay for this?” - [Jacob] Growing up, my sister was really not afraid of anything.

I think that's just her base of her personality.

- Hi Katye.

- She's always found ways to do things for herself.

But if I found out I was a match for the surgery, I'll jump up on the kitchen table, do it now.

- [Joseph] She's my big sister.

Shes the strongest person I've ever met.

She took care of me.

She's done that our entire life.

She would fight any battle.

- I had a dream last week where I was a fly on the wall and my little brother was on a blind date and the girl asked him if he had any siblings and he said, “I have a brother and I had a sister, but she died.” And then I woke up and still, anytime I think about that dream, it makes me wanna hold on and make sure I do everything I can to stay here because I saw a look of pain in his face that I've never, never want to see.

(ominous music) (clock chimes) I was very excited when Professor Slavin contacted me and said I have a patient.

- [Dr Slavin] Okay.

I met Rela before in England.

At that time we talked about tolerance induction.

- We both wanted to do something for many years.

And finally with this patient, everything came together.

Well done.

- Bye-bye.

There are many different people in our profession.

Some just do it as a job and there are some who are constantly pushing.

For whatever reason I've always wanted to make a difference in the world.

- [Announcer 2] Dr. Rela has found a place of honor in the Guinness Book of World Records, having performed a transplant on a five day old baby.

- I came to the UK in 1985 and at that time I was very frustrated with India.

I didn't think I was progressing enough and I never thought I would return back to India.

- [Announcer 2] Global hospitals in India, pioneers in the field of organ transplant.

The mission is spearheaded by Professor Mohamed Rela.

Dr. Rela in effect initiated the living donor liver transplant program at King's College London.

- But 2009 I started a transplant program there because now there's a huge opportunity to be very innovative in India and the quality of work we do is excellent there.

The decision to do this with Katye was not so easy.

Normally because of her advanced malignancy, Katye would not have qualified to have a liver transplant because with immunosuppression, the risk of recurrence is high.

If we were not going to try transplanting without immunosuppression, I would've never accepted her for transplantation.

And I wouldn't have agreed to it if Professor Slavin was not directly involved.

We put it through our hospital ethics committee.

They really agreed to what we wanted to do.

And I have to say, the institution in India is extremely supportive of me and they wouldn't think that I would do something that unethical that they would worry about.

- We are actually quite lucky the Dr. Rela is willing to do it.

In the medical world, this procedure is what's called a heroic measure.

And in medicine, heroic measures are frowned upon.

It's very hard to understand because heroism generally is considered to be a positive thing.

But I've heard many doctors say, “Oh we can't do that.

That would be a heroic measure” Interestingly, Slavin seems to prefer heroic measures.

- The vast majority of doctors would not take this risk.

Because you can never guarantee that this isn't gonna blow up in everybody's face.

- That risk is there.

But if you're not prepared to face failures, you can't innovate.

(film projector spinning) It was Dr. Thomas Starzl who did it in Denver in the 1960s.

- [Dr Starzl] The starting point was what can I do that will benefit society and have some kind of real meaning.

- Unfortunately, during the first liver transplant, the patient bled to death on the table.

- And many people thought we should stop.

I didn't agree.

Failure is very much part of innovation.

- I'm looking for the part that has the most crust that I could find.

- It's not fancy but it's Kayte's favorite dish.

This scoop looks better.

(phone buzzing) (phone message alert) - What happened?

- What?

- [Jake] Sorry baby.

I have a very good friend with fibrolamellar that I just found out is in a coma.

She's been such an inspiration to me to keep me going.

When she was first diagnosed, they basically told her, she was like 23 at the time, they told her, “If you have anything you wanna do in your life, you need to do it in the next year 'cause you're gonna die within a year.” And she said to me, “I was really sad and and depressed for a day.” And then she said, “Wait a minute, I'm the CEO of this cancer and you're fired.” It's our choice as individuals to decide how we are going to carry whatever burden we're given.

You know, we can be weighed down and let it defeat us or we can carry it and let it make us stronger.

- [Dr. Slavin] And it takes usually 10 to 15 years to introduce a new idea into medicine.

(pensive music) But in the case of organ transplantation, without immunosuppression, it has been more difficult.

- The history of tolerance goes back to 1943.

There was a scientist named Ray Owen in the United States who was called to a farm where these cows were being born.

- Owen was the first one to understand the secret of tolerance is mixing the blood of the donor and the recipient, - These cows were actually twins and they were clearly not identical.

And he found that each cow had a mixture of each other's blood types - And he reasoned that because they shared the same placenta, there was a mixture of blood in utero.

- In the 1950s, there were experiments in mice where they deliberately took fetal mice and they gave transfusions of blood cells from a genetically distinct mouse.

And they found that when the mice grew up you could place a skin graft from the, from the same donor.

And that animal was tolerant.

- The mouse has never lied to me.

If a mouse tells me the story, this is it.

- Basically took 30, 40 years of experiments to get to the conclusion that you could actually induce the state of tolerance by inducing something called chimerism.

The stable mixture of blood cells from two different individuals.

Chimerism, the word derives from Greek mythology.

A chimera was actually three different animals blended into one.

- Most doctors say it's against nature.

And my answer to that is not only is it not against nature, it is nature's most successful experiment.

(baby crying) Because all of us are examples of successful chimerism.

In utero, we should all be rejected.

No one of us is matched with our mother.

Why aren't we rejected in utero?

It is because Mother Nature knows and induces tolerance.

Nobody understands exactly why the fetus is not rejected.

But one of the possibilities is that we know that the fetus ejects stem cells to the mother.

Because if you find in mother's blood, male cells, you know it's a male baby.

So that is why when I was at Stanford, we developed similar strategies to inject blood cells to the patient from the donor, which we proved in mice works.

And I have maybe 50 publications on this topic alone In the medical system, it can be so difficult to introduce new protocol.

You become an enemy of everybody.

You know, they look at you like you're coming to kill their mothers.

You know, they like, like an enemy.

What the hell?

I mean I'm trying to cure cancer patients.

Give me a chance, you know, with a new idea.

- [Howard] In the west, the regulatory environment is such and the legal environment is such that you practically can never get something like this done.

But when you know that you're gonna die, the idea that individual human beings should not have the autonomy to do what they please with their own lives, to me, it's ridiculous.

- Keeping in mind that like I am a member of the profession, there is a reason why you have to get these things done formally and in a way that's scientifically valid.

You know, every jot and tittle of the protocol has to undergo extensive review.

But that's a good thing.

You know, making sure that patients get the right treatment and also minimizing the risk.

Medicine is like an ocean liner, it just doesn't turn on a dime.

- [Howard] But the problem is someone with a lot of disease in the liver, like Katye, doesn't have the time for that.

(birds chirping) (dog barks) - [Jake] It's rough, you know, not for me, but for her.

I want her to be normal, live a normal life again.

(sound from television) - [Rochelle] And I agree.

He and I are sort of opposite ends of the spectrum in terms of - Everything - Physical.

No, but one thing we have similarity to, you know what it is?

We don't dabble in things.

- The thing - Is that we're both very intense about what we...when we do something, we do it full force.

Neither one of us dabble in things.

Howard has always marched to his own drummer.

- Thats right.

- [Gerald] Even as a little boy, I remember when he was interested in nuclear reactors, he knew where the neutrons and protons were going He knew everything.

You know, - At four years old he said to me, "Mom, I'm my own best entertainment unit."

- Life to me is thinking everything is a problem that needs to be solved.

- When you go through medical school, you're taught not to be creative.

You're taught to do everything by the textbooks because you can get in trouble with malpractice if you're creative.

But you know, unfortunately, when the textbooks run out of answers, you need people who can think creatively.

- When my father was old and not well, Howard helped me decide to not allow my father to go into palliative care, which was suggested by the doctors who said he'd be dead in a week.

But the doctors couldn't find any reason why he was dying.

- So I said, well the fact that the doctor says that he's dying from an undiagnosed disease, that's fundamentally an unscientific opinion.

So I told them to give him a couple IVs of saline and then we took him home.

Within a couple weeks he was back to normal and he lived over a year after that, quite happily, right?

- We had a great turnaround.

- The girls would be selling some more raffle tickets.

Well that's our prime rib for lunch.

We're actually having a fish fry this Thursday.

And then the prime rib is the Friday after this.

(people chattering) - [Kayte] I was a little afraid that people would think I was crazy for going to India.

- Come on, you guys.

- My husband and I talked to some transplant surgeons here about Howard's idea.

And although they did not give me one single option, they still told me the idea was completely crazy and that if I did it, I would die.

And it was mainly because, it hasn't been done before.

But everything at one point had never been done before.

At one point the earth was flat.

- [Howard] I think that we would be remiss if we understated the role that Katyes courage plays in all of this.

She's a very brave person.

Healthy people might not understand.

Healthy people would think of her as desperate.

In other words, why not try the treatment since you have no chance otherwise.

But I know from experience, most people who are terminal choose not to do it anyway.

With Katye, we're looking at an N of 1.

We're looking at, right?

We're looking at one human being.

- [Jacob] With this type of cancer, which is so rare that it's not really studied 'cause it doesn't get any kind of attention.

Katye feels like maybe this will help everyone.

- [Katye] I face reality.

I know that this might end badly and it might end badly immediately, but somebody has to be the first.

Somebody has to be the first one to say, “Hey, I'll try it.” (car door slams) - [Hairdresser] Well, gotta get that haircut.

This an inch on longer.

We can start with that.

- I will be in India tomorrow.

I know that I'm going to be very anxious.

I'm definitely gonna take my anxiety pills.

- Alright, ready?

- Ready.

When I get nervous, I just get jittery.

So I'm gonna be ready.

And you have to go in with your fighter spirit.

You gotta go in with all your armor on.

(clipper buzzing) (mellow music) Cancer, I think kind of helps you learn what you are in control of and what you aren't in control of and what you are in control of you have to learn to own and fight and hold onto it because people will try to take it away.

Not just doctors, but people who mean well like family and friends.

They'll try to take away some of your control.

And I fight for it.

Like no one lays out my pills for me.

I do that.

I mean there are times when I've had to rely on, you know, my mom's had to wipe my butt after I've gone to the bathroom.

You know, it happens.

But when you can do things for yourself, you have to stay in control because I mean, otherwise I think you lose your sense of self and that is one of the most important things that you have to hold onto.

And that cancer is - cancer teaches you a lot about who you are and what you're made of.

(dogs barking) - [Jacob] We have known for a little bit that I was the best match for the surgery.

So what I'm gonna do is give my sister a portion of my liver, whichever part that is.

I'm not, I'm not detailed or I haven't been - I don't know the details yet.

I mean, I really don't have any information really.

They're just gonna do what they have to do.

That's gonna be it.

And I'll accept whatever consequences come along 'cause I'm saving my sister with my liver and my bone marrow.

To me, that's all I have to know.

Theres a risk, but death happens.

And if I can save Katye's life through death, then so be it.

But we're gonna give the middle finger to death here.

We're gonna do it.

(mellow music) - We are ready to leave for India.

Katye and Jacob get there before me.

- I've never been to India, you know, and it is a world away.

Of course, it's scary 'cause I love my life.

I love everything about it.

(mellow music) (engines rumbling) (horns honking) (bells chiming) (upbeat music) - [Jacob] We arrive in India the only way I can really describe it is theres just chaos.

(engines rumbling) When we were driving through the streets in the middle of the dodging cows, dogs and vegetable stands, (bike horn blares) - [Cecilia] It was very scary with the driver going very fast in the opposite side of the road or no road.

- I'm watching my sister half awake.

Just kind of like her head flopping around.

I'm thinking in my head, so you met a guy on Facebook, he told you about a Canadian guy, who's a plumber, who has interest in medical journals and now we are in the middle of India.

And it was just crazy.

(cars honking) (waves crashing) (mellow music) - [Cecilia] First both Jacob and Kayte had to go through all their physicals, their cardiologist, all their blood work.

I'm getting that sinking feeling in my gut that this isn't right.

- As I told Jake, I don't know much about women, but one thing I know is that they like chocolate.

So I just bought chocolate without asking.

I knew that they would like it.

I brought all kinds of food mostly for the patients family because it's too much of a shock for them.

(mellow music) This is really exciting.

I've never been to India before.

- You met the patient?

- Pardon me?

- I've never met the patient.

- Oh, I see.

- I've never met her.

- Oh.

- She's never met me.

I helped out someone who had fibrolamellar and... Hi Katye, how are you?

Oh, I got something for you.

I stopped off in Belgium so I got you chocolates.

- Oh thank you.

So nice.

- Hey.

And cookies too.

- Delicious.

I cant wait.

- Hello.

- Hello, this is nice.

- Yeah.

- How are your bones feeling?

- Warm and... - Warm and sore?

- Annoying.

- Yeah.

Yeah, - I'm aware of them.

- Yeah, yeah, yeah.

It's interesting.

You can actually feel those are your blood cells multiplying.

- Yeah.

Every bone, I'm aware of The shot I got yesterday to prepare my bone marrow, it makes me aware of every bone in my body.

Even like the small bones in my hands, I can feel them and they feel like they're charcoal briquettes just cooking away.

- The stem cells like stick to the inside of your bone and they don't do anything unless they're needed.

They'll just sit there forever.

And what this does is it causes them to, it gets them off of the bone and into the blood and it causes them to proliferate.

- [Kayte] Hearing Howard talk about everything does make me feel better, like he has such a depth of knowledge.

- Bone marrow is comprised of all kinds of cells.

I am sanguine about blood cells, if you'll excuse the pun.

I didn't to, you know, sanguine comes from the word sanguis, which means blood.

But anyway - - When I met Howard, he felt like the big brother that I've never really had.

I can understand a little bit how his mind works.

I can only imagine his head he's thinking about 50 different things.

(dramatic music) It's going to improve not just liver transplants, its all progress.

There is something like a hundred thousand transplants in the world each year.

(plane engine rumbling) - If we are successful in this case, not only we cure this charming young lady who is otherwise doomed, but more than that, it'll be a message for so many other patients all over the world that could be cured with the same strategy.

(plane engine rumbling) (car engines rumbling) - [Kayte] Today when I finally met Howard, I was like, Howard, you know, my family just wants to thank you so much for doing all the work that you've done for us.

And he was just like, “That's completely ridiculous.

You don't have to say thank you.” - There's a Hebrew expression.

(Hebrew) In a place where there isn't a person, you have to be the person that's, that's the case.

But I would like to add to Hillel, there isn't another person.

Don't assume that there's another person because there isn't.

- Ah, you never met.

Oh.

- How are you?

- Fine, thanks.

I see, okay.

So this is the reason why we are here.

- She has a bad artery, doesn't she?

Oh, just one specific point.

Right?

Because you're inducing, because you're only inducing tolerance to the the donor.

- I didn't think about that.

- Yeah, you see, that's why he is here 'cause he is good.

- [Howard] Kayte's hepatic artery is in bad shape because some genius in Alabama decided to irradiate her liver.

To of course kill the tumor.

But that damaged the hepatic artery.

Now she requires grafts of blood vessels.

- [Kayte] I had high dose radiation.

a couple weeks later I couldn't eat and I was waking up in the middle of the night with pain.

I couldn't sleep.

And we went in for a CT and they mentioned like, “Oh well some of your liver, you know, it's basically like when you defrost hamburger meat in the microwave, you know some of it gets a little, a little cooked but it's still good.

- [Jacob] Basically, barbecued her insides.

- [Howard] They almost killed her.

If my idea works, hopefully we can start the revolution of curative oncology as opposed to the nihilistic form of oncology that we have today.

You know.

(waves crashing) (crow cawing) - [Kayte] I need to pee.

- Right.

- Somebody must be.

- Yes.

- Otherwise there would be no progress.

- Yes, yes.

(bus engine rumbling) Getting prepared for the surgery, they were like, “I don't know how we're gonna operate on someone so big.” I was like, “What?

Im the smallest I've been in years.” Still a giant in India.

(machine beeping) - [Howard] Right now, Jacob is doing an apheresis, running his blood through a centrifuge to spin out the cells that they need for tomorrow.

- [Howard] Yeah.

- [Jacob] Today, I found out my vein is gonna be used as an artery or my sister and tomorrow the doctors will be cutting into my leg.

It is scary, but glad it's me because I'm the most expendable to be able to send over here and wait for however many months were stuck here.

Because I'm living at home.

You know, I don't have family.

I don't have any anything... Well maybe one remote possibility but that's a weird story all on its own.

- So the name was chimerism.

- Yes.

- Which means its a mixed animal made of the best part of each animal.

- [Dr Fuchs] With bone marrow transplantation, The most feared complication is something called graft-versus-host disease.

A big problem in which a donor's immune system kills everything.

Not just the cancer but the normal tissues of the body.

- I made it very clear to Katye, there are different ways of doing this procedure.

I originally wanted to do the full bone marrow transplant but the hospital in Chennai had no experience dealing with graft-versus-host disease.

So she would've had to have the bone marrow transplant somewhere other than India.

And because of her condition, Katye doesn't have time to do that.

So what Slavin did was he chose an interesting compromise.

- [Slavin] We don't need a full bone marrow transplant.

It's enough to do the bone marrow mini transplant.

In other words, we only need to educate the bone marrow of the patient to accept the organ by transient circulation of donor cells.

You don't even have to do it permanently.

This is called mixed chimerism.

- The only disadvantages, you just have an immune system which has been conditioned to some extent to be tolerant but you don't have any guarantee.

Therefore, if you have an event that wakes up the immune system like an infection, then rejection could happen at any time.

- [Kayte] What was the name of the first complication?

Because itll be very difficult to get a second patient We can put the patient on the side.

Can we?

- [Dr. Rela] Yeah you can.

- Yep.

- Yup.

That operation is going to take five or six hours at least.

And therefore if we do her operation first and then start the donor operation, she'll be anesthetized for a very long time.

That's probably not in her interest really.

So I think we should start with a donor and then the recipient.

I mean, the radiology actually doesn't show.

Well only know when the donor organ is actually nearly ready to come out.

- Okay.

- Yes.

(mellow music) - [Jacob] I can tell everyone's tired and ready for a conclusion Whatever conclusion it is.

I mean, to me, I accept any conclusion because it's the next step for the next people 'cause there will be others who will try, even if it just needs to show a little promise.

And that's good to me, for humanity, that's good enough.

But I would really like my sister to live.

(birds chirping) (waves crashing) (bells ringing) (chanting) (fire crackling) Just ready to get it done.

- Have a good time.

- Alright.

- Bye, yall Love you, Momma.

Love you, Jake.

- You okay there?

- Okay.

(machines beeping) - So, you're going off to sleep, okay?

Sweet dreams.

Well look after you.

- [Kayte] Thank you.

(machines beeping) (ominous music) (liquid trickling) (machines beeping) (indistinct country music) (hammer tapping) (machines beeping) (dramatic music) Everything is going quite smoothly.

The surrounding tissue, it looks like it's in good shape.

They're now waiting for the donor liver to be removed.

(suction machine sounds) This is my first time in surgery.

There's a certain aesthetic appeal to the movement in the operating room.

It's sort of like a dance.

(machine noises) (dramatic music) - [Howard] The level of precision and the sewing skills of Dr. Rela amaze me.

He told me that it wasn't difficult because he's used to doing pediatric grafts where the vessels are much smaller.

- Yeah.

- Mm hmm the liver.

- [Dr. Slavin] I trust you.

- Okay, 1, 2, 3.

(machine beeping) (stirring sound) (ominous music) You can put pressure here.

(indistinct chatter) The operation's finished.

- [Jake] They said that we could see the liver?

- [Dr. Rela] Yes you can.

We normally show the liver to the patients relatives.

- [Dr. Rela] Yeah, these are tumors.

- Uh huh.

- [Jake] We couldn't be happier to be here.

Actually like, you know, we were worried like you have no idea to begin with, but like, we couldn't be in a better place.

(car engine rumbling) - [Howard] This was, I think, a pretty difficult surgery.

But the first couple disastrous things that could happen haven't happened.

Right now the worst case scenario is that tolerance is not induced, in which case Katye would need to be on immunosuppression.

And having a new liver, it would be impossible to conceive because she would be worse off than she was before.

(car horns and engines) (waves crashing) - [Jake] Yeah.

- Yup.

This is the day after Katye's third surgery and, and she's looking so good.

Recovery was going well, but after a few weeks the doctor came in and said, “We have to take you to surgery.” - [Dr. Rela] Postoperatively, she was off immunosuppression for two weeks, but then she did have a low grade rejection.

Her enzymes were slightly up and we had to start her back on immunosuppression.

- [Howard] This failing to induce tolerance is not a disaster.

She still has a new liver in her, which means we reset the clock on the disease.

And so if she relapses, she would start out with a clean liver.

- Possibly.

We may be able to withdraw immunosuppression in the future and still have tolerance.

However, around the third week she had a problem with her hepatic artery, hepatic artery thrombosis.

But we caught that very quickly We re-operated on her and revascularized her artery and subsequently established a good flow.

Yeah, that's good.

Fortunately, Katyes a very strong person.

I was the one who was taking care from the starting.

Yeah, she's very courageous.

Katye won't tell about her pain, okay.

Whenever we go inside, she just smiles She just ask us whether we had a breakfast or everything.

She's a good girl.

She won't complain.

When she goes home, well miss her.

- [Cecilia] This is the day after Katyes third surgery, and Jacob and I are leaving tonight to go home.

And she's looking so good.

And she's gonna be out of here very soon, and have some time to relax and get even better at the hotel and then fly, fly home to the United States of America.

Yay.

(street sounds) (piano notes) (boat engine rumbling) - [Jake] I believe in God, but I just don't feel like he's very fair.

(emotional music) (sweeping sounds) - [Howard] Sunday morning, I got up at, you know, my regular, like 4:00 in the morning, or whatever and I saw an email from India.

You know, my eyes were not adjusted yet, so I just saw words, like I sort of saw “Katye”, and then I saw words which were like a scary size.

But it took a while before my, my eyes could adjust enough to actually read it.

Yeah, thats how I found out.

She died.

- [Dr. Rela] It's difficult to think over all of it.

I mean, I'm very saddened by Katyes death.

It was very unexpected.

She had a problem with her hepatic artery and I used a small part of her hepatic artery.

Perhaps that was a mistake because the artery was probably not completely healthy and it thrombosed.

That was what we call an insult to the liver.

What happened from that insult was probably, she had some necrosis of some parts of the liver from that insult and from then on really, she never became completely normal.

Her liver function tests were quite abnormal for a while and she developed some septic episodes and finally she died of sepsis really.

It's a failing really.

It upsets me enormously.

I don't know what else I can do.

- [Slavin] Unfortunately, it didn't end the way we wanted.

Not because of Dr. Rela or because the theory was wrong, but rather because of the fact that she was so sick.

Maybe that contributed to the complications.

The bottom line is she's not with us.

That's very sad, of course.

- I do question whether I should have done it in the first place.

(seagull sounds) (waves lapping) - Katyes death is just crushing.

As Katie was being wheeled into the surgery, she said, “Well Howard, you got me into this.” In a way, I mean, even the artery that thrombosed was my idea, right?

(phone buzzing) Appliance Timers.

- (indistinct) - That SF number is the number of spitfire controls, but I need the Frigidaire number and that starts with, okay... Now, I work all the time so that I don't have time to feel depressed.

It's just, you know, it's just changed my life a lot, you know?

(people chattering) (baby crying) - [Caroline] Ezee.

(people chattering) (mellow music) - [Jacob] Surprise.

Now that I am living with my wife and son.

The first time I remember seeing Caroline in India, she like just kind of stood there and looked at us like a deer in the headlights.

'cause she, I guess in one moment resigned herself to being the giant American's nurse.

- Id never seen a huge man like that, but, I liked him.

(people chattering) - I wouldn't qualify it as fate, 'cause to me that means it's already written.

When people ask me that and it's like, “You dont believe that was God's plan.” It's like your sister has to get this terrible cancer, need to go to India and die just for you to meet your wife.

No.

If that is a plan, that is a terrible plan.

(people chattering) You wanna see it?

- Yeah.

- It's big.

- It's big.

- And I, I'm still pulling hairs out of the side from where they cut.

Very unpleasant.

Having to dig those out with two to three needles and getting multiple angles, yeah.

(people chattering) I notice I get tired faster and I know I can't lift as much as I used to.

I'm as good as I can be.

I guess, if you wanna put it in percentages, I would say I'm like 75 of what I was before.

I can't feel my left foot.

I think they hit a nerve here when they took that vein.

It's like when I'm walking, I'm really paying attention that the floor is actually under my foot.

It's not the most fun thing in the world, but do it again if I could.

The most important thing is I want Kayte to be remembered.

She's no longer here, but she's definitely not gone.

(intense music) - [Dr Fuchs] Well, I thought he was a telemarketer.

No, I'm just kidding.

You know, I was pretty impressed with Howard's idea and in fact we are going to be doing it at Johns Hopkins.

I have to say that, in a way, learning about Katye Hollingsworth was what made the trial happen.

You know, here's a person with an unwillingness to sort of accept dogma, who said, “I'm not gonna go out, you know, timidly” and you don't oftentimes see that.

- [Howard] This new trial is the idea as what we did in India, but it'll be done in a slightly different way.

Now that we're doing it at Hopkins, we're first doing the liver transplant and then we're gonna do immunosuppression and then when the liver is deemed to be healthy enough, well enough regenerated, we're actually going to use a full bone marrow transplant, which is full chimerism.

And then by the time we're done, after a couple months, hopefully there will be permanent tolerance and then we can remove immunosuppression and hopefully everyone lives happily ever after.

- [Dr Slavin] I'm proud of the fact we did not give up.

That is the credit to Howard, as well as Dr. Rela who was courageous enough to try something new and I hope that he will try to do it again.

- [Dr Rela] I'm ready for it.

If you're not prepared to face failures, you can never innovate.

- For a long time I was depressed because Katye died.

But, I just have to remember that she preferred it that way.

That is she preferred to die trying to do something beneficial for the whole world.

If you invent a treatment to, to treat a particular patient, that trial would be an n of 1, which means the number of patients in the trial is one.

- [Cecilia] She passed away a week before her 27th birthday, but she has left a legacy behind her.

I'm proud of her.

Somebody has to be first in everything.

- [Jacob] She said, “Something has to be done so I'm gonna do it.” That's what Katye always said, “I'll do it myself.” That's what she did.

- [Tal] I think that that's the kind of person when everyone else is saying there's nothing that can be done This one person is not afraid to go and change the world.

- [Howard] You know, the thing is that many people, they have an idea that could make a difference, right?

- [Dr Fuchs] Good ideas can come from anywhere.

You can't have such an ego that you reject something out of hand because you never know where a good idea is gonna come from.

It could come from, you know, basic biology, it could come from physics, it could come from some guy that's walking down the street, you know.

(phone ringing) - Appliance timers.

What's your symptom?

(mellow music) (mellow music continues)