0:02

This

0:02

is an ABC podcast. This

0:05

is Science Friction. I'm Natasha Mitchell and

0:07

in recent shows I've been bringing you all sorts of staggering

0:09

stories about kids. Stories

0:12

I've collected over the years about children whose

0:14

lives have intersected with science in extraordinary

0:17

ways. And today's story is one

0:19

I will never forget. One

0:22

of a kind. In it, a chance

0:24

encounter, a medical mystery, a

0:26

detective quest, science at

0:29

the cutting edge, and one

0:31

hell of a tenacious kid.

0:37

We were talking one day about garden gnomes

0:40

and people not liking them and that.

0:43

And this was when he was young. He said,

0:45

Mum, what's a garden gnome? And

0:48

I said, oh, it's a sort of a cartoon

0:51

statue of a dwarf person.

0:53

He said, oh. Anyway, we'd been away

0:56

on a holiday or something. We pulled up in the driveway

0:58

and he said, well, Mum, the gnome's

1:00

home.

1:03

Hollywood

1:05

could not script something more

1:09

tragic and beautiful

1:12

and bittersweet. I

1:14

think I learned that

1:17

you have to go with your gut feeling

1:20

when you are faced with uncertainty.

1:23

People think medicine and science, you

1:26

know, we've progressed to a particular phase

1:28

in history where we know so many things.

1:32

What I think people don't realise is

1:35

how much we don't know. So

1:38

this is the story of Robbie and the

1:40

DNA detectives. My

1:43

name is Vivian McKee, Robbie's

1:45

mum.

1:46

Gregory McKee, Robert's father. How

1:48

do you? She was infatuated,

1:50

don't worry about that. Cut that out.

1:54

Greg and Vivian fell in love and

1:56

had two boys. Robbie, born in 1982.

1:59

and Stephen two years later. But

2:02

something was up with Robbie from the very beginning

2:04

of his life. We used to

2:07

go to the baby clinic all the time and

2:10

the sister would say to me, you

2:12

know, his head's growing really fast. Robbie

2:16

was found to have a mutation in

2:18

a gene called FGF-R3. It

2:21

causes hypochondroplasia, which

2:24

is a form of dwarfism. But

2:26

then came the genetic double whammy.

2:29

Robbie and his brother Stephen were

2:31

diagnosed with another rare

2:33

genetic mutation that meant they didn't make vital

2:36

immune cells called B cells. They

2:38

pretty much had no immune system. And

2:41

for the rest of their lives, that meant they'd

2:43

have to crowdsource their immunity

2:45

from monthly infusions of immunoglobulin

2:48

containing antibodies pulled from hundreds

2:51

of blood donors.

2:53

But that didn't hold the boys back.

2:59

Fast forward to 2013, and

3:02

Robbie's life is powering along. He's

3:04

holding down a long-term, secure

3:06

job managing a liquor store. He's

3:08

heading to the World Dwarf Games

3:10

in the US to compete in basketball,

3:14

table tennis and soccer. And

3:18

he's in love. Oh, totally.

3:22

Head over heels. He

3:24

met a girl in America and we

3:26

thought, oh, you know, he's coming to his own. Everything's

3:29

going well

3:29

for him. You know, there was talk of marriage

3:32

and all that sort of stuff. And she

3:35

was wanting him to go over to America. We

3:37

weren't sure whether that was gonna be a

3:39

really good idea with his conditions. But

3:42

go to America, he did.

3:46

It was Independence Day,

3:48

I think. He was with his girlfriend

3:51

and her family and they had a family

3:53

picnic I gather and they went tubing

3:56

down the river. He got

3:58

bitten by a mosquito and he...

3:59

got really sick, massive

4:02

headaches and vomiting and

4:05

she wanted to take him into the hospital but he said no

4:07

I'll be fine. And very little

4:10

thought was given to that mosquito bite after

4:12

that. Robbie returned to Australia

4:15

and went back to work but he

4:17

was unusually tired.

4:20

Then one morning, the 11th

4:23

of September, just after four

4:25

o'clock, we heard this almighty being

4:27

in the hallway.

4:29

Something was very wrong. He

4:31

was trying to make it into our bedroom and

4:34

he had some tiny clinic seizures. So

4:36

he was rushed into hospital

4:39

to the intensive care unit where he spent

4:41

about three days. Robbie

4:42

was in and out of hospital after this.

4:45

Something very strange was going on. Things

4:48

were smelling and tasting strange to

4:50

him. It turned

4:51

out these were all it was having.

4:53

He was imagining it was the mind tricking

4:55

everything. The specialists

4:58

suspected epilepsy may be triggered

5:00

by a viral infection in the brain. His

5:02

brain was clearly inflamed. They

5:04

hit him with everything. They thought whatever

5:07

was there would be gone by the time

5:10

within the couple of days because all the

5:12

antibiotics, antivirals are hit him with.

5:15

It takes a lot for

5:17

an infection, a bug

5:20

to reach our brain doesn't it?

5:22

I mean generally our body does its very best

5:24

to protect that precious organ of ours inside

5:26

our skull.

5:27

Totally right. Professor Michael

5:29

Wilson is a neurologist at the

5:31

University of California San Francisco and

5:33

he's one of our DNA detectives

5:36

in this story.

5:36

It's a real pain in the butt

5:39

frankly for people who are trying to develop

5:41

drugs, for diseases that

5:43

affect the central nervous system because

5:45

those drugs have to be designed in a special

5:48

way to get through that blood brain barrier.

5:51

So it can be make it difficult for drug

5:54

development but on the flip side it's a wonderful

5:56

thing for keeping out infections

5:58

and toxins from the brain.

5:59

In Robbie's case, they

6:02

just couldn't work out what had attacked his

6:04

brain. But he seemed to improve.

6:07

He came back home and went back to

6:09

work. But over the next two

6:11

years, it became clear something was

6:14

still wrong. Robbie had changed.

6:16

He wasn't the happy-go-lucky,

6:20

relaxed guy he was before. He was

6:22

very uptight and very

6:24

edgy. His memory had gone

6:27

on him. And

6:29

he got really emotional.

6:30

Yeah,

6:33

he was different completely. He

6:36

was probably very scared, but

6:40

never said anything really.

6:44

The weird symptoms kept coming and coming.

6:47

And he had these unusual ticks, you

6:49

know, you could hear him swallowing in

6:51

the back of the car. It

6:54

made you feel like gagging because that's

6:57

how it sounded in his throat, you know.

7:00

He got rashes, conjunctivitis,

7:03

the shakes. He had two sinus

7:06

operations. There were many times

7:08

that we lobbed into emergency,

7:11

but no one could work it out. Eventually,

7:14

we met with Dan Swan at

7:17

Westmead Hospital.

7:18

So I met Robert

7:21

in February of 2016. Who

7:23

was a godsend to us? I'm a

7:26

clinical immunologist and immunopathologist

7:28

at Westmead Hospital. And I hold

7:30

a second role at Garvin

7:32

Institute, where I'm a research officer in

7:35

the immunogenomics and B cell biology

7:37

laboratories.

7:38

Dr Dan Swan remembers that first

7:40

day. Robbie wasn't walking

7:43

well. He was holding his father's hand

7:45

to steady himself.

7:46

Immediately, it struck me that

7:48

this was an incredibly rare scenario that

7:50

I was already witnessing. Probably

7:53

something no one else has encountered either.

7:57

And when Dan Swan saw the scan of Robbie's brain...

7:59

That is an incredible MRI brain scan

8:02

for a 33-year-old. His entire

8:05

brain was incredibly shrunken, and

8:07

the space that had been left

8:10

is filled with cerebrospinal

8:12

fluid, the fluid that surrounds your brain.

8:14

Dr. Swann admitted Robbie to hospital.

8:16

He needed to investigate further and

8:19

urgently. That's when I got Andrew Duggins

8:21

involved. Andrew and I see a lot

8:23

of very unusual patients together, and I trust

8:25

his judgment. My name's

8:28

Andrew Duggins. I'm a clinical neurologist

8:30

at Westmead Hospital in Western

8:33

Sydney. It became apparent,

8:35

even at that stage, we looked into his case. He

8:38

had had this slow decline

8:40

over the preceding three years.

8:42

I mean, it seemed that his brain was dementing.

8:45

Yes. I thought, somehow, this

8:47

has to relate to his profound

8:50

immunodeficiency, his inability

8:52

to fight infections.

8:53

So began Dan Swann's determined

8:56

hunt, who

8:58

just didn't leave anything, any

9:00

stone unturned. We went for every

9:03

test possible.

9:04

So I think it would be safe

9:06

to say... I got the textbook out. Robert

9:08

had the most extensive

9:11

testing... And looked at all

9:13

the possible causes of chronic

9:15

brain infection. The different herpes viruses...

9:18

Rare things... Fungal things... Bacterial infections...

9:21

Dozens of different viruses... Repeated lumbar

9:23

punctures or spinal taps, and you test the

9:25

cerebrospinal fluid in which the brain

9:28

and the spinal cord is bathed. Put

9:30

the fluid in multiple types of culture

9:32

media... To see if anything appeared spontaneously

9:34

in an unbiased way. We did everything we could. And

9:36

the result? We found nothing. We got nothing.

9:39

They still couldn't find anything. But still, we thought,

9:41

this must be an infection. Andrew

9:46

Duggan's then came serendipity. Yes.

9:49

And you happened to be, in America, a chance

9:51

encounter. By now, it's early 2016.

9:55

Things are very, very desperate for

9:58

Robbie and his family.

9:59

Dr. Andrew Dargons is heading

10:02

to the American Academy of Neurology meeting.

10:04

We think of a room with 10,000 neurologists

10:07

in it, a scary prospect, but there was a

10:09

speaker who was presenting the

10:12

greatest advances of the preceding 12 months

10:15

in neurology generally. And

10:17

just one of a whole range of things she

10:20

mentioned was this metagenomic

10:22

deep sequencing or sometimes called next generation

10:25

sequencing and mentioning the successes

10:27

of the Joe DeRisi lab, Michael

10:30

Wilson and his colleagues at University

10:32

of San Francisco, California.

10:34

What Andrew heard that day made

10:36

him sit up. The team mentioned

10:39

was using a cutting-edge genomic technique

10:42

to essentially solve extraordinary

10:44

medical whodunnits and the results

10:46

they were getting for some of their patients were

10:49

equally extraordinary.

10:50

You can imagine I was just one of these 10,000 people

10:53

in the audience but pushed my way to the front to

10:55

try to catch this speaker before she left

10:58

the podium at the end of the session to say, oh, who

11:00

are these people and how would I get in touch?

11:03

And she just basically said, oh, well, Michael

11:06

Wilson is very keen on getting some

11:08

samples. He's got the technology, he's got some

11:10

funding, send him an email.

11:13

So that's just what Andrew Dargons did. So

11:16

it was an email by Dr. Dargons. I

11:18

didn't know him personally, but he

11:20

had attended a neurology

11:23

meeting in the US. Well, I was

11:25

very surprised. He emailed back almost

11:27

immediately saying, yes. My name is

11:29

Michael Wilson. I'm a neurologist at the University

11:31

of California, San Francisco.

11:33

And Michael specialises in infectious

11:36

and autoimmune diseases that target our

11:38

central nervous system. So diseases like multiple

11:40

sclerosis and HIV, but

11:42

also more obscure viral and

11:45

fungal infections.

11:46

You know, most of these cases,

11:49

they're acute illnesses that present over

11:51

days to two or three weeks,

11:53

but

11:54

some go on for years, even

11:57

decades undiagnosed or misdiagnosed.

12:00

after thousands and thousands of dollars

12:02

of tests and treatments. There's

12:05

the story of the construction worker whose

12:07

mystery illness turned out to be... wait for it.

12:10

The

12:10

organism in this particular

12:12

case turned out to be pork tapeworm. Oh,

12:14

yeah, I really hope you're not eating right now. Or

12:18

there was the fellow who carried the rubella virus

12:21

replicating in his eyeball for

12:24

over 20 years before it

12:26

was diagnosed. This team are

12:28

radically reinventing how

12:30

diseases get diagnosed. And

12:32

a trailblazer behind the technique they're

12:34

using is this man.

12:36

My name is Joseph Derisi, I'm a professor

12:38

in biochemistry and biophysics at the University

12:40

of California, San Francisco, and I'm

12:43

the co-president of the Chan Zuckerberg Biohub.

12:45

Well, effectively, you're a medical detective these

12:47

days. Some people have called you a maverick.

12:50

You've called yourself a biologist who is

12:52

a serious computer nerd. How

12:55

would you describe you and what you

12:57

do now?

12:58

Well, my training is really in biochemistry,

13:01

but I also have a love of infectious disease. And

13:03

I remember growing up in the 80s in high

13:05

school, wondering why

13:08

it was taking so long to figure

13:10

out what the cause of AIDS was. I've

13:12

always enjoyed the thrill of discovery and investigation.

13:15

And so trying to solve

13:17

difficult to diagnose cases is always

13:20

something we've kept on the side of something really

13:22

fun to do. Yeah,

13:23

I know. Only an inquisitive scientist

13:25

would describe infectious diseases as fun. What's

13:28

been the traditional approach

13:31

to diagnosing a disease,

13:34

a mystery illness, to begin with? Well,

13:38

the model for diagnosing a disease, especially

13:40

an infectious disease, hasn't changed that much in a long,

13:42

long time. You know, thorough patient

13:45

interviews and physical exams and

13:47

that sort of thing leads a clinician

13:50

to make very educated guesses about

13:52

what might be there. And

13:54

there's usually confirmed by some kind

13:56

of diagnostic assay. And

13:58

that's all well and good.

13:59

works a lot of the time. However,

14:02

there are many cases in which it doesn't work

14:04

and the guess is wrong.

14:06

Joe Derisi and Michael Wilson

14:08

want to put an end to that guessing game. Instead

14:11

of a doctor testing for diseases

14:13

they think a person might have, they're

14:16

using this next-gen sequencing to test

14:18

for everything in the know-and-universe

14:21

a patient could have.

14:22

These machines now enable us to sequence

14:25

millions if not billions of pieces

14:27

of DNA or RNA from a sample.

14:30

And therefore, we can just sequence

14:32

everything that's in a patient sample regardless

14:35

of whether it's human or not. And

14:37

that makes the informatics challenging

14:40

because you're looking for a needle in the haystack at the end

14:42

of it. But on the other hand, it's

14:45

very unbiased simply to ask

14:47

the question, what is

14:49

not human in this sample?

14:51

I mean, that's a fantastic question

14:53

because we are more bacteria than

14:55

we are human, aren't we? When

14:58

we're talking about the gut microbiome or the total

15:00

number of cells in our body, that's absolutely true.

15:02

However, there are locations in our body

15:04

that truly are sterile. The central nervous

15:07

system and the fluid that surrounds it is

15:09

pristine. A healthy CSF

15:12

sample looks like Evian water. So right

15:14

off the bat,

15:15

we know that there was something in there that didn't belong.

15:18

We didn't know what it was. And therefore,

15:20

the next part of the computational pipeline is to

15:22

compare the remaining sequence to the known

15:24

universe of other sequence that isn't human.

15:27

You know,

15:28

hundreds of thousands of piece jigsaw

15:31

puzzle against a million piece

15:33

jigsaw puzzle matching game.

15:37

Which involves an enormous database

15:39

of everything that's ever been sequenced

15:41

by science and data's pouring into

15:43

that public database every day across

15:46

the world. But back

15:48

to Robbie McKee, because

15:50

the damage to his brain and body

15:52

from whatever was afflicting him appeared

15:54

to be irreversible.

15:56

One option is always to do nothing.

16:00

And we thought about that and

16:03

we discussed my fears about

16:06

finding something that we couldn't treat. And

16:09

we all decided that Robert

16:13

would want to know what was wrong with him. Everyone

16:15

who loved him wanted to know what was wrong

16:17

with him and so did his doctors.

16:20

There

16:20

was no results here in Australia,

16:23

so it was the only way to go. The

16:26

Americans were very confident that they'd

16:28

get a result. If I wasn't an option, they

16:31

believed we'd get an answer.

16:31

But the Westmead team first

16:34

had to get uncontaminated samples

16:36

from Robbie's brain from Sydney

16:39

all the way to San Francisco intact.

16:42

I remember they told us we need to send them a piece

16:45

of brain that's about the size of

16:47

the eraser on the end of your pencil.

16:49

A tiny sample, but

16:51

a very big deal because it involves full-blown

16:54

brain surgery and highly sterile

16:56

procedures, but they managed it.

16:58

FedEx. It came

17:00

by FedEx. Now the race was

17:02

on to work out what wasn't human

17:05

inside Robbie's brain and cerebrospinal

17:07

fluid.

17:08

I'm embarrassed to say it was midnight

17:10

on a Saturday night. Not 22

17:13

anymore and out on a Saturday night.

17:16

A handful of years ago, the results might

17:18

have taken a week. Now we're talking about 15 minutes

17:21

of processing at a cost of around US$2,000.

17:24

And that price is only set to fall,

17:26

so this could all become commonplace.

17:29

And so the data

17:31

came out in around midnight. In

17:33

both samples there was this

17:36

virus that I honestly had

17:38

never heard of before.

17:39

There weren't a lot of sequences matching it,

17:41

but it was in both samples from Robbie

17:43

and that was telling. Michael Wilson

17:46

did what he needed to do to be more certain. And

17:48

then he got on the email again in the middle of the

17:50

night.

17:51

I was a bit nervous to email

17:53

back the doctors in Australia

17:55

because one of the first things I read

17:57

about this virus was that It

18:00

and cousins of it had been seen in different

18:03

parts of the world, but never in Australia.

18:05

Which meant they might have a quarantine

18:08

issue on their hands. That left me

18:10

a bit unnerved. So what did they find

18:13

in Robbie's sample? We found a virus,

18:16

and the virus is called Cache Valley

18:18

virus. And it's something we had never

18:21

seen before, and frankly, I'd never

18:23

heard of. So Cache

18:25

Valley was discovered in the 50s

18:28

in Cache Valley, Utah. What we

18:30

now know is Cache Valley is a virus that's

18:32

mosquito-borne, and it's usually

18:34

in livestock. Sheep

18:37

and cattle and things like this. But it is not

18:39

a well-studied virus, and in humans,

18:41

incredibly rare.

18:42

In fact, there'd only been three

18:45

other reported cases, all in the

18:47

United States, and all showing

18:49

symptoms for only a short period. Not

18:52

three and a half hellish years like

18:54

Robbie.

18:54

And there's really not a lot known

18:57

about it. There's some studies

18:59

in which they've surveyed

19:01

forest park rangers in the United States

19:04

to see how many of them have antibodies

19:06

to this virus, and actually about five

19:08

percent did. So it looks like

19:11

there probably are more people exposed

19:14

to it than we realize. But

19:16

not in Australia. So remember

19:19

that single mosquito bite that Robbie

19:21

had caught while tubing down a river in South

19:23

Carolina back in 2013? That

19:26

was the likely culprit.

19:27

So

19:29

I ran back to the office of the microbiologist

19:31

in my hospital.

19:32

Dan Swan got Michael's email

19:35

from San Francisco. And I said

19:37

to him, do we need to

19:39

issue a public health report through

19:41

any of the government systems

19:43

that we operate within? And

19:45

he said, well,

19:47

the first thing we need to do is we need to confirm

19:49

it. And we were still in the process of doing all of

19:51

this. And then we would

19:53

let relevant people know.

19:55

His colleague, neurologist Andrew

19:57

Duggan, wasn't convinced. At

19:59

first, like...

19:59

I think most other people I was a little

20:02

skeptical. I thought, you know,

20:04

these Americans, they've just looked for their own viruses.

20:07

I didn't really understand the technique at the time. So

20:09

I immediately did some reading and found

20:12

that an Australian group had just a

20:14

month or two before isolated

20:16

a sort of similar virus.

20:19

I emailed back Michael Wilson said, great

20:21

work, Michael, but surely

20:23

it's actually this Australian virus. But

20:26

he pointed out to me that in the analysis

20:28

that they'd already done this

20:29

single report of this Australian

20:33

orthobunya virus had already made it into

20:35

their database. And it was already one of the things

20:37

that they had excluded.

20:38

Still, as Dan Swan puts

20:41

it in science, extraordinary claims

20:43

require extraordinary evidence. They

20:46

needed to confirm that Robbie had

20:48

been exposed to this unusual virus.

20:51

But the thing is, he didn't make antibodies to any

20:53

viruses at all. So that wasn't straightforward.

20:56

They worked out that they needed a special tissue

20:59

stain to detect the virus in

21:01

Robbie's brain sample.

21:03

It was on the maybe fifth Google

21:05

search where I found

21:08

a veterinarian at Texas A&M

21:10

University who had done her PhD

21:14

on how Cache Valley infects

21:17

the brains of sheep. And

21:19

that was the only person who I

21:21

could find who had published a paper in which

21:23

they'd done these special stains that could

21:25

detect this virus. And

21:27

so I emailed her.

21:30

And Dr Aileen Hoffman replied, Michael

21:33

sent the tiny remaining sample of

21:35

Robbie's brain tissue to her in Texas for staining.

21:39

And sure enough, Cache Valley

21:41

virus was there.

21:44

This is when you need to stay

21:47

up late at night on your computer and

21:50

trawl through the literature for

21:53

anything that you think might be

21:55

helpful.

21:58

Incredibly, a diagnosis has been made. had

22:00

landed. Finally, it

22:02

had taken over three and a half years. But

22:05

Cache Valley virus has no treatment,

22:07

so was it too late for Robbie? Dan

22:10

Swann was dogged at this point. He didn't want to give

22:12

up on Robbie.

22:12

So I only turned

22:14

up two things. Dr Swann

22:17

decided to import immunoglobulin

22:19

sourced from American blood donors in

22:21

case it had antibodies to Cache Valley virus.

22:24

We could make him better. He

22:26

could have no impact. There was

22:29

a paradoxical chance we could

22:31

make him worse.

22:32

The infusion didn't work. Dr

22:35

Swann also wrote to a Japanese

22:37

pharmaceutical company developing a drug targeting

22:40

the family of viruses that Cache Valley

22:42

virus belongs to. The emails

22:45

went backwards and forwards for days.

22:47

Would they share it on compassionate grounds, even

22:50

though it hadn't been tested in humans

22:52

yet? It was risky.

22:54

I was slightly relieved

22:56

when they said no in the

22:59

end. My greatest fear was that

23:01

we found a drug that would stop

23:03

the virus replicating and therefore

23:06

stop Robert deteriorating, but

23:09

not improve him, because his

23:11

brain was already so shrunken. He

23:14

was now 34.

23:15

We would keep him in this state, possibly

23:18

for decades. And

23:20

that felt incredibly cruel. We

23:23

told him he had Cache Valley virus.

23:25

We lied to him. We didn't tell

23:28

him the gravity of it. I don't know

23:30

if that was the right thing, but we told

23:32

him,

23:33

we're going to get through this like we get through everything

23:35

else.

23:40

But to get the diagnosis, it

23:43

gave us some sort of relief

23:46

to know that we had left

23:48

no stone unturned and that we'd

23:51

realised that we had done everything possible

23:54

to solve

23:54

it for

23:54

him. You

23:57

can protect

23:59

your children. You can drive them everywhere

24:02

so nothing happens. And

24:06

you get taken out by a mosquito. It's

24:10

unbelievable. In meeting

24:13

this girl in America, he

24:15

was doing what

24:17

every human being wants

24:19

to do, right? He was trying

24:22

to find love. He was trying to explore

24:24

the world despite the

24:27

incredibly bad hand that he had been dealt. And

24:29

he was in the process of that radical self-expression

24:33

when this third incredibly

24:35

rare thing happened to him.

24:37

You just, you can't script that. Robbie

24:41

died in 2017. Robbie's

24:43

father, Greg, died in 2019. My

24:46

thanks to the family for sharing their story so generously

24:49

and also to Drs. Dan Swan,

24:52

Andrew Duggan and Professors Michael Wilson

24:54

and Joe Derisi. I'm Natasha Mitchell. Next

24:57

episode, in real wild child

24:59

on science friction, the secrets

25:02

inside yourselves. I'll

25:05

catch you

25:05

then. And catch me over on the Big

25:08

Ideas podcast now too. I'm the

25:10

new host of Big Ideas, your front

25:12

row seat at some of the best talks, forums

25:14

and festivals across Australia and the world. Find

25:17

it on the ABC Listen app or wherever

25:19

you get your podcasts. And if you love radio,

25:21

you can catch Big Ideas nightly, Monday to

25:23

Thursday, 8pm on ABC

25:25

Radio National, right across Australia.

25:28

See you there.