The cancer drug, the faked data and the superstar scientist

Mark Smyth was one of Australia’s very top cancer scientists. Or, as one former colleague puts it, “the god of immunology."

But Smyth was a god who fell to earth and doubt now surrounds his work after a public unravelling.

Today, The Age and Sydney Morning Herald's national science reporter Liam Mannix on Smyth’s so-called “lab of secrets”, and his faked data, which now underpins a cancer drug being given to patients. 

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Episode Transcript

S1 (00:03):
From the newsrooms of the Sydney Morning Herald and The Age.
This is the morning edition. I'm Samantha Selinger Morris. It's Tuesday,
July 29th. The mouse should have been sick. Very sick.
It was part of a cancer experiment, and it should
have received a big injection of cancerous cells and then

(00:26):
had surgery. But the scientists who captured undercover footage of
the mouse say there's no evidence of cancer or surgery
or injections. There was a name attached to these mice,
Mark Smith. Smith was one of Australia's very top scientists or,
as one former colleague puts it, the god of immunology. Today,

(00:49):
national science reporter Liam Mannix on Smith's so-called lab of
secrets and what it means for a cancer drug that
is still being tested on patients. So Liam, this story
is absolutely crazy and I'm having to restrain myself from

(01:09):
just peppering you with a billion questions because I have
so many. But let's just start with the basics. Who
is Mark Smith?

S2 (01:16):
So Mark was an immunologist. He was one of Australia's
very most important researchers. He was right at the top
of our scientific firmament. He's working at the intersection of
cancer and the body's immune system. And Mark takes an
interest in this burgeoning field of cancer immunology, this idea

(01:37):
that you might be able to use the immune system
to attack cancer. Everybody's very sceptical. Mark's a true believer.
And it turns out that he's right. We get these drugs,
these cancer immunotherapy drugs called checkpoint inhibitors, which the audience
might have heard of. And these are miracles. They melt
away tumors. The people who invented them receive Nobel Prizes.

(01:58):
So Mark's right at the forefront of this field. That
looks like it is changing cancer forever. He's winning huge awards.
He's winning huge amounts of taxpayer research funding, $42 million,
all told, plus charitable contributions, plus money from biotech companies
who want to develop his ideas. One of the people

(02:20):
close to him who we spoke to described him as
like a god, the God of immunology, and his students
and his staff are just in awe of his skills,
his ability to do what he's done.

S1 (02:33):
And of course, that leads me to my next question,
because as you've written, he was a God that fell
to earth. So what happened?

S2 (02:40):
Yeah. In 2021, I received a tip that something had
gone badly wrong at Qimr Berghofer. This is a very large,
very well funded research institute in Brisbane. It's in this
beautiful glass tower with views of the river. It emerged
following that tip that Qimr had been conducting an investigation

(03:02):
of Mark Smith and that investigation concluded that Mark had
committed serious research misconduct. Clearly, something extraordinary had happened up here.
But shimmer, beyond telling us what they'd found about Mark,
were extremely reticent to tell us what had actually happened,
what Mark was alleged to have done, and what science

(03:22):
was affected. They resisted our inquiries. They resisted our freedom
of information applications. So in the end, we really had
to do a big piece of investigative journalism to really
try and answer the question, what actually went wrong here?

S1 (03:35):
And, you know, you did this investigation. You spoke to
many of his former colleagues and I guess, take us back.
What were some of his colleagues noticing about his research? Because,
as you discovered, it stemmed before he started at Qimr
Berghofer to his previous employer many years ago. So what
did you find?

S2 (03:54):
Our investigation stretches all the way back to when Mark
was working in Melbourne at the prestigious Peter MacCallum Cancer Centre.
One important thing to know about Mark is that throughout
his career, he has published a lot of papers. Some
of his colleagues described him as almost a publishing machine.
When he was at Queensland. In just seven years, he

(04:15):
published more than 200 papers, which is a pretty extraordinary number.
So he's putting out a lot of papers and his
results are really impressive. So much so that other research labs,
other teams are trying to replicate them. This is a
very common practice in science. You see somebody do something
and you try and get the same result in your lab.
Sometimes Mark's results could be replicated, but sometimes they couldn't.

(04:37):
And the researchers would ask themselves, why can't I replicate
these results? And typically they thought it was their own fault,
that their hands weren't good enough, that their mice weren't
good enough, that they just weren't quite as good as Mark.
So in 2006, Smith had a research paper which he
had co-authored, published in Nature Immunology, retracted. And this was

(04:59):
sort of the first black mark against his careers. We
then go forward to 2012. And here's what we were
able to reveal on the weekend in 2012. According to
a leaked copy of a secret investigative report from the
University of Melbourne, Marx PhD student was working on a
research project involving mice. The results didn't look particularly promising,

(05:24):
which is classic in science. You do a lot of
experiments and sometimes they don't work. Then, according to the
report of the secret investigation, Mark approached this student and said,
I've been running this experiment myself as a side project.
I have some additional Mice data which we could combine
into one that would make your experiment look much more positive.

(05:46):
This is good news for researchers. They're looking for positive
results so they can publish at research labs like Peter Mac.
Mice are really closely tracked. They track where they live
and when they die and what experiments are run on them.
Mark's student went and checked the database and could find
no record of these extra mice, which raised concerns, he said.

(06:06):
Are these mice real? He took that back to Mark
and said, well, I can't find the record of these.
And Mark, according to the investigative report that we have said, oh,
let's toss the data. If we're not sure about the mice,
let's toss the data. The student instead reported concerns to
Peter Mac. Now, Peter Mac then launched an investigation. And
this investigation, I think is pretty extraordinary and pretty dramatic.

(06:30):
So first, they find that Mark's personal lab book contains
records for 14 of these mice, but they're not very convincing.
They're sort of crowded into unlikely spaces. Six additional mice,
which takes the total to 20, were recorded in the
book of a lab assistant. A third party. But this
lab assistant told the inquiry that she had no memory

(06:51):
of these mice, and that she did not write those
notes in her lab book, and that the handwriting was
not hers. Peter Mac conduct a preliminary investigation and find
that Mark has a case to answer. But in this case,
with an unusual arrangement the Arrangement. The University of Melbourne
is in charge of doing the full investigation. On the
day of the University of Melbourne's hearing, Mark's luck turns

(07:14):
a Peter Mark employee turns up and produces a new
data sheet written by Smith and then mislaid. The employee
says that they found this while cleaning out his office,
and this contains an error riddled record of 20 of
the mice. Now, the University of Melbourne bring in a
handwriting expert, and they find that this rediscovered sheet of

(07:34):
paper and the records from the lab assistants book, the
ones that she says she didn't write, are likely written
by the same person. And that person may have been
Mark Smith, but the expert wasn't sure. And so in
the end, the University of Melbourne found Mark was cleared
of all the charges.

S1 (07:58):
Okay, so let's go to the next step because then
he moves to Qimr Berghofer. And then within a pretty
short period of time, colleagues There also have concerns about
his lab work, and at least one of them asked
him about it and his response was interesting, right? It
was brazen. He seemed unafraid. You know, when a fellow
scientist approached him with concerns to tell us what happened there.

S2 (08:20):
That's right. Sam. So this lab is becoming, according to
the people we've spoken to, quite a toxic place. One
researcher described it as a lab of secrets where you're
not sure who you can trust, you're not sure who
you can talk to, and you're worried that things are
going badly wrong. In one case, one of the researchers
was worried that Mark might tamper with her experiments, and

(08:41):
so they asked for additional mouse testing. Mark refused. And
here's an email that he wrote. If you are implying
we might not be trusted and break the rules, it
is insulting to us all. Please show a bit more
tact writing emails. If you want people to keep helping you,
you have to show some judgment or research. Science will
be a very difficult place for you long term.

S1 (09:03):
And so walk us through this. First of all, there
was numerous whistleblowers, but they according to your research and
your stories on this, they had extraordinary difficulty with actually
knowing who to report to. And then when they did
report it to someone, they got no answers back. That
sort of weren't very helpful. So tell us what this
process was like for them.

S2 (09:25):
Yeah. These people are incredibly, incredibly brave and courageous. There
was no benefit to them for doing what they did.
They were taking on one of the most powerful people
in science in Australia. They were damaging somebody who was
their co-author, which automatically puts all of their own research
into question. But they felt that they had no choice

(09:47):
but to do the right thing. But doing the right
thing proved very, very difficult. Sam. According to an internal
investigation conducted by shimmer, it was almost impossible for these
people to report wrongdoing. Air seemed unable to help. There
was no office for research integrity for at least some
of the time, and the whistleblowers felt that if they

(10:10):
came forward with a full complaint, they may face retribution
or exposure of their identities. They then tried to take
this case to independent bodies. They approached the National Health
and Medical Research Council, which is kind of the chief
body for research integrity in Australia, and they approached the
office of the Chief scientist. And in both cases, those

(10:31):
organisations came back to them and said, sorry, we can't
help you with this. You need to bring this complaint
to Qimr. And this is a really important point, Sam.
The central feature of Australia's Research Integrity System is that
universities and research institutes are responsible for running the investigations

(10:52):
of complaints themselves. Essentially, they're investigating themselves and their own employees.
And as many people have said to us as Kim Carr,
the architect of the system, said to us today, this
creates an almost intolerable conflict of interest because these organisations
are required to regulate themselves and they are required to
investigate themselves.

S1 (11:21):
We'll be right back. So, Liam, do you have any
idea or any sense from your investigation about just how
widespread alleged dodgy research is?

S2 (11:34):
The answer, I think, Sam, is it is uncommon or rare,
but it's also much more common than people would think.
Since we ran this story, the number of people writing
in to say, oh yes, this was common knowledge this
was known about has really well, it hasn't surprised me
because I sort of knew that that's the picture. But

(11:56):
there was an interesting study done a couple of years
ago looking at PhD students. They're sort of the people
who make Australia's science system work, asking them what percentage
of them had seen questionable research practices. The number was
Troublingly high. I think it was around 25%. It's a
big number, isn't it? But it also answers the other question,

(12:17):
which is we know that a significant amount of research
findings aren't reproducible, and some of that's probably chance. And
some of that is probably bad research practice, but some
of that is likely to be research misconduct as well.

S1 (12:30):
Okay. So I have to ask you, you know, what
has Mark Smith had to say since your features have
been published?

S2 (12:35):
Let's start with shimmer. Here's their statement. They say they
received allegations of research misconduct by former researcher professor Mark
Smith in 2020 and acted swiftly in accordance with the
Australian Code for Responsible Conduct of Research, to begin an
independent external investigation. That investigation concluded that Professor Smith engaged

(12:57):
in serious research misconduct. A second independent review found that
while the institute didn't know about the misconduct, it ought
to have known. We spoke to Smith himself at a
house in Brisbane, not far from shimmer. When we put
questions to him, he said he was not interested in
responding and said no thanks. I've been asked a million

(13:20):
times can you please just get away? I'm not interested.
See you later.

S1 (13:25):
Okay. And one thing that we haven't talked about, but
I feel like we really need to, is the issue
of what damage, if any, his misconduct and research has
the possibility to create or has created. Because we know
that there is a cancer drug that's currently being used
on patients, which has marked Smith's research as the foundation
for its existence.

S2 (13:46):
There is Sam, and I think this is where research
misconduct really touches people's everyday lives. Smith, as we said,
was working on how to use the immune system to
attack cancer. He was particularly interested in a receptor called cd96,
which he hoped to turn into a checkpoint inhibitor. One

(14:07):
of those drugs we discussed that kind of melts tumours
away A at the moment there is a trial for
a cd96 drug, a checkpoint inhibitor that is being run
in humans as we speak. The patent makes clear that
it was built on market research and extensively cites his studies.
We've spoken to people who were working on Cd96. They

(14:31):
said they were unable to reproduce his results. Here's one
whistleblower who we've called Taylor. I feel like the project
must have been based on fabricated data. Even if it
does not cause harm, it's still very wrong. GSK, the
manufacturer of this drug, told us that its oncology research
and development programs were robust. Our investigations of this drug,

(14:53):
in combination with other therapies, are always based on the
full breadth of scientific evidence available. I think the other
thing we should talk about here is the effect this
has on confidence in science. When you speak to the
most senior people in Australia's science ecosystem, system. They often say, oh,

(15:13):
we must not do too much to expose research misconduct
because it would harm trust in science. And I always
push back on that and say, well, I think the
thing that really harms it is when stories like this
come out where people can see that Australia's research integrity
system is simply not robust enough to withstand the challenges
it faces.

S1 (15:35):
Okay, so, Liam, to wrap up, I mean, where to
go from here because since your feature was published, you
mentioned before the architect of Australia's Research Integrity system says
it is no longer fit for purpose. So what now?

S2 (15:47):
Sam, the whistleblowers say consistently that if they had an
independent body to complain to one with investigative powers, they
would have been able to go there and get a
fair hearing far earlier in the process and could have
saved Australian taxpayers tens of millions of dollars. Here there
is a growing chorus now for the establishment of such

(16:09):
a body. It's called an office for Research Integrity. Many
other countries like Sweden and the US have these. We've
now got the head of the CSIRO on board. We've
got the former head of the MRC, the whistleblowers, the
investigators in this case and many politicians. The government says
that Australia's research integrity system is under review. I'm hopeful

(16:33):
that we can get some real change that comes out
of that review.

S1 (16:36):
What? We're so lucky that you're looking into this. We
know it's taken a long time, but thank you so much, Liam,
for your time.

S2 (16:43):
Thanks for having me, Sam.

S1 (16:47):
Today's episode of The Morning Edition was produced by Tammy Mills.
Tom McKendrick is our head of audio. To listen to
our episodes as soon as they drop, follow the Morning
Edition on Apple, Spotify, or wherever you listen to podcasts.
I'm Samantha Selinger Morris, thanks for listening.