AFL ANTI-DOPING TRIBUNAL
WEDNESDAY, 21 JANUARY 2015
DAY NINE
(TRANSCRIPT-IN-CONFIDENCE)
- - - - -
CHAIRMAN:
MR DAVID JONES
MR JOHN NIXON
MR WAYNE HENWOOD
COUNSEL ASSISTING:
MR JUSTIN HOOPER
- - - - -
MR J. GLEESON QC with MS R. ENBOM appeared on behalf of AFL.
MR M. HOLMES QC with MR P. KNOWLES appeared on behalf of the
CEO of ASADA.
MR D. GRACE QC with MR B. IHLE appeared on behalf of 32
players.
MR N. CLELLAND QC with MR D. HALLOWES appeared on behalf of
and Mr
- - - - -
1
2
CHAIRMAN:
witnesses?
3
MR HOLMES:
4
CHAIRMAN:
5
MR HOLMES:
7
CHAIRMAN:
8
MR HOLMES:
10
Yes.
I recall Professor Handelsman.
Professor, would you like to go into the witness box
for us; thank you.
6
9
Are we ready to proceed as proposed with the expert
I understand they want to keep cross-examining him.
Yes.
I'm not sure about the Tribunal's convenience this
afternoon.
CHAIRMAN:
What we thought we would do, if it was convenient to
11
everyone, was perhaps we go through to 1 and take a lunch
12
break at 1 until 2, and then proceed from there.
13
14
15
16
MR HOLMES:
tonight.
CHAIRMAN:
MR HOLMES:
18
CHAIRMAN:
20
21
22
We will just burn the midnight oil.
You're used to
doing that.
17
19
Professor Handelsman has to go back to Sydney
Except that he must catch the plane tonight.
He'll catch the plane, don't worry.
All right.
Mr Grace, would you like to continue?
MR HOLMES:
I think Mr Ihle was cross-examining.
Mr Grace had
finished his turn.
MR GRACE:
Could I just introduce to the Tribunal Dr John Vine,
23
who is present.
24
Professor Handelsman's cross-examination.
25
of course involved in this hot tub exercise.
26
CHAIRMAN:
27
MR IHLE:
28
Okay.
He will remain during the course of
Then he will be
Sorry, Mr Ihle, to do you out of your role.
No, not at all.
I'm more than happy to hand over to
my learned leader, if he wants to take it.
29
<DAVID JOSHUA HANDELSMAN, recalled:
30
<CROSS-EXAMINED BY MR IHLE, continued:
31
MR IHLE:
Professor, thank you for coming back.
.AFL Anti-Doping Tribunal
21/01/15
662
I only have a
HANDELSMAN XXN
BY MR IHLE
1
limited number of questions to ask you, and hopefully it
2
won't take too long.
3
questions, there was a journal article that was forwarded
4
through to the solicitors of ASADA that was requested that
5
you familiarise yourself with.
6
read that and digest it?
Just before I do launch into those
Have you had a chance to
7
A.
I read it this morning, yes.
8
Q.
You feel familiar enough with the contents to answer a
9
10
limited number of questions about it?
A.
Yes.
I mean it depends on the depth of the questioning,
11
but I have had limited time to look at it but, yes, I'm
12
happy to have a go.
13
Q.
Before we go into questions on that article can I ask you
14
in all of your expansive research on this topic, Thymosin
15
Beta-4, Thymosin alpha, Thymomodulin, et cetera, et
16
cetera, had you seen that article before?
17
A.
Yes.
18
Q.
You had?
19
A.
Yes.
20
Q.
So, prior to you being provided that by the lawyers for
21
22
ASADA, you had seen that article and read it?
A.
About some months ago, and it was sort of one of - you read
23
it and it didn't stick in my memory particularly, but
24
I have seen it and it was actually referred to in my
25
report.
26
Q.
That article is referred to?
27
A.
I believe so.
I'm not 100 per cent certain, but I have
28
certainly seen it before.
29
in the way that I would be prepared to sort of have such a
30
discussion.
31
Q.
I understand.
But I hadn't really absorbed it
Just put that aside for the moment.
.AFL Anti-Doping Tribunal
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663
I just
HANDELSMAN XXN
BY MR IHLE
1
want to ask you about some of the other articles you have
2
cited in your report.
3
it is cited as the only human study of intravenous
4
administration of Thymosin Beta-4 that you have cited, it
5
is cited at reference No. 99.
One of those articles, and I think
6
A.
Yes.
7
Q.
And it's from the annals of New York Academy of Sciences by
8
9
Ruff and others.
A.
Yes.
10
MR HOLMES:
11
CHAIRMAN:
12
13
Can I just refer to report No. 102.
Can you just remind us, Mr Holmes, where the
professor's - - MR HOLMES:
The professor's report is in AS-4.
At page 64 the
14
report starts.
15
references to that report, and his attention was drawn to
16
99, but 102 is the reference to the report that Mr Ihle
17
was asking about where the professor thought that he had
18
included a reference to it.
19
MR IHLE:
20
Yes.
He's being cross-examined about the
I accept that.
102 is a reference to the
article that's been provided to you.
21
MR HOLMES:
22
A.
23
MR IHLE:
That's at page 88.
Yes, as I recall.
Now, as I indicated, if you could put that to the
24
side for the moment and if we could look at the one cited
25
at 99.
26
A.
Yes.
27
Q.
That's an article that's titled in relation to a study, "A
28
randomised placebo controlled single and multiple dose
29
study of intravenous Thymosin Beta-4 in healthy
30
volunteers"?
31
A.
Yes.
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HANDELSMAN XXN
BY MR IHLE
1
Q.
Just so we have all got that, I circulate copies of that
2
down the Bar table and I can hand some up to the Tribunal.
3
Do you have a copy of that article there?
4
A.
Not in front of me.
5
Q.
There should be 10 copies.
6
CHAIRMAN:
7
MR IHLE:
8
CHAIRMAN:
9
MR IHLE:
Mr Ihle, this is not already in; is that right?
It's not an exhibit.
Do you want to make it an exhibit?
I will be seeking to tender it.
10
CHAIRMAN:
We might as well do that now.
11
#EXHIBIT PG-12 - Article of the New York Academy of Sciences "A
12
randomised placebo controlled single and multiple dose
13
study of intravenous Thymosin Beta-4 in healthy
14
volunteers".
15
MR IHLE:
With the exception of a human trial which was
16
abandoned because the Thymosin Beta-4 used in that human
17
trial was not from a GMP-certified source, this is the
18
only article you have been able to find about the
19
administration of intravenous Thymosin Beta-4 to humans?
20
A.
That's correct.
21
Q.
And the focus of the study that's reported in this article
22
was looking at adverse effects of doses of Thymosin Beta-4
23
on humans, was it not?
24
A.
It's a typical phase 1 study where you are only looking to
25
make sure the dose is safe.
26
of any interest usually.
It's got no efficacy outcomes
27
Q.
They are not looking for benefits?
28
A.
That's correct.
29
Q.
They are looking for any negative - - -
30
A.
They are looking for safety.
31
Q.
Would you agree with this classification: insofar as this
.AFL Anti-Doping Tribunal
21/01/15
665
It's a safety focus, yes.
HANDELSMAN XXN
BY MR IHLE
1
article is concerned, there was no significant adverse
2
consequences for the administration of Thymosin Beta-4 on
3
the subjects sampled?
4
A.
In this study, yes.
5
Q.
If we look at that study - - -
6
MR HOLMES:
7
8
Can I just object to the relevance as to whether or
not significant adverse consequences.
MR IHLE:
9
One of the things that will need to be proved by
ASADA is the three criteria for the addition of a
10
substance to the prohibited list; that is, that it has
11
performance-enhancing benefits, that it's contrary to the
12
spirit of sport or that it's damaging to the athlete.
13
CHAIRMAN:
14
MR IHLE:
15
CHAIRMAN:
16
MR IHLE:
Okay.
This deals with the third of those.
Okay.
We see in this study that the dosages that were
17
administered to the subjects of the study were
18
administered over a course of 14 days?
19
A.
Yes.
20
Q.
And those dosages ranged from 42 milligrams?
21
A.
Yes.
22
Q.
To 140 milligrams?
23
A.
Yes.
24
Q.
420 milligrams?
25
A.
Yes, yes.
26
Q.
To 1,260 milligrams?
27
A.
Yes.
28
Q.
So the highest dosage in relation to the subjects of that
29
study was 1.26 grams a day?
30
A.
That's correct.
31
Q.
And no adverse consequences were noted?
.AFL Anti-Doping Tribunal
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HANDELSMAN XXN
BY MR IHLE
1
A.
In a very limited study.
It is very typical that a phase 1
2
study is kind of like a veto system.
3
that you can't proceed.
4
not determined in this way.
5
much more extensive and more detailed studies.
6
Q.
If it is not safe in
But safety of regular usage is
It requires phase 2 and 3,
At page 229 of that article, immediately above the heading
7
"Acknowledgments", the conclusory sentence is, "These
8
initial results should allow further development of a
9
planned efficacy trial in acute myocardial infarction"?
10
A.
Yes, that is very standard.
11
Q.
And you would agree with that?
12
A.
I would agree with that, yes.
13
Q.
Thank you.
So that has been tendered.
I want to ask you
14
about your 11 December report now.
15
responds to five specific questions that were asked of
16
you.
17
A.
18
CHAIRMAN:
19
A.
20
MR IHLE:
This is the one that
Yes.
Do you have that there, Professor?
I have it here somewhere.
Yes, I have it here.
In relation to the first question Mr Grace took you
21
the other day to the reference to China, and I think you
22
have clarified your intention in relation to that, or at
23
least to some degree you shouldn't have said China, you
24
should have talked about - - -
25
A.
Yes, look, it should have been broader without reference to
26
China.
27
available peptides do come from China.
28
were broader than that.
29
Q.
But, having said that, most of the commercially
But the comments
And you exclude Thymomodulin as being one of the things
30
discussed in that email for a number of reasons.
31
say it has no known performance enhancing benefit, and you
.AFL Anti-Doping Tribunal
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667
One, you
HANDELSMAN XXN
BY MR IHLE
1
assume a performance enhancing context of that
2
communication?
3
A.
Correct.
4
Q.
And you also say that Thymomodulin is obsolete and not
5
6
produced anywhere in the world commercially?
A.
To the best of my knowledge, the original acid lysate
7
Thymomodulin I don't think would be produced in any
8
Western environment, yes.
9
Q.
10
That's not what the report says.
It says it's not produced
commercially anywhere in the world, doesn't it?
11
A.
I think that's correct.
12
Q.
You think that's a correct statement?
13
A.
I do think that's a correct statement.
14
Q.
Did you do any even preliminary searches online to see the
15
16
availability of Thymomodulin?
A.
I can say that if you do put that word into a search engine
17
products will appear from disreputable sites, and I don't
18
believe that it's likely that those represent the same
19
material.
20
substance.
21
Q.
They are just a name that's used for an unknown
But, if someone was to go to those disreputable sites, they
22
could order something they believe is Thymomodulin because
23
that's what it is advertised as?
24
A.
That's possible, yes.
25
Q.
Are you aware that ASADA requested a testing laboratory in
26
Cologne to purchase Thymomodulin and have it tested?
27
A.
No, I wasn't aware of that.
28
Q.
I want to hand you some documents that we have been
29
30
31
provided by ASADA.
MR HOLMES:
Before it is handed up can I just have a moment to
get some instructions?
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BY MR IHLE
1
CHAIRMAN:
2
MR HOLMES:
3
MR IHLE:
Yes, certainly, Mr Holmes.
No objection.
I just want to hand to you - there are two stapled
4
documents there.
5
ASADA marked document ASA-2.0068.2434 through to 2440, and
6
then ASA-2.0068.2442 through to 2444.
7
and I'll hand copies up to the Tribunal.
8
MR HOLMES:
9
MR IHLE:
10
CHAIRMAN:
11
12
One is an email chain which commences
I will hand those
2440?
Yes.
It is headed "Thymomodulin - a question."
So we can
use that for the purposes of identifying it, Mr Ihle.
MR IHLE:
It is an email chain between Dr Stephen Watt from
13
ASADA and Hans Geyer between the date of 20 November 2014,
14
stretching back to 12 February 2014.
15
CHAIRMAN:
16
17
Okay.
I have noted the email chain, 20/11/14 to
12/2/14.
MR IHLE:
18
Professor, this is the first time you have seen these
documents?
19
A.
That's correct.
20
Q.
Through your consultations with the lawyers for ASADA,
21
Dr Watt, counsel for ASADA, no-one made you aware of the
22
fact that at ASADA's request a testing laboratory in
23
Cologne purchased TFX Thymomodulin and had it analysed?
24
A.
25
26
No, I was not aware of that.
I haven't been so informed,
no.
Q.
Does that surprise you in light of the definitive nature in
27
which you have stated that no-one produces it commercially
28
in the world?
29
A.
I think that that comment still applies in the sense that
30
it's as an acid lysate I think at least maybe in the
31
Western world, I should say, but I don't believe that that
.AFL Anti-Doping Tribunal
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HANDELSMAN XXN
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1
product is produced, at least I have not been able to find
2
other evidence that it's produced.
3
product has the name "TFX Thymomodulin", it may or may not
4
have any relationship to what I was referring to as the
5
original thymus extract.
6
Q.
The fact that a
When you now qualify the statement that it's in your report
7
about not being commercially available in the Western
8
world - - -
9
MR HOLMES:
Gentlemen, this chain of correspondence, it's been
10
suggested to the witness that that is a reference to
11
Thymomodulin simpliciter, but TFX Thymomodulin is a
12
totally different substance.
13
the question is based is misleading, on my instructions.
14
So I would ask Mr - - -
15
CHAIRMAN:
16
So the assumption upon which
Perhaps the professor could be asked about that in
terms of TFX Thymomodulin.
17
MR GRACE:
18
MR HOLMES:
Where is the evidence of that?
The professor has a computer.
If my friend wants
19
to challenge this, he can look up TFX Thymomodulin and
20
will find it's a mixture of peptides.
21
substance.
22
MR IHLE:
23
24
not?
A.
25
26
Thymomodulin itself is a mixture of peptides, is it
I think you described it - - -
Yes, it is a soup.
Yes, it is a soup of probably hundreds
and thousands of peptides, yes.
Q.
I just observe that my learned friend will of course have a
27
right of re-examination.
28
document says.
29
CHAIRMAN:
30
MR IHLE:
31
It is a different
This document says what this
No, you continue, Mr Ihle.
I tender both the email chain and the analysis report
of the Deutsche sports school from Cologne in relation to
.AFL Anti-Doping Tribunal
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HANDELSMAN XXN
BY MR IHLE
1
the purported analysis of TFX Thymomodulin dated
2
December 1, 2014 from Professor Mario Thevis, PhD.
3
CHAIRMAN:
Both those documents are PG-13.
4
#EXHIBIT PG-13 - Email chain between Dr Stephen Watt and Hans
5
Geyer dated 20/11/14 to 12/2/14, and an analysis report
6
from Deutsche Sporthochschule Koln.
7
MR IHLE:
Just in relation to that, Professor, you will see
8
that in the analysis report itself the reference under the
9
description to what was tested refers to Eagle
10
Pharmaceuticals Limited?
11
A.
Yes.
12
Q.
Are you familiar with Eagle Pharmaceuticals?
13
A.
No.
14
Q.
You have heard no reference to Eagle Pharmaceuticals in the
15
course of your preparation for this case?
16
A.
No.
17
Q.
I also want to ask you about - sorry, before I do, when
18
you - and I will refer to the question that I asked - now
19
say in relation to Thymomodulin being produced
20
commercially anywhere in the Western world - - -
21
A.
That was a tentative qualification.
I don't believe it's
22
being produced in the way in which it was originally
23
described as an acid lysate of thymus.
24
is, I have no idea.
What this material
25
Q.
It appears to be represented as TFX Thymomodulin?
26
A.
By God knows who and with what sense of responsibility,
27
28
I don't know.
Q.
29
30
31
At least on the face of it it would tend to suggest Eagle
Pharmaceuticals; do you agree with that?
A.
It appears to be.
They could be just simply a post office
box buying products from somewhere else and sending them
.AFL Anti-Doping Tribunal
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HANDELSMAN XXN
BY MR IHLE
1
out.
I don't really know.
2
Q.
Are you aware of a company called Thymus Therapy?
3
A.
No.
4
Q.
When you put the tentative qualifier on "not produced
5
commercially in the world" and include the word "Western",
6
would you include China to be part of the Western world?
7
A.
Look, I can't comment in any depth about where products
8
called Thymomodulin may now be produced.
I'm pretty
9
confident that they are not produced by the standard
10
methods that were used 100 years ago.
11
unlikely.
12
in China are very focused on modern technology.
13
peptides.
14
but they don't usually, as far as I'm aware, extract
15
biological material with unknown potential virus or other
16
contaminations and so on.
17
China that's done much.
18
Q.
I think that's very
I think that the commercial production plants
They make
They sell them sometimes with bodgie labels,
I don't believe that even in
So you don't believe that there would be substances
19
commercially produced in China that are marketed as
20
Thymomodulin?
21
A.
They would be marketed as Thymomodulin, but they are
22
probably a mixture of peptides they make on a peptide
23
synthesiser.
24
the thymus as originally described before Thymosin and so
25
on were identified properly, that's going backwards
26
100 years, which I think in China they don't do.
27
Q.
I don't believe that they are a lysate of
So, coming back to the answer to question 1 of your
28
11 December report, when you exclude Thymomodulin should
29
that be read as "Thymomodulin being the lysate extracted
30
from the thymus gland"?
31
A.
Yes.
.AFL Anti-Doping Tribunal
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HANDELSMAN XXN
BY MR IHLE
1
Q.
2
3
It shouldn't be read more generally as "Thymomodulin that
might be marketed as Thymomodulin"?
A.
Well, no, I agree with your comment that it referred to
4
Thymomodulin as in my original report described as an
5
lysate of the thymus.
6
names, I can't account for that.
7
Q.
If others choose to use misleading
I just want to show you this document.
This has already
8
been tendered.
This is part of - I just want to show my
9
learned friend because I have some markings on it and
10
I want to be comfortable that he's happy for me to show
11
the witness.
12
of Mr Mullaly's affidavit so I can ask the professor about
13
it.
14
MR HOLMES:
15
CHAIRMAN:
16
17
For ease of reference I have extracted parts
No objection.
That's AS-16, the affidavit.
So this is actually in
the affidavit?
MR IHLE:
This is in the affidavit.
I'm not going to tender
18
this.
It has already been tendered.
It is just for ease
19
of reference.
20
deposed by Mr Mullaly, a lawyer at ASADA who you know and
21
have conferred with on a number of occasions; is that
22
right?
Professor, this is an affidavit that's been
23
A.
I have met him.
I have met him, yes.
24
Q.
You see at paragraph 94 and into 95 what he says is that on
25
4 December last year he performed a Wayback Machine
26
search.
27
Machine?
28
A.
29
30
31
I don't know if you are familiar with the Wayback
No, I'm not actually.
It sounds like a bit of science
fiction.
Q.
Sounds like it.
He indicated that using the Wayback
Machine a website from a company called Thymus Therapy
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1
listed a product called TFX Thymomodulin for sale, and
2
that that was for sale on their web page as of about
3
18 February 2012.
4
I have given you the very next page, which is 214 - sorry,
5
those pages might be - 213 and 214 are the extracts of
6
that page.
7
A.
8
9
I don't actually have page numbers like that.
MR HOLMES:
MR IHLE:
11
A.
12
I think it starts at 213.
213.
See he says - - -
I don't have a 213.
I have two copies of page 11 and then
214.
13
MR HOLMES:
14
MR IHLE:
15
I think it starts on 213.
It does, and I apologise for the photocopying error.
I will hand that up.
16
A.
17
MR HOLMES:
18
213 is the start of exhibit DM-23.
Okay.
Perhaps the professor can be given the opportunity
to read 213 to 215.
MR IHLE:
20
21
I have two
copies of page 11 - 214, yes, okay.
10
19
You will see attached to that document
I'm just asking him whether he has seen this and
pointing to him the evidence that's already been given.
A.
No, I haven't seen it, but I do note a very important point
22
in composition.
23
biotechnologically derived", which means it is
24
synthesised.
25
extract.
26
Q.
It says it's "a family of six peptides
It is not purified by an acid thymus
And that's the distinction that you want to make clear
27
today as opposed to the bald statement in your report of
28
11 December?
29
A.
I'm elaborating on what I said.
30
Q.
Clarifying?
31
A.
Clarifying that the Thymomodulin that I referred to is
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1
originally the acid lysate of thymus.
2
that's produced any more, and I think what they say here
3
is probably a little bit ambiguous, but when they say
4
biotechnologically derived six peptides, that can only be
5
produced by a synthesis machine, not by a lysate.
6
is not Thymomodulin by its generally accepted definition.
7
They are just using the name.
8
Q.
9
MR HOLMES:
10
A.
I don't believe
So it
When you say "its generally accepted definition" - - Perhaps he could be allowed to finish.
The term "Thymomodulin" has a significant place in the
11
history of the development of thymus peptides.
12
Goldstein and others have been involved in the
13
purification.
14
specific meaning, and it means an acid lysate of calf
15
thymus.
16
to hijack that name for people who perhaps have not caught
17
up with what's happened in the last 50 years, and remember
18
that calf thymus has got some youth promoting properties
19
and so on.
20
there's enough information there to say that it is six
21
peptides, which means it is made on a peptide synthesis
22
machine, not by an acid extract.
23
MR IHLE:
It has a very firm place.
Allen
It has a
In that sense what this represents is an attempt
Okay.
So I think this is mostly hocus-pocus, but
That is a distinction which you are able to
24
make given your knowledge of the history of Thymomodulin
25
and the studies that have been done by Goldstein and
26
others?
27
A.
From reading them, yes.
28
Q.
And we have no knowledge or you have no knowledge as to
29
whether the people that were party to that
30
communication - - -
31
A.
Which communication?
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1
Q.
2
-- which is the answer to question 1 of your 11 December
report - - -
3
A.
Yes.
4
Q.
-- are so familiar with that background either?
5
A.
I answered the question which was which is the most likely
6
of those in the context of that message.
I wasn't
7
reflecting terribly much on the people who sent the
8
message, other than that there is a sports scientist and a
9
high performance manager.
So their focus is on
10
performance enhancement.
11
I wouldn't infer anything about how they think.
12
Q.
That's what I took.
Beyond that
If you go on, paragraphs 96 and 97 on page 11 of the
13
affidavit refer to the Thymus Therapy web page as it
14
appears on 9 January 2015, taking that on face value?
15
A.
16
Sorry, can you just point me again to where you are
looking?
17
Q.
Paragraph 96.
18
A.
Yes.
19
Q.
On 9 January.
20
A.
Yes, yes, got it.
21
Q.
Mr Mullaly deposes that he performed a direct search of TFX
22
Thymomodulin on the Thymus Therapy web page?
23
A.
Yes.
24
Q.
And he produces a screen dump of that at DM-33, which
25
hopefully you will have, at page 216 and 217.
26
A.
27
CHAIRMAN:
28
MR IHLE:
29
A.
It is probably two-sided photocopying going wrong.
30
Q.
Paragraph 98 - I want to read to you from Mr Mullaly's
31
I have page 15 and 17, no 16.
Yes, we are the same.
I will have a word to my instructor later.
affidavit: "On 5 December I performed an internet search
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1
on a web site called Alibaba.com for Thymomodulin powder."
2
He says that he's "aware that the Alibaba website was a
3
giant Chinese E-retail site that had floated on the New
4
York Stock Exchange", et cetera, et cetera, and he refers
5
to a Mirror newspaper article at DM-34.
6
He then at DM-35 produces a true copy of the search
7
results for Thymomodulin powder on the Alibaba.com
8
website.
9
understand that to be a giant Chinese E-retailer?
That's not there.
So, reading those things together, would you
10
A.
Mm-hm.
11
Q.
A search has been done in relation to their website and he
12
13
has produced the results of that search at DM-35?
A.
I'm quite familiar with Alibaba.
It is well described as a
14
giant retail site, but it's also well known that it will
15
advertise anything that's not nailed down and there's no
16
guaranteeing what's on there is actually available or is
17
as it is described.
It's a huge unregulated market.
18
Q.
Do you have pages 221, 222, 223 and 224?
19
A.
Yes, I do.
20
Q.
Do you see the screen dump that constitutes DM-35?
21
A.
Yes, that's it, yes.
22
Q.
And you will see that starting on 222, the third entry
23
there, Thymomodulin powder?
24
A.
Mm-hm.
25
Q.
"China, mainland.
26
A.
Yes.
27
Q.
Do you see the very next one, "Thymomodulin powder, GMP
One kilogram minimum order"; yes?
28
approval"?
Would you have an expectation that a
29
GMP-approved laboratory or supplier would advertise
30
something as Thymomodulin powder without making that
31
distinction that you have made?
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1
A.
I don't believe for a minute that a GMP-approved place
2
would be selling Thymomodulin powder because the current
3
status of GMP certification is such that they wouldn't
4
meet it if they make it as an acid lysate of thymus.
5
they make it out of peptides just thrown together, they
6
may or may not, but I wouldn't even take the statement
7
that that's GMP approved without further investigation.
If
8
Q.
You would have to look behind the assertion "GMP approval"?
9
A.
Yes.
10
Q.
Especially if it is coming from someone who themselves
11
purport to be GMP approved?
12
A.
Correct.
13
Q.
It goes on "thymus extract powder" under the same heading?
14
A.
Yes.
15
Q.
Over the page, "GMP supplier, Thymomodulin powder.
16
Thymomodulin.
Thymomodulin powder"?
17
A.
Yes.
18
Q.
You see that this stuff is available by the truckload,
19
whatever it is, they call it Thymomodulin?
20
A.
Yes.
21
Q.
And you can buy tonnes of it?
22
A.
So it appears.
23
Q.
Page - - -
24
A.
Many of these - in fact, the last page, all of them are the
25
same thing just repeated.
26
something Pharmaceutical Company.
27
them come from that.
28
come from that.
29
slightly modified headings.
30
31
Q.
They all come from Hangzhou
In fact, I think all of
All of the second and third pages
So it's really just one ad in various
You would agree, would you not, then, that it appears that
an entity purporting to be from China advertises for sale
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something it calls Thymomodulin on a commercial basis?
2
A.
It appears so.
3
Q.
I don't need to tender those documents.
4
CHAIRMAN:
5
MR IHLE:
6
7
Going to that document which you have cited at 102,
reference No. 102.
A.
8
9
It's already in.
That is a paper, the one that you just - the one by
Pierluigi, the first author?
Q.
Yes, "Thymosin Alpha-1: The regulator of regulators".
10
CHAIRMAN:
11
MR IHLE:
What page is this on?
You don't have it.
It is something that has been
12
referred to by the professor in his report, and I'm
13
providing copies now.
14
MR GRACE:
101, I think.
15
CHAIRMAN:
At 101, is it?
16
MR IHLE:
17
Or 102.
He has one.
First of all, that's a paper that you have
referred to in the body of your report?
18
A.
Yes.
19
Q.
And it is a paper that you have relied on in forming the
20
21
opinions of which you have advised this Tribunal?
A.
Yes, in the sense that it was used in various immune
22
stimulating settings, yes.
23
reported that.
It's one of a series that have
24
Q.
25
#EXHIBIT PG-14 - Article entitled "Thymosin Alpha-1: The
26
27
I tender the report, the article.
regulator of regulators".
MR IHLE:
Professor, this article, does it not, focuses on,
28
amongst other things, the effect of Thymosin Alpha-1 on
29
endogenous T regulator cells.
30
A.
It does.
31
Q.
Endogenous T regulator cells, can you tell the Tribunal
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1
2
what they are?
A.
They are an important component of the adaptive immune
3
system.
4
really more related to inflammation and an adaptive one,
5
which is the sort of thing that produces antibodies and
6
responses to viruses or bacteria and so on.
7
to the adaptive immune response; that is, it adapts to the
8
external environment, whether it is chemicals or
9
infectious agents and so on.
10
Q.
The immune system has an innate form which is
Tell me if I'm wrong about this.
So it relates
The T regulator cell has
11
an integral role in regulating the immune system to
12
outside influences, whether they be bacteria, viruses,
13
chemicals, whatever?
14
A.
Yes.
15
Q.
And this article focuses on the effect of Thymosin Alpha-1
16
17
on the T regulator cells?
A.
18
19
about, yes.
Q.
20
21
It's a study of mainly mechanisms, how those things come
And that's why it poses the question: "Is Thymosin Alpha-1
the regulator of regulators?"
A.
Yes, that's a fairly flamboyant description I don't think
22
anybody would accept in the field.
23
title that catches attention.
It's just a vivid
24
Q.
Catchy?
25
A.
Yes, catchy.
26
Q.
When you say "in the field", you mean in the medical field?
27
A.
Well, I meant specifically in immunology, but I think more
28
broadly in medical research.
29
as a somewhat flamboyant description.
30
the Annals of the New York Academy of Science, I think it
31
was chaired by Allen Goldstein, it was a bit of a tribute
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This would be just regarded
This whole issue of
HANDELSMAN XXN
BY MR IHLE
1
to him, so a lot of groups who worked in that area
2
published things more or less paying tributes to him.
3
This is a little bit like that.
4
tricked up.
5
sense that most journals are.
6
Q.
So it's a little bit
It's not a peer reviewed article in the same
But, notwithstanding this Annals of the New York Academy of
7
Sciences, this is at least the second one we have referred
8
to today that you have relied upon in forming your
9
opinions?
10
A.
It contributed to it, yes.
11
Q.
Notwithstanding what you have just said about it being a
12
tribute to Mr Goldstein, under the heading "Conflict of
13
interest" there is no conflict of interest declared; page
14
4?
15
A.
Yes.
16
Q.
I want to take you now to another article that you have
17
I didn't mean as a conflict of interest.
referred to.
Do you have your report there?
18
A.
Yes, I do.
19
Q.
Can you just help me out for a second.
20
at 65?
Is the author Davison?
21
A.
Davison and Brown, yes.
22
Q.
I want to refer to that one briefly.
23
What is the article
Do you have a copy of
that with you?
24
A.
No, I don't.
25
Q.
I will hand up a copy to you and some to the Tribunal.
26
Again, this is an article that you have had some recourse
27
to - - -
28
A.
Yes.
29
Q.
-- in preparing your opinions in this case?
30
A.
It's an editorial that summarises viewpoints.
31
It's not
primary data, but it's thought out.
.AFL Anti-Doping Tribunal
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1
Q.
You don't doubt the veracity of it?
2
A.
It's not a question of veracity.
3
opinion piece.
4
degree with the opinions in it.
5
unreasonable editorial.
6
Q.
7
8
An editorial is an
So you can agree or disagree to some
But it's not an
You don't disagree with the opinions expressed in that
article?
A.
9
Not in any substantial way, no.
I think it's speculative,
but that's the purpose of an editorial.
10
MR IHLE:
I tender that.
11
#EXHIBIT PG-15 - Journal of Sports Science article "The
12
potential use and abuse of Thymosin Beta 4 in sports and
13
exercise science."
14
MR IHLE:
I just want to come back a second to what we were
15
talking about about Thymomodulin being advertised.
As you
16
pointed out in the document annexed at DM-35 to
17
Mr Mullaly's affidavit on I think it was the second and
18
third or the third and fourth page you say the same
19
company is effectively advertising the same - - -
20
A.
Two-thirds of it is one company, yes.
21
Q.
And that's Huajin pharmacy or something?
22
A.
It is Hangzhou Huajin Pharmaceutical something.
23
Q.
I don't have this but we will produce it because it has
24
just been looked up on the i-phone.
But the Huajin
25
Pharmaceutical Company advertises that Thymomodulin - it
26
says, "Thymopeptide (Thymomodulin powder) extracted from
27
healthy cattle thymus organ."
28
they make as to how this is made.
29
true, first of all.
That's the representation
We can't assume that's
30
A.
Yes.
31
Q.
But for the purposes of this question assume that it is
.AFL Anti-Doping Tribunal
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1
true.
2
A.
Mm-hm.
3
Q.
Does that place doubts on the opinion expressed in response
4
5
to question 1 in your report?
A.
Only to the extent that I make that conditional statement
6
of belief which I really doubt.
7
there, I am doubtful that that's genuine.
8
difficult to accept that assumption to make any further
9
interpretation.
10
Q.
Despite what's written
I find it
It's the case, isn't it, that there are in relation to this
11
industry incredibly unscrupulous operators who make
12
representations which are very difficult for someone in
13
your position and of your esteem to accept.
14
A.
To evaluate, yes.
I think that that is true.
I don't know
15
how scrupulous or unscrupulous they are.
16
I mentioned last time where somebody caused harm in milk
17
substitution the heads of those pharmaceutical companies
18
were executed.
19
environment.
20
whether anything's possible or anything goes in China.
21
I don't know that that's true.
22
Q.
I think as
So it's not a totally unregulated, free
So I would say with some caution as to
You would be very surprised, would you not, if a company
23
that was GMP approved produced Thymomodulin powder from
24
extractions from calf thymus?
25
A.
I would find that hard to imagine, yes.
26
Q.
If that company represents (a) that it's GMP approved and
27
(b) that that's how it produces Thymomodulin you would say
28
at least one of those two things has to be wrong?
29
A.
I think that's more than likely, and I think it's a
30
question of caveat emptor.
31
they really should take some effort to make sure that both
.AFL Anti-Doping Tribunal
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If anyone goes to those sites
HANDELSMAN XXN
BY MR IHLE
1
of those facts, if that's what they are, are correct.
2
Q.
You would hope so.
3
A.
You would hope so.
4
Q.
You were asked by ASADA to answer those five specific
5
questions that resulted in your report of 11 December.
6
A.
Yes.
7
Q.
You were taken to specific parts of the evidence upon which
8
they rely, including, for example, consent forms; you were
9
taken to evidence of an SMS in relation to question 1; you
10
were taken to peptide manuals and things like that.
11
A.
Mm-hm.
12
Q.
At any stage of your consideration of the evidence in this
13
case and your communications with ASADA has it ever been
14
brought to your attention that in 2011 there were
15
communications involving the same types of people that you
16
have been asked to comment on where the terms "Thymosin"
17
and "Thymosin Beta-4" were used exclusively to describe
18
two different things?
19
A.
20
That was not drawn to my attention or I'm not aware of
that.
21
Q.
22
MR HOLMES:
23
If that were to be brought to your attention - - Perhaps if my friend can be more specific.
I don't
know what "that" is.
24
CHAIRMAN:
25
MR IHLE:
He's going to.
What this Tribunal has been taken to, albeit subject
26
to objection at this stage, is what is said to be a note
27
of a discussion between someone who claims to be a
28
biochemist or words to that effect and a sports scientist.
29
At AS-3, page 114 - the Tribunal was taken to this
30
yesterday by Mr Grace in relation to the types of
31
questions that might be asked of Mr Charter - there's a
.AFL Anti-Doping Tribunal
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1
reference to what's been described as the shopping list.
2
One of the items is Thymosin Beta-4 and other one is
3
described as Thy.
4
I wanted to draw your attention to.
5
CHAIRMAN:
6
MR IHLE:
7
CHAIRMAN:
8
MR IHLE:
9
Page 114 of AS-3.
Yes, I have it.
The bottom box with the word "Ed" in the left-hand
So
that's not something that was brought to your attention?
A.
12
13
What's the page, Mr Ihle?
column, "Thymosin Beta-4" and then under that "Thy".
10
11
So that's the first piece of evidence
No, and I'm still not aware of it.
So if you want me to
comment on it I would prefer to see it.
Q.
If anyone objects to what I have suggested to you is
14
represented on the page then we will hear the objection.
15
But assuming that to be the case - - -
16
MR GLEESON:
I'm prepared to object.
If what is happening here
17
is that the witness is asking to see a page he's being
18
cross-examined about and that's being resisted, then
19
I would submit that's unfair.
20
it.
21
CHAIRMAN:
22
MR IHLE:
23
CHAIRMAN:
He should be allowed to see
He should be allowed to see it.
I'm happy if he sees it.
It is probably best if the professor sees it.
24
is the document that Mr Ihle is referring to.
25
diary note.
26
MR IHLE:
27
It is a
We are just trying to establish whether he has seen
it or not; that's all.
28
CHAIRMAN:
29
MR IHLE:
30
31
This
I don't think so.
There's that document.
Is that something you have
seen before?
A.
No, I don't believe so.
.AFL Anti-Doping Tribunal
21/01/15
I did get a bundle of documents,
685
HANDELSMAN XXN
BY MR IHLE
1
2
but I have trouble even reading this, and I don't - no.
Q.
3
Can you hand that back.
I now want to take you to in AS-3
page 214.
4
A.
Yes.
5
Q.
This is again an email that the Tribunal has been taken to
6
that bears the date of 16 December 2011.
7
A.
Mm-hm.
8
Q.
You will see in that table that there is both Thymosin
9
mentioned.
10
A.
Mm-hm.
11
Q.
And Thymosin Beta-4.
12
A.
Yes.
13
Q.
Ostensibly as different items.
14
A.
It appears so, yes.
15
Q.
Hand that back, please.
16
Again, is that a document you had
seen before today?
17
A.
No, I don't believe so.
18
Q.
You draw some conclusions in your 11 December report based
19
on a number of things that you have identified.
20
fact that Thymosin and Thymosin Beta-4 were used
21
interchangeably around this time by people who were
22
involved in any way influence your conclusion in relation
23
to answer 1, keeping in mind two things: what we have now
24
said about Thymomodulin and what we have seen in relation
25
to what is advertised as far as Thymomodulin is concerned?
26
A.
The document you just showed me said "Thymosin".
Does the
It didn't
27
say "Thymomodulin".
28
the further comments.
29
and Thymosin Beta-4 it is possible the unspecified form is
30
either Alhpa-1 or Beta-4.
31
I think that's just logical.
.AFL Anti-Doping Tribunal
21/01/15
So I would exclude Thymomodulin from
If there is Thymosin unspecified
686
That is a possibility, and
HANDELSMAN XXN
BY MR IHLE
1
But, nevertheless, I come back to the point that
2
there is no known, suspected or even rumoured performance
3
enhancing effects of Thymosin Alpha-1.
4
like that I don't know why it is listed there twice.
5
There are many reasons why that might happen.
6
still assume that it's more than likely that it is
7
Thymosin Beta-4.
8
it may come in a bottle with just "Thymosin" written on
9
it.
10
Q.
So in the setting
But I would
But where it is not directly specified
With your experience as an endocrinologist and someone who
11
has proffered expert evidence in a number of doping
12
related cases and things like that - - -
13
A.
A very limited number.
14
Q.
Would you be aware, given your understanding of the immune
15
system, that training at a high level of intensity and
16
sustained training at a high level of intensity can have
17
an immuno compromising effect on the body?
18
A.
Not in the sense of a real immuno deficiency or serious
19
immuno competence.
I don't believe that that's true.
20
athletes essentially are healthy - elite healthy
21
individuals.
22
Despite the fact that that's talked about, I think that
23
that's mostly hot air, frankly.
The
I don't believe they have immune deficits.
24
Q.
More susceptible to colds?
25
A.
No, I don't believe so.
26
Q.
You don't believe so?
27
A.
No.
28
Q.
There is no impact on the immune system?
29
A.
I don't believe exercise has a deleterious, adverse or some
30
other type of effect on the immune system.
31
not inherently immune to getting colds and flu, like
.AFL Anti-Doping Tribunal
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Athletes are
HANDELSMAN XXN
BY MR IHLE
1
everyone else.
2
that I have ever seen that they are more likely to get it
3
than others.
4
Q.
But I don't think there is any evidence
You would say even if people are training at high levels of
5
intensity for sustained periods of time that there is no
6
compromise to that person's immune system.
7
A.
I don't believe there is any evidence to support that.
It
8
is something you will read about in the vast echo chamber
9
of the internet, but I don't think it has any evidence to
10
support it.
11
have.
12
due to their exercise program."
13
clear that that is any more common than anybody else
14
getting the flu.
15
it, so it draws attention.
16
frequency or the severity of upper respiratory tract
17
infections, for example, is any more in athletes than any
18
others.
19
Q.
It is one of those folklores that people
So when an athlete gets a flu they say, "It must be
In reality it is not
Their training will be interrupted by
But I don't believe that the
What I want to ask you to do is, if you can, distinguish
20
between that which you have read and that which you
21
believe as an expert.
Do you understand that distinction?
22
A.
There isn't a distinction in this question.
23
Q.
You said that there is a lot of information out there about
24
immuno - - -
25
A.
Yes.
I don't believe it, yes.
26
Q.
And you don't accept that?
27
A.
No.
28
Q.
As a professor of endocrinology you don't accept that?
29
A.
I don't think that the evidence is there.
As a career
30
medical researcher I'm used to looking at claims as to
31
whether they are supported by reliable evidence, and
.AFL Anti-Doping Tribunal
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HANDELSMAN XXN
BY MR IHLE
1
I don't believe that that is supported by reliable
2
evidence.
3
Q.
You know that there has been a number of studies and
4
attempts to boost immunity for athletes because of this
5
alleged compromise of their immune system, don't you?
6
A.
Look, there may be such studies.
The medical research is
7
open to all - it's a real democracy.
8
sort of ideas that can be tested.
9
they have even a priori credibility to start with.
10
Q.
It is open to any
It doesn't mean that
If someone has a cold or a flu and they are training at
11
strenuous levels what will that insult to their body,
12
being the cold or flu, do by way of affecting their
13
ability to recover from the activities they are engaged
14
in?
15
A.
When a person has an infection like that they need to rest
16
a little bit, depending on how severe it is.
17
overexert themselves they will feel unwell and their
18
athletic performance may deteriorate.
19
that amounts to immune deficiency or anything that needs
20
immune boosting.
21
people who are athletes get colds and flu as well as
22
anyone else.
23
Q.
24
25
If they
But I don't believe
That's just hype built on the fact that
The same type of hype or hype that fits in the same
category as giving athletes Tribulus?
A.
26
More or less, yes.
There is plenty of it around, hype that
is.
27
Q.
Don't believe the hype is what you are saying?
28
A.
Yes, look, as a career researcher again my task is to
29
distinguish as much as you can fact from fantasy, and
30
there's a great deal of fantasy that needs a lot of
31
filtering.
.AFL Anti-Doping Tribunal
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BY MR IHLE
1
Q.
And there's a lot of suckers out there too?
2
A.
One born every minute, I think it was said.
3
MR IHLE:
4
CHAIRMAN:
5
MR HALLOWES:
6
CHAIRMAN:
7
I don't have any further questions at this stage.
Mr Hallowes, you are going to ask some questions?
Yes, hopefully about 15 minutes or so.
All right.
We'll complete your questioning, if we
can do it in that timeframe.
8
<CROSS-EXAMINED BY MR HALLOWES:
9
MR HALLOWES:
Professor, I want to actually take you back to
10
some questions you were asked last week about certificates
11
of analysis.
12
A.
Yes.
13
Q.
Although, as I understand from your evidence, you wouldn't
14
suggest you have seen every certificate of analysis from
15
every manufacturer, you obviously have some familiarity
16
with them?
17
A.
Yes, some.
18
Q.
I'm wanting to first of all take you to a certificate of
19
analysis that was referred to last week, which is at page
20
224 of AS-3.
21
A.
Is that the one Mr Grace called the dodgy certificate?
22
Q.
No, it's not the one he called the dodgy certificate.
23
at page 224.
24
appears to be the GL Biochem certificate.
25
CHAIRMAN:
26
A.
27
MR HALLOWES:
It's
It is the GL Biochem certificate or what
Do you have that, Professor?
Yes, I have, thanks very much.
One of the things you referred to last week was
28
that in these sorts of certificates you will have what you
29
might call boilerplate information.
30
A.
Yes.
31
Q.
That you would expect to see in essence for every
.AFL Anti-Doping Tribunal
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BY MR HALLOWES
1
certificate of analysis that came from GL Biochem, there
2
would be certain information that would be replicated
3
every time.
4
A.
Usually, yes.
5
Q.
Putting aside the fact that we have the heading "GL
6
Biochem" and the address down the bottom, which presumably
7
you would expect to see every time, you have also got the
8
warranty which says "GL Biochem warrants".
9
A.
Yes.
10
Q.
I take it you would expect that if a certificate of
11
analysis came from GL Biochem on every occasion that you
12
would see "GL Biochem warrants".
13
A.
I would expect so, yes.
14
Q.
Similarly, this certificate of analysis has information
15
showing that it was prepared and checked by someone?
16
A.
Yes.
17
Q.
And that's what you would expect if it appears on the
18
certificate of analysis from GL Biochem, you would expect
19
that's what they would have every time?
20
A.
I agree with you in general.
But it is possible that a
21
company may be so large or so disorganised that it doesn't
22
always happen the way you expect.
23
general I think you are right, yes.
24
Q.
25
If it was a well-run, well-organised company you would
expect to see those sorts of things repeated every time.
26
A.
27
CHAIRMAN:
28
Yes, certainly.
It's a document of some importance, Professor, isn't
it?
29
A.
30
CHAIRMAN:
31
But in principle and in
Yes, very much.
And the purpose of it is the manufacturer is
saying - - .AFL Anti-Doping Tribunal
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HANDELSMAN XXN
BY MR HALLOWES
1
A.
2
CHAIRMAN:
3
A.
4
CHAIRMAN:
5
This is what's in the product, yes.
"We are supplying this product."
Yes.
"And we have undertaken the process whereby we
certify that this is what's in the product."
6
A.
7
MR HALLOWES:
8
Yes.
I agree it's very important; that's correct.
It also clearly has a stamp on the bottom right
indicating GL Biochem (Shanghai) Limited.
9
A.
Correct.
10
Q.
And again you would expect to see that stamp on every
11
occasion?
12
A.
Yes.
13
Q.
There is some information which is clearly the actual
14
testing results.
15
A.
Yes.
16
Q.
Am I right that that information is within that box that
17
you see there which has the headings "Tests.
18
Specifications.
Results"?
19
A.
Correct.
20
Q.
And that's, as I understand it, indicating the actual
21
testing that was done and the results in relation to the
22
analysis?
23
A.
Yes, I believe so.
24
Q.
Then there is other information above that which would
25
appear to be particular to the actual product that's been
26
manufactured and it's purporting to be; have I got that
27
right?
28
A.
Yes, I believe so, yes.
29
Q.
In relation to this one it is for the product MGF, Mechano
30
31
Growth Factor.
A.
Correct.
.AFL Anti-Doping Tribunal
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BY MR HALLOWES
1
Q.
In terms of the information we see above the box, am
2
I right that that's not information suggesting that that
3
is the result of the testing they have done but that is
4
information about the product itself, its name, what its
5
sequence should be?
6
A.
Yes.
7
Q.
What its molecular weight should be?
8
A.
Yes.
9
Q.
And what its molecular formula is?
10
A.
Yes, it's an intention.
11
12
It spells out what they intended
to provide and manufacture and supply.
Q.
If we just take MGF, Mechano Growth Factor, as an example,
13
if the manufacturer has that as one of the products that
14
they sell and they make, would it be the case that this
15
information might not be entered by the particular
16
operator every single time; that might actually come up
17
every time simply - - -
18
A.
19
20
Yes, it might be a template that they type in the catalogue
number and they get the template out; yes, very likely.
Q.
As you say, it is very likely.
It is unlikely that every
21
single time, if it is something that is being sold and
22
manufactured, that the operator has to look up the
23
sequence or type in the sequence?
24
A.
Yes.
25
Q.
It is likely that that information would simply be there in
26
essence allied to the catalogue number?
27
A.
Yes, I agree.
Agree.
28
Q.
One of the things that comes up is the molecular formula,
29
and you would expect again that that would most likely
30
come up.
31
was preparing this document the molecular formula of MGF,
If the person typed in the catalogue number who
.AFL Anti-Doping Tribunal
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HANDELSMAN XXN
BY MR HALLOWES
1
Mechano Growth Factor, as it is set out there, would
2
likely come up rather than have to be entered by the
3
operator?
4
A.
Yes, very likely, barring any sort of computer failure or
5
circumstances which mean that their system isn't working
6
and that these templates may not be available for some
7
reason.
8
Q.
9
But, yes.
In terms of that molecular formula, you were taken last
week to the way it's written there with the numbers in the
10
lower type.
11
A.
Yes.
12
Q.
Is it fair to say that that's something that if you do year
13
10 science you are probably taught that's the way that you
14
will represent any chemical formula?
15
A.
That's a convention, yes.
16
Q.
But it's a convention that you don't have to be a professor
17
of endocrinology to know about?
18
A.
No.
19
Q.
You'd get taught that in secondary school?
20
A.
It's a very standard convention, yes.
21
Q.
Is it fair to say that in terms of those sorts of things
22
therefore any time that GL Biochem were providing a
23
certificate of analysis in relation to MGF, Mechano Growth
24
Factor, or indeed any other substance, apart from the
25
boilerplate, the warranty, and apart from the other
26
matters that I have taken you to, you would expect that
27
they would be getting the molecular formula in that same
28
sort of notation?
29
A.
Yes.
30
Q.
I just want to take you now to the one which, as you
31
Yes, indeed.
indicate, Mr Grace has referred to as the dodgy - 280.
.AFL Anti-Doping Tribunal
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HANDELSMAN XXN
BY MR HALLOWES
1
A.
I have a copy.
2
Q.
You have a copy.
3
That's the one that's simply headed
"Certificate of analysis".
4
A.
5
CHAIRMAN:
6
A.
7
MR HALLOWES:
You have that, page 280?
I have it.
Yes, we have it.
I have it from last time.
What it doesn't have compared to the one at page
8
224, it doesn't have the heading "GL Biochem", it doesn't
9
have GL Biochem's address, it doesn't have "GL Biochem
10
warrants", it doesn't have anyone preparing and checking
11
it, it doesn't have the stamp.
12
formula written in a different fashion.
It has the molecular
13
A.
Yes.
14
Q.
Given all of those things you would say, "Well, that's
15
16
Yes, it does.
highly unlikely that it would have come from GL Biochem"?
A.
Look, it certainly casts doubt on it.
If I knew that the
17
company was using these boilerplate certificates of
18
analysis consistently then this would really stick out.
19
But there are circumstances in a laboratory, say, for
20
example, the computers are down or somebody bought the
21
product from GL and then decided to add some mark-up and
22
then sell it on themselves, you know, you can imagine
23
scenarios where this would happen.
24
same as the GL Biochem's certificate of analysis.
But this isn't the
25
Q.
There are numerous differences?
26
A.
Yes, sure.
27
Q.
Including one that hasn't been raised.
On page 224 there
28
is in fact a lot number given.
29
certificate of analysis at page 224 for Mechano Growth
30
Factor it says "Lot No.".
31
A.
If you look at the
There is a lot number, yes.
.AFL Anti-Doping Tribunal
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695
HANDELSMAN XXN
BY MR HALLOWES
1
Q.
Which would suggest, would it not, that GL Biochem, apart
2
from having the catalogue identifying the particular
3
substance, for each certificate of analysis there is a lot
4
number that is being analysed?
5
A.
Yes, and you would expect to see something like that.
6
Q.
The catalogue number itself, do I take it that that's not
7
8
some chemical term?
A.
9
10
No, that's an arbitrary number that a company will have in
their own catalogue.
Q.
11
That's just simply that company has a catalogue and for
each item they are selling it has a number?
12
A.
Correct.
13
Q.
You see interestingly in relation to that - and I will take
14
you first of all to another document which is at page 693
15
of AS-3 which you might not have.
16
if you don't.
17
be something that's been downloaded from the internet from
18
GL Biochem's website?
I will hand up a copy
Do you see at page 693 what would appear to
19
A.
Yes.
20
Q.
And do you see that in relation to the products this would
21
appear to be products where under the letter T you have
22
the second one being the Thymosin Alpha-1 acetate?
23
A.
Yes.
24
Q.
Then you have the Thymosin Beta-4 acetate?
25
A.
Yes.
26
27
For some reason the Thymosin Alpha-1 acetate doesn't
have a catalogue number.
Q.
28
Putting that to one side for a moment, do you see the
catalogue number at least for Thymosin Beta-4 is 55820?
29
A.
Yes.
30
Q.
And you see on the certificate of analysis, which has been
31
called into question at page 280, they have the same
.AFL Anti-Doping Tribunal
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HANDELSMAN XXN
BY MR HALLOWES
1
catalogue number?
2
A.
Correct.
3
Q.
So, despite all those other differences, whoever has
4
produced this certificate at page 280 has, it would
5
appear, put in the same catalogue number that in fact
6
belongs to GL Biochem?
7
A.
Yes.
8
Q.
And I think you said in relation to the certificate of
9
analysis last week at page 280 that you would describe it,
10
certainly if an Australian company had produced it, as
11
being substandard?
12
A.
I believe so, yes.
13
Q.
And that was for a number of factors including that for
14
whatever reason it's the wrong molecular weight that's put
15
there?
16
A.
Yes, although - - -
17
Q.
You have given the explanation that it might be transposed.
18
But, however that's occurred - - -
19
A.
But it is certainly not right.
20
Q.
If it was the fact that whatever company had a standard
21
when you put in the catalogue number that all the
22
information such as molecular weight came up, somehow that
23
hasn't happened for this one; they have the molecular
24
weight wrong?
25
A.
26
27
Look, I think it's very likely this is not the same sort of
template that the other certificate was produced by.
Q.
And the other problems you mentioned is the product name,
28
it doesn't properly identify it; it simply says "Thymosin"
29
without identifying what it is actually talking about?
30
A.
Yes.
31
Q.
And the molecular formula is written there in a way that
.AFL Anti-Doping Tribunal
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HANDELSMAN XXN
BY MR HALLOWES
1
you wouldn't expect?
2
A.
That's correct.
3
Q.
They are the questions I wanted to ask about the
4
certificate of analysis.
5
that will take about five minutes, Mr Chair.
6
CHAIRMAN:
7
MR HALLOWES:
There is just one other topic
Go ahead, Mr Hallowes.
This is touching on a matter you raised in the
8
report that you prepared on 11 December 2014.
In that
9
report you referred to an email that you had been provided
10
with from a Mr Charter to Mr Alavi and Mr Dank.
11
relation to answers 4 and 5 you referred to an email that
12
had been sent on 12 January.
13
A.
Okay.
14
Q.
That appears at page 227 of AS-3, Mr Chairman.
In
Yes.
That's the
15
email that I'm referring to.
Just before I ask you any
16
questions, do you see there that you have referred to that
17
email of 12 January from Charter to Alavi and Dank?
18
A.
Yes.
19
Q.
Do you have a copy of that, or I can hand you up a copy if
20
21
necessary?
A.
22
If there's more than just what was in the question, yes,
I would need to look at it.
23
Q.
I will just hand that up in any event.
24
A.
Okay.
25
Q.
You can see that the email was sent, it would appear, at
26
6.42 am that morning?
27
A.
Yes.
28
Q.
In terms of the recommended concentration of TB500
29
(Thymosin Beta-4) do you see that the recommended
30
concentration in that email talks about 10 milligrams per
31
2 millilitres?
.AFL Anti-Doping Tribunal
21/01/15
698
HANDELSMAN XXN
BY MR HALLOWES
1
A.
Mm-hm.
2
Q.
Do you see that?
3
A.
Yes.
4
Q.
Can I ask whether you were provided with any text messages
5
which were sent later that day, being 12 January 2012,
6
between these people, Mr Charter, Mr Alavi and Mr Dank?
7
A.
Not that I can recall directly.
No, I don't believe so.
8
But maybe you could refresh my memory.
9
sequence of text messages we looked at last time
10
11
which - - Q.
12
13
I'm not sure if they were there.
I will hand up two
documents in relation to that to you.
A.
14
15
There was a
Yes, I think we saw some of it, but I'm not sure exactly
which one.
Q.
If you see in relation to the text messages exchanged
16
between Shane Charter and Steve Dank - Mr Chairman, these
17
appear in AS-4 at page 34 of the text messages.
18
CHAIRMAN:
Thank you.
19
MR HALLOWES:
Do you see on page 34 text messages exchanged
20
between Shane Charter and Steve Dank?
If you go down to
21
the third line, 56, after there's been some exchanges
22
about, "Which peptide do you need next," at 56 it says,
23
"Thymosin 20 by five millilitre vial"?
24
A.
Yes.
25
Q.
And then if you go to the other text messages, this is at
26
page 12 of the text messages between Charter and Alavi, at
27
224 you will see, "Hi, mate.
28
millilitre vial".
Thymosin 20 by five
29
A.
Mm-hm.
30
Q.
Do you see that one sent at 10.19?
31
If you go across it has
a date and a time?
.AFL Anti-Doping Tribunal
21/01/15
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HANDELSMAN XXN
BY MR HALLOWES
1
A.
Yes.
2
Q.
12 January at 10.19.
3
A.
Got it.
4
Q.
If you go back to the other one, Dank to Charter, that was
5
at 10.14 am on 12 January?
6
A.
Yes.
7
Q.
Just some simple mathematics.
8
9
20 by a five millilitre
vial, that would be 100 millilitres?
A.
It depends if the 5 ml refers to the fluid in it or just
10
simply the size of the vial.
11
that it refers to 5 mls as a vial, which may have less
12
than 5 mls of fluid in it or whether that's the fluid
13
volume.
14
Q.
So it's not completely clear
Let's take it that at least for the purposes of this
15
mathematics that that's referring to 100 millilitres of
16
Thymosin.
17
A.
Okay.
18
Q.
You would agree that at the concentration referred to in
19
the article on 12 January you would need 500 milligrams of
20
Thymosin, whether it be Thymosin Beta-4 or otherwise, to
21
make up 100 millilitres; correct?
22
A.
Yes.
23
MR HALLOWES:
24
MR IHLE:
25
CHAIRMAN:
26
<FURTHER CROSS-EXAMINED BY MR IHLE:
27
MR IHLE:
Thank you.
I have no further questions.
Sorry, Mr Chairman.
There is one very brief - - -
Okay.
Professor, you were asked some questions the other
28
day about your familiarity with compounding, and
29
I understand that you don't have a great deal of
30
familiarity; but, notwithstanding, as an endocrinologist
31
you would have dealt with solutions and substances that
.AFL Anti-Doping Tribunal
21/01/15
700
HANDELSMAN F-XXN
BY MR IHLE
1
had been compounded; is that fair?
2
A.
Yes, I know about them, a little bit.
3
Q.
You are also familiar with the name Charter?
4
You have been
taken to a number of SMSs and things like that?
5
A.
Yes.
6
Q.
One of the things that Charter has represented in an
7
interview to ASADA which is subject to objection at the
8
moment is that one of his roles in relation to this
9
enterprise was to work out what preservatives these things
10
should be compounded in.
11
A.
Well, if you say so.
12
Q.
I want to ask you about a representation that he made to
13
ASADA.
It may well be hypothetical, we don't know,
14
because Mr Charter is not coming along to be
15
cross-examined.
16
talks about a sodium chloride solution at 35 per cent.
17
A.
At 35 per cent?
18
Q.
Yes.
19
But at AS-7, page 49 of his interview, he
What would you say about someone who talks about
compounding a substance at 35 per cent sodium chloride?
20
A.
I would say they don't know what they are talking about.
21
Q.
It would be sludge?
22
A.
Yes.
If you take it literally as to what that's usually
23
meant to mean to a competent biochemist, yes, it would be.
24
It wouldn't be soluble, probably.
25
you say.
26
Q.
27
Someone who talks about that doesn't know what they are
talking about, I think was - - -
28
A.
29
MR IHLE:
30
CHAIRMAN:
31
It would be sludge, as
I would say that that's a reasonable conclusion, yes.
No further questions.
All right.
We will adjourn until 2.15.
There may
be some re-examination of the professor, Mr Holmes, before
.AFL Anti-Doping Tribunal
21/01/15
701
HANDELSMAN F-XXN
BY MR IHLE
1
we move to the hot tub.
2
<(THE WITNESS WITHDREW)
3
LUNCHEON ADJOURNMENT
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
.AFL Anti-Doping Tribunal
21/01/15
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HANDELSMAN F-XXN
BY MR IHLE
1
UPON RESUMING AT 2.15 PM:
2
CHAIRMAN:
3
4
before we move to the - - MR HOLMES:
5
6
Mr Holmes, do you want to re-examine the professor
No, I don't.
Mr Gleeson would like to ask a
question.
CHAIRMAN:
7
Okay.
Professor, just for a moment, in that
location, and then we will relocate you.
8
<DAVID JOSHUA HANDELSMAN, recalled:
9
<FURTHER CROSS-EXAMINED BY MY GLEESON:
10
Q.
11
Professor, I just wanted to ask you a question about your
report of 11 December.
Do you have that handy?
12
A.
Yes, I do.
13
Q.
Could you turn, please, to paragraph 10 of that report?
14
A.
Yes.
15
Q.
Which is your answer to question 4?
16
A.
Yes.
17
Q.
It's the part of your report where you express the view in
18
the final sentence of the first paragraph of paragraph 10,
19
"These dosage recommendations correspond precisely to
20
those in the consent form for Thymosin, suggesting that
21
the substance was actually TB500 rather than Thymosin
22
Beta-4."
23
email of 12 January, which attaches the article headed
24
"How to use TB500 (Thymosin Beta-4)"?
Now, you refer earlier in that paragraph to the
25
A.
Yes.
26
Q.
I just wanted to clarify with you is it the case that the
27
sole reason that you tend towards TB500 and tend away from
28
Thymosin Beta-4 as expressed there the fact that that
29
article refers first to TB500 and then in brackets
30
Thymosin Beta-4?
31
A.
Yes, it does, and I have to say that's a fairly weak
.AFL Anti-Doping Tribunal
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HANDELSMAN F-XXN
BY MR GLEESON
1
inference but it was sort of on balance going towards
2
TB500.
3
Q.
4
But it may not be correct.
You did say in your evidence that it was a fairly weak
inference?
5
A.
Yes.
6
Q.
The article in question refers in a sort of compendious
7
fashion to TB500 and Thymosin Beta-4, and do you agree
8
that the article doesn't purport to distinguish between a
9
dosage regime for one as distinct from the other?
10
A.
Yes, that's correct.
11
Q.
So, if what the article is purporting to do is to refer to
12
them as being synonymous or indeed not synonymous but
13
similar, either way the dosage specified is the same for
14
both products?
15
A.
Yes.
I mean, essentially neither of those products has
16
well established clinical dosage, so it's very likely
17
these are just more or less somebody's conjecture and they
18
could well be the same or equivalent or similar.
19
It's - I don't think it's a ground for distinguishing them
20
based on any real evidence one way or the other.
21
Q.
Just to be 100 per cent clear, you are not aware of any
22
dosage regime for Thymosin Beta-4 that's separate and
23
distinct from that which is specified in this article?
24
A.
I don't believe there is any dosage regimen for either of
25
them in any substantial form.
For Thymosin Beta-4 there
26
is, as we discussed before, a single study which allows
27
further research to go on, but that doesn't mean it's
28
safe.
29
is no established dosage from that, nor for TB500.
It just means it's safe enough to go on.
30
MR GLEESON:
31
<(THE WITNESS WITHDREW)
So there
Thanks, Professor.
.AFL Anti-Doping Tribunal
21/01/15
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HANDELSMAN F-XXN
BY MR GLEESON
1
CHAIRMAN:
Professor, if you and Dr Vine wouldn't mind going to
2
the Bar table, be seated in the middle there.
3
the lion's den, if I could describe it.
4
be a lion's den.
5
Perhaps you start, Mr Holmes.
6
7
MR HOLMES:
Going into
I'm sure it won't
We will take your evidence from there.
Dr Vine, you realise these are proceedings before
the AFL disciplinary tribunal?
8
DR VINE:
9
CHAIRMAN:
Yes.
We are not swearing witnesses in, Dr Vine, but you
10
understand the importance of telling the truth and
11
expressing your opinions truthfully?
12
DR VINE:
Yes, I do.
13
MR IHLE:
Sorry, Mr Chair, may I suggest at the outset,
14
notwithstanding that Mr Holmes is going to start, as
15
I understand it, cross-examining Dr Vine as well as asking
16
Professor Handelsman the questions, if it hasn't already
17
been marked - - -
18
CHAIRMAN:
19
MR IHLE:
20
21
I think the report is in.
At least as an introductory range of questions he
should be asked whether he adopts the report.
CHAIRMAN:
Yes, I follow that.
I'm pretty sure it is PG-7.
22
You or Mr Grace could do that.
23
Mr Holmes can't do it.
24
MR HOLMES:
25
CHAIRMAN:
26
Dr Vine's report is in.
But there's no reason why
I'm happy to do it.
You do it, Mr Holmes, I think, and then lead into
your questioning and we will move on from there.
27
MR HOLMES:
28
DR VINE:
29
Mr HOLMES:
30
DR VINE:
31
MR HOLMES:
Dr Vine, you prepared a report dated 19 January?
Yes, that's right.
PG-7.
Do you have it in front of you?
Yes, I do.
Paragraphs 1 to 25 respond to some specific
.AFL Anti-Doping Tribunal
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PROF. HANDELSMAN/DR VINE
1
questions that were posed to you by the solicitors' firm
2
Tony Hargreaves & Partners, and the letter is there at
3
JV-2; correct?
4
DR VINE:
5
MR HOLMES:
That's correct.
Then you have given some comments in 26 and 27,
6
which have been objected to.
7
couple of questions, and I think Professor Handelsman
8
deals with this in the report that you responded to.
9
Professor Handelsman, do you have your report dated
10
I want to ask you just a
10 January?
11
PROF. HANDELSMAN:
12
MR HOLMES:
Yes, I do.
Just going to you firstly, Dr Vine, your figure 1
13
in JV-4, it's got a long name at the top.
14
there, and somebody has put in "Thy A-5"; do you see that?
15
DR VINE:
16
MR HOLMES:
17
18
19
DR VINE:
21
DR VINE:
22
MR GRACE:
25
MR HOLMES:
I'm just trying to find my copy, sorry.
I have them
Yes.
You have those two?
Yes, I have.
We just want to clarify it is the same page we
JV-4, page 1, figure 1, the upper figure and the
lower figure.
MR GRACE:
27
MR HOLMES:
Yes.
Dr Vine, the lower figure is a zoom of the upper
figure; correct?
29
DR VINE:
30
MR HOLMES:
31
It is figure 1, upper and lower.
are - - -
26
28
JV-4, page 1.
attached as a separate document.
MR HOLMES:
24
I'm just turning to my figures, sorry.
The lower one is a zoom of the top one.
20
23
"Vania" is
That's correct, yes.
And in the upper figure, in the lower part, in
about the centre there's a very small peak for 4971.429?
.AFL Anti-Doping Tribunal
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PROF. HANDELSMAN/DR VINE
1
DR VINE:
2
MR HOLMES:
3
DR VINE:
4
MR HOLMES:
5
Yes.
And that's been zoomed to create the lower figure?
That's correct.
That is the result of an analysis conducted at
Bio21 in May 2012?
6
DR VINE:
7
MR HOLMES:
I believe so, yes.
Then if you go over the page, figure 2, figure 3,
8
figure 4, figure 5, they all relate to some testing in
9
2013?
10
11
12
DR VINE:
Yes, that's correct.
They were in a separate folder
in the set of files that I was given, yes.
MR HOLMES:
If we go to paragraph 3 of your report, you had
13
some documents provided under cover of the letter.
14
had a USB memory stick, a copy of the software, and you
15
used that software to view the files from Bio21?
16
DR VINE:
Yes, I did.
In the time I had available I used that
17
software as best as I was able, it being a software
18
platform that I'm not familiar with.
19
use it sufficiently to extract some data.
20
MR HOLMES:
Okay.
You
But I was able to
I think in paragraph 16 you came to the
21
conclusion, "All of these materials have peaks in roughly
22
the right range for Thymosin Beta-4.
23
of them can claim to prove the presence of Thymosin Beta-4
24
to any recognised standard"?
25
DR VINE:
26
MR HOLMES:
In my opinion, none
That's correct, yes.
So on all those occasions in figures 1 through to
27
figure 5 there are a rough - I just want to use your
28
words - there are results "with peaks in roughly the right
29
range for Thymosin Beta-4"?
30
DR VINE:
31
MR HOLMES:
Yes.
If we go to Professor Handelsman's report, at
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PROF. HANDELSMAN/DR VINE
1
paragraph 6 he's got test 1 on 9 May 2012.
2
indicating a substance with a molecular mass of 4971;
3
correct?
4
DR VINE:
5
MR HOLMES:
6
Yes.
And for tests 2, 3, 4 and 5 they are all the tests
that you refer to in 2013; correct?
7
DR VINE:
8
MR HOLMES:
9
There's a peak
Yes.
Just so that I have it correct, in paragraph 13 you
refer to Professor Handelsman's tests in 2 to 6?
10
DR VINE:
11
MR HOLMES:
12
DR VINE:
13
MR HOLMES:
Yes.
I take it that's a mistake and it should be 2 to 5?
Yes, that's correct, yes.
Coming back to your paragraph 16, you have looked
14
at the 2012 analysis, that's JV-4, paragraph 1 - paragraph
15
18.
16
your review of that analysis; correct?
17
18
19
20
21
MR IHLE:
The molecular mass of Thymosin Beta-4 is 4971, on
I object to the question, Your Honour.
It begs the
answer - - MR HOLMES:
I will rephrase the question.
Dr Vine, the
molecular mass of Thymosin Beta-4 is what?
DR VINE:
Well, it really depends what you are talking about
22
molecular mass, if you are talking about the average
23
molecular weight, or whether you are talking about the
24
monoisotopic mass that you would see in a mass
25
spectrometer, which would be just one mass of a range of
26
masses that you would expect to see.
27
28
29
MR HOLMES:
What would you expect to see for Thymosin Beta-4 on
the test conducted that appears in JV-4, figure 1?
DR VINE:
I don't know what you would expect to see because the
30
mass spectrometer is not properly calibrated at that range
31
and it doesn't have the resolution to show the mass
.AFL Anti-Doping Tribunal
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PROF. HANDELSMAN/DR VINE
1
2
3
4
spectrum of Thymosin Beta-4 properly.
MR HOLMES:
It it was properly calibrated, what would you
expect?
DR VINE:
It would depend on what the resolution of the
5
instrument is, and I don't know what the resolution of the
6
instrument is other than it appears to produce peaks 10
7
mass units wide or 10 daltons wide.
8
I could sum up and I could say I would expect to see a
9
kind of a blob, something similar to what is shown in the
So I think perhaps
10
zoom trace, and that blob would probably be centred
11
somewhere about 4964 or 4965.
12
the mass spectrometer has been set up, or should I say the
13
lack of the way it has been set up, doesn't really
14
engender any confidence in its mass calibration or its
15
resolution.
16
afraid.
17
18
19
MR HOLMES:
But unfortunately the way
So this is all a little bit vague, I'm
All right.
But you mention that you would have
expected to see 4963; correct?
DR VINE:
I would have expected to have seen something like you
20
can see in that lower figure in figure 1.
21
that about 10 mass units wide unresolved, and the centre
22
of that mass I really would expect to be, if it was
23
Thymosin Beta-4, about 4964, possibly 4965.
24
exactly where it would be because of the nature of the
25
data that's coming out of the mass spectrometer.
26
MR HOLMES:
So a blob like
You can't say
If you were testing for Thymosin Alpha-1 what would
27
you expect to see for the blob when you zoom as you have
28
done on the lower figure?
29
30
31
DR VINE:
You would expect a peak in the range of about 3,000,
somewhere close to 3,000, I think, from memory.
MR HOLMES:
It's clear then, if you had two substances, one you
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709
PROF. HANDELSMAN/DR VINE
1
suspected was Thymosin Beta-4 and one you suspected was
2
Thymosin Alpha, and this was the result of your test,
3
would you agree that that clearly shows of the two
4
alternatives it's clearly Thymosin Beta-4?
5
DR VINE:
Well, that makes the assumption that one of them is
6
Thymosin Beta-4 and the other one is Thymosin 1 Alpha.
7
that was the case, if you were certain that one of them
8
was Thymosin Beta-4 and one of them was Thymosin Alpha-1
9
and you were presented with that data, you could say,
If
10
well, the one with the mass up in the 4000s is Thymosin
11
Beta-4 clearly, the one with the mass in the 3000s is
12
Thymosin Alpha-1 clearly.
13
the data that's presented in these mass spectra be certain
14
to any requisite standard that the peak with the mass
15
4971, or in fact 4974, as I later refer to it, as a result
16
of the zoomed data, you cannot be certain or even
17
comfortably confident that that is Thymosin Beta-4.
18
simply too far out.
19
MR HOLMES:
20
DR VINE:
21
It's
Did you want to say comfortably satisfied?
I'm struggling to find a word that expresses exactly
what I want to say.
22
CHAIRMAN:
23
DR VINE:
24
My thesis is that you cannot on
You use your language, Dr Vine.
As a mass spectrometerist, you would reject that that
peak is Thymosin Beta-4 on those data.
25
CHAIRMAN:
26
DR VINE:
Without other information?
Yes.
There's a fundamental reason for rejecting it
27
anyway, and that is that a single peak in a mass
28
spectrometer can never constitute an identification, not
29
with any degree of certainty.
30
doesn't provide a degree of certainty.
31
fundamental property of mass spectrometry.
.AFL Anti-Doping Tribunal
21/01/15
710
It's an indication, but it
That's just a
One ion is
PROF. HANDELSMAN/DR VINE
1
2
never enough.
MR HOLMES:
Your paragraph 18 says the difference is too great
3
for whatever is present in the material to be
4
Thymosin - designated as Thymosin Alpha-1; correct?
5
6
DR VINE:
No, I said the difference is too great for you
to - sorry, which paragraph are you referring to?
7
MR HOLMES:
8
CHAIRMAN:
9
DR VINE:
18.
18 of your report, Dr Vine.
No, I say in there that the difference between the
10
two is such that that difference between 4970-something
11
and 3,100, I believe, that difference is too great for
12
those molecules to be confused.
13
apart or fail to tell them apart on that basis.
14
as I say, is based on the assumption that they are both
15
what they are supposed to be, and I don't think there is
16
any evidence for that, or not convincing evidence anyway.
17
MR HOLMES:
All right.
You couldn't tell them
But that,
But if you were to be asked whether the
18
result is either Thymosin - either Alpha or Beta-4 it
19
would suggest that that one is Thymosin Beta-4, on a rough
20
and ready basis?
21
DR VINE:
Well, I don't accept that it does suggest that it's
22
Thymosin Beta-4.
23
support it to a degree that would allow you to make that
24
conclusion.
25
MR HOLMES:
26
DR VINE:
As I said, the data doesn't really
Even if it was one or the other?
If you knew with certainty that it was Thymosin
27
Beta-4 and you knew the other one with certainty was
28
Thymosin Alpha-1, then those data together would enable
29
you to distinguish between them, clearly.
30
is we don't know with certainty that either one is what it
31
seems to be.
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711
What I'm saying
PROF. HANDELSMAN/DR VINE
1
CHAIRMAN:
Can I ask you this, Dr Vine: taking those two
2
calculations, would it be correct to say that the lower
3
calculation, that's the 3,000, is not consistent with it
4
being Thymosin Beta-4?
5
DR VINE:
6
CHAIRMAN:
7
DR VINE:
9
CHAIRMAN:
10
DR VINE:
11
CHAIRMAN:
No, not on the face of the data.
It doesn't tell you which one it is?
No.
But it's not consistent with those substances in
those circumstances?
13
DR VINE:
14
MR HOLMES:
15
And, similarly, the upper calculation is not
consistent with it being Thymosin Alpha?
8
12
Certainly not, no.
That's correct, yes.
Could I ask Professor Handelsman to respond to the
same question?
16
CHAIRMAN:
Yes; that's why we are doing it this way.
17
PROF. HANDELSMAN:
I would agree with Dr Vine that if you were
18
to take a - what I'm going to say is that the context is
19
very important here.
20
label, no marking on it whatsoever, and put it into a mass
21
spectrometer and get a peak like that, identification of
22
any particular named substance, that is not sufficient.
23
If you know it's a protein, you would have to have the
24
amino acid sequence.
25
I believe these data arose.
26
compounding chemist who ordered what I think he would have
27
ordered as Thymosin - Thymosin maybe with or without an
28
additional qualification, but it was Thymosin.
29
probably came in a vial which had written on it Thymosin.
30
In my report I said that I thought that there was
31
incomplete information for a really well-done forensic
.AFL Anti-Doping Tribunal
21/01/15
If you were to take a vial with no
But this is not the context in which
712
These data arose from a
It
PROF. HANDELSMAN/DR VINE
1
analysis, and that sort of information on what the sample
2
looked like when it came, what was written on it would
3
have helped a lot.
4
something, they ordered something that was probably
5
Thymosin, and what they are doing in here is a rough and
6
ready way of saying, just making sure that it's - of the
7
two alternatives, which one it is.
8
not a perfect identification as if it arose in a vacuum.
9
But it is a way of identifying which of two alternative
But I think in this context they got
So in that sense it's
10
thymosins that they would have possibly ordered from the
11
external supplier - which it is, and it is clear that the
12
molecular weights are so different that you can't confuse
13
them, even if the machine is a little bit out of
14
calibration.
15
identification from scratch, but it is an attempt to
16
distinguish between the two.
17
That's why in my report I said if the question underlying
18
the analysis - and every analysis has an underlying
19
question that has to be answered, but if the question
20
underlying the analysis was which of these two it was,
21
within the error of the methodology and software, it gave
22
one or other answer in all of those analyses.
23
MR HOLMES:
This is not intended to be a perfect
All right.
That's how I would read it.
Dr Vine, you have said in paragraph 11
24
there's a lack of a reliable calibration and resolution in
25
the first sentence?
26
DR VINE:
27
MR HOLMES:
28
DR VINE:
29
MR HOLMES:
30
31
Yes.
So you have taken the figure of 4974?
Yes.
And you have said that the calibration error was
approximately 10 daltons?
DR VINE:
Yes.
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PROF. HANDELSMAN/DR VINE
1
MR HOLMES:
2
DR VINE:
That's 4974 plus or minus 10?
Well, it appears to be - if the material really was
3
Thymosin Beta-4, then the calibration error would be plus
4
10 on that basis.
5
MR HOLMES:
6
DR VINE:
7
MR HOLMES:
Plus 10?
Yes.
Approximately.
Then you have in paragraph 12, "The data indicated
8
the presence of a substance with a molecular weight of
9
perhaps", and then you have a figure of 4955?
10
DR VINE:
11
MR HOLMES:
12
DR VINE:
13
MR HOLMES:
Yes.
4985?
Yes.
And if you look at that it's 4974 plus or
14
minus - it is plus 11, and just help me with the maths
15
there, Doctor.
16
DR VINE:
The difference between - it's really just a 30-dalton
17
range of a 4955 to - so it's about 10 daltons from 4955 to
18
4965, and then another 10 daltons from 4974 to 4985, 11
19
daltons.
20
quite frankly, looking at the data I can't be certain what
21
the true mass is.
22
So I have applied a range of about plus or minus 15
23
daltons, so I'm encompassing a 30-dalton range, which
24
I don't think on my reading of the data is unreasonable,
25
given the operation of the instrument.
26
MR HOLMES:
So I have taken a bit of a range there because,
All right.
It's impossible to tell from the data.
Your briefing letter at JV-2 from Tony
27
Hargreaves & Partners, 13 January 2015, asked for a report
28
setting out a number of bullet points there?
29
DR VINE:
30
MR HOLMES:
31
Yes.
You have been asked whether or not in the second
last bullet point on that page, "Could it be a substance
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PROF. HANDELSMAN/DR VINE
1
other than Thymosin Beta-4 but with a similar molecular
2
weight, for example, Thymosin Beta-10 and Thymosin
3
Beta-15"?
4
DR VINE:
5
MR HOLMES:
6
CHAIRMAN:
7
DR VINE:
8
MR HOLMES:
9
10
I don't see that.
Where is that?
Sorry, page 2.
Page 2 of the letter of 13 January.
I see, yes.
You don't mention Thymosin Beta-10 or Thymosin
Beta-15 in your report, do you?
DR VINE:
No, but I do say that it could be a - well, in fact
11
it's very likely to be a substance other than Thymosin
12
Beta-4.
13
14
MR HOLMES:
CHAIRMAN:
16
MR HOLMES:
Is this already in, Mr Holmes?
No, this is a new document.
PROF. HANDELSMAN:
19
MR HOLMES:
21
I think this document
was obtained by you, Professor Handelsman, over lunch?
18
20
Can I provide them
to the Tribunal.
15
17
Can I just show you a document.
That's right.
Could you tell the Tribunal what it shows and where
it came from?
PROF. HANDELSMAN:
This is an entry from the National - it's
22
really where the PubMed comes from, the
23
National C - I have forgotten what "C" is.
24
very well established NIH based protein database centred
25
in Washington.
26
reliable information on various proteins - in this case
27
Thymosin Beta-10 homo sapiens, meaning the human version -
28
and it points out that it has 38 amino acids, and it's a
29
single letter amino acid sequence, is at the bottom.
30
subsequently have the accurate molecular mass, which
31
is - the accurate molecular mass is less than 4,000,
Anyway, it's a
It's widely used as a way of identifying
.AFL Anti-Doping Tribunal
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715
We
PROF. HANDELSMAN/DR VINE
1
I think, from memory.
2
MR HOLMES:
I will just show you this document.
3
PROF. HANDELSMAN:
4
MR HOLMES:
5
PROF. HANDELSMAN:
Sorry, the molecular mass is 4367.
Can I hand up four copies of that.
I would add that the nature of amino acids
6
is such that the smallest is a molecular weight of 75, the
7
largest is 200, and adding or subtracting one would
8
certainly be detectible based on that sort of molecular
9
mass.
10
But this figure of 4368, roughly, would be way
separate from the peak in question.
11
CHAIRMAN:
12
#EXHIBIT AS-23 - Documents relating to Thymosin Beta-10.
13
MR HOLMES:
14
Dr Vine, are you able to help us with the molecular
weight of Thymosin Beta-15?
15
DR VINE:
16
MR HOLMES:
17
DR VINE:
18
MR HOLMES:
19
We might formally receive those, Mr Holmes.
No, I don't know what it is off - - Did you look it up at all?
No, I didn't.
Did you download the same documents in respect of
Thymosin Beta-15?
20
PROF. HANDELSMAN:
21
MR HOLMES:
Yes, I did.
Are they the molecular structure documents?
I hand
22
up four copies.
23
lunch break for the molecular weight of Thymosin Beta-15?
24
25
PROF. HANDELSMAN:
Did you also conduct a search over the
Yes.
That's on this document here.
figure is 5229, roughly.
26
MR HOLMES:
27
#EXHIBIT AS-24 - Documents relating to Thymosin Beta-15.
28
MR HOLMES:
29
That
I hand up four copies.
Is the peak we are talking about, in your view,
referable to Thymosin Beta-10 or Thymosin Beta-15?
30
DR VINE:
31
MR HOLMES:
No, I don't think it is.
You then spoke about doing a search on the
.AFL Anti-Doping Tribunal
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716
PROF. HANDELSMAN/DR VINE
1
ChemSpider database.
2
DR VINE:
3
MR HOLMES:
4
5
Yes.
Could you tell me what were the parameters of the
search that you entered in the ChemSpider web page?
DR VINE:
As stated in paragraph 15, I entered a mass range of
6
4955 to 4985 and asked it basically just to look for
7
entries within that database with molecular weights in
8
that range.
9
10
MR HOLMES:
Professor Handelsman, did you do a search on the
ChemSpider web database over the luncheon break?
11
PROF. HANDELSMAN:
Yes, I did.
I would say that we have a copy
12
of it.
13
plus or minus a difference.
14
kind of 30-dalton range that Dr Vine had, but nevertheless
15
we have done a search on using the molecular mass of 4974
16
that he used, plus or minus 11.
It allows you to give a centred molecular mass,
17
MR HOLMES:
All right.
18
PROF. HANDELSMAN:
19
MR HOLMES:
20
CHAIRMAN:
21
PROF. HANDELSMAN:
So I wasn't able to get that
Is that the result of your search?
That is correct, yes.
I tender that search.
That will be AS-25.
The search relates to - - -
It's a search of the ChemSpider database
22
putting in a known molecular weight on the basis that, if
23
the figure from the readout was 4974, what other ones
24
could be around that molecular mass.
25
CHAIRMAN:
So it's a search based on a particular molecular
26
weight?
27
PROF. HANDELSMAN:
28
29
30
31
Correct, a range of molecular masses.
A
range of 22 on either side of 4974.
#EXHIBIT AS-25 - Professor Handelsman's ChemSpider database
search.
MR HOLMES:
Just going through it, in paragraph 11 in the last
.AFL Anti-Doping Tribunal
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717
PROF. HANDELSMAN/DR VINE
1
sentence, Dr Vine, you say, "If the peak with the MZ is
2
4974 is really Thymosin Beta-4 then the mass spectrometer
3
would appear to have a calibration error of approximately
4
10 daltons"; correct?
5
DR VINE:
6
MR HOLMES:
7
Yes.
So we go to the search.
have entered that weight of 4974 plus or minus 11?
8
PROF. HANDELSMAN:
9
MR HOLMES:
10
Professor Handelsman, you
Yes.
What did the result of the ChemSpider website show?
PROF. HANDELSMAN:
I got 20 hits as opposed to Dr Vine's 28.
11
I don't think that's a material difference.
12
matter of how you specify the molecular mass range.
13
got 20 hits.
14
on the second last page, second from the bottom, which is
15
Thymosin Beta-4 acetate.
16
Thymosin Beta-4 with the acetyl group attached within that
17
range.
18
other name Thymosin in that range.
19
20
21
MR HOLMES:
It's all a
We
I draw your attention to the second last one
In other words, it identified
But there was no other Thymosin identified, no
So the ChemSpider website identifies all - is it
all known substances or?
DR VINE:
Perhaps I should say a few words about it.
The
22
ChemSpider database is a database of known chemical
23
compounds compiled by the Royal Society of Chemistry.
24
currently stands I believe at something in the region of
25
22 or 23 million compounds.
26
compiled largely by chemists, and it's a database that
27
isn't particularly I think replete with biological
28
molecules, with proteins and peptides.
29
commonly accepted chemical compounds.
30
means a comprehensive biological database, but it does
31
contain quite a large number of peptides and proteins.
.AFL Anti-Doping Tribunal
21/01/15
718
It
It's a database that's been
It's more the more
So it is by no
PROF. HANDELSMAN/DR VINE
1
It's a way of identifying materials on the basis of
2
various properties that they might have.
3
individual searches such as the one that's been done here,
4
which is a search based on molecular weight.
5
way of finding possibilities when you - in this particular
6
case, when you've run a mass spectrum, you have obtained a
7
molecular weight, you can then go into ChemSpider and
8
determine what substances have this molecular weight.
9
Professor Handelsman has pointed out and as you would
You can do
So it's a
As
10
expect, given that a fairly wide mass range has been put
11
in and that mass range does encompass the molecular weight
12
of Thymosin Beta-4 as the (indistinct) version, it did
13
find what it calls Thymosin Beta-4 acetate, which is the
14
same thing, which is what you would expect.
15
there.
16
that's indicated - and I agree with Professor Handelsman,
17
I don't think there's a material difference.
18
slightly wider mass range.
19
11, but there are also a number of other compounds that
20
are in there as well.
21
Thymosin Beta-4 and those other 20 compounds in that list
22
based on the molecular weight.
23
It is in
But the problem is that within the mass range
PROF. HANDELSMAN:
I used a
Professor Handelsman has used
So you can't distinguish between
Could I add, though, that I think most of
24
these compounds that are listed here do not necessarily -
25
in fact, I doubt that any of them - occur in nature.
26
are just simply chemical structures that are used for
27
identification purposes.
28
artificially created.
29
recognisable that occurs in nature would usually have the
30
annotation as Thymosin Beta-4 does with a CAS number.
31
Those are actually separately searched.
.AFL Anti-Doping Tribunal
21/01/15
They
In other words, they are
I think any one of those that is
719
So, as
PROF. HANDELSMAN/DR VINE
1
I understand it, this means that the only recognised
2
biological molecule in that range is actually Thymosin
3
Beta-4 acetate.
4
DR VINE:
Well, ChemSpider doesn't make that sort of
5
distinction as to what sort of molecule it is.
It only
6
lists what it has in the database.
7
of chemical identity.
8
material, the one that's mentioned in the letter of
9
instruction that I was given, this material is Thymosin
The issue here is one
The proposition is that this
10
Beta-4.
My thesis is simply the evidence does not support
11
the identity of the material as Thymosin Beta-4.
12
possibility, but it isn't a certainty, not by a long way.
13
Given that, as I said earlier, this database is not
14
complete, from my experience of using it, it doesn't cover
15
the area of proteins and peptides particularly
16
comprehensively.
17
sources rather than biological sources.
18
of amino acids and the fact that, while there are
19
naturally occurring amino acids, there are also
20
potentially lots of non-naturally occurring amino acids,
21
in fact probably many thousands of them, and the
22
possibilities and combinations that could all add up to
23
the correct molecular weight would be an enormous number.
24
So it really goes down to whether one has confidence that
25
the material analysed at Bio21 in 2012 was Thymosin
26
Beta-4, and I say on the evidence, on the analytical data
27
that we have before us, it's not that you can't be certain
28
that it isn't Beta-4; I don't think you can really even
29
conclude that it's probable.
30
best.
31
calibrated, and we simply don't know that.
It is a
It's been compiled mostly from chemical
Given the nature
It's perhaps possible at
But a lot depends on how well that instrument was
.AFL Anti-Doping Tribunal
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720
So even that
PROF. HANDELSMAN/DR VINE
1
possibility is tinged with that qualifier.
2
I said earlier, the other qualifier is to what extent a
3
mass spectrum with one peak in it can be said to identify
4
any substance.
5
identification in the case of a criminal matter or even
6
identification in the case of identifying a drug for
7
sports drug testing purposes, such an identification would
8
simply not stand up.
9
reputable laboratory would claim they had identified a
10
drug on the basis of a single peak in a mass spectrum.
11
MR HOLMES:
Then, as
If we were talking here about forensic
It wouldn't even be put forward.
Dr Vine, you have drawn the conclusion in paragraph
12
18 that it's not that of a Thymosin Alpha-1, correct,
13
because the difference is too great?
14
DR VINE:
No
Yes.
Yes, I agree.
I believe it is possible to draw
15
that conclusion that it - even given the inaccuracy of the
16
instrument and its lack of resolution, I think you can be
17
pretty confident that the material that gives the peak at
18
4971 or 4974, whichever you want to use, that that isn't
19
Thymosin Alpha-1.
20
21
22
MR HOLMES:
May it also be concluded that the mass spectrum in
figure 1 is not that of Thymosin 10, Beta-10?
DR VINE:
I would say that's very probable too.
I think the
23
mass that we have been given here is out significantly.
24
We are probably looking at something in the region of 600.
25
We have 4367 as against 4965 or 4.
26
difference.
27
out that far.
28
MR HOLMES:
So that's a very big
I doubt that the mass spectrometer would be
It may also be concluded that the Thy A-5 mass
29
spectrum shown on figure 1 is not that of Thymosin
30
Beta-15?
31
DR VINE:
Yes, I think that's a reasonable conclusion too.
.AFL Anti-Doping Tribunal
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721
PROF. HANDELSMAN/DR VINE
1
Again, you are talking of a mass difference of several
2
hundred.
3
spectrometer, a mass difference of several hundred is
4
sufficient for you to say it's not either of those two
5
compounds.
6
MR HOLMES:
So, again, despite the performance of the mass
May it also be concluded that the Thy A-5 mass
7
spectrum is not that of a mixture of thymosins or
8
peptides?
9
DR VINE:
There is no evidence of a mixture because there is
10
only one peak, although we have to say here, and I'm sorry
11
if I sound repetitive, the peak is 10 daltons wide.
12
there were some other Thymosin with a very, very similar
13
mass within a few mass units of the Thymosin Beta-4, it
14
could be buried in there and we wouldn't know because the
15
peak isn't able to resolve those materials.
16
wouldn't know about that.
17
MR HOLMES:
If
So we simply
Wouldn't that Thymosin of an unnamed variety, other
18
than Thymosin Beta-4, be brought up in your ChemSpider
19
search?
20
DR VINE:
It might be, and it might be one that doesn't have a
21
trivial name, for all I know.
22
it, is a generic term and there are any number of
23
thymosins, I presume.
24
endocrinologist, and the thymus gland is not my area of
25
expertise.
26
peptides and proteins in relation to that particular gland
27
and how it operates.
28
established, whether they are all known, I don't know.
29
point is simply that on the data that we have we really
30
can't be certain about identity.
31
MR HOLMES:
Thymosin, as I understand
I don't profess to be an
But I do appreciate that there are a lot of
Whether they have all been
My
Professor Handelsman, can you comment on that?
.AFL Anti-Doping Tribunal
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722
PROF. HANDELSMAN/DR VINE
1
PROF. HANDELSMAN:
I would add that thymosins are a family of
2
peptides that are most expressed in the thymus.
There is
3
a limited number of them, and the sequencing of most
4
of - of quite a large - probably all of them is known.
5
When it comes to actually - and again context is important
6
here.
7
chemical manufacturers or so on, there's only really two
8
that are actually ever advertised - that's Thymosin
9
Alpha-1 and Thymosin Beta-4.
When it comes to actually purchasing through
There may be others that are
10
available or could be synthesised on request, although
11
heaven knows I don't think the parties involved in this
12
would have the sophistication to ask to synthesise some
13
other Thymosin which is not characterised at all
14
biologically.
15
search didn't turn up any other named Thymosin, it is most
16
likely, and I haven't exhaustively tested each one of
17
them, but it is certainly not Beta-10 or Beta-15.
18
more time, and I only really got to do this at lunchtime,
19
I think we could check each one of these.
20
very surprised if these aren't all artificial compounds
21
which don't occur in nature, which aren't - are just not
22
in the frame for thinking about ordering them and
23
potentially using them the way in which the peptides
24
involved in this case have been contemplated at least.
25
DR VINE:
26
CHAIRMAN:
27
DR VINE:
So I think the fact that the ChemSpider
With
But I would be
Am I able to make a comment to that, Mr Chairman?
Yes, of course.
What I would say there is that certainly my
28
experience with purchasing peptides and proteins has been
29
an interesting one in that when you order these materials
30
it is certainly necessary to check what you have ordered
31
because you often find that what you have ordered isn't
.AFL Anti-Doping Tribunal
21/01/15
723
PROF. HANDELSMAN/DR VINE
1
what you expected.
The industry as a whole, and we heard
2
some of this this morning, contains a number of companies
3
which produce materials of very dubious authenticity, and
4
it could well be that if you have bought something which
5
you think is Thymosin Beta-4 you have been provided with
6
one of these things that the ChemSpider database, albeit
7
an artificial substance, has produced.
8
chemical company's failed attempt to make Thymosin Beta-4
9
or some analogue or some variant of it.
It may be some
The whole point
10
of this is that you cannot be sure when you buy these
11
materials.
12
context that we are looking at here.
13
considering a material that's going to be formulated in
14
some way and then injected into someone, I think it's
15
incumbent upon whoever has sourced that material and will
16
compound it to be absolutely certain that they know what
17
it is, not to be, "Well, it probably is this because the
18
mass is around about where it ought to be."
19
I sit, if I'm on the other end of the syringe needle, on
20
the sharp pointy end, I expect that whoever is putting it
21
into me knows exactly what it is, not just same vague
22
notion that it is probably the right thing.
23
reason in my view it's fundamentally important that these
24
materials are characterised properly, and that clearly
25
hasn't been done in this case.
26
Analytical Services, with these materials, we have done
27
work on the ones we have bought ourselves.
28
done a lot of work for Australian Customs on materials
29
that have been seized for one reason or another as
30
potential prohibited imports, where we have found that it
31
is quite a frequent occurrence for these materials not to
I think this is exceedingly important in the
.AFL Anti-Doping Tribunal
21/01/15
724
When you are
From where
For that
Our experience, Racing
We have also
PROF. HANDELSMAN/DR VINE
1
be what they are labelled to be.
2
between being similar but not quite the same - I cite an
3
example in here of a material that we found to be almost
4
AOD-9604 except one amino acid had been changed; or it may
5
be a totally unknown peptide with goodness knows what
6
properties, or in fact there simply may be nothing there
7
at all.
8
materials are properly identified.
9
10
MR HOLMES:
That can vary anywhere
So for me it is of vital importance that these
Can Professor Handelsman respond?
PROF. HANDELSMAN:
I couldn't agree more in what Dr Vine has
11
established, which is the proper standard the
12
pharmaceutical companies follow.
13
anything like the sort of things we have talked about.
14
they ordered a peptide, they didn't make it themselves,
15
they would sequence it probably several times in both
16
directions to make sure that it is what it is and that it
17
is highly purified.
18
I think what we are talking about in this particular
19
discussion is really people who cut every corner, cut many
20
corners, let's say.
21
there's plenty of people who have less scruple than a
22
pharmaceutical company.
23
that the compounding chemist or someone on his behalf
24
ordered something called Thymosin and they simply wanted
25
to do a check which of the two thymosins it might be.
26
That's about all.
27
pharmaceutical industry standards.
28
standards, and in some cases it is the shortcut of
29
compounding pharmacists, and I think it doesn't exclude
30
the possibility that this is Thymosin Beta-4 at all.
31
fact, the likelihood is, as we have identified in the
They wouldn't do
All of that is perfectly true.
If
But
As Mr Ihle reminded me repeatedly,
I think it is quite plausible
I don't think they are following the
.AFL Anti-Doping Tribunal
21/01/15
725
They follow their own
In
PROF. HANDELSMAN/DR VINE
1
2
search, that it's the most likely candidate for that peak.
CHAIRMAN:
In the end, gentlemen, those points you raise are
3
very important and very valid.
4
all that in the context of this case, which is a bit
5
different from a very good scientific laboratory being
6
operated here, Dr Vine, I can assure you.
7
MR HOLMES:
8
CHAIRMAN:
9
MR GLEESON:
We ultimately have to put
I have no further questions.
Mr Gleeson?
Thank you, Mr Chairman.
Dr Vine, I might have
10
misheard you, so please forgive me if I'm putting back to
11
you something that you just didn't say, but I thought
12
I heard earlier on during your evidence you say something
13
to this effect, that as a mass spectrometerist you would
14
reject that this was Thymosin Beta-4.
15
DR VINE:
Yes.
If I was given the data and I knew that the
16
mass spectrometer was properly calibrated and had its
17
resolution adjusted as well as it could be, I would reject
18
it on two grounds: one, if it was properly calibrated,
19
then the mass is wrong and therefore it can't be Thymosin
20
Beta-4.
21
accurate, this says there is something there with a
22
molecular weight of 4971 or 74, whichever we take as being
23
the correct one, and that means it can't be Thymosin
24
Beta-4 because we know that the molecular weight of
25
Thymosin Beta-4 is - its monoisotopic weight is actually
26
4960, and then you add a proton for the MALDI process, so
27
that would give you 4961.
28
distribution which actually gives you some additional
29
peaks as well.
30
I have also said, you would never base an identification
31
on a single peak in a mass spectrometer.
It can't be out by 10 because the instrument is
Then you have an isotopic
However, on a more fundamental level, as
.AFL Anti-Doping Tribunal
21/01/15
726
You need more
PROF. HANDELSMAN/DR VINE
1
evidence than that to conclude that something's identity
2
has been established.
3
MR GLEESON:
That second point is a rather different point,
4
isn't it?
5
you would reject that it was TB4; that is, you can
6
conclude that it is not TB4.
7
making is that you simply can't be sufficiently satisfied
8
that it is TB4.
9
DR VINE:
You are not saying by that second point that
That's correct.
10
question.
11
single - - -
12
CHAIRMAN:
13
DR VINE:
The second point you are
There are two sides to that
You would never be satisfied on the basis of a
Just on the basis of that single analysis.
Particularly given the resolution of the instrument.
14
The peak is 10 daltons wide.
If you were to analyse
15
Thymosin Beta-4 on a more modern mass spectrometer - the
16
Bruker Microflex is a pretty outdated instrument.
17
one of my protein chemist colleagues refers to it as a bit
18
of an outdated toy.
19
that we use routinely nowadays, it's not a very
20
sophisticated machine.
21
If you analyse it on the sort of equipment that we use in
22
Racing Analytical Services laboratory, instead of seeing
23
that blob 10 peaks wide what you would see in our
24
laboratory, and we have done this because we have analysed
25
a sample of Thymosin Beta-4 for Australian Customs - what
26
you actually see are something of the order of 10
27
individual peaks, and they are the isotopic peaks of
28
Thymosin Beta-4.
29
and there are 10 - set of 10 peaks.
30
you still wouldn't be sure it was Thymosin Beta-4 because
31
you have the fundamental issue that a single mass
It is -
Compared to the sort of instruments
It doesn't have a lot of power.
We can resolve them all into a cluster,
.AFL Anti-Doping Tribunal
21/01/15
727
Even if you got that
PROF. HANDELSMAN/DR VINE
1
spectrometric cluster of isotopic peaks doesn't constitute
2
an identification.
3
CHAIRMAN:
4
DR VINE:
But it would be consistent?
But it would be consistent and it would be a much
5
better indication.
But it still would fall short of
6
definitive.
7
really the only way to be sure this is Thymosin Beta-4
8
would be to actually do a sequence determination on it.
9
You would - for a start you wouldn't just use mass
As I think Dr Watt said in his statement,
10
spectrometry.
You would use liquid chromatography mass
11
spectrometry, which separates mixtures first and then
12
introduces them sequentially into the mass spectrometer.
13
You would treat the molecule with a digestive enzyme
14
called trypsin, which will cleave it into smaller, more
15
manageable bite-size pieces, and then you would analyse
16
those individual pieces to ensure that the sequence of
17
amino acids is the same, because what needs to be borne in
18
mind is that even if you identify the molecular weight
19
absolutely - and the instrument that I'm talking about
20
that we use doesn't measure the molecular weight to one
21
dalton.
22
thousandths of a dalton, which is what's called high
23
resolution mass spectrometry.
24
be sure it's Thymosin Beta-4 because you have the
25
molecular weight, which means all the right amino acids
26
are there but it doesn't mean they are in the right order.
27
You can have a word and you can have all the letters in
28
the word but unless the letters are all in the right order
29
the word isn't there.
30
if all the amino acids are there, if they are not
31
connected in exactly the right order, the molecule is not
It actually measures the molecular weight to two
.AFL Anti-Doping Tribunal
21/01/15
Even with that, you can't
That's how the system works.
728
Even
PROF. HANDELSMAN/DR VINE
1
Thymosin Beta-4.
So, even if the mass was perfectly lined
2
up, it wouldn't provide conclusive evidence.
3
PROF. HANDELSMAN:
I just would like to add a bit of a reality
4
check.
5
perfection, which is certainly ideal, but I would also
6
point out that even a calibration error of 10 in a
7
molecular weight range of around 5000 is 0.2 of
8
a per cent.
9
the perfect standards that are alluded to.
This is really setting a standard of scientific
It is not enormous.
It is enormous maybe by
But this is
10
still a working machine in a very high quality research
11
institute that does very high quality work using that
12
machine.
13
medical research in which they do - have a huge
14
throughput.
15
of good.
16
about the most plausible identification, it doesn't
17
require that level of finesse.
18
MR GLEESON:
If it were so defective it wouldn't be useful in
So I would just say that perfect is the enemy
I think for the purposes that we are talking
Just returning to the first of the two reasons you
19
advanced, Dr Vine, for the proposition that you would
20
reject that this was TB4, if you assume that the
21
spectrometer has a calibration error of approximately 10
22
daltons, then there would be no basis for rejecting that
23
the product in question was Thymosin Beta-4; you would
24
simply adhere, I assume, to the proposition that you can't
25
be certain that it is Thymosin Beta-4?
26
27
28
29
DR VINE:
Yes, that's right, if that were the case, but the
trouble is we don't know whether that's the case or not.
MR GLEESON:
So if I ordered Thymosin Beta-4 and I sent it off
to the mass spectrom - that person.
30
DR VINE:
Yes.
31
MR GLEESON:
And I received the results as depicted in Thy A-5.
.AFL Anti-Doping Tribunal
21/01/15
729
PROF. HANDELSMAN/DR VINE
1
DR VINE:
Yes.
2
MR GLEESON:
And I knew that my spectrometer had a calibration
3
error of approximately 10 daltons, I would say to myself
4
"the results are consistent with what I ordered"?
5
DR VINE:
You could say that to yourself, although I think my
6
comment would be that if you are operating the mass
7
spectrometer and you know you have a 10-dalton error then
8
you are not a very good operator and you shouldn't be
9
doing it.
To knowingly operate an instrument when it is
10
out of calibration is exceedingly unscientific and verging
11
on negligent.
12
PROF. HANDELSMAN:
Again, I'm sufficiently impressed that
13
I will always send samples to Dr Vine because he has such
14
high standards.
15
most machines - mass spectrometers are quite finicky
16
machines and they do get out of calibration relatively
17
often.
They regularly need servicing and calibration and
18
so on.
I don't think an error of 10 daltons in 5000 is
19
hugely material.
20
it's satisfactory.
21
reject the information out of hand.
22
MR GLEESON:
23
CHAIRMAN:
24
MR IHLE:
25
But that is a standard of perfection that
It is not desirable.
You wouldn't say
But it is also not sufficient to
Those are the only questions I have.
Mr Ihle?
Dr Vine, I would like to take you to JV-1, which is a
copy of your curriculum vitae attached to your report.
26
DR VINE:
Yes.
27
MR IHLE:
Under "Qualifications", the last entry that you have
28
there is "National Association of Testing Authorities,
29
Australia, Assessor, 1992 and continuing"?
30
DR VINE:
Yes.
31
MR IHLE:
What does that role involve?
.AFL Anti-Doping Tribunal
21/01/15
730
PROF. HANDELSMAN/DR VINE
1
DR VINE:
Perhaps I'd better start from the name of the - the
2
National Association of Testing Authorities, Australia is
3
a kind of a quasi government body now, I suppose, which is
4
charged with the accreditation of laboratories for
5
competence to do what they say they can do.
6
sole body within Australia that provides accreditation of
7
laboratories generally these days to various international
8
standards, such as ISO 17025, which is the one most
9
applicable to chemical laboratories.
So it's the
It works on the
10
basis of assessing a laboratory in terms of their
11
compliance obviously with the bureaucratic parts of the
12
various international standards and then also with the
13
technical requirements of being able to do what they claim
14
they can do.
15
uses two sorts of assessors.
16
assessor, and then they use a set of scientific assessors
17
who are called in for specific purposes.
18
assessor's job is to look at the methodology of the
19
laboratory, to examine its quality control procedures, all
20
of its technical operations and effectively say, "Is it
21
fit for purpose," I suppose is the most simple way of
22
putting it.
23
to look at how laboratories operate and whether they can
24
actually do what they claim they can do to the required
25
international standard.
26
MR IHLE:
It's very similar to GMP registration.
NATA provide their own
The scientific
That's been my role as a technical assessor,
I might get the acronym wrong, but the national
27
testing measurement institute or the national - the
28
testing measurement institute - - -
29
30
31
DR VINE:
It
I'm not familiar with - I'm familiar with the
National Measurement Institute, NMI.
MR IHLE:
That's the one, NMI.
.AFL Anti-Doping Tribunal
21/01/15
731
Does your role involve any
PROF. HANDELSMAN/DR VINE
1
2
involvement with NMI?
DR VINE:
It does insofar as the Australian Sports Drug Testing
3
Laboratory - that is the laboratory which ASADA use to
4
carry out their drug testing, so that's the organisation
5
that actually does the drug tests - is part of the
6
National Measurement Institute.
7
actually carried out their technical assessments since
8
1992 on - I'm not sure exactly - three or four occasions,
9
and as well as that I have done desk audits of new methods
As a NATA assessor I have
10
from time to time again to assess whether the methods are
11
fit for purpose.
12
MR IHLE:
So when in paragraph 16 you say the following, "I'm
13
unaware of any sports drug testing authority, human or
14
animal, or regulatory agency, human, environmental or
15
agricultural, which will accept identification on this
16
basis", first of all, "this basis" is referring to that
17
HPLC graph, as I understand it?
18
you say "this basis", is that what you are referring to?
Am I right there, when
19
DR VINE:
It is referring to the mass spectrum.
20
MR IHLE:
Yes, the mass spectrum.
When you say you are unaware
21
of any sports drug testing authority, does that
22
include - do you take into that your experience as a NATA
23
assessor?
24
DR VINE:
Yes.
25
MR IHLE:
That includes assessing the very laboratory that
26
ASADA uses for its own drug testing purposes?
27
DR VINE:
Yes.
28
MR IHLE:
Can I take you then to paragraph 9 of your report,
29
and this is something that's been touched on very briefly
30
in relation to questions that have already been asked of
31
you by Mr Holmes.
In the first sentence of paragraph 9
.AFL Anti-Doping Tribunal
21/01/15
732
PROF. HANDELSMAN/DR VINE
1
you distinguish between what we see on the graph as 4971
2
and what you then go on to say, "it appears the peak has
3
an Mz" - shorthand for molecular weight?
4
DR VINE:
It's not exactly.
One of the things that's not
5
appreciated about mass spectrometry is that it appears as
6
if the scale in a mass spectrometry is mass.
7
scale isn't mass.
8
that in many mass spectrometers the charge is 1; that is,
9
it's a single positive charge or sometimes a single
10
negative charge.
11
same as mass.
12
In fact, the
It's mass to charge ratio.
It's just
So mass to charge ratio is in fact the
Often particularly in the mass spectrometry of
13
peptides and proteins charges can be 2, 3, 4, 5, 10, 15,
14
very large numbers.
15
charge ratio.
16
rather than mass, but they are synonymous only when the
17
charge is 1.
18
MR IHLE:
So in those cases you specify mass to
So I always - you should always use M on Z
In this spectrum the charge is 1.
When you go on to say it's actually closer to 4974,
19
by reference to the graph itself can you explain what you
20
mean by that?
21
DR VINE:
If we go to my figure 1 you can see the upper mass
22
spectrum, there's a very, very small peak which has the
23
number 4971.429 printed above it.
24
you might think that's the mass of the particular peak,
25
when you expand that you get the trace shown at the bottom
26
which shows in fact, or appears to show - and this may be
27
where there's some issue with the Bruker Microflex
28
software that I'm not aware of, but it appears to show
29
4971 isn't the centre of the peak, it is actually the
30
front of the peak really, and the centre of the peak, if
31
you use the scale along the bottom, might be more properly
.AFL Anti-Doping Tribunal
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733
While at first sight
PROF. HANDELSMAN/DR VINE
1
estimated at about 4974.
2
dichotomy comes in.
3
4
MR IHLE:
So that's where that sort of
Professor Handelsman, do you agree with that
assessment of peaks in graphs?
5
PROF. HANDELSMAN:
6
MR IHLE:
Yes, I do.
Does that have any significance in the strength of
7
opinion or otherwise that you are able to give to this
8
Tribunal about what we can do with this analysis?
9
DR VINE:
The comment you would make is 4974 is further away
10
from our expected 4964 or 65 than is 4971.
11
moves it a little bit further away.
12
estimate of about 10 daltons of difference in mass comes
13
from.
14
PROF. HANDELSMAN:
So it actually
That's where my
And I would agree that that just encompasses
15
the calibration error.
16
10, in other words you take 10 away from it, it would
17
coincide with exactly what was expected.
18
plausible at least that the calibration error explains
19
that difference.
20
a plausible one.
21
MR IHLE:
If the calibration error is plus
So it is
It's not the only explanation, but it's
Professor Handelsman, you heard Dr Vine say before
22
that we don't actually know what the calibration error is
23
here.
24
25
26
Do you agree with that?
PROF. HANDELSMAN:
He made an estimate of approximately 10, and
I think that that's a reasonable estimate.
MR IHLE:
Dr Vine, do you make that estimate here, or is that
27
an estimate that you allow for should the substance
28
actually be TB4?
29
is sought to be evidenced by this document, by this
30
analysis, you can work backwards or you can work forwards.
31
Do you actually think there has been a calibration error
So if you start from the premise which
.AFL Anti-Doping Tribunal
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PROF. HANDELSMAN/DR VINE
1
2
of 10 or do you simply not know?
DR VINE:
I think what I said originally was if we assume
3
that - if that peak was Thymosin Beta-4 and we are
4
measuring 4974, then the calibration error would be 10.
5
But I think I also made some comment that we don't know
6
what the calibration error is in fact.
7
be an assumption based on assuming that the peak was
8
Thymosin Beta-4.
9
So that would only
The calibration error may well be much more than
10
we know, perhaps less than we know.
11
the instrument appears to have - again, from Dr Watt's
12
report, because I couldn't get - from the data I was
13
provided I couldn't see the reference standards that
14
Dr Watt referred to in his report with sufficient clarity
15
to estimate how well their masses have been assigned.
16
he has I think more familiarity with the software than
17
I do, and his report suggested that there was reasonable
18
calibration of the instrument up to about 3000.
19
beyond that there was no evidence of any calibration
20
standards that had been run.
21
was pretty much unknown.
22
MR IHLE:
23
PROF. HANDELSMAN:
But the problem is
But
But
So beyond 3000 calibrations
You seem to be nodding, Professor Handelsman?
I agree that it's uncertain rather than
24
unknown.
25
it's likely - it's possible that there may be some error
26
beyond that.
27
adequate up to 3000.
28
it would be.
29
DR VINE:
If the calibration up to 3000 is reasonable,
But it's not likely to be enormous, if it is
Having said that, you can't say what
But it wouldn't be enormous.
I don't know that you can say what it would be.
30
the calibration error progressed in a linear fashion,
31
perhaps that might be true.
.AFL Anti-Doping Tribunal
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735
If
But it may not progress in a
PROF. HANDELSMAN/DR VINE
1
linear fashion.
2
behave in a linear manner once they get towards the upper
3
range that the instrument is capable of functioning at.
4
It may well be that the change in calibration accuracy as
5
you go to higher masses is not a linear, that is a
6
straight line, relationship; it may well be an exponential
7
relationship.
8
instrument.
9
PROF. HANDELSMAN:
Mass spectrometer mass ranges often don't
We simply don't know with this particular
I come back to Dr Watt's comment that the
10
calibration appears to have been adequate up to 3000.
11
other words, there is no systematic deviation up to 3000.
12
So to imagine that suddenly deviates beyond that is
13
possible, things like that happen.
14
that if it is in calibration up to 3000 it is not far out,
15
although it may be out a little bit further or beyond
16
that.
17
DR VINE:
In
But the most likely is
I would simply say we don't know.
You would need to
18
know the exact operating characteristics of the instrument
19
to be sure about that.
20
MR IHLE:
You simply can't be sure about it.
Professor Handelsman, I just want to ask you about
21
some of the documents you were able to obtain over lunch,
22
specifically those in relation to Thymosin Beta-15 and
23
Thymosin Beta-10.
24
PROF. HANDELSMAN:
25
MR IHLE:
26
I don't know if you have the marked ones, but the
protein information resource document.
27
PROF. HANDELSMAN:
28
MR IHLE:
29
Yes.
Yes.
I have one which is marked AS-23.
That's the one, as
I understand it, the Thymosin Beta-10; is that right?
30
PROF. HANDELSMAN:
31
MR IHLE:
Which number of residues has it got?
Thirty-eight.
.AFL Anti-Doping Tribunal
21/01/15
736
PROF. HANDELSMAN/DR VINE
1
PROF. HANDELSMAN:
2
MR IHLE:
3
Does thirty-eight residues indicate that there are
38 amino acids?
4
PROF. HANDELSMAN:
5
MR IHLE:
6
PROF. HANDELSMAN:
7
MR IHLE:
8
9
residues, 45; that's on AS-24?
PROF. HANDELSMAN:
11
PROF. HANDELSMAN:
12
MR IHLE:
15
16
17
Yes, that's correct.
Do you have a copy of your first report in front of
you?
PROF. HANDELSMAN:
Yes, I do somewhere.
second I will find it.
MR IHLE:
If you give me a
Yes.
Turn to page 13 of that report.
You were asked
questions about this the other day, you might recall.
PROF. HANDELSMAN:
19
MR IHLE:
Yes.
We will see the diagram in the bottom right-hand
corner of page 13.
21
PROF. HANDELSMAN:
22
MR IHLE:
23
Correct.
That indicates that it's a chain of 45 amino acids.
18
20
Correct.
And in relation to Thymosin Beta-15, number of
MR IHLE:
14
Correct.
Correct?
10
13
Thirty-eight is Thymosin Beta-10, yes.
Do you have that?
Yes, I do.
We have three substances listed with chains of what
purport to be amino acids?
24
PROF. HANDELSMAN:
25
MR IHLE:
26
PROF. HANDELSMAN:
27
MR IHLE:
Yes.
We have Beta-4, Beta-10 and Beta-15?
Yes.
You may not recall - and I can take you to the
28
transcript, but at page 339 of the transcript in reference
29
to this diagram I took you to that in relation to both
30
Beta-10 and Beta-15, and according to that diagram and
31
your evidence on 12 January Thymosin Beta-10 was a 43
.AFL Anti-Doping Tribunal
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PROF. HANDELSMAN/DR VINE
1
2
3
amino acid chain.
PROF. HANDELSMAN:
Look, I recognise what you are saying.
Beta-4 you mean or Beta-10?
4
MR IHLE:
Beta-10.
5
PROF. HANDELSMAN:
Look, I didn't have in my report anything
6
about Thymosin Beta-10, and in fact the first time
7
I really looked it up was today.
8
least from the NCBI protein database is 38.
9
know that particular diagram.
So the correct figure at
I can't explain that
10
discrepancy off the top of my head.
11
sequence - - -
12
MR IHLE:
13
PROF. HANDELSMAN:
Now, I don't
Just looking at the
It also indicates that Beta-15 has 44 amino acids.
All I can deal you is that this is a picture
14
out of a review article by Harrer, which I didn't go into
15
in any great depth.
16
illustration.
17
the bottom, which was the Thymosin Beta-4.
18
just stayed in there more or less unintentionally, but
19
specifically looking at those two thymosins in the NCBI
20
protein database today that's the result that
21
I circulated.
22
MR IHLE:
I just used it as a form of
I actually meant to highlight what was at
The upper part
That article that you pulled those two amino acid
23
chains for Beta-10 and Beta-15 out would seem to be
24
inaccurate in light of the information produced today?
25
PROF. HANDELSMAN:
I would say that that's most likely, and
26
without going into it further I can't account for that in
27
detail at this stage.
28
MR IHLE:
At least that's one example of where someone has
29
represented something as Thymosin Beta-10 which, as we
30
know from the chemical authority, is not actually Beta-10.
31
PROF. HANDELSMAN:
I just haven't had time to go and look at
.AFL Anti-Doping Tribunal
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PROF. HANDELSMAN/DR VINE
1
where the discrepancies are, and I don't quite understand
2
that.
3
forms of Thymosin Beta-10 too.
4
sequence and there is a pro-sequence, a pre-pro, and it's
5
variously chopped up before a final form is made.
6
could be that that's what they call a pro Beta-10.
7
other words it's a slightly longer version which is cut
8
down further.
9
10
11
12
MR IHLE:
But, yes, it's possible that there may be different
Proteins are made in a
So it
In
That amino acid chain of 43 which is represented as
Beta-10 which is probably not Beta-10 - - PROF. HANDELSMAN:
I don't know how far out it is.
I would
have to look at it side by side.
13
MR IHLE:
We know it is out by at least five amino acids?
14
PROF. HANDELSMAN:
15
MR IHLE:
Yes, apparently so, yes.
That which has been represented in the diagram in
16
your report would probably have a molecular weight in the
17
vicinity of that which we see on the graph, would it not?
18
PROF. HANDELSMAN:
It might have.
But I think, as you yourself
19
pointed out, probably the diagram is in error because the
20
databases are more reliable sources of information.
21
are the standard source of information that people use for
22
molecular weights and for structures of proteins and
23
genes.
24
MR IHLE:
They
The point is this, Professor Handelsman: even in
25
learned articles which you yourself cite, people might get
26
the sequence of Beta-10 and Beta-15 wrong.
27
PROF. HANDELSMAN:
Look, it was not the object of my using the
28
diagram to highlight Beta-10 or Beta-15; it was really the
29
lower part.
30
get it right.
There may be other explanations so that it
31
is not wrong.
For example, if it is a precursor form of
But, yes, you are right; people don't always
.AFL Anti-Doping Tribunal
21/01/15
739
PROF. HANDELSMAN/DR VINE
1
Beta-10 then there's no necessary inconsistency.
2
I can't account for that at this moment.
3
MR IHLE:
But
In that instance, though, it would not be Thymosin
4
Beta-10.
5
represented in the diagram that you adopted that would not
6
be Thymosin Beta-10.
7
If you had an amino acid peptide such as that
PROF. HANDELSMAN:
According to the protein database that would
8
not be Thymosin Beta-10.
9
it.
10
MR IHLE:
And Thymosin Beta-15 is the same as represented in
11
the diagram.
12
PROF. HANDELSMAN:
13
14
It might be a precursor form of
Yes.
Well, there's a difference in the
number of residues, that's right.
MR IHLE:
Dr Vine, you gave a brief bit of evidence before in
15
relation to the answers to the ChemSpider interrogation
16
that you did, that you found that there were 28 and
17
I think Professor Handelsman found 22 or 23 substances
18
that fall within the molecular weight range that you
19
identified.
20
relation to ChemSpider based on your experience.
21
often do you use ChemSpider?
22
DR VINE:
You have also identified the limits in
Several times a week, I would think.
23
intensively and sometimes less so.
24
several times a week.
25
MR IHLE:
How
Sometimes quite
But it would average
In your job how often are you looking by the way of
26
mass spectrometry or otherwise at detection of peptides
27
and other molecules?
28
DR VINE:
Relatively frequently, I have to say increasingly
29
frequently as these become more important as sports doping
30
agents.
31
labs had almost no capacity to detect peptide doping
When the ACCC report was released most sporting
.AFL Anti-Doping Tribunal
21/01/15
740
PROF. HANDELSMAN/DR VINE
1
agents.
2
to change that situation, and that's necessitated a huge
3
upgrading of the amount of work we do on biological
4
molecules.
5
potential prohibited imports we get from Customs - they
6
are peptides rather than the more traditional illicit
7
substances that we have been used to seeing in the past.
8
So it is very much a growth area and the number of things
9
that come in that require you to identify proteins and
10
11
Obviously since then we have put in a lot of work
So increasingly - and we see this too with the
peptides is increasing all the time.
MR IHLE:
And in relation to those analyses that you conduct
12
either by way of drug detection in horse racing or
13
assistance to Customs or any other, do you have recourse
14
to ChemSpider in those instances?
15
DR VINE:
Yes.
It's not so much in relation to the testing of
16
the racing animals.
In those tests we generally have a
17
defined group of substances that we are looking for.
18
in terms of the Customs materials, yes, that's one of the
19
sources we use.
20
more traditional sources of protein identification like
21
BLAST searches and things like that and Swiss-Prot
22
database.
23
that you can have access to which you can use when you are
24
trying to sequence a protein.
25
that's available that enables you to do that.
26
use of all of those tools.
27
about ChemSpider, ChemSpider tends not to be all that
28
useful for proteins and peptides compared to the other
29
more specific databases that we use.
But
But we also use the other, if you like,
There are a number of international databases
30
PROF. HANDELSMAN:
31
MR IHLE:
There is a lot of software
So we make
Going back to what I said
Can I - - -
Professor Handelsman, do you use ChemSpider?
.AFL Anti-Doping Tribunal
21/01/15
741
PROF. HANDELSMAN/DR VINE
1
PROF. HANDELSMAN:
2
MR HOLMES:
3
PROF. HANDELSMAN:
4
MR IHLE:
5
6
7
No, I don't use it regularly, no.
I think Professor Handelsman said "can I".
Can I actually come - - -
Well, he can answer the question, with due respect,
and if there is a matter that needs to be clarified - - PROF. HANDELSMAN:
I'm just following on a question you asked
me before and I have an answer now.
8
MR IHLE:
Okay.
Is this in relation to your diagram?
9
PROF. HANDELSMAN:
Yes.
As I suggested, if you look at the
10
Thymosin Beta-10 and the diagram and compare it with the
11
database there are five amino acids at the front end.
12
That is very typically what you see in the way proteins
13
are made.
14
chopped up into its final form.
15
acid version in that diagram is a pro form of it with five
16
amino acids at the front end.
17
They are made in a long sequence and then it is
Presumably the 43 amino
The Beta-15 one has one amino acid less and
18
that's a methionine which is often readily oxidised in the
19
purification process.
20
the purification wasn't reliable enough to identify that
21
there's actually 45 and not 44.
So I think in the end the
22
databases are probably correct.
They are the most up to
23
date.
24
25
MR IHLE:
So the database is correct.
PROF. HANDELSMAN:
27
MR IHLE:
Yes.
And it needs to have 45 in a particular order to be
Beta 15?
29
PROF. HANDELSMAN:
30
MR IHLE:
31
So it needs to have 38
in a particular order to be Beta 10?
26
28
So my guess is that at that stage
Correct.
If there is something that comes in with the amino
acid chain as depicted in those diagrams it would neither
.AFL Anti-Doping Tribunal
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742
PROF. HANDELSMAN/DR VINE
1
be Beta 10 nor Beta 15?
2
PROF. HANDELSMAN:
3
MR IHLE:
Yes.
Going back to ChemSpider, are you in a position to
4
agree or disagree with Dr Vine about how compendious
5
ChemSpider is or is not in relation to peptides and
6
proteins?
7
PROF. HANDELSMAN:
I would defer to his much greater expertise
8
in that sort of analytical chemistry and use of
9
ChemSpider.
10
MR IHLE:
I'm a very occasional user only.
Professor Handelsman, do I understand the gravamen of
11
your evidence to be that you really don't disagree with
12
what Dr Vine says; rather you start from a different
13
question which is, "If this analysis were to be applied on
14
a dichotomous basis, is it one thing or the other, then by
15
way of exclusion of one of them we are left only with the
16
other?"
17
PROF. HANDELSMAN:
Yes, that's how I phrased my report.
If the
18
question was the following, then it's clear.
19
way the instructions went to Dr Vine were leaving the
20
qualification out.
21
MR IHLE:
22
PROF. HANDELSMAN:
In fact the
Why did you insert the qualification?
Because I think it represents the likely
23
scenario.
I think it represents the context in which
24
these analyses were done by a compounding chemist.
25
MR IHLE:
Why?
26
PROF. HANDELSMAN:
Because a compounding chemist takes
27
substances he or she orders from somewhere else and may -
28
sometimes they don't bother to verify them, but in this
29
case they may have decided to verify what it was.
30
31
MR IHLE:
This is just guesswork on your part.
You have seen
no evidence as to why these were analysed?
.AFL Anti-Doping Tribunal
21/01/15
743
PROF. HANDELSMAN/DR VINE
1
PROF. HANDELSMAN:
It is guesswork, but I'm trying to establish
2
a context why this analysis was done, a plausible one
3
given that it's a compounding chemist.
4
MR IHLE:
I want to ask you this specifically.
Have you been
5
taken to any evidence or shown any evidence which suggests
6
that the purpose for these analyses was to determine one
7
of those two alternatives?
8
PROF. HANDELSMAN:
9
MR IHLE:
10
11
No.
So, based on what you have been asked, you have
looked at these and you have made that assumption?
PROF. HANDELSMAN:
Not quite.
There were a number of things
12
I was shown today, for example, like a catalogue that had
13
the word "Thymosin" without any qualification.
14
ordered that they would then be obliged - I mean,
15
commonsense, even a compounding chemist who will cut
16
corners would be obliged to verify whether it is one or
17
the other of the two that would be marketed.
18
MR IHLE:
If someone
Dr Vine, what would you say about that in light of
19
the types of assessments you have done for Customs when
20
you might order one thing, it might be something close, or
21
something different, or something completely different
22
altogether?
23
DR VINE:
I think that's very much the issue.
It is all very
24
well ordering something and it comes with an appropriate
25
label and a certificate of analysis.
26
couple of certificates of analysis mentioned today which
27
don't seem to be really worth the paper they are printed
28
on, and it is often the case that these materials are
29
falsified.
30
growth industry and there are a lot of cowboys out there
31
who are just cashing in on the demand.
But we have seen a
The production of peptides is very much a
.AFL Anti-Doping Tribunal
21/01/15
744
PROF. HANDELSMAN/DR VINE
1
I don't really think you can put your trust in
2
what is on the label unless you have established through
3
experience whether your supplier is a reliable source of
4
supply.
5
that are very reliable sources of materials.
6
Australia, for example, Auspep, Auspep will make any
7
peptide that you want them to make, and what they make is
8
first-class material.
9
is expensive, but you can get it that way.
10
To be fair, there are some companies out there
The one in
It is spot-on what you order.
It
There are one or two other companies that we
11
found to be useful sources of peptides, and invariably
12
whatever we order from them turns out to be the right
13
material.
14
purposes we will always verify it is the right material
15
before we use it.
16
compounding companies where simply it is a question of
17
potluck whether you are going to get what you order.
18
But even when we are ordering it for research
Then there are a number of other
I go back to my point earlier.
I know these
19
compounding chemists cut corners, but if you are
20
compounding something to inject into someone I think you
21
need a degree of certainty in terms of what you have and
22
really the onus is upon you to establish you know exactly
23
what the substance is.
24
MR IHLE:
Professor Handelsman, I want to ask you a question
25
which flows on from some questions that I asked you the
26
other day but in light specifically of this evidence.
27
PROF. HANDELSMAN:
28
MR IHLE:
Yes.
Do I understand correctly that on or about 8 January
29
you had a telephone conference with the lawyers for
30
ASADA - - -
31
PROF. HANDELSMAN:
We had a face-to-face meeting.
.AFL Anti-Doping Tribunal
21/01/15
745
PROF. HANDELSMAN/DR VINE
1
MR IHLE:
You had a face-to-face meeting on 8 January?
2
PROF. HANDELSMAN:
3
MR IHLE:
Yes.
We have been provided with a note.
I'm not sure
4
whose note it is, but it purports to be of a meeting that
5
you had on 8 January in relation specifically to this
6
Bio21 documentation.
7
PROF. HANDELSMAN:
8
MR IHLE:
9
10
We had a meeting on that day.
I understand from the evidence that you gave on
12 January that you yourself don't tend to take notes
during meetings.
11
PROF. HANDELSMAN:
12
MR IHLE:
13
PROF. HANDELSMAN:
I do not, no.
You rely on the notes taken by lawyers?
No, I rely on my memory.
But I ask people
14
who have a particular point to raise or make to confirm it
15
in email to me.
16
MR IHLE:
Is it fair that on 8 January when you were shown
17
these documents or this analysis that is really the
18
subject of most of the questions you expressed a great
19
deal of reservation - well, a deal of reservation both in
20
relation to your expertise of analysing these types of
21
graphs but also what could be determined from these types
22
of printouts?
23
PROF. HANDELSMAN:
Look, we had a meeting at which some
24
documents were shown me across a table.
25
try to - I usually can't absorb them in that way and think
26
about them properly on the spot like that.
27
them away, and in this case got them to give them to me to
28
think about it and then write the report.
29
I said then was the sort of scepticism that comes that
30
I haven't fully absorbed what's there.
31
MR IHLE:
I don't usually
I usually take
So whatever
You were also shown the report of Dr Watt which is
.AFL Anti-Doping Tribunal
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PROF. HANDELSMAN/DR VINE
1
2
now before this Tribunal.
PROF. HANDELSMAN:
I saw little bits of it.
I did not read the
3
whole report and I only saw a couple of particular points
4
in it.
5
actually.
It was not given to me and I haven't read it,
6
MR IHLE:
7
PROF. HANDELSMAN:
8
MR IHLE:
9
So you haven't read it?
No.
Dr Vine, you have been provided with a copy of
Dr Watt's report?
10
DR VINE:
Yes, that's right.
11
MR IHLE:
What do you say about Dr Watt's report?
Do you agree
12
with it, disagree with it, strongly agree, have
13
reservations?
14
DR VINE:
Fundamentally I'm in agreement with what Dr Watt
15
says.
16
I have.
17
you can't be certain it is Thymosin Beta-4.
18
of the analytical evidence doesn't allow you to do that.
19
I think he refers to it as a - I'm trying to think of the
20
words he used.
21
a possibility anyway; I think that would be the gist of
22
what he said, and I would concur with that.
23
possible, but it is by no means established and you
24
certainly can't rely on it.
25
indication or words to that effect.
26
MR IHLE:
I think he has reached the same conclusion that
There is something in that particular sample, but
It won't come to me.
The standard
Nothing better than
It is
I think he called it a rough
Professor Handelsman, I'm trying to get a sense of
27
this conference.
28
meeting.
29
column is cut off, but it seems to say "teleconference
30
with Professor Handelsman".
31
You say there was a face-to-face
This note that I'm about to take you to, the
PROF. HANDELSMAN:
We had a face-to-face meeting and someone
.AFL Anti-Doping Tribunal
21/01/15
747
PROF. HANDELSMAN/DR VINE
1
was on the phone.
2
both face-to-face - it was mostly face-to-face; one person
3
on the phone.
4
5
6
7
8
9
MR IHLE:
I can't remember who it was.
In any event there was some discussion.
So it was
That
discussion involved Dr Watt himself.
PROF. HANDELSMAN:
yes.
MR IHLE:
I think he was the one on the phone briefly,
But that was only for a short period.
I'm going to hand this document down.
It may or may
not be something you have seen before.
10
PROF. HANDELSMAN:
11
MR IHLE:
No, I have not seen this before.
If you could hand those down.
There is one for you
12
and one for Dr Vine and there are three for the Tribunal.
13
I will give you a moment just to read that document.
14
CHAIRMAN:
15
MR IHLE:
16
Do you want to tender that?
I will just ask a question or two about it, but
I will be tendering it.
17
PROF. HANDELSMAN:
18
CHAIRMAN:
19
PROF. HANDELSMAN:
20
MR HOLMES:
21
CHAIRMAN:
22
#EXHIBIT PG-16 - Diary note of 8 January 2015.
23
MR IHLE:
24
I should say I'm struggling to read it.
You are not on your own there, Professor.
I thought it might have been my glasses.
The number is?
It will be PG-16, Mr Holmes.
Perhaps our learned friends could be good enough to
tell us whose diary note it is.
25
MR HOLMES:
26
MR IHLE:
Emily Fitton.
I understand Emily Fitton is a solicitor with ASADA.
27
Six lines down, "Handelsman is worried that we don't have
28
the actual substance.
29
measurements."
30
PROF. HANDELSMAN:
31
MR IHLE:
We only have the files and the
Yes.
Is that an accurate record of something that you said
.AFL Anti-Doping Tribunal
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PROF. HANDELSMAN/DR VINE
1
2
or represented?
PROF. HANDELSMAN:
Well, it's close, but what I said was we
3
would be far better off if we had the actual substance
4
that had come from the compounding chemist or somewhere.
5
Then we wouldn't have all the struggles we are going
6
through.
7
8
9
MR IHLE:
But, yes, that's the spirit of it, yes.
You see there, "The Bio21 information is really just
circumstantial evidence."
PROF. HANDELSMAN:
Yes, I think that's fair enough because it
10
wasn't ordered by ASADA or anybody competent.
11
ordered by a compounding chemist.
12
sceptical - just uncertain what to make of it.
13
in mind at this point I hadn't really looked at them,
14
absorbed it or made any estimate of what it actually
15
showed.
16
17
18
19
MR IHLE:
PROF. HANDELSMAN:
PROF. HANDELSMAN:
22
MR IHLE:
26
27
28
Do you
That wasn't me.
I think that was probably
Steve Watt.
21
25
But bear
remember who said that?
MR IHLE:
24
And so I was
The next reference, "Peaks don't match."
20
23
It was
It goes on, "Steve has issues with calibration."
Yes.
The next entry, "Mass accuracy is really unknown."
Do you remember who said that?
PROF. HANDELSMAN:
I think that's Stephen Watt.
It wouldn't
have been me.
MR IHLE:
Do you disagree with any of these three statements if
they were Dr Watt's?
PROF. HANDELSMAN:
No, I don't disagree.
It's a matter of how
29
much weight you put on them.
30
at that meeting to make a decision one way or the other.
31
MR IHLE:
But I wasn't in a position
The next entry, "Analysis looks like rough check to
.AFL Anti-Doping Tribunal
21/01/15
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PROF. HANDELSMAN/DR VINE
1
look at whether they've got the right number of amino
2
acids there."
3
PROF. HANDELSMAN:
4
5
certain.
MR IHLE:
Do you remember who said that?
That's possibly me, but I just can't be
But it's quite possibly me, yes.
I want to go down to just after point 5 of the page,
6
there's a line that starts "Melissa".
7
that - - -
8
PROF. HANDELSMAN:
9
MR IHLE:
Two lines down from
Sorry, where is "Melissa"?
Yes.
"Can give an opinion, but given his" - this is not in
10
relation to Melissa; I was just using that as a hallmark,
11
at point 5.
12
give an opinion, but given his lack of expertise in
13
protein measurement he doesn't want to be pinned down on
14
it."
15
Professor?
16
Two lines below the line with "Melissa", "Can
Is that a comment that's attributable to you,
PROF. HANDELSMAN:
Look, I think it's a misstatement of what
17
I said, which was that my expertise in mass spectrometry
18
is in steroids and small molecules and not so much in
19
proteins.
20
more - I had some discomfort in that this was mass
21
spectrometry of proteins, yes.
22
of grazing, so to speak.
23
Q.
I think that's just overstating it.
I am done with those questions.
But I was
It is not my natural area
This is a question to both
24
the professor and the doctor.
25
that you were provided were another number of analyses
26
that were conducted or ostensibly conducted on 9 May 2012
27
at Bio21; do you agree with that?
28
PROF. HANDELSMAN:
29
DR VINE:
30
31
Included in the material
I'm not sure what you are referring to.
I think it's the Thymosin Beta-4 and the Thymosin
OOF.
MR IHLE:
No.
You were given a USB stick each, and on that USB
.AFL Anti-Doping Tribunal
21/01/15
750
PROF. HANDELSMAN/DR VINE
1
stick there were graphs in relation to a number of other
2
substances that were tested on the very same day.
3
you have only referred to the one test on 12 May, but in
4
the materials that were provided to you were documents
5
relating to other tests conducted on the very same day.
6
7
8
9
DR VINE:
Both of
This is presumably the Thy A-2 and Thy C and Thy C-2
you are referring to.
MR IHLE:
Yes, I will provide you with copies for ease of
reference.
10
MR HOLMES:
11
CHAIRMAN:
12
MR HOLMES:
Can I just ask a question of Professor Handelsman?
Yes.
That question Mr Ihle is about to ask is preceded
13
on an assumption that they were both given the same things
14
on a USB stick, Mr Ihle, you are talking about?
15
16
17
MR IHLE:
As I understand it.
letter from the AGS.
PROF. HANDELSMAN:
I have the documents and I print out the
18
documents I was given.
19
that's all I have seen.
20
If necessary I can refer to a
MR IHLE:
So I can refer to those.
Let me ask you this then .
But
I will hand these to you.
21
As I understand it, a disclosure notice was served on
22
Bio21 in December of last year.
23
disclosure notice they produced, amongst other things, the
24
document in electronic form the results of analysis, it's
25
been provided on a USB stick, but also printouts.
26
these documents you have ever seen before, Professor
27
Handelsman?
28
PROF. HANDELSMAN:
In relation to that
Are
Let me just refer to the documents that
29
I did receive.
They do not appear to be among the
30
documents I received and they don't look familiar to me.
31
No, I don't believe I received them.
.AFL Anti-Doping Tribunal
21/01/15
751
I have the documents
PROF. HANDELSMAN/DR VINE
1
I received printed out here, the original set, and it's
2
not among those.
3
MR IHLE:
There were documents that you were provided with, but
4
there were also a number of documents you were shown
5
during a conference, including the report of Dr Watt.
6
you agree with that?
7
PROF. HANDELSMAN:
8
fully.
9
10
11
12
MR IHLE:
Do you want some time just to digest this?
PROF. HANDELSMAN:
No, go ahead.
I don't know if Dr Vine has
seen these.
DR VINE:
Yes, I have.
stick too.
14
software.
15
MR IHLE:
16
PROF. HANDELSMAN:
18
I did not read it
I was pointed to one or two things in it only.
13
17
I saw bits of his report.
Do
I have also had access to the memory
So I have looked at the data with the
Do you want five or 10 minutes?
No, go ahead.
If I get to a point where
I need to do that I will tell you.
MR HOLMES:
Can I just object.
But otherwise - - -
There is an element of
19
unfairness here where we are going outside the existing
20
report.
21
which clearly Dr Vine has had time to examine but not to
22
prepare a report on.
23
has not seen it, as I understand the gist of his evidence.
24
So we are using the opportunity for Professor Handelsman
25
being here at the hot tub to get him to look at materials
26
that Dr Vine has already seen but has not put on a report
27
for and to give opinions on the run.
28
of the proceedings which is unfair to the experts where
29
Dr Vine has looked at it and decided not to give a report.
30
That's the decision they make.
31
It is based on a USB stick and some materials
This witness, Professor Handelsman,
That is an extension
But now they want to give evidence on a topic
.AFL Anti-Doping Tribunal
21/01/15
752
PROF. HANDELSMAN/DR VINE
1
which we haven't been given any notice of, and it is quite
2
unfair to the witness to now go into a new area where he's
3
still only got the hard copies, not all the USB stick and
4
looking at it on the screen and conducting the tests.
5
Remember when I started my questions directed to Dr Vine
6
he actually used the software and examined it on the
7
screen.
8
opportunity.
9
CHAIRMAN:
Now Professor Handelsman hasn't been given that
I understand all that.
What's the relevance of
10
this, Mr Ihle?
11
that it would have already been elicited.
12
13
MR IHLE:
It is.
If it was relevant one might have expected
These documents are referred to in Dr Vine's
report.
14
CHAIRMAN:
15
MR IHLE:
Where?
At paragraph 14.
In the body of the paragraph under
16
the table he says, "Other materials analysed under the
17
names Thy A-2, Thy C, Thy C-2 gave a mass spectra which
18
did not contain significant peaks above 2,000.
19
materials clearly do not contain Thymosin Beta-4."
20
relevance is this.
21
that he has confined the question based on an assumption
22
that he made.
23
under the file name "Thy" in May 2012, at the same time
24
the analysis which has been the subject of most of the
25
cross-examination.
26
These
The
Professor Handelsman has identified
This is analysis of other substances saved
We say the relevance is in relation to the
27
question which Professor Handelsman has asked himself in
28
the report.
29
to put forward and it is that really which is set out in
30
paragraph 14 of Dr Vine's report; that there were five
31
analyses that were done on 9 May 2012 purportedly by Vania
It is a very simple proposition that I seek
.AFL Anti-Doping Tribunal
21/01/15
753
PROF. HANDELSMAN/DR VINE
1
all in relation to Thy substances, only one of which
2
returned a result anywhere near anything known as
3
Thymosin.
4
PROF. HANDELSMAN:
Can I say that I have checked - there are
5
five pictures, screen shots, you have provided me with.
6
The third one, the one with .0026, is the same as what
7
I saw and what Dr Vine saw.
8
MR IHLE:
9
PROF. HANDELSMAN:
10
11
12
13
Correct.
But I have not seen the first, second,
fourth or fifth before.
MR IHLE:
All right.
Do you want me to take you through them?
If you think there is any unfairness, you can just say.
CHAIRMAN:
Let's see how we go.
We certainly have to, in terms
14
of evaluating the evidence, take into account the fact
15
that the professor hasn't seen these before.
16
MR IHLE:
Can I also, to answer the objection that's being
17
raised, provide the Tribunal and my learned friends with a
18
letter from the Australian Government Solicitor dated
19
10 January under which these materials were served which
20
said, "The report of Professor Handelsman considered the
21
results of mass spectrometry analysis conducted by Vania
22
Giordani on behalf of Como Compounding Pharmacy at the
23
Bio21 facility.
24
under a disclosure notice."
25
there's been any unfairness, we say it's because there
26
might be a misrepresentation or at least - and I will cop
27
this if it is on me - a misreading of that.
28
documents were served as part of the bundle with which
29
Professor Handelsman's report was served.
30
31
PROF. HANDELSMAN:
These analyses were obtained from Bio21
That's these documents.
If
But these
I have here the letter that came to me from
the Australian Government Solicitor.
.AFL Anti-Doping Tribunal
21/01/15
754
PROF. HANDELSMAN/DR VINE
1
MR IHLE:
I accept that wholeheartedly.
2
be an in-depth analysis here.
3
of questions.
4
MR HOLMES:
There is not going to
There is a very simple set
The objection is based on the unfairness.
There
5
are two sentences there under that square box in paragraph
6
14.
7
not been asked questions on.
8
now, having got the witness here, the witness not having
9
seen the material until now and seeing it in a small form,
They have not been cross-examined upon.
They have
They are not disputed.
10
they are going to go beyond that and use that as a
11
springboard to ask - I don't know.
12
MR IHLE:
13
MR HOLMES:
14
But
I can tell you exactly what I'm going to ask.
It is not in the report and it's not been
cross-examined or asked questions of.
15
CHAIRMAN:
16
MR IHLE:
What are you going to ask, Mr Ihle?
I'm going to ask him to look at each of these
17
analyses and say if he can exclude, based on these
18
analyses, any form of known Thymosin.
19
CHAIRMAN:
20
MR IHLE:
21
CHAIRMAN:
Based upon - - Let's say Alpha-1 and Beta-4, which is the - - Let's see how we go.
The circumstances under which
22
this has arisen, particularly in relation to the position
23
of Professor Handelsman, we will take into account.
24
MR IHLE:
Thank you, Mr Chairman.
25
CHAIRMAN:
26
PROF. HANDELSMAN:
27
CHAIRMAN:
Professor, are you able to - - -
On that basis, with that caveat that I have just
28
stated.
29
PROF. HANDELSMAN:
30
MR IHLE:
31
I'm quite happy to go ahead on that basis.
Yes.
Okay.
Professor Handelsman, you will see the printout which
is numbered 22 in the corner, saved under the file name
.AFL Anti-Doping Tribunal
21/01/15
755
PROF. HANDELSMAN/DR VINE
1
which ends "Thy A-2".
2
PROF. HANDELSMAN:
3
MR IHLE:
4
5
Yes, I see.
That does not tend to indicate the presence of either
Thymosin Alpha or Beta-4, does it?
PROF. HANDELSMAN:
Around 3,000 there could be an error, some
6
little blips there, but there is certainly nothing around
7
5,000.
8
These could be just running control fluids just to test
9
the machine to see if there is any carryover from a
So, no.
But we don't know what these represent.
10
previous analysis.
11
don't appear to have much in the way of the target
12
anolytes in them.
13
MR IHLE:
I don't know what these are.
But they
Turning to page 24 in the corner - just so we can be
14
clear the odd numbered pages have a tabular breakdown of
15
what the peaks are.
16
PROF. HANDELSMAN:
17
MR IHLE:
18
PROF. HANDELSMAN:
19
MR IHLE:
Yes.
Do you agree with that?
Yes.
Although you say there may be something around 3000,
20
the table hasn't picked anything up other than 346 and
21
522?
22
PROF. HANDELSMAN:
23
MR IHLE:
24
PROF. HANDELSMAN:
No, that's correct.
So that would exclude both Alpha and Beta-4?
Yes.
But, as I said, I don't know what
25
these are.
26
know with nothing in them deliberately.
27
MR IHLE:
28
PROF. HANDELSMAN:
29
MR IHLE:
30
PROF. HANDELSMAN:
31
MR IHLE:
These could be control injections for all we
And at 0024?
Yes, same.
Nothing there.
Thy A-5?
Thy A-5 was the one we saw before.
I want you to go back to 0024.
.AFL Anti-Doping Tribunal
21/01/15
756
PROF. HANDELSMAN/DR VINE
1
PROF. HANDELSMAN:
2
MR IHLE:
3
Do you see in the filename at the top that's called
"Thy A-5".
4
PROF. HANDELSMAN:
5
MR IHLE:
6
7
Yes.
Yes, so it is.
Again that doesn't seem to show any substance in the
range of Thymosin Alpha-1 or Beta-4?
MR HOLMES:
Does that have the same number up the top on the
8
right-hand side?
9
different number?
10
PROF. HANDELSMAN:
I'm just asking that.
Is that a
You are right that there is nothing in that
11
range, but it also doesn't go up.
12
doesn't go up to 5,000.
13
be Thymosin Beta-4 in it.
14
Alpha-1 in it, but there could be Thymosin Beta-4.
15
just doesn't go up high enough in the mass to charge
16
ratio.
17
18
MR IHLE:
So you have no idea.
There could
I would say there's no Thymosin
It
The one at 26 is the one that we have been talking
about for most of the afternoon?
19
PROF. HANDELSMAN:
20
MR IHLE:
21
The one with 0024
Yes, we have seen that before.
The one at 28 doesn't show anything in the range of
Alpha or Beta-4?
22
PROF. HANDELSMAN:
23
MR IHLE:
24
PROF. HANDELSMAN:
Beta 4 is not in the range.
There is nothing to indicate the presence of either?
No, that is not true.
There is nothing to
25
indicate the presence of Alpha-1.
It doesn't go up to
26
even test whether - Beta-4 could be there.
27
comment on whether that's true or not.
Dr Vine might
28
MR IHLE:
Dr Vine?
29
DR VINE:
The mass range that's printed in those diagrams
30
appears to only go up to mass 4,000.
31
something above that you simply wouldn't see it.
.AFL Anti-Doping Tribunal
21/01/15
757
So if there was
PROF. HANDELSMAN/DR VINE
1
PROF. HANDELSMAN:
2
DR VINE:
It is the same with the last one, too.
I don't know what the criteria that are applied by
3
the instrument's computer are for listing peaks in tabular
4
form.
5
seem to go above 1,000.
6
that there really isn't anything above there or whether
7
that's subject to the same limited range.
8
saying is the range that's on the sheet of paper may not
9
be the range that was acquired by the mass spectrometer.
The tabulated peaks on the following page don't
I'm not sure whether that means
So what I'm
10
It may be the range that's just been displayed in that
11
graph or it may be that that was the range that was
12
acquired.
You can't tell.
13
CHAIRMAN:
14
PROF. HANDELSMAN:
15
DR VINE:
16
CHAIRMAN:
17
The problem is all we have is that piece of paper.
Yes.
Yes.
So, in terms of what it can tell us, it doesn't seem
to be very much.
18
DR VINE:
19
CHAIRMAN:
20
DR VINE:
No.
Working purely off that document.
I'm not sure if this is admissible, Mr Chairman, but
21
in my paragraph 14 I say there aren't any significant
22
peaks.
23
the files themselves, that I think they did go beyond
24
4,000 but I couldn't see anything in them.
25
recollection, but I would need to recheck that.
That comment was made on the basis of examining
That's my
26
CHAIRMAN:
That's not on the diagram obviously?
27
DR VINE:
It wasn't on the diagrams printed, no.
28
MR IHLE:
Just so we can be clear, in relation to each of those
29
under acquisition parameter, the date of acquisition for
30
each one is 9 May 2012?
31
PROF. HANDELSMAN:
Yes.
.AFL Anti-Doping Tribunal
21/01/15
758
PROF. HANDELSMAN/DR VINE
1
MR IHLE:
2
MR HOLMES:
3
CHAIRMAN:
I tender those documents.
I maintain the objection.
It will be subject to that objection, Mr Holmes.
4
PG-17.
5
necessary.
6
MR IHLE:
7
CHAIRMAN:
8
MR IHLE:
9
How would we describe these, Mr Ihle?
They would be described as the documents - - Documents referred to in paragraph 14 of - - They are documents produced by Bio21 pursuant to a
disclosure notice served upon them by ASADA on 17 December
10
2014.
11
MR HOLMES:
12
MR IHLE:
13
No doubt we will hear submissions as felt
I don't think it is all of the documents.
It is not all of the documents.
But we might say
they are marked ASA-2.0074 - - -
14
CHAIRMAN:
Marked 0022, 24, 26, 28 and 30.
15
MR HOLMES:
16
CHAIRMAN:
17
#EXHIBIT PG-17 -
The odd numbers are on the back.
So just 22 to 30.
Documents marked 0022 to 0030 produced by
18
Bio21 pursuant to a disclosure notice served by ASADA on
19
17 December 2014.
20
MR IHLE:
Thank you, Mr Chairman.
21
MR CLELLAND:
22
CHAIRMAN:
I have no further questions.
Nothing from us, Mr Chairman.
Is there anything further that we need to trouble
23
our learned experts with?
24
for your assistance now over a couple of weeks.
25
you have an aeroplane to catch and we want you to catch
26
it.
27
very much for your attendance.
28
Otherwise we will adjourn until 10 o'clock tomorrow.
29
Professor, thank you very much
So we won't hold you anymore.
No doubt
Dr Vine, thank you
It's appreciated.
ADJOURNED UNTIL THURSDAY, 22 JANUARY 2015 AT 10.00 AM
30
31
.AFL Anti-Doping Tribunal
21/01/15
759
PROF. HANDELSMAN/DR VINE