Peer Review: HISTORY

U27111 at uicvm.uic.edu U27111 at uicvm.uic.edu
Tue Jan 23 02:28:21 EST 1996



gmc0 at ix.netcom.com (George M. Carter) Wrote on  Mon, 22 Jan 1996
14:42:07 GMT:

>It seems to me several ideas have been conflated here (there's
>that word again!)....

Oh... *that* word

>1) I disagree with the notion that we need to produce fewer
>scientists.  As has been noted, there are many practical problems
>that require at the very least, excellent technicians.  However,
>science is not limited just to solving the quotidian horrors of
>our day!  (Or shouldn't be ideally).

I don't know?

Here's another way of looking at it... maybe?

If we made it harder to become a scientists, by making it a more
difficult program to get through (as previously suggested
elsewhere)... then we would have fewer ones being produced... but
they would also be of the highest caliber.

Someone was telling me that in Canada (and Alex could tell us if
this is right or wrong?)... that you have to had graduated in the
top 1% of your highschool class - just get admitted to college in
the first place?

Personally, I found this hard to believe... maybe the top 10%, but
1%?

Whichever the case maybe... maybe this is where we need to start
looking in lowering the number and increasing the quality of
scientists produced?

Additionally... look at the PhD explosion and the number of foreign
doctors coming into this country and receiving federal monies?
Many of these come from countries where there are even lower
biotechnology skills available then here... and some don't learn
English and thus, never quite 'catch-up'?  Or just plain tend to
ignore and abide by US regulations (especially in biohazardous and
radioactive waste handling).  [Then again, I've seen the same thing
in some non-foreign researchers as well?]  oh well.

Anyway, this is also a place where we are losing technical skills?

>2)  I agree with the notion that the bad should be weeded out.
>This does require significant changes in the system that allow
>protection of whistle blowers and appropriate judicial
>intervention and punishment for fraud (whether from the standpoint
>of lying whistle blowers or lies.)

>3)  I thought science was based on the concept of developing a
>hypothesis and then trying to find the case that overturns it?


No.... that's what it has turned into these days.  But that's not
what it originally started out to be.

>Rather than merely providing evidence that supports, actually
>actively seeking the cases that disprove it?

Yes, that's the Feynmen code of conduct I posted previously.
*That's* how it is suppose to be.  Reputations aren't suppose to be
built on who has the better mainstream ideas and selective data to
back it up... but on who pursues the truth the most vigorously...
even if they end up reversing themselves later.  Today, people will
stand up and defend their work out of ego and not wanting to be
wrong... instead of sitting down, rolling up your sleeves and
testing and re-testing until you figured out what the truth really
is (whether you be wrong or right in the first place).

In a lot of ways... it's due to the current system that scientists
feel they cannot afford to be *wrong* - at all costs!  And usually
just end up defending the indefensible.

>As an example, the work of Gallo's lab that showed "cure" in mice
>with Kaposi's sarcoma using a sulfated peptido--polyglycan (SP-PG)
>was not reproduced in another lab.  Nonetheless, a few people
>wound up trying this drug and receiving no benefit or suffering
>"unexpected bleeding and other side effects."  This is merely
>profiting off people's lives.

Exactly (and rasing the stock of the company which produced it).

But look how Gallo just threw off Witte's questions, ignoring them,
calling them silly.  And how the journal Science even refused to
publish her letter.  And how many people in the first place [at
various meetings and what-have-you] who told her to repeat it for
herself before arguing against this study!

Years went by (and this drug proceeded to human testing) before she
was finally able to run the experiments using Gallo's own cells and
to publish the fact she was unable to repeat his work (in JAMA by
the way, Science refused to even publish this paper as well!). All
she went through simply because she 'dared' to question Gallo in
the first place!

And all this WASTE... when it was Gallo's responsibility in the
first place to assure the data was correct and to answer her
questions... even if it meant re-testing things himself!

As Nature wrote on the whole Doty/Baltimore exchange which took
place in that journal during the Baltimore affair.... [excerpt from
'Science on Trial: The Whistle-Blower, the Accused, and the Nobel
Laureate' by Sarasohn, p.248]

     "What are the responsibilities of the authors of a
     published research report?"

     Baltimore's contention that it was for other scientists
     to demonstrate the validity of the disputed data and
     conclusions drawn from them might be "a point of view,
     but hardly a defensible one," the journal stated quite
     starkly.

     "The plain truth is that the authors of all published
     research reports have a personal responsibility for their
     aftercare," Nature said. "They, after all, are best
     placed to carry out the meticulous examination of the
     original data when questions are asked about them and,
     when necessary, to design and carry out all replicate
     experiments."

     Anything less would undermine the whole scientific
     enterprise, according to the journal: Scientist, unable
     to depend on published work, would have to repeat the
     experiments before doing their own work.  "Naturally, it
     must often be a fiendish nuisance for authors to have to
     shoulder this responsibility, especially if many months
     have passed.  But this is merely one of the penalties of
     authorship."

What simply amazes me is how Gallo and his cohorts were able to get
away with this... forcing Witte into the position of having to
physically 'disprove' *his* work.

And how after she was unable to repeat his results... he got all of
his friends (collaborators) to publish letters in JAMA basically
calling *her* work into question.

It was really a no win situation for Witte.

And now the whole issue has been dropped... anytime people bring it
up to Gallo... I believe it's been referred to as 'oh, that
nonsense'.  He blows it off and is allowed to by this community.

This have never been investigated... the paper has never been
retracted (even though the drug was), and nobody says anything
about it... again, condoning his behavior through silence!

So see David... that's a good example of what happens when you do
'pursue all of the available institutional avenues for correcting
[a particular] situation'!

Finally, for you out there who wonder what the hell we are talking
about?
*****************

"Rival Scientists Question Research on AIDS Lesions/Gallo critics
say tests of drug may be invalid"  by John Crewdson, Chicago
Tribune, June 9, 1994.

An article, published in a June issue of JAMA (June 2nd or 9th?,
1994) by a husband and wife research team from the University of
Arizona (Doctors Witte), questions the veracity of a Gallo article
published 2 years ago in Science on Kaposi's sarcoma and a drug
named SP-PG.  The JAMA article "dismisses a central conclusion of
the Gallo piece as 'highly dubious' and declares that 'the validity
of the peer review process and self-correcting nature of scientific
inquiry are also called into question."

Gallo's Science article reports that SP-PG appears to inhibit the
development of KS in mice.  "It really prevents the development of
lesions, " Gallo had said at the time.

In this Science paper, Gallo's lab injected some mice varying doses
of SP-PG, some with different drugs and a control group with none
at all.  It was thought that this would help to show that SP-PG had
the ability to prevent whatever growth factors might cause KS
lesions from leaking out of the blood vessels and forming lesions
in surrounding tissue.

They then infected the mice with KS cells, waited a few hours and
then injected the mice with blue dye via the tail vein.  According
to the Science article, when measuring the amount of blue dye which
had leaked from blood vessels, it was greatest in the non-SP-PG
mice and least in those mice which had received the highest dosage
of SP-PG.

As for the Witte's paper in JAMA criticizing this paper:

At close examination of the Science pictures of the mice, the
Witte's saw something odd... the tails of the untreated mice were
an intense blue color, while the tails of the SP-PG treated mice
were not.

This suggested, to the Witte's, that the results were that from
botched tail vein injections.

The Witte's also questioned Gallo's claim that a sizable amount of
dye-containing mouse blood had leaked into a small KS lesion in
just a few minutes.  According to the Witte's, "Even a localized
scalding burn of that tiny dimension would not cause the loss of so
much blood in such a short amount of time."

Additionally, they wondered how Gallo's lab was able to extract the
dye from the mouse lesions overnight... they noted that dye
extraction from soft tissue is "notoriously difficult".

Finally, they were 'surprised' on the "smoothness" of Gallo's graph
showing the blood vessel leakage decreased in step with increases
in the SP-PG dosages.

Well, they sent all this in a letter to Science, entitled "The
Tell-Tale Blue Tail".  The letter was sent to Gallo who dismissed
it "as an extraordinary waste of time and effort".  Science did not
publish the letter.

"More than 2 years have passed since the article was published and
our efforts to address the validity of the data and conclusions in
an open scientific forum were initiated.  No follow-up studies by
these authors have appeared in print that might clarify the points
in question." said Marlys Witte.

She went on to explain that they turned to JAMA only after both
Science and Gallo had refused to publicly acknowledge their
criticisms.

Dr. Rummond Kennie (deputy editor of JAMA), stated that the Witte's
questions seemed valid to him and that the earlier letter the
Witte's had sent to Science raising these questions "had been
rejected for reasons that didn't hold scientific water."

For all the criticisms the Witte's have faced in this endeavor, the
main one being that they have not attempted to duplicate Gallo's
actually experiment.  Well, this JAMA article does just that... it
contains a report on the 'many' attempts they have made to
duplicate Gallo's results... even to go as far as using Gallo's
exact KS cell line - all with the same results... they were unable
to come up with the same results as Gallo's Science paper.

As the JAMA article concluded, "Perhaps the most serious aspect of
the whole matter has been the reticence and obstacles encountered
to public airing of our questions and the inability of the peer
review process to correct itself once errors and inconsistencies
were pointed out and bolstered by further experimentation."

Finally, in additional information Crewdson provided in this
article... the National Cancer Institute struck a commercial
development deal with Daiichi Pharmaceutical, the Japanese Company
that owns the US-patent on SP-PG, which quickly began plans to try
the drug on American AIDS patients.

The NCI declined to disclose the amount of money Gallo's lab
received from Daiichi, but inside sources put the figure close to
$75,000.  After the deal was announced, Gallo told the Wall Street
Journal that he did not stand to earn anything personally.

Daiichi's stock gained 6 percent on the Tokyo Stock exchange the
day Gallo's Science article came out.

Meanwhile, SP-PG is currently only being tested in 7 patients at
the University of Southern California... where researchers have
recently reported that several of the participates have suffered
from unexpected bleeding and other side effects.  Only 2 of the 7
have appeared to improved since taking the drug.
*****************************

From: tmiller at newssun.med.miami.edu (Todd Miller - Pharmacology)
Newsgroups: sci.med.aids
Subject: Witte vs Gallo (cont)
Date: 29 Sep 1994 13:24:53 -0500
Organization: University of Miami, School of Medicine

        Anyone interested in the response of Dr. Gallo to questions
of his scientific integrity (Witte et al, JAMA 271: 1769) should
read the series of letters in the latest issue of JAMA (272:
916-924).  There are 9 letters (mostly from colleagues of Gallo,
one from Dan Koshland, editor of Science magazine) including a
response from the Witte group.  As I read these, it seems like the
issue is escalating so I think we haven't heard the last of this.
Koshland seemed particularly defensive and angry with his
counterparts at JAMA for publishing the Witte article.
        For those who missed the first few episodes, Gallo
published an article in Science (255: 1437) that appeared to have
some questionable data (you need to read this one first).  The
paper was challenged by the Witte group, but their comments were
rejected twice by the editors of Science.  Frustrated, they went to
JAMA, who agreed to publish their objections to the Gallo paper if
they could provide documented proof of their rejections by Science.
Ahhh, politics.

Todd Miller
******************************

>4) Adequate funding is of course the bugaboo.  From whence comes
>the funding and to whom?  When there is an old boy network that
>funds the familiar faces and when the NIH suffers from a serious
>lack of investigator initated research, again, serious changes
>must be made in the "system" not only at the government level, but
>also in University and private industry.  These changes may need
>to be legislated by Congress, but under current conditions, I'm
>not sure of the likelihood of that nor the value of such
>legislation.  Nonetheless, the discussion here has yielded a
>variety of specific ideas that perhaps someone could synopsize.

??? Whoa... that would be a lot of work.  I'm not sure if I'm
currently up to it?

>Are people here at least agreed that some improvements can be
>made?

I think we all agree improvements are needed... but on which ones
and how to do it seems to be the problem?

-Kathy



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