Scientist
sues journal over truth and defamation
Online war
between Shi V. Liu and Nature went
into legal battle
TFCP
March 18,
2009
The lawsuit charged “Nature” (used here as a collective term to include Nature, some of its editors, NPG and NPG’s
parent company Macmillan) with “4D” actions. These “4D” actions spelled out as “DECEPTION”, “DEFAMATION”, “DISCRIMINATION” and “DISRUPTION”
(more details will become available later).
Liu’s dispute with Nature on iPSCs began in July 2007 when he submitted a
Communications Arising (CA) to Nature. In that CA he challenged the claims made
in two research reports published in Nature
(448,
313 and 318). The Nature publications were heralded as
firm confirmations for an earlier “discovery” made by a Japanese scientist
Shinya Yamanaka. In 2006 Yamanaka
reported in Cell (126, 663) “induction” of pluripotent stem cells from mouse
embryonic or adult fibroblasts by introducing just four factors. However, that original “discovery” did
not catch any big fire because the stem cell research field was still under a heavy
cloud of the Hwang scandal. With
the publication of these “twin” papers (one from the Yamanaka’s group and
another from Jaenisch’s group in MIT of USA) the perception on iPSCs really
changed greatly. After all, who can
resist the lure of “simple
switch turns cells embryonic”
as headlined by Nature (447, 618, 2007)? Who would not appreciate the “engineered
embryonic stem-like cells from normal mouse skin cells… without the use of
donated eggs or embryos” as highlighted by Nature
(448, 260, 2007)?
The
emphasis that iPSCs are “indistinguishable” from embryonic stem cells (ESCs) by
these Nature publications made iPSCs
the much wanted “ethical” replacements for ESCs. Even White House was pleased with this “milestone”
advancement in stem cell research.
With a promise that cancer-free
person-specific iPSCs can be efficiently generated from any normal adult cell
looming over the therapeutic cloning and regenerative medicine field, the stem
cell research underwent a seismic change and entered a new era, as declared by Nature (451, 135, 2008).
However,
after carefully analyzing above Nature
publications and other publications on iPSCs, Liu arrived at a different
assessment on these cells. He
believes that iPSCs are most likely originated from rare pre-existing stem
cells or progenitors that were perceived as “stem cells”. The introduction of those “reprogramming
factors” which are known oncogenes caused these stem cells to transform into
cancer cells. These iPSCs thus
should be distinct from ESCs. Indeed, some differences were already contained
in the publications making the “indistinguishable” claim. However, those iPSCs researchers just
did not recognize those differences and would not even admit the cancer nature
of iPSCs.
Liu’s
sharp vision on the true nature of iPSCs was based on his unique understanding
of cell life (see details at http://im1.biz/Aging.htm
) and cancer biology (http://im1.biz/Cancer.htm
). In contrast to the conventional
wisdom conveyed through the mainstream which
claims that two cells derived from one cell are sister cells of the same
daughter generation, Liu has firmly concluded that these two pairing cells are
actually one pre-existing mother cell and one new born daughter cell. He believes that cell division is a
wrong concept because no cell is actually divided but reproduced. With cell reproduction, a natural cell
age difference exists between any two “paired”. This conceptual change actually ends a
dichotomy in biology that most unicellular microorganisms are perceived as
immortal while all multicelluar macroorganisms are mortal. Liu’s pioneering study on aging in
prokaryotic bacteria in the early 1990s proved that indeed all life forms
follow some same key life principles.
Liu even
described in detail
how cell aging is linked with aging at the molecular
level and came up with a detailed prediction of a regular DNA
segregation pattern in cell reproduction.
Liu predicted that the older DNA template is always retained by the
mother cell and the younger DNA template normally goes into the daughter cell during cell reproduction. Although such
non-random segregation pattern has been observed before such as in some stem cells, its interpretation led to a wrong hypothesis
of “immortal strand” and even the erroneous perception of stem cell
immortality. Liu pointed out that stem cells are actually some older
cells in a body of multicellular organism.
They are mortal and susceptible to aging. As a matter of fact, the oldest DNA they
contain may suffer more DNA aging even if they are not prone to replication
mutations.
Liu
outlined a cell-aging based roadmap for
multicellular development and correctly identified the nature and developmental
location of stem cells and the cell differentiation hierarchy. He also pointed out that some ASCs are
actually the same ESCs lived into the adult age. Thus the real distinction between ASCs
and ESCs is not that they are some different entities but the same entity under
different age and functional status. In Liu’s view, a cell may change its
differentiation status and functions, but its age cannot be reversed. A stem
cell may reproduce a daughter cell that is very similar to it but that does not
mean a stem cell can be self-renewed (see details at http://im1.biz/StemCell.htm and http://im1.biz/Aging.htm).
From
that fundamentally unique perspective on cell life and cell differentiation and
development in multicellular life, Liu immediately sensed some unscientific
nature of the claims made for iPSCs such as “turning back the developmental
clock” and even reversing aging.
Also, based on the repeated observations of very low “induction
efficiency” for iPSCs and other indications of a “universal” activation of cell
reproduction, Liu suspected that the so-called “induction” of “normal”
differentiated cells into the pluripotent stem cells may be better explained by
a mechanism of general activation of cell reproduction and them a selection of
stem cells or even progenitors based on some “stemness” markers.
Liu sent
his CA to Yamanaka first and got a formal response which included the
following: “We agree that the origin of iPS cells may be tissue stem or
progenitor cells co-existing in fibroblast cultures”. Yamanaka even declared
that “We have never claimed that we generated iPS cells from terminally
differentiated cells”, contradicting an earlier generalization made by a
Commentary in Cell (126, 652, 2006) that “Takahashi and
Yamanaka have successfully reprogrammed terminally differentiated cells to a
pluripotent state”. Yamanaka’s
response also proved that Nature’s
characterization of the iPSCs as “engineered embryonic stem-like cells from
normal mouse skin cells” is misleading because normal cells have been perceived as ordinary differentiated cells.
Indeed, the popular mass media and laymen public got just that
perception of any cell can be turned into a stem cell with that “induction”
process.
Liu
submitted his CA (with Yamanaka’s “agreement”) to Nature. Nature did not accept it as should
be. Instead, Nature put Liu’s CA into a peer review process which resulted in
the final rejection of Liu’s CA.
Under such a circumstance, Liu published this CA (as submitted to Nature) in Logical Biology (7, 63, 2007). He also published others papers in Logical Biology (7, 69, 2007 and 7,
73, 2007) to refute the review
comments on his CA submitted to Nature.
Liu sent copies of these publications to Nature,
Yamanaka and other related parties for response. However, none of them offered any
counter-argument over these PUBLISHED criticisms.
Since then, Liu
has published a series of analyses on almost every original reports
on iPSCs (see a list at http://im1.biz/Cloning.htm
). Liu’s efforts caught attention
of many researchers, especially from his popular blog in
However,
despite these published critical assessments on iPSCs, Nature and other top journals still presents
an image of inducing embryonic-like cancer-free pluripotent stem cells from
normal cells to the public. To
overcome this deception in science, Liu began to confront
Nature head-on by posting his views
directly on the comment windows of different Nature News on iPSCs. Under the news “Stem cells: a
national project” (Nature 451, 229, 2008) Liu began his series of
comments with an open invitation to engage stem cell researchers into a
constructive dialog or dispute (http://www.nature.com/news/2008/080116/full/451229a.html). However, so far no one have publicly
answered Liu’s invitation and expressed their counter-argument against Liu’s
criticisms. The silence and also
the ignorance are both amazing.
But, from his decade-long experience in running double-open
new-generation scientific journals (http://im1.biz
), Liu knows very well why scientists nowadays are unwilling to participate in
any public debate (Nature 447, 1052,
2007).
Not to Liu’s surprise, his courageous actions were
not liked by all people. Actually
some people even developed resentments towards
him. Many of Liu’s scientific
comments were removed by the moderators of Nature
News, as best exemplified by the
incidences happened under Nature News
“Stem cells: 5 things to know before jumping on the iPS bandwagon” (452, 406, 2008; http://www.nature.com/news/2008/080326/full/452406a.html
). But some defamatory remarks on
Liu were allowed and kept in Nature News
even until today. These anonymous
comments called Liu as “madman”, “just plain neurotic” and “a nuisance”
and trashed Liu’s publications.
They characterized the journals publishing Liu’s view as “hilarity” and degraded Liu’s supporters as “little fan
club with this mockery of the scientific process”. It is really unbelievable that an allegedly scholarly journal like Nature would allow such distasteful
personal attacks running in a professional place.
Recently, Nature published an Editorial “It's good to blog” (Nature 457:1058, 2009). In response to Nature’s call that “there are societal debates that have much to gain from the uncensored voices of researchers” Liu posted several comments in the discussion forum “Science, journalism or public discourse?”(http://network.nature.com/groups/naturenewsandopinion/forum/topics/4044 ). These comments emphasized the value of blog in exposing scientific mistakes and even potential misconduct. However, Liu’s comments were immediately removed. Later, many other comments supporting Liu’s views were also removed. The moderator who is the publishing executive editor of Nature even concluded that “this forum discussion is being abused by a spammer who is using a range of pseudo-identities” and “They are all by the same user, using different false identities.”
However,
that conclusion of a single spammer contribution for all the deleted comments
is simply untrue and was specifically challenged by a different person other
than Liu. Comments criticizing Nature’s censorship flew in. Under such situation, the moderator of Nature had to “lock” the blog from
direct posting. However, during the
locked period of more than three days, only one outside comment (submitted via
email to the moderator) was posted which actually questioned the value of this
censored blogging in Nature.
The disruption
of normal blogging was stopped with a re-opening for direct posting. However, as soon as Liu’s comment on the
activities of this blog was posted, the blog was re-locked and Liu’s comment removed. Liu’s comment detailed many irregular
actions by the moderator and pointed out the defamation nature of some comments
against the alleged single “spammer” (such as calling him as a “pest”).
After
this repeated disruption of normal blogging, Nature’s publishing executive editior sent Liu an email which
states “Please refrain from using Nature Network or any other part of
nature.com. As you know, we have written to you to tell you that your comments
on our websites are not welcome.”
Why would Nature discriminate
Liu? Does Nature have a right in suppressing Liu from expressing his
scientific opinions and protest against personal attack on him?
It will
be interesting to see how Liu’s lawsuit against Nature goes. After all,
there is no such precedent to such single individual
scientist with relatively limited influence and means in
terms of achieving a major impact in the scientific community and yet has
dared to stand up against a powerful publishing house. However, it seems that the truth is on
Liu’s side because recent studies on iPSCs have shown observations that
are more consistent with Dr. Liu’s assessments. For example, higher “induction” efficiencies
have been observed in several studies that started the “induction” from clearly
identified stem cells (Nature 454, 646, 2008; PLoS
Biol 6,
e253;
Cell 136, 411, 2009). More and more studies now show distinctions
between iPSCs and ESCs. Even the
strongest defender of the “indistinguishable” claim now published a paper in Cell (136, 964, 2009) to show “Factor-free
hiPSCs ……[are]
more closely related to hESCs than to hiPSCs carrying the transgenes”. As to the cancer-free claim for some
earlier “safe” iPSCs, none seemed to pan out. Yamanaka even showed some “abnormality”
caused by his “safer” iPSCs as reported in a “note added in proof” to his Science paper and publicly “thanked” Liu
for offering criticisms (Science 321,641, 2008).
Now, the research on iPSCs is focused on how to
silence, remove, or even avoid those oncogenic “inducing” factors. But Liu has predicted this is the only
way that iPSCs can be made “safe” for therapeutic cloning and regenerative
medicine. Liu even pointed out
iPSCs research is a great detour because eventually people will come back to a
realization that iPSCs are not the same as ESCs and even normal ASCs. Liu stated that those “inducing” factors
may even be unnecessary if activation of cell reproduction and isolating stem
cells based on stemness marker is the true mechanism for the so-called “induction”. This is because there were already some successful
ways to do so as exemplified by the pioneering study of a Chinese physician
Rongxiang Xu. But Xu’s work has
been largely ignored by the western scientists in the same research field.
Unfortunately, as the funding shifted towards the
easy-to-do “induction” of pluripotent stem cells or transformation of normal
cells into cancer cells, more and more research will be performed in this area
and more and more publications will come out. Some people even used this phenomenon as
an argument of the “success” of iPSC research. However, Liu asked people to relearn the
“polywater” lesson. Hundreds
research papers were published on “polywater”. But does “polywater” exist?
The credibility of Liu as an intelligent scientist
seems unquestionable. Many of his “preliminary” discoveries such as bacterial
aging, regular DNA strand segregation in cell reproduction, and stem cell
mortality have been verified. Liu’s far-vision on the end of iPSCs may also
come to a close view if the mainstream dam is broken.
But whether
or not Liu’s ways of seeking truth and speaking out for the truth are
acceptable to the mainstream of scientific society is still questionable. Some believed that he has gone too far
or at least jumped at the gun too early.
Some said his outspoken style is to harsh to normal scientists. But, when the mainstream scientific
communication are dominated by some powerful peers who would not even allow
expression of any alternative views, what can a normal scientist do? After all, Hwang’s stem cell deception
was not caught by any expert reviewing his manuscript or spotted by any spinning article commenting on his publication. Hwang’s
scandal might even not be exposed if it was not because of the internet blogging started from an anonymous post on a bulletin board maintained by ''PD Notebook''. So
it is indeed good to (soundly) blog as stated by the
recent Nature editorial and not good
to block the blog as protested by Liu against Nature’s locking on a blog.
Nature published a correspondence from Liu in 2000 (403, 592) which stated “Debating
controversies can enhance creativity” and even allowed for
a reference to Liu’s pioneering effort in starting double-open (open
access and open review) scientific journal called Logical Biology (http://logibio.com
). Now when that openness led to
some criticisms over Nature’s own
publications and behaviors, Liu became “unwelcome” by Nature. Should this be
tolerated by the scientific community or not? This should be clear in favor of the latter option if
science and scientific truth are to be advanced.
Liu said that he is willing to sacrifice himself and
become a victim in his war against top corruption in science. In his view, no one should be empowered
with a dictatorship in science because science is a process of seeking truth,
not a course of dictating dogmas. Before truth is known, every one has a right
to seek truth. In front of truth,
everyone is equal regardless of his social status. However, what the reality is in today’s
scientific world? Today’s scientific community is dominated by some dictators
in science!
Let us hope a legal process can yield some right
answers to the urgent societal questions regarding scientific research and
communication. Let us wish justice
will be fair to truth-seeking scientists no matter how “abnormal” his ways of
seeking truth are.