Sunday, January 01, 2006

January 1, 2006: More on Hwang Woo-Suk

It's 2006, and it's safe to say that patent reform 2005, earlier declared back burner by Orrin Hatch, is dead. Also, one notes that Hwang Woo-Suk still maintains that the patient-specific embryonic stem cell work was done. However, as noted further below, there were some clear indications that the paper as submitted to Science on March 15, 2005 contained errors that could have been caught by a reviewer.

from the Korea Times :

SEOUL (Yonhap): Disgraced South Korean scientist Hwang Woo-suk has denied his landmark 2005 paper on cloning was a sham and called on prosecutors to conduct a probe into his claim that his patient-matched stem cells were stolen, according to a Buddhist newspaper Saturday, December 31, 2005.

Hwang, once celebrated as a national hero for his team's cloning breakthroughs, is now derided as a con artist for seemingly fabricating all of the stem cell lines he claimed were tailored to patients in the paper carried in the U.S. journal Science.

"It is certain that a switch was made and experts will be able to see this immediately. An investigation by prosecutors will only take about two days," Hwang said in an interview with the Beopbo newspaper.

Earlier this month, Hwang filed a complaint with the prosecution, saying Kim Seon-jong, who admitted to duplicating photographs of DNA carried in Hwang's paper, might have been involved in swapping Hwang's stem cells with fertilized eggs from MizMedi Hospital.

On Thursday, Seoul National University's investigation panel said new stem cell lines allegedly created by Hwang did not in fact exist, confirming that he fabricated his research results for the 11 patient-tailored stem cells.

Hwang claimed in the paper published in May that he had created 11 colonies of human embryonic stem cells that were genetically matched to specific patients. The paper has now been largely discredited.

Probes into Hwang's other groundbreaking experiments, including one to verify that he legitimately produced the world's first cloned dog, are still underway at the university where he worked before stepping down last week.

Meanwhile, other allegations came to light that Hwang received a promise from his female researchers to donate their ova for experiments conducted for his 2004 paper, also carried in Science. His 2004 paper put him as the first scientist to clone a human embryo.

Hwang was forced to resign from all public posts after admitting on Nov. 24 that he had violated ethical guidelines by using in his research eggs donated by two female assistants working under him.

But he denied that the female researchers were forced to donate their eggs, saying he was not aware of how exactly the eggs were procured for the experiments.

"There are suspicions that he made some kind of agreement with his researchers before the paper came out in 2004," the Rev. Lee Dong-ik, a member of the National Ethics Committee, said. "It shows there may have been an atmosphere of coercion, forcing them to donate their ova."

During an interview with PBS, a Catholic radio broadcasting station, the priest recalled hearing that a researcher under Hwang had made a testimony to that effect.

"So I raised the issue at a meeting of the committee on Friday, and the committee will try to ascertain the truth," he said.

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Woo Suk Hwang's name does appear on some US patent applications.

Among them:

Gfp-transfected clon pig, gt knock-out clon pig and methods for productions thereof, 20050076399 (filed November 30, 2004, published April 7, 2005)

First claim:

A method of producing a cloned pig expressing a green fluorescent protein gene, comprising the steps of: (a) preparing a nuclear donor cell by culturing a cell line collected from a pig; (b) mixing pEGFP-N1 and a lipid component or non-lipid cationic polymer vehicle to form lipid (or cationic polymer)-DNA complexes, and adding the resulting complexes to a culture medium of the nuclear donor cell and further culturing the nuclear donor cell to introduce said GFP gene thereinto and express said GFP gene therein; (c) transferring the transfected nuclear donor cell into an enucleated pig recipient oocyte to generate a transgenic nuclear transfer embryo, and activating said nuclear transfer embryo; and (d) transplanting the nuclear transfer embryo into a surrogate mother pig to produce live offspring.

***
The blog by Dram Man discusses Korean patent applications by Hwang. These were filed in 1999 and 2000, and thus are years earlier than the 2004 and 2005 scientific publications that are currently at issue.

***Of Hwang's co-author Gerald Schatten:

Schatten, who created the world's first genetically modified monkey Andi using an egg that had been modified to include a simple jellyfish gene, has been instrumental in helping Hwang's achievement in stem cell research gain international recognition. Schatten added he still believed Hwang's team is responsible for "landmark discoveries accelerating biomedical research."

from http://english.chosun.com/w21data/html/news/200511/200511130019.html

***Of informed consent in Hwang's research:

from Concerning Oocyte and Somatic Cell Procurement for Stem Cell Research:

In our article, “Oocyte and Somatic Cell Procurement for Stem Cell Research: The South Korean Experience,” we outlined and defended the informed consent procedures that we reported that Dr. Jung designed for the Hwang team’s 2005 patient-specific stem cell study. In our article, we claimed that the Hwang team followed these rigorous informed consent procedures to procure eggs and somatic cells for their 2005 stem cell research.

However, on December 16, 2005, we began to doubt whether the Hwang team had actually used any of these eggs and somatic cells to generate data for their 2005 Science study. Our doubts were raised by some of Dr. Hwang’s remarks during his press conference that same day and also by the two to three month timeline now widely acknowledged by scientists to be necessary to culture new stem cell lines.

Our first concern was that the timeline for the volunteers’ egg and somatic cell donations did not match the timeline necessary for the Hwang team to produce data for their March 15 article submission to Science. The process we described was not in place prior to January 23, 2005. [LBE note: Ergo, the content of footnote 8 of the Hwang paper in Science, 2005, 308, 1777, was false on its face, and the falsity could have been recognized by a reviewer in March 2005.]

Furthermore, Dr. Hwang publicly declared that several patient-specific stem cell lines were contaminated on January 9, 2005, which would suggest that the team performed some of their cloning research well before to the activation of Jung’s informed consent procedures. We reported our concerns immediately to a member of the Hanyang Hospital IRB and the leadership of the International Society for Stem Cell Research (ISSCR) and its bioethics committee.

On December 23, 2005, the SNU investigative body announced not only that the Hwang team had fabricated their data, but that they had also used far more eggs than they had initially reported to Science. These extra eggs most certainly were not procured through our described informed consent procedures. Indeed, we wonder whether any of the eggs and somatic cells donated through our informed consent procedures were ever used for research. If not, then Hwang and colleagues may have allowed egg donors to expose themselves to risk needlessly. So, in addition to the problems of the Hwang team’s scientific integrity, serious ethical charges of informed consent must now be explored.

We are extremely disappointed by the evidence of the Hwang team’s scientific and ethical misconduct. However, we remain steadfast in our belief that the informed consent procedures we describe in our article are ethically rigorous and that they provide a useful starting point for developing tough guidelines for tissue procurement for stem cell research. Unfortunately, we were lead to believe that the Hwang team had actually used these procedures to produce the patient-specific stem cell lines they reported to Science.

Insoo Hyun and Kyu Won Jung

***
Of fluorescent animals, note the story "Taiwan breeds transgenic, fluorescent, green pig," from ABCNews through Reuters:

By injecting fluorescent green protein into embryonic pigs, a research team at the island's leading National Taiwan University managed to breed three male transgenic pigs, said professor Wu Shinn-Chih of the university's Institute and Department of Animal Science and Technology.

"There are partially fluorescent green pigs elsewhere, but ours are the only ones in the world that are green from inside out. Even their hearts and internal organs are green."

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