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It was all a lie

False research results oblige Science to retract and reopen debate on science and ethics

HÉLIO DE ALMEIDAThe news that the researches into human cloning carried out by South Korean Woo-Suk Hwang were no more than a fraud caused perplexity all over the world. Dumbfounded, many scientists asked themselves what could have been the motivation that led a scientist respected in his country to put together a farce that, sooner or later, would inevitably be revealed. There was no lack of incursions into the terrain of psychiatry, but the problem really was located in the field of ethics.

“In search of the Holy Grail of science, which is the clone, he did the fraud. We have to understand that the scientist, regarded as an angel in the 19th century, has to be seen as a vain human being, full of ambitions”, explains José Eduardo de Siqueira, the president of the Brazilian Bioethics Society. The fact is that, in two articles published in the prestigious Science magazine, in 2004 and 2005, Hwang described, for the first time, the cloning of human embryos.

He claimed that he obtained strains of human embryonic stem cells from them, which would prove the validity of therapeutic cloning. The feat had a spectacular repercussion and was regarded as a landmark, since it opened up real prospects for cellular therapy. In November of last year, accusations appeared in the South Korean press that Hwang had forced women that were part of his team to donate eggs for the study – and had paid them something around US$ 1,400 -, casting suspicions on the use of unethical procedures in carrying out the researches.

This fact triggered off  an investigation by the Institutional Review Council of the Ethics Committees of the Hanyang University Hospital and the Seoul National University. In December, Hwang himself advised Science about “unintentional” errors in four images published by the magazine that were said to have been come out in duplicate. Days afterwards, the editors received a letter from one of the 24 authors of the article published in 2005 – Gerald Schatten, from the Medical Center of the University of Pittsburgh – asking for his name to be removed from the paper.

At the end of December, the Seoul National University found “scientific misconduct”, involving specific DNA data and unverifiable claims about the number of stem cell lineages actually created. The report only preserved the studies that resulted in the production of the first clone of a dog, the Afghan hound Snuppy, presented last year. Hwang can now be criminally indicted for undue use of public funds, since his laboratory consumed US$ 65 million from the government of South Korea.

Back to the past
Besides being a surprise, the corroboration of the farce put research in therapeutic cloning back in square one, at least in terms of publication. “These studies could have brought important information about the behavior of the genes”, says Mayana Zatz, a geneticist and the coordinator of the Human Genome Study Center of the University of São Paulo (USP).

“It was a pity”, comments Rosalia Mendez Otero, a researcher from the Federal University of Rio de Janeiro (UFRJ). “If it were true, it would be a great advance in the researches with stem cells, for being a quicker and easier method for getting lineages.” She recalls, though, that Hwang was not alone in this enterprise and that not all is lost. “Other groups, like the one that cloned Dolly the ewe, are also trying to use this same method.” But nothing has been published yet.

The recrudescence of expectations in relation to therapeutic cloning, though, “has stirred up the hope” of using embryonic stem cells, ponders Lygia da Veiga Pereira, a geneticist from USP, the only line of investigation authorized by the Law on Biosafety in Brazil. She understands that the Hwang should have the effect of a “warning” for researchers all over the world to proceed with more caution in relation to the disclosure of the results of research. “This frenzy with stem cells and this story of making publicity about small advances has to be interrupted.”

The explanation from Science
The fraud led Science to justify itself. “Fraudulent research is a particularly disturbing fact because it puts in jeopardy an enterprise constructed on the basis of confidence. Fortunately, cases like this are rare – but they harm all of us. Fraud will hardly be completely eliminated from the process of scientific publication, and the truth of science depends, in the last instance, on confirmation”, claimed the magazine’s editor- in-chief, in an editorial published in the January 13 issue.

He also announced the decision to do a systematic revision of the editorial history of the two papers and of the procedures adopted for evaluating them. “I have already mentioned in the past that even a particularly rigorous peer review of the kind we adopted in this case can fail to detect a well-constructed fraud”, argued the editor. And he revealed that, together with the members of the Board of Reviewing Editors and of the editorial board, he will be “analyzing options for providing additional procedural safeguards”. These options may, for example, require all the authors to detail their specific contributions to the research and to sign declarations of agreement with the conclusions of the work.

The editorial in Science has reinforced a concern amongst Brazilian scientists: that, from now onwards, the researchers from developing countries may have difficulties in publishing articles in international magazines. “They will be more demanding with regard to corroboration. In the works published by American researchers, information ‘data not shown’ is common. That does not happen when the article is published by Brazilians”, says Mayana Zatz.

Peer review
There were those who attributed to Science a certain carelessness in approving the publication of a research that subsequently proved to be a farce. “The magazine’s committee and the whole editorial board have to do a technical and ethical analysis of the project. If they did it, it was not done well”, comments the president of the Brazilian Bioethics Society. But the great majority of researchers do not attribute any responsibility to the magazine. “No system is perfect. What escapes the reviewers is short-lived”, reckons Lygia da Veiga Pereira.

The international scientific magazines, like Science itself or Nature, select the articles for publication by means of a procedure known as peer review. If the article sent by a researcher – or a group of researchers – is within the magazine’s scope of interest, it is forwarded for evaluation by reviewers who may, occasionally, ask the authors for more information.

It was like that with the scientific article about the genetic sequencing of the Xylella fastidiosa bacterium, signed by 27 Brazilian researchers, which was the cover story of issue No. 6792 of the Nature magazine, published on July 13, 2000. Between the date the article was sent and its publication, two months went by, recalls Fernando Reinach, a researcher from USP, a director of Votoratim Novos Negócios and one of the authors of the paper.

In his assessment, the reviewers have the function of verifying whether the information presented by the researchers is consistent, from the scientific point of view. “The role of peer review is not audit, it was not conceived for that. Proofs are requested with the objective of seeing whether the science is good, setting off from the principle that people are honest”, he emphasizes. Only an audit, like the one done by the University of Seoul, can find out the fraud.

Reinach considers it “a mistake” to think that everything that is published is the truth. In his assessment, science has internal mechanisms for determining frauds and errors, and the main one of these is the principle of “repetition”. “Nature is repetitive. Someone tries to do it again and doesn’t succeed”, he explains. That was what happened with researchers Stanley Pons and Martin Fleischmann, who, in 1989, announced in Nature having discovered cold fusion, an uninterrupted source of energy. No other scientist managed to reproduce the experiment, and the two authors had a little more than their 15 minutes of fame before their conclusions were covered with suspicions.

The problem is that human cloning – the Holy Grail of science, according to Siqueira – is not cold fusion: the researches are directly related to human beings. “The theme is polemical from the scientific and technological, ethical and religious points of view”, explains Volnei Garrafa, the coordinator of the Unesco Bioethics chair of the University of Brasilia (UnB), the president of the Advisory Committee Unesco’s of Latin American and Caribbean Bioethics Network (RedBioética) and an ex-president  of the Brazilian Bioethics Society.

For this reason, he argues, Science ought to have “quadrupled” the precautions and, besides peer review, checked the evidence of the research. “The damage is great and may break credibility in such a promising area. Science, though, will follow its glacial path, just as glacial as ethics.” For Carlos Vogt, a linguist and FAPESP’s president, the Hwang case is the result of the current scenario of science, in which ethics is frequently confronted with competitiveness.

“This creates a sort of new morals of results, unleashes fierce reputations, and attracts the obsession of the market, involving not only the scientific fact but also their experience in the media and in society”, he says.

The fraud by Hwang, in his assessment, associates mechanisms of scientific intelligence – since it indicated a solution for technical restrictions in the case of research with embryonic stem cells – with ethical and religious ingredients.

“The whole preparation of codes of conduct creates normative principles, which leads to a different rhythm from the rhythm of competitiveness”, he says. “And this subject merits much reflection.” The advance of the researches will demand, besides the ethics commissions – “like those that exist and have been working, at local level” -, a greater participation of society. “We have to have a more democratic model of governance of science. Who should say where researches are going? The government? The scientists? Society?”, he enquires.

In the evaluation of Manoel Barral Neto, an immunologist and the director of the Life Sciences area of the National Council for Scientific and Technological Development (CNPq), the ethics committees have no way of detecting frauds like this one. “But farce is ephemeral, since it will be revealed when the results cannot be repeated”, he says. And he warns. “The scientific community has to keep alert for dazzling promises. The advance of science takes place step by step”, he says.

In the evaluation of both Garrafa and of the current president of the Brazilian Bioethics Society, the rules for researches with human beings have to be revised. The argument is that, in the 19th century, scientific investigations – for their nature and object – did not have a direct relationship with human values, and today they have. “The United Nations (UN) and Unesco ought to create structures for controlling certain lines of research, to increase the social control over investigations that involve human beings”, Siqueira suggests. “If Hwang’s work had been examined by a multidisciplinary committee, this would not have happened.”

Equal, but not too much
The rules for research involving human beings were defined in 1964, at the 18th World Medical Assembly, in Helsinki, in Finland, and corrected three times: in the Assembly in Japan, in 1975; in the one in Italy, in 1983, and in Hong Kong, in 1989. “Up until today, the principle prevails that the subjects of research are equal. This is the winning thesis of the 20th century: it was like that in relation to women, Indians and minorities”, Garrafa underscores.

This principle, according to him, is under threat. “The United States has been trying to impose an ethical imperialism, proposing in all the forums in which they participate a double standard for research: distinct methodologies that could be accepted for different peoples”, says Garrafa. The researches with antiretrovirals in Kenya, he exemplifies, can be different from those carried out in France.

“In 2004, isolated, they gave up. But the research  funded by American agencies have to face this problem.” It seems to be the case, according to his comments, of the research about malaria vectors carried out in Amapá, interrupted at the end of last year by a decision of the National Health Council (CNS), suspected of using as human guinea pigs 40 inhabitants from two communities, in exchange for a daily payment of R$ 12. The research is coordinated by the American NGO Institutional Review Board, financed by the University of Florida/National Institutes of Health of the United States, and involves researchers from various Brazilian universities.

Senator Cristovam Buarque (PDT-DF), the president of the Federal Senate?s Human Rights Commission, visited the two communities. “The group that did the research submitted to the CNS’s National Ethics in Research Commitee different documents from those used in the field”, the senator finds. The document presented to the commission talked of the use of inhabitants as collectors of the malaria mosquitoes.

But the term of consent signed by these collectors provided for them to feed the insects until they were sated, four times on the same night. ‘That is not ethical, it’s false”, the senator explains. The term of consent, he goes on, is in Portuguese, but, in the middle of the text, it includes some passages in English. “On the document, there is the rubber stamp Approved by University of Florida stamped”, says Buarque.

The investigations to determine whether there was or not an unethical procedure are under way. “We are going to do public hearings in February and March to listen to the various bodies involved, including the Ministry of Foreign Relations. We want decisions for this not to happen again.” Robert Zimmerman, from the University of Florida and one of the coordinators of the research project, in an interview to the O Estado de S.Paulo newspaper, claimed that he did not see any problems in the use of human bait, and that the complaints were groundless. He explained that the collectors were exposed to the mosquito bites with the intention of evaluating the survival of these insects after they are sated. But it was found that “that was not a good idea”.