September 2023


Science fiction in university labs?

By Jackson Ryan
Microscopic image of Multiple Myeloma cells

Microscopic image of Multiple Myeloma © Medicshots / Alamy Stock Photo

The case of UNSW and an “anti-cancer superdrug” highlights issues with self-regulation in universities about what constitutes research misconduct

I’ve never seen a desktop like the one David Vaux deals with every day. Word docs, PDFs, spreadsheets and file types I can’t even recognise fill practically every inch of his laptop’s screen. As I sit next to him in the red-brick University House at the University of Melbourne, his cursor searches for a file among the clutter. He tells me, half-jokingly, to forget what I’m seeing – almost all of the material concerns investigations into research misconduct in Australian universities. Some are ongoing. Some are confidential.

The one I’m interested in is not a secret. It’s a case Vaux, one of Australia’s most respected scientific integrity advocates, has been following for more than a decade. In fact, he’s one of the case’s major protagonists – Captain Ahab in search of his White Whale. It’s a case centred around Levon Michael Khachigian, a highly regarded vascular biologist at the University of New South Wales (UNSW). In the past two decades, Professor Khachigian has published more than 250 research articles and brought in more than $30 million of funding to the university in a quest to understand blood vessels and the pathology of cancer.

Vaux double-clicks a document on the desktop. An 80-page timeline expands across the screen. The first date, at the top of the page, is June 1995. It references a seminal paper by American scientists regarding a new type of therapeutic drug, known as DNAzymes. But for Vaux, this story starts 14 years later: August 25, 2009. It remains unfinished.

On that day, after spotting a duplicated image – a potential sign of data manipulation or fabrication – in a scientific paper authored by Khachigian and some of his students, Vaux sent an email to alert the vascular biologist to the issue. Most researchers would be immediately concerned by this kind of correspondence and eager to correct the scientific record. Khachigian’s response, Vaux says, was blasé.

Khachigian’s cavalier attitude settled somewhere deep in Vaux’s mind. More than three years later, in 2012, the memory of that interaction re-emerged as Vaux assessed images in another paper by Khachigian, published in the Journal of Biological Chemistry. The paper suggested a protein could be blocked by an experimental drug developed by Khachigian and his team at the UNSW Centre for Vascular Research, known as Dz13, which prevented the narrowing of blood vessels in rabbits. Vaux was concerned by duplicated images in the paper, just as he had been in 2009. This could be an innocent error or, more worryingly, a potential sign of falsified data and scientific misconduct.

By this point, Khachigian had been writing the story of Dz13 for almost a decade. It was a story full of promise. The drug had led the hype for a burgeoning new field of cancer treatments. It was easy to produce and easy to administer. UNSW had called it a “superdrug” in social media videos. The Sydney Morning Herald’s science editor, captivated by its potential, dubbed it a “cure-all”. And, in a very small clinical trial, the drug had shown signs of activity against skin cancer. It appeared relatively safe. The story of Dz13 was becoming a tale of triumph for Khachigian, his laboratory and university.

Vaux’s discovery suggested parts of that story may have been fabricated. And, unbeknownst to him, a former student of Khachigian had been raising the same alarm behind the scenes, leading to a series of secretive investigations by UNSW. By the time those investigations were complete, the story of Dz13 would require a fundamental rewrite.

Enzymes underpin basic physiological processes across the diversity of life. They’re made up of long chains of amino acids that bend and fold to accelerate chemical reactions, sometimes up to a billion times. Pepsin, for instance, helps kickstart the process that breaks down food in the human gut, whereas a brain-eating amoeba requires the enzyme ERG2 to keep its body stable.

In 1982, Thomas Cech’s laboratory at the University of Colorado discovered that RNA, most commonly recognised as a single-stranded molecule used to carry information and build proteins, could also act like an enzyme. Then, in 1994, Ronald Breaker and Gerald Joyce at the Scripps Research Institute in California were able to fashion an enzyme made from DNA. It was able to break down the information-carrying RNA molecules, which meant it could be designed to stop cellular processes, including those associated with cancer.

Breaker and Joyce’s molecules are those that would later be named “DNAzymes”. They are sometimes described as a pair of “molecular scissors” or “shears” because they chop up a type of RNA known as messenger RNA (mRNA), which cells use to build proteins. For Levon Khachigian, they represented a “new class of therapeutics”, and he began to explore this niche with his own experimental DNAzyme in the early 2000s. It was called Dz13.

Dz13 was designed with a specific target in mind: the mRNA of c-Jun, a protein that helps cells grow and survive. Khachigian describes c-Jun as a “godfather gene” and in abnormal conditions, such as skin cancer, arthritis, eye disease and heart disease, c-Jun is much more active. Its increased expression in those pathologies suggests it might play a role as a master regulator, controlling how the diseases progress. That raised a tantalising possibility: destroying c-Jun with Dz13 might just be able to cure some forms of cancer.

Its potential was apparent to NewSouth Innovations, the commercialisation arm of UNSW, too. Khachigian, along with NewSouth, patented the experimental drug in 2002. Now he had to assess how well it worked.

At just 39 years of age, Levon Khachigian stood at the summit of Australia’s science mountain. It had been a long, and perhaps unlikely, climb.

Khachigian was born in Beirut to Armenian parents who had worked as missionaries throughout the Middle East in the 1960s. In 1966, his parents moved to Naremburn, on Sydney’s lower North Shore, where they started the Armenian Brotherhood Holy Trinity Church. Khachigian was predestined to become an active member of the church, but his ascent in science was born of a curiosity he developed in high school.

“I became interested in science because I was encouraged to ask questions,” he said in a Sydney Morning Herald profile published in 2006.

Though he remained active in the church, serenading crowds at baptisms with his violin, his curiosity drove his science to greater heights. Before his 40th birthday, he was awarded the Commonwealth Health Minister’s Award for Excellence in Health and Medical Research, an Australian Museum Eureka Prize and the Australian Academy of Science’s Gottschalk Medal. The recognition came largely for his contributions to understanding the cells and molecules responsible for diseases of blood vessels. At the time, in 2003, his work with Dz13 was just beginning to make waves.

In 2002, he published in the Journal of Biological Chemistry his first study showing how c-Jun helps control the cellular response when blood vessels are injured. The same study provided evidence Dz13 was able to inhibit the formation of a neointima, or scar tissue, which can form in response to surgery. It was the earliest hint his drug might be useful as a therapeutic. Further studies, in 2004, demonstrated Dz13 could reduce the size of solid tumours in rodent models. Hype for the drug began to build.

Khachigian continued to accumulate awards and professional recognition while working with UNSW’s Centre for Vascular Research. He also accumulated money, bringing in research grants and fellowships totalling more than $16 million between 2002 and 2007, including leading a huge project funded by the National Health and Medical Research Council to the tune of more than $13 million. His lab was flourishing.

In March 2007, postdoctoral researcher Ying Morgan started in the lab and, a few months later, another postdoctoral student, Hong Cai, was hired. Both researchers were to study different aspects of Dz13 in preclinical work. Morgan focused on the drug’s effect on melanoma, the most serious form of skin cancer. Cai helped investigate two other forms, basal cell carcinoma and squamous cell carcinoma.

Cai paid special attention to the delivery of Dz13, focusing on how to inject the drug into tumour cells so it can chop up c-Jun. Her work involved the use of a lipid particle to deliver the drug into tumours in mice. In one experiment, she injected immunocompromised mice with tumour cells, and then assessed tumour growth using an ultrasound machine. Her experiments, in Morgan’s words, were 100 per cent perfect. In the messy world of science experimentation, that seemed unusual.

But it was the ultrasounds that became a sticking point for Morgan. When Cai presented the data at a laboratory meeting on August 25, 2008, Morgan raised concerns with Khachigian and the other staff present. She didn’t believe the results Cai presented were possible, because she didn’t think Cai had access to the necessary hardware or software to analyse the ultrasound data. Morgan says Khachigian dismissed her, suggesting she should not ask any more questions along those lines. Like David Vaux, she was surprised by his cavalier reaction to a question about academic rigour.

After the meeting, Morgan went straight to her lab book. “What a shock!” she scribbled down. “Results of SCC animal work need to be reexamined!!!”

Ying Morgan wears a jade monkey pendant around her neck. The totem is something she picked up in an airport and, though she’s been wearing it for decades, it holds no special significance for her. Even as I prod, looking for some hidden meaning or interesting anecdote, she doesn’t budge or embellish: it’s a jade monkey pendant she bought in an airport. She likes it. That’s all.

It’s a facet of the Chinese-born researcher I come to appreciate. It’s not that she doesn’t have something to say. When she speaks about her time in Khachigian’s lab it feels like she’s reliving every moment of her studies concurrently, like she’s hopping through a multiverse of her experiences all at once. Although she belabours some points, the stories never change. No stray details emerge, no new multiverses open up.

Her time in Khachigian’s lab was stressful, Morgan says. She would often spend evenings running experiments related to Dz13. She recalls it being a particularly busy time. She would head into the university after putting the kids to bed and, sometimes, she would stay until the morning cleaning crew turned up at 5am. The drug was being prepared for a human trial and she felt compelled to ensure it was safe and effective.

Yet the data she was producing did not inspire confidence. Doubts had started to creep into Morgan’s mind. At times, she’d note the tumours shrinking after injection of Dz13, but, a few weeks later, they began growing again. Other groups, including two composed of researchers from pharmaceutical giant Johnson & Johnson, found the anti-tumour activity of Dz13 was non-specific. It seemed to prevent tumour growth in some experiments, but not by chopping up c-Jun mRNA. (These non-specific effects were also seen in a study in 2010, authored by Crispin Dass and Peter Choong, researchers at St Vincent’s Hospital Melbourne).

It was against this backdrop that the results Hong Cai was presenting at lab meetings became suspicious.

When Morgan called Cai out in the lab meeting of August 25, 2008, it wasn’t the first time questions had been raised about her colleague’s results. Three months earlier, Morgan alleges another scientist in the laboratory, Lionel Lourenço-Dias, pointed out duplicated images during one of Cai’s presentations. During that meeting, Khachigian casually reprimanded Cai for the errors, according to Morgan. No lab members present at the meeting responded to my requests for comment.

Though Morgan had quietly raised concerns with Khachigian inside the lab’s four walls, it would take another year for her to bring them to the attention of UNSW. In October 2009, she discussed her concerns with Nicholas Hawkins, then UNSW’s head of the School of Medical Sciences. A week after the conversation, Hawkins emailed the senior associate dean in the faculty of medicine, Terry Campbell, with Morgan’s allegations about potential data manipulation and fabrication in Khachigian’s lab. Campbell, per UNSW protocol, forwarded the email to Les Field, the deputy vice-chancellor of research.

Morgan also claimed that falsified data produced by Cai had been included in manuscripts prepared by Khachigian and sent to prestigious scientific journals, including Nature Medicine. Just before the end of 2009, she emailed Khachigian to note she had “no confidence with Dr Hong Cai’s research data and results” and would like her name to be removed from the manuscript.

Though Morgan was performing the bulk of the preclinical work related to Dz13, her contract with UNSW and the Centre for Vascular Research was not renewed at the end of 2009. There are differing accounts as to why. Morgan believes it was because she was asking too many questions. Three months after she left, she emailed Khachigian again, reiterating her stance on authorship. He responded, giving her another chance to reverse her decision and claiming he had undertaken “a number of measures to confirm the integrity of the results”.

For Morgan, those were just words. She wanted to see evidence. It was no longer about whether her name ended up in the author list of a scientific paper. She knew clinical trials of Dz13 would soon begin, and the drug would be injected into humans for the first time. In her experiments, she’d recorded instances of inflammation in the lungs of mice injected with Dz13. It was a side effect she was worried might repeat in human trials.

Her back-and-forth with Khachigian over authorship also included a pointed question. In an email on March 24, 2010, she reminded Khachigian of an interaction the two had while she was still in his lab. Khachigian had asked her in a previous email, given what she knew about the drug’s effect on basal and squamous cell carcinomas, if she’d be willing to take part in a clinical trial of Dz13.

“I answered very clearly,” she wrote. “No.”

While Ying Morgan was privately raising complaints about potential misconduct in Levon Khachigian’s lab, unbeknownst to her, David Vaux was raising questions about falsified images in papers previously published by Khachigian in the Journal of Biological Chemistry.

Vaux, a specialist in cell death at the Walter and Eliza Hall Institute in Melbourne until his retirement in 2019, is arguably the most recognisable face in Australian scientific research integrity. Climb to the top of the nation’s science mountain and you’ll likely see Vaux somewhere up on the peak, scrounging around for fabricated data. He also serves on the board of directors for The Center for Scientific Integrity, a non-profit organisation with the goal of improving transparency and integrity in science. The CSI is the parent organisation of Retraction Watch, a website that maintains a database of retractions from scientific journals.

Modern science is built on publishing papers, short accounts of research that take the readership on a journey of discovery and understanding. Papers are the currency of academia, and publishing groundbreaking articles in major international journals has become a shorthand measurement for a researcher’s excellence. Bigger, better papers land you in better, more lucrative university positions, which presents more opportunities for funding, which results in better papers. The cycle continues.

These incentives have seen more and more science papers tilt towards fiction. There are cases of outright fabrication of data, plagiarism of other researchers’ work and, most commonly, manipulation of images – stretching, cropping, duplicating or rotating experimental photographs to pass them off as different, new or more impactful. Co-founders of Retraction Watch Ivan Oransky and Adam Marcus wrote in the US health and science publication STAT in December 2022 that “a retraction for image manipulation happens about once every other day”.

When a scientist’s work is found to be deliberately fabricated or falsified, it’s struck from the record with a retraction. This is a problem that has been increasing in recent years. In 2002, there were 119 retractions across the scientific literature, according to Retraction Watch. In 2022, that number was more than 4600.

Vaux’s efforts over the past two decades have led to more than a dozen retractions. He’s become adept at spotting statistical flaws and dodgy figures, in images of western blots, for instance – a type of experiment to detect specific protein levels in a sample – or photographs down a microscope used multiple times in the same paper but inverted or cropped in different ways. Along with integrity crusaders such as Vaux, a whole cottage industry of amateur image sleuths has popped up, scouring journals for inconsistencies. The website PubPeer, where the public can leave comments about scientific papers, has become a free-fire zone for claims of misconduct.

(Vaux himself has been accused of image manipulation on PubPeer. He and his co-authors owned up to some incorrectly duplicated images and attempted to rectify them with the relevant journals, though some remain uncorrected.)

In December 2009, as Morgan was finishing up at UNSW, Vaux contacted the editors of the Journal of Biological Chemistry alleging that one of Khachigian’s papers contained duplicate images. By February 5, 2010, the paper had been corrected, but the correction also contained duplicated images passed off as two separate experiments. Vaux alerted the journal in May 2010 to the issue, asking the editors to “please try to obtain data from these authors that readers of the JBC can trust”. The paper had just two authors: Mary Liu, a postdoctoral student in Khachigian’s lab, and Khachigian himself.

Three months before a clinical trial was scheduled to start injecting Dz13 into patients, the Liu and Khachigian paper was retracted altogether. The withdrawal came as a surprise to Liu, who wrote to the ABC in 2016 that she was never interviewed by any UNSW panel investigating research misconduct, even though she co-authored one of the retracted papers. She also noted that she was not aware corrections had been made to her paper, nor that it was being retracted. She did not wish to comment about specifics for this essay, saying “I really have no time and energy to talk about this.”

An additional two papers in which Khachigian was the most senior author were also retracted from the Journal of Biological Chemistry. The retraction notices only state that the papers were “withdrawn by the authors”, as was standard practice for the journal at the time.

Though none of these three papers related to work with Dz13, the triple retraction cast a long shadow. It was the second time Vaux had personally raised issues of image manipulation in regard to Khachigian. It would not be the last.

Despite concerns being raised by Morgan internally since August 2008, and Vaux’s communications with scientific journals about the veracity of data in several Khachigian papers, a first-in-class clinical trial to test the safety and tolerability of Dz13 was registered with the Australian New Zealand Clinical Trials Registry in February 2010. It was to be funded with Cancer Institute NSW donations, to the tune of $3 million.

The DISCOVER trial, as it was known, was scheduled to begin in September 2010. It would recruit nine patients with nodular basal cell carcinomas, then treat them at the Royal Prince Alfred Hospital in Sydney. The patients would be split into three groups of three, with each group receiving a different dose of Dz13 – either 10, 30 or 100 micrograms. In animal models, the trial registration states Dz13 was “well tolerated at doses 35-fold higher than the highest dose that will be used in this study”.

Though Morgan was no longer working at UNSW, she made another set of formal allegations of research misconduct in Khachigian’s lab to Les Field in March 2010. Field found, two months later, that no prima facie case existed for Morgan’s claims and he did not pursue them further.

Morgan was disappointed with Field’s response and became increasingly concerned about patient safety in the trial. In August 2010 she emailed Field again, this time with a 39-page PDF containing a comprehensive list of allegations regarding the work of Hong Cai, pointing to examples of data she believed was falsified. Notably, these allegations focused on work Cai performed using Dz13, including the ultrasound data presented at the 2008 lab meeting.

By October 12, Field had established there was a prima facie case for a finding of research misconduct. The Australian Code for the Responsible Conduct of Research describes research misconduct as a “serious breach of the Code which is also intentional or reckless or negligent”. It also notes that “repeated or persistent breaches will likely constitute a serious breach, which will trigger consideration of research misconduct”.

Even though Morgan’s allegations related to potentially falsified data around Dz13, the chair of the Human Research Ethics Committee (HREC) with oversight of the trial, Rob Loblay, was not notified of the prima facie findings until March 2011, when the trial had already been running for seven months. He was notified by Khachigian, the subject of the allegations and the holder of the patent for Dz13, along with NewSouth Innovations. At the time, Les Field was the chairman of the board for NewSouth.

Field did not respond to specific questions I put to him about his position or the timing of notifying the HREC, stating that “matters concerning Professor Khachigian were investigated thoroughly more than 10 years ago and the processes have been reviewed at length. I won’t make any further comments on these matters.”

Finally, in May 2011, an external panel was established by the deputy vice-chancellor (academic), Richard Henry, as per protocol, to investigate Morgan’s allegations further. Its three members were cancer researcher Brandon Wainwright, solicitor Nancy Dolan and esteemed molecular biologist Robert “Bob” Williamson. But the clinical trial was never paused, even with the pending investigation, and continued to run until its completion in October 2011. This meant there was a possibility the recruited patients could receive an injection of an experimental drug underpinned by potentially falsified data.

The Williamson panel took almost a year to return its findings. In February 2012, it determined Khachigian and Cai had not engaged in any “research misconduct” and there was no reason to question the integrity of the data underpinning the trial. Vaux notes the panel members did not include anyone who had ever conducted a clinical trial and the patients were never informed of the allegations.

Khachigian and his team later published a paper in one of the world’s most highly regarded medical journals, The Lancet. The paper, which went to press in May 2013, analysed the DISCOVER trial, highlighting the safety and tolerability of Dz13. It reported seven adverse events in four of the nine patients. Three were regarded as “treatment-related”, including swelling of the injection site, discomfort and nausea. Khachigian’s team concluded that further development of Dz13 would help establish the efficacy of the drug in skin cancers and potentially other diseases. The stage was set for DISCOVER 2.

As Khachigian and his team were gearing up for the second trial to begin in 2013, Vaux had read a media piece regarding a new paper from Khachigian’s lab in Science Translational Medicine. This paper contained some of the work underpinning the human clinical trial. The first author was Hong Cai. There’s no indication the paper contains falsified data, but the media coverage inspired Vaux to revisit other work from Khachigian’s lab, just in case there was anything he missed. He still had Khachigian’s cavalier response from 2009 ringing in his head.

He went back to a 2010 paper, authored by students Jun Ni and Alla Waldman, in addition to Khachigian. The paper reportedly showed Dz13’s effects in the blood vessels of rabbits. Vaux immediately noticed a problem. Six problems, in fact.

On Valentine’s Day 2013, Les Field’s inbox dinged. It was not a secret admirer. It was David Vaux, and he was carrying urgent news.

Vaux had annotated the Ni, Waldman and Khachigian (NWK) paper, highlighting images he was concerned about, and sent them to Field. He believed six figures in the paper, mostly photographs of cells taken down the lens of a microscope, had been duplicated or altered. If these were deliberate duplications, they could undermine the scientific integrity of the work.

Vaux also made sure to copy others into the email: the National Health and Medical Research Council and the new deputy vice-chancellor (academic) at UNSW, Iain Martin. Vaux was aware Dz13 had been used in human trials in skin cancer patients. This was particularly worrying.

“If the results in this paper are not genuine,” he wrote, “the HREC that approved the trial might have been misled, and the patients receiving the drug might not have been able to give properly informed consent.”

A UNSW statement in 2013 stated “at no stage has patient safety been jeopardised”.

The NWK paper featured a number of results related to Dz13’s capabilities in treating heart disease. Field began a preliminary investigation quickly, and on February 21, 2013, requested that Khachigian provide a copy of the original data underpinning the research contained in the NWK paper. Khachigian quickly obliged, sending 79 pages. Field also asked for consulting giant Deloitte to present a report on images in the paper.

Field then made a second request, on March 26, 2013, asking for the “original laboratory books in which the experiments were recorded and the raw data underpinning the experiments”.

On April 4, 2013, three books were handed to Field. Two were authored by Jun Ni. A third – a red-covered, hardbound Collins notebook with the words “Alla Waldman 2006 B/CVR” written on the cover and spine – was also handed in and became known as “the Red Book”.

Shortly after, the Deloitte report on the images in the NWK paper was delivered to Les Field. Deloitte’s findings lined up with the image manipulation allegations Vaux had made. As a result, Field began the second prime facie investigation of Levon Khachigian, on June 24, 2013. This time, ahead of a pending second clinical trial, Field took just four days to notify the HREC.

A third prima facie investigation was opened by Iain Martin in September 2013, regarding issues with a paper published by Estella Sanchez-Guerrero and overseen by Khachigian in the open-access journal PLOS One.

On November 29, 2013, a second independent panel was established by Martin to look into both the NWK paper and the Sanchez-Guerrero paper. It was led by Peter Brooks, a cancer researcher at the University of Melbourne and featured molecular biologist John de Jersey, cancer biologist Gail Risbridger and research scientist David Cox. The team of four were to determine if Khachigian and other members of his lab had breached the university’s research code of conduct. Their investigation would help uncover a remarkable truth.

The Red Book was not what it seemed.

The Brooks panel interviewed Alla Waldman on February 13, 2014. Despite her name appearing on its cover, and Field’s specific request for original data, the Red Book was not an original laboratory book, and Waldman was not its author.

During the interview, Waldman revealed Khachigian called her in March 2013, sounding quite urgent, looking for her original lab books. He couldn’t find them. He asked her if she knew where they might be, but didn’t explain why he needed them, despite the fact Waldman was a co-author on the NWK paper under investigation – it was her research being called into question. Khachigian told the Brooks panel he couldn’t mention it to her at the time for “reasons of confidentiality”. Waldman believed her lab books had remained in the lab.

Khachigian visited Waldman in the early morning hours of April 3, during one of her shifts at the Royal Prince Alfred Hospital. It’s unclear how long the meeting lasted, with Khachigian recalling “an hour” and Waldman citing just “10 to 15 minutes”. He presented her with a reproduction of her lab book – some of which contained work found in her thesis published eight years earlier – and asked her to certify that it was faithful to her original. She flicked through the Red Book and believed it to contain her work, so much so she signed a declaration Khachigian produced that said the Red Book contained original data she generated between 2003 and 2006. She also initialled some of the pages “AW”, but later claimed Khachigian had also inscribed her initials on some pages.

After the Brooks panel discovered the Red Book was not an original, they grilled Khachigian in a February 28, 2014 interview. Brooks recalls Khachigian began to sweat under their questioning, pulling out a handkerchief to dab his forehead. The panel members appear incensed in the recorded transcript. Risbridger said she thought the panel had been “misled”. Cox was taken aback by the notion Waldman could have remembered data she generated almost a decade earlier, in order to certify the tables of numbers Khachigian had included in his dupe book. He found this “inherently disbelievable”. Khachigian told the panel he should have indicated the Red Book was “a copy of original data” but that there was “nothing made up in this”.

The Monthly is not suggesting that Khachigian has engaged in any fraudulent or illegal behaviour by reproducing the data contained in the Red Book.

After Brooks emailed Iain Martin on the panel’s deliberations, a separate inquiry, related to the provenance of the Red Book, was opened on May 16, 2014. This investigation was conducted by Kevin Lindgren, a former Federal Court judge. Over the next month, Lindgren interviewed Waldman and Khachigian, and had the professor identify where he had sourced the Red Book material from, page by page. He found Khachigian had added handwritten notes into the Red Book, including five dates from 2006.

Khachigian told Lindgren that when he had compiled the Red Book, “he did not see any distinction between an original lab book and a lab book that was later compiled consisting of original data”, and this is why he didn’t notify anyone associated with the investigation.

Vaux’s characterisation of this course of action could hardly be more damning. “Faking your own lab book is pretty much a cardinal sin,” he says, “but faking your student’s, in the context of a research misconduct investigation, when you are asked for the original by the deputy vice-chancellor, brings it to a whole other level.” A second researcher I spoke to for this story, who did not wish to be named, made the point that “you can generate a thesis from a lab book but can’t generate a lab book from a thesis”.

Lindgren’s report, which was handed to UNSW on June 29 of that year, found that Khachigian’s conduct was not deliberate, intentional or calculated to deceive. In response to a request for comment in this essay, Lindgren noted his inquiry was confidential, that he had no recollection of the details of the case and retained no papers relating to it.

Similarly, the Brooks panel eventually found that “genuine mistakes” had been made that did not affect the conclusions of the NWK paper. Though these mistakes breached the UNSW research code of conduct, they did not constitute research misconduct. Khachigian had survived two major investigations. It seemed like the end of the story. But the NWK paper would continue to haunt him.

By the end of 2014, UNSW had established a prima facie case for research misconduct in Khachigian’s laboratory on six separate occasions. Three papers in which he was the senior author were retracted. The paper led by Estella Sanchez-Guerrero, published in PLOS One, was corrected in June 2013 due to a duplicated image. Another paper, published in Nature Biotechnology, was corrected in June 2015, this time due to incorrectly labelled graphs and images.

On November 26, 2015, the university released a statement regarding the investigations, noting multiple panels of inquiry had found there had been breaches of the UNSW research code but they were never deliberate or intentional. Khachigian returned to work and his NHMRC funding was reinstated.

Two more of his papers have been retracted since, both as a result of concerns that images had been duplicated and used to show results for different experiments.

The first, published in the journal Circulation Research in 2009, was not related to Dz13. It was retracted in 2016, due to “unresolvable concerns” with the original data underlying two of the paper’s figures. The retraction notice states UNSW commissioned an independent, external report to examine this issue, and it was unable to locate in original lab books any records of the images used in the paper. However, this report, instigated by Iain Martin and conducted by University of Auckland professor Louise Nicholson, was not consistent with the Australian Code for the Responsible Conduct of Research, which states independent panels “should normally be constituted with a minimum membership of three people”. Nicholson did not respond to a request for comment.

In May 2017, UNSW established a panel of three to review whether previous findings made against Khachigian, when viewed together, amounted to research misconduct. It was chaired by former solicitor-general of Australia Justin Gleeson and was an on-papers review. It concluded there was a “significant number of findings of breaches” of both the UNSW research code and the Australian Code for Responsible Conduct of Research and “clearly real problems in the research environment that was established and managed” by Khachigian. Ultimately, it concluded Khachigian had been negligent, but that this negligence fell short of “gross and persistent”. In documents summarising the Gleeson panel’s findings, there is no specific reference to the Lindgren report regarding the Red Book. Jeh Coutinho, a barristers’ clerk at Banco Chambers where Gleeson practises, told me that “Mr Gleeson does not recall with sufficient precision” if the panel was provided with the report.

The most consequential retraction for Dz13 came a year later, at the end of 2018. The NWK paper was eventually retracted by the Journal of Biological Chemistry in December, three years after the Brooks panel and four years after the Lindgren report was handed down. The Brooks panel did make a finding of research misconduct in regard to Jun Ni, the former student in Khachigian’s lab and the first author of the paper, but the errors – again, duplicated images – were found to be “minor, honest and unintentional”. Those were corrected in 2013 but this wasn’t enough to satisfy the journal. It raised questions with the authors about two figures in the paper: bar graphs representing an experiment with Dz13 in rabbits. The corresponding figures were labelled 1A and 5B.

During the Brooks panel interview in 2014, Khachigian pointed to these two figures in regard to the Red Book. “If we’re talking about the [NWK] paper, then we’ve got electronic data that underpins … figure 5B, 1A” he told the panel. The primary data for these graphs was reportedly generated by Alla Waldman.

But by December 2018, the raw data underpinning those graphs “were no longer available”, according to the retraction notice in the Journal of Biological Chemistry. Khachigian had made a point to the Brooks panel suggesting the reason he compiled Waldman’s data into the Red Book in the first place was because it provided “longevity”. He said that book contained the original data. But the data has since disappeared. Khachigian did not respond to questions about the paper or the Red Book.

There have been no findings of research misconduct by Waldman, or Hong Cai.

UNSW’s external communications manager, Larissa Baiocchi, provided a statement to me on April 3, 2023, stating the “allegations of research misconduct against Professor Levon Khachigian were extensively investigated and received media attention over a period of years. The outcomes of those investigations determined Prof Khachigian did not commit Research Misconduct within the Australian Code.”

There are only five Australian scientists who have more retractions than Levon Khachigian. But Khachigian’s six stand out. David Vaux says he can’t think of any other Australian researcher with “this many investigations where the institution claims there was no misconduct”. The cases still rankle him. It’s not just about one professor, but a system ill-designed to handle cases of misconduct.

“I want to see the completely incompetent people at the University of New South Wales held to account,” he says. “They’ve collected from Khachigian … you know, tens of millions of dollars of money that should have gone to other researchers.”

For Ying Morgan, the ordeal has been a waking nightmare for more than a decade. After leaving UNSW in 2009, she never worked in a lab again. She says it has had an impact on her children and her family life. She feels let down by the system. And yet, she keeps fighting. Her dedication borders on obsessive and can stray conspiratorial. But she’s spent years compiling data, investigating papers and raising the issue with other researchers.

Then there’s those involved in the major panel investigations. In 2016, Bob Williamson wrote to the Australian Research Integrity Committee, which was investigating the handling of the Khachigian cases by UNSW, to say that his panel found Khachigian had committed an act regarded as proven misconduct “on at least seven separate occasions”. He was advised by UNSW that the panel could not aggregate these to add up to “research misconduct”.

Peter Brooks, who led the second panel, told the ABC in 2019 that he was frustrated his panel was unaware of concurrent investigations into Khachigian in 2014 and wasn’t able to assess the pattern of behaviour. “How many minor issues of misconduct do you have to have before it’s classified as a major one?” he asked. The answer, at present: more than you count on two hands.

The case was also brought before the NSW Independent Commission Against Corruption, but, according to Larissa Baiocchi at UNSW, it “did not pursue claims of Conflict of Interest related to Prof Khachigian’s research”.

There is no formal independent body to investigate cases of research misconduct in Australia, which means universities and institutes are relied upon to investigate themselves. The conflict of interest presents a “real disincentive for an institution to investigate its own researchers”, according to Bruce Lander, former Federal Court judge and South Australian Independent Commissioner Against Corruption. Lander recently completed an inquiry into allegations of research misconduct at the QIMR Berghofer Medical Research Institute.

Professor Levon Khachigian continues to work at UNSW, leading the Vascular Biology and Translational Research Laboratory. In 2020, he received a Vanguard Grant from Australia’s Heart Foundation. The Heart Foundation did not disclose the sum of money awarded. On February 1, 2022, he was awarded a Cardiovascular Senior Researcher Grant from New South Wales Health worth $749,970.

What of Dz13? It appears Khachigian has all but abandoned the molecule he once dubbed a “potential superdrug”. His work is now, at least partially, focused on a chemical compound his laboratory discovered known as BT2. In a 2020 interview with UNSW, he noted that it “shuts down a key cell signalling pathway that serves as an ‘on switch’ for many diseases”. It’s the kind of molecule that, with a little more work, might just turn out to be capable of treating a whole range of abnormalities, including inflammatory diseases and blindness.

It’s the kind of molecule with the potential to be developed into a superdrug. It could also end up being one of the most scrutinised.

Jackson Ryan

Jackson Ryan is the former science editor of He was awarded the 2022 Eureka Prize for Science Journalism.

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