Issue 4 Article 6

The Legal Implications of Scientific Misconduct

25/4/20

By:

Lee Zhe Yu, Nathan

Edited:

Wu Yuxuan

Tag:

Ethics and Current Issues

Society has had more than its fair share of scientific malpractice scandals, with an average of 1.97% of scientists admitting to fabricating, falsifying or modifying data or results at least once according to a survey by the University of Edinburgh. With the total number of scientists standing at 8.8 million as of 2021 and counting, this means that more than 173360 scientists have committed some form of scientific malpractice. The mere mention of names like He Jiankui and Hwang Woo-suk elicits memories of once-promising researchers permanently tarred by hasty or even fraudulent research activities. With these cases dominating media headlines in the 21st century, it has become a topic of intrigue by the scientific community to find out how scientists are punished for malpractice. In this article, we will delve into the case of Han Dong-Pyou, a vaccine scientist who was convicted of fabricating and falsifying data in Human Immunodeficiency Virus (HIV) vaccine trials and sentenced to 57 months in prison.

A Brief Primer

The Human Immunodeficiency Virus (HIV) is a form of retrovirus that attacks cells of the immune system of the body. Specifically, these cells are called CD4 T cell lymphocytes, a form of T helper cell that helps stimulate other immune cell types to produce an immune response against foreign pathogens. With the immune system response against pathogens compromised, the patient is now more susceptible to opportunistic pathogenic infections. This condition is also known as Acquired Immunodeficiency Syndrome (AIDS). There are two main types of HIV, HIV-1 and HIV-2, of which HIV-1 is more predominant in the world with a higher prevalence and transmission rate. Hence, HIV vaccines tend to target HIV-1 rather than HIV-2.

HIV vaccines tend to be either preventive or therapeutic. The former is administered to healthy patients to prevent them from contracting HIV, while the latter is provided to HIV patients to prolong their lifespan and boost their immune system. Preventive HIV vaccines typically involve the injection of an inactive glycoprotein that would be able to bind and neutralise HIV, preventing HIV infection.

The Crime

Dr Han began research into HIV vaccines under a research team led by Dr Michael Cho at Case Western Reserve University as early as 2004. In 2008, their promising research led them to receive initial National Institute of Health (NIH) funding. Dr Cho was later hired by Iowa State University in 2009, the year that they were awarded a full 5 year grant from the NIH to research on HIV vaccines for rabbits. However, when another team reviewed their work in 2013, the blood samples the researchers used turned out to be contaminated with human antibodies. Dr Cho, who was unaware of the tampering of samples, immediately raised it up with the university’s Research Integrity Office, trying to ascertain whether it was a case of a simple mix-up or a deeper case of misconduct. When samples consistently returned positive for human antibodies, it became clear that the samples were intentionally tampered with. The suspect was quickly narrowed down to Dr Han by August 2013, who admitted his responsibility in spiking the samples soon after.

Dr Han’s misconduct stemmed from two main misdeeds. The first was the aforementioned tampering of samples of rabbit sera, derived from the blood of rabbits. To the initial vaccine mixture comprising peptides from HIV glycoprotein 41-54Q and its related agents, Dr Han either added human immunoglobulin G (IgG), a human antibody, or the HIV-1 glycoprotein 120. Both of these had well-established neutralising properties against HIV-1, the former through preventing HIV from binding to cellular receptors and the latter through preventing viral entry into the CD4 T cells. The consequence of such actions was that the vaccine falsely showed a capability of neutralising a broad range of HIV-1 strands, when in fact the unaltered sera was weakly or non-reactive to HIV-1 viruses.

The second misdeed involved Dr Han deliberately altering data of such experiments such that samples which showed low or no activity were instead reported to be highly reactive, misleading his colleagues and superiors into thinking that the experiments had succeeded. Ultimately, these misdeeds led the researchers to believe that they were pursuing something promising, resulting in them wasting precious time pursuing useless research. In addition, NIH had also paid 5 million USD as of May 2013 to fund the research, which was ultimately for nothing. These funds could have been instead diverted to research projects with greater potential to positively benefiting human lives.

The Consequences

In 2015, Dr Han was sentenced to 57 months in prison for fabricating and falsifying data in HIV vaccine trials. He was subsequently fined 7.2 million USD, subjected to 3 years of supervised release after leaving prison, and had signed a federal agreement barring him from working on research projects funded by the federal government for 3 years.

While Dr Han’s wrongdoing is undeniable, critics, including a former associate director of investigative oversight at the Office of Research Integrity (ORI), allege that the sentence was harsh. This was especially since barring a science researcher from working on projects receiving federal funding usually ends their career, regardless of ban length. This calls into question the utility of an additional jail sentence.

Looking at the Statutes

According to Dr Han’s plea agreement, Dr Han pleaded guilty to two counts under Title 18, Section 1001 of the United States Code. This section states that anyone who:

“knowingly and willfully—

falsifies, conceals, or covers up by any trick, scheme, or device a material fact;
makes any materially false, fictitious, or fraudulent statement or representation; or
makes or uses any false writing or document knowing the same to contain any materially false, fictitious, or fraudulent statement or entry;

shall be fined under this title (and) imprisoned not more than 5 years”.

As stated in Dr Han’s plea agreement, to convict him of an offence under the statute, the government had to prove beyond reasonable doubt that:

“The defendant knowingly, voluntarily, and intentionally made, or willfully caused another to make, a fraudulent representation to the National Institutes of Health;”
“The representation was material to the National Institutes of Health;”
“The false representation to the National Institutes of Health was a matter within the jurisdiction of the agency.”

The first two criteria were clearly met, as Dr Han himself admitted knowingly tampering with the rabbit sera samples which caused Dr Cho to misrepresent his experiments to the NIH, causing the NIH to devote substantial amounts of funding to support the research.

Regarding the third condition, Dr Han agreed that his false representations were made in a matter within the jurisdiction of the NIH. This would be sufficient to convict Dr Han of his offences under the statute.

Sentencing

As agreed by the parties involved in the case, the damage caused by Dr Han’s offence was valued to be between 7 to 20 million USD, which seems suitable given that the NIH grant amount disbursed totalled at least 5 million USD by May 2013, excluding the initial funding Dr Cho’s research team received prior to the 5 year grant. The plea agreement references Section 3B1.3, Section 3B1.1, Section 3B1.2 and Section 2B1.1(b)(10) of the US Sentencing Guidelines (USSG) as relevant to Dr Han’s sentencing.

In the US federal sentencing system, adjustments can increase or decrease a defendant's offense level based on factors like the victim's vulnerability, the offender's role in the crime, and obstruction of justice, ultimately influencing the sentencing range.

According to the plea agreement, Dr Han qualifies for an enhancement based on Section 3B1.3, while neither an upward nor a downward adjustment should be applied based on Section 3B1.1 and Section 3B1.2. It also states that Dr Han’s offence did not involve sophisticated means, meaning that he would not be subject to Section 2B1.1(b)(10).

Section 3B1.3 states that "Public or private trust" refers to “a position of public or private trust characterized by professional or managerial discretion”, where “persons holding such positions ordinarily are subject to significantly less supervision than employees whose responsibilities are primarily non-discretionary in nature” and “the position of public or private trust must have contributed in some significant way to facilitating the commission or concealment of the offense” for an adjustment to apply.

Section 3B1.1 states that an upward adjustment would be applied if:

“If the defendant was an organizer or leader of a criminal activity that involved five or more participants or was otherwise extensive”
“If the defendant was a manager or supervisor (but not an organizer or leader) and the criminal activity involved five or more participants or was otherwise extensive”
“If the defendant was an organizer, leader, manager, or supervisor in any criminal activity other than described in subsection (a) or (b)”

Section 3B1.2 states that a downward adjustment would be applied if:

“If the defendant was a minimal participant in any criminal activity”
“If the defendant was a minor participant in any criminal activity”

Section 2B1.1(b)(10)(C) states that an upward adjustment would be applied if the offence “involved sophisticated means and the defendant intentionally engaged in or caused the conduct constituting sophisticated means”.

By applying these guidelines to Dr Han’s case, the following conclusions can be drawn out. Dr Han’s position as a government-contracted researcher on Dr Cho’s team, and thus subsequent access to resources provided, enabled him to tamper with the rabbit blood sera. This directly resulted in the false representation of the research results being conveyed to the NIH. Hence, Dr Han would hence qualify for an enhancement adjustment per Section 3B1.3, as stated by the plea agreement.

Although Dr Han’s criminal action was significant to the NIH, he was neither in a position as an “organiser” to the criminal activity nor involved more than 5 other participants since he acted alone. Hence, the stipulations stated in Section 3B1.1 would not have applied to him.

Similarly, by acting alone, he was a major participant in the criminal activity, hence the stipulations stated in Section 3B1.2 would have similarly been inapplicable.

According to his plea agreement, the addition of IgG and HIV glycoprotein 120 did not constitute sophisticated means, hence he would also not be subjected to upward adjustments based on Section 2B1.1(b)(10). This is in contrast to United States v. Igboba, in which the defendant-appellant was unsuccessful in his appeal against having such an adjustment applied on his sentence removed. In this case, he “purchased [PII] from an overseas broker through an ‘anonymous’ electronic ‘black market financial network’ and concealed his actions through complex methods such as VPN software”, which were not “software and internet procedures available to the general public” as he claimed. In addition, he “used corporate shell companies—

specifically, the Fingerprint Store and Bubbly Fashion—to receive tax refunds”, which was “paradigmatic example of using sophisticated means”. As per the sentencing guidelines and illustrated through United States v. Igboba, “sophisticated means” refers to the use of “especially complex or especially intricate offense conduct pertaining to the execution or concealment of an offense”. Dr Han’s actions of merely adding IgG and HIV glycoprotein 120 pale in complexity to such means of execution, and he also did not take any other action to conceal his wrongdoing beyond his falsification of the data. Hence, Dr Han means in both execution and concealment of his offense would not qualify for such an adjustment.

Using these sentencing guidelines and based on the sentencing scheme as stipulated in Section 2B1.1(a)(2) and Section 2B1.1(b)(1), Dr Han was subjected to a prison term of 57 months, which is just 3 months shy of the maximum prison term as stated by Title 18, Section 1001. However, based on the sentencing table used by the US legal framework, such a sentence would be expected given the great amount of monetary loss experienced by NIH.

Context changes everything

That being said, those guidelines were applied in the context of “Basic Economic Offences”, which usually involve businesses rather than non-profit research entities like Iowa State University. Since scientific research usually entails high upfront costs, a greater monetary loss would correspondingly follow research fraud as compared to business fraud. Taking the words of Dr Alan Price, the aforementioned former associate director of investigative oversight at the ORI, which oversees investigations into alleged misconduct involving NIH funds, “criminal prosecution is unusual for a “medium-level” fraud case such as Dr Han’s”. The ORI had earlier barred him from receiving federal grants for three years, which was the maximum penalty it generally imposes on junior investigators like Dr Han. Dr Price later adds “in most cases, I don’t think [Dr Han] would have been [criminally charged and prosecuted]”.

For that, Dr Han would have to “thank” Republican Senator Charles Grassley from Iowa, who has a history of investigating misconduct in biomedical science research. Quoting his letter to the ORI in February 2014, “[a ban from receiving federal funding for 3 years] seems like a very light penalty for a doctor who purposely tampered with a research trial and directly caused millions of taxpayer dollars to be wasted on fraudulent studies”. After extensive media coverage of the case and Senator Grassley’s reaction to it, the federal prosecutor in Des Moines pressed charges against Dr Han, which would lead to his conviction and sentencing.

Conclusion

As a result, the small number of researchers that face criminal charges are usually those whose cases generate the most media attention rather than those who have caused the most harm to other scientists’ careers or to science in general. By focusing on individual cases, society has lost sight of the “larger picture”, claims Dr Nicholas Steneck, an expert in research integrity at the University of Michigan in Ann Arbor.

This view is echoed by Senator Grassley, who contends that “lawmakers would not need to involve themselves in such matters if some government agencies that oversee research grants could levy harsher penalties and had more capacity to investigate alleged fraud”. He worries “that other cases may go unnoticed or unaddressed if there isn’t a public outcry”.

Scientific research remains one of humanity’s sole pathways to chart a better future for themselves. Negative media coverage of such scandals can and will harm public perception of scientific research, leading to lower support for such activities. This would ultimately deprive society of progress and result in much potential to benefit human lives remaining unrealised. At the same time, research fraud is a serious issue as funds could be channeled away from useful research which could benefit society into lost causes that bring about no societal benefit. It would be necessary to balance scientific progress with appropriate regulation so as to provide a conducive environment for research without wasting resources on fundamentally useless pursuits.

References:

Issue 4 - Apr 2025

The Legal Implications of Scientific Misconduct