David Sanders Lab

Current Research

Peer Review

One day in the late 1980s, I walked into the biochemistry laboratory at the University of California, Berkeley, where I was a PhD student, and declared that since Time magazine had a “man of the year” (it was only renamed “person of the year” later), Science magazine should have a “molecule of the year”. It happened that I was well positioned to make the suggestion: my supervisor, Daniel E. Koshland Jr, was the editor of Science.

The response to my proposal was the expected ridicule from my lab colleagues. Nevertheless, some time after I left the lab, Dan called me and said: “Guess what is going to be in the end-of-the-year issue of Science?” I guessed that it was something related to the lab’s research. “No,” he replied gleefully: “Molecule of the year!”

Far too much emphasis is placed on who is proposing to do the research and the institutions with which they are associated, rather than on the actual science. Therefore, I recommend that review be conducted in two stages. Reviewers should initially receive only descriptions of the proposed research, written in the third person, with no preliminary results section or indication of the authors’ identities or affiliations. This would require that the proposal be evaluated and scored solely on the detail of its merits.

The second step would see the reviewers provided with the usual biosketches, preliminary results, facility statements and so on, to help them evaluate the capacity of the researchers to conduct the proposed research. There can be no denial that the investigator’s track record is a relevant factor regarding a project’s potential for success. It is, however, inequitable if their identity or affiliation is the dominant factor in assessment. 

The purpose of this two-part review is to reduce the biases, unconscious or conscious, that currently affect the evaluation of proposals. 

Accountability could be further improved by attributing each review to its author. Some might object that confidentiality allows reviewers to be more honest, fearing retaliation less. In fact, confidentiality allows reviewers more scope to favour friends, retaliate against foes and exploit their privileged access to the information in the proposal to advance their own research programmes. The National Institutes of Health reports having detected examples of these forms of misconduct.

Peer review is a powerful method for evaluating research funding proposals. However, improving the fairness and accountability of peer review is a necessity if the modern scientific enterprise is to achieve the more equitable and wider distribution of resources necessary to fund innovative exploration.

Excerpted from a recent publication https://www.timeshighereducation.com/opinion/peer-review-should-be-two-stage-science-first-process

Scientific Publication Ethics

Who is ultimately responsible for the integrity of the scientific literature, the ultimate and enduring product of the research endeavor?  Authors and reviewers clearly have a major role, but journals and research institutions should play their parts as well.  Conflicts of interest, however, militate against the fulfillment of their obligations.  We are working on solutions to these problems.  

In academia, people are judged primarily on the basis of their output, which is most frequently in written form. It is, therefore, imperative that credit for the generation of that product be apportioned appropriately.

The US Federal Research Misconduct Policy defines plagiarism as “the appropriation of another’s ideas, processes, results, or words without giving appropriate credit”. So it is a violation to copy or to use a slightly modified version of another’s words without attribution – where attribution means not only citing the source of the text but also explicitly (by means of quotation marks or offsetting) indicating exactly which words are being reproduced. After all, academics could produce a much greater volume of writing if they didn’t have to actually craft their own text.

A more serious kind of academic plagiarism is the abuse of peer review. Reviewers are provided with privileged information on the condition that they will not share it with others and will not use it to advance their own scholarly activities. But readers of published articles often recognise duplicated texts, or may have strong reason to suspect that results described have been reproduced or materially influenced by a manuscript of their own that the author was asked to review.

Such behaviour is unfair and promotes the wrong concept of the route to academic success. Yet while students are held to account for plagiarism, academics rarely are. One major reason is that journal editors, the first line of defence in the battle against plagiarism, are highly reluctant to penalise plagiarism.

As for self-plagiarism, journals explicitly state that authors must not recycle their own writing – and certainly not without proper citation. It is not fair to those who follow the rules and write novel material each time for others to be able to publish a mosaic of their past writings as a new article.

The current incentive system rewards those who publish often. If there is no penalty for regurgitating previously published material, then we have a formula for undermining originality and creativity and honouring laziness and intellectual theft.

Excerpted from a recent publication https://www.timeshighereducation.com/opinion/we-must-take-academic-plagiarism-seriously


CRISPR and Gene Therapy

Our most recent laboratory project involves delivering CRISPR technology to cells using viral vectors to knockout viral receptors, specifically those required for entry of Ebola virus and Zika virus.

Putting Ebola Virus to Good Use--
Gene Therapy

Retroviruses, through the process of pseudotyping, can acquire the glycoproteins of certain other enveloped viruses and can utilize them for entry into cells. We have demonstrated, for example, that the Ebola virus glycoprotein can be incorporated into replication-defective retroviruses and that it can mediate viral entry into cells. Our experiments allow us to study the entry of viruses such as the Ebola and Marburg viruses in a fashion that is independent of the other steps in the viral life cycle and to do so in a safe and quantitative manner. Our pseudotyped viruses may also have applications in gene-transfer and gene-therapy experiments.

Using the system that we have developed, we have found, for example, that the biochemistry of Ebola virus entry resembles that of bird retroviruses. Our research supports the hypothesis that these viruses shared a common ancestor. This indicates that it is likely that the Ebola virus either currently has a bird as its natural host or that it has evolved from a bird virus. The idea that the natural reservoir for Ebola virus is a migratory African bird is consistent with the epidemiology of Ebola virus outbreaks. Biodefense Ebola virus Bioterrorism

Our studies have also allowed us to determine the disulfide-bond map of the Ebola glycoprotein and to propose that reduction of the disulfide bond between the two subunits of the Ebola glycoprotein complex, GP1 and GP2, is a critical step in the entry of Ebola virus into cells. Furthermore, we have shown that removal of a region of O-glycosylation of the protein enhances processing and its incorporation into recombinant pseudotyped retroviruses. This modification allows for a greatly improved efficiency of gene transfer by the recombinant viruses. Our recombinant viruses bearing the Ebola virus glycoproteins are particularly suited for gene therapy for diseases such as cystic fibrosis.

Article describing Ebola virus research
Article explaining pseudotyped viruses

Gene Therapy for the Liver and Brain

We have invented viruses that have the shells of alphaviruses and the cores of retroviruses. These novel pseudotyped viruses have numerous advantages as gene delivery/gene therapy agents. We have recently demonstrated in a collaboration with researchers at the University of Iowa that these viruses have superior capacity for introducing genes into the liver and brain glial cells in vivo. They therefore possess great promise for the treatment of a number of diseases.

Article describing alphavirus pseudotypes