Questions about MERS, MTAs and mistakes.

Edited by Dr. Katherine E. Arden

This is a story that stretches back to June 2012-nearly 12 months ago. That's when virologist Prof Ali Mohamed Zaki reportedly notified (or not, depending on the article) the Saudi Arabian Ministry of Health about a fatal case of severe acute respiratory infection in a 60-year old man for which the standard laboratory tests yielded no answers. He sent a sample to researchers at the Erasmus Medical Center (EMC) and followed that up with more testing. He and the Dutch researchers found a new coronavirus (CoV). What seems to be missing from this process was any formal release of that sample by the Saudi Arabian Ministry of Health (MOH). Prof Zaki's ethical position could be seen as murky at best.

On September 20th, an eMail Prof Zaki sent to ProMED was published notifying the world of his process (including how he detected the virus using PCR and grew the virus in culture-processes he conducted while working in Saudi Arabia) and his findings.ProMED was subsequently dressed down by Deputy Minister for Saudi Arabian Public Health, Prof Ziad Memish for publishing the eMail about which the Ministry was unaware. Prof Zaki signed off his eMail from the Dr Fakeeh hospital Jeddah Saudi Arabia, a private hospital.

Prof Zaki's eMail served as a trigger for the testing of another ill male from Qatar who had been airlifted to the UK September 12th - that test yielded the second case of the novel coronavirus.

If Prof Zaki did not follow protocol and sent a specimen without the knowledge or permission of the Kingdom it is interesting, in light of the expected harsh consequences, to speculate on his reasons for doing so. Did Prof Zaki have the supervisory and ethical approval to send a clinical sample out of the country? Did the EMC challenge him on this before accepting the sample(s)? Had Zaki taken the approved steps (if he did not, that is) to notify his superiors and request permission to send a specimen for further characterisation, would he have received timely permission? Would he ever have received permission?

As a result of this situation, an article was published this week that, although lacking in clarity due to machine translation issues, vilifies Prof Zaki for his actions.WHO spokesperson Gregory Hartl was quoted during September 2012 as saying that the coronavirus "is now an international issue"; a comment that raises some questions in light of this latest article about Prof Zaki's actions. Some have expressed frustrationin recent days about the slow provision of information on new MERS-CoV cases. Would the new coronavirus have been made into an international issue if not for the actions of Prof Zaki? Is the Kingdom capable of characterizing a novel CoV? If the Kingdom did proceed with announcing the MERS-CoV and inviting international experts to advise, would it have done so in time to precede one of the most successful hajj gatherings ever? Nearly 4 million pilgrims attended that gathering in 2012. A real concern exists that cases of this unknown virus could disseminate globally because of just such a gathering. That did not happen but at the time no-one could be sure it wouldn't - the risk was evident and remains so for the coming hajj.

Also this week another cause for argument arose when National Microbiology Laboratory researchers in Canada stated that they were not allowed to pass on samples of the MERS-CoV to other laboratories (40 labs have received the virus from the Erasmus researchers to date). This restriction was stipulated in the Material Transfer Agreement (MTA) that accompanied the sample from the Dutch researchers at Erasmus Medical Center (who characterized HCoV-EMC, now known as the MERS-CoV). The comment that China "gave away" H7N9 samples has been used as an example of a better way to conduct collaborative research on emerging pathogens.

MTAs are a pain in the neck. They slow things down. They are not necessarily crafted by the researchers themselves but by the legal advisory team and administrators to protect new knowledge and discoveries. They can also manage and record where and to whom a putative pathogen is sent and what is done with it by the recipient. Is that a bad thing? MTAs are not uncommon in science. They protect many things. Yes, they can protect intellectual property-with the potential to make some money. Good luck with that - there are as many scientists who have found riches in this endeavor as there are Tony Starks and Bruce Waynes.In this case the MTA, among other things, reportedly limits the distribution of what iscurrently a virus with a case fatality rate of 50%. That sort of virus needs to be worked with by experts using expert facilities with suitable restrictions and pre-existing ethical, genetic manipulation and biocontainment standards in place. We observed the uproar among scientists recently when a recombinant influenza pathogen that had the (unproven) potential to be as lethal was created in secure laboratory environment.

Why has no such uproar accompanied the shipping of observably lethal viruses around the world in the absence of MTAs and tighter restrictions?

If other labs would like the virus, they can also apply to the lab that has gone to the effort to detect, characterize, isolate, grow, purify and store it - just as the NML did. The US CDC noted similar caveats on sharing MERS-CoV were put upon it by the UK laboratory that provided it with samples, presumably form the Qatar case.How long will the attacks on Prof Zaki continue? Hard to know. He is no longer working for the Kingdom. Is losing one's job enough punishment for his putative protocol breach?

It is encouraging to read that samples from various potential animals will be sent to researchers in the US who have the expertise to conduct the studies necessary to track down a possible host.

The first human case of MERS-CoV was in June 2012 - it's now May 26th 2013.