The Survival of "Global Health" - Part Seven: Patents and Potential Pandemics
I wouldn’t want to be Dr. Ali
Zaki right now. The Egyptian physician/scientist is in the center of a
maelstrom that unfolded this week in Geneva, Switzerland at the sixty-sixth
session of the World Health Assembly. And if history applies to this latest
brouhaha in the ongoing MERS-CoV SARS-like virus outbreak mess, Zaki was wise
to abandon his job at Dr. Soliman Fakeeh Hospital in Jeddah, leave Saudi Arabia,
and ply his trade in Cairo.
Saudi Arabia's Deputy Health Minister Ziad Memish told the World Health Organization meeting that “someone” – a reference to Zaki – mailed a sample of the new SARS-like virus out of his country in June 2012, and gave it to Dutch virologist Ron Fouchier of Erasmus University in Rotterdam. And Fouchier “patented it.”"The virus was sent out of the country and it was patented, contracts were signed with vaccine companies and anti-viral drug companies and that's why they have a MTA (Material Transfer Agreement) to be signed by anybody who can utilize that virus and that should not happen," Memish charged in a speech at the World Health Assembly.
Memish claimed that the Saudi government’s failure to share samples of the MERS-nCoV virus with other countries – including neighbor states that had their own cases of the disease – stemmed directly from Zaki’s actions. Though Memish referred to a “patent” in his remarks to the Assembly, the Dutch team has not patented the viral genetic sequence, but has placed it under a Material Transfer Agreement, or MTA, requiring sample recipients to contractually agree not to develop products or share the sample without the permission of Erasmus University and the Fouchier laboratory. Memish’s comments were a bit confusing, but he seems to be saying that Saudi Arabia refused to sign an MTA with a foreign government for a virus that originated inside Saudi Arabia and has taken its greatest toll on the Saudi people.
As of today 44 cases of MERS-CoV have been confirmed, 33 of them in Saudi Arabia, largely in the country’s eastern date palm agricultural area. Worldwide, the virus has caused cases in seven countries, and killed 22 people. MERS-CoV (“Middle Eastern Respiratory Syndrome coronavirus”) is part of a class of viruses for which there are no effective cures or vaccines. Like its close cousin the SARS virus, MERS ravages the lungs of infected people, causing pneumonia and acute respiratory distress. Also like SARS, it is previously unknown to human immune systems, so reaction to infection can include the classic “cytokine storm” reaction of an over-responsive immune system that hits the virus with all its got, creating collateral damage all over the body. But unlike SARS – worse – it also attacks the kidneys, causing renal failure.
Epidemiologically, MERS seems to be quite similar to SARS, as it is easily spread by close contact, and can be airborne transmitted between people. Both viruses are dangerous for healthcare workers, and easily spread within hospitals. (WHO insists SARS was considerably more threatening for nosocomial transmission than MERS has been.) There is no rapid diagnostic test for MERS, which puts doctors and nurses at special risk as they cannot easily discriminate the symptoms differences between early stage MERS-CoV patients and regular pneumonia. The MERS cases should be handled with maximum quarantine and protective gear, which the routine pneumonia case rarely poses a risk for the healthcare worker or other hospital patients. But there is no easy way to recognize which is the case in any given patient. Until a rapid diagnostic is developed, anxiety among healthcare workers in affected areas will remain high.
Memish charged this week that the lack of a reliable diagnostic test for MERS was directly due to the “patents” taken out by the Dutch. In the absence of such a test (with only PCR DNA assays to work with)), "We think contact isolation needs to be applied, because some patients present with diarrhea or vomiting, which we think could be the source of the transmission," Memish said, noting that such procedures are costly and trying psychologically for both patients and medical staff. The WHO endorses this high level of hospital caution.
"There was a lag of three months where we were not aware of the discovery of the virus," Memish told the WHO meeting. Zaki sent his samples to Rotterdam in June 2012; Fouchier, Zaki, and others co-authored an analysis that appeared in the November 2012 issue of the New England Journal of Medicine.
WHO Director-General Margaret Chan listened carefully to simultaneous translation of Memish’s remarks, and then lashed out.
"Making deals between scientists because they want to take IP (intellectual property), because they want to be the world's first to publish in scientific journals, these are issues we need to address. No IP will stand in the way of public health actions," Chan stated. She exhorted the Assembly delegates to "share your specimens with WHO collaborating centers, not in a bilateral manner. Please, I'm very strong on this point, and I want you to excuse me. Tell your scientists in your country, because you're the boss. You're the national authority. Why would your scientists send specimens out to other laboratories on a bilateral manner and allow other people to take intellectual property rights on a new disease?"
The new MERS-CoV is shrouded in mystery right now, as Saudi investigators have been unable to determine its reservoir species – where did it come from – how it is spread from that species to people, a method for rapid diagnosis, proper treatment and best approaches to hospital infection control. Suspicions point to fruit bats in the eastern Al-Ahsa province of Saudi Arabia, where the bulk of the cases have occurred. Like the Nipah virus in Southeast Asia, a model is suggested, but not proven, in which people working in the date tree harvests are exposed to the virus as it is passed from date-eating bats. Bats tend to take fruit into their mouths, chew it until they reach the pits, and then spit the pits out. The virus may be passed in bat saliva that coats the chewed, regurgitated fruit parts.
But that is at this point speculation.
"We have a high level of concern over the potential... for this virus to have sustainable person-to-person spread," WHO deputy chief Keiji Fukuda told the Assembly. Fukuda concurred with Memish’s assessment telling reporters that WHO “is struggling with diagnostics" because of the Dutch Material Transfer Agreement.
In March, before this controversy exploded, Zaki shared his side of the story with The Guardian. Eleven months ago, Zaki said, he was called in as a consultant on a mysterious case in his hospital. Using his skills as a virologist, Zaki tried to identify the virus, but the patient died less than 24 hours after he received the sample. Soon, a second case came his way, and Zaki knew that he needed help. So last June he mailed a sample to his friend Ron Fouchier. Three months later Zaki sent a notice in September 2012 to ProMED, a disease alert system run by the Infectious Diseases Society of America. Under pressure from the Saudi government, Zaki’s hospital fired him when the ProMED notice was posted, and he eventually moved to Cairo.
The ProMED post read in part:
Date: Sat 15 Sep 2012
From: Ali Mohamed Zaki <email@example.com> [edited]
A new human coronavirus was isolated from a patient with pneumonia by
Dr Ali Mohamed Zaki at the Virology Laboratory of Dr Soliman Fakeeh
Hospital Jeddah Saudi Arabia.
The virus was isolated from sputum of a male patient aged 60 years old
presenting with pneumonia associated with acute renal failure. The
virus grows readily on Vero cells and LLC-MK2 cells producing CPE in
the form of rounding and syncetia formation.
[The clinical isolate] was initially tested for influenza virus A,
influenza virus B, parainfluenza virus, enterovirus and adenovirus,
with negative results…..
Meanwhile, contrary to Memish’s depiction this week in the World Health Assembly, the general recognition of the existence of this new disease was not prompted by a Fouchier/Zaki research paper, but by the case of a Qatari man who, after visiting Saudi Arabia, flew to London and came down with acute respiratory distress and kidney failure. Physicians at St. Thomas’s Hospital saw Zaki’s ProMED posting, noted the patient had traveled in Saudi Arabia, and concluded they were dealing with a new virus. The London team isolated a viral sample, and compared it to the genetic sequence Fouchier had prepared of Zaki’s sample – they were a match. UK authorities went public with the news, spawning the first tier of worldwide attention to the existence of a new human virus.
In March, Fouchier told The Guardian that “very little is being done to find out,” how and where the virus was circulating in the Middle East. He hinted at lack of response from Saudi authorities, concluding that it was up to Europe to learn all it could, and create systems to protect its peoples. (Fouchier's claim that "very little is being done" is untrue, according to sources that decline to be named because of delicate working relations with the Saudi government: They insist detailed study of the resevoir/animal host issue, as well as human epidemiology, is underway and will soon be released.)
The situation in the Middle East is, indeed, dicey. Though the wars and conflicts of Syria and Iraq have not reached bucolic Al-Ahasa, Saudi Arabia has many reasons to keep such outbreaks quiet. Chief among them is the country’s role as the home of Islam, and host of the Haj to Mecca. Concern about spread of disease during the annual Haj, which is attended by Moslems from every corner of the planet, has been a constant since the 14th century, when that Black Death exploded across Arabia and spread via infected religious pilgrims across the Islamic world.
Several research teams from the United States and Europe have offered their services to the Saudis since September, but the situation is extremely complicated. The Saudi Kingdom is a Wahabi Sunni state, but the affected region includes a large Shi’a population. Tensions throughout the Middle East make free movement of Western – especially American – scientists dangerous, and impossible if they are government officials. In this situation academic scientists such as Dr. Allison McGeer of Toronto's Mt. Sinai Hospital or Columbia University’s Ian Lipkin have more possibility of investigating the ground situation than do government epidemiologists from the United States or European Centers for Disease Control.
Which takes us back to this patent, or MTA dispute.
Memish only yesterday to send samples of the virus to the U.S. CDC for analysis, in hopes of identifying the animal reservoir for the disease. Presumably he has had these samples for some time, and could have passed them on months ago. It is not clear why a Dutch MTA related to the genetic sequence of a virus could have prevented open sharing of these samples months ago. (We are aware of an arrangement under which samples have been shared from Memish's office to a foreign lab, and data may soon be released. The arrangement is not public at this time, and the research is not completed.)
In contrast, China shared H7N9 flu sequences with open source Internet sites within four weeks of the first patient cases in Shanghai, and sent viral samples all over the world within less than two months. Canada’s National Microbiology Laboratory Director Francis Plummer told the CBC in mid-May that his Winnipeg lab had signed the Dutch MTA, and obtained a research sample, after prolonged legal negotiations. Plummer contrasted his difficulties in obtaining a sample from the Dutch to China’s immediate and open sharing of H7N9 influenza samples with his facility.
In a carefully crafted yesterday Erasmus Medical Center spelled out the terms and understandings of its original MTA “patent” (I put “patent” in quotation marks because an MTA is not a patent at all, but media accounts, Memish and Saudi officials have framed it as such). It states unequivocally, “Erasmus MC was the first to identify the new coronavirus (MERS coronavirus).” The press release continues:
“It is clear that all research institutions worldwide that want to carry out such research will receive the virus free of charge from Erasmus MC. Indeed many research institutions already received the virus together with additional materials and information from Erasmus MC. For shipment of the virus it is mandatory that a material transfer agreement (MTA) is signed by the recipient institution, as is common practice when shipping viruses. Such an MTA covers issues like liability and limitations to commercial use. Consequently the virus may not yet be used for commercial purposes and may not be distributed to third parties without permission. These are the usual conditions covered by a MTA.
“MTAs were implemented to facilitate scientific research as well as exchange of materials to the benefit of public health. Ab Osterhaus and Ron Fouchier of Erasmus MC stress that ‘every research or public health laboratory that complies with the safety criteria for handling MERS coronavirus can work with it’.
“It is clearly a misunderstanding that Erasmus MC owns the virus. Only specific applications related to it, like vaccines and medicines can be patented.”
In an interview with the Dutch researchers insisted that they are freely sharing their samples, and there are no patent disputes on the table.
This is not likely to placate the new World Health Assembly wrath. Chan called upon the gathered delegates to stand against intellectual property blocks to epidemic responses and the crowd cheered. The question of ownership of discovery has become The Number One wedge issue in global health today, underscoring debate on everything from to availability of antibiotics for TB care.
Chan and WHO are especially sensitive to the issue because of the 2007-08 battle between the agency and the Indonesian government regarding the H5N1 flu virus and then-Minister of Health Siti Supari’s insistence on the existence of "." Supari declined to share samples of the dangerous bird flu viruses that were then rampant in her country with outsiders on the grounds that they would be used to manufacture patented products that would benefit foreign companies, and the products they produced would be unaffordable to Indonesians. Supari contended the H5N1 virus was made by the CIA with the intention of afflicting the Islamic world and bringing financial instability to countries that were compelled to buy U.S. products. She created the notion that a virus found first in any given country was the sovereign possession of that nation.
Supari’s contentions spawned a long, difficult period of negotiations that ultimately led to the , the WHO’s Pandemic Influenza Preparedness (PIP) Framework. The PIP augments the International Health Regulations, creating a series of understandings that are flu-specific regarding sample sharing, patents, and profits from products derived from viral discovery. Chan's tough response to Memish’s accusations no doubt stems from her concern that the Saudis could invoke provisions of the flu-specific PIP, demanding control over the MERS-nCoV samples, patents, and products.
I will leave detailed analysis to great legal experts familiar with the IHR, WTO, TRIPS, PIM, and other alphabet soup of trade and patent fights. The best in my book comes from David Fidler of the University of Indiana, who with Canadian media this week.
Meanwhile, the virus is spreading – somehow – from an unknown reservoir host to people in the Middle East. While fame-grabbing scientists, shame-averse Saudis and possible patent-pawing product developers compete, Nature is doing its thing.
This is simply disgusting.
This is the final essay in my series related to the sixty-sixth session of the World Health Assembly.
Nations that have confirmed cases of MERS-CoV to date:
UPDATE TO ABOVE BLOG, ADDED MAY 27, 2013
MARGARET CHAN GAVE BRIEF CLOSING REMARKS TO THE ASSEMBLY, PRIMARILY FOCUSED ON THE MERS CoV SITUATION. Key elements of her speech are:
"Ladies and gentlemen,
Transparency and solidarity. These are words I heard repeatedly during the session, and especially during discussion of the item on the International Health Regulations.
Looking at the overall world health situation, my greatest concern right now is the novel coronavirus.
We understand too little about this virus when viewed against the magnitude of its potential threat. Any new disease that is emerging faster than our understanding is never under control.
We do not know where the virus hides in nature. We do not know how people are getting infected. Until we answer these question, we are empty-handed when it comes to prevention.
These are alarm bells. And we must respond.
The novel coronavirus is not a problem that any single affected country can keep to itself or manage all by itself. The novel coronavirus is a threat to the entire world. As the Chair of committee A succinctly stated: this virus is something that can kill us.
Through WHO and the IHR, we need to bring together the assets of the entire world in order to adequately address this threat.
We need more information, and we need it quickly, urgently.
As I have announced, joint WHO missions with the Kingdom of Saudi Arabia and Tunisia will take place just as soon as possible. The purpose is to gather all the facts needed to conduct a proper risk assessment.
I thank Member States for supporting my views on the seriousness of this situation."