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Whatever Should We Do About These New Biotechnology Capabilities?

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I've held onto this nifty comic for 30 years, knowing it would come in handy some day.

I’ve held onto this nifty comic for 30 years, knowing it would come in handy some day.

My high school days were filled with intrigue and controversy at the national level. On the political front, the Watergate scandal was playing out, with Nixon resigning in the summer between my junior and senior years. Another drama was also playing out at that time, but I only became fully aware of it a few years after its most dramatic events. In July of 1974, only a month before the Nixon resignation, a remarkable publication (pdf) appeared in the Proceedings of the National Academy of Sciences. First, the paper is remarkable for its lack of an author byline. The members of the committee who authored the publication are listed at the very end. More remarkable still is that the publication marked the announcement of a voluntary moratorium by biological scientists. Several types of constructs using newly developed gene-splicing capabilities would not be attempted until the group had more fully studied the risks involved and come up with a plan for mitigating these risks.

Just under a year later, a follow-up publication (pdf) in the same journal appeared. This time there was an author list (and they finally let a woman join the authors–Maxine Singer had been involved in the discussions all along but was not listed in the 1974 paper). The risk mitigation strategy proposed in this paper has set the stage for the bulk of the work with recombinant DNA that has followed (and which allowed me to get a PhD in Molecular Biology in 1983). In the 1975 paper, Paul Berg and colleagues described a graduated level of biological and physical containment of organisms generated in recombinant DNA experiments, with the level of containment based on the relative risk perceived for the new DNA combinations that were being generated.

It should be noted that the concept of working with dangerous biological organisms was not new at all. Infectious diseases have been studied throughout the history of medicine and so the concept of biological containment of dangerous pathogens was not new to these scientists. They relied on these established practices of containment, which have continued to evolve into the current containment guidelines such as those published by the Centers for Disease Control (pdf) for containing pathogens.

Work with recombinant DNA took off quickly once the moratorium was lifted and a number of wonder drugs are now in use through this technology. Engineered plants are also in widespread use in agriculture, but implementation at least in the case of Bt corn has been mismanaged to the point that resistance is beginning to break out.

Fast forward to my impending old age and a very different sort of moratorium reared its head in a very ugly way in December of 2011. Read more →

H7N9 Continues Slow Spread, Animal Reservoir Still Uncertain

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A steady, but slow and at least for now, not accelerating, spread of the new H7N9 bird flu virus continues. Although infection of poultry in markets in Shanghai has been confirmed and thousands of birds culled, ongoing work on the virus has yet to provide what appears to be a full description of how the virus spreads in animal hosts and gets transmitted to humans.

The latest figures from China put the death toll at 9 and the number of confirmed cases at 28 people infected. The question of whether the virus can be passed from one person to another is still under intense investigation, and two possible family clusters are being investigated. WHO spokesman Gregory Hartl was quoted by Xinhua:

“At this point, there is no evidence of sustained human to human transmission,” he said, adding that there are some “suspected but not yet confirmed cases of perhaps very limited transmission between close family members.”

“They are still being investigated,” he said.

Hartl told Xinhua one of the suspected family clusters was in Shanghai, with three family members having similar symptoms and one of them being confirmed of H7N9.

The confirmed case died, so has another suspected family member, according to Hartl.

The other suspected family cluster, which included two family members with one of them being confirmed, was in Jiangsu Province, he said.

Hartl said that even if the infection of H7N9 is confirmed in other family member, further investigations are still needed to make sure whether that’s a human to human transmission between constant and close contacts or an infection with virus from the same environmental source.

That final point from Hartl illustrates the difficulties that scientists face in developing a full description of how the disease is transmitted. At the same time that we do not yet know fully which animals are the reservoir from which humans are infected, we are simultaneously trying to determine whether family members are passing the virus to one another. That question is complicated by the fact that because the family members live in close proximity to one another but by definition also are exposed to the same local environment, multiple family members could have been infected from the same animal source or one family member could have passed the disease to another.

Moving to the question of the animal host, the same Xinhua article that quotes Hartl also informs us that no pigs have been found to be infected with the virus. Recall that large numbers of pig carcasses had been disposed of in rivers in the same areas of China around the same time H7N9 emerged, so some scientists wondered whether the virus arose in pigs and caused those deaths. There were also observations of dead birds. Xinhua has new information on analysis of bird infections: Read more →

Shanghai Culls Poultry as H7N9 Spreads, But Relevant US Research Remains Suspended Due to Security Theater

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Partial screen capture of the home page of the Chinese news agency Xinhua (http://www.xinhuanet.com/english/), showing the culling of poultry in Shanghai.

Partial screen capture of the home page of the Chinese news agency Xinhua (http://www.xinhuanet.com/english/), showing the culling of poultry in Shanghai.

Yesterday saw a number of developments in the ongoing story of the emerging H7N9 virus in the Shanghai region of China, as the virus was identified in pigeons being sold at a meat market and the culling of all poultry at that market was initiated. One close associate of an infected person still is being monitored in isolation after developing possible symptoms of the virus and might turn out to be the first case of person to person transfer of the virus. Meanwhile, the CDC already has started work in the US that could lead to a vaccine.

As I pointed out yesterday, key questions to be addressed in understanding how dangerous this virus will be revolve around the issue of how the virus jumps from one host to another and whether it acquires the ability to transfer from one person to another. Sadly, the most directly relevant research in the US on these questions remains suspended due to a cowardly display of security theater by the National Science Advisory Board for Biosecurity. Back in late 2011, I wrote about this board asking two prominent scientific journals to censor work that had been approved for publication. The work eventually was published, but only after a hiatus of about six months. As I pointed out at that time, the fears expressed by NSABB were then shown to be entirely unfounded.

In their report online today on the latest developments in the H7N9 emergence, CNN provided a link at the bottom of their story to this story they published back in January, with the headline “Bird flu research resumes — but not in U.S.” From that report:

 Drama surrounding research on the deadly H5N1 avian flu continues, as 40 scientists urge work on the virus to continue in countries that have established guidelines on the safety and aims of the research. The United States is not among them.

This new correspondence, a letter from researchers published Wednesday in the journals Science and Nature, comes after a “voluntary pause” in the research, which scientists announced in January 2012.

/snip/

In many countries, those objectives have been achieved, according to the letter, and researchers who have permission from their governments to continue this research should do so.

Ah, but the US never misses out on an opportunity to over-play its hand when it comes to security theater, so the work hasn’t restarted here:

But the United States has been unclear about how long it will be before it issues official guidelines for conditions under which H5N1 transmission research can continue, the letter says. As such, laboratories in the United States and facilities abroad that receive U.S. funding should not proceed with their transmission studies.

Back when the NASBB first proposed to censor the work that had been done, I had this to say (emphasis added):

However, in the case of the bird flu version of influenza virus, the basic flu virus is found worldwide and undergoes rapid changes. The fact that flu virus changes rapidly suggests that, as mentioned in the snippet above from ScienceInsider, a version similar [to] that developed in the controversial experiment could even arise naturally. Those who would suppress publication of details on how Fouchier’s group developed the pathogenic virus would prevent responsible researchers repeating the work in order to develop an effective treatment for the virus.  Since the virus could arise naturally, preventing work on a treatment is completely irresponsible.

In the CNN article, we have this from one of the scientists whose work has been put on hold (emphasis added again):

“It’s so easily mutated, so the risk exists in nature already, and not doing the research is really putting us in danger,” Kawaoka said at a press conference Wednesday.

While NSABB was busily subjecting us to needless security theater, nature produced what could be the virus for which scientists were trying to prepare us. They were working with the H5N1 virus to address the very questions of host-jumping and person to person transmission that now lie at the heart of the H7N9 emergence. In the best of all worlds, H7N9 will turn out not spread quickly enough to turn into a deadly pandemic. In that good scenario, H7N9 will serve as a wake-up call to once again free the hands of researchers to carry out work that is vital to understanding deadly bird flu virus outbreaks. The alternative is too terrible to consider. If we see widespread death from H7N9, we will be left to wonder how many of those deaths could have been prevented if this important research had not been suspended.

H7N9: A New Influenza Virus Emerges

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This post is in two parts. The first part deals with the news that a new flu virus has emerged. The second part, which comes below the fold, provides a bit of biological and public health information to help put the news into perspective.

According to the latest reports I can find, there are now three confirmed deaths and ten confirmed cases of people infected with a new strain of Type A (bird) influenza virus that has been designated H7N9. All cases have been in eastern China. The good news is that there is not yet evidence to suggest that this virus can spread from one person to another (although that question has not yet been fully answered), which is a prerequisite for a pandemic. The bad news, though, is that the animal host from which the infections were acquired has not been identified.

Earlier this week, Laurie Garrett began assembling what is known about the emerging cases of H7N9 infection and putting those cases into the context of mysterious mass die-offs of pigs and birds in the same general region of China (Garrett is asking important questions here since previous flu pandemics have come from swine or bird hosts):

By the end of March, at least 20,000 pig carcasses and tens of thousands of ducks and swans had washed upon riverbanks that stretch from the Lake Qinghai area all the way to the East China Sea — a distance roughly equivalent to the span between Miami and Boston. Nobody knows how many more thousands of birds and pigs have died, but gone uncounted as farmers buried or burned the carcasses to avoid reprimands from authorities.

While environmental clean-up and agricultural authorities scrambled to remove the unsightly corpses and provide the anxious public with less-than-believable explanations for their demise, a seemingly separate human drama was unfolding. On Feb. 19, a man identified by Xinhua, China’s state news agency, only as Li, an 87-year old retiree, was hospitalized in Shanghai with severe respiratory distress and pneumonia. On March 4, Li went into severe cardio-respiratory failure and succumbed.

On Feb. 27, a man identified only as Wu, a 27-year-old butcher or meat processor, fell ill with respiratory distress, was hospitalized, and died on March 10. The day Wu succumbed a third individual, a 35-year-old woman identified as Han, was hospitalized in the city of Nanjing, though she came from distant Chuzhou City, in Anhui province, about 300 miles northwest of Shanghai. Han is reportedly in critical condition, in intensive care. To date, no connection between the three individuals has been found.

The key question of whether person-to-person transmission of the virus can occur is made somewhat murky by the family of Li:

The elderly Li may have been part of a family cluster of illness, as his 55-year old son died of pneumonia in March, and another 67-year-old son suffered respiratory distress, but has survived.

On March 31 — Easter in the United States — China’s newly created National Health and Family Planning Commission (which includes the former Ministry of Health) announced that 87-year-old Li, Wu, and Han all were infected with a form of influenza denoted as H7N9 — a type of flu never previously known to infect human beings. The commission insisted that Li’s two sons (one dead, the other a survivor) were not infected with the flu virus — their ailments were reportedly coincidental, though they occurred at the same time as the elder Li’s demise.

Garrett goes on to point out that Chinese authorities have blamed a non-influenza virus for the pig deaths, but she casts some doubt on this claim, since the virus cited by the Chinese is known to kill young piglets but not adult pigs. The dead pigs found tossed into rivers primarily were adults.

Garrett rightly states that our knowledge of what is going on here is highly dependent on the accuracy of the tests that authorities are carrying out:

If the pigs, people, and birds have died in China from H7N9, it is imperative and urgent that the biological connection be made, and extensive research be done to determine how widespread human infection may be. Shanghai health authorities have tested dozens of people known to have been in contact with Wu and Li, none of whom have come up positive for H7N9 infection. Assuming the tests are accurate, the mystery of Li and Wu’s infections only deepens. Moreover, if they are a “two of three,” meaning two dead, of three known cases, the H7N9 virus is very virulent.

“At this point, these three are isolated cases with no evidence of human-to-human transmission”, the WHO representative in China, Dr. Michael O’Leary, told reporters on Monday. But, O’Leary added, the possibility of a family cluster of illness could not be ruled out, and, “We don’t know yet the causes of illness in the two sons, but naturally, if three people in one family acquire severe pneumonia in a short period of time, it raises a lot of concern.”

 

The key phrase above is “Assuming these tests are accurate”. When a new virus emerges, it is difficult to know what tests to conduct to detect the virus and how to conduct those tests. More detail is clearly needed to know what level of confidence can be placed on the Chinese claim that Li’s family members were not infected with the same virus that killed him.

Garrett puts these questions into more context in the Reuters article linked above:

However, China has yet to find any animals infected with H7N9, meaning how the humans got it remains a mystery.

“We know that it was originally a bird virus. We also know that it has taken on some genetic attributes that are not seen in bird viruses,” Laurie Garrett, Senior Fellow for Global Health at the Council for Foreign Relations, told Reuters in New York.

“In other words, it seems to have adapted somehow to mammals, to humans. How that happened, we don’t know,” added Garrett.

 

Update: Via Twitter, Laurie Garrett points out that Chinese authorities now have evidence that pigeons in Shanghai have been infected with a version of the H7N9 virus that is a genetic match to the viruses isolated from humans, so pigeons may be the source. More can be read here.

Read more →

Science Wins Out: Bird Flu Virus Experiments Will Be Published Without Redactions Despite Continued US Fear Mongering

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Back in December, the National Science Advisory Board for Biosecurity (NSABB) asked that two papers pending publication on scientific research into deadly forms of the H5N1 bird flu virus be redacted when published. This was a bad decision for several reasons, as I pointed out:

At this point, if the details of just which precise mutations occur in the pathogenic virus that was developed are published, it should make no difference, because press reports have already confirmed that the most basic approach one could take, involving a simple genetic selection experiment, gives the result of the more pathogenic virus. It’s even likely there are other combinations of mutations that would make an extremely pathogenic virus if the selection process were repeated in a new experiment.

But the folly of the NSABB decision goes much deeper and is just another aspect of the hysteria that has gripped the United States since the al Qaeda attack on 9/11 and the anthrax attack just a few weeks later. One aspect of this hysteria has been an attempt to make far too many things secret. Much attention has been paid to the over-classification of intelligence information, but the over-classification of scientific information is just as insidious.

No matter how many bits of intelligence or scientific information are made secret, the fact remains that determined terrorists have a multitude of fully described weapons systems to employ in an attack. By stifling publication of basic scientific research into materials that could have weapons potential, the opportunity to develop useful countermeasures becomes significantly diminished.

The “genetic selection” experiments to which I referred are described in one of the two papers that were up for redaction. It showed that by simply passing the bird flu virus through ferrets multiple times, a version of the virus that is more deadly to mammals (and presumably humans) was produced. But as I pointed out in the post, bioterrorists already have available a number of deadly agents that don’t require further research to make them effective. By censoring the work on more deadly bird flu, flow of information to researchers who wish to develop treatments for the disease (and these researchers vastly outnumber bioterrorists) is inhibited. Although those wanting to censor the work intended to make the full details available to a select few, that “solution” is untenable in that it predetermines just who is “important” enough to receive the information. Free flow of information is key to research and one can never predict just who will make the next advance, so pre-selecting those who get the key information is a silly notion.

The good news is that scientific research is an international process, and so “advisory” boards hand-picked by the US “homeland security” lobby do not have the final say. Today’s New York Times, in a front page story, reports that the scientific papers will be published in their entirety. The narrow-mindedness of how the US government has come to stifle scientific thought comes through loud and clear in this article. The final decision on publication was made at a large meeting held by the World Health Organization in Geneva: Read more →

In Ferreting Out Science’s Secrets, There Is No Room for Censorship

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Ferret photo via Wikimedia Commons

On Tuesday afternoon, the Washington Post announced that the National Science Advisory Board for Biosecurity (NSABB) has officially asked two scientific journals to censor portions of manuscripts that are pending for publication:

The federal government on Tuesday asked two science journals to censor parts of two papers describing how researchers produced what appears to be a far more dangerous version of the “bird flu” virus that has circulated in Asia for more than a decade.

/snip/

After weeks of reviewing the manuscripts the board recommended their “general conclusions” be published but “not include the methodological and other details that could enable replication of the experiments by those who would seek to do harm.”

The board — 23 scientists and public-health experts from outside the government, and 18 from within — cannot stop publication. Its advice goes to the Department of Health and Human Services, whose leaders will ask the journals — Science, published in Washington, and Nature, published in London — to comply.

The folly of the board’s request is monumental. First of all, it’s already too late for the workers to “not include the methodological and other details that could enable replication of the experiments”. Read more →