Indo-U.S. Workshop on Challenges of Emerging Infections and Global Health Safety Summary of a Workshop (2016) / Chapter Skim
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4 The Biotechnology Revolution: Exploring New Territory Together
4 The Biotechnology Revolution: Exploring New Territory Together
Pages 77-104
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From page 77... ...
All three -- microbes, hosts, and the environment -- concern us. In addition to the loss of human life and suffering as a result of the Ebola outbreak, there are also important effects of events like these on public health infrastructure, on social infrastructure, and economic and political infrastructures as well.
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From page 78... ...
This is an immensely important capability and it is exemplified by DNA synthesis, DNA shuffling, and other types of technologies. Second, there is a related but distinct type of technology that is motivated by the goal of deliberately designing a particular life form.
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From page 79... ...
This is certainly true of RNA viruses and most DNA viruses. This technology is actually quite old.
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From page 80... ...
What Relman thinks is even more interesting today, he said, is the idea that one could engineer entire communities of organisms, not single organisms, but organisms that normally interact together so that they feed each other synthetic, newly-engineered compounds and help each other make resulting products that no organism alone might have produced. With the help of advanced technology, kits are available for experiments that might have taken months to years in earlier times.
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From page 81... ...
2 These experiments were a deliberate effort in the laboratory to see if H5N1 viruses could acquire enhanced transmissibility between 2 For a brief overview of this research, see: http://www.nature.com/news/therisks-and-benefits-of-publishing-mutant-flu-studies-1.10138; accessed April 10, 2016.
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From page 82... ...
The first study, by Ron Fouchier, began with a highly pathogenic Indonesia influenza isolate and he created deliberate redesigns of the genome as well as passaging and found that he could isolate a virus that had the property of enhanced transmissibility and, to our knowledge, no great reduction in virulence. A subsequent follow-on study has provided everyone with the five mutations that together allow this virus to have these properties.
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From page 83... ...
He noted, however, that scientists must accept the fact that despite all efforts, there could continue to be outbreaks, both natural and potentially man-made, and the public health infrastructure and other countermeasures used as defenses must be strengthened in order to mitigate the negative effects. Just several weeks prior to the workshop, the United States announced a pause in conducting certain types of experiments due to the concerns regarding the risks of these experiments.
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From page 84... ...
Discussion The discussion following Relman's presentation focused primarily on the importance and influence of ecology in the study of viruses. Referring to mutations in viruses, a participant asked Relman about the example of HIV.
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From page 85... ...
A participant noted that not only is it important to understand emerging diseases, but it is also important to understand when diseases fade out. This is generally not taken into consideration.
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From page 86... ...
Nair described hospital-based surveillance, culture-dependent and independent methodologies, and the relationship between pathogens associated with co-infections such as community diarrheas, fecal microbiota of healthy children, and the gut microbiome of Indian children with varying nutritional status. Nair described a simple hospital-based study that he and his colleagues conducted on the etiology of diarrhea in Kolkata a few years prior to the workshop.
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From page 87... ...
toxin gene EAEC – aggR adherence factor gene EPEC – eae pathogenecity related gene A subset of stool samples was examined by culture techniques; 59 samples contained sole pathogens, 9 samples had mixed infections, and 54 samples had no detectable pathogens. When they followed the 7 For more information, see: Gopinath Balakrish Nair, et al.
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From page 88... ...
80 (28.1%) Note: Vibrio cholerae :- Vibrio cholerae O1 + Vibrio cholerae O139 + Vibrio cholerae non O1 non O139 Parasites :- Blastocystis hominis + Entamaeba histolytica + Giardia Lamblia + Cryptosporidium spp.
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From page 89... ...
Likewise, Vibrio cholera exhibited an odds ratio with various pathogens that appear to be associated only with Giardia lamblia. FIGURE 4-2 Odds ratios showing odds of rotavirus co-occurring with various other pathogens.
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From page 90... ...
Thus, the third key message is that apparently healthy children living in poor sanitary conditions ingest a high concentration of fecal bacteria that colonize the small intestine. Nair then discussed a study of the fecal microbiota of apparently healthy children who participated in a community-based trial of a probiotic in Kolkata.
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From page 91... ...
At every collection period, healthy children were found to be excreting Vibrio cholera, V parahaemolyticus, Campylobacter jejuni, Salmonella typhi and Salmonella typhimurium, and rotavirus.
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From page 92... ...
"Vibrio cholerae/mimicus in fecal microbiota of healthy children in a cholera endemic urban slum setting in Kolkata, India," Microbiology and Immunology.
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From page 93... ...
colis. The fourth key message was that the intestines of apparently healthy children carry enteric pathogens for extended periods of time at low levels in disease endemic settings reflecting the effects of constant exposure to fecal bacteria and enteric pathogens.
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From page 94... ...
Discussion The discussion following Nair's presentation focused on sanitation issues and the potential protective nature of pathogens at low levels. A participant asked if the cases with multiple infections were using shared toilets or perhaps open toilets.
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From page 95... ...
He also provided examples of innovative steps that are being taken in resource poor situations to improve diagnostics. For Rao's first example, he described fungal keratitis, which is a very common disease that causes blindness.
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From page 96... ...
Thus, there is a critical need to develop novel therapeutic approaches for treating fungal keratitis. Rao and his colleagues examined fungal keratitis under several conditions as organisms in culture, and found them to be very clever organisms.
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From page 97... ...
His group started a project several years ago on a novel molecular diagnostic for eye diseases. The object of the project is to develop a rapid, simple, and inexpensive diagnostic method to detect mutations of eye diseases and a signature sequence of pathogenic organisms.
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From page 98... ...
Rao's group has developed this diagnostic by using computer algorithms to draw the desired design with wax. They dissolve the wax in particular solvents and make a solution that can be put in a pill, and with a blotter the structures can be drawn onto the paper diagnostic chip.
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From page 99... ...
Looking at publications addressing a variety of biology topics, truth tables and data sheets are often found. A truth table in a biological setting is essentially a metric that indicates if there is a certain input concentration, a promoter or repressor, and what the output concentration would be in terms of protein.
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From page 100... ...
And recently, a special community of biologists has been working on developing standard compositions. There is a bit of concern, however, about whether the recombinant DNA technology is going to be obsolete in the future because if one can create a recombinant vector on the computer, email the sequence to the DNA synthesis company, and receive the entire vector, does one really need to copy and paste small sequences here and there?
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From page 101... ...
Do we really understand what we have created? A synthetic organism is different from a traditional recombinant DNA biology experiment where the entire genome is cloned or copied.
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From page 102... ...
Sensing the alarming situation that might arise in future, the top-most gene synthesis companies have come together and formed a consortium, which represents 80 percent of the commercial global synthesis capacity. This is difficult to regulate because these companies are now investing in creating desktop DNA synthesis printers.
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From page 103... ...
10 The question of placing the Pandemic Influenza Preparedness Framework into the context of sequence data has arisen because there is concern that once a sequence is known, the virus is known. This is worth considering, the participant said.
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