Posts Tagged ‘Agriculture’
Humans think they’re so smart, giving themselves credit for inventing stuff like the the wheel, fire, and agriculture. Well think again, because we’re not the first to invent farming. Cultivation of crops for nourishment has evolved a few times among eukaryotes. The best known examples include ants, termites, beetles, and, around 10,000 years ago, humans. It turns out that the soil fungus Morchella crassipes acts as a bacterial farmer, involving habitual planting, cultivation and harvesting of bacteria.
It’s fairly obvious what the fungus gets out of this arrangement – it’s in it for all the lovely reduced carbon those tasty bacteria provide. But what about the bacteria – do they get some benefit from the arrangement? It seems that they might. Soil is not the easiest medium for cells to disperse in, and by using the fungal hyphae as a sort of motorway network, this would seem to be more of a mutualistic arrangement, albeit one in which some of the cells wind up as lunch for the farmer.
Last week I was struck by this article in The Verge, Dead meat: how to raise livestock in a post-antibiotic era. I was particularly interested in this because only a week earlier I had been teaching our first year students about emerging infectious diseases and the growing feeling that we are entering the post-antibiotic era. As this paper published in 2005 put it:
“The indiscriminate and inappropriate use of antibiotics in outpatient clinics, hospitalized patients and in the food industry is the single largest factor leading to antibiotic resistance. In recent years, the number of new antibiotics licensed for human use in different parts of the world has been lower than in the recent past. In addition, there has been less innovation in the field of antimicrobial discovery research and development. The pharmaceutical industry, large academic institutions or the government are not investing the necessary resources to produce the next generation of newer safe and effective antimicrobial drugs. In many cases, large pharmaceutical companies have terminated their anti-infective research programs altogether due to economic reasons. The potential negative consequences of all these events are relevant because they put society at risk for the spread of potentially serious MDR bacterial infections.”
Alanis, A. J. (2005) Resistance to antibiotics: are we in the post-antibiotic era? Archives of medical research, 36(6), 697-705
The medical profession has rightly received a lot of criticism for undermining antibiotics by handing them out far too freely for trivial infections which though inconvenient, are self-limiting. That situation is now largely historic, and in most countries over-prescribing of antibiotics has ended, or at least decreased, although it is still worrying that in some countries antibiotics are still available without prescription to anyone who can afford to buy them. But medics don’t deserve a fraction of the criticism due to the worst offenders – the agricultural industry, where antibiotics have been used for decades as “growth promoters” in livestock production. The term “growth promoter” means that these valuable compounds are not being used for animal welfare to treat veterinary infections – which is entirely justified – but in a blanket fashion to make animals put on weight faster so they can be sold at a younger age, increasing profit.
I first became aware of this problem many years ago when I was visiting a student on an industrial placement with a major pharmaceutical company who told me proudly about their production of growth promoters and how many thousands of tons and antibiotics they sold to farmers each year. The recent report from Johns Hopkins University puts this ongoing problem into perspective. After decades of this misuse, we are paying the price, with multidrug-resistant bacteria now common in foodstuffs.
For decades we kept ahead of this impending catastrophe by discovering and marketing new antibiotics, but that pipeline has essentially run dry. Although we may find a few useful new compounds from coral reefs or deep sea hydrothermal vents, we are having to admit that we can no longer run fast enough to outpace bacterial evolution. And as future prospects decrease, so economics pays us back.
“In many cases, large pharmaceutical companies have terminated their anti-infective research programs altogether due to economic reasons.”
This is not a problem that the free market is likely to solve. So where do we go from here? Personally I’m not optimistic about the prospects for probiotics making all our problems go away. I don’t think persuading cows to gargle garlic tea is going to save us at this point. So what will (if anything?). The only realistic hope I can see on the horizon is the application of nanotechnology to build new anti-infective compounds rather than relying on snatching them from nature. Realistically, that prospect is decades away. Less realistically, it is also not without risks, such as the grey goo scenario of runaway nano-machines which keeps Prince Charles awake at night.
So are we all going to die? Yes, of course we are – such is the nature of life. But we have a choice of how and when depending on how hard we work on the problem. If future generations of microbiologists can learn enough about the molecular mechanisms which pathogens need to function, then we will have the opportunity to build a new generation of nanobiotics which will keep us ahead of the bacteria. For a little while. But never forget that bacteria have been around a lot longer than we have, and they’re not about to give up just yet.
- Antimicrobial nanotechnology: its potential for the effective management of microbial drug resistance and implications for research needs in microbial nanotoxicology. (2013) Environmental Science: Processes & Impacts, 15(1), 93-102
- Drug-Resistant Bacteria: To Humans From Farms via Food
- Phasing Out of Antimicrobial Growth Promoters
I’ve spent the last five years trying to persuade students to do a research project with me looking at issues around the scientific evidence concerning bovine tuberculosis and badgers – without success, no takers (they all want to do projects about HIV). Fortunately, now they don’t have to as the Royal Society has published a comprehensive (by which I mean yes, everything) review of the subject:
A restatement of the natural science evidence base relevant to the control of bovine tuberculosis in Great Britain. Proc. R. Soc. B August 2013 doi: 10.1098/rspb.2013.1634
Abstract: Bovine tuberculosis (bTB) is a very important disease of cattle in Great Britain, where it has been increasing in incidence and geographical distribution. In addition to cattle, it infects other species of domestic and wild animals, in particular the European badger (Meles meles). Policy to control bTB is vigorously debated and contentious because of its implications for the livestock industry and because some policy options involve culling badgers, the most important wildlife reservoir. This paper describes a project to provide a succinct summary of the natural science evidence base relevant to the control of bTB, couched in terms that are as policy-neutral as possible. Each evidence statement is placed into one of four categories describing the nature of the underlying information. The evidence summary forms the appendix to this paper and an annotated bibliography is provided in the electronic supplementary material.
Because you are unlikely to read this landmark paper O gentle reader, I’ve read it for you, and here are the highlights:
Why should we care about bovine tuberculosis (bTB)?
Bovine tuberculosis (bTB) is a major disease of cattle that can also affect humans, and many other livestock and wild animal species. Human infection has not been a major public health problem in developed countries since the introduction of milk pasteurization. Advanced cases in cattle experience loss of condition, and this directly affects the economic value of the animal, but in most developed countries detection of infection leads to movement restrictions being placed on the herd, mandatory slaughter and economic losses for farmers. The English and Welsh governments estimate that they have spent £0.5 billion in the last decade on testing, compensation and research with further costs being borne by the agricultural industry.
Why not just vaccinate cows against (bTB)?
EU law currently prohibits the vaccination of cattle as it can mask the detection of infection. Vaccination of badgers is the subject of intense current research, and vaccination has been under way in Wales since 2012. The main protective effect for cattle vaccinated with BCG is to reduce the severity of disease. This is measured experimentally at post-mortem by comparing the extent of infection within the bodies of vaccinated and control cattle. A recent field trial in Ethiopia found that the carcasses of 13 vaccinated calves had 56–68% less disease than was seen in 14 control calves. If vaccinated cattle do become infected, it is likely that a reduction in the extent of disease will limit their infectiousness, reducing onward transmission to cattle and to wildlife.
Which got TB first, the badger or the cow?
Cases of bTB in cattle occur more frequently in regions that support higher densities of both badgers and cattle. Most studies that have looked for an association between high badger densities and elevated cattle TB incidence have not found one. Transmission occurs within wild badger populations; there is insufficient evidence currently available to say definitively whether the disease can persist in British badger populations without on-going transmission from cattle. Little is known about how M. bovis is transmitted between badgers and cattle. Transmission may be indirect; for example, through contamination of pasture, feed and drinking water. Alternatively, direct transmission via aerosol droplets at close contact may occur, possibly inside farm buildings as well as outdoors.
Why not just kill the infected badgers?
(Well, apart from the moral issues around this…) Badger culling was used routinely in the past, and its effectiveness was the subject of a major experiment, the Randomised Badger Culling Trial (RBCT), which ran from 1998 to 2006. The RBCT found that annual proactive culling, as conducted in the trial, resulted in a relative reduction in new confirmed cattle herd breakdowns inside culling areas, which persisted after the final culls in 2005 but subsequently diminished over a 6-year period. While culling was being carried out, there was an increase in the incidence of confirmed herd breakdowns on land surrounding (within 2 km) the RBCT proactive culling areas, though this rapidly waned after culling stopped. Reactive culling was discontinued in 2003 because bTB in these areas were significantly higher than in no-cull areas. Culling badgers is known to disrupt badger social structure, and this has been shown to cause badgers to move more frequently and over longer distances. This effect is known as perturbation. The idea that perturbation may result in increased disease transmission. It is not currently known whether alternative culling methods (e.g. shooting of free-ranging badgers or snaring) could reduce badger densities more or less effectively in Great Britain than the cage trapping used in the RBCT, nor how different reductions in badger numbers inside culling areas would influence impacts on cattle bTB on adjoining land.
What about better testing?
The gamma interferon (IFNg) test is used as an auxiliary test to the cervical tuberculin test (SICCT or ‘skin’ test) and has lower relative specificity (median animal-level specificity of 98%). IFNg identifies some exposed cattle not identified by the skin test and has a median estimated animal-level sensitivity of 67%. The IFNg test requires only a single farm visit and is then conducted in the laboratory, where it can be more consistently interpreted.
In other (i.e. my) words, we could probably control bTB using a combination of vaccination and better testing methods. If we wanted to.
Alternatives to antibiotics are urgently needed in animal agriculture. The form these alternatives should take presents a complex problem due to the various uses of antibiotics in animal agriculture, including disease treatment, disease prevention, and growth promotion, and to the relative contribution of these uses to the antibiotic resistance problem. Numerous antibiotic alternatives, such as pre- and probiotics, have been proposed but show variable success. This is because a fundamental understanding of how antibiotics improve feed efficiency is lacking, and because an individual alternative is unlikely to embody all of the performance-enhancing functions of antibiotics. High-throughput technologies need to be applied to better understand the problem, and informed combinations of alternatives, including vaccines, need to be considered.
This article discusses alternative approaches to animal (and therefore human) health, such as:
- Feed additives such as pre- and probiotics
- Phage therapy
- Mixing additives: potentiated probiotics and synbiotics
Approximately 30 percent of all infectious diseases that emerged between 1990 and 2000 were caused by arthropod-borne viruses (arboviruses). This is probably the result of a combination of factors including a dramatic increase in travelling and commercial exchanges, climate and ecological changes and increased livestock production. In addition, changes in trading and commercial policies have created optimal conditions for the movement of infected vertebrate hosts and invertebrate vectors over wide geographical areas.
Schmallenberg virus (SBV) was discovered in Germany (near the town of Schmallenberg) in November 2011 and since then has been found to be the cause of malformations and stillbirths in ruminants. SBV has spread very rapidly to many European countries including the United Kingdom. Very little is known about the biological properties of this virus and there is no vaccine available. In this study researchers developed an approach (called reverse genetics) that allows the recovery of “synthetic” SBV under laboratory conditions. They also developed a mouse model of infection for SBV and showed that SBV replicates in neurons of experimentally infected mice similar to naturally infected lambs and calves. Using thes tools they created SBV mutants that are not as pathogenic as the original virus due to the inability to counteract the host cell defences.This work provides important experimental tools to understand how this newly emerged virus causes disease in ruminants. In addition, it will now be possible to manipulate the SBV genome in order to develop effective vaccines.
Schmallenberg Virus Pathogenesis, Tropism and Interaction with the Innate Immune System of the Host. (2013) PLoS Pathog 9(1): e1003133. doi:10.1371/journal.ppat.1003133
Schmallenberg virus (SBV) is an emerging orthobunyavirus of ruminants associated with outbreaks of congenital malformations in aborted and stillborn animals. Since its discovery in November 2011, SBV has spread very rapidly to many European countries. Here, we developed molecular and serological tools, and an experimental in vivo model as a platform to study SBV pathogenesis, tropism and virus-host cell interactions. Using a synthetic biology approach, we developed a reverse genetics system for the rapid rescue and genetic manipulation of SBV. We showed that SBV has a wide tropism in cell culture and “synthetic” SBV replicates in vitro as efficiently as wild type virus. We developed an experimental mouse model to study SBV infection and showed that this virus replicates abundantly in neurons where it causes cerebral malacia and vacuolation of the cerebral cortex. These virus-induced acute lesions are useful in understanding the progression from vacuolation to porencephaly and extensive tissue destruction, often observed in aborted lambs and calves in naturally occurring Schmallenberg cases. Indeed, we detected high levels of SBV antigens in the neurons of the gray matter of brain and spinal cord of naturally affected lambs and calves, suggesting that muscular hypoplasia observed in SBV-infected lambs is mostly secondary to central nervous system damage. Finally, we investigated the molecular determinants of SBV virulence. Interestingly, we found a biological SBV clone that after passage in cell culture displays increased virulence in mice. We also found that a SBV deletion mutant of the non-structural NSs protein (SBVΔNSs) is less virulent in mice than wild type SBV. Attenuation of SBV virulence depends on the inability of SBVΔNSs to block IFN synthesis in virus infected cells. In conclusion, this work provides a useful experimental framework to study the biology and pathogenesis of SBV.
Professional Exposure to Goats Increases the Risk of Pneumonic-Type Lung Adenocarcinoma: Results of the IFCT-0504-Epidemio Study. (2012) PLoS ONE 7(5): e37889. doi:10.1371/journal.pone.0037889
Pneumonic-type lung adenocarcinoma (P-ADC) represents a distinct subset of lung cancer with specific clinical, radiological, and pathological features. Given the weak association with tobacco-smoking and the striking similarities with jaagsiekte sheep retrovirus (JSRV)-induced ovine pulmonary adenocarcinoma, it has been suggested that a zoonotic viral agent infecting pulmonary cells may predispose to P-ADC in humans. Our objective was to explore whether exposure to domestic small ruminants may represent a risk factor for P-ADC. We performed a multicenter case-control study recruiting patients with P-ADC as cases and patients with non-P-ADC non-small cell lung cancer as controls. A dedicated 356-item questionnaire was built to evaluate exposure to livestock. A total of 44 cases and 132 controls were included. At multivariate analysis, P-ADC was significantly more associated with female gender (Odds-ratio (OR) = 3.23, 95% confidence interval (CI): 1.32–7.87, p = 0.010), never- smoker status (OR = 3.57, 95% CI: 1.27–10.00, p = 0.015), personal history of extra-thoracic cancer before P-ADC diagnosis (OR = 3.43, 95% CI: 1.10–10.72, p = 0.034), and professional exposure to goats (OR = 5.09, 95% CI: 1.05–24.69, p = 0.043), as compared to other subtypes of lung cancer. This case-control suggests a link between professional exposure to goats and P-ADC, and prompts for further epidemiological evaluation of potential environmental risk factors for P-ADC.
- Schmallenberg virus was first isolated in Schmallenberg, Germany, in November 2011.
- Schmallenberg virus is a Bunyavirus, one of a large group of of negative-stranded RNA viruses.
- Why should I care? In cows, Schmallenberg virus causes fever and a drastic reduction in milk production. In sheep it causes congenital malformations and stillborn lambs (also stillborn calves in cows).
- Schmallenberg virus was first identifed in the UK on 23rd January 2012.
- Like Bluetongue, Schmallenberg virus is transmitted by midges (Culicoides spp.), which means we will be unlikely to be able to eradicate it – vaccination of anaimals is the only likely effective response.
- Where did Schmallenberg virus come from? The virus genome is most closely related to sequences of a different Orthobunyavirus called Shamonda virus which belongs to the so-called Simbu serogroup known to infect ruminants and be transmitted by midges. In other words, it has form. But whether it is newly evolved (unlikely) or just newly discovered we don’t yet know.
- How did Schmallenberg virus reach the UK? We don’t know. It could have been due to animal movements, but since it was first identifed in eastern England, it’s possible that it arrived in midges travelling under their own steam.
- Is Schmallenberg virus going to spread to other parts of the UK and other countries? Yes, you can bet on that (just like bluetongue did).
- Can I catch Schmallenberg virus? Honest answer: We don’t know. Possibly, but there have been no reports of human illness from areas where the virus is known to exist, so I wouldn’t worry too much.
- Where can I find the latest news about Schmallenberg virus? Right here.
- OK, one last time, why should I care? Because Schmallenberg virus is going to cost European and probably worldwide ecomonies millions of pounds. And that will affect you.
- Tobacco mosaic virus (TMV)
- Tomato spotted wilt virus (TSWV)
- Tomato yellow leaf curl virus (TYLCV)
- Cucumber mosaic virus (CMV)
- Potato virus Y (PVY)
- Cauliflower mosaic virus (CaMV)
- African cassava mosaic virus (ACMV)
- Plum pox virus (PPV)
- Brome mosaic virus (BMV)
- Potato virus X (PVX)
“I see only ONE virus in the major list – African cassava mosaic begomovirus (ACMV) – that infects and causes severe losses in one of the four major food crops grown on this planet: all the rest, excepting viruses infecting the also-ran potato, are pathogens of fruits, vegetables or horticulturally-important plants. Or hardly pathogenic at all, as in the case of BMV – and before anyone argues, I probably have the best collection of African (and other) isolates of the virus in the world, and a lot of experience of it in the field.”
I have a feeling this could go on for some time :-)