At this exponential rate of spread, the entire population of Hong Kong, where there's currently about 400 cases, would be infected in about 14 weeks.
The United States currently has about 50 cases. At an exponential rate of propagation, this would leave the entire U.S. population infected in about 23 weeks.
WEEK # OF CASES 1 100 2 200 3 400 4 800 5 1600 6 3200 7 6400 8 12800 9 25600 10 51200 11 102400 12 204800 13 409600 14 819200 15 1638400 16 3276800 17 6553600 18 13107200 19 26214400 20 52428800 21 104857600 22 209715200 23 419430400Obviously, there are mitigating factors. But the danger of a pandemic with this unknown bug is high. There is no vaccine and no known effective treatment. What's more, the disease is thought to be a variant of a coronavirus, often a cause of common colds, and is spread likewise. It doesn't take long for colds to spread through populations....except this cold incapicitates its victims putting 15-20% into intensive care and 4-5% in the morgue.
Of course, another key issue given the suspicious timing of this outbreak is: Where did it come from?
Watch this story closely as it is only now starting to unfold.
By Rob Stein
Washington Post Staff Writer
Thursday, March 27, 2003; Page A15
At least 80 percent of people stricken by a mysterious new lung infection spreading around the globe appear to recover, but the rest become critically ill and about half of them die, health officials said yesterday.
Victims who are older than 40 and have other health problems, such as heart or liver disease, are most likely to move to the life-threatening phase of the infection, officials said.
New details about the disease, dubbed severe acute respiratory syndrome (SARS), emerged yesterday when about 80 doctors treating patients in 13 countries participated in an unprecedented electronic meeting organized by the World Health Organization. The "electronic grand rounds" enabled doctors trying to save patients worldwide to exchange information over the telephone and Internet about how best to diagnose and treat the disease.
"For the first time, we brought all the clinicians together," Mark Salter, who is coordinating WHO's clinical response to the new disease, said in a telephone interview. "The WHO has never brought together this many clinicians with such rapidity. It's groundbreaking."
SARS, which emerged in southern China in November, has spread to at least 13 countries in Asia, Europe and North America, sickening more than 1,300 people and killing at least 49. U.S. health officials are investigating 45 possible cases in 20 states, including three in Virginia.
A distinctive pattern of symptoms has become clear, Salter said. Two to seven days after being exposed, patients suddenly develop a high fever -- 104 degrees Fahrenheit or higher -- start shaking and experience chills, shortness of breath and a dry cough. Some also experience headache, muscular stiffness, loss of appetite, malaise, confusion, rash and diarrhea.
Laboratory tests show that white blood cell and platelet counts drop in some patients. Chest X-rays usually reveal a distinctive pattern in which a cloudy area appears in one part of a lung and then spreads across both lungs.
After about six or seven days, about 80 percent to 90 percent of patients begin to improve. The remaining 10 percent to 20 percent deteriorate and require intensive care, with many needing a mechanical ventilator to help them breathe.
About 40 percent to 50 percent of those patients die, making the overall mortality rate for the disease about 4 percent. Salter said that mortality rate is similar to that of the mosquito-borne West Nile virus, which first appeared in the United States in 1999.
No antibiotics appear to work against SARS. The antiviral drug ribavirin has been used by a number of doctors, but its effectiveness remains unclear. During yesterday's meeting, doctors agreed to quickly organize a study to determine ribavirin's usefulness.
Treatment has been complicated, because many of the victims have been doctors and nurses who were infected by some of the first patients. That left hospitals, particularly in Hanoi and Hong Kong, short-staffed.
"Clinicians around the globe are stretched to the limit," Salter said. "Everybody is working very hard to try to not only identify the agent that's causing this, but to find methods that might be effective in treating it."
The disease appears to be spread by tiny droplets that become airborne when a sick person coughs, or through contact with other body fluids, such as blood.
Scientists from at least 11 laboratories are racing to identify the cause. Researchers have found two previously unknown viruses in patients and are trying to determine whether either one, alone or in combination, causes the disease. One is a previously unknown strain of a virus that usually causes the common cold. Both also cause illnesses in animals.
"Hypotheses include a virus known to cause disease in an animal that has jumped the species barrier to infect humans, or a known human virus that has mutated to acquire properties that are causing much more severe disease in humans," WHO's statement said. "It is increasingly certain, however, that SARS is a serious new disease caused by a newly recognized pathogen."
International effort reveals links between SARS outbreak and Chinese pneumonia, and possible agent. | By Robert Walgate
Margaret Chan, Health Director of Hong Kong, said today that the source of the current international outbreak of Severe Acute Respiratory Syndrome (SARS) seems to be a doctor from Guangzhou, the capital of Guangdong, the southernmost region of China, which saw 300 cases of a mystery pneumonia between November 2002 and February 2003. Chan's comments are reported in the Hong Kong Standard.
China only recently agreed to cooperate with the World Health Organisation (WHO) and the US Centers for Disease Control to share data and samples from that earlier outbreak.
The doctor stayed on February 21 with six other first ("index") cases of the current outbreak on the same floor of the Metropole Hotel in Mong Kok, Hong Kong. He died later in hospital.
The importance of this observation is to link the two outbreaks, so data can be pooled. For example China earlier claimed that the Guangdong disease had weakened after successive transmissions, although David Lowe, the Canadian doctor attending to the nine cases in Toronto — the first of whom, a 65-year-old woman, is believed to have stayed at the Metropole Hotel during the Chinese doctor's visit — told The Scientist that in his experience so far the disease had been equally severe in each successive case.
Julie Hall of WHO's Global Alert, Response and Operations Department — which is managing the WHO response to SARS — told The Scientist that the Chinese government had requested assistance in analysing its own data. "They have a mass of data from November through to February — epidemiological data and samples. The first wave of the investigation will be epidemiological, and WHO is helping China select experts who could help, and facilitating with the government in Beijing."
Meanwhile tentative identification in Germany and then Hong Kong of the causative agent as a member of the paramyxovirus family — viruses associated with other respiratory infections including the parainfluenza viruses and respiratory syncytial virus (RSV), as well as mumps and measles — is being treated with caution.
Hall warned "What [the German team] saw under the electron microscope were particles — not a whole virus, just fragments from one sample — of a paramyxovirus. The whole family look the same. It gives us a clue, but doesn't definitively diagnose it. We don't know which member of the family it is, and some of them are incredibly common, like RSV, which causes coughs and colds in children and is very prevalent. If it's a little bit of that it means absolutely nothing."
"But what the collaborating laboratories are doing now is PCR tests to check the DNA to try to identify which member of the family it may be, and antibody tests in patients against a whole range of paramyxoviruses. WHO is coordinating that," said Hall.
John Tam of the department of microbiology of The Chinese University of Hong Kong later confirmed detection of a paramyxovirus in local samples by electron microscopy, and subsequently with PCR, but it is still not clear if SARS can definitively be attributed to such a virus.
The Paramyxovirinae is a huge family also found in monkeys, cattle, pigs, dogs, mice, pigeons, and even seals, dolphins and rattlesnakes, and it is conceivable an animal form has "crossed over" into humans in South China and begun the present outbreak of SARS.
The past 25 years of increasing commercial exploitation of genetic engineering in both agriculture and medicine may have unleashed the potential for creating viruses and bacteria more virulent than nature's worst. Dr. Mae-Wan Ho calls for a halt to all further releases of GMOs.
Man-made, synthetic viruses with the ability to multiply by the millions are "very close", Clyde Hutchison of the University of North Carolina in Chapel Hill, N.C. told the annual meeting of the American Association for the Advancement of Science in February [1]. The technology holds much promise, but could also "potentially be misused". Already, researchers associated with a biotech company in Texas are believed to be making pieces of DNA big enough to generate viruses. But they are not releasing details of the work for "proprietary reasons".
Hutchison’s team is trying to figure out the genetic recipe for creating a free-living organism from scratch. While that task is proving difficult, viruses are much easier, as they are not free-living organisms, but genetic parasites that depend on hi-jacking the cell’s metabolism to replicate. According to Hutchison and other geneticists, it will soon be a relatively easy matter to tinker with existing micro-organisms to create new, more virulent varieties, and to recreate organisms that have lately become extinct. "In principle, one day someone could make smallpox".
One of the major hurdles to creating life is that although sequencing genomes billions of basepairs in length is relatively easy, making DNA in the test-tube much bigger than a few thousand basepairs gets much more difficult. That is because the enzymes that copy DNA, or RNA (the genetic material most usually found among viruses) are prone to errors. The errors are corrected by proof-reading mechanisms present only within the living cell.
This hurdle has prevented RNA viruses larger than a few thousand bases from being cloned, ie, isolated and replicated in the test-tube; until recently, that is [2]. In order to clone the virus, the RNA has to be reverse-transcribed, or copied into a complementary DNA (cDNA) sequence, which is then incorporated into a bacterial plasmid (a genetic parasite) for replicating in the bacterial cell. However, the enzymes that do the job, the reverse transcriptase and polymerase chain reaction (RT-PCR) are very error-prone, and some of the errors result in ‘poison sequences’ that make the cDNA unstable. Furthermore, very few vectors can accommodate long cDNA inserts.
The fidelity of RT-PCR can be improved, and has been with the help of high-fidelity reverse transcriptases becoming available. Even so, mistakes remain that have to be corrected. This procedure was used successfully in cloning the hepatitis C virus. Poison sequences arise probably because the bacteria have not been adapted to such foreign sequences. Bacteria also tend to selectively replicate certain viral sequences, so that cloned sequence (replicated in the bacterial host) is not representative those in their natural hosts. Poison sequences can be avoided by cloning the viral genome in shorter segments, which are joined together afterwards. This strategy was used in cloning flaviviruses. For vectors that can accommodate long cDNA inserts, bacterial artificial chromo-somes (BAC) are the answer. A BAC was indeed used to clone the 150 kbp herpes simplex DNA virus.
Last year, geneticists in Spain succeeded in cloning a coronavirus [3], the transmissible gastroenteritis virus (TEGV) that infects newborn piglets, giving 80% mortality. Coronaviruses include numerous economically and medically important viruses respons-ible for many common colds and possibly gasteroenteritis and neurological illnesses such as multiple sclerosis. These viruses contain a RNA genome of 17 –32 kb, more than twice the size of the largest conventional RNA viruses. Within the cell, the viral RNA is replicated entirely in the cytoplasm, outside the nucleus containing the cell’s own genetic material.
The research team cloned the region containing the poison sequences last before inserting the whole into a BAC. The viral cDNA was placed under the control of a promoter from the cytomegalovirus (CMV) and the ends of the viral RNA were carefully engineered to match their natural sequence. This viral cDNA, cloned in E. coli bacteria, produced RNA viruses when injected into pigs. This was a surprise because the viral cDNA had to be transported into the nucleus of the pig cells, there to be transcribed into RNA and transported back to the cytoplasm before it could be replicated; something that the natural virus does not do. So, the research team had in effect created a new virus through genetic engineering.
Their results also showed that the ‘spike’ protein encoded by one of the genes of the virus is sufficient to determine its disease-causing ability, thus accounting for how a pig respiratory coronavirus emerged from the TEGV in Europe and the US in the early 1980s. The ease with which new viruses can arise, with or without the help of intentional genetic engineering should be a cause for great concern.
Since the dawn of genetic engineering in the 1970s, geneticists have found that the cDNA of many RNA viruses inserted into bacterial plasmids, were able to complete their life-cycles in bacteria. In fact, RNA genomes produced in the test-tube can also successfully transfect bacterial cells and complete their life-cycles [2]. Bacteria in the environment therefore provide a convenient reservoir for storing, multiplying and recombining viral genes to create new viruses.
The top news in the Jan. 13 issue of the New Scientist [4] was on a deadly virus created accidentally by researchers in Australia who were trying to genetic engineer a contraceptive vaccine for mice. They spliced a gene for the protein interleukin-4 (IL-4) into the relatively harmless mousepox virus in the hope that IL-4 would boost the immune system to make more antibodies. When the researchers injected this vaccine into mice, all the mice died. In fact, this synthetic virus was so lethal that it also killed half of all the mice that had been vaccinated against mousepox.
The mice killed were genetically resistant to the mousepox virus in the first place [5]. Genetic resistance to mousepox varies among inbred laboratory mice, and depends on natural killer (NK) cells and cytotoxic T-lymphocytes (CTL) responses to viral infection, both of which destroy cells that have been infected with virus so as to clear the body of the virus. The researchers found that IL-4 suppressed both NK and CTL responses. So, the virally-encoded IL-4 not only suppresses primary antiviral immune responses but also inhibits immune memory responses.
In previous experiments [6, 7], the IL-4 gene was inserted into the virus used in vaccinations against smallpox, the vaccinia virus, and it delayed the clearance of the virus from experimental animals and undermined the animals’ anti-viral defence. Thus, IL-4 may function similarly in all viruses in the same family, which also contains the human smallpox virus.
These findings raise the spectre of biological warfare. But the far greater danger lies in the unintentional creation of deadly pathogens in the course of apparently innocent genetic engineering experiments.
Genetic engineering involves facilitating horizontal transfer and rampant recombination of genetic material across species barriers, precisely the conditions favoring the creating of new viruses and bacteria that cause diseases. We now know of cases in the laboratory where such viruses have been created. But what of other viruses we know nothing about, that may have been created over the past 25 years of increasing commercial exploitation of genetic engineering in both agriculture and medicine? Genetic engineering uses the same tools and makes similar constructs, whether in agriculture or in medicine; and therefore carries the same risks.
The accompanying New Scientist editorial [8] remarked that five years ago, when biomedical researchers were asked if genetic engineering could create "a virus or bacteria more virulent than nature’s worst", they replied it would be "difficult if not impossible". Some of us have been warning of ‘accidents’ such as this for at least the past six years. We published a detailed review on the evidence suggesting links between genetic engineering and the recent resurgence of drug and antibiotic resistant infectious diseases in 1998 [9]. We were by no means the first. Scientists who pioneered genetic engineering in the mid-1970s declared a moratorium precisely because they were concerned about this dire possibility.
Unfortunately, overwhelming pressures for commercial exploit-ation cut the moratorium short. The scientists set up guidelines based largely on assumptions, all of which have fallen by the wayside as the result of new scientific findings. Instead of tightening the guidelines, our regulators have relaxed them as commercial pressures built up. Transgenic wastes are even being recycled as food, feed, fertilizer and landfills under the current EC Directive on Contained Use [10].
Genetic engineering may have unleashed an uncontrollable, self-amplifying process of horizontal gene transfer and recombination that can sweep across the whole of the living world, with the potential indeed, of creating viruses and bacteria more virulent than nature's worst. It is time we call a halt to all releases of GMOs and to make sure that further research takes place only under strictly contained conditions.
"Making life from scratch is now ‘imminent’: From minimal genomes: Viruses the size of HIV are likely to come first" Margaret Munro, National Post Wednesday, February 21, 2001 EDITION National Discovery PAGE A15 SAN FRANCISCO.
Lai MMC. The making of infectious viral RNA: No size limit in sight. PNAS 2000: 97: 5025-7.
Almazan F, Gonsalex JM, Penzes Z, Izeta , Calvo E, Plana-Duran J and Enjuanes. Engineering the largest RNA virus genome as an infectious bacterial artificial chromosome. PNAS 2000: 97: 5516-21.
Nowak R. Disaster in the making. New Scientist 2001: 13 Jan. 4-5.
Jackson RJ, Ramsay AJ, Christensen CD, Beaton S, Diana F. Hall DF and Ramshaw IA.Expression of Mouse Interleukin-4 by a Recombinant Ectromelia Virus Suppresses Cytolytic Lympho-cyte Responses and Over-comes Genetic Resistance to Mousepox. Journal of Virology: 2001: 75: 1205-1210.
Bembridge GP, Lopez JA, Cook R, Melero JA and Taylor G. Recombinant Vaccinia virus coexpressing the F protein of respiratory syncytil virus (RSV) and interleukin-4 (IL-4) does not inhibit the development of RSV-specific memory cyto-toxic T lymphocytes, whereas priming is dimished in the presence of high levels of IL-2 or gamma interferon. Journal of Virology: 1998: 72: 4080-7.
van den Broek M, Bachmann MF, Kohler G, Barner M, Escher R, Zinkernagel R and Kopf M. IL-4 and IL-10 antagonize IL-12-mediated protection against acute vaccinia virus infection with a limited role of IFN-g and nitric oxide synthetase 2. The Journal of Immunology: 2000: 164: 371-8.
"The genie is out" New Scientist editorial 2001: 13 Jan. 3.
Ho MW, Traavik T, Olsvik R, Tappeser B, Howard V, von Weizsacker C and McGavin G. Gene Technology and Gene Ecology of Infectious Diseases. Microbial Ecology in Health and Disease 1998: 10: 33-59.
"Dangerous GM wastes recycled as food, feed and fertilizer" ISIS News 6, September 2000