Pathogens and Biotechnology

Throughout history pathogens have been responsible for more human deaths than any other factor, by far, with hundreds of millions in the 20th century alone. The Spanish flu for example, that broke during the First World War, reached up to 100 million deaths in about one year. 5 times more than the war itself.

Today's international health experts are afraid of a pandemic that would affect the entire world. They estimate that a fifth up to half of the world population could die in case of an influenza outbreak for example. And according to many, including the infectious disease expert Professor Michael Osterholm "It’s not a matter of ‘if’ influenza pandemic is going to happen, but when".

Pandemics such as influenza trigger a chain of events that can change the world overnight, as we witnessed in the recent swine flu, bird flu and SARS pandemics (for more information please read our document about past pandemics ).
Even if the pandemic’s source is a new strain of a known virus (like influenza), this knowledge would have no impact on the spread of the virus in the first six months and would likely play an extremely limited role worldwide since it takes about that time for a vaccine to be available for production.
And even when not only the pathogenic source is known but also the vaccine is, it would still take a while for the population to be immunized, largely because it would not be available (stockpiles of vaccines and antiviral drugs are very limited and the production of new ones takes time).
Only a few privileged areas of the world have access to vaccine-production facilities and previous incidents show they don’t share. And this scenario is only when the source of the pandemic is known or a vaccine for the virus is known. In totally new pandemic cases, when humans have no idea what the source is (or know but have no idea how to develop a vaccine for it), like in the case of AIDS, it can take much longer (for further information regarding the first years of the AIDS pandemic please read our Manifest ). Just think what would happen if a number of unknown pathogens are released at once…

Today some experts assess that even with modern antiviral drugs, vaccines and prevention knowledge, the return of a virus equivalent in pathogenicity to the Spanish flu virus strain, would likely kill over 100 million people worldwide, more than it did a century ago, when the virus was first spread.

Royal London Hospital virologist John Oxford says: "Many governments have not created comprehensive pandemic emergency plans. The investment so far ... is very, very, very small."
International experts agree - The whole world is clearly unprepared to face a lethal pathogen, while without a doubt it would be a global issue.
An outbreak would quickly turn worldwide. "Mega-cities" and the prevalence of international travel would spur the rapid spread. Although the transmission rate of SARS pales in comparison to that of influenza, it demonstrated how quickly such an infectious agent can circle the globe, given the ease and frequency of international travel. SARS spread to five countries within 24 hours and to 30 countries on six continents within several months.

All these global impacts are the result of spontaneous and random outbreaks or at least unpremeditated outbreaks of pathogens, so imagine what an intentional, focused, educated, and highly motivated operation using genetic engineering can accomplish.

Of the 1,500 pathogens known to cause disease in humans, the CDC (Center for Disease Control) formed a list of the most deadly ones that might be weaponized for "Bioterrorism". These pathogens are divided into 3 Categories:

Category A:

Biological agents that are highly lethal and spread quickly. Category A agents are:

  • Anthrax (Bacillus Anthracis) (Bacteria)
  • Botulism (Clostridium Botulinum Toxin) the toxin of C. botulinum Bacteria
  • Plague (Yersinia Pestis) (Bacteria)
  • Smallpox (Variola Major) (Virus)
  • Tularemia (Francisella Tularensis) (Bacteria)
  • Viral Hemorrhagic Fevers (Filoviruses [Ebola, Marburg] and Arenaviruses (Lassa, Machupo) (Virus)

Category B:

Biological agents that are moderately easy to disseminate and have low mortality rates. The Category B agents are:

  • Brucellosis (Brucella species) (Bacteria)
  • Epsilon Toxin of Clostridium Perfringens (Bacteria)
  • Food safety threats (e.g., Salmonella species, E. Coli O157:H7, Shigella)
  • Glanders (Burkholderia Mallei) (Bacteria)
  • Melioidosis (Burkholderia Pseudomallei) (Bacteria)
  • Psittacosis (Chlamydia Psittaci) (Bacteria)
  • Q fever (Coxiella Burnetii) (Bacteria)
  • Ricin Toxin from Ricinus Communis (Castor Beans) (Bacteria)
  • Staphylococcal Enterotoxin B (Bacteria)
  • Typhus Fever (Rickettsia Prowazekii) (Bacteria)
  • Viral Encephalitis (Alphaviruses [e.g., Venezuelan Equine Encephalitis, Eastern Equine Encephalitis, Western Equine Encephalitis])
  • Water safety threats (e.g., Vibrio Cholerae, Cryptosporidium Parvum)

Category C:

Biological agents which are pathogens that might be engineered for mass dissemination because they are easy to produce and have potential for high morbidity or mortality. The Category C agents are:

  • Nipah Virus
  • Hantavirus
  • Multi-Drug Resistant Tuberculosis (MTB)
  • Tick-Borne Encephalitis Viruses
  • Yellow Fever (Virus)

All those pathogens, including the ones in the A category, potent and fearsome as they may be, are still inadequate at their current state (at least according to a swift research).
None of these is yet the highly lethal, highly contagious, drug resistant pathogen that is required, but they have a potential clearly worth investigating.
Some already possess parts of the mentioned qualities (The mortality rate of the Zaire Ebola virus reaches more than 90%, the smallpox virus is already highly infectious, and the anthrax bacterium has a high resistance spore form).
Research and development are required of course. It is known that classical bio-warfare agents can be made much more effective than their natural counterparts, with even the simplest genetic techniques.

Today, according to U.S. biological weapon experts, underground groups are already able to obtain the means necessary for a global pandemic that can kill hundreds of millions of people.
C.J. Peters, an infectious diseases expert that for the last 30 years worked for the U.S. Army and the CDC (Center for Disease Control), said referring to the category A pathogens: "Every one of these agents has been weaponized by the U.S. or the Soviets or both. Each one of them is known to have been aerosolized, and each has a high morbidity rate and mortality rate."

In addition, totally new pathogen can be formed by simple genetic engineering. Kenneth Alibek, once head of the Soviet Union germ warfare research program, now a U.S. biowar consultant says: "This knowledge exists, this knowledge is, let me say, widely published, and there is no significant problem to developing genetically engineered pathogens."

Means as raw materials, equipment and biotech knowledge are getting increasingly available by the day. Supplies, such as custom made DNA segments and growth media can be obtained by mail-order. Anyone can receive them within the few weeks of shipment. Large-scale manufacture equipment are also becoming more and more within reach as well as portable (for example- experts who examined the subject found that they could produce 14 million lethal doses of anthrax for a cost of less than $100, check at: http://www.fas.org/irp/congress/2005_hr/bioterror.html)

"An advanced grad student could do it" says Roger Brent, head of the Molecular Sciences Institute in Berkeley, California. He even took a few steps ahead and wrote about the scenario of a group of militants who inflict themselves with a highly contagious disease, such as reformulated SARS, and then cough on people, with the consequence of millions of deaths.

Information can be easily obtained from open sources, such as national Patent Offices (DNA information has been patented by genetic technology businesses), microbiology books that were published several decades ago before the bioterrorism scare, constantly published biotech papers, and of course stands at the top of the list - the internet.
Freely available in online public databases are DNA sequences of dangerous pathogens such as Polio virus, Spanish flu, Plague and Smallpox. While only two known samples of the Smallpox virus exist in the world, stored in maximum security laboratories (in the USA and Russia), the blueprints are free online.

The publishing of the full genome of the Spanish flu virus (also called the 1918 influenza) on the internet in the GenBank database was followed by a great deal of criticism (In 2005 even further concerns were raised by the successful recreation - the "rebirth" of the 1918 virus in a US laboratory).

The editors of the American Association for the Advancement of Science journal, noted that "Both the authors and Science's editors acknowledge concerns that terrorists could, in theory, use the information to reconstruct the 1918 flu virus.
An open-ad on the New York Times titled 'Recipe for Destruction' said: "No responsible scientist would advocate publishing precise designs for an atomic bomb, and in two ways revealing the sequence for the flu virus is even more dangerous.
First, it would be easier to create and release this highly destructive virus from the genetic data than it would be to build and detonate an atomic bomb given only its design, as you don't need rare raw materials like plutonium or enriched uranium. Synthesizing the virus from scratch would be difficult, but far from impossible. An easier approach would be to modify a conventional flu virus with the eight unique and now published genes of the 1918 killer virus.
Second, release of the virus would be far worse than an atomic bomb. Analyses have shown that the detonation of an atomic bomb in an American city could kill as many as one million people. Release of a highly communicable and deadly biological virus could kill tens of millions, with some estimates in the hundreds of millions."

Counterterrorism authorities of a number of countries have studied the biowarfare implications of the avian flu and drawn up scenarios that involved the use of a contagious new bird flu strain as a weapon. They concluded that creating an efficiently transmitted H5N1 (the bird flu virus) should be relatively easy by forming an agent that would swiftly disseminate worldwide and be very hard to control. This can be done by the technical ability to engineer a flu virus taking genes from a virulent but not highly transmissible strain and combining them with the genes of a contagious flu virus.

The flu case exemplify how, other than the CDC’s bioterror list above, there are many pathogens that can be marked as great candidates. Authorities acknowledge that pathogens excluded from the list can, with advances in technology and science, pose "a significant threat in the future". They also admit that it is virtually impossible to prevent access to such a verity of pathogens, many of which are widely available in nature, even category A ones.

Yersinia Pestis bacteria, the agent of plague and a category A pathogen caused multiple worldwide pandemics and led to an estimated 200 million deaths. It caused the Black Death, one of the deadliest pandemics in human history (killed between one-third and two-thirds of Europe's population).
Nowadays, plague is available in its natural form, in many countries across Africa, Asia and the Americas (including the southwestern United States). Because of its natural availability, the publication of its genome raise less fuss and gone smoothly, certainly not because it poses less of a threat in its variants. The Y. pestis wide distribution, along with its potential for a lethal aerosol dissemination, make it one of the most dangerous bioterrorism agents according to authorities. Also, the Y. pestis culture techniques are significantly simple, available and rapid (in 10 hours a single Bacterium can produce a billion others).
In 1995, a strain of plague with higher resistance to antibiotics was incidentally found in Madagascar. In addition, today the genetic introduction of antibiotic resistance into bacteria is routine work in almost any microbiology laboratory. So maybe the desirable pathogens already exist and are just "waiting to be found".

Another group called Hemorrhagic Fevers Viruses (HFVs) is listed as top bioweapon agents, some are classified as category A such as the Ebola and Marburg viruses. Most of these viruses are readily available in nature, each having a defined geographic distribution. The fear of HFVs is based on their potential to cause widespread illness and death, and on the limited strategies either to prevent or treat these infections.

In 1995, during an Ebola outbreak in Kikwit, Zaire, the New York Times wrote referring to a natural mutation of the virus: "it is not hard to imagine an outbreak that could threaten the globe. A modest genetic change might enable Ebola to spread rapidly through the air and infected travelers could spread the virus widely before anyone realized they were sick".

All four known Ebola strains have displayed the ability to be spread airborne under research conditions, and there are evidences outside of the labs as well. The lethal Marburg virus, Ebola’s closest relative, was made airborne according to scientists from the former Soviet Union.
In an analysis of recent outbreaks of Ebola in Africa performed by virologist Peter Jahrling, principal scientific adviser to the U.S. Army Medical Research Institute of Infectious Diseases, clusters of deaths were found - in which victims had no known contact with one another. That made it in Jahrling’s words, difficult to exclude a component of aerosol transmissibility.
Also no approved vaccine or treatment exists for Ebola despite excessive research over decades.

Even in the case where there are methods to deal with a certain pathogen, biotechnology can get around them. The same way it can alter many other traits. The biotechnology revolution allows biologists to swap genes in and out of different organisms to increase the virulence, resistance to antibiotics or evading vaccines.
One example is the USSR's 'invisible anthrax', resulting from the introduction of an alien gene into Bacillus Anthracis that altered its immunological properties. Existing vaccines proved to be ineffective against this new genetically engineered strain.

Moreover, considering the rapid development of molecular biology, even the artificial assemble of an entire deadly pathogen from scratch is already possible. Researches have already proved they are able to piece together DNA strands hundreds of thousands of letters (base pairs) long.
For comparison - the smallpox genome is 185,000 letters in length, the Ebola is 19,000, the influenza genome has 13,500 letters and polio 7,741. The last two have been synthesized in labs a few years ago (the 1918 virus rebirth was earlier mentioned in the text).

The research team that had created the polio virus started with the genetic sequence of the agent, which is available online, ordered small, tailor-made, DNA sequences and combined them to reconstruct the complete viral genome. In a final step, the synthesized DNA was "brought to life" by adding a chemical cocktail that initiated the production of a living, pathogenic virus.

The possibilities are amazing, especially while taking into account that molecular biology and genetic engineering are considered to be in their infancy.

As a result of the constant and rapid growth of the field, regulations fail to always catch up with the technology.
Dozens of biotech firms offer to synthesize complete genes (DNA sequences) from the chemical components of DNA. Some, up until recently, virtually without carrying out checks on what they are being asked to make, or for whom.

An indication of the wide-open loophole made headlines as DNA sequences of one of the most deadly pathogens known- smallpox, were bought over the internet and sent by post to a Guardian reporter, in an investigation which showed the ease with which ingredients of biological weapons can be obtain.
The 78-letters sequence of DNA, which is part of one of the smallpox virus's coat protein genes, was delivered at the cost of £33.08, plus an additional £7 for postage.
The reporter ordered a smallpox sequence that was slightly modified. It had three changes built into it (so the purchase won’t raise any suspicions due to the Anti-terrorism, Crime and Security Act). After discovering that it had supplied a small sequence of modified smallpox DNA, the biotech company carried out several checks but none of them raised any alert.

The Variola major virus, which causes Smallpox, is at the top of all biowarfare agents lists. Smallpox is a highly contagious fatal disease with no known cure, that particularly thrives at populated areas and in the 20th century alone an estimated 300 million people died from it. Smallpox which was brought to America by the European conquers is the main cause of death of nearly all of the native inhabitants in both Americas- as the mortality of native population came to 90% – 95% and at some places reached 100%.
Smallpox is said to be eradicated from the world since 1977, which makes it even more dangerous because a society that haven’t been exposed to the virus for several decades is much more vulnerable.

In addition, the Variola major virus is known to be particularly easy to produce, highly contagious and airborne (natural strains so far are known to travel by aerosols and infect in closed settings). Furthermore, the virus can spread effectively among humans, as inhaling a single virus may be enough to cause infection, and each infected person spread millions of infective viruses into the environment.

The fact that a British journalist easily got hold of the no. 1 bioterror threat indicates that there are accessible loopholes.

In many ways and aspects (much like with computers and internet security), the authorities are at least one step behind. Initiatives such as programs to stockpile vaccines or developing pathogens detecting mechanisms are likely to be ineffective since the biowarfare specialists can simply design a pathogen that circumvents them. The soviet 'invisible anthrax' that sidesteps current vaccine is such an example.
It’s a non-stop arm-race in which law enforcement agencies are always at a disadvantage. Lawmakers can’t prevent access to the technology and information mentioned above.

Michael V. Callahan a program manager for biodefense and mass-casualty care at the Defense Advanced Research Project Agency (DARPA) expressed alarm at the easy availability of biotech knowledge that is spreading like wildfire as biotech businesses and research surge. He said that in the first third of 2005, "there are 19 papers that have been produced which provide heavy, excellent answers for the challenges facing a biological weapon scientist".
Callahan said the rate of open-source publication of biotech papers was outpacing the Homeland Security Department's ability to monitor them to assess the threat of the published information. "We are just picking up the big stuff, and we are probably about a year behind. We have received several red alerts this month for publications that will show up next month."

Former deputy director of the secret biological weapons facilities of the Soviet Union’s Biopreparat, Ken Alibek, mentioned another way to get hold of the smallpox virus in his book Biohazard, that cover the Soviet bioweapon programs activities over more than two decades. Alibek revealed that besides creating genetically altered version of some of the world’s worst bacteria and viruses, the Soviet Union’s biowarfare scientists also gathered new mutated strains, more deadly than the original ones. For 30 years there was an operation conducted in Siberia to unearth dead smallpox victims, frozen in their tombs, to extract the samples. The assessment is that it’s "not inconceivable" for the Soviet Union to hold 300 different strains of the original virus using this method.

Theoretically speaking, there’s no reason why this smallpox recovery project wouldn’t last to this day.

The latest expedition we know of was reported in 1991 when scientists unearthed a frozen grave trying to extract the intact virus from the body of 19th century smallpox victim. At that time they didn’t manage to do so, however antibodies against smallpox reacted with the extracted tissue indicating the virus (or at least remains of it) are still present. Today we know that it doesn’t require a preserved intact sample of a pathogen in order to obtain the organism. All it takes is the characteristic DNA segments of the pathogen.

The "rebirth" of the 1918 flu virus was made possible in this manner.
Three missing DNA segments were discovered in the corpse of an Inuit woman buried for nearly a century in the Alaskan permafrost. Other five critical segments were already at hand. Putting together the eight segments inside a lab influenza strain- researches created the 1918 strain.

"The genome is essentially the design of a weapon of mass destruction" said the open-ad on the New York Times with the 1918 strain reassemble, and obtaining such a weapon has never been more likely than today. Perhaps the thing that best expresses the current fenceless reality is that the US lawmakers are concerned over amateur adolescents "gene hackers" slicing up genes at their parents' garage.