Ebola: 'Dress Rehearsal' or Show Closer?

Rapid biomedical progress will soon make epidemics ancient history


Ebola virus

Don't panic. Ebola may be "just a plane ride away," but it is highly unlikely to become an epidemic threat in the United States and other rich countries. The virus is transmitted by close contact with the body fluids of infected people, making transmission much more difficult with Ebola than with a respiratory virus like influenza. This intimate mode of transmission makes it much easier for public health officials to trace people who come in contact with those infected by the virus, to monitor them, and to isolate them from the public.

The spread of the disease in West Africa is occurring largely because that region lacks adequate systems for this tracing, tracking, monitoring, and isolating. In Sierra Leone, the current epicenter of the outbreak, people who are supposed to be quarantined in their houses and monitored by police still receive visitors and go shopping. Many are also refusing to go to hospitals for treatment because they regard them as death traps. The government is now calling out soldiers to enforce the quarantines.

David Quammen, author of Spillover: Animal Infections and the Next Human Pandemic, told NPR this week that the current Ebola outbreak is "a dress rehearsal for the next big one." By the "next big one," Quammen means an epidemic caused by a respiratory disease microbe jumping from an animal species into the human population. Researchers worry that a deadly epidemic could result from the respiratory transmission of a mutated bird flu virus, or a coronavirus like the ones responsible for Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS). Yet the SARS example shows how prompt isolation and quarantine measures can stop a nascent respiratory disease outbreak. Since 2004, there have been no cases of SARS reported anywhere in the world.

If Ebola is a dress rehearsal, the good news is that biomedical researchers are developing a variety of show closers. The "secret serum" from Mapp Biopharmaceuticals injected into infected American aid workers Kent Brantly and Nancy Writebol is an example of a whole suite of new biotechnologies being developed to treat and prevent infectious diseases. The serum, called ZMapp, combines three monoclonal antibodies. One makes the virus visible to a patient's immune system, which then attacks it, while the other two neutralize it so that it can't infect human cells. ZMapp is not a vaccine; instead it confers passive immunity. (Cautionary note: The treatment's true effectiveness cannot be determined based on what amounts to a clinical trial of two people.)

Mapp Biopharmaceuticals produced the antibodies by injecting mice with a protein from the virus. This provoked the mouse immune systems to create cells that produce antibodies against the protein. The researchers fused the antibody-producing cells with cancer cells in order to have a steady supply of them. They then identified the genes for the specific three antibodies and genetically engineered them into tobacco plants to produce greater quantities. Identifying and producing monoclonal antibodies as treatments against infectious diseases is now slow and expensive, but new techniques are being developed to speed up the process. (Interestingly, the biotech company Crucell has identified a monoclonal antibody that confers near-universal immunity to influenza virus strains.)

It is impossible to survey all of the new biomedical techniques that are being developed to fight infectious diseases, but we can take a look at few of the more promising projects.

The fall in the price and availability of genetic sequencing systems is opening up a new field of "genomicepidemiology" by making it easier to quickly identify disease microbes. Next comes reverse vaccinology, which uses the genomic information to identify genes that produce targets, usually microbial proteins, for vaccine development.

In 2013, researchers at the J. Craig Venter Institute used synthetic biology to pinpoint the genes for target proteins in particular influenza virus types. Before this, the time required to create the seed strains needed for producing vaccines was 4 to 6 weeks; now it's less than a week. It takes six to nine months to make flu vaccines the conventional way, using eggs. But a new recombinant seasonal flu vaccine that the Food and Drug Administration approved last year—produced using insect cells—can be formulated in only two months.

Researchers at Arizona State University have devised a clever way to deliver DNA from pathogenic microbes as a vaccine. They have created a weakened version of Salmonella bacteria that have been genetically modified to live on a non-natural sugar. The DNA from the pathogens is inserted into the Salmonella bacteria, which are then swallowed and quickly invade host cells. Without access to their non-natural sugar supplies, the Salmonella explode, releasing the pathogenic DNA, to which the host cells develop an immune response.

"The universal DNA vaccine platform technology represents an important advance in the ability to rapidly engineer and scale up effective vaccines for influenza and other potentially lethal pathogens for biodefense," notes Global Biodefense. "The technique also permits large quantities of DNA vaccine to be produced rapidly at low cost, freeze-dried and stockpiled to be used when needed." 

Given how much progress has been made toward rapidly devising new treatments for dangerous infectious diseases, you may wonder why only a handful of ZMapp serum doses are available? Ebola outbreaks are rare, and they mostly affect people in poor countries. This small, penurious market, combined with the protracted and costly drug approval system, provide pharmaceutical companies with little financial incentive to develop therapies aimed at Ebola. The development of ZMapp was largely funded by government agencies as biodefense research. There are also a number of Ebola vaccine candidates in the pipeline, all of which have also been largely supported by government biodefense funding.

What about the future? Advances in fields like genomics, proteomics, reverse vaccinology, synthetic biotechnology, and bioinformatics are exponentially improving the knowledge of researchers about how pathogens and the human immune system interact. All of the tools involved with identifying pathogens and producing treatments like monoclonal antibodies and vaccines will continue to fall in price and become more ubiquitous. Thus will compounding therapies become ever faster and cheaper. Long, complicated, and expensive clinical trials overseen by hypercautious regulators will no longer be required for validating the safety and effectiveness of targeted, rationally designed therapies. A couple of decades hence, infectious diseases will still strike, but any patient with a fever will be tested, her infection immediately identified, and a personalized treatment regimen crafted just for her will be administered. We may reach a time when epidemics and pandemics are ancient history.