Kendall Hoyt #34

Biosecurity Expert

Assistant Professor, Geisel School of Medicine 

Dartmouth College

Author of Long Shot; Vaccines for National Defense




Interview By Heidi Legg

Vaccination is a hot topic in some circles. I hear it mostly amongst those with young children or the medical profession worried about protecting the herd. As recipients of the golden age of vaccination, deadly diseases are not part of our every day. Rather, the subject makes headlines when we find a protection against cancer, suffer a virulent flu season or when an outbreak like SARS in 2002 or Anthrax drive fear into the general public psyche. But then the fear goes away, for most of us. As with many things in life, we react in the moment, hoping that when we need it, someone will have stockpiled it, or someone will have planned for it and in our age of ATM, nanosecond viral information and instant messaging, we expect there will be an immediate solution at the ready.

I sat down with Kendall Hoyt, an expert in bio-security who worries about this all the time. She teaches and lectures at Dartmouth College on national preparedness and wrote Long Shot, Vaccines for National Defense, to explore how America has long developed vaccines and what needs to happen to incentivize Pharmaceuticals and Biotechs to have solutions in the ready. She argues development times for new vaccines are too long and that innovation in vaccines has been falling, not rising since World War II when with technology, the opposite should be true. 

What keeps you up at night?

I worry about another event like SARS that we experienced in 2002-2003. This was an unfamiliar virus that seemed to come out of nowhere and suddenly it was everywhere. If it hadn't burned out, if it had continued to collect victims at the same rate that it had been, we would be asking ourselves, ‘Why haven’t we devised an emergency pathway for drug/vaccine development that allows us to catch up to these nasty surprises?’  This matters because new infectious diseases emerge all the time. 

We need to shorten the time it takes from the moment we identify a new pathogen to the moment we administer a safe and effective countermeasure. This is not about inventing the next new vaccine, but about reengineering the development process itself for public health emergencies.

Do we know where SARS came from now?

We think the virus originated in bats. One theory is that humans became infected after eating civet cats in China that acquired the virus from bats.

What about bioterrorism? Is it a real threat?

Yes. We saw it with the anthrax letters in 2001. It's not theoretical. We know that the Former Soviet Union and other states have invested in biological weapons and we have evidence that non-state actors like Al Qaeda are interested in these weapons as well.

Which do you worry about most?

I probably worry about naturally emerging infectious diseases more than I worry about engineered threats. Mostly, I worry about how are we going to get the medicine that we need when we need it. It’s one thing if we encounter a familiar strain of smallpox or anthrax and we have stockpiled effective countermeasures. It is quite another if we encounter something unusual like SARS. That's the scenario that scares me the most. Have we put in place everything that we need to have the fastest possible response from the moment we identify a new pathogen to the moment we deliver safe and effective countermeasure? No. Not even close. We need to invest in the research tools, technologies, protocols and systems that will allow us to “run faster.” It’s about accelerating that path and I don't think that we have invested sufficiently in creating an accelerated pathway for those situations.

Who can make this change? Who’s in charge?

Government, industry and academia need to work together to build this capability. It’s a massive coordination problem. It’s a massive systems engineering problem. For so many different players to be coordinated effectively, this would have to be a top priority for the Administration.

How long does it take to develop vaccines today?

It typically takes anywhere from ten to fifteen years which is far too long if you have people dying at a high rate from an unusual pathogen. We need to learn how to condense that to eight weeks, twelve weeks, even two months. It is not unrealistic to think that we could do this.  We already generate new flu vaccine on six-month schedule every year. As developers begin to exploit new technological opportunities such as flu gene synthesis, new cell cultures, and vaccine platforms, we will condense the timeline even further.  Flu is a special case because annual sales, and government funds sustain the research, development, and manufacturing base for these recent advances. It is much trickier to find a sustainable business model for many emerging infectious diseases and biothreats, but not impossible.

So we can do this for other diseases outside of the flu?

Yes. There are a number of promising models and technologies.  The Vaccine and Immunotherapy Center, here at MGH, directs a consortium that can generate pre-clinical vaccine candidates using self-assembling vaccine platforms and new genomic tools in 120 days.

What are the drawbacks of acceleration?

Essentially, you don't want the perfect to be the enemy of the good. You have to consider relative risk. If you have a 50% chance of dying from something that's circulating in the population and you have an opportunity to take an experimental vaccine that may be 30% effective with some side effects, well, that might be a risk you'd be willing to take.  I think most people would be thankful to have the option.

That sounds less than perfect. And it feels like this SARS-type drama is our generation’s new reality. Is that the case? 

It many ways, it has always been our reality, but globalization, urbanization, and climate change are definitely giving pathogens more opportunities to travel. We’re coming out of a golden age of vaccine development and wide-scale vaccination where we haven’t seen a lot of this in our generation.

Harvard University Press recently published your book, Long Shot; Vaccines for National Defense.  What is it about?

I take a close look at the research practices that accelerated development times and innovation rates in the 20th century. These lessons can inform our strategic response to fast moving pandemics/bioterrorism/EID and provide a roadmap for industry and academia to make more productive investments in accelerated development.

When did you know you were onto something?

I wish there had been a single aha moment, but it was a very incremental process. I was compiling vaccine license data, which was fiendishly difficult because our records are incomplete and inaccurate.  Slowly, I started to build a picture of innovation rates over time and I discovered that innovation had been falling, not rising since World War II.

Traditional market-based formulas for innovation in industrial settings predict that greater economic incentives, technological opportunities, and firm capabilities in the latter half of the century should have led to a corresponding rise in innovation rates. Yet the data demonstrate a decline. I began to investigate the developmental history of individual vaccines and I noticed that historically successful vaccine development programs often used a consistent set of integrated research practices.

Thomas Francis Jr. used these top-down, coordinated techniques when he developed the first licensed Influenza vaccines in the 1940s, as did Jonas Salk when he developed the first licensed the first Polio vaccines in the 1950s, and Maurice Hilleman when he developed the Adenovirus, Measles, Mumps, Rubella, Meningococcal Meningitis and Hepatitis B vaccines. They set the agenda and defined problems so that epidemiologists, clinicians, bench scientists, bioprocess engineers, and regulators could all understand the upstream and downstream requirements of their collaborators. These programs, which pre-dated strong intellectual property regimes for biologicals, also facilitated information exchange and technology transfer through personal interactions and collective problem solving.

Why did so many new vaccines derive from military research?

Prior to WWII, soldiers died more often of disease than battle injuries.  War magnifies the spread and severity of disease by causing large-scale social dislocations and by consolidating large populations of physically stressed individuals. Not surprisingly, the military invested in preventative measures.

The Walter Reed Army Institute for Research (WRAIR) became a center of excellence for infectious disease research and vaccine development and instilled an entire generation of vaccine scientists with a unique set of interdisciplinary research skills. WRAIR alumni filled top positions in academia, industry, and government and they often worked together to facilitate the development of many mid-century vaccines.

Why did this system stop working?

By the end of the cold war, funding for vaccine research began to shift from WRAIR to the NIH.  While the NIH excels at early stage discovery, it is not as well suited to the highly collaborative development work required to generate viable vaccine candidates for industry.

Since the 1970s, the time and cost of drug development has increased dramatically, from an average of $199 million and 6 years to market, to 1.5 billion and 13.5 years to market today.

What public opinion would you change?

There are two I would like to change.

First, I would like to change the idea that vaccination is a personal decision. We vaccinate ourselves to create a firewall to protect individuals (the young, the old, the immune-compromised) that cannot be vaccinated safely or effectively. We need to have a stronger sense of community and responsibility to one another when we make vaccination decisions.

Second, I would like to change the idea that antibiotics are a commodity. They are a precious resource that requires careful stewardship.  Any time we use antibiotics in people, plants, farm animals, and materials, we put selective pressure on bacteria in our environment to breed resistance. Large-scale use of antibiotics as a growth promoter in agriculture, for example, is irresponsible and shortsighted. With very few new antimicrobial drugs coming onto the market, I would like to see more stringent regulations on the use of antibiotics and more government support for the R&D of new drugs.

It’s unclear to me who is in charge. Who is going to take on the leadership of having us vaccine ready?

That's a great question. We have to think about incentives. Small biotech companies can't always afford to have the big picture view, and large, publicly held pharmaceutical companies have huge opportunity costs. Leadership will need to come from governments (which have population health and security as their mandate) to structure incentives so that private industry, both large and small biotechs, puts as much effort into the next Yellow Fever vaccine as they did for Viagra or Lipitor.  

Why do you think Boston is the epicenter of the life sciences and biotech industry right now?

Biotech is an exciting industry to be in right now.  Biology will be to the 21st century what physics was to the 20th and the nuclear age. Many of the big problems and their solutions will derive from the life sciences: climate change, overpopulation, food safety, drug resistant bugs, pandemics, emerging infectious diseases, etc. We have new methods of mining data and understanding highly complex systems. I think it's the era of big biology.

Before moving to Lyme, New Hampshire you lived in Boston and studied at MIT and then the Kennedy School. What are some of your favorite places around town?

I loved to run around the river.  I especially loved the Harvard end where the natural beauty of the shoreline is still intact. Leo Marx at MIT used to talk about the magic of liminal spaces – spaces caught between the city and nature- and this has always been one of those spots for me.

How is life in around Dartmouth College?

I love it. I feel like I'm in my natural habitat.

Any favorite haunts to share up north?

There is a secret place with privately groomed trails for cross-country skiing in Lyme and it is downright magical.

Don’t you have the most amazing Co-op on the planet?

The Co-op grocery store is extraordinary because we're very close to the source of food production for cheese, vegetable, and meats. We have extraordinary selection of locally produced, fantastic stuff.

My favorite restaurant up there is called Hen of the Wood in Burlington, Vermont.