National Institutes of Health's Rosemary Hunziker: Could Silk Eliminate the Cold Chain?

Could an NIH funded study that looks at stabilising vaccines and antibiotics with silk spell the end for the vaccine 'cold chain' and pave the way for the development of enhanced delivery and storage in the third world?

In this interview Rosemarie Hunziker, Ph.D. Director of Tissue Engineering and Regenerative Medicine at the National Institute of Biomedical Imaging and Bioengineering (NIBIB) within the National Institutes of Health (NIH) in the US Department of Health and Human Services (DHHS), shares her insights on the recent findings with Andrea Charles from Cold Chain IQ, and addresses how we can improve success rates in innovative drug research.

Cold Chain IQ: Please could you briefly outline of your role and responsibilities at the National Institutes of Health?

R Hunziker: The NIH, as we call it, is a very, very large place. We have a budget of over $30 billion a year to allocate and our major role is to fund the cutting edge research that will generate ultimately the next generation of medical advancement and breakthroughs for therapies to keep us all healthy and to help us deal with disease and injury.

The NIH is divided into 27 different parts and each of us has a narrower area of responsibility than the whole spectrum of public health and so the part of the NIH that I’m involved in, which is the National Institute of Biomedical Imaging and Bioengineering is largely concerned with the cutting edge technology in the area of imaging modalities and also in the area of novel approaches to solving problems largely with engineering ways of looking at problems and also with biomaterials and medical device development.

Cold Chain IQ: The NIH funded Dr. David Kaplan's research behind the stabilisation of vaccines and antibiotics in silk. Please could you briefly explain the study and what was the rationale behind this?

R Hunziker: We have been funding Dr. David Kaplan, who is the principal investigator on this project for many years and he has been interested in the quite unique and robust and very interesting properties of the silk protein for probably a couple of decades now.

I suspect that the main reason he got interested in this research to begin with was because anyone who’s taken the time to look at silk, either as the major element of a cocoon that a silkworm spins or as part of a spider web has seen that it’s very strong and very flexible but it’s also very easy to work with.

It’s easy to manufacture from the glands of the animal and also to produce in great quantities. And so we started studying the biological and chemical properties of this and one of the things that he’s been able to do is look at the three-dimensional structure at a molecular level and it turns out that this particular protein, which is called fibrillin, this silk protein, is structured very interestingly in that parts of the molecule are stacked up one on top of each other – we call it a beta pleated sheet structure, so it’s sort of stacked up in layers – and other parts of the protein are more globular, they look like big cotton balls.

And so he was able to look at the chemistry of this molecule in that way and realised that it was entirely possible that it would be a wonderful agent for helping to stabilise other proteins and the reason for that would be that parts of the proteins would be attracted to interact with the globular parts of the silk protein which was where all the water in the environment of the molecule was placed and once those proteins found themselves in that vicinity, they could probably tuck themselves into the beta pleated sheet part of the protein and that way they would be in an environment where there was very little water and there was a lot of stability and so this is, I think, the rationale behind the research.

So, he tried to do a few experiments to see if he could indeed stabilise other proteins and it worked. I think it worked fantastically well. So, the whole issue of why one has to find other ways to stabilise proteins is that proteins are incredibly reactive molecules. Everybody who’s ever been to the grocery store knows this because you know that when you come home with your groceries and you empty your bag there are some things you just put on your counter and you save them for later, put them away when you want to. There are other things like milk and cheese and meat that you have to put into the refrigerator right away. And the major reason for that is because the bulk of what makes up these foods are proteins and because they’re so fragile and so susceptible to the action of water and also whatever bacteria might be around, they spoil very easily.

And so that’s the issue with the vaccines and antibiotics that Kaplan and his team have stabilised with silk. The issue is that there are lots and lots of proteins and so in the same way that all of your groceries are susceptible to the spoiling, they are too. So, when you make a pharmaceutical or a product in this case, an antibiotic or a vaccine, part of what you have to do is to keep that preparation in the cold pretty much all the time because otherwise it will degrade and it will lose its power and its potency. So, what they’ve been able to do is to create a formulation where once they mix these elements with silk, then the preparation is very stable at room temperature or even at higher temperatures, so you don’t need to refrigerate it any more.

That’s an incredible cost savings, because if you think about, for example, delivery of vaccines to the third world, once you ship them from your plant, they have to stay under refrigeration the whole time, until they get to the place where they’re going to be used and that’s an incredibly expensive process and it also leads to a lot of waste because if something stays outside of the cold for very long, for more than a few hours, it’s not good anymore, so you can’t use it.

Cold Chain IQ: This research could potentially help people in the developing world. How do you think healthcare delivery could benefit directly from this research?

R Hunziker: It’s pretty clear, I think, that if you don’t have to have so much emphasis on keeping the items cold, that’s hard enough. That’s difficult enough in the United States or in Europe or in the developed world, because we have things that could go to airports and sit on shipping docks, and so, we have to worry about keeping things cold during that process. That’s difficult enough, where there’s essentially unlimited access to the kinds of power that we would need to keep these things fresh and viable. But in the third world, where the access to electricity could be limited, this would really be a problem because, as we know, even when there are large shipments of food to countries where people are starving, if the food isn’t kept preserved properly, it rots and the same thing would happen to these products. If they weren’t stored properly, they would not be good anymore.

If you had a product that was stable, basically at room temperature, ambient temperature and even at hot temperatures indefinitely, you could just pack it up in boxes and ship it in ships and it wouldn’t have to go by special conveyances or special airplanes. It would just get there in its own time and so the cost of these things would be radically reduced and maybe much more affordable. In addition they would be much more available because they would have a shelf life that would be much longer.

Cold Chain IQ: And what potential impact do you think that Dr. Kaplan’s team of research will have on the biopharmaceutical community?

R Hunziker: The impact of this would be in that largely the cost of manufacturing these products would go way down because we wouldn’t have the need for the refrigeration during their processing and during their fabrication. But also the same things would apply. They would last longer, they would be stored longer, so the cost and also the effectiveness would be better because of the ability to store them at ambient or room temperatures.

Now, that said, one would have to do a little bit of research also to make sure that the preparation was as robust for each individual molecule of protein that we wanted to store in this way. You couldn’t just assume that because it worked perfectly for the antibiotics that we used in this paper that it would just be the same process across the board. You would have to test it individually. So, initially there might be a little bit more time and expense in trying to make sure that the results were transferable across all different preparations but once that was accomplished, then the cost would go down radically. Cold Chain IQ: How do you think we can improve success rates in innovative drug research? Interesting question. Since I’m at the National Institute of Health, I’m probably going to be biased towards the fact that we could always do with more research. More basic and applied research is always the answer to innovation because we all pay for the scientists who pursue their informed and bright new ideas and for example in this particular case, Dr. Kaplan’s team, when they first started studying silk, did not set out to solve the problem of stabilisation of proteins. They were investigating silk for a number of different reasons because they knew it had interesting biological properties and that it would be able to be used for many different things.

As they found out more and more about the properties that are protein, they were able to realise that it would have the potential to stabilise other molecules as they have now put it to use but that wasn’t obvious at the beginning. The more of the novel and interesting research that we can fund, the more better ideas we will have about how to solve our important medical problems. So, that’s essentially the perspective that I take on it, I think, further down the line in the drug development process would probably have a different answer.

Interview conducted by Andrea Charles. The research was led by grantees of NIH's National Institute of Biomedical Imaging and Bioengineering (NIBIB), David Kaplan, Ph.D., and Jeney Zhang, Ph.D. candidate, at Tufts University School of Engineering in Medford, Mass. The National Eye Institute and the National Institute of Dental and Craniofacial Research at NIH also contributed to this research. The researchers reported on their findings in the online issue of Proceedings of the National Academy of Sciences on July 9, 2012. Stabilization of vaccines and antibiotics in silk and eliminating the cold chain : http://www.pnas.org/content/early/2012/06/29/1206210109.abstract

Have a question about this research? Rich Ellinger, Principal, Temperature Assurance Group, puts your questions Dr. David Kaplan http://www.coldchainiq.com/supply-chain-security/columns/nih-funded-silk-study-questions/