A lot of time, money and research go into the medicines that people take every day — much more than one might think. Whether it is a simple pain reliever or a drug targeted at treating a specific disease, an incredible amount of work goes into that medicine before it gets to market.
Take something as common as ibuprofen. Listed as an essential medicine by the World Health Organization, ibuprofen is considered one of the safest and most effective medicines in a health system. Still, it took more than eight years to get ibuprofen approved for human use.
This is common in the pharmaceutical industry, and some drugs can take much longer to develop and approve. While the drug development pipeline varies greatly, it follows four stages: discovery and screening, lab testing, animal studies, and human clinical trials.
Each stage can take between three and six years, and approval for wider use can take an additional year or two. So, it is possible that a single drug could take up to 20 years to get through the pipeline.
Given the need to improve and streamline drug development, researchers at Los Alamos National Laboratory are working on a technology that could do just that; they are creating an artificial heart that has the same biological content and structure as a human heart, and replicates beat rate and the blood flow. It could one day be used to test new drugs safely and efficiently. (Link to video: https://youtu.be/xlK00ITbMOA)
For a number of reasons, most drugs never make it to market. Most fail before they get to animal trials, but many fail in human clinical trials because they are not safe or effective. While human trials try to represent a globally diverse population, unexpected side effects can still emerge when a drug is marketed around the world.
In 2018, a record high of 59 new drugs were approved for use in people. However, with a failure rate of 90 percent in human clinical trials and an average cost of $35.1 million per trial, companies lost $18.6 billion in 2018 trying to get new drugs to market. However, even after this approval process there is still the risk that once a drug finally makes it to market, it could still fail if it causes unforeseen side effects.
The artificial heart can greatly improve this process. It uses real heart cells called cardiomyocytes that are created from a new biotechnology called induced pluripotent stem cells. These are cells taken from an adult (a skin cell for example) and genetically reprogrammed in the lab into a new specific cell type like a cardiomyocyte. When enough of the heart cells are put together in a structure that mimics the human heart, they begin to beat.
With technology like this, researchers can identify negative side effects on the heart in early drug development and increase drug safety and efficacy by getting predictive feedback before having to test in humans. This artificial heart can also represent a globally diverse population by giving researchers the opportunity to virtually test a drug on any demographic they choose, helping to eliminate unexpected side effects and even eventually removing the need for animal testing.
Animal studies raise ethical concerns and are not always representative, as animals can be so genetically different from humans. Right now, the Los Alamos team is working to prove that drug testing on the artificial heart is just as predictive or even better than animal studies. The artificial heart also has the potential to improve personalized medicine — treatments tailored to an individual person.
A good example is how doctors currently treat cancer; they do a profile of genes in the cancer, and from that profile determine the specific chemotherapy drugs that will work really well or identify others that may not work. The artificial heart could work in a similar fashion, helping doctors identify the best treatment for a heart condition proactively, instead of trying out different drug cocktails and seeing what eventually works.
The artificial heart has the potential to transform the way researchers create new medicines. This innovative technology could one day speed up the drug development pipeline, help us create better medicine and ultimately, save lives.
(Research into the artificial heart began at Los Alamos in 2013 with the ATHENA project, which worked to develop an artificial lung, liver, and heart.)
Kent Coombs is a bioengineer in the Biosecurity and Public Health group at Los Alamos National Laboratory working with the Host and Pathogen Biology team developing artificial organ technology. Coombs’ work is funded by the Laboratory’s Entrepreneurial Postdoctoral Fellowship and the Defense Threat Reduction Agency.