To receive this monthly update from the a16z Bio Team, sign up for our bio newsletter here.
What’s next in In Dx/Rx/Px: CRISPR’s First Published Human Proof Point
Andy TranA new clinical study this month demonstrated a CRISPR milestone in the safety of genome editing in humans. Scientists at Peking University attempted to generate an HIV “cure” through CRISPR-based genome editing, by knocking out the CCR5 gene from donor stem cells before they infusing them back into the patient. The study design was actually inspired by a two HIV-positive patients that were cured, after receiving stem cell transplants from people born with a variation of the CCR5 gene that makes them resistant to HIV.
Although in the end the treatment didn’t cure the patient’s HIV infection, the CRISPR-edited cell treatment was shown to be safe, provoking no immune response in the patient. There also seemed to be no off-target effects, i.e. random mutations that can occur during CRISPR’s double-stranded break cutting mechanism. In short, this study was among the first to allay some of the most common concerns and potentially dangerous side effects for the human application of CRISPR-based gene therapy. So seeing these validated data points is very promising for the prospect of eventually ensuring gene editing will be safe in humans—and that we will have many more such therapies coming. As renowned immuno-oncology physician-scientist Carl June wrote about the study, “the genie is out of the bottle with genome editing.”
Care Delivery: Food as Medicine
Julie YooThere is an increasing recognition of the importance of services around “social determinants of health”—like access to transportation, food security, and other forms of social support. Factors like these have such a large relationship to our overall health status they may actually contribute more than classic clinical factors like medical care, drugs, and procedures.
Food insecurity, in particular, is a very real issue for too many Americans: in 2017, the USDA estimated as many as 1 in 8 Americans were food insecure, including more than 12 million children. Greater and greater numbers of seniors are also food insecure; government funding for nutrition programs that would benefit seniors has fallen dramatically in recent decades. This can result in a domino effect of negative impacts to healthcare outcomes and costs. A vicious cycle ensues: seniors get sick, long hospital stays cause them to lose their food benefits, they get discharged into the home without sufficient nourishment, and end up back in the hospital. This is a very literal illustration of the concept of “food as medicine”—when sick patients don’t get food, they deteriorate; on the other hand, a steady supply of nourishment can keep a patient well. In short, as the data in the figure below show, the less we spend on food, the more we spend on healthcare.
Which means there is huge opportunity for innovation in this area, with a whole range of approaches, from tele-nutritionist services bundled into more comprehensive senior care-at-home programs; to the incorporation of medically-informed meals packaged with medications and delivered into seniors’ homes in last mile pharmacy delivery services; to innovation in food production itself (imagine a “3D printer for meals” in the home of every chronic disease patient). As Judy and Ridhima note below, the engineering methods to make this futuristic vision a reality are at a tipping point. Add to that reimbursement dollars and provider attention flowing into this space, and we believe a whole category of companies can and will be built to address this important, unmet need in the market.
Bio as a Platform: Scaling Up for the Flexitarian
When it comes to ideas about nutrition, protein has taken center stage over the last few decades as the central component in every meal. But in the American diet a major source of that protein is animal meat—which raises concerns about health, ethics, and sustainability. As we talked about in our last newsletter, meat eaters now have a real alternative with the advent of engineered protein products that either mimic animal proteins or “grow” them from cells. This is giving rise to the “flexitarian”: people who eat meat, but attempt to reduce their meat consumption. Tl;dr, meat eaters—not just vegetarians and vegans—are driving a lot of consumer demand for these products. 98% of people who purchased plant-based meat also bought regular meat.
At the Good Food Institute conference we attended this month, large food companies like Kroger, Morningstar, Perdue, Tyson and others talked a lot about how to address the rising number of these “flexitarians”—even through potential blended products that combine both plant-based protein plus animal meat. While the nutritional properties and taste of these plant-based and “cultured meat” products are key, their success or failure often depends on the company’s ability to scale production behind the scenes.
For plant-based meat, companies like Beyond and Impossible initially struggled to put together a supply chain that could meet volume of demand. For “cultured” meat, the scaling challenges are very technical: the costs of materials fed to the cells (“growth media”); scaffolding for them to grow on; equipment required for manufacturing—all of these are currently too difficult or too expensive to support large-scale commercialization of the product. There are people trying to address different pieces of this puzzle—Dr. Yuguo Lei, for example, shared his research in creating an edible, dissolvable biopolymer to use as a scaffold for growing stem cells; Dr. Amy Rowat talked about her lab’s research on the mechanical properties of cell growth in production environments; other teams at the conference discussed more efforts to decrease costs of critical components of the process. But there is an enormous opportunity for more researchers to enter this field and propose new designs for scale-up manufacturing (we want to hear about those!).
There’s no question that the future, and potential market, of flexitarianism is booming. But single technical advances around the proteins themselves aren’t enough to make this a reality for consumers everywhere. Companies will have to innovate in all aspects of scaling up, and tackle the distribution problem head on. If new product launches continue to be successful, in the long term they will spawn a whole new ecosystem of suppliers and contract manufacturers in the food industry—but in the short term, companies will have to build out these pieces for themselves.