A conventionally sourced sea bass from a fishery.
Ever wonder why you've never heard of wild-caught organic fish? It's because there's no way to certify a food that has a mysterious history. Mike Selden, a 26-year-old biochemist with an animal lover's heart and an entrepreneur's mind, decided there must be better way to consume one of our planet's primary sources of animal protein. A way that would eliminate the need to kill billions of fish per year while also producing toxin-free, cheap, delicious fish meat for your dinner table. Enter Finless Foods, a young startup with a bold vision. Selden took time out of chauffeuring fish carcasses around San Francisco (no joke!) to share his journey with LeapsMag.
What is the biggest problem with the way fish is consumed today?
There are a lot of problems ranging from metals to animal welfare to human health. Technology is solving those problems at the same time. You've got extreme over fishing, which is collapsing ocean ecosystems and removing populations of fish that are traditionally used as food sources in developing nations.
In terms of animal welfare, fish are killed in massive numbers, billions a year. Even if people don't care too much about that, we want to give them another option.
In terms of health, which I think for most people is the most convincing argument, current fish have mercury and plastic in them. And if you're getting that fish from a farm, you will also have high levels of antibiotics and growth hormones if you're getting it from outside the U.S. What we're doing is producing fish that doesn't have any of those contaminants.
What gave you the idea to start a company around lab-grown fish?
I studied biochemistry and molecular biology at UMass Amherst, traditionally an agricultural school out in the woods of Massachusetts. I have always been an environmental activist and cared about animals. I thought, animal agriculture is so incredibly inefficient, what could be done to change it?
"The worst way you can possibly make a hamburger is with a cow."
Agriculture is a system of inputs and outputs, the inputs being feed and the outputs being meat – so why are we wasting all of this input on outputs we don't care about? Why are we creating these animals that waste all this energy through sitting around, moving around, having a heartbeat, blinking? All of this uses energy and that's valuable input.
The worst way you can possibly make a hamburger is with a cow. It's an awful transfer of energy: you have to feed it many times its own weight in food that could have fed other people or other things.
In February, I got funding from Indie Bio, a startup accelerator for synthetic biology, and moved out to San Francisco with my co-founder Brian Wyrwas. We started working in our lab in March. We're the newest company in the space.
Walk me through the process of creating edible fish in the lab. Do you have to catch a real live fish first and get their cells?
We have a deal with the Aquarium of the Bay, and whenever a fish dies, they call me, I get in a zip car, drive over, and bring the fish back to the lab, where Brian cultures it up into a cell culture. We do use real, high-quality fish stock. From there, we get the cells going in a bioreactor in a suspension culture, grow them into large quantities, and then bring them out to differentiate them into the cells people want to eat—the muscle and fat tissue. Then we formulate it and bring it to people's tables.
How long does the whole process take from the phone call about the fish dying to the food on the table?
There are two different processes: One is a research process, getting the initial cells and engineering them to be what we're looking for.
The other is a production process – we have a cell line ready and need to grow it out. That timing depends on how big of a facility we have. Since we're working with cell division: If you have 1 cell, in 24 hours, you'll have two cells. Let's say you have 1 ton of cells, in 24 hours you'll have two tons of cells.
"We want to give people the wholesome food they are used to in a healthier setting."
How are you looking to scale this process?
We're trying to find a middle ground between efficiency and local distribution. Organic farming is hilariously bad for the environment and horrifyingly inefficient, but on the other hand, industrial agriculture requires lots of transport, which is also bad for the environment. We're looking to create regionally distributed facilities which don't require a lot of transit, so people can have fresh fish even extremely far inland.
What kinds of fish are you "cooking"?
Our first product will be Bluefin tuna. It's a high-quality fish with high demand and it's also a conservation issue. We also currently have a culture going with Branzino, European sea bass, that we're really happy with.
There's a concept in science called a model organism – one that is extremely well studied and understood. Like the fruit fly, for example. For fish, it's the zebra fish, which is used for genetic research, but no one eats it. It's tiny, so we started by thinking: what fish do people eat that is also close evolutionarily to the zebra fish? We came up with carp, even though it's not too widely eaten.
But our process is very species agnostic. We've done work in trout, salmon, goldfish. Any fish with a dorsal fin works with our process. We tried a wolf eel but it didn't work. Eels are pretty far evolutionarily from fish, so we dropped that one.
From left to right, Ron Shigeta (IndieBio), Brian Wyrwas (Finless Foods), Amy Fleming (The Guardian), and Jihyun Kim (Finless Foods) tasting the first ever clean carp croquettes.
(Courtesy Mike Selden)
Why fish as opposed to, say, a cow?
Scientifically, there are a lot of advantages. Fish have a simpler structure than land animals. A fillet from a cow has complex marbling going on between the fat and muscle. When it's fish, like sashimi, it's in layers of muscle and fat. So it's simpler to build, plus fish are cold-blooded, so because they breathe underwater, our equipment needs less complexity. We don't need a CO2 line and we don't need to culture our cells at 37 degrees Celsius. We culture them at room temperature.
It's also easier to get to market since there's much higher value. Chicken in the last year was $3.84 per pound in America, whereas Bluefin tuna is between $100 and $1200 a pound. Because this is about dropping cost, we can get to market faster and give investors a better value proposition.
What's also cool is that something like Bluefin tuna is something many people haven't had the opportunity to eat. We can get these down in cost until there is price parity with any cheap conventional fish. We want to give people a choice between buying something like albacore tuna in a can –with mercury and plastic– or high-quality tuna without any contaminants for the same price.
Do you shape them like fish fillets to help the consumer overcome whatever discomfort they might feel about eating a bunch of lab-grown cells?
Yeah, people want to continue eating food they are eating, and that's fine. We want to give people a better option. We don't want to give them something weird and out there. We want to give them the wholesome food they are used to in a healthier setting that also solves some environmental issues.
How about the taste? Have you done any blind side-by-side tests with the real thing and your version?
Not blind taste tests. But we have been tasting it, and it is firmly fish. I even tried leaving it outside of the fridge – and man, that tasted like spoiled fish.
We want it to have the exact same properties as real fish. We don't want people to have to learn how to cook with it. We want them to just bring it into their homes and eat it exactly like they were doing before, but better.
What you're growing isn't the whole fish, right? It is not an actual organism?
Right, we're only growing muscle cells. It doesn't know where it is. There is no brain, nervous system, or pain receptors.
Are you the only people in this lab-grown food space working on fish?
We're the only ones doing fish so far. Other companies are doing chicken, duck, egg white, milk, gelatin, leather, and beef.
Are people generally weirded out by sci-fi lab food, or intrigued?
It's been very positive. When people sit down and talk to us, they realize it's not some crazed money grab or some weird Ted talk, it's real activists using real science trying to solve real problems. Sure, there will be some pushback from people who don't understand it, and that's fine.
When can I expect to see Finless Food at my local Whole Foods?
We plan on being in restaurants in two years, and grocery stores in four years.
What about people who aren't big fans of fish in the first place? Like those who don't eat sushi, because consuming something raw with an unknown history isn't very appetizing.
There are too many examples of food poisoning because fish are in a less clean environment than they should be, swimming around in their own fecal matter, and being doused in antibiotics so their diseases don't transmit. It's a bit of a mess. That's why as an industry, we're calling this clean meat. Fish is a healthy thing, or at least it should be, with Omega 3 and 6, and DHA. This is a way for people to continue getting those nutrients without any of the questions of where it came from. For people who are skeptical of fish, we invite you to dive in.
Brian Wyrwas, Co-Founder & CSO, and Mike Selden, Co-Founder & CEO
(Courtesy Mike Selden)
Nine experts break down the biggest biotech and health breakthroughs that didn't get the attention they deserved in 2022.
New drug targets for Alzheimer’s disease
Professor Julie Williams, Director, Dementia Research Institute, Cardiff University
Genetics has changed our view of Alzheimer’s disease in the last five to six years. The beta amyloid hypothesis has dominated Alzheimer’s research for a long time, but there are multiple components to this complex disease, of which getting rid of amyloid plaques is one, but it is not the whole story. In April 2022, Nature published a paper which is the culmination of a decade’s worth of work - groups all over the world working together to identify 75 genes associated with risk of developing Alzheimer’s. This provides us with a roadmap for understanding the disease mechanisms.
For example, it is showing that there is something different about the immune systems of people who develop Alzheimer’s disease. There is something different about the way they process lipids in the brain, and very specific processes of how things travel through cells called endocytosis. When it comes to immunity, it indicates that the complement system is affecting whether synapses, which are the connections between neurons, get eliminated or not. In Alzheimer’s this process is more severe, so patients are losing more synapses, and this is correlated with cognition.
The genetics also implicates very specific tissues like microglia, which are the housekeepers in the brain. One of their functions is to clear away beta amyloid, but they also prune and nibble away at parts of the brain that are indicated to be diseased. If you have these risk genes, it seems that you are likely to prune more tissue, which may be part of the cell death and neurodegeneration that we observe in Alzheimer’s patients.
Genetics is telling us that we need to be looking at multiple causes of this complex disease, and we are doing that now. It is showing us that there are a number of different processes which combine to push patients into a disease state which results in the death of connections between nerve cells. These findings around the complement system and other immune-related mechanisms are very interesting as there are already drugs which are available for other diseases which could be repurposed in clinical trials. So it is really a turning point for us in the Alzheimer’s disease field.
Preventing Pandemics with Organ-Tissue Equivalents
Anthony Atala, Director of the Wake Forest Institute for Regenerative Medicine
COVID-19 has shown us that we need to be better prepared ahead of future pandemics and have systems in place where we can quickly catalogue a new virus and have an idea of which treatment agents would work best against it.
At Wake Forest Institute, our scientists have developed what we call organ-tissue equivalents. These are miniature tissues and organs, created using the same regenerative medicine technologies which we have been using to create tissues for patients. For example, if we are making a miniature liver, we will recreate this structure using the six different cell types you find in the liver, in the right proportions, and then the right extracellular matrix which holds the structure together. You're trying to replicate all the characteristics of the liver, but just in a miniature format.
We can now put these organ-tissue equivalents in a chip-like device, where we can expose them to different types of viral infections, and start to get a realistic idea of how the human body reacts to these viruses. We can use artificial intelligence and machine learning to map the pathways of the body’s response. This will allow us to catalogue known viruses far more effectively, and begin storing information on them.
Powering Deep Brain Stimulators with Breath
Islam Mosa, Co-Founder and CTO of VoltXon
Deep brain stimulation (DBS) devices are becoming increasingly common with 150,000 new devices being implanted every year for people with Parkinson’s disease, but also psychiatric conditions such as treatment-resistant depression and obsessive-compulsive disorders. But one of the biggest limitations is the power source – I call DBS devices energy monsters. While cardiac pacemakers use similar technology, their batteries last seven to ten years, but DBS batteries need changing every two to three years. This is because they are generating between 60-180 pulses per second.
Replacing the batteries requires surgery which costs a lot of money, and with every repeat operation comes a risk of infection, plus there is a lot of anxiety on behalf of the patient that the battery is running out.
My colleagues at the University of Connecticut and I, have developed a new way of charging these devices using the person’s own breathing movements, which would mean that the batteries never need to be changed. As the patient breathes in and out, their chest wall presses on a thin electric generator, which converts that movement into static electricity, charging a supercapacitor. This discharges the electricity required to power the DBS device and send the necessary pulses to the brain.
So far it has only been tested in a simulated pig, using a pig lung connected to a pump, but there are plans now to test it in a real animal, and then progress to clinical trials.
Smartwatches for Disease Detection
Jessilyn Dunn, Assistant Professor in Duke Biomedical Engineering
A group of researchers recently showed that digital biomarkers of infection can reveal when someone is sick, often before they feel sick. The team, which included Duke biomedical engineers, used information from smartwatches to detect Covid-19 cases five to 10 days earlier than diagnostic tests. Smartwatch data included aspects of heart rate, sleep quality and physical activity. Based on this data, we developed an algorithm to decide which people have the most need to take the diagnostic tests. With this approach, the percent of tests that come back positive are about four- to six-times higher, depending on which factors we monitor through the watches.
Our study was one of several showing the value of digital biomarkers, rather than a single blockbuster paper. With so many new ideas and technologies coming out around Covid, it’s hard to be that signal through the noise. More studies are needed, but this line of research is important because, rather than treat everyone as equally likely to have an infectious disease, we can use prior knowledge from smartwatches. With monkeypox, for example, you've got many more people who need to be tested than you have tests available. Information from the smartwatches enables you to improve how you allocate those tests.
Smartwatch data could also be applied to chronic diseases. For viruses, we’re looking for information about anomalies – a big change point in people’s health. For chronic diseases, it’s more like a slow, steady change. Our research lays the groundwork for the signals coming from smartwatches to be useful in a health setting, and now it’s up to us to detect more of these chronic cases. We want to go from the idea that we have this single change point, like a heart attack or stroke, and focus on the part before that, to see if we can detect it.
A Vaccine For RSV
Norbert Pardi, Vaccines Group Lead, Penn Institute for RNA Innovation, University of Pennsylvania
Scientists have long been trying to develop a vaccine for respiratory syncytial virus (RSV), and it looks like Pfizer are closing in on this goal, based on the latest clinical trial data in newborns which they released in November. Pfizer have developed a protein-based vaccine against the F protein of RSV, which they are giving to pregnant women. It turns out that it induces a robust immune response after the administration of a single shot and it seems to be highly protective in newborns. The efficacy was over 80% after 90 days, so it protected very well against severe disease, and even though this dropped a little after six month, it was still pretty high.
I think this has been a very important breakthrough, and very timely at the moment with both COVID-19, influenza and RSV circulating, which just shows the importance of having a vaccine which works well in both the very young and the very old.
The road to an RSV vaccine has also illustrated the importance of teamwork in 21st century vaccine development. You need people with different backgrounds to solve these challenges – microbiologists, immunologists and structural biologists working together to understand how viruses work, and how our immune system induces protective responses against certain viruses. It has been this kind of teamwork which has yielded the findings that targeting the prefusion stabilized form of the F protein in RSV induces much stronger and highly protective immune responses.
Gene therapy shows its potential
Nicole Paulk, Assistant Professor of Gene Therapy at the University of California, San Francisco
The recent US Food and Drug Administration (FDA) approval of Hemgenix, a gene therapy for hemophilia B, is big for a lot of reasons. While hemophilia is absolutely a rare disease, it is astronomically more common than the first two approvals – Luxturna for RPE65-meidated inherited retinal dystrophy and Zolgensma for spinal muscular atrophy - so many more patients will be treated with this. In terms of numbers of patients, we are now starting to creep up into things that are much more common, which is a huge step in terms of our ability to scale the production of an adeno-associated virus (AAV) vector for gene therapy.
Hemophilia is also a really special patient population because this has been the darling indication for AAV gene therapy for the last 20 to 30 years. AAV trafficks to the liver so well, it’s really easy for us to target the tissues that we want. If you look at the numbers, there have been more gene therapy scientists working on hemophilia than any other condition. There have just been thousands and thousands of us working on gene therapy indications for the last 20 or 30 years, so to see the first of these approvals make it, feels really special.
I am sure it is even more special for the patients because now they have a choice – do I want to stay on my recombinant factor drug that I need to take every day for the rest of my life, or right now I could get a one-time infusion of this virus and possibly experience curative levels of expression for the rest of my life. And this is just the first one for hemophilia, there’s going to end up being a dozen gene therapies within the next five years, targeted towards different hemophilias.
Every single approval is momentous for the entire field because it gets investors excited, it gets companies and physicians excited, and that helps speed things up. Right now, it's still a challenge to produce enough for double digit patients. But with more interest comes the experiments and trials that allow us to pick up the knowledge to scale things up, so that we can go after bigger diseases like diabetes, congestive heart failure, cancer, all of these much bigger afflictions.
Treating Thickened Hearts
John Spertus, Professor in Metabolic and Vascular Disease Research, UMKC School of Medicine
Hypertrophic cardiomyopathy (HCM) is a disease that causes your heart muscle to enlarge, and the walls of your heart chambers thicken and reduce in size. Because of this, they cannot hold as much blood and may stiffen, causing some sufferers to experience progressive shortness of breath, fatigue and ultimately heart failure.
So far we have only had very crude ways of treating it, using beta blockers, calcium channel blockers or other medications which cause the heart to beat less strongly. This works for some patients but a lot of time it does not, which means you have to consider removing part of the wall of the heart with surgery.
Earlier this year, a trial of a drug called mavacamten, became the first study to show positive results in treating HCM. What is remarkable about mavacamten is that it is directed at trying to block the overly vigorous contractile proteins in the heart, so it is a highly targeted, focused way of addressing the key problem in these patients. The study demonstrated a really large improvement in patient quality of life where they were on the drug, and when they went off the drug, the quality of life went away.
Some specialists are now hypothesizing that it may work for other cardiovascular diseases where the heart either beats too strongly or it does not relax well enough, but just having a treatment for HCM is a really big deal. For years we have not been very aggressive in identifying and treating these patients because there have not been great treatments available, so this could lead to a new era.
Regenerating Organs
David Andrijevic, Associate Research Scientist in neuroscience at Yale School of Medicine
As soon as the heartbeat stops, a whole chain of biochemical processes resulting from ischemia – the lack of blood flow, oxygen and nutrients – begins to destroy the body’s cells and organs. My colleagues and I at Yale School of Medicine have been investigating whether we can recover organs after prolonged ischemia, with the main goal of expanding the organ donor pool.
Earlier this year we published a paper in which we showed that we could use technology to restore blood circulation, other cellular functions and even heart activity in pigs, one hour after their deaths. This was done using a perfusion technology to substitute heart, lung and kidney function, and deliver an experimental cell protective fluid to these organs which aimed to stop cell death and aid in the recovery.
One of the aims of this technology is that it can be used in future to lengthen the time window for recovering organs for donation after a person has been declared dead, a logistical hurdle which would allow us to substantially increase the donor pool. We might also be able to use this cell protective fluid in studies to see if it can help people who have suffered from strokes and myocardial infarction. In future, if we managed to achieve an adequate brain recovery – and the brain, out of all the organs, is the most susceptible to ischemia – this might also change some paradigms in resuscitation medicine.
Antibody-Drug Conjugates for Cancer
Yosi Shamay, Cancer Nanomedicine and Nanoinformatics researcher at the Technion Israel Institute of Technology
For the past four or five years, antibody-drug conjugates (ADCs) - a cancer drug where you have an antibody conjugated to a toxin - have been used only in patients with specific cancers that display high expression of a target protein, for example HER2-positive breast cancer. But in 2022, there have been clinical trials where ADCs have shown remarkable results in patients with low expression of HER2, which is something we never expected to see.
In July 2022, AstraZeneca published the results of a clinical trial, which showed that an ADC called trastuzumab deruxtecan can offer a very big survival benefit to breast cancer patients with very little expression of HER2, levels so low that they would be borderline undetectable for a pathologist. They got a strong survival signal for patients with very aggressive, metastatic disease.
I think this is very interesting and important because it means that it might pave the way to include more patients in clinical trials looking at ADCs for other cancers, for example lymphoma, colon cancer, lung cancers, even if they have low expression of the protein target. It also holds implications for CAR-T cells - where you genetically engineer a T cell to attack the cancer - because the concept is very similar. If we now know that an ADC can have a survival benefit, even in patients with very low target expression, the same might be true for T cells.
Look back further: Breakthroughs of 2021
https://leaps.org/6-biotech-breakthroughs-of-2021-that-missed-the-attention-they-deserved/
