Is animal testing even needed anymore?
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In the 1930s, the S.E. Massengill Company of Bristol, Tennessee had a problem. They wanted to convert a pill into a liquid, and they wanted to market that liquid as an elixir. Now, the pill was sulfanilamide, an active ingredient that fought streptococcal infections. The liquid would make it easier to ingest. The only problem? It tasted terrible.

So the company added a bunch of stuff to make it more palatable. Things like raspberry extract, saccharin, and another sweet-tasting solvent called diethylene glycol. Now, there's a good chance that you've smelled diethylene glycol before because it's more commonly known as antifreeze.

Well, this elixir went on to kill more than 100 people, including more than 30 children. And that disaster led to a pivotal law passed in this country in 1938, one that has stood unchallenged for more than 80 years until 2022. Mr. President, I rise today to talk about a bill that would lift a mandate in the law dating back to the Great Depression.

So that was Kentucky Senator Republican Rand Paul in September of 2022 testifying in favor of the FDA Modernization Act 2.0. Now, the specific mandate Senator Paul is referencing there is to the 1938 requirement that all new drugs be tested on animals for safety before they move on to clinical trials.

The FDA Modernization Act 2.0 is the first major step that could bring an end to pharmaceutical animal testing. It authorizes FDA to accept alternatives to animal testing that have been developed in the past 50 years, things like computer modeling and stem cell research. It's often said that the definition of insanity is doing the same thing over and over again and expecting a different result.

We've mandated animal testing for the last 84 years, and it meant slower approval for promising drugs and cures. The time has come for the law to finally catch up with the science. President Joe Biden signed the act into law three months later in 2022.

Well, earlier this year, FDA officially announced that it's phasing out animal testing requirements for some therapies and drugs in favor of more effective human-relevant methods, as it says. FDA Commissioner Dr. Martin Makary spoke on The Megyn Kelly Show on April 17th.

So these new technologies have the promise of replacing some of this routine animal testing. You would cut six months out of that approval process. You lower R&D costs for pharma companies and inventors, which could lower drug prices for everyday Americans.

Well, today, we're going to further explore whether animal testing is becoming obsolete in the development of new pharmaceuticals. And if so, how to ensure that technological replacements are as safe or actually even safer in modern-day drug development as that development becomes more personalized and sophisticated.

Well, Dr. Donald Ingber is founder of the Wyss Institute for Biologically Inspired Engineering at Harvard University. He's also founder of Emulate, a company that's a leading manufacturer of what's known as organ-on-a-chip systems.

Dr. Ingber, welcome to On Point. Thank you. It's my pleasure. Okay, first of all, let's talk specifically about what FDA has announced, because I want to get your understanding as to how much of drug development this actually covers, because it's specific to monoclonal antibody therapies. It's actually not specific. It's saying that's where they're going to start. That's where they're going to start. Okay. But they've

Since the Modernization Act 2.0 in December 2022, they have stated that they are open to reviewing investigational new drug applications, which is what pharmaceutical companies submit to get drugs approved, that include data from alternative models, including organs on chips, and

in lieu of animal data. So they've been open for a while, but what this does that's different is that it really is saying they're making it a priority, and also there are incentives there in that they'll give accelerated reviews and try to accelerate the process if applications include

data from these alternative models. And that's a game changer, I think. Okay. So we'll come back to that. But help me understand specifically, what is mono... Again, as the starting point for phasing out animal testing, what are monoclonal antibody therapies? Yeah. So...

Most drugs that we've known since we grew up with are small chemicals. They're very, very tiny. Monoclonal antibodies are engineered antibodies, just like we make antibodies to fight off infections. But scientists have developed ways to engineer them so they could target specific antibodies.

molecules on cells that, you know, for example, a pathogen or something that's involved in mediating inflammation, let's say an inflammatory bowel disease. They are larger and they have different types of toxicities and some are so specific for human targets that they

they can't cross-react with animals. So they have to use non-human primates. And even sometimes non-human primates don't work for these highly specific therapies. And other therapies that you hear about, like CRISPR gene therapies, those are very human-specific as well. Okay. So...

FDA has announced that AI-based computational models are under consideration, organoid toxicity models and testing. So we'll talk about all of that. But again, for background purposes, I mean, obviously animal testing on things like cosmetics has not been required for a long time, right? That's why we see on shampoo bottles and things not tested on animals. Right.

But tell me a little bit more about currently what's sort of the typical process. When does animal testing come into the process of developing a new drug? Well, I mean, if you start in the beginning, you know, most research that leads to drug development is funded by the federal government, right? You know, NIH, FDA funds work, DARPA, ARPA-H, things like that.

Those studies are largely mouse-based because people have developed ways to engineer mice so that they look a little bit more like human diseases. And so that's the early stage. But the drug companies...

To bring a drug for FDA approval, you usually have to test for toxicities in two different species, often rats and dogs. That's why you see pictures of beagles. For some reason, beagles were used a lot in the past. And then some monoclonal antibodies often have to go to non-human primates.

because of that targeting specificity. Right. So it sounds like at multiple key points in the development of new therapies, I mean, animals, as the process is practiced thus far, our animal testing is still essential. Oh, it's a central part of the whole business of science and medical science and drug development. But let me say, FDA is primarily focused on toxicity. Drug companies also are looking for

efficacy, new target discovery, and that is largely animal-based as well. It has been in the past. And this is a big place where human alternatives are, I think, going to be enormously valuable and are beginning to be enormously valuable. That is an important distinction. Okay, so FDA is looking like, will it hurt you? Will it make you sick? Yeah, safety. But

But what doesn't actually work is a whole different... They're obviously interested in that. But that is really what the clinical trials are going to demonstrate. And there has to be demonstration animal models before that. But before they ever go to the FDA, these drug companies have spent...

15 years, you know, 10, 15 years, hundreds of millions. And a lot of that involves animal work as well. Okay. So let's talk now. We're going to spend the rest of the hour now talking about what these new technologies are that could make animal testing in pharmaceutical development obsolete. I mentioned the phrase organ on a chip. What is that?

So organs on chips, which we started developing, you know, 15, 20 years ago at this point, are small devices. They're the size of a thumb drive or a computer memory stick or an old –

School eraser, if you're old enough to remember those. You can put them in, you know, hold them between two fingers. They're optically clear. They're made out of a flexible rubber-like material. But what we do is originally we call them chips because we use computer microchip manufacturing techniques to make them because you have control over

over features at the same nanometer to micrometer, you know, incredibly small size that living cells and tissues live at. So we make hollow channels less than a millimeter wide. We have two parallel to each other. You could think of them as, you know, two tunnels you drive cars through. One goes one way, one goes the other. But we have holes in the wall between them.

So we could put different tissue types on either side. So in one channel, let's say the first chip, we put the lining cells of your lung air sac with air over them. And on the channel below, we put your capillary blood vessel cells.

with medium or even we could even flow blood through them for short times as well. So it's replicating the space where air from your lungs gets transferred into the blood. Exactly. And this is basically what makes, we called it organ on a chip, not a cell or tissue, because an organ are two or more tissues that come together, new functions emerge automatically.

Almost always you have to have a blood vessel because you need oxygen, nutrients, etc. The other trick is that we develop ways to mechanically, cyclically stretch these tissues so we mimic breathing in the lung as well. Now, we use the same chip with intestine and we put intestinal lining cells, like say your colon on one side and your blood vessel cells or your connective tissue cells, and we mimic peristaltic motions. In the kidney, we can mimic...

the way the kidney glomerulus, where you have blood filtration into urine, every heartbeat stretches with the pulse of the blood, and we mimic that on this. And because we mimic the chemical environment, the physical environment, and these 3D tissue-tissue structures or interfaces,

We get recapitulation of the function or physiology of your organs and disease states at a level really never seen before. And it's all human. This is what answers a question that I had about the process because, you know, in my mind I thought, okay, well, if it's just like cells, that's not the same thing as the function of an entire organ. But you're mimicking the function here.

So we're mimicking the structure. The structure and function at a microscopic level. And we have a window on...

the molecular activities in these cells while they're in this tissue organ context, because it's optically clear, we could look under the microscope. We could collect the outflows so we could take samples of the blood vessel channel just like a doctor takes blood sample out of your vein, and we could use that to discover new biomarkers of disease or new clinical biomarkers of drug response. We could collect the outflow of the intestinal lumen channel, and we have biomarkers for stool samples. I see.

We also can grow microbiome, which has been like one of the major changes since I went to med school, paradigm shift, that, you know, we didn't learn about, but it's a major part of health. We can grow complex human microbiome, literally gut microbiome, in an intestine chip for extended time and see how it affects the host and vice versa. Dr. Donald Ingber, hang on for just a second. We're going to talk a lot more about alternatives to animal testing in a moment. This is On Point.

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Dr. Ingber, you were describing to me what the organ on a chip system is. A little bit later, we're going to hear about something else called an organoid. That's another new technology here. What are organoids? It's another great technology. And I think one thing that's great about the FDA's announcement is that they're combining, they're exploring many different technologies. Organoids are little balls of cells that you form by collecting cells

a biopsy from an adult where you get stem cells. These are the cells that replenish your tissues. Like, your intestine turns over every three days. So there's cells in there that can keep forming all the specialized cells of your organs. And so they would take a biopsy from a patient, for example. You collect these stem cells. You grow them in a jello-like material, and they grow into a ball. And if it's an intestinal cell, they'll begin to form structures that look like your intestinal villi.

But these are more, I call them tissue-oids in general because it's one tissue type. They don't have the blood vessels. They don't have the immune cells. They don't have the connective tissue. You also can make them by using a technique called induced pluripotent stem cells, IPS, which basically is take a cell from your blood, a cell from your skin connective tissue, and

throw in a few genes and chemicals, and you make an embryonic stem cell-like cell that can form almost any tissue type in your body. And so people are using that, for example, for brain. And there you get many different types of brain cells, which is quite interesting. And if you go long enough, they begin to form interesting multicellular structures. But again, they lack...

The difference about organs on chips is that we now take, we actually use organoids as a source of cells. We grow them in the gel, but then we break them up, put them on one channel, and we interface them with the other tissue types that they see in the body. And we could have flow and air and peristalsis and breathing. And what's important about that is, one, we can mimic the

The way drugs actually change their levels over time in the body is called pharmacokinetics. But, you know, your doctor will prescribe a drug once a day or three times a day or you go to the hospital, you get a continuous infusion. That's because the same drug at a totally different dose or timing will give you different results. Different results. Toxics. I mean, aspirin can kill you, obviously. Right. So we can mimic precision.

Precisely, the dose changes over time because we have flow. And is the idea that ultimately, because you talked about taking samples from a patient, that you would even find out specifically the response that that patient, specific patient would have? Absolutely. We just published a paper with a collaborator at McGill, a surgeon, Lorenzo Ferry, and he had patients with esophageal cancer.

cancer and they get resistant to therapy and basically you don't know which therapy to try next. He's made these chips with their cells and he flows in the drugs, the various ones that he's choosing between at doses they would see in the patient through the channel that's analogous to the blood vessel channel, the way they would see it, not just giving it to cells in a dish.

And you actually can determine what drugs to give the patients. They used organoids actually as a comparison. And because of this ability to mimic changes in drug exposure profiles, the chips were more effective than the organoids. However, they used both in combination because organoids are actually a higher throughput. You could do studies often faster with many at a time.

So each one of these has power. And the organoids are very effective at modeling the cellular level response. Yes. The organ zone chips kind of get you that higher level complexity. So we see them as...

partners in this whole thing. Okay, so let's listen to Nicole Klein-Stroyers, the acting director for program coordination at NIH. And she spoke with On Point and told us NIH is going to focus on increasing funding.

I can't believe I just said that in these times, but NIH will focus, that's what they say. I'll believe it when I see it. On increasing funding and public awareness around alternatives to animal testing. And here's what she said. You know, we have no intention of just phasing out animal studies overnight. We know that animal studies are still very important now.

and often scientifically justified. There are lots of areas where validated human relevant models are not yet available, but we are seeing rapid progress. And the more we invest in this space, the better those human biology based integrated systems will become.

And the less we will have to rely on animal models moving forward. So, again, that's Nicole Klein-Stroyer, acting deputy director for program coordination, planning and strategic initiatives at NIH. Dr. Ingber, when she says there are lots of areas where validated human relevant models are not yet available, tell me more about that. Well, that's an important point because.

For the FDA, for example, they use the term qualify. And that means you have to show that one of these alternative systems replicates the normal function of an organ.

as well as can be as good or better than an animal model at predicting the response to drugs. You have to prove it. Yeah, exactly. So, for example, Emulate, the company that you mentioned I founded, is the farthest along in going through a program that FDA has called iStand, which if it gets through that successfully, the FDA will sort of certify it so that any company can use that model to replace, in this case,

a liver toxicity model, okay? But that required Emulate to test 870 chips

Created with cells from three different human donors. And there's four different cell types to create this organ level structure in these chips. They tested 27 different drugs. So which we already knew the results in rats and dogs and humans. Of which many of these drugs were wrong. Because most times these animal models are wrong. Right. And...

And we could show that this liver chip was about seven to eight times more effective at predicting the results in humans than the animals. Now, that has been in the iStand program. The first letter of intent was in the spring of 2022, and it's still going. Okay. So one thing is how quickly this will be done, but the other is every chip you have to get –

you'd have to go, or organoid model, or computer model, would have to go that sort of qualification. And this is where the real challenge lies. So it's not going to happen overnight. Yeah, but it makes a lot of sense though, right? Because if you don't validate these things, then it's just like, well, just another fancy toy. You want it to actually predict what's going to happen in humans, like you said, better than animal testing. It's perfectly reasonable, but it has to be accelerated in terms of the pace. Okay. Let's talk about

Let me ask you one thing, because you talked about the original tissue for the organ on a chip or even organoids that's coming from humans. It's human tissue. Now, in this day and age, anytime I hear that, it's hard not to imagine that politics can creep in because, you know, for example, you said stem cells. And we know that, you know, politics around abortion have oftentimes sort of entered the space when it comes to stem cell research.

You talked about patient original samples. Where are the other human tissue samples coming from? None of these are embryonic cells. And these are usually coming from cadavers where people have agreed to donate their tissues and companies sell them. Or surgical, a biopsy for...

Basically, they're looking to see if you have ulcerative colitis, but they take a sample, turns out to be normal, and the patient has volunteered that it can be used. The induced pluripotent stem cells are, again, from patients who have volunteered to donor. So none of this is embryonic. Okay.

So let's go into a lab now, because earlier this week, On Point producer Will Wacke visited Dr. Jenny Tam, director of the Wyss Institute's Synthetic Biology Platform in Boston, Massachusetts. So this is our stem cell culture room. We're very clean in here. We don't want to get our stem cell cultures contaminated with anything, so we put our lab coats on and our gloves on to keep everything clean.

Dr. Tam's research includes screening drug treatments for bipolar disorder. And to do so, her lab uses organoids that we talked about a little earlier. So a layperson's way of describing them might be small, tiny balls of stem cells. And at the lab, Dr. Tam obviously uses freezers to keep the cells at just the right temperature and robots to pipette small amounts of fluid onto the organoids.

There's like 96 wells in that plate and you can see all these plates that need changing. They need to be fed. So if you kind of think of your child, you have like in each well as a child, you need to feed all 26. What are you feeding them with?

So this is media, so they're just nutrients that helps your cell growth to grow. But there's a specific cocktail that's specific to these stem cell cultures. It usually takes months, Dr. Tam says, but once the organoid grows, it can mimic even different parts of the brain. And I was curious about this. The final product does not just look like a miniature brain.

So you might say, "How can you tell me what you're showing me is real?" So this is an instrument called a microelectrode array device. So there's like a little square with like lots of like 26, over 26,000 individual electrodes. They put the, place the organoids on top of each area of the microelectrode array and those electrodes are so tiny

that they can interact with different parts of the region of a single neuron. And so you can measure that neural activity across the cell and how that neuron interacts with other neurons inside that organome.

So this is important because you only know for sure what you can measure. And in Tam's lab, they can compare drugs introduced to organoids grown from the stem cells of patients that have been diagnosed with bipolar disorder, and they compare those to those grown from a control group. So we introduce the drugs in the media over a specific time point, and we have done that, and we have tested...

both lithium, which is a standard drug that's often used for treatment in bipolar, and really exciting, we discovered a new drug that has not been used in bipolar using our platform. And so we have tested that drug on our organoids as well, and so we saw that the drug was

normalize that neural activity back to someone who has not had bipolar. Dr. Tam has photos and videos of other types of organoids, like livers, kidneys, and even beating hearts, which she showed to our producer.

And Tam says she got interested in bipolar research specifically because the disorder is so hard to treat. You heard her mention lithium there earlier, a very commonly used but far from perfect therapy. Bipolar affects 40 to 60 million people worldwide. And on average, it can take as much as eight years to even diagnose. And then when you look at the cross section of...

is not diagnosed correctly, I mean, it's just mind-boggling and heartbreaking. And that we can't get treatments to people quickly is terrible. I think it's a derelict of duty in some ways. Tam also currently works with some lab animals, and she says overall they're ineffective for bipolar disorder research.

So for mood disorders, it's hard to give a survey to a mouse to ask if you're feeling very depressed that day or you're feeling hyper excited that day.

So we do, oh, like behavioral models. So we measure how fast, like a mouse will be spinning on a wheel. We'll measure like how much they'll move in inside of a cage. And then we, there are associated genes that are related to bipolar. This, again, this is just a specific example.

behavioral model and then we'll knock out certain genes. Knocking that out means removing those certain genes that have been implicated in genetic studies towards bipolar. So we'll knock out those genes and say what is that effect? As we just discussed, there's multiple genes associated with bipolar disorder. So looking at one gene is not enough.

It shows that it's one aspect, but it's a very slow way of doing that. Dr. Tam is hopeful that organoids can be a more useful test or systems for drug development because they, again, use human cells, even as she acknowledges the technology's current limitations. So as we kind of create different brain regions, we would like to merge these different brain regions into more complex systems

model systems. I mean, right now that is an advantage that the mice have over, you know, some of these in vitro models because they have the complete organ system. But we're still working on those advances.

So that's Dr. Jenny Tam, director of the Wyss Institute's Synthetic Biology Platform in Boston, Massachusetts. Dr. Ingber, in fact, a little bit earlier you talked about sort of what organoids do well and what organs on a chip do well, and you called them complementary. Listening to Dr. Tam's examples there from bipolar disorder research, it makes a lot of sense. But what do you think are still the major areas of advancement, research,

to make these technologies as effective as possible in drug development? Like what do they still not do that you'd like them to do? So first I have to say, because I collaborate with Jenny, my team and the team she works with in George Church at the Wyss Institute, is that it's a great example where AI actually complements organoids as well as we've done this on organ chips.

and that we've used AI-based computational approach to come up with the drugs that they're finding actually have activity in those organoids. And the other thing is that in the organoids, they can visualize organoids

Thousands of gene changes at once because you have this whole multicellular structure where in the mouse they have to like knock out one at a time. And you can see these drugs actually, for example, these bipolar patients have problems with circadian rhythm and sleeping at night, for example. You could see these organoids light up, the brain cells light up activity in cyclical ways, normal, healthy, normal.

brain organoids, but not in the bipolar, and you could kind of try to reverse that with drugs. So you can do levels of complex functionality and responses in these systems that's hard to do in mice. But let me ask you, when we talk about toxicity, though, again, like, again, if the organoids or the organ on a chip is sort of really focused on one organ,

physiological system. What if there's a toxicity response in another organ system? Right. So, first off, you know, early on, I was funded by DARPA to create a human body on chips. Okay? So, we were funded to create 10 different organs, which we did, to link them together by their blood vessel

channels fluidically, meaning transfer fluid to the other and keep them alive and then for a month using an automated instrument. We did that. That was the beginning of Emulate effectively. But it's very hard to do because you have to get them all running one at a time. But

You can actually do that, transfer fluids from one to the other to look at toxicities across the whole body. Okay. Dr. Donald Ingber, hang on for just a second. When we come back, we're going to hear from another person in the world of biomedical research about why they think animal testing is still essential to drug development. So we'll hear that in just a moment. This is On Point. On Point.

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We wanted to speak with someone who still believes that there is a place for animal testing when it comes to pharmaceuticals. And for that, we spoke with someone at Charles River Laboratories. It's a pharma company.

Based here in Boston as well, they had some $4 billion in revenue last year. Birgit Gierschik is the company's chief operating officer, and she told us that animal breeding and testing is a major part of Charles River's business. It's a core function of our company, supported by many different in vitro technologies, mostly to assure patient safety.

but also to provide early insights into a molecule and its suitability to become a drug product.

Not that FDA's announcement did not have an impact on Charles River Laboratories. The company's stock tumbled almost 30 percent the day after FDA's announcement. But Gierschik says she actually welcomed the news. It's a great signal to the world, to society, but also to us in the industry. Because she sees FDA's announcement as validating work Charles River Laboratories is already doing.

Because in the world of animal testing, Gierschik tells us that researchers abide by three R's to reduce animal use in the name of science. Replacing animals when there are good alternatives, like organ on a chip. Reducing the numbers of animals necessary for an experiment. And refining studies when animals are absolutely needed for testing.

So in some parts of their lab, Gierschik says the number of lab animals has actually dropped by 50% over the past decade using those guidelines. So we are currently...

doing roughly $200 million of revenue using these technologies, so organoids, organ-on-chip, in silico, in all different areas. And they're used as part of the drug development continuum. They're used side-by-side with animal studies. And we believe that over time, more and more hybrid studies will be run. Okay, and that's exactly why she thinks...

that animal testing won't come to a complete end yet because, as we've discussed before, there are hurdles, such as modeling very complex systems and responses to a drug on an entire body. The safety profile of many molecules are still not known. So there's a high risk that once this molecule, once this drug enters a body,

and this would be the human body, you don't know what happens. So you don't know if it's accumulating in the thyroid. And if you don't have a platform that can replicate a human body, which would be all 78 organs of a human body, you don't know what other side effects it could have.

Girshik says the future for now is hybrid models, primary studies using organoids or organ on a chip, also AI, as we talked about earlier, but then coupled with smaller animal studies that could get new drugs to clinical trial faster and ideally cheaper, but not jeopardizing patients.

A living body is not like anything else in the world. It's not a machine. It's not a computer. It's reacting depending what, if you had enough sleep or not, if you're taking out a drug, how it's interacting. There's so many variables that you need to consider. And that's why so many drugs are failing, right? Because it's...

If it would be easy, we would all do it. And we would all do it today. So that's Birgit Gierschik, chief operating officer at Charles River Laboratories. So, Dr. Ingber, a few minutes ago, you did acknowledge that it's really hard to model an entire human body, which is what Gierschik is saying there. I mean, so what do you think about this idea of sort of hybrid testing regimes? Yeah.

I think that's exactly what's happening now and needs to happen right now. And we're not going to get rid of animal studies right away. I mean, there's things like, you know, cognitive disorders and schizophrenia and things like that. It's just very hard to model some of these things in vitro. But you can hear from Jenny Tam that you could start...

approaching some things that you'd never think possible before. I think... But Dr. Tam also said you can't do a mood survey on a mouse. Exactly, right. I also want to mention that, you know, yes, the whole human body is important, but AI can help with a lot of this because we know a lot of results. There are examples where drugs were totally toxic in animals and they weren't toxic in humans. We always worry about how many good drugs we lost because of that. There's...

Often failures in clinical trials because of comorbidities, meaning like a patient has three other disease processes. They're not healthy mice. We can model that in chips. For example, when we take a lung chip with cells from a patient that has chronic obstructive pulmonary disease, COPD.

They're 10 times more sensitive to viral infection on chip, just like they are in real life. So you could be testing for drugs and picking up complexities that come from other disease processes, which you can't really do in animals. I think the answer is it's going to be these three R's, like progressively replacing, reducing, refining. Yeah.

The FDA will only approve a replacement for a specific context of use. So, for example, the liver chip that we're moving along to get approved for to replace drug-induced liver injury is only with small molecule drugs, and it's only for liver injury. Now, the speaker was right at Charles River that when you do—

when you're testing for liver toxicity in animals, the same time you're testing in all the other organs. So they're going to still be doing those animal studies, but the reality is that very, very frequently they get completely different results in dogs and rats and human cells in vitro, and they don't know what to do, and they kind of wing it, and that's why there's lots of failures, okay? So...

The context of use would be to use this human liver chip, particularly in those situations, to say, do we go, no go? And these are huge, expensive decisions for these companies. Okay. So many more questions. We're running out of time here, so I'm going to go as rapidly as I can, Dr. Ingber. You mentioned expense. Now, Marty Makary at FDA and the NIH person that we heard earlier, everyone's talking about that ideally these new technologies could actually –

well, could potentially make drug development cheaper, which then those cost savings would ideally be passed on to patients in this country. But what I'm also hearing at the same time is development of very, very sophisticated new technologies. And those technologies have to be getting patented. Right.

Right? And so those patents, so then you'd be licensing those technologies to the mercs of the world. I actually see the potential for things becoming more expensive. Well, I'll give you two quick examples. One, the Liver Chip paper had an economic analysis that basically estimated that the pharmaceutical industry would save $2 to $3 billion a year by preventing late-stage failures just from that one test.

And if you did that for all the organs, it would be like $27 billion a year. The second example is that the company Moderna that developed the COVID vaccine, and they've presented this publicly, so I think I can say this. They've allowed us to use these slides. They have been using in-house the liver chip technology.

human liver chip instead of non-human primates because they... to select which lipid nanoparticles, the delivery vehicle for vaccines and their mRNA drugs, which ones could be toxic, which ones could be safe. They were using non-human primates. Non-human primates are incredibly expensive, like $50,000, $60,000 an animal besides the ethical issues. Right. They basically can do the same amount of tests in about one-tenth the time and one-tenth the cost. I see. Okay, so I...

And the chips are very expensive in the early stages because it's a young field, but they will decrease in cost due to economies of scale over time. I think there will be a major savings. Animal studies are expensive, very expensive. And then you also, of course, mentioned the ethics, which are underlying of

All issues for animal testing. But you quickly went over a point. I just want to emphasize this, that the idea is if there are a few with these new technologies, there could potentially be fewer failures, as you've called them, or late stage, which are huge costs. So drugs that end up going through the whole process, but not getting approved or not working, which are most most drugs fail. So by reducing that number, that should have a cost savings overall.

I think the biggest game changer, okay, right now big companies will spend, you know, hundreds of millions on the drug development, tens of millions in a big clinical trial, almost always fail. And then they go back and see, is there a genetic subpopulation, very similar, that responded better? And they'll do a small trial, get approved for a narrow application. You could flip it on the head with stem cells, patient-derived cells, organoids, organs on chips,

Select a small group of patients that are very similar. Test the drugs for efficacy. Test for toxicity. Use them for a small trial. Faster, cheaper, more likely to succeed. It would be a total game changer, I think. It would be a game changer for the companies. I will let...

reality settle in to see whether those companies actually pass the savings on to patients, right? I mean, like, I'm not going to ask you to answer that question. Do you want to answer that question? Because I think... That's beyond our knowledge base. Yeah. So I always listen skeptically to lawmakers when they're like, it will make it cheaper for patients. But if one company does it,

They will all do it. And if one company does it and starts charging less, that may push things down. That would be the hope. Okay. Well, if any CEOs listening to this, I invite you to be the first company that does that. Okay. We've got about five minutes left, Dr. Ng, where we could talk about the details and the technical details of organ on a chip, AI, et cetera, for hours. Sure.

But, I mean, come on. You and I are having this conversation, like saying, hooray FDA for finally announcing that they'll accept these alternative testing models at the same time that FDA, NIH are being gutted by the Trump administration, that funding for research, period, is being wiped off the board, right?

I mean, it's impossible to talk about this in only rosy terms when that is the other reality of, I mean, labs like yours, labs like Dr. Tam's. So talk to me about the impact that these politics and the funding cuts are having on this very area of research. Well, I mean—

I'm at Harvard. So, you know, I got two of the first stop work orders and they both were on organ chip related work. But more importantly, the government's cutting funding across the entire nation. NIH, NSF, every university is getting hit. So we have... And then there's a proposed 40% cut in the next budget. So everything's going to slow. But more importantly, we're losing our young people. And they...

We've basically lost a generation, I think, already of scientists in America because it's too much uncertainty. And most of them are foreign students with visas because we attract the best and brightest who usually stay here, build companies, build the economy. And remember, the economy is driven by technologies and science drives technology. So I think this is going to have a huge negative impact on the economy overall.

But in this area, it's going to be hard. They're supporting this sort of work and alternatives. But whether you're going to see funding there, I just don't know. I want to hear this again. You received two stop work orders for organ on a chip related research. Absolutely. What was that research? One of them was from BARDA, and it was using chips to make models of human lung, intestine,

bone marrow and lymph node and to look at the effects of gamma radiation to model radiation injury. And then we're using AI and various sophisticated chemical screens and genetic screens to develop countermeasure drugs that can protect you from radiation. For example, in the case of a nuclear disaster or war and so forth, you know, a nuclear war. And

And also for the other one was, came from NASA, and we were basically developing chips with cells from the Artemis II astronauts who were going to the moon. And these chips were going to go up there alongside them to look at the effects of both microgravity and radiation, because you're not going to get to Mars unless you have countermeasures against radiation. And the idea was that you're only about four astronauts on a mission, but if we can prove that this worked, you could do many chips together.

on these missions and begin to develop countermeasure drugs. So there's no work happening on those two right now? No, those have stopped completely, yeah. Now, you know, the Trump administration says, well, the Harvard-specific cessation of funding is to combat anti-Semitism. Was your research anti-Semitic? Well, I'm Jewish, and God, no. I mean, you know, and the Wyss Institute is sort of a separate 501c3. We're in Boston. We're nowhere near it. And also the anti-Semitism

Semitic issues, events that happened were in 2023 in the fall. And the university leadership has changed based on that. They've made amends. They've made new policies. Is it perfect? No. But there's actually a legal process where a government can go and try to ask for specific changes. This is pure. I said in another interview, it's pure punitive lunacy. It's just, it's retribution for something that we don't know what, why they're taking it out on science and

At a time where international competitiveness with places like China depends on science, I do not know. It does feel to me that we're handing American primacy on the development of these life-changing technologies to China. I was in China in the fall, and they are putting something like a half a billion dollars into an institute bringing the best and brightest from all over the country to one site to develop human organ technology.

emulation systems, basically. I think it's human organ physiological emulations. Hope was what it was called. So no, absolutely. They're moving full force and we're giving it to them on a silver platter. So on the one hand, we have...

Right.

But on the other hand, they're cutting off that research at the knees. Well, you know, we're eating the seed corn of science, right? I mean, maybe for the next few years, the drug companies will start using these. But the pipeline of the future, the better models, models that have, you know, bells and whistles that we need, like different types of sensors and real-time analysis and AI integrated, that's going to slow down.

Well, Dr. Donald Ingber, founding director of the Wyss Institute for Biologically Inspired Engineering at Harvard University and also founder of Emulate. It's a leading manufacturer of organ on a chip systems. By the way, we also did reach out to FDA directly for comment or if someone from FDA could join us. They did not respond to our request in time for comment.

the broadcast of this episode. But Dr. Donald Ingberg, it's been a great pleasure to have you. Thank you so much. Oh, my pleasure. Thank you. I'm Meghna Chakrabarty. This is On Point.

Support for this podcast comes from Is Business Broken? A podcast from BU Questrom School of Business. How should companies balance short-term pressures with long-term interests? In the relentless pursuit of profits in the present, are we sacrificing the future? These are questions posed at a recent panel hosted by BU Questrom School of Business. The full conversation is available on the Is Business Broken podcast. Listen on for a preview.

Just in your mind, what is short-termism? If there's a picture in the dictionary, what's the picture? I'll start with one ugly one. When I was still doing activism as global head of activism and defense, so banker defending corporations, I worked with Toshiba in Japan. And those guys had five different activists, each one of which had a very different idea of what they should do right now, like short-term.

Very different perspectives. And unfortunately, under pressure from the shareholders, the company had to go through two different rounds of breaking itself up, selling itself and going for shareholder votes. I mean, that company was effectively broken because the leadership had to yield under the pressure of shareholders who couldn't even agree on what's needed in the short term. So to me, that is when this behavioral problem, you're under pressure and you can't think long term, becomes a real problem.

real disaster. Tony, you didn't have a board like that. I mean, the obvious ones, I mean, you look at, there's quarterly earnings. We all know that you have businesses that will do everything they can to make a quarterly earning, right? And then we'll get into analysts and what causes that. I'm not even going to go there. But there's also, there's a lot of pressure on businesses to, if you've got a portfolio of businesses, sell off an element of that portfolio. And as a manager, you say, wait, this is a really good business. Might be down this year, might be, but it's a great business.

Another one is R&D spending. You can cut your R&D spend if you want to, and you can make your numbers for a year or two, but we all know where that's going to lead a company. And you can see those decisions every day, and you can see businesses that don't make that sacrifice. And I think in the long term, they win.

Andy, I'm going to turn to you. Maybe you want to give an example of people complaining about short-termism that you think isn't. I don't really believe it exists. I mean, you know, again, I don't really even understand what it is. But what I hear is we take some stories and then we impose on them this idea that had they behaved differently, thought about the long term, they would have behaved differently. That's not really science.

Find the full episode by searching for Is Business Broken wherever you get your podcasts and learn more about the Mehrotra Institute for Business, Markets and Society at ibms.bu.edu.