Why is Cancer So Hard to Cure?

Dustin Grinnell (00:00:00 --> 00:02:20)
I'm Dustin Grinnell, and this is Curiously.

Cancer. It's hard to find anyone who hasn't been touched by its cruel grasp, whether through personal experience or through the stories of others. Its impact is undeniable. From the gripping narratives of Ken Burns' documentary, The Emperor of All Maladies, to the heartbreaking journey chronicled in the book When Breath Becomes Air, cancer's shadow looms large, leaving behind a trail of pain and loss. No one is immune.

Cancer doesn't care if you're a scientist, a businessman, an artist, or a politician. It can strike without warning, affecting the young and the old alike. We've all felt the fear, the frustration, and the anger that comes with its presence. We yearn for a cure, for an end to the suffering it causes. But despite our best efforts, cancer continues to evade us.

It challenges our treatments, it defies our understanding, and it can leave us feeling powerless in its wake. Yet amidst the darkness, there's a glimmer of Despite the setbacks and losses, scientists persist in their quest to unravel cancer's mysteries. And it's in this pursuit that we find resilience, determination, and incremental progress. Today on the podcast, I'm talking with cancer researcher, Dr. Susanna Kakishova. Together, we confront the reality of cancer, exploring the science, the stories, and the ongoing battle against one of the greatest adversaries of our time.

Dr. Kakishova has a scientific background in virology, molecular biology, cancer research, and genetic engineering, and she's currently a group leader at the Institute of Organic Chemistry and Biochemistry in Prague, Czech Republic. Previously, she worked as a postdoctoral fellow in cancer research in the laboratory of Dr. Robert Weinberg at the Whitehead Institute of Biomedical Research. Dr. Zuzana Ketkošova's lab is dedicated to discovering and understanding new ways our cells naturally fight cancer. By studying tissues and cell types that are rarely affected by tumors, she and her lab aims to learn from their advances against cancer, and to one day, in the hopefully not-so-distant future, use this knowledge to develop better therapies. So join us as we delve into the complexities of cancer biology in the quest for life-saving breakthroughs.

Dustin Grinnell (00:02:23 --> 00:03:09)
I wanted to talk about cancer at a very high level. This is a topic that many of us know much about, uh, personally. We also see it in movies and in the media. We read about it. Cancer is one of humanity's one of the greatest plagues, I think, and it strikes fear in the hearts of many of us. And I think one of the reasons why I wanted to talk with you is because of your background, but also just to go back to the basics on cancer, you know, like what is it, what causes it, why is it so evasive to effective treatments, and how does your work play into understanding the basic biology of cancer? So I was wondering if you could briefly kind of give a background on how you got into your field and what it is you do.

Dr. Susanna Kakishova (00:03:10 --> 00:05:36)
So right now I'm a junior group leader at Institute of Organic Chemistry and Biochemistry in Prague. And I work in cancer research. So my project started during my postdoctoral stay at Massachusetts Institute of Technology. And what I was very interested about in cancer is the fact that When I started working in cancer research, and I was fascinated by the fact that cancer is actually not one disease, cancer is actually over 200 different diseases that have different causes and different progressions. And cancer can arise from almost any organ or any cell type.

So I started to be interested, are there actually any cell types or tissues in human body where cancers do not arise? Because many of us heard that this and this person was diagnosed with bone cancer or breast cancer or lung cancer. But I don't think we ever heard that this and this person was diagnosed with heart cancer or skeletal muscle cancer, cartilage cancer. There are actually certain types of cancers that are nonexistent or very rare. And I started to be really interested in— because this points to the possibility that actually these tissues or these cell types already found a way how to fight cancer.

And we just have to research it and look into it and find out how these tissues and cell types are doing it. And once we find it out, then let's just copy it. Let's just try to mimic what they are doing, do exactly the same thing, and let's just— that can help us with therapies against cancer. So I started looking into these cancer-resistant tissues, as I call them. And this led to me identifying some potential proteins that might actually really kill cancer cells if they are expressed in cancer cells.

And these proteins are called tumor suppressors.. And in my lab now in Prague, I'm actually researching this topic. And one of the proteins that I found is called Lactamase B-like. And this protein— so in my lab we are researching, we found the mechanism of action, and we are trying to reactivate this protein in cancer cells. And reactivating this protein then leads to the therapeutic effects of these compounds that can reactivate it.

Dustin Grinnell (00:05:37 --> 00:05:56)
So before we get back to your specific research and the questions you're trying to ask, I was wondering if we could just kind of zoom way out and put cancer as a disease in perspective. What are the general statistics that we should be aware of in terms of incidence, death rates, things like that?

Dr. Susanna Kakishova (00:05:56 --> 00:08:12)
Despite considerable efforts in the last decades to find a cure, cancer-related death remains one of the leading causes of death worldwide. It is actually a second leading cause of death after cardiovascular diseases. Approximately 10 million people die each year from cancer. There are many different types of cancers and some of them are very frequent, for example lung, breast, colon, rectum, prostate, or skin are frequent cancers, while some are quite rare, for example, stromal tumours or pancreatic neuroendocrine tumours. Also, the incidence of cancer has been steadily increasing over the years due to factors such as aging population or changes in lifestyle behaviours, for example, smoking, stress, poor diet, lack of exercise, and so on.

And also, Improved detection methods. Of course, now we have pretty good detection methods, so we are— we can detect more cancers. However, over the years, I mean, cancer researchers and cancer field really evolved. So nowadays we are happy that some cancers are actually well treatable. You know, the prognosis is very good.

For example, one of the best treatable cancers are thyroid cancer or testicular cancer. Some types of skin cancers, prostate cancer, cervical cancer, and some types of breast cancers. Then of course, unfortunately, there are those types of cancers that are notoriously difficult to treat. For example, pancreatic cancer is a classic example, or there are some brain cancers. Then there are some types of skin cancers and liver cancer, hepatocellular carcinoma.

Dustin Grinnell (00:08:12 --> 00:08:28)
From like a basic biological perspective, what is cancer? Like at a fundamental level, if you are sitting in front of a clinician and they say you have a certain type of cancer, what's going on? What's actually happening?

Dr. Susanna Kakishova (00:08:28 --> 00:09:48)
The tissues don't know how to do their function anymore. And cancer can develop in almost any organ and tissue in the body and can affect people of all ages. So it's not anymore a disease of old people. And there are more than 200 different types of cancer. So you have to take this into account.

So sometimes I hear that people are saying, oh, there are like so many cancer researchers working on it for so many years, how come you didn't come up with a cure? Cure yet. And this is a little bit unfair because people need to realize that it's not one disease. It's not like corona, which was one virus, or HIV, which is one virus. This is over 200 different types of diseases that are caused by different mutations and different mistakes in the cells and have different progression, and they require different types of treatments.

Dustin Grinnell (00:09:48 --> 00:09:59)
And what differentiates one type of cancer from another? So pancreatic versus brain cancer, why would you develop brain versus pancreatic?

Dr. Susanna Kakishova (00:09:59 --> 00:10:47)
Individual cancers start through dysregulation of different pathways. You know, different genes get affected. So for example, I don't know, colon cancers are caused by mutations or inactivations of APC gene. APC gene normally controls how often a cell divides or how it attaches to other cells, how stable is the chromosome. And so on. So in a colon cancer, this gene gets dysregulated, or some other genes might get dysregulated in colon cancer, like KRAS or NRAS genes. So, for example, in brain cancer, it's different types of genes that get mutated or dysregulated. And brain cancer has mutations, for example, in EGFR or PTEN or p53. So they differ, the different types of cancer differ by different mutations in different genes which start different processes.

Dustin Grinnell (00:10:47 --> 00:10:59)
And the mutation is driven by what? It's a mistake, a mistake in the just natural processes of biology, or is it caused by outside forces or both?

Dr. Susanna Kakishova (00:10:59 --> 00:11:34)
Both, actually. Cancer can have either genetic background, yeah, so you get born with some inherited mutations and genetic mistakes, or the mistakes can be introduced through external forces, yeah, UV radiation, tobacco, or it can get introduced through viral infections and other pathogen infections. There are many viruses are known to cause cancer, or unhealthy lifestyles, as we know, the stress and unhealthy diet and so on. So all of this can lead to dysregulation in replication of your DNA and introduction of mistakes.

Dustin Grinnell (00:11:34 --> 00:11:48)
Are you able to, at a very high level, just make the link between, say, like UV light and then uncontrolled cell growth, or stress in your life in uncontrolled cell growth? Like, what is that mechanism?

Dr. Susanna Kakishova (00:11:48 --> 00:12:03)
So the UV light, there is actually a direct mechanism because UV light can really directly modify DNA and cause breaks in DNA. Yeah. And if these breaks are not correctly repaired, then you get mutations in the genes.

Dustin Grinnell (00:12:03 --> 00:12:08)
But they, would you say often they are repaired? So you're getting these breaks all the time?

Dr. Susanna Kakishova (00:12:08 --> 00:12:38)
Yeah. Under normal circumstances, our cells have a fantastic and very finely tuned machinery how to repair damages to our DNA. And it works beautifully. However, here and there it can happen that there was so much damage or that the cell is not functioning properly and it does not repair the mistake. And then these mistakes accumulate. These mistakes can lead to activation and overt activation of certain genes that then drive the cell into proliferation, into dividing itself too fast, and then these mistakes accumulate.

Dustin Grinnell (00:12:38 --> 00:12:48)
What is so nefarious about cells out of control? Why does that overwhelm systems? Why isn't that snuffed out?

Dr. Susanna Kakishova (00:12:48 --> 00:13:13)
Well, if cells divide too fast, then they stop obeying the rules. They take too much, let's say, nutrients. They don't allow healthy cells to have enough nutrients. You know, they start spreading in the body and then they start disrupting the normal functioning of the tissues because they don't do their function anymore. So the liver cells are not doing the function associated with liver and, you know, they're just out of control.

Dustin Grinnell (00:13:13 --> 00:13:23)
Yeah, like the liver, for example, cancer cells will kind of just crowd out the functioning of healthy cells. They'll vacuum up things that healthy cells need, and then they just compromise the organ.

Dr. Susanna Kakishova (00:13:23 --> 00:13:31)
Yes, definitely. Yeah. So the organ, the liver itself, will not be able to function anymore. They also give the wrong signals to the healthy cells of what to do, the surrounding cells.

Dustin Grinnell (00:13:31 --> 00:13:37)
What do they say to the healthy ones? Like, give me all you got, kind of?

Dr. Susanna Kakishova (00:13:37 --> 00:13:45)
Yeah, they're just, give me all you got. "don't do what you're supposed to do" and, you know, "change your pathways to this and that" and so on.

Dustin Grinnell (00:13:45 --> 00:13:58)
And that quote-unquote communication is done by chemicals, yes? Molecules. Give me one example of, like, maybe, like, in the liver or somewhere else where cancer cell is talking to a healthy cell. How does it talk?

Dr. Susanna Kakishova (00:13:58 --> 00:14:34)
Yeah, so for example, I will give you an example from breast cancer because that's what I am. So breast cancer is definitely, like, one of the causes of breast cancer is an overt activation of hormone receptors. Hormone receptors, which under normal circumstances, they should only react to hormones. When the body is producing hormones, they react through growing. But even then, when they are growing, they're still obeying some rules. Yeah, they don't grow too much. But in cancer, these kind of receptors are not listening to any inhibitory stimuli. So they are on all the time. So then you can't really stop them.

Dustin Grinnell (00:14:34 --> 00:14:57)
Things go wrong in the body all the time, right? It's a try to maintain balance, homeostasis. You have to— things go awry, and in nature, our biology, we've evolved to bring them back into focus. Like, why did this particular malady— why did the mechanism of uncontrolled cell growth and the hoarding of resources in the body— why did this one evade nature's, like, defenses?

Dr. Susanna Kakishova (00:14:57 --> 00:15:37)
Yeah, because it's your own body. The cells that usually fight all the pathogens, viruses, and bacteria, they don't recognize it as a foreign body. It's our own cells. So immune system doesn't see it. It sees it as a healthy, normal functioning cell. So it's difficult for them to see it, that it went wrong. And under normal circumstances in human body, when a cell is faulty, the cell can recognize that it's faulty and it starts a process of suicide called apoptosis. It kills itself because it knows it's faulty. However, this process is is inhibited in cancer cells. They don't do it. They know they are faulty, but they are not killing themselves.

Dustin Grinnell (00:15:37 --> 00:15:55)
So they really— you know, a cancer cell is incredibly clever. So it's deactivated its suicide mechanism. It's figured out how to grow and crowd out healthy cells. Like, how did it get so intelligent? How did it get so diabolical in a way?

Dr. Susanna Kakishova (00:15:55 --> 00:16:22)
Yeah. Well, they are not really intelligent. There's just so many of them, you know, billions of cells in a tumor that are just evolving lots of different directions. And there's always a subset of them that will find a way how to do something different than the rest of them. And then that can give it an advantage to grow even more. Or as I say, to leave the site of the tumor and start metastasizing in different tissues, which might have even better characteristics for it to grow more.

Dustin Grinnell (00:16:22 --> 00:16:39)
I don't know why this popped into my head, but I almost see them as like zombies. Like if you think of a zombie movie, a zombie in and of itself, one of them isn't really that difficult to you can run circles around it, you can throw rocks at it, you can defeat it quite easily. But it's the hordes that get you.

Dr. Susanna Kakishova (00:16:39 --> 00:17:36)
And as it evolves, it's just a continuation and enlargement of this mistake. When pathogens invade a body, like viruses or bacteria, they want to procreate, they want to spread from human to human. And that's kind of understandable. Yeah, they're just trying to survive. However, cancer cells don't have anything like this in mind.

They kill the host, and with killing the host, they die themselves. The cancer cells, they don't want anything. It's just a nasty blob. Of your own cells, which are on a self-destruct path. And ultimately and unfortunately, they take the rest of the body with them.

Dustin Grinnell (00:17:36 --> 00:17:42)
So why would that be evolutionarily useful? I guess it is just truly a mistake.

Dustin Grinnell (00:17:42 --> 00:17:42)
Yeah.

Dustin Grinnell (00:17:42 --> 00:18:12)
Because you think about viruses, you think about highly virulent viruses like Ebola, they'll just burn through a body and be highly virulent. And I think the reason is because the human body will start bleeding and that'll just make for a highly contagious virus. And so it'll spread. So that's the trade-off versus something that's not very virulent, which won't compromise the host. But cancer, like you said, is on a self-destructive mission. To fulfill its potential, it will kill the host, which seems like not very—

Dr. Susanna Kakishova (00:18:12 --> 00:18:59)
Yeah, that's why I'm saying it's a mistake. You know, like, don't try to find anything logical behind it. It's a mistake that is unfortunately a byproduct of a great complexity of living systems. You know, they have lots of different cells that really need to coordinate and cooperate for the body and the living systems to live. And of course, with certain bad influences, this coordination is out of balance. And then this is what happens. And as I said, unfortunately, immune system doesn't recognize it as a bad thing because immune system in our bodies is very good at recognizing foreign objects, something that they are not used to that comes into the body, and then they can fight it very efficiently. But they don't have this ability to fight their own cells, or not to such an extent.

Dustin Grinnell (00:18:59 --> 00:19:15)
So immune cells just swim by it, but the cell itself understands there's a problem and tries to blow itself up, but it's been overridden. Yes. Is cancer natural? You said it's like a byproduct of a complex civilization. Would you say that it's natural?

Dr. Susanna Kakishova (00:19:15 --> 00:19:17)
Like it's— Yeah, I would say it's natural. You would expect it? Yes.

Dustin Grinnell (00:19:18 --> 00:19:19)
Yeah.

Dustin Grinnell (00:19:19 --> 00:19:19)
Yes.

Dustin Grinnell (00:19:19 --> 00:19:23)
And is this just a part of a complex organism?

Dr. Susanna Kakishova (00:19:23 --> 00:19:29)
Yes, it is. And cancer, it's not only a human problem. I mean, lots of other animals have cancer also.

Dustin Grinnell (00:19:29 --> 00:19:31)
Give me an example of that.

Dr. Susanna Kakishova (00:19:31 --> 00:19:48)
Well, dogs, cats. I mean, there are common cancers there. Of course, as I say, we humans are more prone to cancers. We live much longer. We have, you know, usually faster metabolism, and we have some bad habits that accelerate this process. Right. Stress.

Dustin Grinnell (00:19:48 --> 00:19:50)
Yeah, one of them.

Dustin Grinnell (00:19:50 --> 00:19:50)
Food.

Dustin Grinnell (00:19:50 --> 00:20:24)
Sitting out in the sun for extended periods of time. So after cancer becomes symptomatic, or you get a diagnosis, it becomes clear to medical practitioners that there's a problem here, and now it needs to be treated. So what is, like, the brief history of humans trying to manage cancer? Like, how do we treat it? How have we tried to treat it? And then we can talk about how cancer has just become really good at evading those treatments.

Dr. Susanna Kakishova (00:20:24 --> 00:21:23)
Yeah, take it out, cut it out, you know, remove it as soon as possible. Then, however, you can almost never completely cut out a tumor. Some cells are already disseminated, they are already part of the microenvironment around it, or they already metastasized. So then with the progress of medical research and molecular biology and therapeutics, then the chemotherapy started. Yeah.

So which was targeting the remaining cancer cells in the body. And then it was radiation therapy. And now it's targeted therapy, which means that you know already what's wrong in that cancer cells and you're targeting specifically that pathway. Now, in recent years, of course, it's immunotherapy where you are educating your immune cells that this is a bad cell and destroy it. Once you educate it, then the immune cells knows, ah, this is what I need to destroy.

Dustin Grinnell (00:21:23 --> 00:21:47)
And it seems like though everything we try is effective sometimes, ineffective other times, different for every person. Like you said, you cut it out, but there's some left over, or it's spread somewhere else. Chemotherapy may not get it all. Like, why is cancer so wily? You know, how did it get so good at it?

Dr. Susanna Kakishova (00:21:47 --> 00:22:30)
Yeah, so you usually really have to do combination of therapies. Because cancer cells are heterogeneous. So it means they are not completely identical. Many of them have different genetic backgrounds, they have different responses to drugs because they are not completely identical. Also, when the cancer cells metastasize into the new tissue, it again acquires different characteristics. So it might not be reachable by some targeted therapy that is working in the primary tumor, but it's not working on metastasis. So all of these things you have to take into account. And it's That's why the combination therapy works pretty well, because it's targeting different things at once. Okay.

Dustin Grinnell (00:22:30 --> 00:22:35)
Let's go back to your work as a researcher. Like, why this field for you? How did you get into it?

Dr. Susanna Kakishova (00:22:35 --> 00:23:54)
By training, I'm not a cancer biologist. I'm actually a virologist. I did my master's degree and PhD in virology, where I worked on HIV virus and mouse polyoma virus. And as— when I was finishing my PhD, I wanted to try something different. Also, HIV field was enormously competitive.

There was thousands of researchers working on one virus that has 9 genes. So you really were always pressed. Whatever you discovered, it was immediately had to be published. And it was just very stressful and very competitive. And you didn't have the scientific luxury to think too much about it and too deep about it because you had to be fast.

So sometimes I missed some connections which which could have led to some nice discoveries. So I wanted to step back a little and go to the field where I can still find my own niche and where I can take time to really go deeper into the mechanism and find things out. And this was, at that point, it was definitely cancer because it's a much, much bigger field. As I say, there are over 200 different types of cancers. So you can still find your own niche and you can really research lots of things that are super interesting.

Dustin Grinnell (00:23:54 --> 00:24:04)
Yeah. And then so how did you come upon this really intriguing observation that some tissues don't get cancer? When did that say, "I want to study that"?

Dr. Susanna Kakishova (00:24:04 --> 00:26:47)
And when I was switching from virology to cancer research, the very first thing I had to do was to read about cancer research. So I read "The Biology of Cancer," a very famous book by Robert Weinberg. Which is like 1,600 pages. And I've read this book just to get into the cancer research. And I really— it just popped up in my mind that it seems that the whole field of cancer research is orienting itself in researching mechanisms of why cancers evolve in certain tissues, which is of course understandable.

You wanted to know how cancers can evolve and what goes wrong in those tissues and so on. However, what I really missed was. And what I found extremely important to know is the other side of the coin. Why cancers do not form in some tissues. Because as I said, I mean, knowing this, how they do it, they probably already discovered a way how to do it.

Let's look into it, let's research it, and let's learn from it, you know, and then use it for our benefit. So I started looking into statistics, like which cancers are just not there or are very rare. And then yes, there are indeed cancers like that. And then I made it my project. It was my side project, actually, during my postdoc.

And it evolved into a beautiful story that is now leading— thanks to this story now, I characterized several proteins. One of them is called Lact-B that might be a very good tumor suppressor, which means that if I will express it in cancer cells, it kills cancer cells. And I continued this research in my lab where now I characterized 4 additional tumor suppressors from these cancer-resistant tissues.. And now my lab is really working hard on actually translational aspect of this work. So now we found chemical compounds that can reactivate these tumor suppressors in cancer cells.

They can awaken them in cancer cells. And through awakening them, then these proteins start to kill cancer cells. So it has a therapeutic effect. So my lab now has a very strong translational angle, also basic research where we are studying these tumor suppressors, these proteins that can kill cancer cells, but also where we are finding compounds. And we already did lots of in vitro, 2D and 3D experiments, in vivo experiments, mouse experiments.

Dustin Grinnell (00:26:47 --> 00:27:19)
And you did a study on Lact-B protein, and I understand under certain circumstances they killed cancer cells, right? And one of the things that I'm really interested in as more on the kind of artistic, emotional side of talking with people is what did that feel like versus what was the findings. I want to know, like, what was the moment of discovery for you? And what was it like to know something about nature that maybe no one had seen yet?

Dr. Susanna Kakishova (00:27:19 --> 00:28:28)
Yeah, so I actually remember this when we were receiving the first results, and it was fantastic because we were testing several of the genes that are expressed in cancer-resistant tissues, and we were testing them whether they can function as tumor suppressors, whether when I express it in cancer, tissues, whether they can kill cancer. And then we were doing these experiments in mice, just small numbers of mice. And then I remember the veterinarians calling me, like, there is one cohort of mice where we have the Lact-B gene and the tumors just disappeared within 2 weeks of inducing. And we were, you know, very happy about it. But then that was just a preliminary experiment. So we had to repeat it. So we repeated it on a bigger number of mice.. And I remember the moment when the person called me again and she said, oh my gosh, they are disappearing again. And it was fantastic. And I even kept the animal cards, yeah, just where they were measuring the size of the tumors, how it was going down and down and down. And initially we were even thinking like whether we didn't swap the mice because they had big tumors and then 2 weeks later they had zero tumors, but they were the correct mice.

Dustin Grinnell (00:28:28 --> 00:28:35)
So, but I still kept the cards and I actually have them In my lab. What does that mean to you?

Dr. Susanna Kakishova (00:28:36 --> 00:29:03)
It means tangible evidence of a good scientific question. Yeah, because the experiments that we did is that we formed human tumors in mice of breast, so human breast tumors. And then when they were a certain size, when they were big enough to detect and to feel and to see, then at this point we induced, we started expressing Lact-B in them. And then this led to a serious shrinkage or disappearance of the tumors.

Dustin Grinnell (00:29:03 --> 00:29:12)
So mechanistically, is what happened the tumor— you fooled the tumor into thinking that it was among the types of tissues that doesn't grow cancer?

Dr. Susanna Kakishova (00:29:12 --> 00:30:00)
No, no, no, no. What it was is that in those cancer-resistant tissues, this gene Lact-B is responsible for differentiating those tissues. Differentiation is a process where you force the cell to obey lots of rules. And one of the rules it needs to obey, it can't divide, or it really has to have lots of positive stimuli to divide. It can't grow without lots of stimuli. So by expressing this protein in cancer cells, you force these rules upon cancer cells, and the cancer cell stops dividing. However, cancer cells, they don't just stop dividing. They're already so messed up that they either divide or die. So by stopping them to divide, you usually also kill them.

Dustin Grinnell (00:30:00 --> 00:30:25)
Interesting. So I think a lot of people would say you saw the reduction in tumors in mice and it's like, that's it, right? That's a cure. Like, why aren't we— why isn't that a medicine? And why is it so hard to go from that really compelling set of experiments to a drug that your doctor can prescribe?

Dr. Susanna Kakishova (00:30:25 --> 00:31:56)
Like, yeah. So that's a very long path still to a drug. So first, of course, you show it in mice. It is human tumors in mice, but it is still quite far from what happens in human body. Yeah.

So that's one, of course, problem. So it can be completely different in human body. But the second problem is that it's not so easy to reactivate these genes in human body. I do it experimentally in mice because I manufacture those cells. That I inject with the possibility of easy reactivation of Lact-B.

However, you don't have this in humans. I can't, you know, genetically change humans to do that. So in humans, you actually have to find a chemical compound or some way how to reactivate that silent protein in human cells. And that is the difficult part. Yeah.

So something that can be injectable or digestible and that will reach the cancer cells and will lead to the reactivation of Lact-B. But fortunately, we actually already found those compounds and we are now patenting them. There are 3 compounds that can do exactly this. Through injections or through digestion, they can get to the site and can reactivate Lact-B. However, this is still, and even in this stage, it is still quite far because there was lots of tests done now on mice.

Dustin Grinnell (00:31:56 --> 00:31:57)
But is this where you're going?

Dustin Grinnell (00:31:57 --> 00:31:58)
Yes.

Dr. Susanna Kakishova (00:31:58 --> 00:31:58)
Yeah.

Dustin Grinnell (00:31:58 --> 00:32:00)
And this is what you hope to do.

Dr. Susanna Kakishova (00:32:00 --> 00:32:40)
You hope to put those compounds to the test to see if they're safe and effective. Yes. We are all super excited about this, that we reached this stage. And yeah, we also are getting some very nice investments and private funding to continue in this research. But I have to say that so we have 3 compounds for reactivation of LAG2B, but as I say, we found 4 other tumor suppressors. And they are— now we have compounds for their reactivation also. So the work is really branching out. And so we are not putting all the eggs in one basket. We have several baskets with several eggs. So hopefully at least one of them or some of them will lead to some fantastic effects in humans.

Dustin Grinnell (00:32:40 --> 00:33:03)
Yeah. You mentioned a name of a somewhat well-known cancer biologist, Robert Weinberg. And I'm joking because he is a founding member of the Whitehead Institute. And a renowned cancer biologist, and you were in his lab. That's where we met when I was working at the Whitehead, and I saw him often, was in the same suite, and I saw you often.

Dr. Susanna Kakishova (00:33:03 --> 00:35:10)
And as I said, when I finished my PhD in HIV in virology, and I made the decision to go into cancer research because I was fascinated by cancer research, you know, I have to say that I was insulted by cancer. You know, I was insulted. How is it possible that cancer cells are so rude and they destroy such a beautifully functioning system as living bodies that were evolved for so many millions of years to function and be balanced? And then a cancer cell comes and just destroys it within, like, years. Yeah, a few years, sometimes even months.

And I get angry and insulted, and I said, I'm going to research it, and I want to revert this process if possible. I want to join the ranks of those fantastic scientists and cancer researchers that are trying to do this. So I made a decision to transfer to cancer research, and then I was thinking, where should I apply? And coming from virology, I actually didn't have a very strong background in cancer research. I didn't even have courses of cancer research at the university, which I'm quite ashamed to say, but that's how it was.

So the only name I knew was Robert Weinberg because Of course, everybody knew Robert Weinberg. It didn't matter, like, what field in science you're studying. Yeah. And everybody knew about his work on oncogenes, tumor suppressors, and everything. So I looked up his lab and it was at MIT.

Dustin Grinnell (00:35:10 --> 00:35:10)
And—

Dr. Susanna Kakishova (00:35:10 --> 00:36:53)
Yeah. So I applied for a position in his lab to be a postdoc. Which means it's a position right after you finish PhD, so you're kind of like a junior scientist. And I also applied to other labs in Boston area, and then I was selected to come for an interview, which on its own was fantastic. I was so looking forward to it.

And I came here and I presented my virology research, and everybody could see in the room that I'm way off the usual expertise that they have. In the lab. And then I had a full-day interview, which I was not accustomed to. It was so difficult. I was sweating so much.

I spoke to like 7 postdocs from his lab. Then I had a presentation for 1 hour. Then I had a discussion for 1 hour. Then I had a one-on-one talk with Professor Weinberg. I was exhausted by the end of it.

Yeah. And then I remember that I was waiting for his reply.. And the reply was not coming and not coming. And I already got offers of positions from those other two places that I interviewed in Boston. But I wanted to go to Bob Weinberg's lab.

So I was waiting for his reply. Nothing was coming. And then eventually I wrote to him like, "Please, Professor Weinberg, could you just tell me whether I'm accepted or not so that I can finally sleep and eat?" Because I really— I didn't get like 3 nights' sleep and I didn't have appetite. So please tell me. I mean, I'm fine with whatever, even when I'm not accepted.

I just want to sleep and eat again. And he replied back to me and he said, oh, didn't I reply? Of course you are in. So this was it. I still have that email, you know?

Dustin Grinnell (00:36:53 --> 00:36:54)
Yeah.

Dustin Grinnell (00:36:55 --> 00:36:58)
And that's how I got in. Wow. Why you? What did he see in your work?

Dr. Susanna Kakishova (00:36:58 --> 00:37:01)
What did he see in you as a scientist?

Dustin Grinnell (00:37:01 --> 00:37:04)
I didn't dare to ask this question in the beginning.

Dustin Grinnell (00:37:04 --> 00:37:04)
Yeah, sure.

Dustin Grinnell (00:37:04 --> 00:37:07)
I actually kind of think you probably learned it over time.

Dr. Susanna Kakishova (00:37:07 --> 00:37:56)
He's even on the on the international board of advisors at my institute in Prague. So we really, like, see each other even in Europe now. And I always visit him when I'm in Boston and we email each other quite frequently. So we have a very, very good relationship now. And I did ask him, like, why me?

You know, I was a virologist. I didn't know anything about cancer research. My English was not that great. I was, you know, very shy. I didn't know how to present myself.

Dustin Grinnell (00:37:56 --> 00:38:50)
And what he realized is that I have a different way of thinking, and that's what he likes. And I think that's— I talked with Jingkun Wang, who is a PI at the Whitehead, last episode. And I was really curious about, well, what is that way of thinking, right? And there seems to be something in the Whitehead culture of thinking differently, of being independent and not necessarily focusing on, like, the incremental progression of scientific questions, but really just, like, taking even, like, an unpopular view and coming in from the— he must have saw that you were strongly independent thinker, and even your outsider status to the field would have been a benefit. And probably also that you're just incredibly passionate about that question. But tell me about the thinking that you think he saw.

Dr. Susanna Kakishova (00:38:50 --> 00:39:56)
But during my master's degree and PhD and even high school, I mean, I did won quite a lot of awards for alternative approaches and new things. And in Europe, we have something called Olympics in mathematics and biology. And I did lots of things during my— and I was representing Slovakia as the only person, you know, in sciences in the international forums and so on. So, I think he liked it. He liked the drive and he liked that I'm not afraid of failures.

I have plenty of those also. And when I was actually applying to his lab, what I did and what I would recommend the other scientists to do if they want to get to these top labs is that I even wrote a research proposal, what I want to do in his lab. And, I mean, it was something completely crazy. At the end, I never worked on it. And when I read it a few years later, I was like, oh my gosh, like, this is completely crazy.

Dustin Grinnell (00:39:56 --> 00:40:05)
So I think that's what, you know, attracted him to invite me for an interview. Yeah, it's something about hunger and drive and even ambition, you know.

Dr. Susanna Kakishova (00:40:05 --> 00:40:46)
But I have to say that he immediately told me that people in his lab need to be independent. He's not micromanaging anybody. You know, you really need to go into kind of a senior scientific mode. And of course, in the beginning, it was difficult for me because I was not— I was eager to do it, but I was not experienced enough to do it in the beginning. So I made lots of mistakes in the first 3 years. But what is fantastic that he really gives you time to mature as a scientist. He gives you guidance. He's telling you what you did wrong, how you should go, what is his feeling about this, your direction, where it should go, who should you talk to that can give you the best advice.

Dustin Grinnell (00:40:46 --> 00:41:40)
And the whole spirit of his lab was very, very collaborative. You know, like I said, I was in the same suite as the Weinberg lab, and I used to see— I had the unique perspective of seeing all of you, all of you postdocs, go into his office and speak with him. And I always was very curious about, like, what was it like to be on the receiving end of his direction and wisdom and redirections? And I always thought to myself, he was kind of like playing the orchestra kind of thing. You know, like, you know, you guys were the musicians and he was playing the orchestra. And I kind of felt like he just was at this high level listening to your results, your experimental results, and what you wanted to do next. And he would kind of just like steer you in the right directions based on his knowledge and understanding of the field.

Dr. Susanna Kakishova (00:41:40 --> 00:42:11)
Yeah. Definitely. I mean, you know, Bob Weinberg, and I can imagine that many of these top world scientists, he already has a feel of which direction might be the correct one. You know, for me as a scientist, I couldn't decide which direction to take because for me all of them were fascinating and all of them were equally possible. Is this gene involved in apoptosis or differentiation or this and that? You know, For me, all of it was acceptable, all of it was excitable. But Bob looked at it and he just said, "I would concentrate on this and this direction." And it could save you 2 to 3 years.

Dustin Grinnell (00:42:11 --> 00:42:11)
Exactly.

Dr. Susanna Kakishova (00:42:11 --> 00:43:35)
What I also really liked about— he was not only supporting us professionally, scientifically, but also on a human level. You know, for example, like when I was starting in his lab, he told me like, "Look, Susanna," You are starting to be a postdoc here. In your postdoc years, you know, you will probably want to have a family, have children. I just want to tell you that we are very supportive in it in my lab, and we will reconfigure your science and your approach so that you can have both. You can do fantastic science and you can also have a family.

You absolutely don't sacrifice one for the other. Both of them are possible, and we will give you the support to do both. Both. So he was very nice also in this way. What I also liked is that he allowed us to have our own project, like really independent project.

And that's the strategy of his mentorship. You do projects that are generally in line with what he does in his lab. So when I came, it was the epithelium-mesenchymal transition, the examination of the research of the metastasis. So one of my projects was in line with his research, yeah, epithelium-mesenchymal transition. But then he told me on the side, you should also develop your own project that would be completely your intellectual property and that you can take and have it in your own lab if you will wish to do so in the future.

Dustin Grinnell (00:43:35 --> 00:43:40)
And that was the cancer-resistant tissues and cells project.

Dustin Grinnell (00:43:40 --> 00:43:40)
I see.

Dustin Grinnell (00:43:40 --> 00:43:44)
And so you came up with that and nourished that idea under his mentorship.

Dr. Susanna Kakishova (00:43:44 --> 00:45:44)
And so So when I came to him, and it was— I was already 2 years postdoc in his lab, and I came to him and I told him, like, "Bob, look, I want to work in these skeletal muscle cells and these cancer-resistant tissues." And he just looked at me and he said, "You came to my lab and you want to work on skeletal muscle tissue?" And I said, "Yeah, yeah, I would like to. I'm really interested in it, why certain tissues, why cancers don't evolve in them." He was thinking for a bit and then he said, "Okay, you can work on it, but do not present it." Because why? Because it was just— Because he thought it was, and he did say that this is a wacko project. I didn't know what wacko means at that point. So I asked other postdocs and then they explained it to me.

So what he believed that it can either go fantastic or it can completely like crash within a few months or years. So he just wanted me to take time to find out whether actually a viable project and so on. So that's what I did. I worked on it on the side, and I discussed it with my colleagues, but I didn't present it anywhere, like, outside of the Whitehead Institute, just trying to see whether it will lead anywhere. And I even asked him when he said, like, you can work on it but don't present it, and I asked him, so I was a little crushed, and I said, so why do you want me to?

Dustin Grinnell (00:45:45 --> 00:45:53)
Isn't that science? It's sort of embracing the possibility for serendipity. Saying like, this doesn't seem rational, but let's give it a go.

Dr. Susanna Kakishova (00:45:53 --> 00:46:02)
Yeah. And it's fantastic. But not many bosses would do that because they have to pay for it. And that money can go into something they believe more.

Dustin Grinnell (00:46:02 --> 00:46:05)
So I used Bob's money to work on this project.

Dr. Susanna Kakishova (00:46:06 --> 00:46:26)
And it was one of those bets that paid out, that worked. Yes. And I think that even now that he's following my career, and I think there is this inherent curiosity, like, is this going to work? And now that he sees the compounds and everything, I mean, I think that he's quite excited about it.

Dustin Grinnell (00:46:26 --> 00:46:26)
Yeah.

Dustin Grinnell (00:46:26 --> 00:46:44)
It must also just be, as a mentor, as a senior scientist, it must be really like a source of pride to see one of his junior scientists become a senior scientist, become really established and really working toward something really special.

Dr. Susanna Kakishova (00:46:44 --> 00:47:29)
Yeah, I hope so. I mean, we will see how it goes. I'm still a junior scientist. I don't have a tenure position yet, so it's going to be a surprise for me also. But I have to say that the science really works very nicely, and that's why my whole lab and all the lab members are super excited. And even some former colleagues from Bob Weinberg's lab and friends from Bob Weinberg's lab are keeping in touch with this project. And for example, One of the PhD students then switched into the patent law, is now doing the patents for Lactobee. So it's like it's staying in the family. Another person that is doing consultancy services is consulting me how to develop it further. So it's really like it's staying in the Weinberg family, this project.

Dustin Grinnell (00:47:29 --> 00:48:09)
That's amazing. We've talked before about your path towards science and what appeals to you about being a researcher. And I think you wrote or said somewhere, "Since childhood, I've been fascinated by various branches of science. My path to biology led through geology and archaeology when my mother read me stories as a little girl about the German archaeologist Heinrich Schliemann, who discovered Troy." You said, "My father then bought me a geological hammer, and when I broke all the rocks in the far and wide vicinity, I became interested in astronomy, black holes, and I already imagined that I would become an astrophysicist." How do you think hearing Schleinmann before going to bed influenced you?

Dr. Susanna Kakishova (00:48:10 --> 00:50:38)
I loved the intrigue and, you know, I was very curious about the ending and everything. And then when I was like 8 to 10 years old, I had a little crisis because I realized that they are just fairy tales, that none of it is real. You know, there are no There are no talking trees, and there are no dragons flying around, and, you know, that there is no magic in the world. You know, and then my mama told me the story about Heinrich Schliemann and how he discovered Troy, and I was absolutely amazed by it because, of course, I knew the story about Troy, and I assumed it was just a fairy tale. And now it was shown that it really happened, and somebody called Heinrich Schliemann actually believed that fairy tale and decided to find out about it and to discover the ancient town of Troy, and he really did succeed.

For me, you have to realize I was an 8 to 10-year-old kid, so of course I was thinking with a child's brain. For me, that was amazing because that showed me that really some fairy tales can come true, and it also showed me that science is actually magic. It is just magic explained. So, if you would ask a Victorian lady, if you would show her what we are using now, everything would look magical to her. For us, it's explained, it's normal, it's commonplace because we already know why it works.

And so, this really brought me to science, that science is full of magic, but we can discover why is that so and how it works and so on. We can explain it. And I love this. And as you said, I mean, for example, the story about Troy really gave me the belief that that it is possible to follow your dreams, and sometimes it is possible to really fulfill them. And that's why I wanted to become an archaeologist.

But, you know, while some kids played with dolls, or some girls, I asked my dad to buy me a geological hammer. And I was just, you know, I wanted to be an archaeologist, so I was breaking everything around. And then it was the astrophysics, because I was fascinated by black holes and singularities and all these things. However, then I realized that even though astrophysics and astronomy is fantastic, it is quite distant. I wanted something more interactive, something where I can see the effect more and it would really affect humanity in hopefully like near future or at least during my lifetime.

Dustin Grinnell (00:50:38 --> 00:51:02)
And that led me to the viruses and that led me to the cancer research. There's almost a connection between whatever that mindset is that archaeologists used to discover Troy. In a way, you did that that with your project? You believed in something that wasn't— you weren't sure about, that may have been a failure, but you went for it anyways.

Dr. Susanna Kakishova (00:51:02 --> 00:51:58)
Was that like consciously or unconsciously in your mind? Look, I am a very stubborn person. I'm stubborn. And I have to say that I believe being stubborn is a good trait in science because in science we are uncovering new connections, we are uncovering new things. And many times we are in an unknown area. We are not sure whether what we are doing actually will have any result, whether the logic was sound, whether it will prove to be right. And in that case, you don't have nothing, you don't have anything psychological to lean on except your own belief in yourself or your stubbornness. You know, you're just going step by step and you're stubborn and I will keep on going and I will keep on trying trying until I'm completely, completely sure that it doesn't work. And this is the stubbornness that just keeps it going. So I consider it actually a good trait in science to some degree.

Dustin Grinnell (00:51:58 --> 00:51:58)
Yeah.

Dustin Grinnell (00:51:58 --> 00:52:06)
You also said another trait is in a way kind of like arrogance. You said, I'm not an arrogant person. I just have arrogant dreams.

Dr. Susanna Kakishova (00:52:06 --> 00:53:52)
And I did realize it. I'm really like nobody would ever call me arrogant, I hope, and I believe. But my dreams do sound arrogant because when people ask me, what do you want to do? I say, you know, I want to cure cancer. Yeah.

Or I want to cure HIV. I want to cure cancer. Lots of people, at least in my culture, it is considered to be arrogant to even think that you have a chance to do this. You know, you should be more humble about your expectations of life. Grandiose.

Yeah. You should be more realistic. And they even ask me, like, why? Like, it's an unrealistic goal. And I told them, you know, it's my dream.

And unrealistic goals are actually definitions of a dream. Yeah, that's a definition of a dream. Small dreams are just possibilities. For something to be called a dream, you have to dream big. So I'm just trying to dream it, and we will see how far we get.

But for example, this dream gets me, got me not only in the basic research, but I really am trying to push it further into translational research and further into the clinical research. So this is why I'm following the path. We will see. If it doesn't work, perfectly fine. I realized a long time ago that when I imagine myself as a senior person, an old person, I know that I would regret terribly if there was something that I didn't try what I wanted to try.

That would be the real wound in my mind and in my body that I didn't try something. I wouldn't regret if I tried something and failed. Failed, that's okay. It gave me the answer and that's it. But if there was something that I didn't try, I would regret it.

Dustin Grinnell (00:53:52 --> 00:53:57)
Yeah, I remember Jinka saying doing experiments is almost becoming ambivalent to the outcome because you don't know.

Dr. Susanna Kakishova (00:53:57 --> 00:55:39)
You know, things don't work, your theory is not right, you get scooped, you're tired, you know, you don't know the result of experiment for years and then it didn't work. So lots of stresses. So what really gets me going is actually that I also have outside hobbies, you know, like you can't do just science alone, you have to have some support outside of science that will keep your psychology going. And also I have to say that I am a naturally very positive person and quite happy. So this enthusiastic vibe, you know, that gets me going.

Optimism. Yeah, optimism. And I have to say that this was not acquired. This is inborn. You know, optimism is born.

Like, for example, I can see it with my younger son. Yeah, I have two beautiful boys, two sons. And my younger son, I just have to say that I have a little story that we went to an ice skating rink. And he was 7 years old. He's 8 now.

He was 7 years old, and he was skating and skating, and he was absolutely terrible at it. I mean, he was falling all the time. And he came to me at the end with like a big smile on his face, and he said, "Mommy, did you see that? Did you see out of all the kids, I was the best at getting up?" "Up." And this is really like the glass is half full. Like, even there, it was an absolute disaster, but even there he found something to be proud of and enthusiastic about.

Dustin Grinnell (00:55:39 --> 00:55:48)
Would you say that he was falling down more than the others? Yeah. And one could say if he took a half-empty perspective, "Oh, Mom, I fell down more than everybody else." Yeah.

Dr. Susanna Kakishova (00:55:48 --> 00:56:10)
But he took the opposite. Like, "I was the best at getting up." And this is the strategy that people should be adopting also in science. So if somebody's listening out there and they had a bad day and, you know, screwed up and something didn't go well, don't worry about it. Maybe your destiny just wants you to practice your getting up skills.

Dustin Grinnell (00:56:10 --> 00:56:35)
What's the ancient wisdom? Fall down 6 times, get up 7 or something? Japanese proverb or something? I heard that. But there's a famous Michael Jordan commercial with Nike where he's voicing over him playing basketball and he's like, He's saying how many shots he's missed, like how many game-winning shots that he'd been entrusted to take and that he'd missed in the moment.

Dr. Susanna Kakishova (00:56:35 --> 00:56:41)
So he'd actually missed more game-winning shots than he won. Of course.

Dustin Grinnell (00:56:41 --> 00:56:43)
Failure is an absolutely natural part of success.

Dr. Susanna Kakishova (00:56:43 --> 00:57:26)
It's like redirection. Yeah, and it teaches you so many things, and it teaches you to be psychologically strong, actually, which you will use in many aspects of life forever. So when, you know, I have actually I have a wardrobe with 2 drawers in there. I always had it since childhood. And one drawer is for successes and another drawer is for failures.

You know, successes where I put letters that I received grants or that I was accepted somewhere and failures that I didn't receive grants. And I have to say that I have now 1 drawer of successes and 2 full overflowing drawers of failures. But it's part of it. You know, I even know my ratio. I mean, I fail terribly 8 times and on the 9th time something works.

Dustin Grinnell (00:57:27 --> 00:57:28)
That's how it is.

Dr. Susanna Kakishova (00:57:28 --> 00:57:40)
Yeah, it's just part of the process. And in science, you really get so many times into, you know, that something doesn't work and you think what you are doing has no meaning and that science doesn't like you.

Dustin Grinnell (00:57:40 --> 00:57:49)
So you have to find a way around it. Is there a time when you thought there was no meaning or significance? You were studying history at Harvard.

Dr. Susanna Kakishova (00:57:49 --> 01:02:16)
You tell your personal experience of a crisis for perspective. Yeah, yeah, yeah, yeah. So, for example, the first crisis was at the end of my PhD. My PhD was very intense. I was working nonstop all the time, and when I was not working in a lab, lab, I was doing part-time jobs, and I was very poor with a very bad lifestyle.

But, you know, so at the end of PhD, I was really very tired, and that's when I actually got accepted to Bob Weinberg's lab. That was the last bit of energy that I put into that interview. And then when Bob Weinberg hired me, he said— so it was sometimes in March— and he said, okay, so you can, you can start in And I said, like, Professor Weinberg, would it be possible to actually start next year? Take the summer or be out even longer? I even said one year.

Would it be possible to start next year? Like, I'm really tired from my PhD. I said it openly, you know, I'm really tired from my PhD. And even though I still love science, I don't think I have energy right now to start. And I always had a dream, dream to travel around the world.

So I would like to take this opportunity to go and backpack around the world. With my friend. And Bob Weinberg looked at me, and this was like right in the beginning of actually working for him. And Bob Weinberg looked at me and he said, this is a good time to do it. Go, we will wait for you, and, you know, come back refreshed and full of ideas and full of energy.

So that was the first time. So he allowed me to travel, and I, and I fulfilled one of my big dreams. And then I came back, absolutely, you know. And then, uh, yeah, and then I started in Bob's lab. And however, unfortunately, nothing worked the first 3 years.

So this was not like 6 months. When now scientists tell me that they are super stressed because something didn't work for 4 months or 6 months, I mean, I just look at them like, come on, I mean, what do you expect? You know, this is— we are not, you know, trying doing miracles here and stuff. So anyway, so it didn't work for 3 years. And really at that point, like, you know, my theories were flawed, the experimental designs were not properly set up or executed, And then I started to wonder whether this is the right path for me.

I knew I like science, but maybe science doesn't like me. So, I had a second love in my life, and that's history, ancient history. So, I thought that maybe I should just quit science and follow the ancient history, you know, so much calmer there. And I actually applied to Harvard University to the Graduate Schools of Arts and Sciences for their history program, the Ancient Roman History and Philosophy Studies. And I got into the program, and then I came to Bob and I said, Bob, you know, I'm on the crossroads here.

I love science, but I think that, you know, something is not going well, and I have these doubts whether I shouldn't change it for history and so on. And I got accepted to Harvard, and maybe Maybe I would like to take a year or two to research whether that's the right path for me. And again, Bob Weinraub, it's amazing how, you know, his guidance and how many chances he gave me. And Bob said, Zuzu, that's how they call me, all the people, Zuzu, I have been on crossroads before, so go try it. I will give you one year.

You will still be a postdoc in my lab. You still have to work. Every day, but during the day you can go and do your courses at Harvard, and then in the evening you will come and do your postdoc work in my lab. So this is how we did it. So for 1 year, I was doing both.

Yeah, I had this double life. You know, I was a student, Harvard student during the day, and then I was the MIT postdoc in the evenings. And he even gave me a fantastic lab technician that was helping me with work. And it was exactly in this moment, this year at Harvard, that gave me the idea for cancer-resistant tissues because I came with a completely different mindset, looking at things from a completely different perspective, and I really planned very well how to do the experiments. Yeah.

Dustin Grinnell (01:02:16 --> 01:02:23)
What was it specifically about the history program? What did you find in it that inspired the scientific question?

Dr. Susanna Kakishova (01:02:23 --> 01:03:50)
I would like to just quickly explain this by an example. When I was traveling around the world, one of the stops was in Japan. And I went to this Zen garden in Japan, and there were 12 stones in that garden. And they claimed that you can never see all 12 stones from one angle. Angle.

Yeah, when you're walking around the garden, and I've really scientifically explored it, I really walked around the garden, and it's true, you could never see all 12 stones at once. You could see 9, 10, 11, but never 12. And the whole idea, kind of a philosophical idea of this garden, is that you can never see the whole truth from one angle. Science was one angle. For many people, they have the other angle.

For them, it's something else. It's sports, it's art. For me, it's history. You know, it gives you different perspectives. If you start thinking about things differently.

Dustin Grinnell (01:03:50 --> 01:04:14)
Yeah, it's interesting. It made me think of doctors who are trained with a literature background. Yeah, yeah, yeah. The field of narrative medicine, it's training clinicians and healthcare providers on close reading of literature and movies and reading patient stories and things like that in order to see illness and health from a different perspective.

Dr. Susanna Kakishova (01:04:14 --> 01:04:39)
Yeah, different perspective. It's like a different pattern of how things are happening in those fields. And I really believe And I like it when people have something else outside science. I think it inspires them. It shows them new ways of thinking, or it just simply calms them down, you know, and gives them something else to do, and then the brain can rest. So when I'm hiring people, I actually like when they do other things also.

Dustin Grinnell (01:04:39 --> 01:04:40)
Do you ask?

Dustin Grinnell (01:04:40 --> 01:04:40)
Like, what are your hobbies?

Dr. Susanna Kakishova (01:04:40 --> 01:04:52)
What do you do for fun? You know, it's usually part of the CV, actually. They write the hobbies, and I'm happy with I just don't want them to do it professionally because then it would take too much time.

Dustin Grinnell (01:04:52 --> 01:04:59)
But yeah. Except if someone came and said, "I'd like to do a year of this," you'd maybe think of Bob in the background.

Dr. Susanna Kakishova (01:04:59 --> 01:05:18)
Yeah. I mean, I can't do that to my own people yet because I'm still a junior group leader. So I can't just let somebody go for one year. I actually really need their work. In my senior years, if I have a big lab, then I would love to do it also. I would like to really hopefully be as nice about it as Bob was.

Dustin Grinnell (01:05:18 --> 01:05:30)
How do you plan to— do you have the image of Bob in the background and his mentorship? Do you plan to model it? Are you modeling it? How do you plan to be a senior scientist for young scientists?

Dr. Susanna Kakishova (01:05:31 --> 01:05:57)
Yeah. You know what? I think that I definitely have his mentorship design in the back of my head when I'm doing. But at this point, because my lab is very small and we have lots of projects that I need to start to get them going. I can't unfortunately follow his path, but once I'm a senior, I would be happy to allow my people to do 1-year internships or get a rest.

Dustin Grinnell (01:05:57 --> 01:06:15)
But of course, it also depends what work they do and how they try and so on. Say more about how hobbies and your outside life keep you buoyant and keep everybody buoyant. Why is it so important not to be just singularly focused on one thing?

Dr. Susanna Kakishova (01:06:15 --> 01:07:16)
I mean, throughout my career, I studied at University College London, at Columbia University, MIT, Harvard. So really, they are considered to be top scientific establishments. And I really have to tell you, if there is a person that is living purely for science, there is a big chance they are going to burn out. I mean, you cannot keep up with that lifestyle and with that speed for too long. And I have seen it many times that this indeed happened.

You need to have something on your side where your brain can change directions or just calm down, you know. And also very important psychologically is to know that you didn't have to sacrifice all the other aspects of life for science. Science doesn't require it, you know. Many times people are pushing themselves into But science doesn't require the top world scientists. I mean, always had something on their side.

Dustin Grinnell (01:07:16 --> 01:07:50)
Science is fine that you have something else also. That's interesting how science is kind of indifferent to your striving and burning yourself out. But then, you know, Einstein's an interesting example, right? Because it was through the productive rest you know, the playing of the violin. He just took time away from the equations and the pounding out on paper. But that was a way for him to think in a way that was, like, subliminal. Like, it was a way for the ideas to marinate. I feel like you think that way too. It's like you've shut down the engines, but there's still things going on.

Dr. Susanna Kakishova (01:07:50 --> 01:08:09)
Oh, yeah, definitely. The subconsciousness is working. You're still searching for patterns, you know, but you're doing it in a more calm mode, more detached mode. And that's why you are getting less emotional about it. About it and less stressful about it. And that's what I feel brings results. Of course, with every person it's different, but I think it helps in general.

Dustin Grinnell (01:08:09 --> 01:08:12)
Do you do anything else? Do you hike? Do you ride bikes? Like, what are you—

Dr. Susanna Kakishova (01:08:13 --> 01:08:48)
how do you give yourself a break? I love to read, but non-scientific literature, right? So reading, cooking, and traveling. Yeah, especially cooking. Cooking is a very quick fix. Cooking gives me what I don't get in because cooking produces quick results, good results. They look good, smell good, taste good, and my boys love it, and they consider me the best mom. So it really gives me the fast and quick satisfaction. Lots of people actually ask me whether I do any sports, and that's one thing I do not do.

Dustin Grinnell (01:08:48 --> 01:09:02)
I don't like sports. And last question, any advice for a young scientist, you know, a little researcher, whether they're young, young in middle school, or they're maybe starting their scientific career?

Dr. Susanna Kakishova (01:09:02 --> 01:10:09)
Don't think that you have to sacrifice everything in your life for science. You can do fantastic science and still love life and do other things. And also, follow your dreams and actually don't get discouraged by other people. You know, many times they mean well, but you know, sometimes it's difficult to continue your path when you see discouragement from so many sides, you know. And sometimes this discouragement comes that they either misunderstand your idea, or they laugh about it, or they mock you about it, or they, you know, psychologically manipulate you into thinking that it's so unrealistic, that it's silly to do, you just don't follow it.

Like, really trust yourself and go and try it. You know, the world works on the principle that what works for some people doesn't work for another. You know, you have different types of characteristics. You are driven by different things. Maybe what didn't work for other people will work for you, and you will never know until you try it.

Dustin Grinnell (01:10:09 --> 01:10:19)
So just believe in yourself and try it. It's a beautiful message, and I think we'll leave We'll leave it, we'll leave it there. Thank you for coming to talk.

Dr. Susanna Kakishova (01:10:19 --> 01:10:23)
It's a really insightful and fun conversation.

Dustin Grinnell (01:10:23 --> 01:10:46)
Thanks for listening to this episode of Curiously. I hope you enjoyed this conversation with Dr. Suzana Kekesova. If you're enjoying this podcast, please consider leaving a review. They encourage people to listen and help attract great guests. If you like what you've been hearing and would like to sponsor the podcast, please consider supporting me on my Patreon account.

Thanks again for listening, and stay tuned for more conversations with people I meet along the way.