Explaining fentanyl and its dangers; the human genome project's significance; signs of concussion: Upstate Medical University's HealthLink on Air for Sunday, May 1, 2022

Host Amber Smith: Coming up next on Upstate's "HealthLink on Air," the medical director for the Upstate New York Poison Center discusses the dangers of fentanyl ...

Vincent Calleo, MD: ... Over the last several years, there has been a large increase in the number of contaminated recreational substances that are out there. Some of the ones that we see commonly are things including heroin or even cocaine. But now we've actually been seeing some increases in medications you can swallow that havefentanyl contaminated within those, too ...

Host Amber Smith: ... and a neuroscientist explains what's important to know about the completion of the human genome ...

Stephen Glatt, PhD: ... Having this sequence of the genome now much more complete will enable us to determine what are the differences between individuals in their DNA code and how that relates to what diseases they get or what diseases they're resistant to...

Host Amber Smith: All that, and a visit from The Healing Muse, coming up after the news.

This is Upstate Medical University's "HealthLink on Air," your chance to explore health, science and medicine with the experts from Central New York's only academic medical center. I'm your host, Amber Smith. On this week's show, we'll learn about the significance of the human genome, which scientists recently completed. But first, we'll hear from the medical director of the Upstate New York Poison Center about why fentanyl remains a threat to people who abuse opioids.

From Upstate Medical University in Syracuse, New York, I'm Amber Smith. This is "HealthLink on Air." The Drug Enforcement Administration recently sent warnings to federal, state and local law enforcement agencies about a nationwide spike in fentanyl-related mass overdose events. This is an issue that the Upstate New York Poison center is very familiar with, and today I'm talking about it with its medical director, Dr. Vincent Calleo. Welcome back to HealthLink on Air, Dr. Calleo.

Vincent Calleo, MD: Amber, thank you. It's great to be here.

Host Amber Smith: This warning from the DEA said that fentanyl is killing Americans at an unprecedented rate. Can you explain what fentanyl is?

Vincent Calleo, MD: Fentanyl is an opioid medication, and very commonly it's used to treat pain in the emergency department or in the hospital setting. Now, sometimes it can be used on an outpatient basis as well. And most commonly we see this as a prescription for something like a fentanyl patch, where it's applied to the skin and it helps to deliver pain control over a longer period of time. So when used from a prescription standpoint, fentanyl is a medication that can be very helpful for a lot of individuals. But when it's taken or used from a non prescribed standpoint, that's where we can run into trouble.

Host Amber Smith: So it can be used legitimately with a prescription. A doctor can prescribe it and people might be taking it. How addictive is it, even if it's prescribed?

Vincent Calleo, MD: So like any of the opioid medications, it does have the potential to develop long-term dependence if it's used, particularly for a longer period of time.

So there definitely is that potential to develop an addiction to it if it's used for an extended period of time there.

Host Amber Smith: What effects does it have on the body?

Vincent Calleo, MD: So it depends. So in the overdose setting, it's a little bit different than when people use it therapeutically, or like we would in the hospital, or from a prescription standpoint. Most commonly it can be used to help improve pain when there's a condition that's causing that, but in the overdose setting, or when too much is taken, you can develop some pretty scary and life-threatening conditions, including decreased ability to breathe and a change in your mental status, such that you may not be awake or be able to protect your airway, for example, if you were to vomit.

Host Amber Smith: When fentanyl is misused, how is it misused? Is it smoked, or injected, or swallowed? Or, what form is it in?

Vincent Calleo, MD: So there can be a lot of different forms that people can misuse fentanyl, and very commonly it's actually accidentally misused. So what we found is that over the last several years, there has been a large increase in the number of contaminated recreational substances that are out there. Some of the ones that we see commonly are things including heroin or even cocaine. But now we've actually been seeing over the last few years, there have been some increases in medications you can swallow as well that havefentanyl contaminated within those, too. So depending on the route, it can be used in several different ways. So that could include smoking, injecting, or being swallowed along with even dermally on the skin, if people are using a fentanyl patch or something like that, if it's not prescribed to them.

Host Amber Smith: So do you believe that many of the overdose victims had no idea that they were ingesting fentanyl?

Vincent Calleo, MD: Yeah. You know, sadly, that's one thing that we have been hearing in the last several years is that a lot of people that are buying some of their recreational substances of use, they don't actually know what's in those substances. And in many cases, someone who has a heroin use disorder, for example, may use the normal amount of heroin that they typically use. But if they're not aware that it's contaminated with something like fentanyl, they could actually become much sicker and potentially develop significant life-threatening complications, including respiratory depression, where their ability to breathe is decreased or mental status depression, where they can't protect their airway and they may choke if they vomit, for example. So yeah, a lot of people are unaware that they have a product that's been contaminated with fentanyl.

Host Amber Smith: So the dealers that are producing and selling these drugs on the street, if fentanyl is such a dangerous substance, why would the drug traffickers secretly mix it into their drug product?

Vincent Calleo, MD: Well, you know, I feel like there are probably a lot of different answers to this question and many of which I don't know the answer to, but one of the reasons it's commonly placed in products is it does, in many cases, give someone a more powerful high. That's one of the reasons, to develop an increased addiction potential to the substance. Now, sometimes they will mix it with other substances, including cocaine or a number of other things too, that are not necessarily opioids like heroin is, but they oftentimes will mix it in with other substances too. And it's hard to say the exact reason all the time, but in many cases, it's to increase the addiction potential.

Host Amber Smith: You mentioned that it could be transmitted dermally, through the skin. Would a drug trafficker face danger, if they're working with fentanyl to mix it? Would it potentially get into their skin when they didn't intend for it to?

Vincent Calleo, MD: Yeah. So that's actually a great question, Amber, and a really salient one to what we've been seeing a lot of in the news lately, which are concerns for first responders, including police officers and EMS and fire fighters being exposed to, or potentially exposed, to fentanyl. The good news is, if you were looking at the data coming from some of the various toxicology experts in the country, what they put out as a position statement kind of states that in order to get toxicity from dermal exposure -- so skin exposure, or even inhaled exposure -- you really have to have a lot of exposure for a prolonged period of time, essentially, meaning that it's really unlikely for an accidental dermal exposure to result in clinically significant symptoms. And those include the changes in the mental status or the change in the breathing abilities. So it's actually really, really rare and unusual for that to happen. Fentanyl, even as a patch, if you put it on, it requires a special vehicle in order to get into the body. And usually that takes a few hours after you put it on your skin. So it would be really unusual for an accidental small exposure to the skin to result in clinically significant symptoms.

Host Amber Smith: A while back we heard about carfentanil. Can you tell me about the difference between carfentanil and fentanyl?

Vincent Calleo, MD: Yeah, of course. So carfentanil is a medication that is also an opioidlike substance, so in some ways it's similar to fentanyl in the way that it works on the receptors in the body. But it is different in the sense that it's a much more potent version of that. And it's about 10,000 times more potent than morphine. Whereas fentanyl is only about 50 to 100 times more potent than morphine. There was a lot of concern, particularly several months ago, that there was some increased exposure to this substance. And fortunately, at least within our area, we haven't had very many recorded cases of a confirmed carfentanil exposure, though it is something we always are concerned about.

Host Amber Smith: This is Upstate's "HealthLink on Air," with your host Amber Smith. I'm talking with Dr. Vincent Calleo, the medical director of the Upstate New York Poison Center.

Now the Drug Enforcement Administration mentioned several mass overdose events involving fentanyl, where more than three people overdose around the same time in the same location, in cities in Florida, Texas, Nebraska, Colorado, Missouri and Washington, DC. They said in recent months there were 58 overdoses, including 29 deaths. Do you know how many fentanyl-related deaths have been recorded in Central New York?

Vincent Calleo, MD: I don't know the exact numbers for all the Central New York, but I did recently review some of the data from the Onondaga Health Department website, and what it looks like is that over the course of the last year or so, in 2021, it was reported that of the 139 deaths that were from opioids within the Onondaga region, it reported that about 91% of those deaths were fentanyl-related. And about 38 were possibly from fentanyl and heroin related together. So that makes up the vast majority of that number. And so I'd say that at least in Onondaga,County, a good number, or a large number of those deaths was related to fentanyl in some way, shape or form.

Host Amber Smith: So this is a threat here that we need to be kind of mindful of?

Vincent Calleo, MD: Yeah, absolutely.

Host Amber Smith: Now, what do you think makes the difference between life and death? Because I saw that there's a lot of overdoses, but maybe half resulted in death. What determines who lives and dies?

Vincent Calleo, MD: Well, again, there are a lot of different pieces that really go into that equation, but I think one of the biggest things that can help reduce the number of deaths is going to be early administration of naloxone, which is an antidote to help people breathe again. And in addition to that, it's good supportive care, which is essentially helping people to breathe. So if you notice anyone who is found down and there's, a naloxone kit available, administering that may be the difference. It may help that person live. And early health care treatment, including calling 911 and getting someone who can help the patient breathe on their own or assist with it, early on, may be the big difference between life and death. Because the vast majority of deaths that occur from fentanyl overdoses tend to be related to hypoxia, which is a condition where there's not enough oxygen in the blood. And in many of these cases, it's because the body is unable to breathe as it normally does, as a result of the exposure to the fentanyl.

Host Amber Smith: When a person who's overdosed arrives in the emergency department, the doctors aren't going to know what they took, necessarily. How do they find out whether it's fentanyl or do they just, at this point, assume that it is and treat for that?

Vincent Calleo, MD: So in addition to working as a poison center doctor here, or a toxicologist, I also work in the emergency department too. And I've encountered this situation, not uncommonly. Now, when we think about opioids as a whole -- which fentanyl falls into that opioid category -- what we really think about is a collection of signs and symptoms that we typically see when someone comes in. To be honest with you, when I'm an emergency doctor and I'm seeing someone who's coming in after an opioid overdose, it doesn't really matter to me acutely what they took that caused their symptoms, but more importantly, what I'm going to do to treat them. So if I look at them and I have a history for an opioid exposure, or I see a collection of signs and symptoms, including that change in mental status and that decreased ability to breathe, one of the highest things on my list for what could be causing this is an opioid. And the most important thing like I alluded to earlier is helping the patient to breathe early on and getting their oxygen levels back up. And if we're able to, what we typically will consider giving will be some doses of naloxone, though again, the dose and how much we give to these patients will kind of depend on a case-by-case basis. But in general, the bigger thing when we're seeing patients come into the emergency department is focusing on treating them and helping them to breathe, making sure that they're protecting their airway. And supporting them in all the other ways they need is going to be the first thing of importance on my list.

Host Amber Smith: I understand from October 2020 to October 2021 more Americans died of drug overdose than from gun- and auto-related deaths, combined. Aside from raising awareness, as we're doing right now, are you aware of efforts to reverse that trend?

Vincent Calleo, MD: There's a lot of stuff that's been going on in the public health sphere, including a push to make people aware of naloxone and how to administer it. Because like I alluded to earlier, having early and quick access to naloxone administration could be the difference between life and death for a number of different people. And it's really, really important to help people to recognize what some of the signs and symptoms are, because early recognition and early treatment can really help to save a life. And so I think it's really important to make people aware of what to watch out for, what a overdose from fentanyl or really any opioid may look like, and what steps can be taken to help try to mitigate that or reduce the harm from the exposure.

Host Amber Smith: For people who purchase illicit drugs and, they don't know what's in them necessarily. Is there any way that they can protect themselves, or is there any way that they can verify that what they're about to take doesn't have fentanyl.

Vincent Calleo, MD: Yeah, you know there are a number of different things out there. And there actually are some fentanyl test strips that people can use. There are different ways that these can be utilized, but in many cases, what will happen is if people take a small amount of the substance and test it with one of the strips through the steps that are provided in an individual kit, it does in many cases show if there is some fentanyl in there, though, I always do urge people to take this with a grain of salt because tests are not always perfect. And if you take an entire batch of a substance there, there may be a small portion that you're testing that may not contain the fentanyl, but it might be in other parts of the batch, or it might just be that the test is not perfect at detecting it. So there are things that we call false positives and false negatives. So it could be that the test that you're doing, even if it comes back negative, may not necessarily be safe. It's something to certainly consider. And I would consider recommending to people if they want it to test for that, there are things out there, but just remember, no test is perfect. And the safest thing is to not use those substances.

Host Amber Smith: Right. One other thing, though, in New York state, the naloxone you can purchase without a prescription, right? To have...

Vincent Calleo, MD: Yep, that's correct.

Host Amber Smith: ... at the ready.

Now for people who overdose on fentanyl, but don't die, I'm wondering what the recovery is like.

Vincent Calleo, MD: It really depends on the person, and a large part of that depends on how quickly they receive treatment and how low in particular their oxygen levels may have dropped. For most people after an overdose, if they receive very rapid health care administration, as well as administration of naloxone in a lot of cases, the majority of people actually recover very well, As long as they don't have any significant, prolonged period of decreased oxygen to the body and the brain. Most people will do well if there hasn't been significant what we call "down time," where they have beenunresponsive or not breathing for a while. Though, sadly, in some cases where people have had prolonged down time or they had a significant amount of time without oxygen getting to the brain or the rest of their body, those can have very significant and poor long-term outcomes, though fortunately early treatment and administration of healthcare can help to really improve a patient's likelihood of having a full recovery.

Host Amber Smith: Will their bodies crave more of a drug that almost killed them?

Vincent Calleo, MD: The way the receptors in the body work are very, very complicated. And, there are lots of things that we in the health care field don't fully understand, but are trying to study more and more fully. But one thing that we do know is that the opioid receptors in the body, still are firing. And from the physiologic standpoint, or the standpoint that affects the body, there is that very high likelihood of that dependence still being there and the body is still craving it, even if it's a substance that could have potentially resulted in significant harm.

Host Amber Smith: Interesting. Well, I appreciate you making time for this interview, Dr. Calleo.

Vincent Calleo, MD: Absolutely. And thanks so much for having me, Amber.

Host Amber Smith: My guest has been the medical director of the Upstate New York Poison Center, Dr. Vincent Calleo. I'm Amber Smith for Upstate's "HealthLink on Air."

Why does it matter that the human genome is complete? Next, on Upstate's "HealthLink on Air."

From Upstate Medical University in Syracuse, New York, I'm Amber Smith. This is "HealthLink on Air." Two decades ago, we celebrated the mapping of the human genome, but it wasn't until March 2022 that scientists announced a fully assembled genetic blueprint for human life. For help understanding why this matters so much to science, I'm talking with Upstate professor Stephen Glatt. His areas of scientific research include neuroscience and physiology, psychiatry and behavioral science and public health and preventive medicine. Welcome back to "HealthLink on Air," Dr. Glatt.

Stephen Glatt, PhD: Oh, thanks Amber. It's great to be back.

Host Amber Smith: Can we start with some background, please?

Stephen Glatt, PhD: Well, yeah, I mean, it's such an exciting topic because we all took for granted that the first draft of the human genome was completed back in 2001. There was a huge public dissemination effort made around this, and that ushered in an era of expectation around personalized medicine. "Now we know what the draft of the human genome is; we can take advantage of that to design better medicines that take advantage of us knowing everyone's genetic background." But it simply wasn't the case. That was the first draft. And I think the scientists at the time were appropriately cautious to say, this is a blueprint, but it's not the full volume, right? It's not the unabridged version of the encyclopedia. It's just the draft. And so it's taken a long time to fill in the gaps, but it's estimated that that first draft covered maybe 70 plus percent of the genome. And a lot of it was still unmapped. Now, we're at a point here in 2022 where 99% or more of the genome is mapped. And so we can consider this a complete human genome. There's still probably intricacies in there that need to be worked out a little bit as well.

Host Amber Smith: So why was the human genome project originally launched? What did we want to learn from this? And why did we think it was important to embark on?

Stephen Glatt, PhD: Well, it's such a complicated question, but I'll try and do it justice. In essence, our DNA code holds the recipe for making proteins, and proteins are the parts of our bodies that combine to make things like receptors for drugs, or natural chemicals, or the elements of our muscle tissue or skin, or our nerve cells in our brains. Everything that you can lay your hands on, on your body, is made out of protein.

And the instructions for assembling those proteins are in our genomes. And the little, minute differences between you and I and other individuals in our DNA code determines subtle differences in the proteins that we'll make. And which proteins we have determine how effective certain drugs will be. For example, one type of protein that I might make based on the recipe in my DNA code may bind more strongly to a drug or to a natural chemical than the protein that you've made.

And that's in large part determined by what DNA code we've inherited. So the scientists intuited that if we understand everyone's recipe book, everybody's individualized recipe for how they're building proteins, we may understand why some people get sick and others don't, even though they're both exposed to the same environmental circumstances. It may be because one person's making a protein that's better or worse under some certain environmental condition than another person.

So it was really intended to give us a sense of everyone's reaction range, it's called, how they're going to respond to things in their environment, based on the proteins that they're capable of making.

Host Amber Smith: Do you know how many scientists worked on this project collectively, and were they just United States-based scientists?

Stephen Glatt, PhD: Oh, no. The U.S. made a major push to formalize the human genome initiative and was one of the leaders in that initiative, but scientists from over 200 different groups participated in this, in countries in the UK and France, China and Japan, and several other countries around the world. So this was not an initiative that was led or that could have been led by any one group, any one laboratory or even one country or government. This had to be a collaborative effort. And then all the results generated in all these labs around the world needed to be stitched together, which was another huge effort.

Host Amber Smith: So did all the different labs, did they all take different pieces of the genome? Do you know how it was, I mean, because there were sequenced roughly 3 billion letters. I mean, how did you divide the work up?

Stephen Glatt, PhD: That's right. You just don't everyone set about it randomly, and let's all see what we can produce. You assign certain chromosomes, of which we have dozens of these, divide them amongst the different labs that are interested. And then each lab would go about sequencing some part of the chromosome or an entire chromosome. And then stitch those results back together based on the overlapping sequences that are detected.

Host Amber Smith: We recently heard that there were gaps in the human genome project. Can you explain what those gaps were that have recently been, closed?

Stephen Glatt, PhD: Sure. Yeah. I think you could say that we sequenced the easy part, but none of it was easy. But it was just that it was more accessible. If you think about each chromosome as kind of a letter X, the part where the letter X, the two lines cross in the middle, that's called the centromere. And that's a place where the DNA is really tightly wound. And because it's so tightly wound, it's not really accessible. It's being broken down or sequenced by the technologies that were in place at that time. So the centromeres were kind of off limits, and they weren't part of the original sequence draft.

The same is true of the telomeres, which are the tips of each line in the X. So there's four tips on the line of the letter X. Those outer ends, they get degraded over time, and they're very difficult. They have highly repetitive sequences, which are hard to map too. So imagine if I asked you to remember a phone number. You could do that if the numbers have some repetitive pattern. Or if people remember the digits in pi. Some people can memorize that. But what if the digits in pi were just repetitive over and over again? 3.14, 3 1 4, 3 1 4, and so on. You might lose your place. And that's kind of what happens with sequencing technology. When there's a lot of repeated letters of the genome, those A's, C's, G's and T's that are the nucleotides in our genome. When those just repeat in sequence over and over again, it's very hard for the sequencing technology to keep track of where it is. And in the telomeres where there's these repetitive segments of DNA, they kind of left those areas out of the original draft, as well. So the extended outer arms of those chromosomes, as well as the central part of those chromosomes are what have been filled in now with better sequencing technology.

Host Amber Smith: You mentioned the X chromosome. Does this apply to the Y chromosomes, too? They have the telomeres on the ends?

Stephen Glatt, PhD: Well, that's true that the Y has telomeres, and I wasn't referring to the sex chromosomes. I know it's confusing without a visual aid. But there's X and Y chromosomes that determine which sex we are. But I was using more of the visual symbol of an X, because all the autosomes, which are all the other chromosomes, besides your sex chromosomes, also have that X-like shape.

Host Amber Smith: I gotcha. So there's equipment that we have today that allows us to do more than we could do 20 years ago, essentially?

Stephen Glatt, PhD: That's right. The process for sequencing at that time called Sanger sequencing was very methodical, very precise, but very slow. And so a lot of different laboratories were deploying Sanger sequencing and then assembling those reads into one map. Now we have something called next generation sequencing, which uses a totally different technology to sequence lots of fragments of DNA in the same sample, in parallel. So it's not just reading one. It's not like pulling one thread through a needle eye. It's like passing many threads on a loom at the same time. That's what Sanger sequencing was, is passing a thread through an eye of a needle, one strand of DNA. Whereas now, it's like multiple strands of DNA being sequenced simultaneously.

Host Amber Smith: This is Upstate's "HealthLink on Air," with your host, Amber Smith. I'm talking with Dr. Stephen Glatt. He's a professor at Upstate, and we're talking about the importance of scientists completing the mapping of the human genome.

What more can you tell us about this newly sequenced section of the genome? I think I read something that it had something to do with aging?

Stephen Glatt, PhD: Well, it's true that those telomeres -- which are the outer tips of the chromosomes, not the centromere, the central part, but the telomeres -- those have long been thought to be involved in aging, because what we've noticed is that as people and animals age, their telomeres shorten. As cells go through division cycles, as we age, your cells are constantly dividing to regenerate to make new ones, and those cells pull apart, and they pull those chromosomes apart to make new cells that each have a set of those chromosomes. And the points of attachment for those chromosomes are the telomeres. So you can imagine if you're pulling those apart repetitively, you're going to lose some fabric at the ends, and that's what's happened in telomeres. So telomere shortening is actually a proxy for one's biological age. And so having the sequence of those telomeres and finding out what areas of the telomeres are being degraded and how that correlates with aging phenotypes or disease phenotypes, that's why that's so important because it's already an area of the chromosomes that we know is related to how well or poorly an animal or an individual ages.

Host Amber Smith: Can you envision concrete ways in which this completed genome might contribute to human health?

Stephen Glatt, PhD: Oh gosh, it boggles the mind. I don't want to overpromise because what we've fallen into in the past, even with the first draft of the human genome, is we set up an expectation that by knowing the sequence of the human genome, it would enable personalized medicine, and all of our problems would be fixed. Now, none of us in science believed that, but sometimes the translation of the message gets lost.

And so while knowing the genome sequence has enabled so many great advances in medicine and technology, we also know that there's a lot more to do to translate just knowledge of the structure of the genome into things that help people. But what I envision for the future really is that having this sequence of the genome now much more complete will enable us to determine what are the differences between individuals in their DNA code and how that relates to what diseases they get or what diseases they're resistant to? And that, in turn, will help us design better interventions, whether those are medicines, whether those are nonmedical interventions, but things that target our genomes in ways that we couldn't envision or understand without knowing what our blueprints are.

I think it will also help in prediction of disease so that people can understand their risks so that they can avoid certain environmental exposures that might compound those risks. For example, if your DNA code says that you're at a heightened risk for lung cancer, you certainly might benefit knowing that information, so you could avoid that first cigarette. I envision a lot of uses both in terms of the design of better medicines, the interventions that can be done in the clinical practice of medicine, but also in prevention.

Host Amber Smith: Would we ever see a time when everyone's genome is mapped and recorded for medical or identification purposes, or is that science fiction?

Stephen Glatt, PhD: I think we will see that time. And even at this stage, it's possible for each of us to have a rough map of our own whole genome sequence derived for a few hundred dollars. We can generate whole genome sequences now pretty readily on most people. We may not have all the telomeric information or the centromeric information from everybody, but you can get a readout of your own blueprint for less than a thousand dollars.

The issue is not generating those genomes. It's storing the data and using the data. If you can believe it, this generates a massive amount of data, and to store and manipulate and move that data is much more difficult than faxing over an X-ray. It takes huge computational resources to process and align and store that DNA sequence data. And it's even more difficult once that data is generated and can be passed around on your personal flash drive or something, let's say, to make sense of that. A lot of science has to happen understanding how those DNA codes that we have relate to the proteins we can produce in the diseases that we're at risk for, or the medications we may or may not respond to. A lot more science has to be done first, before we can capitalize on knowing our sequence. We can generate and we can keep our sequences, but what does it all mean? How can we use it? That's the frontier that we haven't crossed just yet.

Host Amber Smith: So a person who got their entire genome done through one of the services that does that, they could bring that to their doctor today, but what is that doctor going to do with it?

Stephen Glatt, PhD: That's the question without an answer.

There's nothing; aside from very significant, major changes in the structure of your chromosome, it's very hard to take information about tens of thousands of small changes in your genome and what that means for your health. So for example, with knowledge of a family history of a significant disease, such as breast cancer for a BRCA-1 or -2 mutation, or early onset Alzheimer's disease from a presenillin-1 or -2 mutation, if you know that these diseases run in your family, it may very well behoove you to seek out your sequence information, maybe not even for your whole genome sequence, but for these loci that I've mentioned to see, am I a carrier of this gene that puts me at very significant risk for a life-altering diagnosis?

On the other hand, most of the diseases that have high morbidity or mortality, that cause a lot of sickness and death, are not those that are caused by a single genetic event. They're more like what we call complex disease or multifactorial disease. Things like mental illness, things like cancer, most forms of these diseases are caused by a combination of genes and environmental factors, and not just the effects of one gene or 10 genes, but hundreds, if not thousands of genes.

And when I say genes, I mean these little individual changes in your DNA code. And so the personalized suite of DNA changes that you possess may set some level of risk for you, and the environment in which you are raised or that you choose may set another level of risk. And then those two combine to determine how likely you are to have a disease like depression, or like colon cancer. And so knowing your sequence at any one of those thousands of genetic sequences is not going to help you much because none of those individual genes is necessary or sufficient to cause disease. They're just risk factors.

You can have your genome sequence, but then what? Like, what do you make of that? Just knowing it is not enough. It may be readily apparent in someone's genome sequence that they have a huge problem. And if they have a huge problem, that's worth knowing. But you still can't correct it. You can't fix it. You may change the way you deal with the disease that's owing to that. I mean like a portion of their entire genome, like millions of nucleotides, may be repeated or deleted. That's a big, big problem. That's just not you having an adenine and me having a cytosine in one position, one nucleotide. I'm talking millions of those being deleted. That's a big, big problem. And that has a lot of effects for the person. Knowing that helps manage the sequella that come from that, right? But what can you do with those minor kind of risk predisposing alleles, most of which have a minute effect on your liability toward a disease? And none of which, as I mentioned, are necessary or sufficient. If you have it, it increases your risk. If you don't, you still can get the disease because there's lots of other redundant factors that increase your risk. So I think having whole genome sequences of ourselves at our fingertips is more noise than signal right now. That's where you need the bioinformatics and the data analytics to understand what are the important ones? What's their likelihood, in combination with other important ones and environmental factors, that this person will have a disease? Then you could start to intervene.

Host Amber Smith: Upstate's "HealthLink on Air" has to take a quick break, but stay tuned for more about the human genome with professor Stephen Glatt.

Welcome back to Upstate's "HealthLink on Air." I'm your host, Amber Smith, talking about the human genome with Dr. Stephen Glatt. He's a professor at Upstate whose areas of research include neuroscience and physiology, psychiatry, and behavioral science and public health and preventive medicine.

This now completed blueprint of a full human, is it a woman or a man?

Stephen Glatt, PhD: This is a misnomer to say that it's one individual's genome. It's actually an amalgamation of different individuals. And in this case, it's a cell line that was sequenced, that was taken from an individual long ago. But even the original draft of the human genome was an amalgamation of several individuals. And so the next frontier is for us to get much more representation from individuals across the globe of different ancestries, men and women, so that we have a better sense of the range of variation.

Host Amber Smith: I'm just curious now. So we have this blueprint of a full human. Can we clone this person now that we have this blueprint?

Stephen Glatt, PhD: Well, theoretically, and technically, it's possible that that sequence could be used, but it's not the sequence information that's going to allow the cloning. You could clone an individual today. And in fact, a scientist in China claimed to have cloned a human being a couple of years ago, and that was met with a lot of scorn in the scientific community and the ethical community, because it's not a thing that should be done, ever. But it's not knowing the sequence information that enables the cloning. Actually just having access to a DNA sample enables the cloning. You don't need to know what those sequences are in order to necessarily clone them. You could do that in a biological way. But I think having the access to the new sequence that we have enables some cloning of individual proteins that may be helpful for purifying these to make medicines. But I don't think anyone's intending, nor should anyone be intending or imagining, that we're going to use advanced sequencing technologies like this to develop clones of animals or humans.

Host Amber Smith: The sequences, would the sequence be different based on ethnic or racial differences in the person whose cell line it's drawn from?

Stephen Glatt, PhD: Indeed. There are major differences in the DNA sequence of different ancestral groups around the world. And in fact, even with existing technologies, we can readily detect those differences. So if we genotype individuals of Northern European ancestry, Latin American ancestry, East Asian ancestry on standard genotyping technologies, and then we look at everyone's code, we can sort people into bins of ancestry based on what DNA markers they have. So it's pretty clear that a lot of our DNA code is related to our ancestry, and that's how it's intended. We're intended to inherit these things. But the differences among the ancestral groups and especially in America start to dissolve. We are a melting pot, both sociologically and ideologically, but also genetically in America. And so mapping ancestry of people in a place that's highly, admixed like America, results in very different findings than if you were to genotype individuals in a more ethnically or ancestrally homogeneous place, where there's not a lot of immigration or emigration.

But yes, your ancestry does relate to which sequence variations you carry forward. Some of those will be related to the prevalence and risk for disease, and others of those are just related to the structure of the DNA and how it holds together.

Host Amber Smith: Have we completed genomes for other animals? Horses, cows, dogs, chickens?

Stephen Glatt, PhD: A lot of species have been sequenced over time. And those, each of those has been a huge breakthrough for science and there's been a queue: "let me get my species into the queue where we can generate its entire genome." And I think for farming, for livestock, for crops, agriculture, knowing those sequence variations, scientists want to capitalize on those the same way they do for human health to make better crops, to make more disease-resistant animals and so on. But there's a litany of species that have been sequenced in a similar manner.

Host Amber Smith: I'm assuming that the human genome is the most difficult. Is that right?

Stephen Glatt, PhD: No, that's not right. There are other species that have intricacies to them that make them much more difficult to sequence than humans, such as circular DNAs, for example. Ours are in an X shape, but some species have their DNA wrapped in other configurations that make it even more difficult to sequence. Highly repetitive sequences abound in other species as well. So I would say the human genome is no more or less difficult than the average animal.

Host Amber Smith: So I was wondering, do scientists learn anything that helps in human medicine from studying the genomes of plants or animals?

Stephen Glatt, PhD: There's this entire kind of scientific pursuit of genome biology, whether it's done in animals or plants or humans, whatever we learn from one pursuit, we want to disseminate widely and adopt those principles in the pursuit of advances in human health. And largely those are technological, but sometimes those are theoretical game-changing discoveries about the biology of the genome. So there's still a lot that we have to discover, and I think it's let a thousand flowers bloom. You know, study plant genomes, study animal genomes and human genomes at the same time.

Host Amber Smith: So, what do we have to look forward to next in human genomes? Because 20 years ago there was news coverage that it was complete, but it really wasn't entirely complete. But now we're being told it is entirely complete, but is it really?

Stephen Glatt, PhD: It's very, very close. There are still some aspects of the genome that are being mapped, but it's very, very close to a final map of an amalgam of individuals, or this one cell line. So what we obviously need to do is repeat this process many, many times, because the sequence information you gleaned from one, or even a handful of individuals may not contain all of the variation of individuals of a different ancestry. So we need to complete genomes of many, many people so that we have a reference set against which any new individual with some disease can be sequenced and compared to find what's different in their genome that might have caused them to have that debilitating disease. So we need to generate lots and lots more genome sequences themselves. And then the other aspect that's going to grow very fastis exploration of how those individual changes in the genome, that we all have, relate to the types of proteins that we make and how that in turn relates to our risk of disease or our response to interventions like medications.

Host Amber Smith: Would the genome have changed over time? If the genome was completed 200 years ago, versus today, would there be differences just because of the span of time?

Stephen Glatt, PhD: So genomes do change and evolve. But 200 years in genomic time is actually a relatively short period of time. The average genome of a human now is pretty much the same as it was of the average human 200 years ago. Although, genomes do change and acquire new mutations, especially due to cancer causing agents, things that are introduced into the germline and passed on from generation to generation. We also have DNA repair mechanisms. And so when those changes are introduced, we generally fix them. But sometimes mutations do sneak through. Sometimes they're advantageous and they lead to better fitness and passing on more of that gene to the next generation. Sometimes they're deleterious or harmful, and they lead to less fitness and less success in passing them onto the next generation. And sometimes they're neutral and they just go for the ride.

Host Amber Smith: Could prehistoric humans be sequenced, possibly from fossils or remains?

Stephen Glatt, PhD: Well, absolutely in fossil remains, there is detectable amounts of DNA at times. So it is conceivable that the sequences of, for example, Neanderthal or other proto-humanoids will be sequenced. And that's interesting as well. You can already, for example, know the Neanderthal genome and compare when your genome is sequenced, how much Neanderthal do you have in your genome? I think I have 2%.

Host Amber Smith: Well, I appreciate you making time for this interview, Dr. Glatt.

Stephen Glatt, PhD: Oh, it's my absolute pleasure. It's the most exciting thing going on in my field of psychiatric genetics, but also in a lot of medicine. There's a lot of buzz about this, so I'm glad that you've dedicated the time to tackle it and share it with your listeners.

Host Amber Smith: My guest has been Upstate professor Stephen Glatt. His areas of research include neuroscience and physiology, psychiatry and behavioral science, and public health and preventive medicine.

I'm Amber Smith for Upstate's "HealthLink on Air."

Here's some expert advice from rehabilitation psychologist Dr. Debbie Spinks from Upstate Medical University. What's important to know about concussion?

Debbie Spinks, PhD: A few physical symptoms are usually the first ones kids are aware of, headache being the No. 1 most obvious symptom, followed by maybe some dizziness, nausea with the headache, blurry vision, double vision, even briefly, after an injury, light sensitivity to the sunlight or the other lights at school, noise sensitivity, cafeterias, things like that bothering them more often, and just things in their daily life bothering them more often, like TV and computer screens, the noise with their families at home.

You don't have to lose consciousness to have sustained a concussion. It is one of the criteria that helps diagnose it. It makes it pretty clear that a concussion occurred if you lost consciousness, but if you have an altered mental status, confusion, you're dazed or can't remember moments, seconds or minutes around your injury. That can also clarify that the brain was injured enough that it likely sustained concussion.

There's no actual test at this time. There is research people have heard, and there might be buzz about, like a blood test. But that's still in the early stages, and nothing like that exists at this point. And there's no brain imaging that confirms concussion or not. The brain imaging technology we have could rule out bigger issues, but it's not usually helpful in diagnosing a concussion at this point.

A majority of concussions may have symptom resolution on their own in days to weeks. At times, there's a large minority that might have some persisting symptoms that, weeks in, might benefit from a nudge in the right direction, and those treatments include physical therapy or occupational therapy.

Rest, avoiding stimulation, cutting back on school and physical activity can usually help in the early days and weeks for the symptoms to resolve on their own as well.

Host Amber Smith: You've been listening to Dr. Debbie Spinks, a rehabilitation psychologist from Upstate Medical University.

And now, Deirdre Neilen, editor of Upstate's literary and visual arts journal, The Healing Muse, with this week's selection.

Deirdre Neilen, PhD: Some of our most visual and poignant poems are those describing family members. Sibling love. Here are two from our latest issue.

First is Jeremy Gadd from Australia, who offers us a portrait of opposites when young, but now finding common ground.

Here is "We Were":

We were orange and apple,

yin and yang, chalk and cheese

as children; quiet to your loud,

near to your far, circle to your square,

sharing only unruly hair and shelter

from the storm of parental repression

and mutual amusement at our

teenage indiscretions but, now,

more bonded in dying than

in life by a genetic disease,

we share more laughter than depression,

more love than any previous sibling aggression.

Zoe FitzGerald-Beckett is from Maine, and she takes us back and forth in time to pay tribute to sisters' love. Here is "Sleeping with My Sister":

We were sleeping together again, rain drumming

on the roof. Rain and tears in torrents, and the salt

and sweat of love's labor to save her. To vanquish

all fears, and the monster growing in her brain.

Our childish fears often drove us both out of bed

in the past. Her fear of everything. My fear our parents

might disappear. We'd meet in the dark and cling together,

crying and comforting, in whatever bed would have us.

Our grown-up fears were in bed with us that night, silencing

the hard questions. What is her brain tumor doing? Is there

nothing left we can do? Truth banished to the darkest

corner. No answers but the drumbeat of rain on the roof.

She was the beauty of the family; the baby sister who followed

me everywhere, sure I knew everything. She always asked, Where

are you going? Can I come too? I'd say, Yes. Sometimes. Or, No.

Leave me alone. That night I prayed, Don't ever leave me.

The rain was slowing. Her voice a drifting mist. She said, Listen,

it sounds like music. What does it mean? Knowing nothing, I

could only ask, What? She said, The back and forth, the back

and forth. And I could only whisper -- O, Pioneer. O, Dear Heart.

Host Amber Smith: This has been Upstate's "HealthLink on Air," brought to you each week by Upstate Medical University in Syracuse, New York. Next week on "HealthLink on Air": what you need to know about temporomandibular joint dysfunction. If you missed any of today's show, or for more information on a variety of health, science and medical topics, visit our website at healthlinkonair.org. Upstate's "HealthLink on Air" is produced by Jim Howe, with sound engineering by Stephen Shaw. This is your host, Amber Smith, thanking you for listening.