Chris Powell  00:00

Welcome to Season Four of Tiny Expeditions. This season is all about the promise of a better future through genetics and biotech.

Sarah Sharman  00:08

We’ll explore how DNA technology is crucial to our fight against growing threats to our livelihoods—  from climate change to food security to future pandemics. I’m Dr. Sarah Sharman here to help you understand the science.

Chris Powell  00:21

And my name is Chris Powell, I’ll be your storytelling guide. So, Sarah, it’s a new season and we’re going to start this one out with a bang—no pun intended—because we’re talking about forensics. So, are you a true crime genre kind of fan? Do you like this kind of conversation?

Sarah Sharman  00:43

Absolutely, Chris, and I feel like the true crime genre is everywhere right now. You can’t go anywhere without books, podcasts and TV shows that just dive into the world of forensics. But I often wonder, is that all factual?

Chris Powell  00:56

Yes. So that’s a great question. It’s incredibly hard to separate what’s fact from fiction, especially when fiction looks so stinking cool on TV. But there are a few like real world cases that have come up recently that have brought to light the science behind the technology that’s used in forensics and one of those was the Golden State Killer.

Sarah Sharman  01:20

The Golden State Killer was a serial rapist and murderer who committed a string of crimes in California during the 1970s and 80s. He was responsible for at least 13 murders, 50 rapes, and 120 burglaries in California between 1974 and 1986.

Chris Powell  01:37

These crimes began as home invasions and burglaries but soon escalated the sexual assaults and, eventually, murder. Despite a massive manhunt and years of investigation by multiple law enforcement agencies, the Golden State killer eluded capture for decades. He was known for meticulous planning and evasion techniques, including using disguises, stalking his victims, and avoiding leaving behind evidence.

Sarah Sharman  02:02

In 2018, advances in DNA technology led to the arrest of Joseph James DeAngelo, a former police officer identified as the Golden State Killer. DNA evidence linked him to the crimes, and investigators built a case against him using genealogy websites and traditional police work. He pled guilty to 13 counts of murder and numerous other charges related to the Golden State Killer crimes in June 2020. He was sentenced to life in prison without the possibility of parole.

Chris Powell  02:31

The case was considered one of the most significant cold case breakthroughs in history, and it provided closure to the victims and their families after decades of uncertainty and fear. This is just one of many examples in the news and pop culture where DNA technology was used to resolve an unsolved crime.

Sarah Sharman  02:48

During the next two episodes, we’ll be joined by three special guests who will help us understand the technology and answer ethical questions about using DNA technology to solve crimes.

Chris Powell  02:58

First up, we’ll hear from a brand-new voice to the podcast, Angelo Della Manna. He’s the Director of the Alabama Department of Forensic Sciences.

Angelo Della Manna  03:06

I’m Angelo Della Manna. I’m the Director of the Alabama Department of Forensic Sciences, and I have the great privilege of directing one of the nation’s oldest and premier forensic science agencies.

Sarah Sharman  03:19

You’ll also hear from a familiar voice to the podcast, Dr. Greg Barsh.

Greg Barsh  03:23

This is Greg Barsh, and I’m a faculty investigator at HudsonAlpha and the Smith Family Chair of Genomics and my expertise is in human genetics and animal genetics.

Chris Powell  03:34

And finally, another familiar voice Dr. Thomas May. Now we’re going to save his introduction for the next episode because he’s going to help us process through the ethical questions surrounding this DNA technology.

Sarah Sharman  03:50

All humans have DNA in most of the cells in our bodies. Although 99% of your DNA is the same as the more than 7 billion other people on Earth, the 1% difference makes us all unique. It’s this uniqueness in our DNA that allows forensic experts like Director Della Manna to use it to solve crimes.

Chris Powell  04:09

Director Della Manna directs the entire Alabama Department of Forensic Sciences, which deals with a lot more than just DNA analysis. If you’ve ever seen CSI or other criminal justice shows, you know that many different tests and analyses go into investigating crimes.

Sarah Sharman  04:24

The death investigation section performs autopsies for unattended, unexpected, potentially criminal, or undetermined deaths across Alabama. In the forensic toxicology section, experts perform analysis of biological samples like blood for the presence of toxins, including poisons and drugs. Similarly, the drug chemistry section identifies unknown substances at crime scenes.

Chris Powell  04:47

Director Della Manna’s team is also in charge of the implied consent in breath alcohol testing section, as well as the firearms and tool mark section which analyzes firearms and tools found at crime scenes to help investigators solve criminal cases.

Sarah Sharman  05:03

These divisions are all important and work together to help law enforcement solve criminal cases. But today, we’re here to talk about a specific section, the DNA section, which handles all forensic biology analysis for the state of Alabama.

Angelo Della Manna  05:16

The section that that handles all of the forensic biology work is the DNA section. And so typically that that work has also changed dramatically over the course of my career. And we conduct generally, DNA work and forensic biology analysis on cases that involve both the identification of biological fluids as well as the downstream DNA analysis of those fluids. So, all of that testing, those stains are generally in a dried state. So, we have not just standards from victims and potential suspects and maybe consensual partners in a sexual assault investigation. But we also have DNA testing that’s conducted on bloodstains and semen stains and saliva stains on a cigarette butt, for example. And on touch DNA that is very small, minute amounts of biological material that may be left behind on a steering wheel or a gearshift lever or a doorknob of a suspected residence, for example.

Angelo Della Manna  06:27

And that is all conducted with the premise of you are trying to associate or exclude individuals as being the source of genetic material in what is commonly referred to as the crime scene triangle. So, you’re either trying to associate a victim with a suspect, a suspect with the crime scene, and the victim with the crime scene. Those are the three points of that triangle, and forensic biology and serology and DNA work does an excellent job in that regard.

Sarah Sharman  07:01

But before we get into the weeds about the work that the forensic lab is performing, let’s learn about the two types of DNA technology they’re using.

Greg Barsh  07:08

And so, there’s actually two ways of thinking about what happens today and what’s going to happen over the next five years in how genomics can be applied to forensics. One of them is exactly what you said and exactly what happens today in most forensic laboratories, and that’s basically DNA fingerprinting. The other is something that’s also pretty popular in the news. And that’s the notion of using companies or databases like GED match, or 23andme, or ancestry.com. And the DNA fingerprinting approach used by forensic labs, and the genetic genealogy or GED match ancestry approach, use two kinds of different technologies with different sorts of implications.

Sarah Sharman  07:56

Forensic genetic genealogy is a fascinating new tool law enforcement is using, and we’ll get there at the end of the episode. But first, let’s dive into the older technique, DNA fingerprinting. Chris, when you hear the term DNA fingerprint, what do you think of?

Chris Powell  08:11

Okay, so the fact that you’re asking me this question means that there’s probably more there than what I would normally think. But when I hear the term, obviously, fingerprint is what jumps out. So are you telling me this is very much like traditional fingerprinting, right, where you have a print, you’re able to match it up? And if it’s a one to one match, then you can say this person was at the crime scene? Is that what we’re talking about here?

Sarah Sharman  08:33

Yeah, it turns out DNA fingerprinting is very similar to traditional fingerprinting only a little bit more complicated. Basically, experts match pieces of DNA to each other.

Chris Powell  08:43

To match the DNA it means that you have to have a DNA sample. So that brings up a whole separate host of questions like how are we able to get the samples from crime scenes?

Angelo Della Manna  08:53

The analysis in that section generally proceed from the very general to the very specific. So, the first thing is in a homicide case, for example, if we have suspects clothing, and we see some reddish-brown stains on the jeans or on the shirt from an identified suspect. The first question is really, is that reddish brown stain a blood stain? Or is it Taco Bell sauce, or ketchup or some other stain that may present as a reddish-brown stain? So, we can go through a battery of very quick chemical tests that are specific for components of blood that will then give us an indication- yes, that is indeed a blood stain. So that’s a very general quick test. Once we’ve determined that, yes, it is indeed a blood stain, then the hierarchy of getting more and more specific is, is it a human blood stain, or is it deer blood, dog blood, cat blood, that sort of thing? We then conduct the battery of DNA testing that is very specific for human DNA. And we look at specific markers or addresses on the DNA that we know are very unique between individuals. And then we compare that downstream DNA profile to the profiles of the individuals in a case. If there is no suspect in the case, and we are successful in developing a DNA profile, we then enter that DNA profile into the Combined DNA Index System, which is commonly referred to as CODIS. This is the national DNA database system that’s available to law enforcement and forensic laboratories throughout the country to compare DNA profiles that try and associate criminal acts to one another and individuals to one another.

Sarah Sharman  10:54

CODIS is more than just a database, though. It also refers to the identifying parts of DNA that can differentiate one individual’s DNA from everyone else’s DNA.

Greg Barsh  11:03

DNA fingerprinting makes use of what are called CODIS markers. CODIS is Combined DNA Index System. So, in that Combined DNA Index System, there really are a couple of important points. First of all, let’s talk about the word index. And so what that implies is that you can sort of look up the identity of an individual based on some aspect of their DNA. And in fact, that’s what makes the CODIS system and DNA fingerprinting so powerful. And so to do that, what you need is a way to distinguish one individual on the planet from every other individual on the planet because what you don’t want is to say, ‘oh, gosh, you know, your DNA matches evidence left at a crime scene, but also, there could be hundreds or thousands or tens of thousands of individuals who also match that. And the index part of DNA fingerprinting is something that speaks to the singularity and uniqueness of the approach.

Greg Barsh  12:18

And so, in fact, the way that CODIS system actually works in practice in forensic laboratories is they don’t actually determine the sequence. What they do is they measure the length of the fragment of DNA that contains the repeated elements. And that’s done using the exact same approach that is used for nearly all aspects of genomics, and that’s the polymerase chain reaction: PCR. So, you take little bits of DNA that are absolutely unique, like a 20 nucleotide fragment, and you take another 20 nucleotide fragment that’s absolutely unique. We call those primers. So only those match to one unique place in the genome that surround the repeated part of a CODIS marker. And then you use the polymerase chain reaction to make a lot of that product. And you say, well, how big is it? Is it 200 nucleotides long? Is it 210? Is it 220?

Greg Barsh  13:19

And, of course, these are on autosomes, the parts of the genome that are on chromosomes, and so all of us have two copies. And so, everyone will have actually two values, you might have a 210 and a 212, you might have a 218, and a 224. And that is your genotype at the CODIS marker. So, when we talk about often human disease, and SNP genotyping and ancestry, and we talk about a genotype, we’re saying, ‘oh, well, you are an AC at this position, or you are a GG at that position,’ GG meaning that you got a G from your mother and a G from your father. But the way the CODIS marker works is we’re not talking about an A or C, we’re talking about length. And so, you can be 210. Maybe you got that from your mother and 218 that you got from your father. And so, the way that it’s actually done is to use the polymerase chain reaction to make these small fragments, and then look at the size of the fragments using a system called capillary electrophoresis.

Sarah Sharman  14:28

Our experts have given us a lot of information so far. Let’s make sure we’re all on the same page. Police arrive at a crime scene and collect a sample believed to contain DNA. They take it to a forensic lab where they confirm whether or not it’s human, then their forensic experts use PCR to make a DNA profile. This profile is entered into the CODIS database to hopefully identify a match.

Chris Powell  14:52

It’s not until the DNA is in a CODIS profile that investigators are able to compare it to the other known profiles that are in the database. Now there’s a whole set of questions that we’re going to have to ask on the next episode regarding the ethics of putting people’s profiles into the database. And we’ll get there. But today, we need to understand what the database is. And this database is fairly complex. It’s not just a single database of criminals. There are many different uses for this database.

Angelo Della Manna  15:28

One of the interesting things also about CODIS is the different types of what we call indexes that are within the database. So, we have a forensic index, which is a bucket if you will of DNA profiles that are all from the crime scene, right? And so that’s in our forensic index. So, this would be DNA profiles from sexual assault cases, DNA profiles from homicide cases, the actual evidence, stain DNA profiles, those go into the forensic index. Then you have your convicted offender and arrestee index where the known reference samples of individuals go in. And then, obviously, those two indexes are searched against one another every day.

Chris Powell  16:17

These first two databases are compared against each other to solve crimes. But there’s a third database that caught our attention that Director Della Manna told us about,

Angelo Della Manna  16:26

We have the relatives of missing persons and our unidentified human remains index. So, this is a special index where we have occasions where in a specific example that comes to mind, you have an individual that runs away from home. And let’s say she’s a teenager, and her parents do not know, you know, as an 11th grader, as a junior in high school, if she’s a runaway, and has become the victim of foul play, or if she’s a runaway and headed west to, you know, find a new calling. And so fast forward  you know, let’s say a couple of years later. Somebody’s hiking in the desert in Arizona, they find what looks like a human femur, or thigh bone in the desert. And so, the Forensic Laboratory in Phoenix, the Arizona Department of Public Safety, conducts a DNA testing upon that femur, you have no idea who who that belongs to. And they enter that DNA profile from that femur into the unidentified human remains index.

Angelo Della Manna  17:43

And then, in Alabama, for example, the parents of that runaway could have provided a mouth swab for entry only into the relatives of missing persons index so that when the routine search of CODIS happens, we can say that femur that was found in Arizona could be the biological offspring of these parents from Alabama, and so help to identify previously unidentified human remains cases in that manner through the missing persons index. What’s important about the missing persons index is that as parents submit consensual samples to enter to try and find their relatives, it’s important that they recognize that those samples are not searched against our crime scene samples. It’s not lawful to do so and CODIS can’t do it. So, you know, we want individuals who are truly the relatives of missing persons to be comfortable providing samples for entry into the database, so it can be searched against the skeletal remains that are found throughout the country, and not worry about, is my sample going to be searched against unsolved cases, you know, in the in the forensic index, because it’s just not going to be it’s not available.

Sarah Sharman  19:06

DNA fingerprinting has been used to create millions of profiles and solve countless crimes. But you might be asking yourself, how accurate is it actually? What are the chances that my DNA might be accidentally linked to a crime scene?

Angelo Della Manna  19:24

If the state of Alabama map is like the DNA molecule, we’re focusing on a specific address for each one of our markers. So, I am looking down Discovery Way, for example, and I come down to Discovery Way and at 500 Discovery Way now I know through a variety of genetic research that individuals can only have 15 different types of houses there. You can have a five-story apartment building, you can have a bungalow, you can have a side split, you can have a red brick house. But those are the 15 possibilities at that particular address on the DNA. That’s very polymorphic, which means if I have a crime scene stain, and I zoom down to 500 Discovery Way, and I find a two-story red brick house on my crime scene stain and now I have the victim and the suspect’s reference samples and I conduct DNA testing on them and I look at 500 discovery way and I see that one individual had a two-story red brick house at that location, but somebody else had a white side split with a carport, well, now I know the individual with the white side split could not have donated the crime scene stain because they didn’t have that trait at that location. And so, we conduct that kind of metaphor, that example, not just for one marker. Originally, we looked at 13 independent markers that were very discriminating and allowed us to get very specific about who could or could not be the source of a crime scene stain. And as I mentioned earlier, that is the true power of forensic DNA testing is that across those 13 markers, the exclusion possibility of an individual picking them out at random, okay, it was greater than 99.999999%.

Chris Powell  21:35

The technology that’s behind DNA fingerprinting is quite impressive. And to hear the stats, the accuracy stats that Director Della Manna just told us those are, those are impressive to hear. But Sarah, when we were pitching the beginning of this episode, we said that DNA fingerprinting is only one of the DNA tools that are available. And some of these other tools are quite impressive.

Sarah Sharman  21:57

That’s right, Chris. So, we just heard that in order for DNA fingerprinting to work, you must have a match in CODIS. But sometimes that just doesn’t exist. So, forensics experts have started coupling DNA technology with a method that has long been used by geneticists to trace familial relationships.

Greg Barsh  22:15

Genetic genealogy is becoming increasingly popular and increasingly applied in a number of situations, some of which are a lot of fun and some of which have important societal implications. And, the approach that’s taken by the three major companies that engage in direct-to-consumer genetic testing, is to look at about a million different places in the genome. And recall CODIS, so it just looks at 20 different places. Whereas now, genetic testing you would get from 23andme, or ancestry.com looks at a million different places. And at each of those million places, you can be in either an A, C, G or T. But since most of those places are on autosomes, you can actually two values. So, one place, you can be an A or an AT or a GC and so on. And when you have the value for the genotype, the place that you got from there, the value you got from your mother ACGT, and the value you got from your father, ACG or T at a million different places, that’s a very powerful way to look at lots of different things. Like what your ancestry is, you know, whether you are Portuguese or Irish or West African. And how much of that ancestry is actually present in your genome.

Greg Barsh  23:57

It’s also a very powerful way to look at relationships because individuals that are related will share values at differing proportions of those million different places. So identical twins are identical at all of the places. Parent and children are identical at exactly half of the places. And siblings, brothers and sisters or brothers and brothers, are identical at, on average, about half of those million different places. And then you can sort of continue that line of thinking and say that well a grandchild grandparent relationship would be about 25% of the places would be identical and a great grandchild grand great grandparent relationship would be about 12 and a half percent. And the chance that any two people if you just take two people who are totally unrelated, and say, well, you know, at what proportion of those million different sites are they the same, it’s generally not higher than a percent or so. And so, anything above a percent or so indicates that you know, you’re not too distantly related from the individual that has that.

Sarah Sharman  25:27

Joseph James DeAngelo, the Golden State Killer, was caught using forensic genetic genealogy. Throughout his crime spree, he was never caught for other crimes and entered into CODIS, so law enforcement never made a match. However, law enforcement entered a crime scene DNA profile into a public genealogy website and found a distant relative of the individual the sample belonged to. Then they constructed a family tree using information from the genealogy website and historical and public records. Through their investigative work, they identified several individuals who lived in the area around the time of the crime.

Chris Powell  26:03

After identifying these several individuals, investigators creatively found ways to obtain DNA samples to then compare to the records they had. Next week, we’re going to talk about this in more detail with our bioethicist, Dr. Tom May. He’s going to help us walk through some questions about the usage of technology and obtaining samples. But the thing we want you to see today is that this takes a whole lot of time and energy. Time and energy that many forensics departments just simply don’t have.

Angelo Della Manna  26:36

A lot of the direct consumer databases, so for example, ancestry.com 23andMe, those are not searched in a law enforcement or forensic setting. Okay, GED Match and Family Tree DNA where individuals opt-in and say I welcome the opportunity for searching and helping to identify remains samples from throughout the country, those are the databases through next-generation sequencing profiles that are routinely searched. But it’s not a one-off. Certainly, it’s certainly going to be the next wave of technology. The two limitations I would say today about genetic genealogy is it’s extremely labor-intensive to develop. The sequence profile is not as labor intensive, but then building the pedigree and the family tree and then going through public census records and birth certificates and death certificates and obituaries and trying to geographically identify who could be potential relatives that might be the perpetrator is an extremely laborious process that is not conducted within a forensic laboratory. The forensic laboratory we in Alabama have begun using genetic genealogy for very specific cases. And specifically, it’s really been very successful in unidentified humans remains cases. It’s going to be, I think, the next wave. But everybody needs to be careful that it can’t happen overnight. And oftentimes, you want to make sure that the balance between the statutory allowance and the technology is kept as it as it proceeds.

Chris Powell  28:35

There are limitations with any technology. But what is available to investigators now is quite impressive. And one of the things that we’ve learned as we’ve walked through many different DNA technologies is that it’s constantly evolving. And as the technology evolves, it opens up new doors. And so well, each day that passes, there’s a chance for new breakthroughs in cold cases in forensics.

Angelo Della Manna  29:02

And as we sit here today, you know, in Alabama, we search CODIS every day and the database has grown now nationally to over 22 million DNA profiles. And so, I still recall the early days of our DNA database, where when we got to what we called a cold hit where we had an unsolved case and we identified the perpetrator because they submitted a sample pursuant to a conviction, it was a big day in the forensic laboratory. You know, we would ring the bell and, oh my goodness, we’ve solved this case. Okay. As we sit here today, that happens every day. Last year alone, over 800 times, we identified the perpetrator of an unsolved case through a search of our CODIS index. So that’s twice a day every day for a whole year.

Chris Powell  29:58

Sarah, it’s time to wind this episode down. But before we go, I need to ask you, you mentioned before that you are a CSI watcher. So, our conversations with Director Della Manna, did it seem to line up with the reality that you see in these TV shows?

Sarah Sharman  30:14

I think for me, the thing that stood out was just the time and effort that goes into solving these cases. Oftentimes on TV, it seems like you automatically get DNA from a sample, and you automatically make a match in CODIS and go out and make an arrest, when in reality, it’s just not that easy. And it is getting there with advances in DNA technology. But it does still take a lot of time.

Chris Powell  30:37

And no doubt the advancing will continue. And so, it’ll be interesting to come back to this topic in a year, two years, five years and see what new advances are happening and where the world of forensics is now with DNA technology.

Sarah Sharman  30:51

Thank you for joining us for this tiny expedition into the world of forensics. And like we mentioned throughout the episode, we’re not done with this topic yet.

Chris Powell  30:59

Next episode, we will discuss the ethical questions surrounding the entry of DNA into CODIS, privacy rights as it relates to genetic genealogy searches, and much much more.

Sarah Sharman  31:09

Tiny Expeditions is a podcast about genetics, DNA, and inheritance from the HudsonAlpha Institute for Biotechnology. We’re a nonprofit research institution in Huntsville, Alabama.

Chris Powell  31:19

We’ve got a campus full of scientists doing public research alongside companies developing products and services, all with one aim to translate genomic discoveries into real world applications that make for a healthier, more sustainable world. That includes everything from cancer research to agriculture for changing climate,

Sarah Sharman  31:37

If you find this podcast helpful, do us a favor and leave us a review wherever you’re listening to this and tell someone that you listened to this interesting little story about genetics. Knowledge is better when you share it. Thanks for joining us!