What is a DNA Fingerprint?

Gel featuring DNA bands from three individuals compared to an unknown sample.

Gel featuring DNA bands from three individuals compared to an unknown sample.

Today in Kingston, ON, a man was arrested in connection with a kidnapping and sexual assault that took place in Calgary, AB, 20 years ago. The police were able to connect the suspect to the case by comparing his DNA to samples from the Calgary cold case.

I was asked to talk with the CTV reporter covering the story to explain DNA fingerprinting. RCMP forensics scientists-the real experts who made this type of arrest possible, aren’t available on Sundays. But if you happen to be Director of Science and Technology for a company called Life Science Forensics, and the sister of said reporter, you tend to be more available on Sundays.

One of the big questions from today’s interview was “how does this technology work?” Now, in the interview, my answer was pretty quick, because there wasn’t too much time to really explore the details-the story wasn’t about the science, or at least not ALL about the science. So here is a chance to go into a bit more detail.

The first thing to understand about DNA fingerprinting (the preferred term is actually genetic profiling) is that all of a person’s DNA (called the “whole genome“) is NOT sequenced. Only pieces of the DNA are sequenced. Your DNA contains TERABYTES of data. (The MacBook pro that I am writing this on has only 500 gigabytes of storage-it wouldn’t even hold the information that your DNA holds.) It would take a very long time to sift through the data from a whole genome, especially since 99.9% of our DNA is the same as everyone else. And thanks to evolution, we have a whole lot of junk DNA that we just kept with us as we climbed the evolutionary ladder.

What scientists use instead to build a DNA “fingerprint” are genetic markers called short tandem repeats (STR). These are areas of your DNA that present in every human, but are highly variable (polymorphic), meaning that they differ from person to person. There are typically 13 STR loci that forensic scientists use to create a genetic profile.

Simple overview of steps in DNA profiling.

Simple overview of steps in DNA profiling.

Steps:

1) DNA sample is collected: could be blood, hair, saliva

2) The DNA is then broken up into smaller pieces, using an enzyme that cleaves DNA at specific locations

3) The DNA markers are amplified by a technique called PCR (Polymerase Chain Reaction). This means that the original DNA sample can be quite small-maybe only 20 DNA containing cells.

4) The DNA pieces are then run through a technique called gel electrophoresis, where a high voltage current is applied to a gel that contains the DNA fragments. The fragments separate out based on size, with the smaller fragments travelling faster. The result is the band-like structure seen in the picture at the top.

The bands on a gel from the unknown sample will be compared to suspects (in the case of criminal DNA testing). If the unknown DNA is a match for a suspect, the bands on the unknown sample will exactly match. Take a look at the samples in the picture at the top. Can you identify which suspect is a match for the sample from the crime scene? (Answer at the bottom.)

Each of these STRs are independent, meaning that a particular sequence of one does not influence the other. In probability terms this means that each of these is an independent event. The result is a one in several trillion chance of two sequences from two individuals being identical. The notable exception being identical twins, who by definition have the same DNA.

Me, talking to CTV.

Me, talking to CTV.

What has changed since 1995?

Well, the techniques are better, we can use smaller samples of DNA. We can even now put together samples from degraded ancient DNA. We can’t quite use those samples to clone a velociraptor (a la Jurassic Park); however, we can use the sample to identify remains of those long dead. Analysis of mitochondrial DNA was how the remains of Richard III were unequivocally identified in 2013.

Better, faster, more sensitive techniques allow for identification that may not have been possible in 1995. Further, PCR was developed in 1991, meaning that 20 years ago, it was still relatively new. Today we are much more comfortable with DNA analysis, as is the legal system.

Check out the story on CTV:

http://calgary.ctvnews.ca/video?clipId=595358

*The unknown DNA sample in the top image is a match for suspect number 2

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Dates, Jobs, and Balance in Science

I think it has been pretty clear that I have not been writing as much for Curiosity Science as I would like, even though there is so much to share in the world of science. That has to do with my new adventure: an actual paying job! I am working for Paracel Laboratories as the new business development person for the lab starting in Calgary. What is particularly awesome is that this is also a joint venture with Life Science Forensics. This has given me the opportunity to learn in a new field and also I will be writing for Life Science Forensics blog. It is a great opportunity, but all of this has me spread pretty thin and lacking the inspiration to move forward.

Me and the boy, getting ready for date night.

Me and the boy, getting ready for date night.

Luckily I have a great partner. He’s that handsome one on the right. He knew it was time for us to go out and have a date night. It was a Thursday. Where does he plan to take a scientist who is getting burned out, lacking balance, and getting low in inspiration? He takes her to the Telus Spark Adults Only Night!

Adults Only Night! I am so excited.

Adults Only Night! I am so excited.

 

This has to be one of the best dates that we had, and we have had some pretty great dates. (And yes, I am wearing molecule earrings. I try to dress on point.) I have always loved going to Telus Spark (or in Edmonton, the Telus World of Science) during regular hours, with all of the kids. My nephew has great fun there, and of course, Auntie will always take him, because, science. But this was BETTER! And not just because they were now selling booze (though, it is a charming perk) but you get to play in all of the exhibits without worry that some kid is going to cut in front of you and grub up what you are looking at. Sure, some rowdy adult might do that, but while people really give you the side-eye if you get annoyed with a six year who is wrecking your wind tunnel experiment with their mindless block stacking, they applaud you for pointing out the line to hold the snake. (I don’t really get mad at 6 year olds; I do point out lines. I like order.)

A fossil on display; a loan from the Royal Tyrrell Museum.

A fossil on display; a loan from the Royal Tyrrell Museum.

This time they had the Dinosaurs in Motion exhibit. Art + Science = Amazing! These are sculptures of dinosaurs that are also like big metal puppets. So you learn about the dinosaurs, you learn about how the sculpture was built, and also how to make them move.

Making a T-Rex move requires some decent force!

Making a T-Rex move requires some decent force!

Ever paid homage to a pulley? The pulley is one of the basic, simple machines, reducing the force required to lift an object. It reminded me of first year physics, where we actually had to calculate the amount of force that pulley would reduce the movement of a load by. Why did none of those problems involve us moving a T-rex? Seriously, it might have actually been an interesting exercise if I had to do that calculation.

Me trying to make this guy move with the playstation controller. It isn't going well.

Me trying to make this guy move with the playstation controller. It isn’t going well.

I can tell you that I was not very good at moving the sculptures attached to playstation controller. Apparently moving passed the simple machine of the pulley was too challenging for me. This exhibit was so neat. I loved the art work. The artist that created these sculptures did a wonderful job. What really struck me with this though was that it was an artistic impression of physics, paleontology, and metallurgy. Science isn’t some esoteric field of study that can only be found in the recesses of dusty books; science is in every part of life, allowing us to create beautiful innovations. Whether it is moving dinosaurs or a new app for our smart phones, science can inspire. And the sheer number of adults queued up behind me just to try their hand at making this guy move, is a testament to just how fun expressions of art and science can be.

After playing with dinosaurs we explored the rest of the exhibits and found that there was a display of reptiles. Now, my partner LOVES snakes! (He may have been the adult that I had to point out the line up to.)

The boy and Steve.

The boy and Steve.

Me and Steve.

Me and Steve.

So that is how we met this guy: his name is Steve and he is a rat snake. And if you can’t tell, the look on my partner’s face is his “quick, stick him your purse and make a run for it” look. Of course, we didn’t. It wouldn’t be right. But we did enjoy snuggling with Steve for a few minutes. Snakes are pretty cool.

This date  was so fun. It was different and amazing. It reminded me of why I love science, why I love talking about science, and why it was important for me to start this project in the first place. I love what I am doing with Paracel and Life Science Forensics. I am just having a little trouble in finding that thing called balance. But luckily for me, Telus Spark had a whole display demonstrating balance in the Dinosaurs in Motion exhibit. Hopefully now I can find some.

Thanks Telus Spark: we had a great date!

Heading home after a great date!

Heading home after a great date!

Chemicals are Your Friends-Well Most of Them Anyway

As a chemist, one of the hardest things that I deal with is the fact that most people HATE chemistry. It seems to be the most hated of all the sciences. And of all of the chemistry classes people take in university, the one they hate the most seems to be organic chemistry. This adds to my heartbreak because that is the type of chemist I am. I love chemistry and I really love organic chemistry. You don’t spend 11 years in university studying something that you only have tepid feelings about. So when the first thing people say to me after they find out I am a chemist is “ugh, I hated chemistry,” I start to feel defensive. “Oh ya, well…I hate your chosen profession…you…accountant.” This is of course made worse by idiots who have no clue what chemistry is and want to scare you with “chemicals” and making them sound like something nefarious that Snidely Whiplash is pouring into your water supply.

Here’s the thing: not all chemicals are bad. Actually most of them are great. In fact, you sitting there, reading this, you are a giant, walking, talking chemical reactor. Your cells use chemical energy to function. Your food is all chemicals. Your body is doing some pretty complex chemistry just to make your heart beat. The chemical bonds in fats, proteins, and sugars are broken down and put back together in important ways that allow you to survive. Chemistry is life.

There are some chemicals that are terrible for you, both man made and natural. Strychnine comes to mind as a chemical that is not so good for you. Botulinum toxin, produced by the bacterium C. botulinum, causes botulism-not a good chemical, unless you’re the bacterium. Man made chemicals are an interesting mix: we make them to solve certain problems, but they might also create a few problems of their own. Here’s a quiz for you: name the chemical that you think has saved the most lives? I am talking of hundreds of millions of lives. What did you guess? Did you guess DDT? That’s right, the pesticide DDT has actually saved the most lives. It is the most effective chemical in killing malaria-carrying mosquitoes. It is also inexpensive compared to alternate pesticides, which is matters greatly, since the vast majority of people impacted by malaria are in the developing world. Now, I am not advocating for the use of DDT. Its environmental impact is severe. But I do think it highlights some of the complexities regarding what makes a chemical “good” or “bad”.

Now when people hear chemical names, they sometimes get scared because they think “well that sounds like a toxic compound I do know, so this must be bad too”. I remember hearing a woman say that the traces of tertiary butylhydroquinone in fryer oil was harmful to human health because “butyl” is like the lighter fluid “butane”. These two compounds are so different, it is kind of like saying Michael and Michelle at your office are practically the same person because their names are so close. I hear variations of this argument a lot. “This chemical is ALMOST the same as a really bad one, therefore it must also be bad.” The thing is, when you look at the periodic table, the different between each type of element (all 118 of them) differ only by one single proton. But that proton makes a huge difference. Just like changing one proton in an atom changes the element, changing one atom in a molecule can drastically change that molecule.

Take a deep breath in, let it out. Are you still alive? Great! That is because what you breathed in was mostly nitrogen gas (and some oxygen of course, but mostly nitrogen.) The nitrogen in our atmosphere is comprised of two atoms of nitrogen bonded together with three bonds (triple bonded). That nitrogen floats around not killing anyone, perfectly happy and inert. Now, let’s change one of those nitrogen atoms to carbon. So instead of two nitrogen atoms triple bonded together we have one carbon atom triple bonded to one nitrogen atom. Take a deep breath of this compound and now you’re dead. See one carbon atom triple bonded to one nitrogen atom is cyanide.

So the moral of this post is that not all chemicals are bad. Don’t believe anyone who says they have something for you that is “chemical-free” because they are lying. If you have questions about chemicals, especially additives and preservatives, send me a message: thecuriosityscience@gmail.com I would love to answer your chemistry questions, especially if your source is food babe, Gwyneth Paltrow, or Dr. Oz: you deserve someone who actually knows what they are talking about.

I love chemistry!

Dear Pro-Vaxxers: Lay Off Jenny McCarthy

Vaccinations: I am guessing that by clicking on this entry you are expecting either some fear-mongering piece on how vaccinating your kid will make them more sick than the disease and it is all pseudo-science or you are expecting a self-righteous piece on how vaccines are safe and those not vaccinating your kids are guilty of child abuse and you are responsible for the deaths of babies. 

Sorry to disappoint, but this particular blog is my attempt to recognise that people who offer trepidation about vaccination do have some valid questions and they should not be mocked for asking them. I am writing to the pro-vaxxers: we have the science on our side, let’s maybe stop calling people who question it idiots and maybe instead help them understand. By being combative, we are not doing anything to stem the anti-vax movement, and that is something that impacts all of us.

The anti-vax movement can be traced back easily to Andrew Wakefield’s fraudulent studies on a relationship between autism and the MMR vaccine. I don’t really feel like going too much into Andrew Wakefield as I would equate him to the Bernie Madoff of science. There have been no less than 16 000 peer reviewed papers by reputable scientists in everything from epidemiology to chemistry who have since studied vaccines and found that there is no link whatsoever and we should all line up and get the shot. The damage done by this study is upsetting.

So why then are people still buying into the “anti-vax” movement? I would have to say that such a study simply caused people to ask questions that previously they just accepted: what is in these vaccines? Why do I have to get so many? How are they tested? How do we KNOW they are safe? It obviously didn’t help that high profile celebrities like Jenny McCarthy and Jim Carey were often seen at anti-vax rallies and Jenny McCarthy even wrote the introduction to Andrew Wakefield’s book. 

 Ah, Jenny McCarthy-she is really why I am writing this particular entry because recently she has backed off her “anti-vax” stance writing an op-ed piece for the Chicago Sun Times stating “I believe in the importance of a vaccine program and I believe parents have the right to choose one poke per visit. I’ve never told anyone to not vaccinate.” Well you know the internet, this immediately caused a backlash of people calling her a hypocrite, citing every “anti-vax” statement she ever made. There is even a website called Jenny McCarthy Bodycount which shows the number of preventable deaths caused by previously eradicated diseases. 

I am a staunch pro-vaxxer. It is in the interest of public health that we get vaccinated. The situation in Disneyland is great reminder of why it is important that we vaccinate. It is how we will cure diseases and ensure no one ever gets them. Seriously, if you are the kind of person donating money to any sort of disease cure, chances are some of that money is going toward finding vaccines. With all this in mind I was utterly disappointed to see the reaction toward Jenny McCarthy’s change. DEAR PRO-VAXXERS: THIS IS WHAT WE WANT! We want people to realise that vaccines are important to the health and safety of everyone in society. We want people who were previously anti-vax to take comfort in the science of vaccines and recognise their importance and feel comfortable in choosing vaccination for them and their children. People are not likely to do that if they see someone like Jenny McCarthy get completely torn apart for changing their mind. I, for one, think it was a brave move of Jenny McCarthy to write a piece explaining that she now has a more “pro-vax” stance.

 As a matter of fact, there have been studies to show that in the face of all the evidence, people are less likely to change their minds. We are not going to make easier by being jerks when someone decides to change their minds. The Guardian published this article emphasising that being jerks about vaccination is not helping things.

 “Dumbledore says people find it far easier to forgive others for being wrong than being right,” said Hermione.  (Harry Potter and the Half Blood Prince, page 95)

 I really feel that as scientists we need to be more accessible as experts. We need people to start realising that we are the “real doctors” and that there are more resources out there to get the answers than their general practitioner physician. Don’t get me wrong, physicians are great. They are great at what they do but they are not experts. They refer you to oncologists, surgeons, dermatologists, etc., when you need an expert for a medical malady. This works the same for research. Physicians are not experts. They rely on the work of experts and yet they are the ones that have to field the questions. Let’s help physicians out and get the experts out there because an immunologist is much more suited to addressing the question of “why do I have to get my baby vaccinated every 2 months?” than your public health nurse or general physician. Again, let me stress: public health nurses and physicians are great-but they are not the only resource.

 Here is where Curiosity Science can help you. I am here, with a network of science connections to help you find answers to your vaccine questions. No judgement, just science. Send us an email with your questions at thecuriosityscience@gmail.com. Also keep reading our site. There will be plenty of information relating to vaccines and how they work, like some of these previous posts on the immune system or vaccine truth.

 So for all of you, pro or anti-vax, I hope you keep reading my series with an open mind to learning something new. For all of you pro-vaxxers: please be kind when talking about the vaccine debate. I know that it can be frustrating, but remember that much of it started with simple questions, which is something that as scientists, we embrace. We have the science on our side; we don’t need to resort to childish name calling or “anti-vax shaming”. Shaming has never been a winning strategy. We are not trying to win a debate. We are trying to provide information that makes parents feel that they are doing the right thing by vaccinating their children. For all of you anti-vaxxers: please keep an open mind to peer-reviewed science. You should always feel comfortable asking questions about why your child is receiving any kind of treatment, but you should also know where to get answers that are based on fact. Unfortunately the internet is a big place and anyone can post whatever they like. It can be a challenge just to sort out what sources are valid and which ones are not. Vaccination is about more than just you and your child, though: it is about community health.

The Immune System: Your Own Personal Military

 To understand how vaccines and other pharmaceuticals work, we need to understand the immune system. You can think of your immune system like your own personal army protecting you from outside threats. With this in mind, the first term that we should define is pathogen: an agent that causes disease. These can be foreign bacteria, like Streptococcus pneumoniae, which causes pneumonia, or it could be a virus, like the Measles virus. Your immune system is designed to protect you from pathogens. Pathogens carry foreign proteins that are referred to as antigens and these antigens are what trigger your immune army to attack.

Figure 1: White blood cell types.

Figure 1: White blood cell types.

So who is involved in this very important immune army?  The immune cells are called lymphocytes (aka white blood cells) and are made up of T cells and B cells (Figure 1).  There is a difference between T cells and B cells in where they are produced and how they interact with antigens, but for simplicity, I am not going to delve into the differences. Both T cells and B cells work synergistically to create long term immunityI am going to focus my explanation on B cells. 

Figure 2: B cell function.

Figure 2: B cell function.

B cells produce and secrete little Y-shaped proteins that bind to antigens (Figure 2). These Y-shaped proteins are referred to as antibodies and are specific to a particular antigen. These antibodies then roam around your blood system and if they encounter the pathogen they are specific for, they will bind to the antigens on the virus or bacteria pathogen. This marks the pathogen for destruction. Large cells called macrophages will come along and eat the virus or bacteria cells marked with antibodies and destroy them.

Your Body at War: A Summary of Your Immune System

A foreign invader (a virus or bacteria) enters your body and makes you sick. Your immune system sends in its troops, the White Blood Cell corps, to fend off the invaders. The cells create and secrete proteins called antibodies that will mark the invaders. Then large cells called macrophages come along and eat the foreign cells that have been marked by the antibodies. After you’ve defeated the enemy, you keep the antibodies. The antibodies will then continue to patrol your body’s perimeter and if that particular invader tries to come back in, the antibodies will mark it for destruction before it can even cause disease.

How then does vaccination work?

The idea with vaccines is that you trick your immune system into thinking that it has the disease. You provide your immune system with the necessary antigens to create an immune response, but doesn’t provide it with the actual disease causing agent. Therefore you get an immune response but you don’t get sick. Your body will produce antibodies against that particular disease so that when you are exposed to the actual disease, your immune system immediately marks the pathogens and destroys them before they have a chance to make you sick.  

I said above that your immune system usually wins, so why do we even care about this? Well, just because your immune system may win, it doesn’t mean that it does not suffer some losses. For example: measles, you may not die, but you may end up losing your hearing. Mumps: you may actually lose your ability to reproduce. Polio: you may be paralysed for life. And of course, you can actually die. The flu causes over 100 000 deaths world wide every year, and that doesn’t even count the millions who have died in massive flu pandemics prior to the advent of the vaccine. 

Big Science News in Calgary: BPS Impacts Zebrafish Brains

Big science news out of the University of Calgary: researchers have found that BPS impacts brain behaviour in zebrafish! You may have seen it in the new this week: it made it on CBC, the Toronto Star, the National Post and many other news sites. Some contained alarming headlines like “Attention pregnant shoppers: study says those cash register receipts could harm your unborn child. (National Post)” But really, is that what the study said? The title, published in Proceedings of the National Academy of Sciences, reads “Low-dose exposure to bisphenol A and replacement bisphenol S induces precocious hypothalamic neurogenesis in embryonic zebrafish” Seems a bit of a reach to say that you may be harming your unborn child, doesn’t it? And here lies some of the challenges in science communication: making the study accessible to the public, without oversimplifying or over reaching the conclusions. It is a tough balance. This study helps highlight those challenges and it also gives an opportunity to explain how these studies are really important to communicate; how they impact our understanding of our human health and development; and the impact that we have on the world around us.

This study, led by Dr. Deborah Kurrasch at the University of Calgary, is pretty interesting science. What’s more, is that her and her team said they were surprised by the results. So let’s have a look at what Dr. Kurrasch’s team discovered.

bisphenola

Figure 1: chemical structure of bisphenol A

The story begins with the compound bisphenol A, abbreviated as BPA. It wasn’t long ago that BPA was making the headlines: it was dangerous and has since been banned from baby bottles. Many of us are now purchasing BPA-free water bottles, baby bottles, plastic packing etc. So what is BPA anyway? It is the compound here on the right. It is used in making plastics, most commonly polycarbonate plastics, but also used in epoxy resins. These are just various types of plastics that have all kinds of uses. Soon it became apparent that we were finding BPA EVERYWHERE. In all kinds of places it shouldn’t be. As someone who studied polymers, I can say what surprised me about this compound is that, unlike some other additives to plastics, it is chemically bonded right into the polymer. The fact that it was leaching out was a bit of a surprise. But what is worse is that BPA behaves as an endocrine disruptor. Endocrine disruptors are a group of compounds that behave similarly to hormones in your body. In this case, BPA behaves similarly to thyroid hormones.

The endocrine system is one of the systems in your body that is responsible for communication and regulation of body functions such as growth, reproduction, metabolism, and behaviour. Hormones are the chemicals produced by your endocrine cells and secreted and transported throughout the body as the chemical communicators. Chemicals that are structurally similar to hormones can bond to hormone receptors in your body and therefore disrupt the communications, which can cause problems with your body’s development.

200px-Bisphenol_S.svg

Figure 2: chemical structure of bisphenol S

Now knowing that BPA is an endrocrine disruptor, it became apparent that it should be removed from materials. The trick is to find something else that can function in place of BPA, but won’t pose the same problem. Manufacturers started using bisphenol S, or BPS, in place of BPA. (BPS is shown here on the right.) This compound is used in place of BPA, meaning that BPA-free products may contain BPS in its place.

So we know that both of these compounds are present in the environment, we know that there are found in organisms, that they bioaccumulate, and that they are endrocrine disruptors. Great, so how does this actually impact you? Well…we don’t exactly know. Enter: Dr. Kurrasch and her team.

The study uses zebrafish (Figure 3) as a model organism (Model organisms are other living things that are used in experiments because it would be unethical to test on human subjects.) Zebrafish actually have a spinal cord and a brain, but also reproduce rapidly, making them good models for neural development. (The rapid reproduction allows you to get enough subjects so your results actually mean something without waiting a hundred years.)

Figure 3: zebrafish

Figure 3: zebrafish

Using VERY low doses of bisphenol a and bisphenol s (1000 times less than typical human daily exposure), the team treated the zebrafish embryos and found that they were producing more neurons (brain cells) during development, which resulted in hyperactivity in the zebrafish babies.

The studies on human development are still emerging, meaning that we don’t yet know the long term impacts on human health, or the exact mechanism of how these chemicals work. These studies from the University of Calgary help give in sight into those mechanism and also suggest that it isn’t just BPA that is a problem, but chemicals that are the same class. It also suggests that very minute amounts of these compounds can have an impact on brain development.

Take home messages of this study:

-BPA and its relative BPS both impact the brain development of zebrafish embryos

-Only minute quantities are required to see an observable difference in brain development of zebrafish

-It may be important consider removing all bisphenol compounds from consumer materials

-The impact on human health is still unknown

-These results do give in sight on potential mechanisms on human brain development

Pharmaceuticals-How Are They Produced?

I thought I would talk a little about pharmaceuticals. Chances are you take some, know someone who takes them, and have all complained about their prices. A few years ago while I was in grad school I took a pharmaceutical chemistry class taught by scientists from Gilead, and I must say it was very enlightening. I thought I would share some of the lessons I learned and some of the key problems that face those charged with making these chemicals that many people depend on.
Let’s start with a poignant news story. What would you do if you were suddenly unable to get a hold of a medication that you require? When a company decides to stop producing a compound, what can be done? Is that right or wrong? How should medications be priced? These are questions that are very difficult to answer.
To understand a little bit about the complexity of the issues with the pharmaceutical industry I think it is first important to understand how these medications are produced. I know I found it eye opening. Guess how long it takes to produce a drug? 0-5 yrs? 5-10 yrs? 10-15 yrs? 15-20 yrs? If you guessed 15-20 yrs, then you would be correct. It takes 20 years and (as of 2008) $1.7 billion to develop a SINGLE drug. 
The timeline:
Discovery/Preclinical Trials
Time: 1-3 years
In this time, the company will begin by identifying a medical need, such as anti-HIV medications, and then study that disease to determine where drugs can target the disease and the possible interactions of the drug. This is where potential contenders for a drug are determined. This amounts to some 30 000 chemical compounds will be screened! These preclinical trials will involve pharmacodynamics and pharmacokinetics.
Pharmacodynamics: studies how a drug interacts with a target-this is the impact of the drug on the body. Is the drug going to do what is was intended to do? Is it going to do something else? 
Pharmacokinetics: this is how a drug is transported to the target-this is really looking at the impact of the body on the drug. This looks at four things: absorption, distribution, metabolism, and excretion. Remember, your body is one self contained complex chemical reactor. I think one excellent example of the importance of studying this effect is the notorious thalidomide. There are two versions of thalidomide: R and S. One is an anti-emetic (R) while the other causes birth defects (S). Yes it is possible to separate the two and give a person only the version that DOES NOT cause birth defects; however, once in the body, the drug is inter-converted to the other form (a process called racemisation).
Any potential drug will be screened for toxicity using two species: one rodent and one non-rodent. They will be tested for single and repeated dosing. They will be tested by various delivery methods. (Side note: a 14-day rat trial costs $250 000.)
During this time, chemists will be answering the questions of: can the drug be made? How many steps (hint: more steps, more costly, more trouble)? What are the yields (not all chemical conversions give 100% yield-actually very few give 100%)? Is chemical manufacturing possible, feasible, and affordable? 
After all of this, about 100-200 of the 30 000 compounds will make it on to the next step. 
Safety Review
Time: about 30 days 
This is where the pharmaceutical company is trying to get approval from human clinical trials. All of the information gleaned in the preclinical trials must be presented to the regulatory bodies, including the synthetic routes for production. This is also the time that a company will take out a patent on a compound (a process in the tens of thousands of dollars for each one). 
Clinical Trial: Phases 1, 2, 3:
Time: 2-10 years
This is where the human trials begin. 
Phase 1: 
– 10-100 volunteers
– months to 1 year
– involves “proof of concept” and determines whether the drug is adequate, safe, tolerable. 
– 50-70% of the compounds (that made it to clinical trial) will be abandoned. 
Phase 2:
– 50-500 patients 
– 2 years
– 60% of the compounds (that made it to phase 2) will be abandoned
Phase 3:
– 500-2000 patients
– 3-5 years
– only 4-10% of compounds will succeed
Approval:
Time: up to 7 years
This is the stage where regulatory bodies determine if a drug is safe enough and effective enough to sell to the population. 
Now if you have been keeping track, we are about 15 years from when the patent was filed to the point that the drug can be sold. A patent is only good for 20 years; therefore, a company only has about 5 years to recover the cost of the production. This also means that drugs that are currently hitting the market were just getting out of preclinical trials in 1998.
During this time, optimisation is ongoing to make the manufacturing process safer, cheaper, and more efficient. However, if the process is changed too much, it may mean that a company will need to refile their drug for approval. 
There is lots of interesting chemistry in pharmaceutical production. I think I will leave that for another entry, but if you have found this interesting, please check out these course notes for reference material.  

I originally published this on Chemistry is Awesome