Ford Lecture Series (Sept. 21, 2023)
“Science and Ethics of HeLa Cells”
Ivan Martinez, Researcher Professor, West Virginia University Cancer
The Dwain L Ford Lecture Series is sponsored by the Department of Chemistry & Biochemistry in honor of former Chair and Professor Dwain L Ford who started this seminar program in 1965. The Series provides students, faculty and the wider community an opportunity to hear guest speakers from academia, industry and government present topics of current interest and importance in chemistry.
Our co-host for this lecture is Mr. Johann Roque, Graduate Student, Synthetic Chemical Biology, Professor Brittany Morgan’s lab, at the University of Notre Dame, South Bend, Indiana.
Guest Speaker Bio:
Dr. Ivan Martinez is an Associate professor in the Department of Microbiology, Immunology and Cell Biology at West Virginia University (WVU) as well as the WVU Cancer Institute. Originally from Mexico City, he finished his undergraduate education with honors from The National Autonomous University of Mexico (UNAM). He completed his Ph.D. in Molecular Genetics and Biochemistry at the University of Pittsburgh in Dr. Saleem Khan’s Lab studying the interactions between Human Papillomavirus infections and microRNAs. Dr. Martinez continued his training as a postdoctoral fellow in the Department of Genetics at Yale University School of Medicine in Dr. Daniel DiMaio’s Lab in collaboration with Dr. Joan Steitz’s Lab studying the importance of microRNAs in cellular growth arrest. After his training, he was recruited at WVU in 2013. The goal of Dr. Martinez research is to understand the importance of different types of non-coding RNAs in human cancers as well as viral infections.
Dr. Martinez has been invited to present his research at prestigious institutions such as Harvard University, University of Massachusetts Chan Medical School, the National Cancer Institute at the National Institutes of Health (NIH), at Gottingen University-Max Planck Institutes in Germany, and the National Institute of Genomic Medicine (Instituto Nacional de Medicine Genomics) in Mexico. He is also involved in the organization of International Meetings such as the Workshop on Long Non-coding RNAs and Artificial Intelligence at the Institute of Electrical and Electronics Engineers (IEEE) International Conference on Bioinformatics and Biomedicine for the last 4 years as well as the 2022 Keystone Symposia “Small Regulatory RNAs: From Bench to Bedside” in Santa Fe, New Mexico. Finally, Dr. Martinez is a member of the World Health Organization (WHO) COVID-19 Animal Model Group since 2021.
Okay so we are recording um we want to again welcome everyone to this is our second um session our second episode if you will for Andrews University chemistry Department uh seminar program last week we had a change day where we went out in the community and try to
Improve the community that we live in and so we are back this week um for a very interesting seminar topic and presentation today my co-host comes from notra Dame um his name is Johan Rook I hope I’m pronouncing it correct correctly yeah and okay and uh we have
An ongoing collaboration with his group um he’s a graduate student but his Professor is on here I think uh Professor Morgan she actually did a presentation for us now about two years ago I believe um and Michelle is uh one of our students here at Andrews who is um part of that
Collaboration so um Rohan the time is yours to introduce our speaker um all right well our speaker today is Dr Ian Martinez Ivon Martinez who comes uh who is an associate professor at the department of microbiology immunology and cell biology at Western Virginia University as well as the Western Virginia University Cancer Institute
Originally from Mexico City he finished his undergrad education with honors from the national autonomous University of Mexico he went on to complete his PhD in molecular genetics and biochemistry at the University of Pittsburgh under Dr Saleem Khan’s lab uh studying the interactions between HPV infections and micro rnas Dr Martinez continued his training
As a postto fellow in the department of genetics at Yale University School of Medicine in Dr Daniel daal’s lab in collaboration with Dr Joan Stites lab studying the importance of micro rnas in uh cellular growth um arrest after his training he was recruited at the Western univers uh Western Virginia University
In 2013 the goal of Dr Martinez’s research is to understand the importance of different types of non-quoting rnas in human cancers as well as virus infections uh Dr Martinez has been invited to present his research at prestigious institutions such as Harvard uh the University of Massachusetts uh Medical School the National Cancer
Institute at the National Institute of Health um at the gten gens University uh Max plank institutes in Germany and the National Institute of geomic medicine at Mexico in Mexico he is also involved in the organization of international meetings such as the workshop at long coding rnas and artificial intelligence
At The Institute of electrical and electronics engineer International Conference on bioinformatics and biomedicine for the last four years as well as the 2022 Keystone symposia named small regulatory rnas from bench to bedside in Santa Fe New Mexico finally Dr Martinez is a member of the World Health Organization Co animal model
Group since 2021 and with that being said guys please welcome Dr Ivon Martinez thank you thank you so much uh Desmond and Johan first uh for the invitation to have the ability to talk to you guys um it’s it’s great to be with you guys here and thanks again for
The invitation uh Johan thank you so much for the kind introduction um so I was um talking to this mon before that even though the title says science and ethics of Heil cells most of my my presentation is going to be in the science part because as a scientist I
Definitely feel more comfortable talking you talking to you guys about science and how Kila cells literally changed the biomedical world that’s that’s um you know the the Legacy that we have from herx and yes I going to talk a little bit about harax and at the end I’m going
To probably open the forum for all of us to discuss the ethical part of this of these um cells but more than anything else I want to introduce you into the the world of hila cells and their benefit that not only give to the world
But also give to my lab and in from basic science to apply science so um just to uh show you uh the first slide is this is her Alx this is a photo with her husband David in 1945 and uh this is a a painting this is
A portrait by K Nelson that she wants to capture the kindness of HRI LX to the world and the cells that she gave to the world uh there was there was an exhibition in New York City a couple of years ago but who is henrix so henrix uh was
An African-American woman uh whose cancer cells are the source of the hiloc Celine the first in mortalized human cell so that’s very important to to notice for many many decades uh scientists were trying to grow human cells in vitro and they were trying and they were very unsuccessful uh for
Several reasons but was not until henrietta’s cells uh were putting vitro in plastic to grow that was the first time that we achieve uh that goal and open a new a new door to to the biomedical field um she was the source of these cells U
By a tumor biopsy during a treatment of cervical cancer at John Hopkins Hospital in Baltimore Maryland in 1951 so actually the beginning of 1951 she she went to joh Hopkins that at that time was the only Hospital in the area that treat black patients and she went
There because she felt she said a not in her womb she was feeling sick um and she went just to see the doctors and see what they they they thought that she will have so her doctor Howard W Jones um took a biopsy of a mass found in her
In her cervix and did some lab test on that and then soon after he actually uh said that she has this malignant epidermoid carcinoma of the cervix uh at that time of course we didn’t help with the technology that we have right now but in 1970 actually was um
Recharacterized this tumor as an adenocarcinoma so it was not a carcinoma was actually adenocarcinoma but um few months after August 8 1951 uh LAX uh who at that time was only 31 years old uh she went back to a routine treatment at Hopkins uh they normally was treating her with
Radiation with these radium tube inserts they put inside of the cervix and asked uh to be admitted to continue with uh because she has this uh severe abdominal pain and uh unfortunately she actually passed on October 4 1951 so you can see here that was really
Fast uh when she went to the doctor in the beginning in January and passing in October um her disease was really really uh in a late stage and unfortunately for her she you know she couldn’t survive this disease but she actually gave us um um
Her C and and that’s what I’m going to be mostly talking about so they found this cervical cancer what is exactly cervical cancer it’s a type of cancer that you can see here that is normally in the cervical region before the uterus and uh and and after the
Vaginal wall so normally uh clinicians when they look at this they see they start to see this tissue these changes in the tissue as you can see here when you see a normal cervix by a clinician they see the this very smoooth region in the cervix no problems when they start
To see some changes in the tissue that’s when they start actually start getting worri and of course they can develop in different stages on like um late stage of cervical cancer so unfortunately for for henria when she show up in in at Hopkins she already had a big um
Cancerous tissue in her cervix and that’s the one they actually were able to pull out some of the biopsis from there but something interesting is um now we know at the time they didn’t know this as the herx was infected with human papiloma virus um and that’s why that
Was one of the first evidence that these viruses actually are related to cervical cancer so something I don’t know if you know this but most of the most of the cancers that are in the world 15% of them are actually caused by um infections that doesn’t mean that the
Cancer is um infectious that means that an agent like a virus or a bacteria could potentially be the first um punch to develop cancer so it’s interesting to show you that a good percentage around 15% of new cancers around the world are actually by infection agents just like
Viruses just like human papula virus or HPB and actually 1976 uh Dr Harold surus was the first one to publish that human papula virus are actually important in their role to cause cervical cancer was uh specifically a subtypes I’m going to tell you a little bit about the subtypes
Of hpvs but in this case HPV type 16 and HPB type 18 um now we know for example that Henri LAX uh was infected with uh HPV 18 so hila sales are actually hpv18 positive they still have the virus and I’m gonna show GNA show you why but interestingly
Enough for for this discovery uh Dr zous actually he won the the Nobel Prize in 2008 and I always kind of joke with my students is telling them hey if one day you really want to uh win the Nobel Prize you should be studying uh viruses
That cause cancer because if you look in the history of tumor virology that I’m not going to go in detail here but I just want to show you in these red boxes these are all the viruses that scientists since 19 early 19 1900 all the way to 2008 all these viruses are
Being related to different type of cancer cancers uh not only hbv but other ones and turns out these discoveries of tumor virology most of these um researchers that studi them they actually won the Nobel priz so uh why because cancer is a such a multifactorial disease that is hard to
Understand it uh when a patient comes with a tumor it’s it’s hard to understand what this person this patient was exposed to you know there’s so many factors so many genetic factors environmental factors that is almost impossible to know exactly where was the first like the first evidence of of of
Carcinogenesis but studying viruses actually and these viruses that are related to the development of cancer are actually quite uh easy to follow because you infect the cell and then you ask the question question what happened what is the first things that happened inside the cell After The Infection and what of
These things that happen inside the cell could potentially give you an idea of um carcin the beginning of carcinogenesis so most of these guys won the Nobel Prize precisely because of that most of the cancer bi cancer biology even though most cancers I I show you most cancers
Are not related to viral infections viral infections actually given the first hint of how to discover specific enco jeens or specific tumor suppressor genes but let’s go back to HPV so HPV we know is important in uh cervical cancer uh just like henrix and hila
Cells come from and um just to just show you uh cervical cancers around the world 99.7% of cervical cancers are HPV positive meaning that literally every single cervical cancer that you can find in the world will be because they have an infection of HPV um but not only cervical cancer most
Anogenital cancers are related to the infection of these virus like anal cancer vaginal cancer vulval cancer and even penal cancer uh related to HPV infection interestingly enough oral fenial cancer now is between 60 to 70% of them are HPV positive uh 30 years ago if you asked me
The question how many aenial cancers are related to HPV infection I will tell you that maybe only like 20% so in the last 20 30 years there been an high increase of oral cancer actually related to the infection of HPV and every year uh here in the United
States between 20,000 to a women to 11,000 men they develop a cancer associated with the infection of HPV and around the world more than half a million cases are new uh of hbb infection showing you that is one of the most important even not the most important infectious cause of cancer in
The world so again there the importance of HPV but because of heila cells that was the first ones that we were able to manipulate in in the lab gave us so many so many Clues so many ideas of how to study HPV and how to study cancer now here on papular transmission
You can see here is mostly B seexual Transmission um increase depending on how many parts do you have and um and they can be coinfected this could be coinfection of of of new NES new babies but they are rare they could they could avel respiratory papillomatosis but in
General uh the most uh prevalent way to get infected with human pap virus is by sexual contact fortunately for us uh for mostly the new generations we have a vaccine against HPV uh that can Target um the the latest one is Gil uh 9 that is was developed in
2014 and that one uh we um is the one that the clinicians are using right now that one can actually cover against lowrisk hpvs and high-risk hpvs so what do that means lowrisk and highrisk like here you show you that um there are around 200 genotypes of hpvs that infect humans and they’re
Divided in low risk and high risk um low risk meaning that these viruses will never develop or they are nothing related to cancer they can only develop warts they can be genital warts or they could be warts that we develop in our hands or our feet uh but the high risk
Are the ones that related to cancer hpv6 18 and N other ones but um 18 is the one that uh heal our cells and herax actually was infected but why these viruses are oncogenic like why what is the purpose why the virus cause cancer or is involving in causing cancer because the
Viruses in general they don’t want their host their person is infecting to develop a disease the only reason a virus wants the only reason a virus infect a cell is to make more virus that’s the only reason so turns out U if you look at the Genome of hbbd it’s a
Very simple genome they only have a very few genes but there are two very important genes in this uh in this genome that is called E6 and7 if you can see here the Genome of the virus is circular yeah it’s a circle that in a moment it goes inside of the cell they
Stay as a circle and interestingly enough the virus Express a protein called e two that comes from this Gene and this protein comes and repress the expression of these two genes E6 and E7 so the virus wants to stay in a kind of like a dormant state after infection
Doesn’t want that the cells know that they’re infected so the immune system doesn’t detect the cells so they want to stay kind of quiet but now we know by several groups that just the infection of the virus can cause C genomic instability meaning chromosom start getting fragile and this event the thing that
Happen is the virus actually breaks around this region where E2 protein is coming from and now the Genome of the virus integrate into the human genome by accident and now we have the viral genome inserted into the human genome and because it’s linearized in the the region where this
E2 protein come from now the E2 protein doesn’t exist and now E6 and E7 genes of the virus can be expressed and turns out E6 Target a very important protein in our cells called p-53 p-53 and RB also known as retinoblastoma are the two main tumor suppressor genes in our cells meaning
These proteins are always checking our cells their their only job is to check that our cells are fine that there are no mutations that everything is going okay so what happened in the moment that the virus goes in and integrates and express this oncogenic protein C6 and7
They bind to p53 and bind to RB and they destroy them and the destruction of p-53 on RB cause immortalization of a cell so interestingly enough these viruses need when you when people are having um intercourse or or having sex the virus actually has to go through a
Cut or a brace to infect the Bassel cells of our skin our epithelium and then it start going going through the process of differentiation with the cell and make more viruses so this is the normal life cycle of the virus the virus wants to make more viruses but if the virus
Integrates into the genome and get rid of these two proteins now the cells are immortalized and now the cells they have to accumulate more mutations to become a cervical cancer so I always tell my students um you have to differentiate between an immortalized cell and a cancer cell so heila cells are immortalized
Meaning our normal cells if you take out if you’re able to take out part of your cells and put them and grow them in vitro your cells will not divide more than 60 times that’s the average number of division our normal cells have but if you put HPV inside the cells
And get rid of like I told you the p-53 and RB protein now your cells are Immortal meaning as long as you give them food they will divide forever and that’s exactly what happened with herx cells because because they were infected with hpv18 her cells became Immortal and now
Even though she died in 1951 thousands of lives around the world have her C and we can grow them as many times as we want to because they’re Immortal because of that virus the infection of the virus caused the immortalization and now of course we
Know that we can do that with any cell that we can think of we can grab neuron cells we can grab bone cells we can grab any type of human cell and artificially add HPV inside of them we can immortalize and that’s a huge advantage in research field because now we can
Manipulate them we can grow them as much as we want to and and we can ask questions but like I said E6 and E7 oncoproteins from the virus not only target these two very important uh tumor suppressor genes p-53 and RB now we know in the last several decades that Target
Many many other proteins in our Geno and all these proteins are involved in different steps of carcinogenesis so it’s not a simple as I just told you the story but uh but clearly p53 and RV are the most important targets for the virus but why why the virus wants to
Immortalize cells what is the purpose of the virus immortalize cells Well turns out there are different hypothesis one hypothesis is again like I told you before the virus wants to make more viruses that’s the only reason the virus infect the cell but if a cell for
Example in this case is in a g0 state meaning is dormant is not dividing and is infected by the virus the virus needs to wake her up because viruses need to steal the Machinery of the cell to make more copies of themselves and if the cells is
In a kind of like a dormant state they’re not going to have enough Machinery to steal with so the thing that virus does is get rid of that dormant State make the cell replicate and now they can steal more of that machinery and that’s how they can make more
Viruses so unfortunately for us is this could potentially develop uh you know could be a consequence of cancer or the other hypothesis is that the cell is just dividing happily and then suddenly get infected by the virus and then the cell says oh my gosh I’m
Infected by a virus I’m gonna stop I’m gonna tell my immune system please get rid of it but then the virus says no wait a second I gonna I’m gonna get rid of your tumor suppressor genes I’m gonna avoid immune system and now you’re going to make more viruses uh or you’re going
Or I going to stay with you every time you divide so there def there are definitely different hypothesis that why these viruses are related to oncogenesis in humans but going back to heal cells um heal cells like I said 1951 it was a huge accomplish by scientists to be able to
Grow a human cell in vitra before hila cells the only cells were actually be able to grow in vitra was chicken cells actually but no human cells and because of this because of this discovery and how to uh see the conditions of growing and the media that
You need for growing was the beginning of the establishment of of cell lines of human cell lines and here I just going to give you a brief list of cell lines that came after hila from different organs all human uh cell lines um but um because of hila cells we
Were scientists were able to manipulate the media manipulate the conditions and now we were actually able to grow other type of cell lines from different organs from different uh different type of tumors in in human in human cells um and again this is just a very
Short list since 1990 right now if you ask me how many human sell lines we have I will say more than a thousand um sell lines um that U every lab yeah around the world are developing uh for studying several diseases but Heil s technically was the first line of immortalized human cells
And I just want to tell you a little you know know interesting data about hila cells if you look at a normal cell cotype yeah this is the way it should look if you remember your um genetic classes we have um 23 pairs of chromosomes humans
As you can see here and that’s way a normal cell should look like yeah every pair chromosome number one the pair of chromosome number two and so on and then the X chromosomes now look at the hila cell cotype this is the cotype of hilos they have an amazing amount of mutations and
Amplifications and duplications of chromosomes so just tell you the genetic differences between heila cells and a normal cells it’s out it’s outstanding and I think because of that there that’s where we able to grow them in vitro so easily in the beginning not only that there have been studies showing
That hila cells evolve even outside of HRI Alx meaning this study collect 13 different heila cells from different labs around the world and then they did genetics on them and they realize now the hila cells that I have are different from the hila cells that somebody has in Australia and the hila
Cells that somebody else have in Europe because every time you grow them and you pass them in vitro they’re going to start accumulating mutation they’re going to start evolving they’re going to try to adapt to their new environment so it’s just fascinating to show that even
A sell line that has been with us for so many years there actually has the capability still to adapt and evolve and continue growing in different conditions and not only that you know this is another interesting uh thing Kila was the first celline they went to space uh the Russians actually took him
Uh PAB poic he took hila cells just first to check if radiation in in human cells how detrimental radiation was in human cells but interestingly enough when they went in space and look at how fast the hila cells were dividing turns out they were dividing faster in space than in on
Earth telling you that microgravity conditions also could affect the division of cells so these are just a few but I’m going to just give you a very brief list of achievements that science had um because of heila so for example 1952 that was established establish heila cells yeah and over the
Next 60 years thousands of scientists with over 111 110,000 researcher Publications are publishing with hila cells I’ve been fortunate to have several Publications uh with hila cells too then in 1953 actually hila cells led the ground work for poly vaccine so scientists discover the Hiles are found to Be an
Effective tool to grow large amounts of poly viruses and and and and try to develop this poly vaccine 56 understanding the effects of x-rays in human cells so that’s why I was telling you uh this um people were radiating the cells and understanding how could damage cells and how could damage
DNA 1956 developing cancer research methods a lot of Bio uh biomedical methods that we have in our lab are actually were standardized using heila cells again going down to space 1964 in 1960 sport2 um uh shedding light of tratment of blood disorders so Heil are used to study the potential
Treatment between the drug called hydroxyurea against certain blood cancers and CLE cell anemia again they were very important to understand CLE cell anemia and and and how we can U uh understand the disease 7 three um determine how salmonella causes infections so scientists use hila cells to look at
Um they discover actually Aila cells get infected with salmonella faster than other cells and that actually helped them to be a more cost-efficient ways to understand and develop um uh drugs against that 1985 um again this is what I was telling you Dr through house and W
Know price by understanding that HPV is the main um one of the main causes to developing of certain uh cancers then uh 85 uh slowing cancer growth again uh people were using this uh compin um to reduce U to as a as a drug against cancers and they first sell
Line they use was Hil even though this type of drugs work now with aarian long Serv cancers too um I’m sorry um 88 HIV infections in the beginning of HIV pandemic uh scientists discover the heel have notic it infect with HIV and because of that actually be able to
Understand more in the mechanisms of how HIV needs certain conditions and certain receptors to get inside the cells and heila helps to understand which receptors were important for that um how cells age and that’s one of the the the few things I’m going to tell you in
A little bit that’s one one one of my research how how aging could be related with hila cells hila cells show us how cells can actually age or not um sell Imaging uh Ebola and HIV uh Nobel prizes and I think the most important one is in
2013 that um hila cells allow research to continue to advance science while protecting privacy so the National Institute of Health reached an agreement with the descendant of her acts to allow biomedical research control access to the whole genome data of hila cells access to the whole genome data of the
Cells will be a valuable reference tool for researchers to study the cause and effect of many diseases with goal of developing treatments this Landmark agreement exemplifies ni contined commitment to see research participants and partner researchers inter prise so in this case the NIH National Institute of Health got with an agreement with HRI
L’s family to be able to get the whole the consent of the whole genome because like I showed you before the hila cells are already evolving they already Genetically speaking they’re not going to look the same than herx so to study really the original Genome of HX for
That you need a permission of family and you need a permission to have access and then you can actually compare them and help you to understand how from noncancer cells in her cervix became Kila cells in my lab one of the things we’re studying is sence meaning
Aging I don’t know you guys know this but like I was telling you before our cells has a certain amount of Divisions after 60 divisions they become ccent they age they become old and now we know of course that the older we get the more senescent cells we’re going to have in our
Bodies so one of the things that we studyed in my lab is how to induce artificially sence in cells and turns out one of the best models for sence are actually hila cells because Hela cells like I told you before they have hpv18 inside of them so
The p 53 and RB tumor suppressor genes are not present but if we artificially at E2 to the hila cells we can actually push the cells to become senescent in four days something that in the laboratory takes months doing this we can have all the cells completely sessed in four days so
That was a huge traumatic difference that we’re actually able to use for research um we have several controls where we infected with the E2 protein but we still were able to artificially uh repress the tumor suppressor Gene so the cell still proliferating and other control just to
Be sure that we are actually able to induce inessence in a different way so having this we were looking at the expression of micr rnas because for in my lab we were trying to understand these micras were involved in cesses um what are micr rnas I’m going
To give you a very brief introduction of what micro are if you remember your central dogma molecular biology every single time I talk about this um in in my lectures I I I love to to to show you why I’m so passionate about no cating rnas because turns out if you follow the
Central dogma of molecular biology we know that the DNA is where we have all the information all the genetic information to form an organism yeah and we know that this DNA has to be transcribed to RNA and at the end the final products are proteins this is the
Dogma this is the thing we following for the last 60 years in the biomedical research turns out in the early 2000s when people were able to sequence a human genome and the Genome of several or other organisms we not only sequence the DNA but we sequ the RNA and something was not
Matching so for example this is imagine that this blue circle is the the DNA of a bacteria yeah how much of this DNA is transcribed to RNA we know that 98% of the DNA is transcribed to RNA in bacterias yeah how much of these RNA is translated to proteins
95% yeah but if you ask the same question for an insect for example how much of the DNA of an insect is transcribed to RNA same around 90% sorry 95% of the r the DNA is RNA but when you say how much of this RNA is translated to proteins goes down to 70%
Yeah but what happened with humans when you ask the same question in humans how much of our DNA is transcribed to RNA we’re still talking about close to 90% of our genome is transcribed to RNA how much of these RNA translate to protein 2% why why we have this universe of rnas
In our cell that doesn’t translate to protein and now we in the beginning people thought was just chunk that we have in our genome but now we consider that as the dark modal biology okay because it’s there but we have absolutely no idea where is our function my
Goodness so now we know that there all these rnas are called noncoding rnas and that’s exactly what my lab is doing is trying to understand the function of noncoding rnas and one of these non-coding rnas is called micro rnas these micro Ras I’m not going to give you all the details of them
They have a specific T biogenesis uh but we have around 2,654 human macron in our genome they can regulate 70% of our genes and they’re very important in diseases so I use hila cells actually to discover that certain microorgan are important inessence we were the first group to show that micrornas were actually
Actually specifically these families Mir 29 and M 30 were involved in human cell cesses and we use heila cells for that we also demonstrate that these are regulated by other transcription factors and um I’m not going to give too much detail to this but just to demonstrate that yes these micr rnas
Were regulated by the pathway that is the retino blastoma pathway that is the one affected by HPV in heila cells so at the end of the day the virus is actually affecting the population of micr rnas and affecting aging and sinesis but finally I guess we need to talk about
The ethics of this you know I told you all the science part of hila cells but at the end of the day these these hila cells came from from Henri Al and it was shocking for me the first time I heard that the family of H La
Didn’t even know that people for decades were growing her C and um starting thousands and thousands of different uh experiments and benefiting you know taking the benefit of them to to for the world uh and the family of course they like I said here how is that that Mr LX family
Didn’t even know of this G great gift she gave to the world they didn’t know until very recently and I think that’s why uh you know in the last 10 10 years um came the suing of the family uh to uh thermal Fisher it was the first
Company that was sued now we have to always put I think this in in the context of history when John Hopkins obtained the cells from herax at that time there was no really protocols to obtain tumors or obtain samples from patients and and follow a very strict
Regulations that we have right now that time didn’t exist and Hopkins uh University still says that they didn’t um benefit economically speaking from these sales but these these companies did termal fure and I think there’s still another Sue against other company because they actually benefit uh economically speaking from the cells and
If you ask me I will say that 80% if not more of biomedical Laboratories in the world have heila cells so we all benefit from it and I think this is definitely an important uh achievement by the family to number one get the credit that her LAX deserved number two to
Uh not only get the economic benefit from these companies but also demonstrate that even though it was many many years ago uh we still have the responsibility as a scientist and as a society to give credit who deserves it economics is piing and also the the credit they deserve to like I just
Showed you uh C cells uh open the biomedical field um to the rest of the world so um I’m very happy very glad that this um settlements are happening uh I said like I said I’m pretty sure right now there’s another one running against another company but
At least the thermal fusure one was was was uh done uh a few few months ago and uh and we as a scientist and as a research Community we have to really think about this carefully you know like things that we think are ethical right
Now how they going to see it in 30 50 100 years from now and we really given credit to the patient that is donating their samples to science are we um not only giv credit economically speaking but um you know every time we publish a paper saying
Thank you very much for uh you know sometimes you don’t want to give of course the patient names um that’s a hi regulation but at least give credit to the person that actually donate their Sal and I think it’s a it’s it’s a tricky question sometimes because you want to you want to
Give the credit who deserves it but at the same time you don’t want people to feel that scientist is going to take advantage of them so it’s it’s a balance that we need to achieve where both sides are satisfied and uh we are not um end
Up like um you know HRI family uh fighting for decades uh to get the credit that that she deserve so uh that’s it okay thank you very much let’s thank you so um so um Jo you want to start us off comments question what uh um honestly Professor you uh very
Informative I had one question actually um I wanted to know um if you knew like when that p-53 protein isn’t disrupted by the HPV what is its mechanism for suppressing tumors like when it’s normally functioning yeah very good question very very good question so p53 is is called
Like the Sentinel of our genome he’s going around the genome checking that there’s no mutations checking that there is no um uh DNA damage normally in normal situations your DNA can break and in the moment they break they send a signal and the signal is actually CAU by the by
P-53 and p53 can say can p53 has the ability to sense the cell and said okay we can maybe fix the problem but if we cannot fix the problem I’m going to send the cell to apoptosis meaning I’m gonna kill the cell I see so that has that
Efficiency and not only that is is 53 is a very unique uh protein that is involving many many many regulations yeah thank you so much Professor okay other questions either on chat or you could verbalize it speak loud no you have questions don’t you yes so you make statement that hbd was
In early hea cells you know those cells have been passaged I mean a bazillion times not to exaggerate and I may not be exaggerated and and you know what do the earliest unmolested samples the ones that have been passage the least do they have HPV in them I mean what we you
Know I just I I question the shity with with which people say he was there because it been so Universal and so aggressive um and so what’s the earliest passage is that they still have then do they contains yeah that’s a good question so uh Hopkins has the earliest of passages
Because that’s where the sample was collected and um yes every single passage of heila cells no matter what you get it has hpv18 on them actually the the virus is already integrated in the genome 60 times but there’s 60 copies of hila of hpv18 in hila cells doesn’t matter where
You go in the world you have between 60 to 80 copies and the early stages uh early passages of hila cells they still have HPV we know that in cervical cancer infection of HPV is a very early um is a very early event actually I didn’t
Tell you this but like if you grab a 100 person right now and you screen for HPV I can guarantee that 20% of them will be HPV positive In This Moment HPB is a very um is the most infectious um more prevalent um um infectious uh Disease by um U sexual transmitter
Disease but fortunately for us even though you can be infected with HPV most of the time your body is able to recognize the cells are infected and Destroy them and eradicate the infection only only five% of women infected with HPV end up developing cervical cancer questions this was a fascinating
Uh talk actually I can jump in here again if you don’t mind on your slide looking at the the prevalence of HPV and the variety of cancers to had the the biggest increase that we’ve been able to tell of course is a oral figal cancer that it moved from very low percentages
Up to 60% um talk to me about the public health implications of that I you probably are not a public health educator but what would you say to a young person who’s seeing that and ask me well how’s that happening yeah so we we still trying to understand
Why there are several hypothesis number one is um 30 years ago there were more head and neck cancers related to tobacco and alcohol intake meaning people were smoking more and they were drinking more than now the new generations so that’s one that’s one uh one of the little
Pieces of the puzle I think that makes the difference of increasing changing the the percentages the other one is uh early sexual activity and oral sex there’s evidence that oral sex and the number of sexual uh um partners that you have the higher you have the more more
Um uh potential U um infection you’re going to have uh in the rural cavity so there are changes at the cultural level are changes of the social level but if you ask me exactly what is the reason unfortunately I don’t have a straight answer I don’t know
Yeah okay I I have a question too um is is HPV the only virus that could immortalize cells no okay no it’s not um there are other oncogenic viruses like sv40 that can immortalize cells um there are EP by virus that can immortalize cells so there are SE there are several uh human
Viral infections that could potentially immortalize cells but none of them are as good as HPB okay HPB is very good in doing that and that’s why some people use them as a tool like they when they’re studying let’s say a very specific type of neuron let’s say that
Is very hard to grow in vitro but they want to study that neuron sometimes scientists they infected with HPV and now the neuron is immortalized and now they can grow them in vitro for many many you know years has there been any connection between like coid virus and cancer is there any connection
There coid and cancer uh there are some start to be some evidence that the coid is SARS cve 2 virus uh is a completely different type of virus it’s an RNA virus uh that infects several different type of else but there’s start to be some Publications showing that
Inflammation of the lungs by coid could potentially be one of the first um punches to develop certain type of of lung cancers um but unfortunately again um we need to wait sometimes many years or even decades to see if um the infection of that virus could cause certain uh cancer
Diseases yeah okay any students have questions did you did you hear the question I couldn’t hear it I’m sorry I couldn’t hear that’s okay um I think the question is where does the HPV virus insert into the human genome right if it doesn’t 60 times is there a pattern of where it
Inserts yeah yeah that was actually a very good question too in the beginning we thought that was just completely random uh because in the beginning you saw that the uh some some HPB sound lines they only have like two copies of HPB other ones they can have all the way to 500
Copies um hila Sals like I said is have something between 60 to 80 copies um the in the beginning of research of HPV people thought was just completely random and looks random but in the recent years people start to realize that there are certain chromosomal fragile sites H that HPB for whatever
Reason likes to integrate more than other places and interestingly enough some of these fragile sites are close to certain human enogen so there’s already publication showing that the integration of the virus also could disrupt human enogen and even help more in the developing of cervical cancers so
Our biochemist got all excited about the proximity to ancle jeans could you like elaborate on this some more so the rest of us could understand why he’s all you know yeah there is a very a very good publication in the 19 I think it was 19 late
1990s um that they demonstrate that the integration of hbb uh likes to integrate close to Anin called simic and S is very important in certain Cancers and um and they demonstrate that the integration kind of modify and activate the promoter of simic and now there’s more expression of the
Enogen okay enene is enene is a gene that it’s Express tends toward disrupting cell metabolism and cell regulation in leene is connectc okay so okay viruses could trigger cancer does bacteria is there information evidence that bacteria could also trigger cancer oh yes okay there’s that evidence H bori helicobactor
Pylori is is the only example we have of a BAC IA that is involved in stomach cancer oh yeah actually the guy that discovered the guy discover H pylori uh has to do something crazy because nobody believes him that bacteria could live in our stomach when we have a pH you know
Of two it’s like impossible that a bacterial well he actually infect himself with H pylori and demonstrate that they can develop ulcers in the in the stomach and that ulcers and that inflammation is involved in the developing of stomach cancer what yeah so the guy so the guy
Was completely rejected by all the consensus of science right and so he he truly believed this so he did not have ulcers he took a sample or two of this H py and medically got ulcers he then cured himself with an antibiotic and publish wow yeah so you know be careful about
Consensus in science I mean consensus is important consensus honestly science yeah no it’s true it’s true but there is as far as again I’m not I’m not a follower of n pylori and and and I’m not uh uh I’m not involved in gastro cancer but the few papers that
I heard and this actually a person working here at WBU working with hpylori and inflammation of the stomach um they can actually show that yes the the bacteria develop inflammation the inflammation change the immun system and there are some models of or of gastric cancer using H pylori now how they mimic
The real world again these are animal models these are inv vitro models I know there are specific plasm that H pylori has that makes so much poori um um uh uh U strains more prone to De to cause inflammation and other ones so yes we have to be careful I
Agree with with where the the information the liter come from but I think there’s at least good good evidence um several groups showing that there’s at least a link between the the bacterial infection and and and stomach cancer all right we are at around 5:30 now um we want to thank you very
Much um in fact in fact in fact in class today we were talking about when scientific presentations are done uh sometimes we are overwhelmed with um jargons and abbreviations and I think you are a good example of how to avoid those but good communicator yes very good I think all
Of my students would appreciate that thank you very much thumbs up dude yes thank you so much appreciate it thank you so much for the invitation okay thank you you thank you it’s okay all right thanks thank you take care very good very good even for non- biochemist I was able to follow
Stuff thank you all right take care see you okay