Hi, you're listening to Cultivate Curiosity, a. Podcast that inspires the next generation to stay curious. Cultivate Curiosity is brought to you by the Emerald Coast Science Center, a nonprofit. Interactive science museum and STEAM educational facility in Fort Walton Beach, Florida. This podcast is perfect for anyone curious about the world we live in, because. You never know what we'll talk about next. Hi, I'm Jacie, the social media coordinator at the Emerald Coast Science Center. Hi, I'm Harley and educator and the community affairs coordinator. And hi, I'm Diane, the director. And today we're going to talk about an episode that is very near and dear to my heart. Our episode today is going to be on National DNA Day. So National DNA Day is an annual global celebration of the discovery of the DNA double helix structure. This year is an extra special year because people across the world on April 25, 2023, will commemorate both the 20th anniversary of the Human Genome Project's completion and the 70th anniversary of the discovery of the DNA double helix. Published in The Nature Journal, the Human. Genome Project is one of the greatest scientific feats in history. The project was a voyage of biological discovery led by an international group of researchers looking to comprehensively study all the DNA known as the genome of a select set of organisms. Launched in October 1990 and completed 20 years ago, in April 2003, the Human Genome Project's signature accomplishment, generating the first sequence of the human genome, provided fundamental information about the human blueprint, which has since accelerated the study of human biology and improved the practice of medicine. So let's talk a little bit about the discovery of the DNA shape. 70 years ago, two scientists had a flash of insight that changed the world. On February 28, 1953, james Watson and Francis Crick discovered the structure of DNA, the now famous double helix. On April 25, 1953, the discovery of the structure of DNA was published in The Nature Journal. Their discovery helped unlock the mystery of our genetic code, and it helped us understand what makes us us. Roslyn Franklin produced a crucial X ray photograph of DNA that was used by Watson and Crick. Franklin is widely acknowledged as playing a major role in the discovery of DNA's double helix structure and, in fact, published a paper on her findings that accompanied Watson and Crick's research. So let's talk a little bit about Roslyn Franklin. Rosalind was a British chemist and X ray crystallographer whose work was central to the understanding of the molecular structure of DNA RNA, viruses, coal and graphite. Although her works on coal and viruses were appreciated in her lifetime, franklin's contributions to the discovery of the structure of DNA were largely unrecognized during her life, for which she has been referred to as the wronged heroine. A feminist icon and the Sylvia Plath of molecular biology. Franklin is best known for her work on the X ray, diffraction images of DNA while at King's College London. Particularly photo 51 taken by her student, Raymond Gosling, which led to the discovery of the DNA devil helix, for which Francis Crick, James Watson and Maurice Wilkins shared the Nobel Prize in Physiology or Medicine in 1962. Okay, so before we move on, I have to put in my little two cent about Roslyn Franklin, only because I'm a science history nerd and this is the kind of stuff that I just absolutely love to roll around in. So we wouldn't have known much at all about Roslyn Franklin's contributions to DNA if it wasn't for a book that James Watson wrote shortly after winning the Nobel Prize. And the book is called The Double Helix. And everybody that was mentioned in the book was supposed to have an opportunity to read the book before they went to publish it. Well, by this time, Roslyn Franklin had already passed away. So she died of cervical cancer, which is another reason why she wasn't included in that Nobel Prize. Nobel Prizes are only given to three individuals in any discipline and also they are not handed out posthumously. So because she had already passed away when they went ahead to go and give out the Nobel Prize in 1962, that's why she wasn't included on it. So in his book, he just rips her to shreds. And even James Crick and Maurice Wilkins read the book and they were like, this is not exactly the way things played out. And honestly, I think it's more like maybe Watson knew that he couldn't have done it without her work and so he just decides to totally to go for her and in order to make it seem like, yeah, I'm the one that did all of this, but he couldn't, he absolutely could not. They would not have had access to the insights that they, quote, had it not been for being able to see photo 51, which Roslyn Franklin did not show to him, but her lab partner, or he's not her lab partner because they had kind of an antagonistic relationship. But Maurice Wilkins had showed Watson and Crick because Crick and Wilkins had been friends for a number of years. So Maurice Wilkins fed all of Roslyn Franklin's data to Watson and Crick and that's how they were able to come up with the, quote, insight, that eureka moment. And also it was a lot of other people's work. So when they went to go publish the article in the journal Nature to talk about how they had discovered what the structure was, they realized that Franklin had never published her work and her X ray crystallography work. So then they couldn't explain how they came up with what they did unless her work was also published. And they did. Three papers were published in the same issue of the journal Nature. Watson and Cricks was published first, then the second paper, and the last paper to be published was Roslyn Franklin's. So that way it made her work appear like she was confirming what Watson and Crick said, as opposed to actually her work being the foundation for what Watson and Crick had done. So she had been severely maligned. And I'm happy to say that over the course of the years, more about her has come to like and I think that she is finally getting the recognition that she deserves for all of the work that she did. And when she went into this lab at King's College, she was, like, 31 years old. She was a female. It was right after World War II. She was Jewish, and she wasn't even allowed to eat lunch in the lunchroom because it was for men only. So, I mean, she really fought a lot of battles, and she was a very driven individual and very, very focused on her work, which kind of put people off, because they didn't expect that in a woman. Exactly. Anyway, so I just had to give some love to Roslyn Franklin, fight for. Her one more time. Yeah, exactly. Put it out there that she was a rock star. So now we're getting ready to talk about another rock star in the field of genetics and DNA, also another one that had been completely overlooked until somebody wrote a book about her. But this is henrietta lax. And there was an incredible book by Rebecca Sclud called the immortal life of henrietta lax. And her contribution didn't really get the recognition that it deserved until that book came out. So if you haven't read that book, I highly recommend that you read the book because it's an excellent, excellent story. So, in 1951, at 31 years old, henrietta Lax died from an aggressive form of cervical cancer only ten months after seeking treatment at John Hopkins for what she felt was a knot in her womb. During her treatment at the hospital, samples of her cancerous tissues were taken from her cervix, and these cells went on to become the immortal cell line known as the Helicells. The HeLa cells are immortal as they have an overactive version of the enzyme telomerase that prevents the shortening of the chromosome telomeres and so prevents cellular aging and cell death. HeLa cells can also proliferate abnormally fast, even in comparison to other cancer cells, and have the ability to contaminate other cell lines. So up until that point, they had tried to grow human cells outside of the body to use for testing, and they hadn't had any luck at all until they had come across these cells. Now, Henrietta Lax was black, and at the time, in the 1950s, john Hopkins had a ward that was for people that were black. And so a lot of those patients weren't paying patients. And so they didn't have an issue with taking these cells because they kind of looked at it as a form of paying for the work that they were having done, because they weren't paying patients now bioethics is completely different. A lot of that having come out of the fact that they had taken her cells. In John Hopkins defense, they never charged anyone else, they made no money off of her cells and they sent her cells out to everywhere in the world. They have been used like everywhere in every type of major medical research that there is. Everybody uses the HeLa cells. So much so that John Hopkins is building a brand new building right now and it is going to be named after Henry Adelax. They understand that things have changed over the years and they didn't recognize her contribution in the manner that they should have and so now they are trying to fix that because we are still using the HeLa cells in all of this research. So a couple of areas that it has made huge contributions to is in polio eradication. So Jonas Salk developed a polio vaccine in the early 1950s but he was struggling away to find to test N field trials and he was using Rhesus monkey cells at the time but they were really expensive for a large scale study. And so in 1952 he was able to use the HeLa cells and continue his polio vaccine research on those as well using the HeLa cells we have also learned a lot more about how to improve cell culture practices because we did say that the HeLa cells could also contaminate other cells. So now we know that we need to use certain procedures like what types of containers to put them in, how to have sterile rooms, how to handle them so that they don't contaminate and they don't get contaminated. So this is again a lot of general standard operating procedures in cellular biology that we have learned through the use of the Helocells and some other things. The idea of us having 23 chromosomes came from the use of HeLa cells. Previously, they believed that we had had 24 chromosomes. But by using the HeLa cells to research this, they determined that we have 23 chromosomes. And then genome mapping. And that kind of goes into the human genome project as well, but also genome mapping in order to help us to find what the genes are, where they're located and who is responsible for protein production and what areas are just parts of junk DNA. And then the last one that has become a really big help has also been the HPV vaccine, the human papilloma virus vaccination. And this is shots now that young girls can get in order to help them not develop this type. It can develop into cervical cancer and so this could help reduce the cervical cancer rates by 70% by having the HPV vaccination and this also came from the HeLa cells. So she has very, very far reaching implications and it was kind of just like a random thing. I can remember if you read the book or you listen to the story about her. It talks about the researchers when they come in, like, the next day, and these cells are proliferating and they're growing like, whoa, hey, that's never happened before. Oh, my gosh, this is crazy. So she is definitely one of those people that has had a huge influence on the lives of every single person moving forward. All right, what we're going to talk about next is Jennifer Duna and Emmanuel Sherpinier. Jennifer Duna is an American biochemist who has done pioneering work in CRISPR gene editing that's CRISPR and made other fundamental contributions to biochemistry and genetics. Emmanuel Charbenier is a French professor and researcher in microbiology genetics and biochemistry. In 2022, they received the Nobel Prize in chemistry for the development of a method of genome editing through CRISPR. This was the first science Nobel Prize ever won by two women only. CRISPR gene editing is a genetic engineering technique in molecular biology by which the genomes of living organisms may be modified. It is based on a simplified version of the bacterial CRISPR CAS Nine antiviral defense system. By delivering the CAS Nine nuclease complex with a synthetic guide RNA or gRNA into a cell, the cell's genome can be cut at a desired location, allowing existing genes to be removed and or new ones added in vivo. It can be used in the creation of new medicines, agricultural products, and genetically modified organisms, or as a means of controlling pathogens and pests. It also has possibilities in the treatment of inherited genetic diseases as well as diseases arising from somatic mutations such as cancer. In 2012, Duna and Sharpene were the first to propose that CRISPR CAS Nine enzymes from bacteria that control microbiome immunity could be used for programmable editing of genomes, which has been called one of the most significant discoveries in the history of biology. Since then, Duna has been a leading figure in what is referred to as the CRISPR revolution for her fundamental work in leadership in developing CRISPR mediated genome editing. And you guys remember we had two female rats that were donated to us at about the same time in 2020 when they announced the Nobel Prizes. We named them Jen and Emma after Jennifer Downett and Emmanuel Sharpignier. Yeah, because that was I forgot such a cool thing to have. It was really woman only. Yes, it was. CRISPR also had a huge impact on sickle cell patients. Sickle cell anemia is a well known disease affecting millions of people worldwide and is the most common blood disorder in the United States. This is identified around 100 years ago, and sickle cell anemia was the first disease that was proven to have a molecular cause and has been widely researched. Sickle cell anemia is a genetic blood disorder that affects hemoglobin, the oxygen transporting molecule in red blood cells. Sickle cell disease causes the body to produce hemoglobin S, an abnormal form of the molecule that distorts the shape of the red blood cells and disrupts their function. These rigid, distorted cells obstruct blood vessels and inhibit circulation, causing severe pain and recurrent infections. Sickle cell anemia is caused by the mutation of a single base in the DNA sequence of the bGlobin gene HBB. In healthy individuals, position six of the resulting amino acid sequence is glutamic acid gag. However, in sickle cell anemia patients, this is substituted for Avalene, then resulting in GTG. This mutation results in the formation of hemoglobin S, the disease associated form of the protein. Treatment options for sickle cell anemia are currently limited. Patients typically require frequent blood transfusions, and medications are typically recommended to relieve the pain attacks or reduce their frequency. Some medications can promote fetal hemoglobin HBF production to replace the faulty adult hemoglobin, however, they carry associated health risks. Antibiotics are often prescribed to patients in order to prevent frequent bacterial infections, particularly in children. A transplantation of bone marrow from a healthy donor is also an approach, but it has significant challenges, including identifying a suitable donor, immune, rejection of the transplant, and graft versus host disease, which is also known as Gbhd. So as sickle cell disease is caused by a genetic mutation, it is a perfect candidate for CRISPR mediated gene therapy. In 2020, there were CRISPR trials to see if sickle cell disease and beta thalassemia could be treated. Using what is known as CTX One therapy. This trial extracted hematopoietic stem cells from the bone marrow of two patients, one with sickle cell disease and one with beta thalassemia. The BCL one one, a gene in the cells, was the CRISPR edited in order to restore HBF before cells were reintroduced into the patients one year after treatment. The results of the trial have been extremely promising. Both patients displayed increased levels of HBF with blood and bone marrow cells, maintaining high levels of allelic editing and no need for subsequent blood transfusions. While there appear to be some side effects of the treatment, all have been treatable. Victoria Gray, the patient who had sickle cell disease, says her life has been transformed. In March, she was in London to describe her landmark experience at the Third International Summit on Human Genome editing. The summit brought together more than 400 scientists, doctors, patients, bioethicists, and others from around the world to air the promise of gene editing as well as host a lot of questions that the technology is raising. I would just recommend. There's a great book called The Gene by Siddharthur Mukherjee, and he kind of goes into the whole entire history of DNA, starting with Darwin, to mendel, to where we are now and written very, very well in very layman terms. So that's a great book if you just want to learn a little bit more about it. Every book that he writes has been fantastic. His latest book is called The Cell. So he treats the cell in basically the same way, like the total history of the cell and all the different parts and pieces reside within a cell. There is another good book about Jennifer Daldna, and it's called The Code Breakers, and it talks about her and Emmanuel Sharpignier's work in discovering and developing CRISPR techniques. So that's another great book. And then just this morning, when I was riding the bike at the gym, I rewatched the Nova episode of photo 51. And that goes into a great detail about the discovery of the DNA structure and sort of like the worldwide battle and race that was going on to figure out who was going to be the first person to elucidate the structure of DNA. So that's a great episode. So I highly recommend that one as well. All right, that's all for this episode today. We will see you guys in two weeks, and thank you for listening. Thank you for listening. Thank you. Bye. Thanks for listening to this week's episode of Cultivate Curiosity. If you have any questions, feel free to email us at socialmedia@ecscience.org. Tune in for our next episode in two weeks.