This Discovery Takes Us A Step Closer To Curing Genetic Diseases | HuffPost

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Our basic knowledge of diseases and cancer will continue to grow through research advances with CRISPR-Cas9, paving the way for the discovery of more effective treatments. And CRISPR will enable developments in industrial, agricultural and ecological engineering that may parallel advances in human health and medicine.

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Pediatrics Resident Physician, Global Health Epidemiologist, Munk Global Journalism Fellow

Pediatrics Resident Physician, Global Health Epidemiologist, Munk Global Journalism Fellow

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A few months ago, I had a chance to take part in TEDMED as a TEDMED Scholar. The TEDMED event, focuses entirely on the world of health and medicine. The whirlwind week included poignant presentations from researchers, innovators, policymakers and physicians.

Dr. Sam Sternberg was one of a handful of researchers presenting innovative basic science, and his presentation was accessible to scientists and non-scientists alike. His talk discussed CRISPR -- a hot topic lately both for its promise and controversy.

Just last week, the prestigious Gairdner awards honoured advances in this technology. I recently had a chance to chat with Dr. Sternberg about his work and all things CRISPR. His full talk is available here.

This article is the last of a three-part series interviewing engaging speakers from TEDMED -- speakers that aimed to push the envelope in their work, and innovate the world of health and medicine today and into the future.

AK: Thank you for your excellent TEDMED talk. Can you share a bit about what got you interested in genetics and genome engineering?

SS: To be honest, I never originally intended to conduct genetics-related research. When I first arrived at UC Berkeley to start my PhD, I had a more general interest in studying a molecule called ribonucleic acid (RNA), and so was naturally drawn to Dr. Jennifer Doudna's lab.

At the time, CRISPR was a fledgling research topic being researched by just one post-doc and one grad student in the lab. But I was immediately hooked because of the crucial role played by a molecule of RNA, aptly called CRISPR RNA.

As a biochemist, I wanted to figure out how the RNA was produced, what it looked like, how it interacted with proteins, and what it was used for. Soon we learned that the RNA targeted DNA for destruction during viral infections, and that CRISPR could be transplanted into human cells to perform genome editing.

It was clear that this discovery could revolutionize biology. And so, while I continued tackling research questions related to CRISPR biology, my focus increasingly shifted to CRISPR-Cas9 and to genome engineering.

AK: That sounds like quite the journey! Your research is focused on CRISPR-Cas9, can you explain to our readers what CRISPR is, and how its relevance for diagnosis and treatment?

SS: CRISPR -- an acronym that stands for Clustered Regularly Interspaced Short Palindromic Repeats -- refers to bizarre repeating stretches of DNA that are remarkably widespread in bacteria. In 2007, scientists at a yogurt company discovered that CRISPRs endowed milk-fermenting bacteria with a powerful form of viral resistance, by targeting specific viral DNA sequences for destruction.

In 2012, Martin Jinek, a labmate of mine, identified a molecular machine called CRISPR-Cas9 as the crucial DNA-cutting enzyme, and showed that with a few simple tweaks, CRISPR-Cas9 could be programmed to cut virtually any DNA sequence of interest. Moreover, CRISPR-Cas9 could introduce surgical changes to the genome when introduced into human cells.

Soon, the CRISPR craze took off as scientists all around the world adopted the technology to edit DNA in a wide range of plants and animals, to study the functional importance of different genes, provide better models for cancer, and even correct genetic defects associated with genetic diseases.

[Dr. Sam Sternberg speaking at TEDMED, Palm Springs, California, November 2015. Photo Credit: Jerod Harris]

AK: What are some of the diseases that could effectively be "cured" in our lifetime if CRISPR is widely adopted? How far along are we in clinical trials for these diseases?

SS: CRISPR could theoretically be applied to treat any disease that results from genetic mutation(s). In mice and cultured human cells, it has been applied to target sickle cell anemia, cystic fibrosis, Huntington's disease, beta-thalassemia, fragile X syndrome, severe combined immunodeficiency and many others.

But a lot of work still remains to move CRISPR into the clinic. Editas Medicine, one of the first companies to develop around the CRISPR technology, announced its plans to begin clinical trials using CRISPR in 2017, and two other companies -- CRISPR Therapeutics and Intellia Therapeutics -- are sure to follow closely behind.

[CRISPR-Cas9. Credit: Dr.Jennifer Doudna, UC Berkeley]

AK: Recently there was an international conference on CRISPR, and much media attention around the ethics of CRISPR. Can you clarify what was actually discussed and specifically the ethics around genome editing?

SS: The international summit on human gene editing was convened to discuss emerging scientific, ethical, and societal questions surrounding genome editing in humans. A major focus was the controversial topic of human germline editing, in which genetic alterations made to eggs, sperm or human embryos would create permanent DNA changes that would be passed on to subsequent generations.

Germline editing became a center of attention in 2015, when Chinese scientists reported the first-ever attempts to modify the genome in human embryos using CRISPR.

There are numerous, justifiable concerns about germline editing, both from an ethical and safety standpoint, which is why a group of scientists, including myself, published an article in early 2015 calling for a pause on germline editing.

In their official statement, the summit's organizing committee stressed the need for continued basic and preclinical research, as well as the pursuance of clinical uses in somatic cells (i.e. not in the germline), while calling for careful risk/benefit analyses.

On the topic of germline editing, the committee stated that any clinical uses would be "irresponsible... unless and until" safety issues are resolved, broad societal consensus is reached, and proper regulatory oversight exists.

AK: There has been a lot of discussion around engaging young people -- specifically young girls -- in STEM (Science, Technology, Engineering and Medicine), but the emphasis has largely been around the technology (e.g. coding) aspect. What are some ways we can get the next generation interested in breakthrough science that could effectively lead to paradigm shifts in medicine?

SS: I think both strong mentorship and in-lab experience are invaluable tools to get students interested in scientific research. There's something about hands-on experience that brings science to life, in a way that textbooks and lectures never will.

The CRISPR breakthrough also serves as an inspiring example of just how exciting and transformative basic academic research can be. Despite starting out as an oddity confined to the bacterial world, CRISPR has become a multi-billion dollar industry in just three years, has been hailed as this century's most influential biotechnology discovery, and offers the promise of curing genetic disease.

CRISPR reminds us of the urgent need to continue following our curiosities and imagination in studying the wonders of nature.

To the specific issue of getting young girls interested in STEM, I think Jennifer, along with her CRISPR-Cas9 collaborator, Emmanuelle Charpentier, serve as fantastic examples of how high one can reach as a female in science.

They've co-founded promising biotech start-ups to apply CRISPR-Cas9 therapeutically and won prestigious awards for their research, all while running their own laboratories and mentoring the next generation of researchers.

AK: In your wildest dreams, where would you like CRISPR-Cas9 to be in five years, 10 years, 20 years? And what are the greatest obstacles (policy, funding, resources, etc.) to getting there?

SS: I believe we'll see a growing number of genetic diseases cured with CRISPR-based therapies. Our basic knowledge of diseases and cancer will continue to grow through research advances with CRISPR-Cas9, paving the way for the discovery of more effective treatments. And CRISPR will enable developments in industrial, agricultural and ecological engineering that may parallel advances in human health and medicine.

There is even talk of applying CRISPR as a way to eliminate mosquitoes and mosquito-borne illnesses like the Zika virus.

Finally, the use of CRISPR-Cas9 to edit the genome of human embryos, for clinical use, seems inevitable. The ethical debate surrounding this issue will only intensify as safety concerns of the technology are addressed, and it will be critical to continue having open, inclusive conversations with all the relevant stakeholders present, to decide how society should proceed.

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21 Rare Diseases

Gigantism(01 of21)

This disease, which according to the NIH is most often caused by a begnin tumor in the pituitary gland, results in an excess of GH, or growth hormone. This causes sufferers to grow abnormally large, not just in terms of height, weight but also organ size. It results in complications like delayed puberty, increased sweating, and secretion of breast milk.

Pica(02 of21)

Characterized as an eating disorder, Pica causes people to eat what the National Organization for Rare Disorders describes as "non-nutritive" things. That umbrella term can include (but isn't limited to) dirt, clay, paper, and paint. Interestingly, it's not unusual for young kids to experience transient pica as a kind of phase, and pregnant women are also known to develop temporary pica cravings. The cause? Unknown. But in order to be diagnosed with full-blown Pica, a person's symptoms must last for more than a month.

Maple Syrup Urine Disease(03 of21)

MSUD, which is passed down through families, is a life-threatening metabolic disorder passed down through families that stems from the body's inability to process certain amino acids, leading to a build-up of them in the body. According to the NIH, symptoms usually surface in early infancy and can include vomiting, lack of energy, seizures, and developmental delays. MSUD takes its name from another symptom -- the urine in affected infants smells like caramel or maple syrup.

Situs Inversus(04 of21)

Situs Inversus is a congential condition in which internal organs of stomach and chest lie in mirror image of their normal body position -- something many sufferers aren't aware of until they seek medical help for an unrelated problem. People with Situs Inversus typically wear some form of identification to help doctors in the case of a medical emergency.

Trigger Thumb(05 of21)

Trigger thumb, or trigger finger as it's sometimes known, causes a person's finger or thumb to get caught in a locked position. According to the Mayo Clinic, it can then stay stuck or straighten with a painful "snap." The cause? It depends. Trigger Thumb is the result of a narrowing of the sheath around the tendon in the problem figure, but that can be caused by a lot of things, including any activity that requires people to grip things frequently. Trigger Thumb is also more frequent in women.

Scurvy(06 of21)

Once the disease of sailors and pirates, scurvy does still exist in the United States, though predominantly in older, malnourished adults. It usually stems from a Vitamin C deficiency, which can result in gum disease, skin leisons, and swelling of the joints. (credit:Getty )

Wilson's Disease(07 of21)

This progressive genetic disorder causes sufferers to store excess copper in tissues, including the brain and liver. Though the Mayo Clinic says that the body depends on copper in order to use iron and sugar, too much of it in the body can have real consequences. Which is why sufferers of Wilson's Disease are prone to liver failure.

Foreign Accent Syndrome(08 of21)

According to researchers at the University of Texas at Dallas, this speech disorder causes people to experience a sudden shift in their accents and though it is known to be caused by things like brain trauma, conversion disorder, or multiple sclerosis, an exact reason behind the syndrome is unknown. Sufferers of FAS dramatically shift their speech in terms of timing and intonation, which often causes them to sound foreign, but they remain totally comprehensible. Documented accent shifts include from American English to British and from British to French.

Stiff Person Syndrome(09 of21)

People who suffer from this acquired neurological disorder experience repeated, often painful, muscle spasms as well as muscular rigidity and stiffness. According to the National Organization of Rare Diseases, spasms can occur at random or they can be caused by something as seemingly benign as light physical contact or an unexpected noise. The cause of Stiff Person Syndrome isn't yet known, but symptoms can be stabilized with medication. Left untreated, however, a person can lose the ability to walk.

Carcinoid Syndrome(10 of21)

According to the National Organization of Rare Diseases, about 10 percent of people with carcinoid tumors -- which the Mayo Clinic says are slow growing tumors that produce excess serotonin and usually appear in the gastrointestinal tract or lungs -- get this syndrome. It occurs only in patients whose tumors have metastasized to the liver. The symptoms? Wheezing, hotness, and extreme facial blushing.

Cyclic Vomiting Syndrome(11 of21)

Children and adults afflicted with CVS experience recurrent episodes of severe vomiting, which can last for days, followed by sudden periods of no vomiting. While kids are likely to experience more frequent attacks, adults's often last longer. To date, the cause of CVS is unknown.

Peeling Skin Syndrome(12 of21)

This obscure, genetic skin disorder does exactly what its name implies: causes sufferers to experience constant shedding of their skin. (In some patients, peeling is limited to the feet and hands.) Along with that, sufferers often feel itching and redness -- symptoms that can appear from birth or develop later in life. Although the exact cause is unknown, a mutation in the TGM5 gene has been identified in many sufferers.

Platelet Storage Pool Deficiency(13 of21)

This is a blanket designation for several rare platelet abnormalities, most of which lead to mild or moderate bleeding disorders. According to the NIH, the problem stems having limited granules -- the parts of platelets that, among other things, store ADP -- the energy released when a molecular bond is broken. That reduction in storage space inhibits the platelets' ability to secrete ADP in a speedy fashion, which is thought to be what causes the bleeding. Classic symptoms of a Platelet Storage Pool Deficiency are nosebleeds, excessive bruising, and profuse bleeding in surgery.·

ACDC(14 of21)

Only nine people in the United States are known to have this disease, which was just given a name in a recent study in the New England Journal of Medicine. ACDC, or arterial calcification due to CD73 deficiency, results in calcium build-ups in the arteries below the waist of sufferers and in the joints of their hands and feet. According to the NIH, the breakthrough discovery found that the disease is related to a variant in the NT5E gene.3

Conversion Disorder(15 of21)

This condition, which typically occurs after an extremely stressful emotional event, causes a person to experience sudden blindness or paralysis that can't be otherwise explained. People with mental illlnesses are at particularly high risk and psychological treatment can help lessen the symptoms.·

Ochronosis(16 of21)

Ochronosis results in black or blue external tissues, often the ear cartilage or eye, though it can occur throughout the body. It affects people who suffer from certain metabolic disorders, but it can also be caused by exposure, though scientists aren't exactly sure to what. Not just a cosmetic issue, the affected areas can become brittle and degenerate over time.

VLCAD Deficiency(17 of21)

This condition, which is caused by genetic mutations in the so-called ACADVL gene, keeps people from converting certain fats to energy. According to the NIH, the deficiency often presents during infancy in symptoms including low blood sugar, weakness, and lethargy.

Hairy Tongue(18 of21)

As the name suggests, Hairy Tongue is a condition in which the tongue develops a black, hairy texture. According to the Mayo Clinic, the disease is "harmless" and is caused by an overgrowth of bacteria in the mouth, which can be treated with antibiotics. The NIH reports that hairy Tongue can also present as brown, yellow, or green discoloration. ·

Ochoa (Urofacial) Syndrome, or, Peculiar Facial Expression(19 of21)

This obscure, inherited disorder presents at birth and causes infants to grimace when, in fact, they are attempting to smile. The disorder also includes an extreme urinary abnormality: an obstruction that interrupts the connection between nerve signals in the spinal cord and bladder, leading to incontinence. Though treatment does exist in the form of antibiotics and bladder re-education, some patients can develop renal failure in their teens and 20's, which can be life-threatening.

Eagle Syndrome(20 of21)

This syndrome, caused by a particular calcified ligament or elongated bone, frequently causes sufferers to feel that something is stuck in their throat. (Scientists don't know the reason behind said elongation/calcification.) Other symptoms can include ear and throat pain as well as difficulty swallowing. According to the NIH, it can be treated surgically or non-surgically with steroid injections and other anti-inflammatories.

Progeria(21 of21)

According to the Mayo Clinic, only around 130 cases of this devastating genetic disorder have been documented since it was discovered in 1886. Affected babies normally appear normal at birth, but within 12 months begin to have symptoms like hair loss and wrinkles. According to the Mayo Clinic, progeria is caused by a genetic mutation, but not one that's passed down through families; it's a chance event that affects only one egg or sperm. The average life expectancy for sufferers is 13.

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