Research to the People

In America there are currently over 30 million people with rare diseases. These patients often lack access to the most current research techniques and medical capabilities within personalized healthcare. When traditional medicine leaves patients with few options besides symptom management, broader sequencing and multi-omics data analysis can help inform treatment options. 

Research to the People facilitates the use of collaborative genomics research with direct patient involvement. We support patients in leading their own research cases by helping them generate high-quality sequencing data with partner companies like Personalis and Oxford Nanopore, and coordinating hackathons that bring together hundreds of leading researchers. At these hackathons, RTTP's multidisciplinary teams work together to analyze the data, resulting in new recommended treatment options for not only the specific patient but their community of affected individuals. Scaled globally, our organization will continue to facilitate scientific and clinical breakthroughs for patients who have exhausted their clinical options. 

We help patients who no longer have a "standard of care" and have reached the end of their clinical trials to explore the next steps in their treatment. This includes patients with rare cancers, rare diseases, metastatic cancers and those with undiagnosed conditions.

• Cancer alone afflicts approximately 5.5 percent of the US population. Globally the share of people with cancer reached 1.3% in 2017. (https://ourworldindata.org/can...)
• Fewer than 3% of these patients participate in clinical trials (https://www.ncbi.nlm.nih.gov/books/NBK50895/)
• And of those, only 3.5% will have a successful response. (https://www.acsh.org/news/2020...)
• So assuming a population of 330 million, the problem affects more than 500,000 people in the US.
• And assuming a population of 7.8 billion, the problem affects about 12.5 million people worldwide.

The crux of the problem is that treatment of this class of illnesses involves research, not clinical science, so funds expended for this in our healthcare system are not reimbursable.

Instead of centering on money, or on the disease, we focus on the patient.  By bringing the patient, his/her data and a research network together in the same room for several days, we've managed to get some good results.

Our solution is to generate the best and most cutting-edge research-grade diagnostic testing data for the patient at no cost to them, testing that they would likely not be able to afford or have ordered by their physicians. We then crowd-source the analytics of that data to a curated list of credentialed research scientists or medical practitioners, who use algorithmic or computer science approaches to integrate the data into a cohesive picture to find molecular explanations for the patient’s suffering. In some cases, we take it a step further, and use these diagnostic findings in tandem with the patient’s clinicians to expand their therapeutic options, especially in life-or-death situations, like cancer. It is very much a whole-of-community approach. 

Technology-wise, we use long-read sequencing platforms from Pacific Biosciences or Oxford Nanopore (sometimes supplemented by Illumina), Bionano Genomics’ optical genome maps, algorithmic genome assemblers like Wengan D, diagnostic software like from Qiagen, and so on. 

Usually the researchers involved are affiliated with top institutions, like MIT, Harvard, Stanford, UC Berkeley, UCSF, and so on. Overwhelmingly, they have backgrounds in biology, genetics, computer science, bioinformatics, and/or computational biology. PhDs and MDs are common participants in our program.

As described previously, we help patients who no longer have a "standard of care" and have reached the end of their clinical trials to explore the next steps in their treatment.

This includes patients with 1) Rare Cancers, 2) Rare Diseases, 3) Metastatic Cancers and 4) Undiagnosed Conditions.

Our process starts with a patient application followed by a patient interview.

Speaking with each applicant individually allows us to better understand their individual needs. We prioritize applications from patients who come from underserved and diverse backgrounds.

Generally, the goal for patients with rare cancers is to discover off-label therapeutic candidates and the goal for undiagnosed patients is to understand what is happening. Both classes of solutions require us to reach out to our network of researchers and data scientists and let them know the patient history and describe the -omic data that the patient and his care team have gathered. Often, the data is insufficient, so we partner with sequencing companies and universities to generate new data as required.  This data is research-grade, not clinical-grade.

Critical to the process is to develop a close relationship with every patient as well as their friends and caregivers.  Here are some examples of the way we’ve presented past patient’s cases. https://www.researchtothepeople.org/cases 

Each case is individual, as is each set of needs and results provided. For example, in Onno’s case, one team identified off label use of Lapatinib. In John’s (Undiagnosed-1) case, one team discovered a TNXB mutation. In Bill’s case, he discovered a team willing to work with him and is exploring two different therapeutics.  For Bill, each of his hackathons resulted in peer reviewed papers, which he has been able to use to get more interest in his case, and many more results.

Many of our patients go on to be leading advocates for their illnesses. You can learn more about each of our amazing patients through media and links here:

Onno:

• [Neo.Life / 1] https://medium.com/neodotlife/...
• [Neo.Life / 2] https://medium.com/neodotlife/...
• [Neo.Life / 3] https://medium.com/neodotlife/...
• [Neo.Life / 4] https://neo.life/2018/06/the-c...
• [TedxSanFrancisco Video]

Bill:

• [KCCure] https://kccure.org/2018/03/bil...
• [Clemson News] https://news.clemson.edu/stude...
• [Bill's Blog] http://rarekidneycancer.org/

Shirley: 

• [Micron] https://www.micron.com/insight...
• [USC News] https://news.usc.edu/109794/sc...
• [NIH] https://www.cancer.gov/about-n...
• [Bloomberg] https://www.bloomberg.com/opin...
• [Washington Post] https://www.washingtonpost.com...
• [Harvard] https://dbmi.hms.harvard.edu/e...
• [Berkeley School of Information Video]

John

• [Invitae Video]

Gigi:

• [HerStemStory] https://herstemstory.libsyn.co...
• [Mayo Clinic Transform 2019 Video]

We are well-aligned with the Challenge. We address the unjust burden of rare diseases faced by disinvested communities and historically underrepresented identity groups by selecting for these patients for our program. We promote community and connection among rare disease patients and their advocates by supporting them through data generation with their cases, forming a scientific team to analyze their cases, and bringing together scientific supporters at our hackathons. We unlock collaboration among patients, scientists, and health care providers to improve patient outcomes and leverage big data and analytics to improve the detection and diagnosis of rare diseases at our hackathons.

We are between the Pilot and Growth stages. For the past four years, we have hosted hackathons at Stanford, Salesforce, Invitae and Google: 

1. Onno Farber / Neurofibromatosis / 2017  / 150 attendees.

2. Bill Paseman / Rare kidney cancer / 2018 + 2020 / 120 attendees.

3. John / Undiagnosed patient / 2019 / 130 attendees.

4. Leila Janah / Epithelioid Sarcoma patient / 2020 / 40 attendees 

In 2020, we partnered with Dr. Michael Snyder, the Stanford Medicine Genetics Chair and Ben Rolnik of the Stanford Healthcare Innovation Lab (SHIL). We received $250K in funding from Alexion. 

By early 2022, we expect to be in high growth phase, after completion of our current 4 patient cases:

1. Vanessa Slavich / desmoid tumor / June 2021 Hack4Rare + September 2021 at Stanford

2. Shirley Pepke / Ovarian cancer / September 2021 

3. Gigi Kreibich / Hypophosphatasia / Winter 2021 

4. Naomi / Undiagnosed patient / Winter 2022 

This program is the true realization of the Precision Medicine Initiative. The key is in combining advanced research technologies (in this case Oxford Nanopore, Bionano Genomics, and Pacific Biosciences) to eliminate sequence gaps in patient genomes, providing clarity and contiguity impossible with previous technologies. According to Dr. David Bick of the HudsonAlpha Institute for Biotechnology, Illumina’s short-read sequencing technology has only a 30% diagnostic yield. Considering 10% of the American (as well as global) population has a rare disease, that leaves over 20 million people searching for diagnostic answers in the USA alone.  

Our solution is innovative through technology because it is able to get the most complete picture of the genome for every patient, with limited or no data loss, making the diagnostic phase as precise and accurate as possible.

Our solution incorporates crowd-sourcing, involving researchers who have interest in the relevant syndromes of our patient cohorts. These researchers often employ artificial intelligence or machine-learning algorithms on the data, as well, which is able to sift through vast amounts of information at inhuman speed.

Our solution is innovative for many reasons, but, above all, because it is both accurate and timely so that the rare disease and cancer communities get a molecular diagnosis fast enough to save their lives. We believe a paradigm shift is needed, and that our approach not only benefits the patient but benefits us all, by giving us a better picture of disease and human biology.  That moves healthcare forward as a whole.

With the recent completion of Chromosome X and 8 using a combinatorial approach, with Oxford Nanopore & Pacific Biosciences data to look for large structural changes, and an Optical Genome Map as a scaffold for accurate assembly (among other technologies), contiguous, even telomere-to-telomere genome assembly has been made possible, which will illuminate sequence gaps and repetitive regions, where many rare diseases lurk.  

Many rare disease and cancer patients are unable to get diagnoses due to these dark areas. 

This is how currently-available Illumina sequencers work.  Illumina chops up the 3.2 billion base pairs in our genome into segments of only 150bp long, sequences them, and reassembles them in a computer. The problem with this is that some areas are very repetitive, and when the computer is confused about where to put two pieces that are identical, that data is often dropped, and a hole emerges in the genome assembled from these smaller segments. What we do is incorporate long-read sequencing (more distinct, longer segments), the same technology that enabled a gapless assemblies of Chromosomes X and 8. We use the best AI algorithms to assemble that genome with the highest fidelity, and then we take that assembled genome and make it available to multiple interested parties who have been developing diagnostic software to run on that assembled genome. This makes it so that the patient gets a premium genome and multiple diagnostic approaches on their data, to find the needle in the haystack that is causing them to suffer so much.

For this section, we will be sharing publicly available papers or videos.  We particularly wanted to share the Undiagnosed-1 event, featuring one of our patient cases, John, who was sequenced three times by prominent testing centers using Illumina’s whole genome sequencing platform, and he was misdiagnosed because his problem gene was in an area with a sequence gap (a hole in the data).  With Oxford Nanopore sequencing and Qiagen’s bioinformatic pipeline, it took one of our teams just two days to find the TNXB gene that had been causing John a lifetime of suffering with Ehlers-Danlos Syndrome.  We believe John is just one among many whose molecular diagnosis will be enabled with this approach, and we believe Precision Medicine will be impossible without using these technologies and a communal approach to diagnosis.  Below the technical papers are videos of John’s experiences at his Undiagnosed-1 event.

Researchers use long-read genome sequencing for first time in a patient: https://med.stanford.edu/news/...

Scientists achieve first complete assembly of human X chromosome: https://news.ucsc.edu/2020/07/...

Complete chromosome 8 sequence reveals novel genes and disease risks: 

https://www.sciencedaily.com/r...

Undiagnosed-1 Post-Event Trailer:

Undiagnosed-1 Invitae Commercial:

Undiagnosed-1 Final Presentations:

The Research to the People approach has a rigorous application process in order to access open-sourced patient data, so only those who have been extensively vetted will be looking at this information.  While one may hesitate due to privacy concerns, this “risk” is actually a benefit, because it is the only way in which the patient can have a second, third, fourth, fifth, and tenth opinion at the same time, making it so that tunnel vision does not cause harm to the patient.  Our patient, John, actually suffered as a result of this tunnel vision.  As mentioned before, he was sequenced three times, and each of those three sequences had a gene for fructose metabolism flagged -- ALDOB.  John, already cachexic (106 pounds at 5’10”) was forced to go on a sugar-free diet for half a year, when ALDOB was not a gene causing him any problems (and sugar was one of the primary ways he maintained his weight).  He lost even more weight as the doctors insisted that it was likely the cause, all due to inadequate Illumina data, which could not find his TNXB defect, and dogmatic geneticists, who based everything on inferior technology.  One could safely argue that the greater risk is in NOT going through our program, as trying to identify a patient’s disease genes without a complete or near-complete genome assembly could lead to red-herrings, and these red-herrings, as in John’s case, could lead to harm to the patient as they are evaluated.

Our program has been focused on being high quality and low volume during the pilot phase -- we currently work directly with 4 patients. As we enter the growth phase, we intend to expand our program to serve 100 patients over the next 5 years. We expect the scientific insights and learnings from our program to be exponentially useful for other patients and future research. We hope to touch 1 million patient lives with resulting research from our work.

The sum effects of the research that comes out of our hackathons has an even greater impact. So far, the research insights that come out of our hackathons could impact at least 892,000 patients. (Annually worldwide there are 33,000 patients with Neurofibromatosis2, 400,000 kidney cancer, 39,000 Ehler-Danlos Syndrome, 17,000 Epithelioid Sarcoma, 25,000 desmoid tumor, 300,000 ovarian cancer, 78,000 hypophosphatasia and countless undiagnosed/misdiagnosed cases per year). As our program expands, we have the ability to impact millions.

Funding: After working on a shoestring budget, RTTP has found in a home in 2020 at the Stanford School of Medicine.  In addition to getting access to world class scientists and wetlab space, this has allowed us to expand our reach, visibly and influence considerably.  

Patient: On a per patient basis, the primary KPI is a mutation of significance or a therapeutic.  For example, in Onno’s case, one team identified off-label use of Lapatinib.  In John’s (undiagnosed) case, one team discovered a TNXB mutation.  In Bill’s case, he discovered a team willing to work with him and is exploring two different therapeutics.  Also, each of his hackathons resulted in peer reviewed papers, which he has been able to use to get more interest in his case.

One goal is to push the clinical/research data boundary.  To have future physicians apply their work from Bench to Bedside in a way that helps patients who have exhausted all clinical options.  The primary KPI will be the number of patients that they have helped using research (vs. clinical) grade data.

Funding: After working on a shoestring budget, RTTP has found in a home in 2020 at the Stanford School of Medicine.  In addition to getting access to world class scientists and wetlab space, this has allowed us to expand our reach, visibly and influence considerably.  

Patient: On a per patient basis, the primary KPI is a mutation of significance or a therapeutic.  For example, in Onno’s case, one team identified off-label use of Lapatinib.  In John’s (undiagnosed) case, one team discovered a TNXB mutation.  In Bill’s case, he discovered a team willing to work with him and is exploring two different therapeutics.  Also, each of his hackathons resulted in peer reviewed papers, which he has been able to use to get more interest in his case. 

One goal is to push the clinical/research data boundary.  To have future physicians apply their work from Bench to Bedside in a way that helps patients who have exhausted all clinical options.  The primary KPI will be the number of patients that they have helped using research (vs. clinical) grade data.

Full-time

• Emily Wang: Co-Founder, Director

• Pete Kane: Co-Founder, Director

Part-time

• Dr. Michael Snyder: Principal Investigator

• Ben Rolnik: Business Development Director

• Dr. Fereshteh Jahaniani: Science Director

• Dr. Tejaswini Mishra: Scientific Lead

Contractors: 

• All patients 

  • Onno

  • Bill 

  • John

  • Shirley 

  • Vanessa 

  • Gigi 

  • Naomi

• Web and Design Team

  • Kexin Cha

  • Kaixi Yang

  • Qinyi Yao

Our team is positioned to succeed in bringing hackathons for patients with rare illnesses. All team members come together to combine industry leading skills in genetics, community building, and business development.

Our team is not limited to our full time and part time members - our former patients all continue to dedicate time and offer help that is integral to the success of our organization. They have experienced rare diseases of their own and as former participants of the program, they are uniquely positioned to help future patients as they integrate with our program.

For Peter, diversity and inclusion on the leadership team has always been a core value. In their first successful health-tech community organization (Healthcare.mn) Peter's co-founders were both of African-American descent. The organization built a strong health tech community in Minneapolis and never missed an opportunity to elevate Black, POC, LGBTQ and women in health-tech.

Growing up in a family where most of his siblings were trans-racially adopted, it has always been important for Peter to stay conscious of diversity and inclusion. This was reflected in the founding volunteer team for Research to the People (then called Silicon Valley Artificial Intelligence, SVAI) where roughly 90% of the team identified as women, POC, LGBTQ or non-binary.

Research to the People's Co-founder, Emily Wang is an Asian American woman and an immigrant. She has always been involved in social entrepreneurship for underrepresented groups. Previously, she was the director of events at Period, a non-profit organization donating menstrual care products to homeless shelters across the country. She also founded the Food Pharmacy network, a network of 15 free clinics that receive free fresh produce to give to low-income patients and has volunteered at the Ithaca Free Clinic, an organization that provides free western and holistic medical care, for over 5 years.

In our current work, diversity and inclusion is equally important in the patients we serve and the research community we bring together. Our current patients are all women including Asian, Black and LGBTQ identities. 

Emily Wang is the co-founder and director of RTTP. Previously, Emily was a student at Cornell studying biology and chemistry before she left her junior year for the Thiel Fellowship to found a respiratory health monitoring and diagnostics startup that was acquired in Summer 2020. Emily strongly believes that the work she does in life should be mission oriented - she started the respiratory health company because her friend passed away from lung cancer at 22. Then, in Winter 2020, Emily suffered from choriocarcinoma, a rare and fast-growing cancer that occurs in a woman's uterus (womb) that occurs in 2 to 7 out of 100,000 pregnancies. After experiencing a life-threatening cancer at 22 herself, Emily felt she had a second chance at life after a successful surgery eliminated the cancer. The three months she was bedridden and nauseous before her diagnosis were the most uncertain months of her life. It was therefore a no-brainer for her to join the RTTP team in 2021 as the Director to follow her passion for helping patients with rare illnesses come up with treatment plans and to help the team grow and scale in order to change systems around how research for rare illnesses is conducted.

We are applying to the Horizon Prize Challenge because we hope to bring our program into the Horizon Therapeutics and MIT ecosystem, fund more patient cases, collaboratively engage researchers and engineers in Boston, and produce more open science. We could not have achieved everything we have without institutions like Alexion and Stanford. We admire how Horizon Therapeutics is dedicated to putting rare disease patients first through advocacy, education, and bringing medicines for those with unmet needs. As an organization that also puts patients first and is working on a variety of illnesses, we see potential in hosting hackathons in diseases that Horizon Therapeutics targets, including chronic granulomatous disease, nephropathic cystinosis, and thyroid eye disease, amongst many other ways we could collaborate.

We also have so much to learn from the Solve program and other participants. We see MIT Solve as more than just an initiative, it’s a community of social entrepreneurs making incredible progress - seeing high value partnerships across all industries between members and solvers, like Beyond conflict’s partnership with Twilio and MediCapt and the Patrick J. McGovern Foundation demonstrates the ability of the ecosystem to produce these quality relationships. We also know that as a younger organization just entering our growth stage, we have a lot to learn from other Solvers' experiences both within our challenge and outside. As we expand our program across the world in the next five years, having the diverse worldwide MIT Solve network will be invaluable.

Research to the People has benefited greatly from constant guidance and advice from the community of patients and scientists we serve. They have helped us develop the program's look and feel, in addition to donating time and services in Legal, Finance, Regulatory, Public Relations, and Technology.

As an organization that exists to serve patient and scientific communities, we are diligent and malleable to our communities evolving needs and how they donate their time and expertise to us. The four key areas we are seeking more help in are:

Business Model: Our program has excellent product market fit, and we're seeking to develop a more sustainable financial model. We think there will be incredible and unforeseeable business model opportunities as our program grows. We have not been in a rush to push any specific model, choosing to stay focused on improving our product while we stay conscious of evolving business model opportunities.

Measuring Impact: The data and opportunity for precision medicine research our organization is beyond anything else in the industry. To truly measure impact we will need to develop more sophisticated systems. This is a top priority.

Product: The medical insights our community produces is our most valuable product. We're eager to work with technologists, designers and data scientists, and information architects to create a beautiful, interactive and useful product.

Technology: We're developing our first technology infrastructure right now. Our technology will help convey insights from research teams submitting analysis on our patient cases.

Research to the People maintains a wide web of relationships and we hope to partner ubiquitously across academia and industry. We're proud that our model allows individuals and organizations that are normally competitive to come together to advance research and help patients.

 Many MIT students have participated in our past cases and we have enjoyed collaborations with MIT Hacking Medicine via Hack4Rare and Children's Tumor Foundation.

 Similar to how we are being supported at Stanford University, we hope to collaborate with Genetics, Bioengineering and Precision Medicine people, programs, and institutions at MIT. Our ideal partnerships include:

 -Manolis Kellis, the head of computational biology at MIT. 

 -MIT Center for Precision Cancer Medicine (https://cpcm-mit-edu.ezproxyberklee.flo.org)

 -The Koch Institute for Integrative Cancer Research at MIT (https://ki-mit-edu.ezproxyberklee.flo.org)

 -MIT Computational and Systems Biology Program

 An ideal entry point may be hosting an Independent Activities Period program (https://web-mit-edu.ezproxyberklee.flo.org/iap). The duration and format of IAP is very appealing to us.

 We want MIT students and faculty to be aware of the opportunity to use their skills to help advance real patient cases through Research to the People. Our feeling is that members of the scientific community have the capacity and interest to contribute to at least one patient case per year.