Amy Lynn Santiago’s three-year-old son Nicholas Volker was suddenly, terribly ill. Problems that had started with a fever and an abscess that would not heal now trapped the boy in the hospital for years. He endured multiple surgeries, chemotherapy, dangerous and powerful drugs, and the permanent removal of his colon. Finally, as Nick’s care exceeded the family insurance’s two million dollar lifetime benefits cap, the physicians in his Milwaukee hospital decided to sequence his genome.
Upon discovering that he had two rare genetic diseases, they were able to successfully treat them with a bone marrow transplant. However, Nicholas, now 11, lives with long-term side effects from his ordeal, including PTSD, learning disabilities, social issues from living in near isolation for four years, and a permanent ileostomy.
His parents believe that gene sequencing could have saved him and others from much of what he went through, and advocate for this sort of personalized medicine through their nonprofit One in a Billion Foundation.
Dr. Michael Goldman and the San Francisco State University Department of Biological Sciences also see the promise of personalized genomic medicine, and hosted a one-day conference in South San Francisco June 2nd to highlight developments in the field.
Personalized medicine, with specialized treatments for particular patients, or groups of patients, isn’t a new idea. Hippocrates devised a personal way to treat each patient given their temperament and the seasons. Nowadays, though, customizing treatments has become possible at a more refined level given modern DNA analysis technologies, and Barack Obama called for investment into research in the field in his 2015 State of the Union address.
Dr. Esteban Burchard, professor of bioengineering and therapeutic sciences and medicine at the University of California – San Francisco (UCSF), explained how clinical trials that include minorities allow medical researchers to see how different social subgroups with different genetic backgrounds may differ in terms of health risks and treatment responses. For example, in some of the studies he showed, African-Americans seemed less likely to develop multiple sclerosis, Latinos seemed more likely to suffer from asthma, and Asian-Pacific Islanders were less likely to respond to the drug Plavix, which prevents blood clotting.
Dr. Burchard was careful to point out that we need to control for the effects of demographics, social conditions and the environment when we attempt to search for genetically based differences among racial groups. However, as in the Plavix case, some variations did appear to have a genetic component.
Computerized ‘big data’ analysis can allow researchers to identify biological and genetic variations more efficiently.
Dr. Dexter Hadley, also at UCSF, outlined an effort to figure out how to save the lives of some of the nearly 21,000 people who die each year from dengue fever. Many people get dengue fever, get sick, and recover, but some become much more ill and die. Is there an identifiable difference between those who are likely to die? A large group of grad students and post-docs, recruited by social media, are working to classify and input descriptions of dengue fever patients into a computer database for comparison.
Prostate cancer is also much more dangerous for a small subset of patients, and scientists have hoped for decades to find out how to predict if a patient’s cancer will metastasize and become much more lethal. Dr. Colin Collins of the Vancouver Prostate Center explained how researchers have now observed that prostate cancer changes not just the cancerous part of the tumor, but much more of the entire ecosystem of a person’s body. There are now blood tests for certain biomarkers of prostate cancer that are linked to probable metastasis, lessening the need for invasive prostate biopsies. Image recognition learning is also improving the accuracy of mammograms, reducing the number of false positives for cancerous tumors and thus unnecessary breast biopsies.
Dr. Christos Petropoulos, vice president of LabCorp, outlined the dramatic progress made in HIV/AIDS treatment over the past forty years. With slides reminding us of the top ten pop songs and hairdos of each decade, he took us back in time to when HIV positive patients had to take 30 or more pills per day and could only expect to live perhaps 10 years after diagnosis. Now, thanks in part to customized drugs targeting different phases of viral infection of immune cells and viral replication, patients can live for decades with HIV in remission, without active symptoms.
After a healthy, vegetable-filled lunch, we returned to see a bright red Ferrari on the screen in the front of the room. AvidBiotics CEO David Martin discussed what are known as CAR-T cells, now developed into ‘convertible’ CAR-T cells through medical science. These immune cells, although not literally ‘cars,’ can be highly driven to destroy cancerous tumors as they have receptors that bond to antigens, substances on the surface of tumors. However, using the car analogy, these cells can function like vehicles with no steering and no brakes, binding to and destroying normal tissue that resembles a tumor. Researchers are working on disabling these cells, rendering them inert until activated by a substance cancer patients can ingest.
Next up was Genentech’s Ragnar von Schiber, who outlined Genentech’s efforts to promote biotech education for children and teens in South San Francisco, the school district nearest its offices. These programs include a company-sponsored science competition, a teaching facility, and mentors for students.
Dr. Bernat Baeza Raja of Second Genome, Inc. outlined research into the effects of the bacterial colonies living on our skin and inside our bodies. He suggested that dysfunction within our intestinal bacterial ecosystems could be involved in a variety of conditions, including obesity, anorexia, Crohn’s disease, and diabetes. Efforts are underway to identify the species of bacteria that live symbiotically with humans and the proteins they produce. Different people have varying internal bacteria because of our lifestyles and environments – where we live, what we eat, what we encounter throughout life. And these differences could also affect how we experience disease and respond to medical treatment.
Dr. Ed Rebar of Sangamo Therapeutics discussed how scientists cleave, or cut up, DNA in the lab. Right now they use zinc-finger proteins to snip DNA in medical research. A new technique, the CRISPR/Cas9 system (the Cas9 enzyme normally cuts DNA after sequence repeats known as CRISPRs and can be harnessed to selectively cut DNA) is cheaper, faster and easier, but less safe for medical research as we have less experience with the technique. Dr. Rebar illustrated that the older zinc-finger technique is getting more accurate, enabling scientists to cut DNA at specific nucleotide bases. This has potential applications for treating genetic conditions, such as Huntington’s disease, where extra repeats in DNA cause problems with cell function.
Dr. Marica Grskovic of CareDx Inc. explained how we might be able to identify whether a transplant patient’s body is rejecting a donor organ earlier and faster by looking for DNA from the organ donor in the recipient’s blood. Cells only live so long before undergoing apoptosis, natural cell death, and the DNA from these dead cells is cleared within half an hour by our liver and kidneys. However, there is more of this cell-free DNA floating in the blood after an injury or during organ rejection, when there is more apoptosis than normal. So, we can test for this to see if the recipient’s body is starting to reject an organ.
Finally, Dr. Charis Thompson, of the University of California, Berkeley, and the London School of Economics, urged us not to forget the social implications of an avenue of medical research that can tend towards a focus on the individual.
She outlined some ways that we can use the tools of personalized medicine to work towards a more just society and the welfare of the public.
Aware that some of this research might touch on controversial issues, she encouraged us to come together as a society and focus on areas where we can agree and accomplish some good, rather than fighting over areas that are too divisive to confront now.
‘We can call people in, bring them up to where we are by educating them,’ she said, ‘rather than calling them out, excluding them when correcting them.’
Increasing genomic inclusion, collecting data on the environment, biology, and lifestyle of a representative sample of the United States that does not overlook minority groups, is one way to do this. Also, we can strive to become more accurate and avoid inadvertent, sloppy assumptions about the complex interactions between social and cultural groups’ environments and their genetics.
Exploring crowdfunding and other models to ensure that research will be funded even for rare diseases can help those patients. As Dr. Thompson said, we can think of how lucky we are not to need certain levels of help from others, rather than wondering why society doesn’t seem to give us what it gives someone else who has a unique problem.
She outlined some past social movements related to health, pointing out how the general public helped to call attention to social issues that contribute to illness and that should be studied by scientists. And, she discussed how some conditions, such as obesity and addiction, were thought of as moral character failings and are now starting to be considered as biomedical issues. However, queer and disability justice activists warn of the danger of overmedicalizing natural human variation. Not every difference needs to be considered a problem and treated.
Dr. Thompson closed her talk by encouraging us to look at the impact of our new medical technologies on society. Are we going in the direction making health more accessible to all people or only benefiting some? She pointed out that big data could be harnessed to examine the social impacts of and access to our emerging medical technologies and that we could incorporate equity and access goals into the design of our research projects.
Afterwards, the biology students at San Francisco State University showed off the posters related to their research while we enjoyed a sumptuous reception. Given what I saw at the conference, the next generation of science seems to be proceeding well and in good hands.