Cancer

I recently had the opportunity to talk in-depth with Stanford clinicians and faculty members about how the U.S. Supreme Court decision on the Myriad gene-patenting case may affect patient care. The answer? Surprisingly little (at least in near future). That’s in part due to the large proprietary database of BRCA mutations amassed by the company. As I wrote in my article:

…Although the ruling may be an ethical and philosophical triumph for those who believe that human genetic information should not be claimed by any corporate entity for profit, it’s not likely that patient care will change immediately, according to breast cancer clinicians at the Stanford Cancer Institute. Myriad’s experience in the field of BRCA gene testing and interpretation will be difficult to surpass, at least for a while, they said. Over time, however, the ruling should result in a freer research atmosphere that will translate into improvements for patients.

Maybe, like me, you read everything you could get your eyes on last week about the gene patenting case, and spent several days pondering the implications of the ruling by the Supreme Court that companies like Myriad Genetics can’t patent isolated human genes. Or, maybe you’re a busy person with not much time to dive deeply into the issue. If so, you might find today’s summary by the National Geographic - 7 Takeaways from Supreme Court’s Gene Patent Decision – a useful primer.

The article quotes Jake Sherkow, JD, and Hank Greely, JD, from the Stanford Center for the Law and Biosciences, who each provided comment on the case for us and other members of the media last week. I found point 2 – “Synthetic DNA is fair game” – to be particularly interesting, since it’s one of the first discussions of what the ruling allows, rather than prohibits:

While companies can no longer patent genes with the same sequences found in cells, the decision allows edited forms of genes not found in nature—known as complementary DNA, or cDNA—to be patented.

cDNA is not useful for diagnostic tests, but it is crucial for producing protein-based drugs, explained Robert Cook-Deegan, a professor of genome ethics, law, and policy at Duke University’s Institute for Genome Sciences and Policy.

“Those are the billion-dollar molecule patents,” Cook-Deegan said. “Biotech companies care a great deal about cDNA patents, and it should be reassuring to them that those patents are still fine.”

Hank Greely, a bioethicist and law professor at Stanford University, predicts cDNA patents will become even more valuable as scientists move beyond merely exploiting naturally occurring proteins.

“In the longer run, as we move into an era of synthetic biology, where we start trying to improve upon nature, then I think [cDNA patents] will be important,” Greely said.

Previously: A closer look at Supreme Court’s decision on gene patenting, Supreme Court rules on Myriad’s “gene patenting” case and Are genes patentable? A summary of the Supreme Court case

Yesterday’s Supreme Court ruling declaring that isolated genomic DNA is not eligible for patent protection, but that cDNA – “cloned” or “complementary DNA” – can be patented ignited a frenzy of news stories and commentaries about the decision. In a segment on KQED’s Forum this morning, Mildred Cho, PhD, associate director of the Stanford Center for Biomedical Ethics and a professor of pediatrics,  joined the discussion on how the ruling will affect medical and science research. Listen to the full discussion here.

Previously: A closer look at Supreme Court’s decision on gene patenting and Supreme Court rules on Myriad’s “gene patenting” case

Wow, what a busy day for gene patenting discussions! This morning’s decision (.pdf) by the Supreme Court that isolated DNA is not patentable has sparked a wave of stories, press releases and announcements across the web. I thought I’d pull together some of the most useful information I’ve found today on the topic.

Twitter provided a forum for immediate responses to the ruling, my favorite of which was authored by NIH director Francis Collins, MD, PhD:

SC: “A naturally occurring DNA segment is a product of nature and is not patent eligible merely because it has been isolated” Woo Hoo!!!

— Francis S. Collins (@NIHDirector) June 13, 2013

(Collins later followed-up with a much more staid official statement, but I still love the “Woo hoo.”) The Twitter feed from the National Human Genome Research Institute was only a bit more restrained:

Huge news: Supreme Court decision says naturally occurring DNA is not patentable http://t.co/rhhtY2N4GI

Several Stanford experts weighed in as well, including Stanford law professor and bioethicist Hank Greely, JD, who had a slightly different reaction to the ruling:

Very 1st reaction w/o reading full opinion: cDNA exception won’t help Myriad or other test cos. Deeper reaction – the issue isn’t important.

— Hank Greely (@HankGreelyLSJU) June 13, 2013

Why unimportant? Only 1 “bad” company, patents expire, technology workarounds. On the other hand, Myriad has some strong “trade secrets.”

— Hank Greely (@HankGreelyLSJU) June 13, 2013

Geneticist Carlos Bustamante, PhD, also tweeted his thoughts about the issue of consumer choice (scroll down to read tweet series).

As the day wore on, it became apparent that those on both sides of the issue were claiming a victory of sorts. Myriad issued a positively worded release highlighting the Court’s decision to uphold the company’s cDNA patents. Stock in Myriad (and other biotechnology companies) initially jumped after the announcement, but ended the day down about 5.6 percent.

Two genetic testing companies (Ambry Genetics and Gene by Gene, Ltd) that I know of (there could well be more) jumped into the fray this afternoon with announcements that they will immediately begin offering BRCA1 and BRCA2 testing to patients at prices much lower than the $3,000 to $4,000 charged by Myriad. It remains to be seen, however, how much of an advantage Myriad’s proprietary database (used to interpret the sequence results and deliver risk estimates to patients) will confer to savvy patients who may choose to pay a premium for access to this cloistered information. Personally, I’m really interested in the effect the ruling will have on an end-around effort by researchers trying to reconstitute Myriad’s database by compiling individual patient’s reports from the company.

Finally (for now), for a general overview of the history of BRCA gene patenting and the field of genetic testing, check out this excellent article from Nova Next. I have a feeling I’m going to be reading it more than once as I (along with many experts in both law and biology) puzzle through the issues for these next few days and weeks.

Previously: A closer look at Supreme Court’s decision on gene patenting, Supreme Court rules on Myriad’s “gene patenting” case and Are genes patentable? A summary of the Supreme Court case

As previously discussed here and elsewhere, the Supreme Court today issued its opinion in the gene patenting case Association for Molecular Pathology vs. Myriad Genetics, Inc. In a unanimous decision (.pdf) authored by Justice Thomas, the Court declared that isolated genomic DNA was not eligible for patent protection, but that cDNA – “cloned” or “complementary DNA” – could be patented. This was largely the outcome some predicted after oral argument. And while the actual business and research effects of the decision remain to be seen, this does bring to a close the longstanding practice of patenting isolated portions of the human genome in its native state.

This likely brings to a close Myriad Genetics’ saga of aggressively enforcing its patents directed to BRCA1 and BRCA2 testing

The Court’s decision was relatively simple. It began with a largely accurate, and lengthy, recitation of the molecular biology behind transcription and translation. This factored significantly into the Court’s discussion of the differences between isolated genomic DNA and cDNA, particularly the absence of introns from cDNA molecules. It then assessed the patents’ claims at issue, which were generally directed to “an isolated DNA” of varying lengths and sequences. The opinion noted that, “Myriad’s patents would, if valid, give it the exclusive right to isolate an individual’s BRCA1 and BRCA2 genes… by breaking the covalent bonds that connect the DNA to the rest of the individual’s genome.” And the Court concluded its opinion by declaring that claims directed to molecules of isolated genomic DNA, themselves, were unpatentable “products of nature” because Myriad did not “alter any of the genetic information encoded in the BRCA1 and BRCA2 genes,” nor did the isolated genomic DNA possess “markedly different characteristics from any found in nature.”

The Court rejected Myriad’s claim that it created a new chemical entity because, in isolating the genes from their surrounding chromosomes, Myriad necessarily cleaved the chemical bonds of the chromosomes’ phosphate backbones. This was irrelevant because “Myriad’s claims are simply not expressed in terms of chemical composition, nor do they rely in any way on the chemical changes that result from the isolation of a particular section of DNA.”

As for Myriad’s cDNA claims, however, the Court – in a single, short paragraph – declared them eligible for patent protection because the “non-coding regions have been removed,” thus creating a new molecule not found in nature. Interestingly, the Court recognized the possibility of retrovirii potentially creating identical DNA transcripts to the cDNAs at issue, but dismissed this concern in a footnote: “The possibility that an unusual and rare phenomenon might randomly create a molecule similar to one created synthetically through human ingenuity does not render a composition of matter nonpatentable.”

Bizarrely, Justice Scalia joined the Court’s opinion in its entirety except for its preliminary scientific discussion. In a separate concurrence, Justice Scalia wrote: “I am unable to affirm those details on my own knowledge or even my own belief.” Typically, Justice Scalia does not qualify the factual portions of opinions he joins, even where they involve science. And notably, in the Court’s recent decision in Maryland v. King involving the constitutionality of warrantless DNA tests for arrestees, Justice Scalia’s dissent is replete with the factual differences between DNA and fingerprint testing.

This likely brings to a close Myriad Genetics’ saga of aggressively enforcing its patents directed to BRCA1 and BRCA2 testing. Myriad will continue to offer its BRACAnalysis product, which, because of its trade secret mutational database, is likely still the most robust BRCA test on the market. And competitors will be able to enter the BRCA testing market and make use of Myriad’s methods, although they will have to do so without the benefit of certain cDNA molecules or Myriad’s clinical data.

But the decision leaves a number of legal questions unanswered: What about other patents directed to “isolated and purified” natural products? Are cDNAs nonetheless obvious, and therefore unpatentable for that reason? And, considering the Court’s mention of retrovirii, how “unusual and rare” must a “natural phenomena” be to still be patent eligible if synthetically created? These are issues that the lower courts are likely to struggle with going forward, and issues that may, one day, be back in the hands of the Supreme Court.

Jake Sherkow, JD, is a fellow at Stanford Law School’s Center for Law and the Biosciences. His current research focuses on the intersection of patent law, biotechnology, and agency regulation.

Previously: Supreme Court rules on Myriad’s “gene patenting” case and Are genes patentable? A summary of the Supreme Court case
Photo in featured entry box by Mark Fischer

This morning, the U.S. Supreme Court issued their anxiously awaited decision in the case of the Association for Molecular Pathology vs. Myriad Genetics, Inc. Often called the gene patenting case, the case raises the issue of whether companies like Salt Lake City-based Myriad Genetics, Inc. can patent genes, in this case, the BRCA1 and BRCA2 genes. Mutations in these genes confer a substantially higher risk of breast or ovarian cancer.

The Court ruled that naturally isolated DNA is not patentable, but that synthetic DNA (such as the cDNA for the BRCA1 and 2 genes) is patentable. The decision was unanimous. From the decision:

A naturally occurring DNA segment is a product of nature and not patent eligible merely becauseit has been isolated, but cDNA is patent eligible because it is not naturally occurring.

…

cDNA is not a “product of nature,” so it is patent eligible under §101. cDNA does not present the same obstacles to patentability as naturally occurring, isolated DNA segments. Its creation results in an exons-only molecule, which is not naturally occurring. Its order of the exons may be dictated by nature, but the lab technician unquestionably creates something new when introns are removed from a DNA sequence to make cDNA.

We’ll have a longer comment about the decision later today or tomorrow from Jacob Sherkow, JD, a fellow at Stanford Law School’s Center for Law and the Biosciences. Sherkow recently wrote a wonderful blog post for us summarizing the oral arguments in the case, which took place in April. And the SCOTUS blog carried a great, ‘made simple’ synopsis of the issue earlier this year for readers who want to quickly get up to speed.

The decision is likely to have far-reaching implications for the many other gene patents granted by the U.S. Patent and Trademark Office since the first gene (chorionic somatomammotropin) was patented by the University of California, Berkeley, in the early 1980s. The National Society of Genetic Counselors now estimate that around 20 percent of all human genes are patented.

Previously: Are genes patentable? A summary of the Supreme Court case, At Stanford event, cancer advocate Susan Love talks about “A future with no breast cancer” and BRCA patients use Stanford-developed online tool to better understand treatment options
Photo by Mark Fischer

I just learned of a new Reuters blog, Cancer in Context, written by a reporter who was recently diagnosed with Stage 4 lung cancer. Debra Sherman has chosen to talk publicly about her experience (“There seems no reason to stop [writing health stories] now that my health is so compromised,” she wrote], and her aim for the blog is to use her journalistic skills to “report on the latest cancer research from the perspective of a patient.” I found her introductory post from earlier this month quite poignant:

As a Reuters journalist I have been writing about medical technology and healthcare for more than a decade. I’ve covered the major medical meetings, including the big one on cancer. I’ve written stories about new cancer drugs and treatments, about how many more survive the disease (true for breast, colon and some other forms, though not so much for lung cancer), and how a diagnosis can lead to bankruptcy, even for those with health insurance.

I wrote those stories objectively and never imagined any would ever apply to me.

Previously: A journalist opens up about her struggles with depression and anxiety and Fighting a stage IV cancer diagnosis

Interventional radiology, like its cousin interventional cardiology, is one of those medical specialties that runs along quietly without much fanfare until it does something that’s impossible in any other fashion. Surgery, even the minimally invasive sort that has traded big incisions for smaller ones, still has limitations — particularly in certain organs and for certain patients. Such was the case for Gwen McCane, a dynamo of a lady in her 70s, who had already passed successfully through chemotherapy and radiation for pancreatic cancer when tumors emerged deep in her liver. Any sort of surgery was just not possible, but interventional radiology offered her hope.

“The great thing is that we don’t need to make large incisions in our patients,” said Stanford interventional radiologist Gloria Hwang, MD, who treated McCane. “We can go in with just the poke of a needle.”

Guided by imaging, Hwang applied microwave heat to destroy the cancerous tissues. McCane went home the next day. “Every day we see people who have a real need, and they’re scared and they want to know they have options,” Hwang said. “My mission as a doctor is to offer them these options and to offer them newer, better ways of treating their cancers.”

Now McCane is back to playing golf, conducting self-esteem workshops at a county juvenile hall, meeting friends to play cards, working in her garden and being a sparkling companion to her husband of 50 years. “I feel good,” she said. “I’m just enjoying life.”

McCane’s story is captured in the Stanford Hospital video above.

Previously: New clues arise in pancreatic cancer from Stanford researchers

These days smartphones are increasingly becoming an invaluable medical tool. Researchers are experimenting with various applications and add-ons capable of a range of health-related tasks, including analyzing biological smears to identify illnesses, screening for oral cancer, monitoring lung health and diagnosing ear infections.

Now engineers at Cornell University have created a new smartphone-based system, consisting of a plug-in optical accessory and disposable microfluidic chips, allowing health-care workers in-the-field to diagnosis of Kaposi’s sarcoma, a cancer linked to AIDS that remains prevalent in sub-Saharan Africa. According to a release:

Unlike other methods that use smartphones for diagnostic testing, this new system is chemically based and does not use the phone’s built-in camera. Instead, gold nanoparticles are combined (or “conjugated”) with short DNA snippets that bind to Kaposi’s DNA sequences, and a solution with the combined particles is added to a microfluidic chip. In the presence of viral DNA, the particles clump together, which affects the transmission of light through the solution. This causes a color change that can be measured with an optical sensor connected to a smartphone via a micro-USB port. When little or no Kaposi’s virus DNA is present, the nanoparticle solution is a bright red; at higher concentrations, the solution turns a duller purple, providing a quick method to quantify the amount of Kaposi’s DNA.

The main advantage of the system compared to previous Kaposi’s detection methods is that users can diagnose the condition with little training. “Expert knowledge is required for almost every other means of detecting Kaposi’s sarcoma,” Mancuso says. “This system doesn’t require that level of expertise.”

Researchers are collaborating with colleagues at Weill Cornell Medical College to develop a portable system for collecting, testing,and diagnosing samples that could be available for use in low-resource countries within the next year. The system, they say, could be used to detect a range of other conditions such as E. coli infections, hepatitis and methicillin-resistant Staphylococcus aureus .

Previously: Developing a smartphone app to monitor lung health, Using smartphone medical images to evaluate patients from afar, Diagnosing ear infections using your iPhone? Not so far-fetched and Stanford bioengineers create an ultra-low-cost oral cancer screening tool

Maryland high school student Jack Andraka burst into the international scientific scene last year after winning the Gordon E. Moore Award at the 2012 Intel International Science and Engineering Fair. He was awarded the top honor for developing a novel paper sensor that detects pancreatic, ovarian, and lung cancers in five minutes and costs as little as 3 cents. The rapid diagnostic test is 168 times faster, 26,000 times less expensive and more than 400 times more sensitive than the current test.

Andraka was inspired to create a better way to detect pancreatic cancer after a close family friend, who Andraka often says was like an uncle to him, was diagnosed with the disease and passed away shortly afterwards. After conducting research and learning that the current test for detecting the disease is 60 years old, and that the majority of pancreatic cancer cases are diagnosed at a late stage, he set out to invent a better method and hopefully save lives.

This fall, Andraka will deliver the opening keynote at the Stanford Medicine X conference, where he’ll talk about curiosity, open source research and the new scientist. I recently had the chance to ask him a few questions about his work.

At what point did your quest to learn more about pancreatic cancer transform into a research project to create a faster, cheaper and more accurate diagnostic test?

When my uncle was first diagnosed I really didn’t understand the gravity of the disease. I didn’t even know what a pancreas was! When he died so quickly after his initial diagnosis I was so surprised. I spent a lot of time on the Internet learning about the pancreas, pancreatitis and pancreatic cancer. I learned about how the disease was often discovered when it was advanced and how the lack of a reliable early detection screening method led to so many deaths. I thought there had to be a better way and started sketching out criteria for what an early detection method would need. At the same time, I was still reading about nanotubes, a subject that fascinated me and that I had done a project on the year before. When I sneaked a paper on nanotubes into biology class one day, the teacher was lecturing us on antibodies. I wondered what if I combined what I was reading about (single walled carbon nanotubes) with what I was supposed to be learning about (antibodies) and made a sensor to detect pancreatic cancer. Of course I had a lot of research to do to even begin making an experimental design!

You contacted more than 200 scientists involved in research on pancreatic cancer requesting space in their lab to test your experiment and only received one response. How did you overcome this challenge and find the motivation to move forward without losing hope?

I spent a lot of time preparing my proposal and I was quite excited about it. I used the Internet to find professors in my area who were working on the subject. I figured I would send some e-mails out and then sit back and wait for the acceptances to roll in! Of course these are busy and successful professionals and many didn’t even take the time to respond to a 14-year-old. Those who did either replied that they had no room, or that they were working on something a bit different or even that my idea was impossible. Many times I was dejected and discouraged and my mom would tell me that maybe in a few years when I was 16 I could try again, or that maybe I could change my research topic. Then she’d tell me that if I believed in my topic I should keep trying. So I’d head back to the Internet and look up some more names. Actually all the rejections helped me because I refined and improved my project and bolstered it with even more detailed material lists, even including catalog numbers. When [Johns Hopkins researcher Anirban Maitra, MBBS,] said “maybe’ and invited me in for a discussion, I knew this was my big chance and came prepared with binders of journal articles and a really well-prepared grant proposal. It only takes one ‘yes’ for a door to open and then it’s up to you to take advantage of the opportunity.

What was it like to be a high school student working in a lab at Johns Hopkins?

I was so focused on convincing a professor to give me an interview to work in a lab that I didn’t think ahead to imagine what it would be like being a freshman high school student working with very experienced researchers in a lab like Johns Hopkins! Again my lack of experience helped me because I was more excited than intimidated. I first realized what I had got myself into when I arrived for my initial interview. There were so many researchers asking me serious questions and they were all much older than me. I wasn’t intimidated though because I was well prepared and enjoyed the discussion. In the lab everyone was helpful. If I asked a question, they took the time to answer. It helped that I tried to be as self-sufficient and prepared as possible and to not have the need to be “babysat.”

Medicine X explores the potential of information technologies to advance the practice of medicine, improve health and empower patients to be active participants in their own care. How have you used information technologies in your own research?

I had no access to any information that wasn’t on the Internet. I was able to educate myself using Google and Wikipedia. These resources can empower not only patients, but researchers like me who do not have access to university libraries or classrooms. I was able to learn the basics and then dig deeper as questions arose. I was able to access research from many fields and then connect the dots to create my new sensor. My mentor, Dr, Maitra, mentioned a colleague who regularly brought home journals from different fields to read and think about. I did not have access to many of these journal articles due to paywall barriers, but the articles I was able to access from many different fields served the same purpose for me. I was able to download journal articles and connect the dots to create my pancreatic cancer sensor.

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