Supreme Court bungles the science in DNA patent decision

[This is slightly modified from my post 2 days ago at Forbes.]

The Supreme Court ruled this week that Myriad Genetics doesn't own your DNA after all.  Myriad holds patents on the BRCA1 and BRCA2 genes, which are linked to an increased risk of breast and ovarian cancer, and they charge exorbitant fees for their DNA diagnostic test of those genes.  As I've written before (such as this 2012 Clinical Pharmacology article), Myriad didn't invent the genes, and the patents should not have been granted.  So in large part the Supreme Court got it right.

But they got the science wrong, as any geneticist reading today's decision will realize immediately. In the very first paragraph, they make no less than three errors of fact.  First, they write:

"The nucleotides that code for amino acids are 'exons,' and those that do not are 'introns.' "

Not correct.  Here's the facts: when making DNA into a protein, the cell copies DNA into RNA.  Big chunks of the RNA are spliced out and discarded.  Those are "introns."  What remains is "exons."  That's it.  The nucleotides that code for amino acids are contained within the exons, but they are not the same thing. It's not unusual for 25% or even 50% of the nucleotides in the exons to be ignored when stringing together amino acids to make a protein.

Error number 2 comes next, when the Court writes:

"They [scientists] can also synthetically create exons-only strands of nucleotides known as composite DNA (cDNA)."

Wrong again.  cDNA stands for complementary DNA, because the DNA produced is the complement of the original strand. This means that each nucleotide is replaced with its complement: A and T are complementary, and C and G are complementary.  The court gets this right later on in the ruling.

Just after this, they write:

"cDNA contains only the exons that occur in DNA, omitting the intervening introns."

Ouch! Wrong again.  cDNA simply means a complementary copy of DNA, which doesn't have anything to do with exons.  If you make a cDNA from a mature messenger RNA transcript, then yes, it will contain only the exons.  But you can make cDNA from other parts of the genome, and from other types of RNA transcripts.

There are more errors further down in the decision. For example, they write that "Nucleotides that do not code for amino acids, in contrast, are known as 'introns.' "  This just compounds one of the errors above.  They also used the term "pre-RNA" instead of the correct term "pre-mRNA."  I could go on.

It's troubling that the highest court in the land can't get even the basic facts of molecular biology right when writing a decision that has such fundamental importance to genetic testing, the biotechnology industry, and health care.  I cannot pretend to know who they got to do their biology background research, but any genetics graduate student could have done far better.

Supreme Court saves the vaccine system

Unbeknownst to most people, the Supreme Court heard a case last week that, had they ruled differently, might have destroyed the vaccine system in the United States. On February 22, the court ruled 6-2 to keep the special Vaccine Court system intact. In particular, they ruled against Russell and Robalee Bruesewitz, who were suing for damages on behalf of their daughter Hannah. But even though the system is saved for now, the two judges who voted in the minority demonstrated a frightening disregard for possible consequences, and encouraged those who would like to take us all back to an era when millions of children died each year from diseases like measles, polio, and whooping cough.

Hannah Bruesewitz's case is heartbreaking: she suffered a seizure in April 1992, within a day of receiving the vaccine for diphtheria, pertussis, and tetanus (DPT), and she had many more seizures in the following months. She was eventually diagnosed with with “residual seizure disorder” and “developmental delay" which she still has today. Her parents blamed the vaccine, and in 1995 they sued in Vaccine Court. They lost, although the Special Master of that court awarded them $126,800 for lawyer's fees and other costs. The Bruesewitzes rejected the award and sued in a state court in Pennsylvania.

The case last week wasn't about whether Hannah's disability was caused by the DTP vaccine. It was only about whether her parents could sue in state court after losing their case in vaccine court. The Supreme Court said no. Had they allowed the case, state courts across the country would have been flooded with thousands of vaccine lawsuits, and it is entirely likely that vaccine makers would simply stop selling vaccines in the United States. The ensuing loss of vaccines would be a public health disaster of enormous magnitude, leading to tens of thousands of deaths from diseases that we now have largely defeated in this county.

This sounds awfully dire. Why do I claim it could happen? Because it almost did, some 25 years ago.

Back in the 1980s, largely due to one incredibly irresponsible, inaccurate television documentary called DPT: Vaccine Roulette "started a firestorm" of panic, as Paul Offit explains in his latest book (1). It also caused an avalanche of lawsuits, and juries were soon making multi-million dollar awards. As Dr. Offit documents, jury awards in vaccine cases increased from $25 million in 1981 to $3.2 billion in 1985. Two of the three companies making the DPT vaccine stopped distributing it, leaving only one company, Lederle (now owned by Wyeth) supplying it.

It wasn't just DPT. Companies making measles and polio vaccines also dropped out of the U.S. market, leaving just one company for each. We were very close to a situation where we simply wouldn't have childhood vaccines in this country.

Then, remarkably, the federal government passed the National Childhood Vaccine Injury Act of 1986. This set up a special fund to compensate anyone damaged by vaccines, covered by a tax on all vaccines. It also created a special Vaccine Court to hear cases, and required that vaccine cases go through this court. The standard of evidence for the court was lower than regular courts: for some conditions, the parents merely have to show that their child suffered the condition soon after getting a vaccine, regardless of whether the vaccine was the cause.

The law also took juries and state courts out of the equation. Vaccine makers were protected, and the childhood vaccination system was saved. The Vaccine Court functions remarkably well, using Special Masters who become far more educated about vaccines and possible side effects than any regular judges can be. There is a very small but real risk of harm from vaccines, and the Vaccine Court has made thousands of awards to compensate victims. Meanwhile, millions of severe illnesses and countless thousands of deaths have been prevented by vaccines.

So I was very dismayed that two justices, Sandra Sotomayor and Ruth Bader Ginsburg, voted against the majority. I usually agree with these two, but their reasoning in this case was wildly off. Sotomayor's dissent shows her to be misinformed, confused, or just plain naive:

"Trial courts, moreover, have considerable experience in efficiently handling and disposing of meritless products liability claims, and decades of tort litigation (including for design defect) in the prescription-drug context have not led to shortages in prescription drugs. Despite the doomsday predictions of respondent and the various amici cited by the concurrence ... the possibility of a torrent of meritless lawsuits bankrupting manufacturers and causing vaccine shortages seems remote at best."

Apparently Sotomayor is unaware of the actual "torrent of meritless lawsuits" from the 1980s that forced Congress to create the Vaccine Court in the first place, although I cannot understand how she could fail to know this history. I am also disappointed by her naive faith in trial courts to quickly dispose of "meritless product liability claims." Perhaps in an ideal world, yes. But a smart lawyer, a sympathetic victim, and a complex medical case can easily confuse both judge and jury, leading to enormous jury awards regardless of what the scientific evidence shows.

Apparently Sotomayor can't bear to limit the ability of plaintiffs to sue wherever they choose. The Vaccine Court, although imperfect, is a much better model for handling complex medical claims than the roulette of a jury trial. We should all breathe a sigh of relief that the Supreme Court kept this system intact.

Of course, the anti-vaccination movement has been quick to attack the decision. Age of Autism, one of the biggest anti-vax sites, posted an article titled "Supreme Court Ruling Abandons Vaccine-Injured Children, Threatens Vaccine Safety" in which they call the decision "a crushing blow to the rights of every U.S. citizen." A coalition of anti-vax organizations including Generation Rescue issued a press release calling the decision "misguided" and making a number of incorrect claims about vaccine safety. But scientists and doctors, notably the American Academy of Pediatrics, applauded the decision.

Reference

1. Paul A. Offit, M.D. Deadly Choices: How the Anti-Vaccine Movement Threatens Us All. Basic Books (2011). See especially pages 2-12.