My breasts. My genes.

Posted 16 May 2013 by M. Wilson Sayres

Angelina Jolie wrote about her decision to have a double mastectomy after learning that she carries a version of the BRCA1 gene with mutations that are significantly associated with developing breast cancer, speaking with her doctor, and considering the risks and benefits to herself, and for her family.

By ILA-boy

Many people have reacted, but I particularly like this response from Judith Soal that introduces the complexity of understanding the genetic component of diseases. We still have quite a lot to learn about the relationship between genes, environment, and disease, but we do know that some genetic mutations increase susceptibility to disease, but also that people without known genetic mutants are often affected by diseases due to environment, to novel mutations, or, by chance. Moreover, rarely is the culprit of a disease a single gene. But, for now, we'll leave this to others.

I want to focus on something else. Something that is relevant to every person. Something that both of these articles touch on. Let me highlight them for you.

From Jolie's article:

"The cost of testing for BRCA1 and BRCA2, at more than $3,000 in the United States, remains an obstacle for many women."

From Soal's article:

"Fortunately I live in the UK, where the NHS offers free genetic screening..."

Both of these articles mention the cost of the genetic screening. In the United Kingdom, this cost is covered, while in the United States, it is quite expensive, at least for health insurance plans in place prior to the passing of the Healthcare Law. But even if covered by insurance, someone is paying a lot of money for this testing.

BRCA1 is on chromosome 17
BRCA2 is on chromosome 13
Wikimedia Commons

Why?
Because a company called Myriad (and their BRCAnalysis) owns the right to know what the DNA sequence is of your (or mine, or anyone's) BRCA1 and BRCA2 genes.

Owns?
Yes, they own it. Myriad holds a patent on the sequence of those genes. This means, even if you wanted to sequence your own BRCA1 and/or BRCA2 genes, you would have to pay a fee ($3,000-$4,000 to Myriad) because Myriad owns the right to know the sequence of every human BRCA1 and BRCA2 gene. All 7.1 Billion people (yes, we all have chromosome 17 an chromosome 13, and regardless of the genetic component are all susceptible to breast cancer, as well as many other associated cancers). This patent is currently being disputed in the Supreme Court.

If it's a patent, what did they develop?
Myriad did not develop the BRCA1 or BRCA2 genes. Myriad did not create the mutations in BRCA1 or BRCA2 that are associated with breast, or other cancers. Myriad has no right to prevent anyone from knowing what the sequence of our genes are.

This patent gives Myriad ownership of information about my body that has always been a part of me. is akin to giving them the right to know (and to tell me, or not) what color my eyes are, even though I could use a mirror to figure it out. Using the mirror (doing it myself), would violate the patent unless I paid Myriad money. It is like allowing Myrad to to charge me thousands of dollars to know what my blood type is (even though I can order a couple, super-nifty, blood-typing cards for twenty bucks ).

Sure, Myriad can offer their test (which uses technology that is no different than thousands of labs around the world use daily). But, they have no right to prevent other people, or companies, or ourselves, from conducting tests to answer the same questions. Questions about ourselves.

Myriad does not own our genes.

A friend texted me the other day:

"What do you think about gene patenting? Seems douchey to me."

I couldn't agree more.

29 Comments

John Harshman · 16 May 2013

So what did Myrad actually do? Design a couple of PCR primers? Or something more?

DS · 16 May 2013

On the other hand, they can't do anything to prevent anyone with a PCR machine from performing the test for themselves. The only thing they could do would be to sue after the fact and that could get expensive, even if they won every time.

https://me.yahoo.com/a/JxVN0eQFqtmgoY7wC1cZM44ET_iAanxHQmLgYgX_Zhn8#57cad · 16 May 2013

The Designer ought to claim the rights.

It probably doesn't because of the liability for inventing faulty genes that it would face.

Glen Davidson

eric · 16 May 2013

https://me.yahoo.com/a/JxVN0eQFqtmgoY7wC1cZM44ET_iAanxHQmLgYgX_Zhn8#57cad said: The Designer ought to claim the rights. It probably doesn't because of the liability for inventing faulty genes that it would face. Glen Davidson

Well, perhaps you point to a solution: if someone is going to claim patent rights over some bit of my biology, I'm going to sue the patent holders for faulty and dangerous product. That solution is not elegant. Its not ideal. But the kludge of "you can patent genes, but no company does because of the legal liability" is probably better than the current situation of "you can patent genes without any negative repercussion."

https://me.yahoo.com/a/g_jqEg0ksIAZZ5mg15fwOz7qqbbg#0eec2 · 16 May 2013

"Douchey" is an understatement.

tomh · 16 May 2013

I'm glad someone pointed out the importance of the current Supreme Court case. The problem is, the Court, which accepts few patent cases, seldom gets them right. If one reads the transcript of the oral arguments you can see that they have, at best, a murky grasp of the science involved. Only Sotomayor seems to actually understand the case. They're likely to issue a very narrow ruling that may invalidate the Myriad patents, (which run out in 2015 anyway), but leave the other 3,000 - 5,000 genes that are patented up for grabs.

someotherguy86 · 16 May 2013

$3-4K is insane. You can sequence an entire transcriptome for less than that.

harold · 16 May 2013

DS said: On the other hand, they can't do anything to prevent anyone with a PCR machine from performing the test for themselves. The only thing they could do would be to sue after the fact and that could get expensive, even if they won every time.

That's effectively what they do, and it is cost effective for them. This is not remotely the only example. (Incidentally, at another level, it would also be illegal for you to market the testing as a clinical result without getting your lab CLIA certified. That is a very beneficial regulation; CLIA certification is not particularly onerous. It isn't perfectly logical in every detail about everything but is a decent system of oversight of clinical labs.) Getting back to "gene patenting"...you would need a sophisticated set up to duplicate the testing. A PCR machine needs a facility and reagents. Thus, you would either be working with an institution, or you would be rich enough to build your own facility. I realize the some people do molecular biology in the garage, and hey, maybe I'll try it sometime, but for the most part what I'm saying here is true. To test for these particular mutations efficiently, you need some resources. Therefore, there is someone with resources for them to sue. In short, if they sue and win or settle, there is someone to collect from. So that's how it works. Their pockets are decently deep, and if you try to defy their patent, douchey as it is, they can sue you, probably win, and if you had a PCR machine and reagents, you probably have something to be sued for.

Ron Bear · 16 May 2013

I’m going to play devil’s advocate.
Disclaimer; I reserve the right to change my position should my post educe superior logic/facts from the forum.

I don’t believe these guys are claiming that they have a patent on the gene. Since our bodies mass produce genes, simply living would violate that patent. I think they have a patent on knowing what this gene does. If you want to know what that gene does in your body then you have to pay. I think Wilson got this correct in her description, but the nomenclature “patenting a gene” seems wrong to me.

Being paid for this information seems ok to me. They had to invest their time / capital to learn what the gene does. If they give this information away they can’t recoup their investment. If there were no patent process then they would have kept the gene’s name / location a secret and just advertised that there is a gene that causes cancer and for a fee we will see if you have it. But there is a patent process and the first step involves disclosing your information. Well information is the entire game for these guys. For every patent in existence there is a description of a process for which there wasn’t formerly a description of said process. If you want to use the process as described you have to pay. Technically you can use the process a few times to test/ understand it and only have to pay for mass production, but that is a quibble.

These guys found some useful information. They claim they found the information at great expense. I lack a foundation to evaluate that claim so I just accept it. They got a patent. That patent allows them to profit from their discovery. Then they will have the resources to make another discovery. To me this patent seems proper and like it is one more validation of the patent process in general.

Ron Bear

ksplawn · 16 May 2013

I'm going to patent the process of finding out what's inside a lump of ore. If you ever find out anything about the contents of ore, you need to pay me.

air · 16 May 2013

There is more than gene patenting involved. Myriad also claims the relationship between BRCA1/2 and susceptibility to breast cancer. They also claim, in an unrelated but important patent, the relationship between blood homocysteine levels and folate/cobalamin deficiency, an important indicator in heart disease. This is not a patent on a method to test homocysteine, but on the relationship between the levels of these two substances, just as this breast cancer claim is not a patent on BRCA1 but on the relationship between genotype and phenotype. The homocysteine patent led to a pretty amusing (for some values of amusing) op ed by Michael Crichton titled "This Essay Breaks the Law" - easy to Google up on the NYT website.

air · 16 May 2013

Ron

This is an incredibly complex issue where what we may or may not believe is very nearly a useless criterion - this is the law, after all. Some of what you posit, such as a requirement of an investment in effort to obtain a patent is now part of this body of law as of 2001, but the idea that a human gene is patentable does include patent rights to the gene within the human body. Myriad claims, consistent with other patents issued, that others cannot isolate and sequence this gene from the body because they own the isolated gene, while others argue that the gene is a product of nature and if they invest effort in isolating it (Myriad does not have a patent on isolation methods) they should be free to exploit that product of nature.

In the Supreme Court case, Justice Sotomayor raised an interesting analogy

"I can bake a chocolate chip cookie using natural ingredients - salt, flour, eggs, butter - and I create my chocolate chip cookie. And if I combust these in some new way, I can get a patent on that. But I can't imagine getting a patent simply on the basic items of salt, flour and eggs, simply because I've created a new use of a new product from those ingredients."

olorin618 · 16 May 2013

Let me weigh in here as a retired patent attorney who has written a number of applications on a variety of biotech subjects.

Ron Bear has a good grasp of the basic problems.

As happens in many patent cases, we have economic considerations on one side, and human-rights considarations on the other. Myriad has poured megabucks into finding a link between these specific gene mutation and breast cancer---probably investigating, at their own expense, thousands of genes and combinations, Why should they not reap some benefit by excluding others from exploiting their investment for a few years? More broadly, as the courts look at these specific cases, what is the incentive for companies to engage in this kind of research at all if others can use it for free? On the other side, this patent covers information about your body. Why should you have to pay anyone a lot of money to find out what is going on in your own body? And who owns your DNA, anyway? (By the way, Myriad is not claiming to own the sequence as such.)

There are two legal issues.

First, the courts have always made a distinction between an "invention," something created by human endeavor, and a "fact of nature" that the inventor only found lying around. For example, it has long been held that no one can patent a physical law. When this rule was developed in the 19thC,, however, there was a clear demarcation between the two. Now, we're not so sure. This is the legal issue (35USC101) as to whether the gene sequence itself is patentable at all.

Second, a patent can claim only what is shown in the application and "equivalents" thereof."Equivalents" (35USC112) has also been a thorny issue for a very long time. Morse tried to patent all methods of sending information by electromotive force. No, no, no, said the courts. You're trying to claim a territory far broader than what you have actually invented or shown. So, can Myriad claim ANY method of determining that sequence, with the specific mutation? How far can they stretch the equivalency issue in this situation? To some extent, this is poor claim drafting on Myriad's part; they should probably have claimed: determining the presence of this specific mutation in this sequence, AND THEN initiating a course of treatment if the mutation is found. Even this may fail the equivalency test: What treatment? Well, anything the doctor prescribes in his own judgment. Vague, and very broad.

These are the two legal issues in the patentability of Myriad's claims. And these must be weighed to achieve a fair balance between the economic factors and the individual-rights factors. Never an easy task. Plus the fact, of course, the the justices do not really understand the technology, and therefore tend to get hung up on glib phrases and appealing sound bites.

I'm glad this decision is above my pay grade.

gnome de net · 16 May 2013

Somewhat related:

Why should you have to pay anyone a lot of money to find out what is going on in your own body?

That's exactly what happens whenever we consult a doctor for any diagnostic procedure, and AFAIK we're not allowed to have our own personal copy of the results.

Chris Lawson · 16 May 2013

1. While Myriad's patent may not, strictly speaking, give them the rights to the BRCA1 gene itself, it certainly means that in practical terms. Even researchers looking to improve breast cancer treatments have had to pay the $3K per test.

2. It's not as simple as having a PCR machine. You need to have the right tools to know where to look for the BRCA1 gene.

3. I don't know about US law, but in Australia you *do* have the rights to your medical records. Under the Privacy Act, patients are allowed access to and a copy of (with minimal fee to cover printing) their medical records. There are a handful of exceptions for very rare psychiatric conditions, but if you go to your doctor and ask, then by Act of Parliament the doctor has to give you all of your records. When you pay a doctor for their diagnostic skills, you are paying for a service and not to create a piece of intellectual property owned by the doctor.

4. As others have already pointed out, while the UK has a preferable system in that the patient is not forced to pay for BRCA gene tests, *someone* is still paying. In this case it's the NHS. And while it's good for the UK public that they can have the BRCA gene test paid for, it's not good for the UK public to have less funding available for other, more reasonably priced, health interventions.

5. There needs to be a separate type of patent for natural discoveries like genes. I'm all in favour of people being rewarded for work that improves the wellbeing of the community, but patent law is a terrible fit for genetics. It's particularly bad that people have managed to get patents simply for sequencing genes, a process that requires almost no intellectual effort, often before anything was known about the genes' functions. The reward should be going not to the company that fired up a thousand parallel PCR machines and churned through the genome looking for previously unreported sequences. The reward should go to the people who find out what the gene does, how it interacts with other genes and the environment, and how to use that knowledge to create therapeutic interventions. At the moment, the bulk of the reward goes to those who trawl the genome and to those who work on the very last (admittedly very expensive) stages of therapeutic design. All the hard work in the middle tends to be left out of the reward system...or in the case of BRCA, actively penalised by the patent system.

glipsnort · 16 May 2013

There may also be scientific issues involved. I note that my boss has filed an amicus curiae brief in the case.

ksplawn · 16 May 2013

olorin618 said: ... As happens in many patent cases, we have economic considerations on one side, and human-rights considarations on the other. Myriad has poured megabucks into finding a link between these specific gene mutation and breast cancer---probably investigating, at their own expense, thousands of genes and combinations, Why should they not reap some benefit by excluding others from exploiting their investment for a few years?

Because they didn't actually invent the gene or its relationship to breast cancer. What this argument consists of essentially boils down to "Hey, this thing was expensive to do, so they should also stand to monopolize all the money related to it. Nevermind that the thing they're monopolizing around has existed before the human species itself and is a basic, fundamental part of human biology." It's clear that I'm not a patent attorney but I think in a common-sense kind of way that this should fail any kind of inventiveness and obviousness tests. It might be different if they patented the process of taking a gene that produces toxin and inserted it into a strain of corn to produce corn that fights off moth larva, but all they're patenting is the knowledge of what a gene does regardless of how you could arrive at that knowledge. That's way too broad.

These are the two legal issues in the patentability of Myriad's claims. And these must be weighed to achieve a fair balance between the economic factors and the individual-rights factors.

I'm not sure such a weighing is necessary in the first place.

realgrumpybob · 16 May 2013

I am sure I can recall that Myriad managed to identify one or both BRCA genes because they had access to the nightly stream of primary sequence data being released by the international Human Genome Project, and that there was a something of a race to analyse those data by several different entities. Though maybe my memory is faulty!

Robert

harold · 17 May 2013

gnome de net said: Somewhat related:
Why should you have to pay anyone a lot of money to find out what is going on in your own body?
That's exactly what happens whenever we consult a doctor for any diagnostic procedure, and AFAIK we're not allowed to have our own personal copy of the results.

You are allowed to have your own copy of the results, and you are also perfectly free to do any procedure on yourself that you would like. You are constrained by law from specifically charging others money for medical advice or surgery, unless you meet certain minimal licensing requirements. Licensing requirements for professions is ubiquitous and uncontroversial throughout the developed world, and in many parts of the developing world. As it happens physicians also have an internal system of recognition of expertise, the certification for completing certain types of specialty training. However, this internal, voluntary, professional accreditation system has no meaning in criminal law. If you graduated from a recognized medical school (anywhere in the world), performed an internship in a recognized program (there are many), and passed a basic set of exams known as the USMLE exams, you can be licensed in any US state. Canada has its own requirements, which are highly similar. So do other developed nations. In practice it requires some academic ability and hard work to become a physician, and requires years of financial sacrifice unless someone is willing to pay for your education. There are also requirements, varying from state to state but always similar, that you avoid certain types of felonies, refrain from certain types of highly unethical behavior, and avoid practicing if impaired by significant substance abuse. It isn't easy, but on the other hand, there are no major barriers, either. Hypothetically, you certainly could have become a physician and could probably become one in the future if you really want to. There are numerous jobs in finance and other fields that literally require appropriate personal connections. Not so with medicine. There are "legacy admissions" to medical schools (the excellent UC Davis Medical School long term studies on affirmative action demonstrated that, as any reasonable person would expect, this is the major source of affirmative action in medical school admissions, even at a state university with strong commitment to diversity), but the vast majority of people got there on their own merits. The sole reason for consulting a physician is to benefit from their expertise. You are no more legally required to consult a physician, with the exception of court ordered mental health interventions when they occur, about your health, than you are to consult a licensed CPA about a complex tax problem, or to consult evolutionary biologists about the diversity and relatedness of life on earth. You are perfectly free to form your own opinions. You can buy almost all the medical equipment you want for yourself. There are environmental regulations that apply to equipment that uses radiation or generates controlled waste, but those are pretty much the only restrictions. The law does restrict you from telling others that you are qualified to charge them money for medical advice or procedures, if you have not met certain qualifications, but as for figuring out your own medical problems - you are 100% free to do so.

fusilier · 17 May 2013

gnome de net said: Somewhat related:
Why should you have to pay anyone a lot of money to find out what is going on in your own body?
That's exactly what happens whenever we consult a doctor for any diagnostic procedure, and AFAIK we're not allowed to have our own personal copy of the results.

You have the right to copies of all diagnostic procedures in the US, as well. A couple of years ago, when I was prepping for a radical prostatectomy, I had an MRI and a Tc-99 bone scan to look for metastases. I asked for copies on CDs and got about 24. Passed them on to our Radiologic Technology program for student use. fusilier James 2:24 Whoopise, almost forgot - everything was clean and PSA scores are below detectable limits. Science works.

gnome de net · 18 May 2013

@harold and fusilier:

I stand corrected. Have we always had rights to copies of our health records, or have there been recent changes? I'm sure either I have or a family member has encountered this problem, but I'm unable to recall any specifics.

gmartincv · 18 May 2013

gnome de net said: @harold and fusilier: I stand corrected. Have we always had rights to copies of our health records, or have there been recent changes? I'm sure either I have or a family member has encountered this problem, but I'm unable to recall any specifics.

The Health Insurance Portability and Accountability Act of 1996 (most commonly referred to as HIPPA) certainly allows individuals to have access to all of their medical records. The compliance dates for HIPPA were either 14 April 2003 or 14 April 2004 depending the size of certain organizations covered by HIPPA. I have no direct knowledge of the state of access before 2003. George

gnome de net · 18 May 2013

@gmartincv:

That explains it — what I'm vaguely recalling predates that by maybe 10 years.

What? You say it's now 2013! I'd better go flip some pages on my calendar....

Mark Sturtevant · 19 May 2013

How many tests per year does Myriad get reimbursed for? Maybe not so many b/c of the cost? If it is mainly done by women with a strong family history of breast cancer then that is why Myriad must charge so much. But suppose if Myriad were to charge just $100-$200 per test. With such a low charge I would think a very large number of women would elect to have the test. Myriad would make money and lives would be saved.

tomh · 20 May 2013

@ Mark Sturtevant

According to Myriads own site there are 250,000 BRACAnalysis tests conducted each year. It's latest quarterly earnings report said, "Revenue from the BRACAnalysis test, which represented 74 percent of total revenue in the third quarter, was $115.4 million, a 9 percent increase over the same period of the prior year,"

Incidentally, Myriad's stock price rose to a three year high after Jolie's announcement.

DS · 20 May 2013

tomh said: @ Mark Sturtevant According to Myriads own site there are 250,000 BRACAnalysis tests conducted each year. It's latest quarterly earnings report said, "Revenue from the BRACAnalysis test, which represented 74 percent of total revenue in the third quarter, was $115.4 million, a 9 percent increase over the same period of the prior year," Incidentally, Myriad's stock price rose to a three year high after Jolie's announcement.

Jonas Salk would be so proud.

air · 20 May 2013

olorin618: It's probably not accurate to state that Myriad 'poured megabucks' into the discovery. Most of the scientists involved were academicians at the University of Utah, NIH, NIEH and other places. It is highly likely that there was grant support but the paper does not acknowledge any financial support (including from Myriad). Of course, whether the amount Myriad spent is relevant is another issue as is the question of how best to incentivize academic researchers to commercialize their results (which is now a legal requirement for grant-funded work).

Realgrumpybob: Myriad published the original work in Science on Oct. 7 1994, well before the HGP; the work was done by much more laborious methods.

dornier.pfeil · 21 May 2013

One of the founders of Myriad chimes in through a WSJ column.
http://online.wsj.com/article/SB10001424127887323582904578487511358752662.html

If you can't access the column just google the title "Gene Patents Drive Medical Innovation". The WSJ usually allows access to a limited number of columns through google per day.

tomh · 21 May 2013

For a different take on it, there is this op-ed in the NYT, "The Outrageous Cost of a Gene Test."