One hundred US medical academics, that is professors and researchers at universities hold 50 US patents concerned with the diagnosis of Lyme disease and with vaccines. The National Institute for Health, a government agency, also holds patents. These include diagnosis methods and vaccines for animals. A patent may be granted to a US government agency such as the National Institute for Health, a national, international or off-shore company, a University, a University spin-off company or an individual. Patents may provide income by royalties, by a share in the profits of a company utilizing the patent or by a share in sales of a product or process utilizing the patent. An academic researcher may finance a patent application through the university or through funds provided by a government agency or through funds provided by a company. Grants to universities by individuals in the USA are tax-deductible, i.e. they reduce the taxable income of the giver, so university academics are used to applying for and obtaining funding for a variety of activities including patent applications and annual patent fees.
As soon as Lyme disease was identified the US academic world as well as companies and government agencies concluded that there were opportunities for obtaining patents for any stage in the diagnosis or the treatment of Lyme disease, or for patents for vaccines against Lyme disease.
It was initially thought that Lyme disease was similar to syphilis as the bacteria looked like the syphilis bacteria in a microscope. Diagnosis and treatment was therefore thought to be relatively straightforward. Diagnosis of syphilis is most commonly carried out by a blood test. As this indicates that some have syphilis who don’t have syphilis, which is called a false-positive result, a further confirmatory test is carried out. The standard treatment for early syphilis is a single dose of penicillin G and for late syphilis ten days of penicillin G. In early syphilis cure rates are extremely high.
These diagnostic methods and penicillin G are now out of patent, that is the patents no longer apply and no royalties are paid. Royalties for the diagnosis of patients and the treatment of Lyme disease would therefore give relatively little income to researchers as the number of cases was believed to be small and limited to certain areas in the North East of the USA. Furthermore the antibiotic penicillin G was out of patent.
The potential for income from a vaccine would, however, be immensely greater. Millions would purchase a vaccine which would be paid for by individuals, and not by the insurance companies or the federal government. An annual booster dose would also be required. Millions would also purchase a diagnosis test as one should not take a vaccine if one already suffers from a disease. It was calculated in the early 1990s that income from diagnostic tests and a vaccine would amount to five hundred million dollars in the USA and five hundred million dollars in Europe.
A bacterial illness may be cured while a virus cannot be eliminated. There is, therefore, a stronger case for a vaccine for viral diseases, such as polio, measles, mumps and chicken pox than for bacterial illnesses. There is, however, a vaccine for tuberculosis which is caused by a bacteria, usually taken by persons travelling to, or living in endemic areas. An argument against the use of a vaccine is that it, with a skin test, would give a false-positive and therefore give no information to a vaccinated individual should they wish to be tested for the disease in question.
A tick infects by injecting saliva into the bloodstream of a mammal and this saliva carries the borrelia bacteria. The borrelia bacteria has a covering of protein on its outer surface which serves to hold it together. In the tick this protein is of a type which was denoted ‘A’. It was thus called outer surface protein A, or for short OspA. The human immune system works by breaking down the outer surface protein of a bacteria. The white blood cells in the blood carry out this attack. In the case of borrelia bacteria they produce antibodies against OspA. However, the borrelia bacteria do something that other bacteria cannot do: they change the composition of their outer surface protein to another protein denoted ‘C’, or OspC soon after entering the bloodstream of the mammal. The immune system is not able to perform a similar change by producing new antibodies, but continues to mount attacks against outer surface protein ‘A’. The borrelia bacteria can thus proliferate throughout the body into tissue and organs without any opposition.
Evidence-based medicine means that groups of cases are used for studies with statistical analysis applied to the results. These are usually designed as what is called a “Randomized controlled trial”, or RCT for short. Evidence-based medicine began to be applied in the 1990s. National health services and insurance companies began to use this idea. Individual doctors could have been professionally responsible for evaluating the evidence and strength of these research studies. However, increasingly health services set up groups to evaluate the various research reports based on evidential methods. These groups then issued guidelines for the diagnosis and treatment of the disease in question. Doctors found these guidelines convenient as they no longer had to learn about diagnosis and treatment of individual diseases. They merely needed to determine which diseases might come under consideration for their patient. They then ordered the tests stated in the guidelines without having to consider how accurate the tests were and which shortcomings they had. If a disease was shown to be present then the treatment dictated by the guidelines was arranged, once again without having to evaluate any shortcomings. This method of procedure by physicians is termed “differential analysis”.
The traditional experience, knowledge and imagination of the individual doctor were thus replaced by guidelines based on evidence-based research. Nearly all such research is carried out by university hospital departments. The research departments of the university hospitals through their research papers thus began to dictate treatment instead of the physician. Many of these research persons were not physicians and never had been physicians. They might be pharmacists or statisticians or microbiologists. They never met patients or had any relationship to patients or responsibility for patients.
Where no evidence existed a problem arose. This is often the case with a new disease as it takes years to carry out and publish evidential research. In the absence of guidelines doctors fell back passing on the problem through referral to specialist departments. As there were and are few or no specialist Lyme departments this could mean a referral to a variety of departments who often had never even heard of Lyme disease or the borrelia bacteria. Another alternative to this dilemma is to refuse to treat the patient at all.
The initial idea that the bacteria could be cured as easily as syphilis was abandoned when it was found that the bacteria was able to change its outer surface protein. However, evidence-based medicine was considered to be essential although too little was known about Lyme disease to make it reliable although researchers continually assumed they knew more than was the case as too much had been assumed initially. Cure rates in double blind tests of a treatment of most diseases were around 100%. However, with Lyme disease, treatments which gave cure rates in research studies of around 50% to 70% were considered acceptable to maintain the fiction of the relevance of evidence-based medicine. Researchers resorted to removing cases from the study or if numbers of subjects were too small to stating percentages instead of small numbers. Physicians running research had studied biology, physics and chemistry as natural science subjects at school. It was rarely the case that they had studied mathematics and statistics. They were and are thus ill-equipped to assessing the relevance of results.
These difficulties increased the hope of the patent holders that a vaccine would turn out to be a more profitable and easier option than treatment.
Faced with these problems an ingenious idea for a vaccine was put forward. This assumed that blood from the mammal would enter the tick before the borrelia bacteria entered the body with the tick saliva. The vaccine would not create antibodies to outer surface protein ‘C’ which would be in the body of an infected person, but the outer surface protein ‘A’ which would be in the bacteria in the body of the tick. The bacteria in the tick would be made harmless before they could reach the person. An inherent problem was that bacteria from the tick might enter the body before the vaccine had broken down all bacteria in the tick. Very little research had been carried out on borrelia burgdorferi bacteria in ticks although some research had been carried out on the borrelia bacteria which cause African relapsing disease.
The vaccine would need approval from the US government before it could be sold. A vaccine prevents a disease and a definition and reliable test for the disease therefore is required before a vaccine may be considered for approval. It was therefore essential that the existing diagnostic methods be approved by the US government agency. An effective method since the nineteenth century of finding bacteria was to examine blood in a microscope when you would see the actual bacteria. Doctors in the 1960s usually had a microscope in their consulting room. This method could not be patented and was of little financial interest to US university researchers.
They sought instead to find a method of finding antibodies to borrelia, a method that would be new as the antibodies would be new and thus able to be patented. It might also be automated which was difficult with a microscopic method.
The diagnostic method put forward to obtain vaccine permission comprised an initial test for antibodies to outer surface protein ‘A’ to see who had the disease and who had taken the vaccine against OspA. This was a test called the enzyme-linked immunosorbent assay method, ELISA for short. This test had been developed in a hurry when it was found that this new disease had emerged. It had many shortcomings, one of which was that it might indicate that a person was infected who was not which would create legal problems in the USA. A doctor would not give the vaccine to a person with OspA antibodies. However, the doctor could be sued if no vaccine were given and a person became very ill after a tick bite as the patient could assert that a vaccine should have been given. To avoid this a confirmatory test on a similar antibody principle was used called the Western Blot. The difference in the methods was in the way the blood was broken down before the test was carried out. The important aspect for vaccine approval and for subsequent legal problems was to avoid finding a person positive who did not have Lyme disease. Finding those who had the disease was of less importance and the aim was to obtain a rough idea of the numbers of persons in the population who might have the disease so that the size and type of US Federal or State action could be assessed.
The US government set up a committee to consider approval for the vaccine and for the requisite diagnostic method at a place called Deerborn in 1994. A new disease brings with it the problem that there are few experts on the disease while the approval systems for diagnostic methods and vaccines in the USA require a large number of independent experts to hear the case put forward by experts asking for the vaccine approval. The Dearborn committee resolved this problem by waiving the normal requirements of independence and of conflict declaration. The committee itself was not independent either as a US agency held several patents.
Many problems were aired, but were resolved by each member voting for approval while expressing pages of reservations.
Approval was obtained for both the diagnostic methods and for the vaccine.
The vaccine began to be given to persons. Problems soon arose as persons became sick anyway and doctors were sued, often those who had the patents, rights and financial interest in some way to the vaccine. Approval was therefore withdrawn.